The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
HCV has evolved multiple mechanisms to evade the immune system and establish chronic infection. It interferes with pattern recognition receptor signaling through cleavage of adaptor proteins by NS3/4A. NS3/4A and NS5A also block RIG-I signaling and JAK/STAT interferon pathways. HCV impairs dendritic cell function and induces T cell exhaustion. The high mutation rate allows escape from neutralizing antibodies and cytotoxic T cells. Combined, these immune evasion strategies enable HCV to overcome host defenses and persist long-term in most infected individuals.
The document summarizes evasion mechanisms used by viruses to avoid the host immune system. It discusses two main mechanisms used by influenza viruses: antigenic drift which involves point mutations in surface proteins, and antigenic shift which involves reassortment of RNA segments between animal and human influenza viruses. It also describes how herpes simplex viruses prevent the transport of viral peptides to the ER through the protein ICP-47, inhibiting antigen presentation through MHC class I molecules on infected cells.
Immunity against Helminths:role of InterleukinsIshfaq Maqbool
The document summarizes key aspects of the immune response against helminth parasites. It notes that helminths typically induce a type 2 immune response characterized by cytokines like IL-4, IL-5, and IL-13. This non-inflammatory response involves alternatively activated macrophages, eosinophils, and other effector cells that work to expel and kill parasites while repairing tissue damage. The response differs from bacterial and viral immunity, with Th1 responses only occurring during early larval migration stages.
Mechanism of immunoevasion in parasites 2018 06-17Rasika Deshmukh
The document summarizes mechanisms of immune evasion in various parasites. It discusses how parasites like malaria, trypanosomes, leishmania, toxoplasma, entamoeba, giardia, schistosomes, trichomonas, and helminths evade the host immune system. Some key strategies parasites use include antigenic disguise, molecular mimicry, immunosuppression through cytokines, inhibiting host immune signaling pathways, disrupting complement pathways, shedding surface antigens, and phenotypic variation. Understanding these immune evasion mechanisms provides insights into host-parasite interactions and disease pathogenesis.
This document discusses a project called Project Mutamba that aims to identify the efficiency of tannins extracted from the Guazuma ulmifolia plant in inhibiting the reverse transcriptase of the HIV virus with lower toxicity. The project seeks to determine the molecular weight of tannin that best inhibits HIV replication while posing minimal health risks. If successful, it could help reduce viral load, preserve immune function, and slow disease progression for those living with HIV/AIDS. The document provides background on HIV/AIDS and how current antiretroviral drugs can cause side effects, justifying the need to explore alternative treatment options from plants like G. ulmifolia that may have antiviral properties with fewer adverse effects.
This document summarizes immune evasion strategies used by flaviviruses. It discusses how flaviviruses evade innate immune responses such as type I interferon responses and complement system activation. It also describes adaptive immune evasion mechanisms, including antigenic variation, antibody-dependent enhancement of infection, and inhibition of antigen presentation. The document provides diagrams illustrating key concepts and cites related studies on flavivirus immune evasion and modulation of host inflammatory responses.
This document discusses the interplay between Mycobacterium tuberculosis (Mtb) and the host immune environment, particularly in the context of HIV/TB co-infection. It presents several key findings:
1. Mtb can detect and respond to environmental cues within the macrophage such as oxidative stress, nutrient limitation, and changes in pH and chloride concentration. This allows Mtb to sense its intracellular location and immune status.
2. Reporter strains of Mtb show an accelerated transcriptional response to stresses like nitric oxide in vaccinated mice, indicating the immune response is developing faster.
3. Drugs like isoniazid have greater activity against intracellular Mtb in naive mice, suggesting the bacteria replicate more in this
Parasitic infection and immunomodulation: A possible explanation for the hygi...Apollo Hospitals
This document discusses the hygiene hypothesis in autoimmune and allergic disease. It proposes that reduced incidence of parasitic infections in developed countries due to improved sanitation may be linked to increased rates of autoimmune and allergic diseases. Parasitic infections induce regulatory immune responses that help the parasites survive while also reducing inflammation. Specific parasite molecules modulate the immune system by suppressing Th1 and Th17 responses and inducing Th2 and regulatory T cell responses. Understanding these immunomodulatory mechanisms could help develop new treatments for inflammatory and allergic conditions.
HCV has evolved multiple mechanisms to evade the immune system and establish chronic infection. It interferes with pattern recognition receptor signaling through cleavage of adaptor proteins by NS3/4A. NS3/4A and NS5A also block RIG-I signaling and JAK/STAT interferon pathways. HCV impairs dendritic cell function and induces T cell exhaustion. The high mutation rate allows escape from neutralizing antibodies and cytotoxic T cells. Combined, these immune evasion strategies enable HCV to overcome host defenses and persist long-term in most infected individuals.
The document summarizes evasion mechanisms used by viruses to avoid the host immune system. It discusses two main mechanisms used by influenza viruses: antigenic drift which involves point mutations in surface proteins, and antigenic shift which involves reassortment of RNA segments between animal and human influenza viruses. It also describes how herpes simplex viruses prevent the transport of viral peptides to the ER through the protein ICP-47, inhibiting antigen presentation through MHC class I molecules on infected cells.
Immunity against Helminths:role of InterleukinsIshfaq Maqbool
The document summarizes key aspects of the immune response against helminth parasites. It notes that helminths typically induce a type 2 immune response characterized by cytokines like IL-4, IL-5, and IL-13. This non-inflammatory response involves alternatively activated macrophages, eosinophils, and other effector cells that work to expel and kill parasites while repairing tissue damage. The response differs from bacterial and viral immunity, with Th1 responses only occurring during early larval migration stages.
Mechanism of immunoevasion in parasites 2018 06-17Rasika Deshmukh
The document summarizes mechanisms of immune evasion in various parasites. It discusses how parasites like malaria, trypanosomes, leishmania, toxoplasma, entamoeba, giardia, schistosomes, trichomonas, and helminths evade the host immune system. Some key strategies parasites use include antigenic disguise, molecular mimicry, immunosuppression through cytokines, inhibiting host immune signaling pathways, disrupting complement pathways, shedding surface antigens, and phenotypic variation. Understanding these immune evasion mechanisms provides insights into host-parasite interactions and disease pathogenesis.
This document discusses a project called Project Mutamba that aims to identify the efficiency of tannins extracted from the Guazuma ulmifolia plant in inhibiting the reverse transcriptase of the HIV virus with lower toxicity. The project seeks to determine the molecular weight of tannin that best inhibits HIV replication while posing minimal health risks. If successful, it could help reduce viral load, preserve immune function, and slow disease progression for those living with HIV/AIDS. The document provides background on HIV/AIDS and how current antiretroviral drugs can cause side effects, justifying the need to explore alternative treatment options from plants like G. ulmifolia that may have antiviral properties with fewer adverse effects.
This document summarizes immune evasion strategies used by flaviviruses. It discusses how flaviviruses evade innate immune responses such as type I interferon responses and complement system activation. It also describes adaptive immune evasion mechanisms, including antigenic variation, antibody-dependent enhancement of infection, and inhibition of antigen presentation. The document provides diagrams illustrating key concepts and cites related studies on flavivirus immune evasion and modulation of host inflammatory responses.
This document discusses the interplay between Mycobacterium tuberculosis (Mtb) and the host immune environment, particularly in the context of HIV/TB co-infection. It presents several key findings:
1. Mtb can detect and respond to environmental cues within the macrophage such as oxidative stress, nutrient limitation, and changes in pH and chloride concentration. This allows Mtb to sense its intracellular location and immune status.
2. Reporter strains of Mtb show an accelerated transcriptional response to stresses like nitric oxide in vaccinated mice, indicating the immune response is developing faster.
3. Drugs like isoniazid have greater activity against intracellular Mtb in naive mice, suggesting the bacteria replicate more in this
Parasitic infection and immunomodulation: A possible explanation for the hygi...Apollo Hospitals
This document discusses the hygiene hypothesis in autoimmune and allergic disease. It proposes that reduced incidence of parasitic infections in developed countries due to improved sanitation may be linked to increased rates of autoimmune and allergic diseases. Parasitic infections induce regulatory immune responses that help the parasites survive while also reducing inflammation. Specific parasite molecules modulate the immune system by suppressing Th1 and Th17 responses and inducing Th2 and regulatory T cell responses. Understanding these immunomodulatory mechanisms could help develop new treatments for inflammatory and allergic conditions.
The study examines apoptosis in mouse splenic T cell and B cell populations during infection with Plasmodium chabaudi chabaudi AS malaria. High levels of apoptosis were found to correlate with high parasitemia and splenomegaly, particularly in CD4+ T cells. Apoptosis levels decreased as parasitemia was cleared but remained elevated compared to normal mice, with CD8+ T cells and B cells returning to basal apoptosis levels while CD4+ T cells remained higher.
The document discusses the immune system and its response to parasitic diseases. It introduces basic concepts of the immune system, including the innate and acquired responses. The innate response acts as a non-specific barrier, while the acquired response involves humoral and cell-mediated immunity. T helper cells can differentiate into Th1 or Th2 subsets, determining the type of response. Th1 supports cell-mediated immunity against intracellular pathogens, while Th2 induces antibody production against extracellular pathogens. CD8+ T cells and natural killer cells directly kill infected cells. Activated macrophages also have microbicidal functions. The balance between protective and pathological immune responses is important for host-parasite interactions.
For centuries, humans have searched for crop plants that can survive and produce in spite of insect pests.
Knowingly or unknowingly, ancient farmers selected for pest resistance genes in their crops, sometimes by actions as simple as collecting seed from only the highest-yielding plants in their fields.
With the advent of genetic engineering, genes for insect resistance now can be moved into plants more quickly and deliberately.
Bt technology is only one example of ways genetic engineering may be used to develop insect-resistant crops now and in the future.
There are two main types of immunity against parasitic infections: innate and acquired. The innate immune system provides initial defenses through barriers like skin and secretions, as well as cells like macrophages. Acquired immunity develops through antibody production by B cells and cellular responses by T cells. However, parasites have evolved strategies to evade the immune system, such as living intracellularly, antigenic variation, immunosuppression, migration, and producing enzymes. This makes the immune response less effective against parasites compared to other pathogens.
