What Is Zika Virus And Its History.
Transmissions Of Zika Virus.
Congenital Zika Syndrome
Molecular Mechanism Of Microcephaly
Role of the Immune System in the Development of the CNS
Diagnosis
The document summarizes the Zika virus, which is a mosquito-borne virus related to yellow fever and dengue. Zika virus was first isolated in 1947 in Uganda and has since spread to parts of Asia, the Pacific Islands, and Latin America. While Zika virus typically only causes mild symptoms, it can also lead to neurological disorders like Guillain-Barre syndrome. Most concerning is the link between maternal Zika virus infection during pregnancy and birth defects in the fetus like microcephaly. Currently, there is no specific treatment for Zika virus, so prevention efforts focus on controlling mosquito populations and protecting against sexual transmission.
The Zika virus is a flavivirus related to dengue, yellow fever, and West Nile viruses. It has a positive-sense RNA genome that can directly produce viral proteins. The genome encodes seven nonstructural proteins that help replicate the RNA and three structural proteins that form the nucleocapsid and envelope. There are two lineages of Zika virus - African and Asian - and the current outbreak strain spreading in the Americas is closely related to the Asian lineage involved in the 2013 French Polynesia outbreak.
This document discusses the Zika virus and its potential link to microcephaly. It begins with background on brain development and microcephaly. Studies are presented that found Zika virus in the brains of microcephalic fetuses and linked Zika infection in pregnant women to fetal abnormalities. Research suggests Zika infects neural progenitor cells, reducing brain size in model systems. The protein AXL is investigated as a potential receptor for Zika entry into brain cells, including progenitor cells, and is expressed in the expected regions. While evidence links Zika to microcephaly, outstanding questions remain regarding transmission and the virus's effects on the developing brain.
This document discusses genetics and how they relate to health and disease. Some key points:
1) Modern science used to believe genetics determined health and disease, but research now shows genetics can be programmed and influenced by lifestyle choices.
2) In 1997, cloning an adult sheep proved that cells retain genetic information from all stages of life and can be reprogrammed, challenging ideas of predetermined aging and health.
3) Each cell contains a "hologram" of perfect health, so if poor health exists, it's due to environmental factors distorting genetic expression over time.
4) Medications, toxins, and poor lifestyle accumulate "junk DNA" that distorts genetic expression and programming,
The document summarizes three scientific articles:
1) A new method can sequence a fetus's genome using only the fetal and mother's DNA, without the father's DNA. This could help study mutations and reduce disease comorbidity.
2) A synthetic protein called EP67 can activate the immune system within two hours, showing potential as a vaccine adjuvant. It was effective in mice infected with flu virus.
3) Medical research investigating the causes of diseases and new treatments is important to advance healthcare and help patients. Studies of fetal DNA and immune-activating proteins could lead to cures for currently untreatable or drug-resistant conditions.
The document discusses several topics related to genetics and biology:
1) Mutations can affect gene expression and the amino acid sequence of proteins. Specialization of cells is usually due to differences in gene expression, not genes.
2) Genetic engineering is used to produce novel products by inserting exogenous DNA into bacterial cells to alter their genetics and express new proteins.
3) The immune system defenses against infection include phagocytes, B-lymphocytes, T-lymphocytes, antibodies, vaccination, and the skin. Differences between bacterial and viral infections are also noted.
4) Compromised immunity can leave individuals unable to fight off usually benign microorganisms.
This document discusses the central dogma of genetics, how DNA is replicated and transcribed into RNA which is then translated into protein. It also discusses how mutated genes can cause cancer and be inherited. Studies found that inherited susceptibility to bowel cancer is common in families with a history of the disease, suggesting wider genetic testing. Retroviruses can integrate their RNA genome into host DNA using reverse transcriptase. Endogenous retroviruses make up about 5% of human DNA and may have played an important role in brain development and function over evolution. Retroviruses could potentially be used in gene therapy applications.
Researchers in Austria examined foreskin tissue from 133 males who underwent circumcision and found:
1) Low-risk HPV genotypes were present in 18.8% of samples and high-risk HPV in 9.77% of samples.
2) The presence of subclinical HPV in males suggests vaccinating boys prior to puberty could help prevent HPV transmission through sexual contact.
3) HPV vaccination for girls is accepted medical practice for preventing HPV infection and cervical cancer, but this study provides novel evidence that vaccinating boys too may help reduce HPV spread.