Dysregulation of macrophage signal transduction by ToxoplasmaIshfaq Maqbool
A brief account of mechanism adopted by Toxoplasma gondii to evade the immune response of the host immune cells particularly macrophages by disruption of macrophage signal transduction
This document discusses interferons and their role in treating viral infections. It notes that there are three main types of natural interferons - alpha, beta, and gamma - which are produced by cells in response to viral stimuli. Recombinant interferons developed for treatment include pegylated forms with longer half-lives than standard interferons. The document focuses on the use of interferons, particularly pegylated interferons, in treating hepatitis C virus infections. It reviews clinical trial results showing the superiority of combination therapy with pegylated interferon and ribavirin over monotherapy or standard interferon treatments. Common side effects are also discussed.
Transglutaminase 2 (TG2) expression was examined in macrophages in response to Toxoplasma gondii infection and stress. TG2 was expressed in RAW macrophages and intestinal epithelial cells. TG2 expression increased at 3 hours post-infection but decreased at 8 hours. TG2 expression was induced by the stress hormone corticosterone, norepinephrine, and T. gondii infection, with maximum expression observed when infection and norepinephrine were combined. Increased TG2 expression may be detrimental to the host by decreasing anti-inflammatory transforming growth factor beta from macrophages and exacerbating inflammation.
Antimicrobial peptides a novel therapeutic agentkarimbscdu
This document discusses antimicrobial peptides (AMPs), which are small proteins that have broad-spectrum antimicrobial activity against bacteria, viruses, fungi and cancer cells. AMPs are part of the innate immune system and are produced by all multicellular organisms as a first line of defense. There are several classes of human AMPs including defensins, cathelicidins and histatins. AMPs kill microbes through mechanisms such as disrupting microbial membranes and interfering with intracellular processes. Due to their ability to rapidly kill pathogens, broad activity and modularity, AMPs show promise as alternatives to conventional antibiotics.
Antimicrobial peptides are polypeptide substances between 12-50 amino acids in length that have antimicrobial properties. They are classified based on their secondary structure as either beta-sheets, alpha-helices, extended coils or loop structures. They are found in many organisms and body locations where they participate in the innate immune system and have multifunctional roles beyond direct antimicrobial activity, including immunomodulation and cell migration. Their mechanisms of action generally involve interactions with and disruption of microbial membranes through electrostatic and hydrophobic interactions.
This document discusses bacteriophage therapy as an alternative approach to antibiotic resistance. It begins with an introduction to antibiotic resistance and discusses the mechanisms and factors contributing to resistance. It then introduces bacteriophage or phages, describing their classification, life cycles, and mechanisms of infecting bacteria. The document outlines methods for preparing and administering phage therapy. It discusses advantages of phage therapy over antibiotics and provides examples of phage therapy applications in food and agriculture. Finally, it addresses some challenges to phage therapy including host range, bacterial debris in preparations, and lysogeny.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Interferons are naturally occurring proteins that are secreted in response to viral infections and tumors. They have powerful immunomodulatory properties. There are two main classes of interferons - type I (alpha, beta, etc.) and type II (gamma). Interferons bind to specific cell surface receptors and induce hundreds of genes involved in antiviral, antitumor, and immunoregulatory responses. High-dose interferon has been shown to improve relapse-free and overall survival rates in high-risk melanoma patients when used as an adjuvant therapy. Interferons are also used to treat cancers like hairy cell leukemia, renal cell carcinoma, and some forms of lymphoma.
Viruses have evolved sophisticated mechanisms to evade the host's interferon gateway, which mediates the innate antiviral response. The interferon gateway induces interferon stimulated genes upon detection of viral nucleic acids via pathways like RIG-I/MDA5 and TLRs. These genes enact antiviral effects to limit viral replication. However, many viruses encode viral evasion proteins that can inhibit interferon production and interferon stimulated genes at multiple levels of the interferon gateway. This allows viruses to continue replicating in the face of the host's antiviral defenses.
This document discusses multidrug-resistant and extensively drug-resistant organisms (MDROs and XDRs). It defines antibiotic resistance and how bacteria can become resistant through improper antibiotic usage and transmission of resistance genes. Common MDROs include MRSA, VRE, and carbapenem-resistant Enterobacteriaceae. XDR tuberculosis is described as being resistant to nearly all drug classes. Treatment of MDROs and XDRs is difficult as few drug options remain effective. The prevention of further resistance development requires appropriate antibiotic prescribing and hygiene practices to limit transmission.
History of the Forgotten Cure - Phage therapyStudent
1) The document provides a history of phage therapy, from its discovery in the late 19th/early 20th century to its decline with the rise of antibiotics and recent rediscovery due to antibiotic resistance. Key figures who discovered and explored phages and phage therapy include Ernest Hankin, Frederick Twort, and Félix d'Herelle.
2) It discusses how phage therapy works, involving using bacteriophages to treat bacterial infections. Advantages over antibiotics include phages' ability to self-replicate and adapt versus antibiotics being fixed molecules.
3) Problems that initially limited phage therapy are addressed, such as host range, bacterial debris in preparations, and lysogeny.
This document summarizes research on the plant pathogenic bacterium Pseudomonas syringae and one of its virulence factors, HrpZ1. Key findings include:
1) HrpZ1 is a type III secreted protein that can form ion-conducting pores in lipid membranes and trigger plant immune responses. However, pore formation and immune activation are separate functions localized to different domains.
2) The C-terminal domain of HrpZ1 is necessary and sufficient for binding to plant membranes and stimulating immunity responses, but not for pore formation.
3) Insertional mutations in the C-terminal domain disrupt HrpZ1's ability to activate immunity, suggesting this domain contains motifs recognized by plant
This document discusses multiple drug resistance (MDR) in bacteria. It begins by defining drug resistance and how bacteria can develop resistance through natural mechanisms or by acquiring resistance over time when exposed to antibiotics. The key points are:
- Bacteria can become resistant through mutations or gene transfer that make antibiotics unable to bind or enable the bacteria to destroy or pump out antibiotics.
- Multiple drug resistance (MDR) occurs when bacteria resist many different drug classes through various mechanisms like altered cell walls or target sites.
- Common MDR bacteria include MRSA, VRE, and ESBL-producing gram-negative bacteria.
- MDR-TB is also discussed, which is TB resistant to at least is
Anti-microbial resistance has become a world health issue today. Therefore it is imperative to know about the methods of acquiring resistance and ways to deal with the situation and prevent resistance.
Duane Duncan, Jeffrey Grierson and Garrett Prestage discuss social research findings on young gay men's sexual attitudes and behaviours, at the Young Gay Men's Symposium at Promises & Limitations, the CSRH social research conference, February 2014.
The study examines apoptosis in mouse splenic T cell and B cell populations during infection with Plasmodium chabaudi chabaudi AS malaria. High levels of apoptosis were found to correlate with high parasitemia and splenomegaly, particularly in CD4+ T cells. Apoptosis levels decreased as parasitemia was cleared but remained elevated compared to normal mice, with CD8+ T cells and B cells returning to basal apoptosis levels while CD4+ T cells remained higher.
The document discusses the immune system and its response to parasitic diseases. It introduces basic concepts of the immune system, including the innate and acquired responses. The innate response acts as a non-specific barrier, while the acquired response involves humoral and cell-mediated immunity. T helper cells can differentiate into Th1 or Th2 subsets, determining the type of response. Th1 supports cell-mediated immunity against intracellular pathogens, while Th2 induces antibody production against extracellular pathogens. CD8+ T cells and natural killer cells directly kill infected cells. Activated macrophages also have microbicidal functions. The balance between protective and pathological immune responses is important for host-parasite interactions.
For centuries, humans have searched for crop plants that can survive and produce in spite of insect pests.
Knowingly or unknowingly, ancient farmers selected for pest resistance genes in their crops, sometimes by actions as simple as collecting seed from only the highest-yielding plants in their fields.
With the advent of genetic engineering, genes for insect resistance now can be moved into plants more quickly and deliberately.
Bt technology is only one example of ways genetic engineering may be used to develop insect-resistant crops now and in the future.
There are two main types of immunity against parasitic infections: innate and acquired. The innate immune system provides initial defenses through barriers like skin and secretions, as well as cells like macrophages. Acquired immunity develops through antibody production by B cells and cellular responses by T cells. However, parasites have evolved strategies to evade the immune system, such as living intracellularly, antigenic variation, immunosuppression, migration, and producing enzymes. This makes the immune response less effective against parasites compared to other pathogens.
Dysregulation of macrophage signal transduction by ToxoplasmaIshfaq Maqbool
A brief account of mechanism adopted by Toxoplasma gondii to evade the immune response of the host immune cells particularly macrophages by disruption of macrophage signal transduction
This document discusses interferons and their role in treating viral infections. It notes that there are three main types of natural interferons - alpha, beta, and gamma - which are produced by cells in response to viral stimuli. Recombinant interferons developed for treatment include pegylated forms with longer half-lives than standard interferons. The document focuses on the use of interferons, particularly pegylated interferons, in treating hepatitis C virus infections. It reviews clinical trial results showing the superiority of combination therapy with pegylated interferon and ribavirin over monotherapy or standard interferon treatments. Common side effects are also discussed.
Transglutaminase 2 (TG2) expression was examined in macrophages in response to Toxoplasma gondii infection and stress. TG2 was expressed in RAW macrophages and intestinal epithelial cells. TG2 expression increased at 3 hours post-infection but decreased at 8 hours. TG2 expression was induced by the stress hormone corticosterone, norepinephrine, and T. gondii infection, with maximum expression observed when infection and norepinephrine were combined. Increased TG2 expression may be detrimental to the host by decreasing anti-inflammatory transforming growth factor beta from macrophages and exacerbating inflammation.
Antimicrobial peptides a novel therapeutic agentkarimbscdu
This document discusses antimicrobial peptides (AMPs), which are small proteins that have broad-spectrum antimicrobial activity against bacteria, viruses, fungi and cancer cells. AMPs are part of the innate immune system and are produced by all multicellular organisms as a first line of defense. There are several classes of human AMPs including defensins, cathelicidins and histatins. AMPs kill microbes through mechanisms such as disrupting microbial membranes and interfering with intracellular processes. Due to their ability to rapidly kill pathogens, broad activity and modularity, AMPs show promise as alternatives to conventional antibiotics.
Antimicrobial peptides are polypeptide substances between 12-50 amino acids in length that have antimicrobial properties. They are classified based on their secondary structure as either beta-sheets, alpha-helices, extended coils or loop structures. They are found in many organisms and body locations where they participate in the innate immune system and have multifunctional roles beyond direct antimicrobial activity, including immunomodulation and cell migration. Their mechanisms of action generally involve interactions with and disruption of microbial membranes through electrostatic and hydrophobic interactions.
This document discusses bacteriophage therapy as an alternative approach to antibiotic resistance. It begins with an introduction to antibiotic resistance and discusses the mechanisms and factors contributing to resistance. It then introduces bacteriophage or phages, describing their classification, life cycles, and mechanisms of infecting bacteria. The document outlines methods for preparing and administering phage therapy. It discusses advantages of phage therapy over antibiotics and provides examples of phage therapy applications in food and agriculture. Finally, it addresses some challenges to phage therapy including host range, bacterial debris in preparations, and lysogeny.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Interferons are naturally occurring proteins that are secreted in response to viral infections and tumors. They have powerful immunomodulatory properties. There are two main classes of interferons - type I (alpha, beta, etc.) and type II (gamma). Interferons bind to specific cell surface receptors and induce hundreds of genes involved in antiviral, antitumor, and immunoregulatory responses. High-dose interferon has been shown to improve relapse-free and overall survival rates in high-risk melanoma patients when used as an adjuvant therapy. Interferons are also used to treat cancers like hairy cell leukemia, renal cell carcinoma, and some forms of lymphoma.
Viruses have evolved sophisticated mechanisms to evade the host's interferon gateway, which mediates the innate antiviral response. The interferon gateway induces interferon stimulated genes upon detection of viral nucleic acids via pathways like RIG-I/MDA5 and TLRs. These genes enact antiviral effects to limit viral replication. However, many viruses encode viral evasion proteins that can inhibit interferon production and interferon stimulated genes at multiple levels of the interferon gateway. This allows viruses to continue replicating in the face of the host's antiviral defenses.
This document discusses multidrug-resistant and extensively drug-resistant organisms (MDROs and XDRs). It defines antibiotic resistance and how bacteria can become resistant through improper antibiotic usage and transmission of resistance genes. Common MDROs include MRSA, VRE, and carbapenem-resistant Enterobacteriaceae. XDR tuberculosis is described as being resistant to nearly all drug classes. Treatment of MDROs and XDRs is difficult as few drug options remain effective. The prevention of further resistance development requires appropriate antibiotic prescribing and hygiene practices to limit transmission.
History of the Forgotten Cure - Phage therapyStudent
1) The document provides a history of phage therapy, from its discovery in the late 19th/early 20th century to its decline with the rise of antibiotics and recent rediscovery due to antibiotic resistance. Key figures who discovered and explored phages and phage therapy include Ernest Hankin, Frederick Twort, and Félix d'Herelle.
2) It discusses how phage therapy works, involving using bacteriophages to treat bacterial infections. Advantages over antibiotics include phages' ability to self-replicate and adapt versus antibiotics being fixed molecules.
3) Problems that initially limited phage therapy are addressed, such as host range, bacterial debris in preparations, and lysogeny.
This document summarizes research on the plant pathogenic bacterium Pseudomonas syringae and one of its virulence factors, HrpZ1. Key findings include:
1) HrpZ1 is a type III secreted protein that can form ion-conducting pores in lipid membranes and trigger plant immune responses. However, pore formation and immune activation are separate functions localized to different domains.
2) The C-terminal domain of HrpZ1 is necessary and sufficient for binding to plant membranes and stimulating immunity responses, but not for pore formation.
3) Insertional mutations in the C-terminal domain disrupt HrpZ1's ability to activate immunity, suggesting this domain contains motifs recognized by plant
This document discusses multiple drug resistance (MDR) in bacteria. It begins by defining drug resistance and how bacteria can develop resistance through natural mechanisms or by acquiring resistance over time when exposed to antibiotics. The key points are:
- Bacteria can become resistant through mutations or gene transfer that make antibiotics unable to bind or enable the bacteria to destroy or pump out antibiotics.
- Multiple drug resistance (MDR) occurs when bacteria resist many different drug classes through various mechanisms like altered cell walls or target sites.
- Common MDR bacteria include MRSA, VRE, and ESBL-producing gram-negative bacteria.
- MDR-TB is also discussed, which is TB resistant to at least is
Anti-microbial resistance has become a world health issue today. Therefore it is imperative to know about the methods of acquiring resistance and ways to deal with the situation and prevent resistance.
Duane Duncan, Jeffrey Grierson and Garrett Prestage discuss social research findings on young gay men's sexual attitudes and behaviours, at the Young Gay Men's Symposium at Promises & Limitations, the CSRH social research conference, February 2014.
St. Paul, MN (August, 2010) – PerksCard Network, an Augeo Affinity Marketing company, is pleased to announce that Wilkes Barre VA Employees Association has become a new client.
This document provides an annual report summary for Jacobs Engineering Group for fiscal year 2003. It highlights increased revenues and record net income compared to previous years. It also summarizes Jacobs' continued focus on safety improvements, client satisfaction, and consistent growth. Jacobs' core values of relationship-based service, growth as an imperative, and its people as the greatest asset are also emphasized.
Dexion helped complete and commission a new cold storage facility in Brisbane, Australia called Murarrie 2 for P&O in time for the Christmas season. The modular design of the facility allowed for fast construction and staged completion to meet tight deadlines. Dexion workers installed racking systems while other areas were still under construction. The innovative design placed refrigeration units above the cold rooms to allow for easier maintenance and more storage capacity.
Highly skilled workforce, some of the best companies to work for in America, and world-class R&D make Rochester, NY an innovation hub. This presentation outlines more reasons to expand your business in the Greater Rochester, NY Region.
Serv-U: Secure File Transfer from SolarWindsSolarWinds
Learn how Serv-U can replace bulky attachments, insecure FTP servers and unreliable (or leaky) web sites, and then prepare you for tomorrow’s network and mobility changes.
Learn more about the major features of Serv-U:
• Virtual folders access local storage, remote shares or both.
• Granular control over bandwidth, storage, permissions, and access.
• Automatic account maintenance (reset password, disable after X days, etc.).
• File integrity checks (MD5, SHA1, SHA256, etc.).
• Support for many languages
EP Energy's flagship asset is the Eagle Ford shale play, where it has over 1,200 drilling locations. The company has optimized its operations in the Eagle Ford, lowering costs per well while increasing initial production rates and estimated ultimate recoveries. EP Energy is also expanding infrastructure like gathering lines and central production facilities to efficiently develop its Eagle Ford acreage.
England Logistics interview questions and answersnahhan45
This document provides materials and advice for interviews with England Logistics, including:
- Common interview questions and suggested answers focused on strengths, motivations for the role/company, knowledge of the company, why the applicant should be hired, and salary expectations.
- Tips for researching the company website, LinkedIn, and press releases to learn about the company's products, history, and culture without reciting every fact.
- Suggestions for questions applicants could ask the interviewer focused on development opportunities rather than salary or benefits.
- Links to additional resources on interview preparation, including types of interviews, thank you letters, and sample questions for different roles.
This document discusses the concept of "flat learning", which uses technology to connect classrooms globally and bring more of the world into the classroom. It describes flat learning as allowing discovery and engagement beyond physical classroom walls. Three key ingredients of going flat are identified: 1) Connection, which involves connecting learners through technologies and professional learning networks; 2) Citizenship, developing students' digital citizenship and global awareness; and 3) Collaboration, teaching and modeling collaborative skills. Going flat creates a holistic, inquiry-based blended learning environment through projects, challenges, and live events. The Flat Classroom concept aims to change pedagogy and education on a global scale.
The document is an affidavit from Jeffrey A. Schaffer, the Managing Member of Spectrum Group Management LLC, in support of a motion by petitioning creditors for the appointment of a Chapter 11 trustee in the bankruptcy cases of Allied Systems Holdings, Inc. and Allied Systems, Ltd. (L.P.).
Mr. Schaffer states that Spectrum is a lender under both the first lien and second lien credit agreements with Allied. He adopts statements from another affidavit in support of the motion. He attaches copies of the second lien credit agreement and several amendments as exhibits.
The summary provides an overview of the 2008 Annual Meeting of the Alumni Association of the North Carolina School of Science and Mathematics:
1) The meeting agenda included introductions of the Alumni Board members, a review of the past year's accomplishments, goals for the upcoming year, and an election for new board members.
2) Accomplishments from the past year included developing role documentation, recruiting new board members, contributing to the Campus Master Plan, and participating on the NCSSM Board of Trustees and Foundation Board.
3) Goals for the upcoming year focused on improving alumni communications, increasing alumni fundraising participation and amounts, and strengthening alumni involvement on campus through volunteering.
Sustainable Transport Practices in Canada:Exhortation Overwhelms DemonstrationBarry Wellar
Sustainable transport concepts appeared in Canadian publications more than 30 years ago, received extensive media coverage during the past three decades, and currently generate millions of ‘hits’ when expressed as keywords in Google searches of Canadian web sites. This country report establishes that governments, interest groups, professionals and citizens significantly affect the extent and rate that sustainable transport practices are achieved, or not, and uses nine best practices as the standard for measuring Canada’s record. The general finding is that despite an early alert about the need to adopt sustainable transport practices, and professed widespread support from citizens, politicians at all levels, and strong representations by alternative transport public interest groups, Canada has made minimal progress in achieving sustainable transport practices.
Este documento trata sobre el vitíligo y las vasculitis. Describe el vitíligo como una enfermedad de la piel que causa despigmentación debido a la muerte de células productoras de melanina. Explica tres teorías sobre su etiología y describe sus manifestaciones clínicas y tratamientos. También define las vasculitis como inflamación de vasos sanguíneos, discute su etiología, síntomas y tratamiento con esteroides, y clasifica los tipos según el tamaño de vaso afectado.
This notice announces a mortgage foreclosure sale of a property located at 5912 Millington Rd in Millington, MI due to default on a mortgage. The property will be auctioned on February 7, 2013 at the Tuscola County Courthouse. The notice provides details on the mortgage, terms of the sale, and contact information for the assignee of the mortgage, Flagstar Bank.
My Blue Community is a national health and wellness community for Blue Cross Blue Shield members - healthcare meets Facebook type social networking site.