The document summarizes the Zika virus, which is a mosquito-borne virus related to yellow fever and dengue. Zika virus was first isolated in 1947 in Uganda and has since spread to parts of Asia, the Pacific Islands, and Latin America. While Zika virus typically only causes mild symptoms, it can also lead to neurological disorders like Guillain-Barre syndrome. Most concerning is the link between maternal Zika virus infection during pregnancy and birth defects in the fetus like microcephaly. Currently, there is no specific treatment for Zika virus, so prevention efforts focus on controlling mosquito populations and protecting against sexual transmission.
The Zika virus is a flavivirus related to dengue, yellow fever, and West Nile viruses. It has a positive-sense RNA genome that can directly produce viral proteins. The genome encodes seven nonstructural proteins that help replicate the RNA and three structural proteins that form the nucleocapsid and envelope. There are two lineages of Zika virus - African and Asian - and the current outbreak strain spreading in the Americas is closely related to the Asian lineage involved in the 2013 French Polynesia outbreak.
This document discusses the Zika virus and its potential link to microcephaly. It begins with background on brain development and microcephaly. Studies are presented that found Zika virus in the brains of microcephalic fetuses and linked Zika infection in pregnant women to fetal abnormalities. Research suggests Zika infects neural progenitor cells, reducing brain size in model systems. The protein AXL is investigated as a potential receptor for Zika entry into brain cells, including progenitor cells, and is expressed in the expected regions. While evidence links Zika to microcephaly, outstanding questions remain regarding transmission and the virus's effects on the developing brain.
This document discusses genetics and how they relate to health and disease. Some key points:
1) Modern science used to believe genetics determined health and disease, but research now shows genetics can be programmed and influenced by lifestyle choices.
2) In 1997, cloning an adult sheep proved that cells retain genetic information from all stages of life and can be reprogrammed, challenging ideas of predetermined aging and health.
3) Each cell contains a "hologram" of perfect health, so if poor health exists, it's due to environmental factors distorting genetic expression over time.
4) Medications, toxins, and poor lifestyle accumulate "junk DNA" that distorts genetic expression and programming,
The document summarizes three scientific articles:
1) A new method can sequence a fetus's genome using only the fetal and mother's DNA, without the father's DNA. This could help study mutations and reduce disease comorbidity.
2) A synthetic protein called EP67 can activate the immune system within two hours, showing potential as a vaccine adjuvant. It was effective in mice infected with flu virus.
3) Medical research investigating the causes of diseases and new treatments is important to advance healthcare and help patients. Studies of fetal DNA and immune-activating proteins could lead to cures for currently untreatable or drug-resistant conditions.
The document discusses several topics related to genetics and biology:
1) Mutations can affect gene expression and the amino acid sequence of proteins. Specialization of cells is usually due to differences in gene expression, not genes.
2) Genetic engineering is used to produce novel products by inserting exogenous DNA into bacterial cells to alter their genetics and express new proteins.
3) The immune system defenses against infection include phagocytes, B-lymphocytes, T-lymphocytes, antibodies, vaccination, and the skin. Differences between bacterial and viral infections are also noted.
4) Compromised immunity can leave individuals unable to fight off usually benign microorganisms.
This document discusses the central dogma of genetics, how DNA is replicated and transcribed into RNA which is then translated into protein. It also discusses how mutated genes can cause cancer and be inherited. Studies found that inherited susceptibility to bowel cancer is common in families with a history of the disease, suggesting wider genetic testing. Retroviruses can integrate their RNA genome into host DNA using reverse transcriptase. Endogenous retroviruses make up about 5% of human DNA and may have played an important role in brain development and function over evolution. Retroviruses could potentially be used in gene therapy applications.
Researchers in Austria examined foreskin tissue from 133 males who underwent circumcision and found:
1) Low-risk HPV genotypes were present in 18.8% of samples and high-risk HPV in 9.77% of samples.
2) The presence of subclinical HPV in males suggests vaccinating boys prior to puberty could help prevent HPV transmission through sexual contact.
3) HPV vaccination for girls is accepted medical practice for preventing HPV infection and cervical cancer, but this study provides novel evidence that vaccinating boys too may help reduce HPV spread.