This presentation was for the 9th World Health Care Congress in Washington DC, April 16 -18, 2012.
This document lists stores in Zone 16 by chain, including the store number, address, city, state, zip code, phone number, and sales metrics like cases rate and monthly rate. There are over 100 stores listed spanning Wisconsin, Illinois, Iowa, and Minnesota, belonging to chains like Roundy's Pick N Save, Woodman's, Festival Foods, Copps Food Center, and Hy-Vee.
4 Way Logistics provides several benefits for businesses needing shipping services:
1) They ask questions to fully understand customer needs and provide quotes within 60 minutes.
2) They research many carriers to find the best shipping option and have contracts with over 6,000 carriers.
3) They monitor carriers' credentials and insurance to minimize risks for valuable shipments.
Este documento es una colección de poemas titulada "Poemágenes" de Luis Tamargo. Consiste en poemas cortos dedicados a alguien y que describen escenas en lugares no especificados. El documento se identifica como una colección original de cuadernos con corazón.
The document summarizes systemic acquired resistance (SAR), a type of induced resistance in plants that confers broad-spectrum protection against pathogens. SAR is activated by initial infection, which triggers salicylic acid signaling and pathogenesis-related protein expression throughout the plant. Key regulators include NPR1, which is required for SAR, and salicylic acid, which is involved in long-distance signaling. SAR provides long-lasting resistance against bacterial, fungal, and viral pathogens.
The document discusses systemic acquired resistance (SAR), which confers long-lasting protection against a broad spectrum of pathogens. SAR is induced by initial infection and involves the signaling molecule salicylic acid, leading to accumulation of pathogenesis-related proteins throughout the plant. Key regulators of SAR include NPR1, which is required for SAR, and salicylic acid, which is involved in transmitting the defense signal systemically.
This document discusses rapid detection of multi drug resistant tuberculosis (MDR-TB). It begins with an introduction to tuberculosis, including prevalence, causative bacteria, types of infection, and emergence of MDR-TB. It then describes the molecular mechanisms of rifampicin and isoniazid resistance. The objectives are to rapidly detect tuberculosis using molecular methods like line probe assay and GeneXpert. The results found both tests had 99% sensitivity and 100% specificity. The conclusions state these tests provide results within hours, allowing faster treatment compared to conventional methods.
This study investigates the mechanisms underlying the serotype-specific differences in interferon induction between reovirus serotypes 1 (T1) and 3 (T3). T3 potently induces interferon responses through phosphorylation of interferon regulatory factor 3 (IRF3), whereas T1 is a poor inducer. The researchers generated single gene reassortant viruses between strains rsT1L and rsT3D to identify which viral genes are responsible for the differential IRF3 phosphorylation. Preliminary results indicate that IRF3 phosphorylation correlates with the L3, S1, and S3 gene segments from the rsT3D strain.
A novel marker, ARM58, confers antimony resistance to Leishmania spp.Carola Schäfer
This document describes the identification of a novel genetic marker, LbrARM58, that confers antimony resistance to Leishmania species. Using a functional cloning strategy with genomic DNA libraries from antimony-resistant and sensitive L. braziliensis clinical isolates, researchers repeatedly selected a region on chromosome 20. This region contains the gene LbrM20.0210, which when overexpressed increases resistance to antimony (SbIII) in L. braziliensis and L. infantum in vitro and enhances parasite survival inside macrophages under antimony pressure. LbrM20.0210 encodes a previously uncharacterized protein with four repeats of a domain of unknown function that is unique to the Leishmania genus.
Photorhabdus bacteria have a mutualistic relationship with nematodes, where they help the nematodes infect and kill insects. These bacteria produce bioluminescence, toxins, and other compounds that help overcome the insects' immune systems. While usually symbiotic with nematodes in insects, some Photorhabdus strains can also infect humans. The bacteria have evolved complex interactions with their hosts and produce many secondary metabolites worth studying for new drug development.
Mecanismos de resistencia del Streptococcus pneumoniaefranklinaranda
This document reviews the mechanisms of antibiotic resistance and tolerance in Streptococcus pneumoniae. It discusses how S. pneumoniae has developed three main mechanisms to resist antibiotics: preventing antibiotic access to targets, inactivating antibiotics, and altering antibiotic targets. Specifically, it describes how mutations in penicillin-binding proteins can reduce affinity for beta-lactam antibiotics like penicillin. It also explains how mutations in DNA gyrase and topoisomerase genes can confer resistance to fluoroquinolones by altering their targets. Recent studies on antibiotic tolerant mutants revealed new insights into controlling bacterial cell death.
Chlorogenic acid may be a potent inhibitor of dimeric SARS-CoV-2 main proteas...LucyPi1
Abstract Background: Since the emergence of coronavirus disease 2019 to date, there is no available approved drug or definitive treatment for coronavirus disease 2019 viral infection, and the identification of novel hits against therapeutic targets has become a global emergency. Echinacea purpurea is a traditional herb utilized to treat cough, fever, sore throat, respiratory tract infection, and so on as an immune stimulant. In this study, in silico molecular docking approach was used to screen phytocompounds from E. purpurea against severe acute respiratory syndrome coronavirus 2 main protease 3C-like protease (3CLpro) and severe acute respiratory syndrome coronavirus main peptidase (96% sequence similarity) to blunt the viral gene expression and viral replication. Methods: Initially, we screened phytocompounds for their druggability and ADMET property. Furthermore, x-ray crystallographic structures of main proteases 3CLpro and main peptidase having Protein Data Bank ID 6LU7 and 2GTB were used as protein targets for the identification of potential drug candidates. We performed docking using AutoDock Vina by PyRx 0.8 software. BIOVIA Discovery Studio Visualizer v2019 was used to analyze ligand-protein complex. The probable protein targets of the selected compound were predicted by BindingDB (P ≥ 0.7). STRING and Kyoto Encyclopedia of Genes and Genomes pathways are utilized to identify the molecular pathways modulated by the predicted targets (FDR ≤ 0.05), and the network interaction between compounds and protein pathways was constricted by Cytoscape 3.6.1. Results: Among all the compounds, chlorogenic acid showed druggable characteristics and scored the lowest binding energy with main protease and main peptidase via interacting with active site 1 domain amino acid residues. Interestingly, chlorogenic acid interacted with Phe140 main protease 3CLpro, which is potentially involved in the dimerization. Enrichment analysis identified chlorogenic acid to modulate insulin resistance, necroptosis, interleukin-17, tumor necrosis factor signaling pathway, legionellosis, T helper 17 cell differentiation, advanced glycation end products and receptor for advanced glycation end products, mitogen-activated protein kinase, Ras, estrogen, vascular endothelial growth factor, B-cell receptor, nuclear factor kappa B, Rap1, hypoxia inducible factor-1, phosphatidylinositide 3-kinase-Akt, insulin, mechanistic target of rapamycin, p53, retinoic acid inducible gene I like receptor, and ErbB signaling pathways. Conclusion: Chlorogenic acid may act as a potent main protease 3CLpro inhibitor and may also inhibit the severe acute respiratory syndrome coronavirus 2 dimerization, viral gene expression, and replication within the lung epithelium. Chlorogenic acid may go a long way in finding one of the multipronged solutions to tackle coronavirus disease 2019 viral infection in the future.
Role of Nonfermenting Gram-Negative Bacilli Responsible for Respiratory Tract...Premier Publishers
The majority of nonfermenting gram-negative bacilli are responsible for respiratory tract infections. The aims of this study are to identify the nonfermenting gram-negative bacilli species in respiratory tract infections, to describe their antibiotic resistance and to describe the factors associated with these bacteria. It is a prospective study of 54 respiratory samples for a period of six months from October 2019 to March 2020 in the laboratory of the University Hospital of Befelatanana Antananarivo. Among the 54 respiratory samples, the microbiological results showed 12 (22.2%) cases of nonfermenting gram-negative bacilli. These bacilli were represented by 7 (58.3%) cases of Acinetobacter baumannii, 4 (33.3%) cases of Pseudomonas aeruginosa and 1 (8.3%) case of Stenotrophomonas maltophilia. Concerning the associated factors, subjects under 40 years (24%) (p=0.77; NS), men (30.8%) (p=0.03) and subjects hospitalized in intensive care units (40.7%) (p=0.003) were the most affected by the nonfermenting gram-negative bacilli. Regarding antibiotic resistance, it varies from 71.4% to 100% for Acinetobacter baumannii and 0% to 100% for Pseudomonas aeruginosa. The Stenotrophomonas maltophilia isolate had a broad spectrum ß-lactamase but was sensitive to the other antibiotics. Nonfermenting gram-negative bacilli are responsible for severe nosocomial pneumonia and the majorities are multi-resistant bacteria.
Immuno microbial pathogenesis of periodontal diseaseGanesh Nair
The document provides an overview of the inflammatory response in periodontal disease. It discusses how bacterial virulence factors like lipopolysaccharide activate the host immune system through toll-like receptors and pro-inflammatory cytokines like IL-1β and TNF-α are released, leading to tissue damage. It also describes other microbial products like fimbriae, DNA, and enzymes that stimulate inflammation and host mediators that perpetuate the inflammatory response and cause bone resorption and tissue destruction.
This document discusses Staphylococcus aureus and antibiotic resistance. It analyzed 34 isolated S. aureus samples from a hospital in China. Antibiotic susceptibility testing found high resistance to erythromycin (95.2%) but no mutations conferring resistance to fusidic acid or mupirocin. Multilocus sequence typing of resistance genes identified mutations in genes related to macrolide and mupirocin resistance in 23 of 28 samples. The overuse of antibiotics is increasing resistance, demonstrating the need for prudent antibiotic use and resistance monitoring to preserve treatment options.
COMPUTER AIDED PERSPECTIVE OF SELECTION OF PLANTS AGAINST VIRUSESManik Ghosh
This document discusses using computer-aided docking studies to select plants that may contain compounds effective against viruses. Key points:
1) Docking studies of phytochemicals from 20 plants against protein targets of influenza, dengue, HIV, and chikungunya viruses identified compounds like flavonoids, curcumin, and gallic acid that gave good docking scores and estimated inhibition constants, suggesting potential antiviral activity.
2) This rational in silico approach could help medicinal chemists more efficiently explore natural products for antiviral leads without random plant selection.
3) Some compounds identified in the docking studies like curcumin, quercetin, and gallic acid were
Application of phage typing and pulsed-field gel electrophoresis to analyse Salmonella enterica isolates from a suspected outbreak in Lagos, Nigeria
Kabir O. Akinyemi et al
Pathogenesis-related proteins (initially named “b” proteins) were discovered in tobacco leaves
hypersensitively reacting to TMV by two independently working groups (Van Loon and Van Kammen,
1970; Gianinazzi et al., 1970)
Covid 19 menace to mankind & covid 19 coronavirusSARVJEET SHARMA
The document summarizes information about coronaviruses and COVID-19. It discusses that coronaviruses are small RNA viruses that infect humans and other animals. Seven human coronaviruses have been identified so far, including SARS-CoV-2 which causes COVID-19. COVID-19 spreads mainly from person to person and causes respiratory illness. While most cases are mild, some can progress to acute respiratory distress. There is currently no approved vaccine but many are in development worldwide using approaches like viral vectors and protein subunits.
Biotechnology and disease management with special reference toSarda Konjengbam
Plant biotechnology can be defined as the use of tissue culture and genetic engineering techniques to produce genetically modified plants that exhibit new or improved desirable characteristics.
PLANT BIOTECHNOLOGY HELPS PLANT PATHOLOGY IN MANY WAYS.
1. The document summarizes biomedical research activities at the Ifakara Health Institute (IHI) in Tanzania, including past and current laboratory-based research in malaria, tuberculosis, HIV, and other infectious diseases.
2. Key areas of research mentioned include monitoring anti-malarial drug resistance, evaluating malaria vaccines and biomarkers, population genetics of malaria vectors, and molecular monitoring of HIV drug resistance.
3. Future research directions discussed are non-communicable diseases, genetic determinants of infectious diseases, mapping and characterizing pathogens/emerging pathogens, drug efficacy monitoring, gene expression profiling, diagnostic development, and understanding pathogen co-infections. The document highlights strengths like laboratory facilities, clinical trial platforms,
Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Correlation of Estrogen and Progesterone Receptor expression in Breast Canceriosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...iosrphr_editor
The current study was carried out in District Abbottabad aimed to determine the common urinary
tract infections in local community to determine the epidemiology of significant diseases in asymptomatic patients
of renal disorder. In this study a total of 1000 urine samples were examined during 3rd February to 1st April 2015
from patients attending Ayub Teaching Hospital Abbottabad by using dipstick and microscopic analysis of urine.
There were 638 females and 362 males patients examined during this period. The range of age groups is between
1.5 years to 80 years. Results of this study was reported as Pyuria 11%, Proteinuria 21.1%, Hematuria 10.4%,
Epithelial Cells 8.2%, pH 7.8 %, Granular casts 7.3%, Triple phosphate 6.6%, Calcium oxalate 6.4%, Glycosuria
6.3%, Bacteria 6.2% and mucous 4.1%. This study concludes that routing urinalysis should be performed for all
individuals to diagnose the asymptomatic diseases that will help in simple therapeutic measurements as urinalysis
is a simple step to determine the root of Urinary tract disorders.
Chest sonography images in neonatal r.d.s. And proposed gradingiosrphr_editor
BACKGROUND : Lung sonography has been used to monitor the patients of R.D.S. in
N.I.C.U. in recent times.
AIMS : To Describe and Grade the changes of R.D.S. by lung sonography.
SETTING & DESIGN : Tertiary care institutional set up in a rural medical college.
STUDY DURATION : September 2014 to May 2015. Follow-up variable, upto 2 weeks.
PROSPECTIVE, ANALYTICAL STUDY.
MATERIALS AND METHODS -This was a single institute study approved by the institutional ethics
committee. Prior informed consent was obtained from the parents. 100 consecutive patients admitted in
N.I.C.U. WITH gestational age < 36 weeks with respiratory complaints were enrolled. Chest x-ray was
obtained within few hours of admission and lung sonography was performed within 24 hours. Follow – up
sonography was performed as and when necessary. Sonography image was graded and correlated with chest
xray and clinical picture
The Comprehensive Review on Fat Soluble Vitaminsiosrphr_editor
This review article deals with brief description of fat soluble vitamins with figures and tables
showing statistical analytical data duly quoting the references wherever necessary. The word “soluble” actually
means “able to be dissolved.” Whether a vitamin is classified as 'fat-soluble' or 'water-soluble' has to do with
how the vitamin is absorbed, stored and removed from the body. Vitamins are tiny organic compounds with a
huge impact on the health and well-being of the body. The body needs a small amount of fat soluble vitamins in
order to stay in optimal health. Fat soluble vitamins play an important role in keeping the body healthy and
functioning from immune system and muscle and heart function, easy flow and clotting of blood as well as eye
health. They are critical to health and wellness–particularly reproductive health and wellness. Low-fat, no-fat
and vegan diets are woefully lacking in fat soluble vitamins. However a diet based on traditional foods can
naturally provide these vitamins. Science is still learning about many of the functions of vitamins. "Too much
vitamin A, D, or K can lead to increased levels that are unhealthy and can cause serious health consequences.
Diseased conditions leading to decreased fat absorption leads to decreased absorption of vitamins. The fatsoluble
vitamins work most safely and effectively when obtained them from natural foods within the context of a
diet rich in all their synergistic partners. If fat soluble vitamins are stored for lengthy time they generate threat
for toxicity than water soluble vitamins and such situation even aggravated, provided they are consumed in
excess. Vitamin products, above the legal limits are not considered food supplements and must be registered as
prescription or non-prescription (over-the-counter drugs) due to their potential side effects. Vitamin A and E
supplements do not provide health benefits for healthy individuals, instead they may enhance mortality, and it is
held proved that beta-carotene supplements can be harmful to smokers
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Reportiosrphr_editor
The document describes a case study of an 18-year-old female patient who developed toxic epidermal necrolysis as a severe adverse reaction to the drug sulfasalazine, which she had been taking for ankylosing spondylitis. She was admitted to the intensive care unit and treated with high dose corticosteroids, fluid replacement, and supportive care. She improved with treatment and was discharged with only post-inflammatory hypopigmentation.
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborniosrphr_editor
Hemolytic disease of newborn (HDN) is an important cause of hyperbilirubinemia in the
neonatal period,and delayed diagnosis and treatment may lead to permanent brain damage. Traditional
neonatal treatment of HDN is intensive phototherapy and exchange transfusion.Intravenous
immunoglobulin(IVIgG) has been introduced as an alternative therapy to exchange transfusion. This study was
conducted to assess the effect of IVIG in HDN .
FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.iosrphr_editor
Nervous fibrolipomatous hamartoma is said to be a rare tumor-like condition involving the peripheral
nerves,in which the epineurium and perineurium are enlarged and distorted by excess of fatty and fibrous tissue
s that infiltrate between and around nerve boundaries. The median nerve is more likely to develop a hamartoma
than other nerves with a predilection for the carpal tunnel.
A fibrolipomatous hamartoma – is a rare, benign, congenital lesion most commonly found in the median nerve,
usually at the level of the wrist or hand.
We report a case of this rare condition in ulnar nerve.
SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...iosrphr_editor
This study examined self-medication practices for oral health problems among dental patients in Bangalore, India. The study found that 100% of the 175 dental patients surveyed practiced self-medication. Toothache was the most common triggering factor reported. Analgesics and herbal remedies were commonly used for self-treatment. Most participants consulted pharmacists for advice on self-medication and would see a dentist only if problems persisted after self-medicating. The high prevalence of self-medication indicates a need for education programs to increase awareness of risks.
Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...iosrphr_editor
Aim: To study the clinico-haematological profile malaria in a rural hospital of Tripura.
Material and methods: A cross-sectional hospital-based study was done from at Kulai District
Hospital,Tripura. This hospital based cross sectional study was done on 60 confirmed cases of falciparum
malaria (either by peripheral smear or rapid diagnostic test) admitted in Kulai District Hospital. A case sheet
proforma was prepared and data (demographic profile,clinical feature, investigation, treatment, and
complication) from all indoor patients was collected and analyzed.
Result: Out of 60 patients, 40(66.6%) were males and 20 (33.4%) were females. Most of the patients were
between the age group 21-40 years with the highest prevalence between the age group of 21-30. Fever was the
most common symptom. Anemia was present in 42(70%) patients, out of which 6(10%) patients had severe
anemia. Thrombocytopenia was present in 36(60%) patients.Abnormal liver function tests were observed in
26(43.3%) subjects while abnormal kidney function tests were observed in16(26.6%) patients. All the 60
patients received Artemisinin based antimalarial drugs.
Conclusion: Early detection, prompt management, and adequate supportive therapy may reduce mortality due
to falciparum cerebral malaria.
Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...iosrphr_editor
The document summarizes a study that tested the antibacterial activity of extracts from three species of wild ginger plants from Indonesia (Zingiber zerumbet, Zingiber amaricans, and Zingiber aromaticum) against Mycoplasma gallisepticum, a pathogen that causes respiratory disease in chickens. Phytochemical analysis revealed the presence of alkaloids, flavonoids, tannins, and terpenoids in the plant extracts. Disc diffusion and minimum inhibitory concentration assays showed that ethanol extracts of dried rhizomes had the strongest inhibitory effects against the pathogen, with minimum inhibitory concentrations ranging from 7.8 to 31.2 mg/ml. The results suggest that extracts from these wild ginger plants
A case of allergy and food sensitivity: the nasunin, natural color of eggplantiosrphr_editor
Abstract: Allergies and food sensitivities can both be considered as "adverse reactions individualistic" to food.
Are pathological and individual forms because they affect a few individuals in way rather serious; immediate
or delayed reactions occur instead with simple effects histamine, or, in severe cases with respiratory and
anaphylactic shock
The eggplant (Solanum melongena L.) is known to cause food allergies in some Asian countries, but detailed
studies on allergies caused by eggplant are lacking, however, it was highlighted the presence of allergens in
edible parts of eggplant with preponderance in the peel .
The purpose of this study was to propose an extraction method rapid, efficient and cost of natural dye from
waste products from the food industry, such as the peels of eggplant, from which it was extracted, isolated and
purified the nasunin,a colored molecule in red-fuchsia.