This document discusses the central dogma of genetics, how DNA is replicated and transcribed into RNA which is then translated into protein. It also discusses how mutations in genes can cause cancer and be inherited. Scientists found that inherited susceptibility to bowel cancer was common among patients with a family history of the disease. Retroviruses can incorporate their RNA genome into host cell DNA using reverse transcriptase. Endogenous retroviruses make up around 5% of human DNA and may play a role in brain cell development and function. Understanding genetic mutations could help develop new cancer therapies like gene editing. Retroviruses may also be used in the future for gene therapy and cancer prevention.
Genomic vaccines offer advantages over standard vaccines by using DNA or RNA instead of proteins or pathogens. Genomic vaccines deliver genes that encode proteins to cells, allowing the cells to produce the desired proteins and inducing an immune response. This approach could allow faster vaccine development for diseases like Zika or Ebola. It may also enable vaccines for multiple pathogens at once and easy updating as pathogens mutate. Clinical trials are studying genomic vaccines for diseases like influenza, Ebola, hepatitis C, and cancers. The technology holds promise but further improvement is still needed before widespread use.
CRISPR Cas9 is a genome editing technique that uses the Cas9 enzyme to cut DNA at specific locations. In 2018, Dr. He Jiankui conducted the first human genome editing trial using CRISPR Cas9 to modify embryos' genes in an attempt to make them resistant to HIV. This resulted in the birth of twin girls known as "Nana" and "Lulu". However, Dr. He's experiment was highly controversial and considered unethical due to safety risks. While genome editing holds promise for treating disease, more research is needed to address ethical concerns before making heritable genetic changes.
Human Papilloma Virus : Cervical Cancer and VaccinesAbhijit Chaudhury
HPV is known to cause cervical cancer. The history of understanding the link between HPV and cervical cancer began in the late 1800s and early 1900s when the infectious nature of genital warts was discovered. In the 1970s, an association between HPV infection of the cervix and cervical intraepithelial neoplasia (CIN) was recognized. In 1983, HPV types 16 and 18 were discovered in cervical cancer cells, and in 2008 the discoverer was awarded the Nobel Prize for establishing the causal link between HPV and cervical cancer. HPV is a small non-enveloped virus that replicates in squamous epithelial cells and causes warts. Certain high-risk HPV types can lead to cancer by disrupting the
Deciphering the Dynamic Coupling of the Human Immune System and the Gut Micro...Larry Smarr
This document discusses Dr. Larry Smarr's research into understanding the relationship between the human immune system and gut microbiome in Crohn's disease. Dr. Smarr sequenced his own genome to identify genetic polymorphisms associated with higher risk of Crohn's disease. He also conducted fine-time resolution sampling to study the distinct dynamics of the innate and adaptive immune system in health and disease. Additionally, he found major shifts in the gut microbiome between healthy individuals and those with two forms of inflammatory bowel disease.
How to protect yourself from Zika virus?PolicyBoss
According to the WHO, the virus was first identified and documented in Uganda in 1947 in Rhesus monkeys and was first detected in humans in 1952 in Uganda and Tanzania. Learn more about this dreaded virus that is doing in the rounds in the news globally.
The human genome consists of DNA stored on 23 pairs of chromosomes, including 22 pairs of autosomal chromosomes and 1 pair of sex chromosomes. It contains over 3 billion base pairs and approximately 20,000-25,000 genes, though only 2% of the genome encodes proteins. While humans vary in physical traits, at the DNA level we are over 99% identical; the small variations that exist are what make each individual unique and can influence characteristics like disease risk. The Human Genome Project, completed in 2003, mapped the entire human genome down to the nucleotide level.
Kyasanur forest disease a disease endemic to the western ghats has been highlighted in the present slide with an exclusive information non its treatment, prevention and the latest updates.
Von Recklinghausen Syndrome with Right-sided Basal Ganglion Abnormalities on ...asclepiuspdfs
Von Recklinghausen syndrome is a genetic disorder characterized by tumors on nerves (neurofibromas) and brown spots on the skin. The document describes a case study of an Iraqi child with Von Recklinghausen syndrome. Brain MRI revealed abnormalities in the right basal ganglia. This represents the first reported case of childhood Von Recklinghausen syndrome associated with basal ganglia abnormalities on MRI. The condition ranges in severity and usually worsens over time, though life expectancy is normal for most patients.