Nasusin was tested on 58 patients to evaluate the potential sensitizing effect on the skin. The results demonstrate
that allergenic effects are negligible and therefore the nasunin can be used as a colorant in various industrial
sectors with a certain safety margin
Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...iosrphr_editor
NMR analysis allowed complete assignments of three known mogrol glycosides, Mogroside IIA2 (1),
II E (2)and IIIA1 (3), isolated from the extracts of Luo Han Guo. Herein, complete 1H and 13C NMR
assignmentsof all threemogrosidesare described based on NMR experiments (1H NMR, 13C NMR, COSY,
HSQC-DEPT, HMBC, NOESY and 1DTOCSY) and mass spectral data.
Nanoemulsion and Nanoemulgel as a Topical Formulationiosrphr_editor
: Nanoemulsion is referred type of emulsion with uniform and extremely small droplet size in the range
of 20-200 nm. Nanoemulsion provides numerous advantages over other carrier such as polymeric nanoparticle
and liposomes, including low cost preparation procedure, high hydrophilic and lipophilic drug loading system
to enhance the longer shelf live upon preserving the therapeutic agents. Incorporating the preparation of
nanoemulsion with hydrogel matrix to produce nanoemulgel exhibited by the two separate systems that forming
it. Nanoemulgel possesses the properties of thixotropic, non-greasy, effortlessly spreadable, easily be removed,
emollient, not staining, soluble in water, longer shelf life, bio-friendly, translucent and agreeable appearance.
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...iosrphr_editor
Aim:Since several factors have been shown to influence the clearance of methotrexate, the purpose of this study
was to identify potential relationships between patient covariates and the methotrexate clearance estimates and
deduce a pharmacokinetic model for the estimation of methotrexate clearance in Egyptian pediatric ALL
patients that may help dosage adjustment and achieve target steady-state plasma concentrations in a similar
sittings.
Patients and methods: A total of 94 pediatric patients with B-cell ALL, of whom 70 were the studied population
and 24 were the test population, were treated with four courses of HDMTX doses 2.5 gm/m2
(low-risk arm) or 5
gm/m2
(standard-/high-risk arm) given every other week by intermittent intravenous infusions over 24 hours as
a part of their treatment protocol. Patients were monitored for the 24 hour MTX concentration and the systemic
methotrexate clearance was calculated for each methotrexate dose
Epidemiology of Tuberculosis (TB) in Albania 1998-2009iosrphr_editor
Abstract : In Albania, many people erroneously think that tuberculosis (TB) is a disease of the past-an illness
that no longer constitutes a public health threat. Surveillance is an integral part of tuberculosis (TB) control.
Albania has a highTB notification rate and there are doubts about underreporting. The evolution of the
incidence of tuberculosis is presented, together with more detailed figures over the period 1998-2009. These
figures were obtained by the monthly forms (called 14/Sh) compared with the individual notification data.
Objective: To examine the distribution and sources of increased tuberculosis (TB) morbidity and reporting
system deficiencies in the Albania from 1998 through 2009. Metodology: The study is descriptive one conductet
during the period 1998-2009. The statistical analysis is based on data reported from regional level (regional
epidemiological departments) to the central level (Public Health Institute). Results: The main findings were:
discordance between the collected data (individual form) and reported data (monthly form); tuberculosis
incidence rate shows little oscillations which ranges from 6.67 to 9.2 cases/100.000 population; 50% of the
regions show a lack of information on the confirmation of diagnosis and laboratory examination type used for
confirmation. Conclusion: TB disease in high-risk populations where it is difficult to detect, diagnose, and treat;
limitations of current control measures and the need for new tests and treatments, including an effective
vaccine; improving information system, regulation of individual form and personnel training.
Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...iosrphr_editor
Study on total phenol and antioxidantactivity ofsugar apple fruits of various solvent, part of fruits, and level of ripening. Solvent extraction used were 80% (v/v) methanol, 50% (v/v) acetone, boiling water, and 50% (v/v) ethanol. Part of fruits thatbeen used for samples were seed and peel which are normally by products of sugar apple processing, level of ripening were unripe, and ripe sugar apple fruits. Total phenol was determined by Folin-ciocalteau method. Total antioxidant was quantified by 1,1-diphenyl-2-picrylhydrazyl(DPPH) method.Therewas a difference in type of solvent, part of fruits, and level of ripeningon total phenol and antioxidant concentration of sugar apple fruits. Seeds have higher total phenol concentration than peels of this fruits. Unripe sugar apple fruits have higher total phenol and antioxidant than ripe fruit. The best solvent for phenol extraction was ethanol 50%butthe best solvent for antioxidant extraction was acetone 50%.
A Review on Step-by-Step Analytical Method Validationiosrphr_editor
When analytical method is utilized to generate results about the characteristics of drug related samples it is essential that the results are trustworthy. They may be utilized as the basis for decisions relating to administering the drug to patients. Analytical method validation required during drug development and manufacturing and these analytical methods are fit for their intended purpose. To comply with the requirements of GMP pharmaceutical industries should have an overall validation policy which documents how validation will be performed. The purpose of this validation is to show that processes involved in the development and manufacture of drug, production and analytical testing can be performed in an effective and reproducible manner. This review article provides guidance on how to perform validation characteristics for the analytical method which are utilized in pharmaceutical analysis.
A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...iosrphr_editor
Non-steroidal anti-inflammatory drugs are the most widely used "over the counter" medication all over the world despite their complications in different major organs. Present studies envisaged for knowing the occurrence and severity of adverse drug reactions from NSAIDs in different ethnic communities of Sikkim. A cross sectional study was undertaken in the medicine outpatients department of a secondary and tertiary care hospital. The patients belonging to Nepalese, Bhutias, Lepchas ethnic communities and others community (settlers from other parts of India) were included to analyzed the data based on the age and gender, ethnicity and ADRs, drugs and ADRs. Severity assessment was done using Hartwing and Siegel scale and causality assessment by Naranjo scale. Total 109 cases of ADRs, predominating in female were detected. Nepalese were the most affected and Gastrointestinal tract (GIT) being the most affected organ in them. Diclofenac showed maximum number of ADRs in all the communities. Maximum number of cases occurred on single day use (40.36%) of drugs. All the cases were belonging to the "possible category" and the maximum being the mild (72.48%) in nature. It is advisable to consider the ethnic/racial differences equally with other factors, to improve the safety and efficacy of a drug.
Climate Impact of Software Testing at Nordic Testing DaysKari Kakkonen
My slides at Nordic Testing Days 6.6.2024
Climate impact / sustainability of software testing discussed on the talk. ICT and testing must carry their part of global responsibility to help with the climat warming. We can minimize the carbon footprint but we can also have a carbon handprint, a positive impact on the climate. Quality characteristics can be added with sustainability, and then measured continuously. Test environments can be used less, and in smaller scale and on demand. Test techniques can be used in optimizing or minimizing number of tests. Test automation can be used to speed up testing.
Infrastructure Challenges in Scaling RAG with Custom AI modelsZilliz
Building Retrieval-Augmented Generation (RAG) systems with open-source and custom AI models is a complex task. This talk explores the challenges in productionizing RAG systems, including retrieval performance, response synthesis, and evaluation. We’ll discuss how to leverage open-source models like text embeddings, language models, and custom fine-tuned models to enhance RAG performance. Additionally, we’ll cover how BentoML can help orchestrate and scale these AI components efficiently, ensuring seamless deployment and management of RAG systems in the cloud.
How to Get CNIC Information System with Paksim Ga.pptxdanishmna97
Pakdata Cf is a groundbreaking system designed to streamline and facilitate access to CNIC information. This innovative platform leverages advanced technology to provide users with efficient and secure access to their CNIC details.
Monitoring and Managing Anomaly Detection on OpenShift.pdfTosin Akinosho
Monitoring and Managing Anomaly Detection on OpenShift
Overview
Dive into the world of anomaly detection on edge devices with our comprehensive hands-on tutorial. This SlideShare presentation will guide you through the entire process, from data collection and model training to edge deployment and real-time monitoring. Perfect for those looking to implement robust anomaly detection systems on resource-constrained IoT/edge devices.
Key Topics Covered
1. Introduction to Anomaly Detection
- Understand the fundamentals of anomaly detection and its importance in identifying unusual behavior or failures in systems.
2. Understanding Edge (IoT)
- Learn about edge computing and IoT, and how they enable real-time data processing and decision-making at the source.
3. What is ArgoCD?
- Discover ArgoCD, a declarative, GitOps continuous delivery tool for Kubernetes, and its role in deploying applications on edge devices.
4. Deployment Using ArgoCD for Edge Devices
- Step-by-step guide on deploying anomaly detection models on edge devices using ArgoCD.
5. Introduction to Apache Kafka and S3
- Explore Apache Kafka for real-time data streaming and Amazon S3 for scalable storage solutions.
6. Viewing Kafka Messages in the Data Lake
- Learn how to view and analyze Kafka messages stored in a data lake for better insights.
7. What is Prometheus?
- Get to know Prometheus, an open-source monitoring and alerting toolkit, and its application in monitoring edge devices.
8. Monitoring Application Metrics with Prometheus
- Detailed instructions on setting up Prometheus to monitor the performance and health of your anomaly detection system.
9. What is Camel K?
- Introduction to Camel K, a lightweight integration framework built on Apache Camel, designed for Kubernetes.
10. Configuring Camel K Integrations for Data Pipelines
- Learn how to configure Camel K for seamless data pipeline integrations in your anomaly detection workflow.
11. What is a Jupyter Notebook?
- Overview of Jupyter Notebooks, an open-source web application for creating and sharing documents with live code, equations, visualizations, and narrative text.
12. Jupyter Notebooks with Code Examples
- Hands-on examples and code snippets in Jupyter Notebooks to help you implement and test anomaly detection models.
In the rapidly evolving landscape of technologies, XML continues to play a vital role in structuring, storing, and transporting data across diverse systems. The recent advancements in artificial intelligence (AI) present new methodologies for enhancing XML development workflows, introducing efficiency, automation, and intelligent capabilities. This presentation will outline the scope and perspective of utilizing AI in XML development. The potential benefits and the possible pitfalls will be highlighted, providing a balanced view of the subject.
We will explore the capabilities of AI in understanding XML markup languages and autonomously creating structured XML content. Additionally, we will examine the capacity of AI to enrich plain text with appropriate XML markup. Practical examples and methodological guidelines will be provided to elucidate how AI can be effectively prompted to interpret and generate accurate XML markup.
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1. IOSR Journal of Pharmacy
(e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219
www.iosrphr.org Volume 4, Issue 1 (January 2014), Pp 12-19
Characterization of StyR-234 non-coding RNA in regulation of
Multi-drug resistance in Salmonella enterica serovar typhi
Siventhiran Balakrishnan1, Sheryna Kaur1, Kishan raj1, Sunitha Paripelli2,
Sathyanarayana Namani2, Suresh V. Chinni 2
1
Faculty of Applied Sciences, AIMST University, 08100, Bedong, Kedah.
2
Faculty of Medicine, AIMST University, 08100, Bedong, Kedah.
ABSTRACT: Non-protein coding RNAs (npcRNA) have been recently recognized in bacterial pathogens as a
new group to regulate multi-drug resistance. Among several pathogenic bacterial spcecices, Salmonella
enterica serovar Typhi (S. typhi) one of the focusing target in order to prevent severe impact in human health
and it pose a problem by causing high fever. we report the characterization of StyR-234, a small antisense
npcRNA, discovered from Salmonella typhi. StyR-234 is located on positive strand and antisense to, bacA gene.
Since bacA is known to participate in MDR, we hypothesis StyR-234 is involve in bacA regulation thus could
have role in drug resistance in S. typhi. Overexperssion analysis show that S. typhi became more susceptible to
six antibiotics (Amikacin, Cefepime, Trimethoprim Sulphamethoxazole, Imipenem, Meropenem, Piperacillin
Tazobactam) while more resistance to two antibiotics (Ampicillin and Cefotaxime). And no changes in
sensitivity for three antibiotics (Ciprofloxacin, Clindamycin and Ceftazidime). The results indicated that StyR234 increasing susceptibility to many antibiotics could be by down regulating antibiotic resistant gene bacA.
KEYWORDS: StyR-234; overexpression; drug resistance; S. Typhi
I.
INTRODUCTION
Salmonella is categorised under the genus of Enterobacteriaceae that fall in the group of enteric
bacteria. They have been very well-studied with respect to virulence mechanisms, microbial pathogenesis,
evolution of the genome and many fundamental pathways of gene expression and metabolism. Based on DNA
sequences, the Salmonella genus could be categorized into two species, S. enterica and S. bongori, which are
further subdivided into subspecies and serovars (>2500 serovars). Salmonella enterica serovar Typhi (from here
we will refer to as S. typhi), is a Gram negative human specific pathogen causing enteric typhoid fever, an acute
life-threatening febrile illness that affects the reticuloendothelial system. According to World Health
Organisation (WHO), 16-33 million cases and 500,000-600,000 deaths are reported around the world annually13
. S. typhi is characterized by its flagellar antigen H, its lipopolysaccharidic O antigen and, in addition, it’s PS
capsular Vi (for virulence) antigen, found at the surface of freshly isolated strains. One of the key features of S.
typhi is its invasive nature and restriction to human host only. The human host restriction has inhibited direct
studies of pathogenicity of S. typhi. Thereby most of the understanding of S. typhi has been achieved from
comparative research with its closer serovar, S. typhimurium, the mouse model. One of the foremost obstacles to
administering effective treatment against Salmonella infection is antibiotic resistance among disease causing
strains4. The emergence of multidrug resistance (MDR) isolates to all first line drugs such as chloromphenicol,
trimethoprim, sulphamethoxazole and ampicillin simultaneously has led to large epidemics and complicated the
management of this serious disease5.
The emergence of ESBL producers along with multidrug-resistant (MDR) isolates poses a serious
problem in the hospital settings6. Although there are new agents within existing classes of antimicrobials,
currently there are no new classes of antimicrobials in the later phases of development with activity against
MDR bacteria7. A major challenge in achieving their eradication is a better understanding of bacterial
pathogenesis processes8. RNAs are also emerging as regulators, enabling the pathogen to adapt its metabolic
needs during infection and to express its virulence genes when required.
There are two types of RNA molecules which are expressed in a cell: messenger RNAs (mRNAs) and
non-protein-coding RNAs (npcRNAs). The first type provides templates for protein synthesis and the second
does not encode proteins but rather exerts various functions at the level of RNA itself. In bacteria, npcRNAs
mostly function as coordinators of adaptation processes in response to environmental changes, integrating
12
2. Characterization of StyR-234 non-coding RNA in...
environmental signals and controlling target gene expression 9-11. During recent years, experimental RNomics
revealed the involvement of a number of npcRNAs in the pathogenesis of different virulence bacteria including
Staphylococcus aureus, Streptococcus pyogenes, Clostridium perfringens, Salmonella typhimurium, Vibrio
cholerae, Pseudomonas aeruginosa12-28.
Multidrug resistance in Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid
fever remains a global health concern especially in developing countries where inadequate water supply and
improper sanitation is prevalent. The emergence of Multidrug Resistant (MDR) strain [defined as strains that
confers resistance to all three first line antimicrobials] in late 1980’s caused the switching from this first line
antimicrobials to fluoroquinolones (FQs) as its primary therapy29. However, extensive usages of FQs have led to
treatment failure which in turn, brought expanded- spectrum cephalosporins and macrolides as the alternative
drugs for the treatment of typhoid fever 30. Unfortunately, there are also reports of few S. Typhi strains, with
extended-spectrum β-lactamases exhibiting resistance to cephalosporin 31,32, which makes the situation even
worst and therefore creates the need to reveal the molecular basis of this phenomenon.
Hitherto, many studies have been conducted to understand the molecular mechanisms underlying
bacterial intrinsic resistance but they were largely focussed on regulation at the gene and protein level which is
mediated by gene operons or other transcription factors33,34. Findings from these studies show that increased
efflux pump expression 35,36, target gene mutation37-40 and plasmid-mediated resistance41-43 are the major
contributors of drug resistance in Salmonella. As a consequence, very few studies were devoted to understand
the roles of newly discovered class of gene expression regulators such as non-protein coding RNAs (npcRNAs)
in mediating drug resistance44. The npcRNAs, which are also widely known as small RNAs (sRNAs), are short
RNA molecules that ranges between 50 – 300 nucleotides in length45 and do not get translated into proteins.
There are increasing evidences that show potential role of this group of RNAs in mediating bacterial drug
resistance. For an example, the overexpression of a sRNA called DsrA caused multidrug resistance in
Escherichia coli by regulating the expression of MdtEF drug efflux pump46. Besides that, MicF and MicC
sRNAs are shown to regulate drug resistance by controlling the expression of bacterial outer membrane proteins
OmpF and OmpC respectively47-49.
Interestingly, in a recent work by our group which identified 97 novel npcRNA candidates from the transcriptome
of S. Typhi50, we postulated that one particular candidate called StyR-234 could be involved in the regulation of the
pathogens’ drug resistance mechanism. This postulation was made based on the genomic localization of this candidate
antisense to the gene which encodes undecaprenyl pyrophosphate phosphatase; a recognized antibiotic resistant protein.
Previous studies show that Simultaneous inactivation of bacA, ybjG, and pgpB is lethal in E. coli. Therefore, this prompted
us to study the effect of StyR-234 overexpression on the development of drug resistance phenotype of S. Typhi.
II.
MATERIALS AND METHODS:
Conservation analysis and multiple alignments: The sequence conservation of StyR-254 sequence was
analyzed using NCBI-BLAST and aligned using CLUSTALW software.
Bacterial strains, plasmids and growth conditions – Bacterial strains and plasmids used in this study are
listed in Table 1. Bacterial strains were grown at 37⁰C in Luria- Bertani (LB) broth or agar. Ampicillin (100µg/
ml) were added when required.
Expression analysis of StyR-234
StyR-234 coding sequence was PCR amplified from the genomic DNA of S. Typhi using the primers
listed in Table 2, which introduced XbaI and HindIII sites at the ends of the amplified fragment. This fragment
was cloned between XbaI and HindIII sites of PCR 2.1 TOPO Cloning vector (Invitrogen) to produce plasmid
pStyR234. To over-express StyR-234, pStyR254 was transformed into S. Typhi via heat-shock.
Transformation of bacteria: Competent cells of S. Typhi were prepared using 1M calcium chloride. The
plasmids PCR 2.1 TOPO vector and pStyR234 were separately transformed in to S. Typhi competent cells by
giving heat-shock at 42⁰C for 45 seconds. The resulted bacteria were screened by growing on antibiotic plates
and PCR. The resulted strains named as ST001+pEmp and ST001+pStyR234.
Induction of gene and harvestion the cells: Bacteria strains (S. Typhi ST001, S. Typhi ST001 + pStyR234)
were grown in LB broth at 37⁰C, shaking at 200 rpm. Ampicillin (100µg/ ml) and 1mM IPTG (Isopropyl-β-Dthiogalactopyranoside) were added to induce the gene. Cells (S. Typhi + pStyR234) were induced at different
phases and harvested at different phases by centrifugation as follows. Cells induced at lag phase and harvested
13
3. Characterization of StyR-234 non-coding RNA in...
at two growth stages, exponential and stationery; cells were induced at exponential phase and harvested at
stationery; cells were induced immediate after inoculation and harvested at stationery;
RNA extraction and Northern blot analysis: Total RNA was extracted using Trizol reagent (Invitrogen),
according to the manufacturer’s instructions. The extracted total RNA was used for Northern blot analysis for
StyR-234 npcRNA expression study. Total RNAs (10 µg) were fractionated electrophoretically in 8%
Polyacrylamide-7M Urea gels and electrotransferred through semi-dry transfer onto positively charged nylon
membranes (Ambion). StyR-234 oligonucleotide was labelled at the 5’-end with 32P using T4- polynucleotide
kinase. The membranes were hybridized with the labelled oligonucleotide in Northern hybridization buffer
(Sodium dodecyl sulfate, Na2HPO4 and NaH2PO4) at 58⁰C overnight and washed with northern washing buffer.
The membranes were then exposed to Kodak MS-1 film for 1-3 days.
Disk diffusion assay – In order to determine the phenotypic effect of StyR-234 overexpression, antibiotic
susceptibilities were determined for S. Typhi ST001, S. Typhi ST001 + pStyr254 and S. Typhi ST001 + pEmp
using Kirby Bauer disk diffusion method. The test was performed according to the CLSI guidelines.