Human papilloma virus (HPV) is a DNA virus that can cause warts and is linked to certain cancers. There are over 100 types of HPV that can infect humans. HPV types 16 and 18 are highly carcinogenic and associated with cervical and other cancers. HPV is transmitted through skin-to-skin contact, usually during sexual activity. While most HPV infections do not cause symptoms and resolve on their own, some types can cause genital warts or warts in the throat. The HPV E6 and E7 proteins contribute to cancer development by degrading tumor suppressor proteins. Vaccines targeting the HPV L1 protein show promise in preventing HPV infection and reducing cancer rates.
This document discusses the central dogma of DNA and its importance in medical research and treatment. It begins with an introduction to the central dogma - that DNA is located in the nucleus and controls protein synthesis in the cytoplasm through DNA to RNA to protein. It then summarizes several recent studies involving controlling gene expression and cell growth, developing RNA vaccines, and using knowledge of the central dogma for therapeutic purposes like improving cancer treatments. In the conclusion, a student observes that understanding how the central dogma relates to medicine today can help with disease diagnosis and treatment.
Mutations are changes in genomic sequences that can be caused by radiation, viruses, or transposons. Mutations may have no effect, prevent gene function, or alter protein production. Heredity is the passing of traits from parents to offspring, allowing variation to accumulate and lead to evolution over generations. DNA carries genetic information and is copied for each new cell, with the location of a sequence on a chromosome called a locus.
This document discusses DNA transcription and folding. It summarizes two studies: one that found a genetic mutation called MAK that causes blindness by disrupting protein production in retinal cells, and another that identified a mechanism by which cigarette smoke can increase fibronectin deposition in lung tissue of COPD patients by activating the NF-kB protein complex. Both studies provide insight into disease pathology and potential future therapies.
The researchers exposed wild type and p53 heterozygous mice to multi-walled carbon nanotubes (MWCNTs) to evaluate pulmonary disease. They found that while no mice developed mesothelioma, p53 heterozygous mice exhibited significantly larger granulomas in the lungs compared to wild type mice, indicating susceptibility to pulmonary fibrosis. The study suggests the p53 gene is a susceptibility factor for lung fibrosis in mice exposed to MWCNTs.
Genetic Engineering: Chapter 1- History of Genetic EngineeringHikmet Geckil
This document provides a history of genetic engineering. It discusses how genetic engineering began with selective breeding of plants and animals in prehistoric times. The modern field of genetic engineering began in 1973 when Herbert Boyer and Stanley Cohen accomplished the direct transfer of DNA between organisms. Since then, major breakthroughs included the discovery of restriction enzymes in 1969, the first recombinant DNA molecule in 1972, DNA sequencing in 1977, and PCR in 1983. Genetically modified foods and medicines have been commercialized since 1976. The latest developments include gene editing technologies and clinical applications of modified cells.
Both research articles discuss the role of specific proteins in human diseases. The first discusses how poor control of amyloid beta and tau proteins may be key to the progression of Alzheimer's disease. It found these proteins are less regulated in brain regions most vulnerable to the disease. The second identifies two Zika virus proteins, NS4A and NS4B, that may be responsible for microcephaly cases. Identifying these target proteins represents an important step towards potential prevention or treatment strategies for both conditions.
Both research articles discuss the role of specific proteins in human diseases. The first discusses how poor control of amyloid beta and tau proteins may be key to the progression of Alzheimer's disease. It found these proteins are less regulated in brain regions most vulnerable to the disease. The second identifies two Zika virus proteins, NS4A and NS4B, that may be responsible for microcephaly cases. Identifying these target proteins represents an important step towards potential prevention or treatment strategies for both conditions.
Zika virus can persist in the male reproductive system and negatively impact fertility. A recent study in mice found that Zika virus infected the testes, sperm, and epididymis up to 21 days after infection. This led to testicular damage, lower sperm counts, decreased testosterone production, and impaired fertility as female mice mated with infected males had lower rates of pregnancy. The study suggests Zika virus prefers cells involved in sperm formation and disrupts the function of Sertoli cells, leading to germ cell death and destruction of seminiferous tubules, indicating Zika infection has the potential to reduce male fertility in humans.
RECOMBINANT DNA TECHNOLOGY AND ITS APPLICATIONStanz Ng
Recombinant DNA technology has had widespread global impacts. It has applications in medicine like producing insulin, vaccines, and cancer treatments. In agriculture, it has led to herbicide and insect resistant crops as well as efforts to engineer nitrogen-fixing plants. It also has uses in animal husbandry such as producing transgenic animals. Additional applications include DNA fingerprinting for forensics, producing monoclonal antibodies, and developing diagnostic tests and gene therapies. While offering benefits, it also raises ethical issues that require ongoing research and regulation.
This document summarizes information about the Zika virus. It describes how the virus was originally discovered in monkeys in Uganda in 1947 and is transmitted by Aedes mosquitos. It can also be sexually transmitted. The virus causes mild symptoms like fever and rash in most cases, but infection during pregnancy is a concern as it can cause microcephaly and other birth defects in babies. Currently there is no vaccine for Zika virus but researchers are working to develop one to protect pregnant mothers and their fetuses.
Eukaryotic cells have their genetic material in the nucleus, in the other side, prokaryotes have it dispersed in the cytoplasm.
From this DNA will be synthesized RNA, which will act as an intermediary, carrying genetic information from the nucleus to the ribosomes located in the cytoplasm to carry out protein synthesis.
genetic code consists of 64 triplets (codons) of nucleotides, each codon encodes for one of the 20 amino-acids used in the synthesis of proteins.
The study of the genetic code, allow s us identify mutations in specific genes, to detect diseases or predispositions to some pathologies such as those proposed by the articles, and with tan information, implement a PREVENTIVE MEDICINE.
Knowing the sequence of genes that cause certain genetic diseases, is essential for GENE THERAPY branch. In brief it consist in introduce a correct copy of the defective gene that was visualized into the cells, by some vectors, previously studied.
With the knowledge of genetic information, can be provided counseling before and after pregnancy to future parents (Give information about the diseases to which it is susceptible and existing treatments), having always instilled an ethical principle: THE HUMAN LIFE RESPECT.
Promote investigation in medicine basic areas, such as cell biology, molecular biology, biochemistry and pharmacology, with the aim of implement humanity solutions .
This document discusses the central dogma of genetics, how DNA is replicated and transcribed into RNA which is then translated into protein. It also discusses how mutations in genes can cause cancer and be inherited. Scientists found that inherited susceptibility to bowel cancer was common among patients with a family history of the disease. Retroviruses can incorporate their RNA genome into host cell DNA using reverse transcriptase. Endogenous retroviruses make up around 5% of human DNA and may play a role in brain cell development and function. Understanding genetic mutations could help develop new cancer therapies like gene editing. Retroviruses may also be used in the future for gene therapy and cancer prevention.
Genomic vaccines offer advantages over standard vaccines by using DNA or RNA instead of proteins or pathogens. Genomic vaccines deliver genes that encode proteins to cells, allowing the cells to produce the desired proteins and inducing an immune response. This approach could allow faster vaccine development for diseases like Zika or Ebola. It may also enable vaccines for multiple pathogens at once and easy updating as pathogens mutate. Clinical trials are studying genomic vaccines for diseases like influenza, Ebola, hepatitis C, and cancers. The technology holds promise but further improvement is still needed before widespread use.
CRISPR Cas9 is a genome editing technique that uses the Cas9 enzyme to cut DNA at specific locations. In 2018, Dr. He Jiankui conducted the first human genome editing trial using CRISPR Cas9 to modify embryos' genes in an attempt to make them resistant to HIV. This resulted in the birth of twin girls known as "Nana" and "Lulu". However, Dr. He's experiment was highly controversial and considered unethical due to safety risks. While genome editing holds promise for treating disease, more research is needed to address ethical concerns before making heritable genetic changes.
Human Papilloma Virus : Cervical Cancer and VaccinesAbhijit Chaudhury
HPV is known to cause cervical cancer. The history of understanding the link between HPV and cervical cancer began in the late 1800s and early 1900s when the infectious nature of genital warts was discovered. In the 1970s, an association between HPV infection of the cervix and cervical intraepithelial neoplasia (CIN) was recognized. In 1983, HPV types 16 and 18 were discovered in cervical cancer cells, and in 2008 the discoverer was awarded the Nobel Prize for establishing the causal link between HPV and cervical cancer. HPV is a small non-enveloped virus that replicates in squamous epithelial cells and causes warts. Certain high-risk HPV types can lead to cancer by disrupting the
Deciphering the Dynamic Coupling of the Human Immune System and the Gut Micro...Larry Smarr
This document discusses Dr. Larry Smarr's research into understanding the relationship between the human immune system and gut microbiome in Crohn's disease. Dr. Smarr sequenced his own genome to identify genetic polymorphisms associated with higher risk of Crohn's disease. He also conducted fine-time resolution sampling to study the distinct dynamics of the innate and adaptive immune system in health and disease. Additionally, he found major shifts in the gut microbiome between healthy individuals and those with two forms of inflammatory bowel disease.