Commercially available antibiotic disks that were used in this test include Ampicillin (10 µg), PiperacillinTazobactam (10 µg), Amikacin (30 µg), Ciprofloxacin (5 µg), Cefepime (30 µg), Cefuroxime (30 µg),
Ceftazidime (30 µg), Trimethoprim Sulphamethoxazole (25 µg), Meropenem (10 µg), Clindamycin(2 µg) and
Imipenem (10 µg). Escherichia coli ATCC 25922 was utilized as the control for potency of antibiotic disks.
III.
RESULTS AND DISCUSSION
Conservation analysis of StyR-234:
In our previous study Chinni et al., StyR-234 was reported as a antisense npcRNA (Fig1). In order to
understand the conservation, we performed a BLAST analysis, which proved that StyR-234 sequence is
conserved in all Salmonella with percentage of identities ranging from 99% to 100%. A sequence alignment
showing the conservation of StyR-234 sequence is presented in figure 2. StyR-234 is conserved in many of
Gram negative bacteria with the range of 70% to 100%. Interestingly it is also conserved in Gram positive
bacteria with significant percentage (~60%-70%) of identities. The fact that this sequence is conserved in Gram
positive and Gram negative further suggests that it could exert crucial roles in their metabolism; besides having
potential role in regulating multi-drug resistance cascade.
3213563
3213774
3213887
bacA
StyR-234
Figure1: Genomic location of StyR-234 in Salmonella Typhi ty2 genome.
14
3214384
4. Characterization of StyR-234 non-coding RNA in...
Figure 2: Conservation analysis of StyR-234 sequence in among Salmonella enterica subspecies enterica and
arizonae. The species or strain name from the top are Salmonella enterica subspecies enterica serovars Typhi
ty2, Typhi Ct18, Paratyphi B, Chleraesius, Paratyphi A, Dublin, Enteritidis, Cubana, Newport, Typhimurium,
Heidelberg, Agona, Bovismorbificans, Gallinarium. The last one is the Salmonella enterica subspecies arizonae.
Cloning and over- expression of StyR-234 in S. Typhi ST001
To evaluate the effect of StyR-234 overexpression in the regulation of S. Typhi’s MDR cascade,
pStyR234 plasmid containing the StyR-234 sequence, was transformed into S. Typhi ST001 cells via heatshock. Total RNA was extracted from 1) S. Typhi ST001 2) S. Typhi ST001 + pStyR234 (uninduced), 3) S.
Typhi ST001 + pStyR234 (induced at lag and harvested at stationery) 4) ) S. Typhi ST001 + pStyR234 (induced
at exponential and harvested at stationery) 5) S. Typhi ST001 + pStyR234 (induced at lag and harvested at
exponential)and 6) ) S. Typhi ST001 + pStyR234 (induced immediate after inoculation and harvested at
stationery). Northern analysis was performed to compare the expression level of StyR-234 in the
aforementioned samples. As shown in fig 3, StyR-234 is not expressed in exponential phase of S. Typhi ST001,
as it expressed only during stationery phase with normal growth conditions. This suggests that StyR-234 could
be a growth-phase-dependent npcRNA, which is probably required for the survival of ST001 under nutrient
depletion condition.
Interestingly, in the presence of pStyR3, ST001 displayed differential expression of StyR-234;
increasing from un-induced to induced,hence, indicated that that the cloning was successful. Apparently, it was
evident that the expression of StyR-234 was higher in all growth stages of pStyR234-transformed recombinant
ST001 cells upon induction with IPTG compared to the uninduced samples. Interestingly, we noted that the
growths of the control cells were also very slow compared to the pStyR3 containing recombinant ST001 cells.
This was probably due to the addition of IPTG to the empty vector which could have become toxic to the cell.
Overall, the Northern blot result demonstrated that we have successfully cloned and overexpressed the StyR-234
npcRNA
in
ST001.
15
5. Characterization of StyR-234 non-coding RNA in...
Figure 3 Northern analyses of StyR-234 npcRNA, at different growth stages of S. Typhi ST001 clinical strain
and pStyR234-transformed recombinant ST001 strain. Fron left to right, first lane is the S. Typhi ST001 clinical
strain exponetial phase, second lane (S. Typhi+234) is the exponential phase of S .Typhi transformed with
pSTyR234. Third lane is the S. Typhi transformed with pStyR234 and induced with IPTG at lag phase and
harvested at stationery phase. Fourth lane is the S. Typhi transformed with pStyR234 and induced with IPTG at
exponetial phase and harvested at stationery phase. Fifth lane (S.Typhi+234+I,L,E) is the S. Typhi transformed
with pStyR234 and induced with IPTG at lag phase and harvested at exponential phase. Sixth lane is the S.
Typhi transformed with pStyR234 and induced with IPTG immediate after inoculation and harvested at
stationery phase.
Overexpression of StyR-233 exerts effect on multi-drug resistance phenotype of S. Typhi.
After successful cloning and over-expression of StyR-234, we performed disk diffusion assay to
determine its effect on the drug resistance phenotype of ST001. We found some interesting result when we
compared the zone of inhibition of ST001 with the pStyR234-transformed-recombinant ST001. The control
strain which possess the empty plasmid was also included in the assay. The assay was performed with 11 types
of antibiotic disks, which belongs to 7 different antibiotic groups (Penicillin, Aminoglycosides, Lincosamides,
Quinolones, Carbapenems, Cephalosporins 3rd generation, Cephalosporins 4th generation and Sulfonamides).
Antibiotics
Group A
Ampicillin
Cefotaxime
Group B
Amikacin
Cefepime
Trimethoprim Sulphamethoxazole
Imipenem
Meropenem
Piperacillin Tazobactam
Group C
Ciprofloxacin
Clindamycin
Ceftazidime
Zone of inhibition (mm)
Strains
ST001
ST001 + pStyR234
ST001 + pEmp
25.33
31.00
3.50
13.67
3.00
35.67
20.33
22.67
31.33
30.33
22.33
22.67
25.67
28.67
33.00
33.33
28.67
28.00
20.00
23.30
30.67
30.00
23.33
22.33
35.33
22.5
29.5
36.00
23.5
29.00
36.00
23.00
27.00
Table 1: The zone of inhibition values in mm with different antibiotics by the recombinant bacteria
(ST001+pStyR234) with respect to negative (non-recombinant S. typhi ST001) and positive control
(recombinant with empty plasmid: ST001+pEMP)
16
6. Characterization of StyR-234 non-coding RNA in...
According to the result obtained (shown in Table 4 and Figure 4), overexpression of StyR-234 does
play role in exerting effects on the bacteria’s drug resistance phenotype. This is based on the observation that
upon overexpression of StyR-234, there was a decrease in the zone of inhibition of a few antibiotics namely
ampicillin, Cefotaxime; suggesting that increased StyR-234 expression leads to reduced susceptibility to these
drugs. On the other hand, it was more interesting to discover that there was an increase in the zone of inhibition
for majority of the antibiotics tested upon overexpression of StyR-234. These drugs include amikacin, cefepime,
imipenem, meropenem, trimethoprim-sulfamethoxazole and piperacillin. This is indeed very interesting as it
shows that overexpression of StyR-234 leads to increased susceptibility to all these drugs. On the hand, there
were three drugs that did not display much change in zone of inhibition size. These include ciproflaxacin,
clindamycin and ceftazidime. The recombinant strain displayed resistance to ampicillin but this should be
ignored as it results from the ampicillin resistant gene present in the pStyR234 plasmid.
Figure 4: The zone of inhibition values in mm with different antibiotics by the recombinant bacteria
(ST001+pStyR234) with respect to negative (non-recombinant S. typhi ST001) and positive control
(recombinant with empty plasmid: ST001+pEMP)
Following the identification of 97 novel npcRNA candidates in S. Typhi, we are now trying to unveil
the function of one particular candidate, called StyR-234. This 119nt-length npcRNA grabbed our attention for
further characterization due to its genomic localization; located antisense to a protein-coding gene, bacA which
encodes for possible antibiotic resistant protein 50,51. The bacA gene product is not essential for growth, but the
product of the reaction, undecaprenyl phosphate, is essential for the synthesis of peptidoglycan and other cell
wall components. At least three additional gene products, YbjG, PgpB, and YeiU, are thought to have
undecaprenyl pyrophosphate phosphatase activity in E. coli52.
According to the result obtained, StyR-234 was successfully cloned and overexpressed in ST001.
Under normal growth condition, StyR-234 was not expressed in all three phases of ST001, but is expressed
increasing order from lag to stationery phases in E. coli, hence suggesting that this ncRNA could be important in
the survival of the pathogen during nutrient-scarcity50.
In contrary, while observing the expression pattern of StyR-234 in the recombinant strain (without induction), it shows that
StyR-234 was differentially expressed, increasing from lag to stationery. Meanwhile, in the induced recombinant strain,
StyR-234 was expressed in all growth stages and the expression was higher than the un-induced sample, which shows that
induction was successful. According to the result observed (Figure 4), StyR-234 over-expression caused reduction in zone
size for a few drugs but it displayed increased zone of inhibition in most of the drugs tested. Three of the most notable
differences is the difference in the zone size of amikacin, trimethoprim-sulfamethoxazole, cefepime, where the recombinant
strain displayed a larger zone compared to ST001 strain. This suggest that overexpression of StyR-234 has the potential to
increase the susceptibility of ST001 to these drugs, which previously S. typhi was resistant to. Besides that, overexpression
of StyR-234 also caused an increase in the zone size for Imipenem, Meropenem, Piperacillin Tazobactam. This suggests that
administration of these drugs can be reconsidered in treatment of typhoid patients. However, the effect of StyR-234
overexpression on the increase of zone size was not very obvious in a few drugs which include ciprofloxacin, clindamycin
and ceftazidime.
17
7. Characterization of StyR-234 non-coding RNA in...
IV.
CONCLUDING REMARKS
In summary, in this work, we showed that StyR-234 the over-expression of StyR-234 displayed some
changes in the drug susceptibility patterns in ST001. The up-regulation of the StyR-234 leading the bacteria
more susceptible to many antibiotics. This susceptibility might be due to the down regulation of the antisense
target gene, bacA, which codes for a antibiotic resistance protein.
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