How to protect yourself from Zika virus?PolicyBoss
According to the WHO, the virus was first identified and documented in Uganda in 1947 in Rhesus monkeys and was first detected in humans in 1952 in Uganda and Tanzania. Learn more about this dreaded virus that is doing in the rounds in the news globally.
The human genome consists of DNA stored on 23 pairs of chromosomes, including 22 pairs of autosomal chromosomes and 1 pair of sex chromosomes. It contains over 3 billion base pairs and approximately 20,000-25,000 genes, though only 2% of the genome encodes proteins. While humans vary in physical traits, at the DNA level we are over 99% identical; the small variations that exist are what make each individual unique and can influence characteristics like disease risk. The Human Genome Project, completed in 2003, mapped the entire human genome down to the nucleotide level.
Kyasanur forest disease a disease endemic to the western ghats has been highlighted in the present slide with an exclusive information non its treatment, prevention and the latest updates.
Von Recklinghausen Syndrome with Right-sided Basal Ganglion Abnormalities on ...asclepiuspdfs
Von Recklinghausen syndrome is a genetic disorder characterized by tumors on nerves (neurofibromas) and brown spots on the skin. The document describes a case study of an Iraqi child with Von Recklinghausen syndrome. Brain MRI revealed abnormalities in the right basal ganglia. This represents the first reported case of childhood Von Recklinghausen syndrome associated with basal ganglia abnormalities on MRI. The condition ranges in severity and usually worsens over time, though life expectancy is normal for most patients.
Human papilloma virus (HPV) is a DNA virus that can cause warts and is linked to certain cancers. There are over 100 types of HPV that can infect humans. HPV types 16 and 18 are highly carcinogenic and associated with cervical and other cancers. HPV is transmitted through skin-to-skin contact, usually during sexual activity. While most HPV infections do not cause symptoms and resolve on their own, some types can cause genital warts or warts in the throat. The HPV E6 and E7 proteins contribute to cancer development by degrading tumor suppressor proteins. Vaccines targeting the HPV L1 protein show promise in preventing HPV infection and reducing cancer rates.
This document discusses the central dogma of DNA and its importance in medical research and treatment. It begins with an introduction to the central dogma - that DNA is located in the nucleus and controls protein synthesis in the cytoplasm through DNA to RNA to protein. It then summarizes several recent studies involving controlling gene expression and cell growth, developing RNA vaccines, and using knowledge of the central dogma for therapeutic purposes like improving cancer treatments. In the conclusion, a student observes that understanding how the central dogma relates to medicine today can help with disease diagnosis and treatment.
Mutations are changes in genomic sequences that can be caused by radiation, viruses, or transposons. Mutations may have no effect, prevent gene function, or alter protein production. Heredity is the passing of traits from parents to offspring, allowing variation to accumulate and lead to evolution over generations. DNA carries genetic information and is copied for each new cell, with the location of a sequence on a chromosome called a locus.
This document discusses DNA transcription and folding. It summarizes two studies: one that found a genetic mutation called MAK that causes blindness by disrupting protein production in retinal cells, and another that identified a mechanism by which cigarette smoke can increase fibronectin deposition in lung tissue of COPD patients by activating the NF-kB protein complex. Both studies provide insight into disease pathology and potential future therapies.
The researchers exposed wild type and p53 heterozygous mice to multi-walled carbon nanotubes (MWCNTs) to evaluate pulmonary disease. They found that while no mice developed mesothelioma, p53 heterozygous mice exhibited significantly larger granulomas in the lungs compared to wild type mice, indicating susceptibility to pulmonary fibrosis. The study suggests the p53 gene is a susceptibility factor for lung fibrosis in mice exposed to MWCNTs.
Genetic Engineering: Chapter 1- History of Genetic EngineeringHikmet Geckil
This document provides a history of genetic engineering. It discusses how genetic engineering began with selective breeding of plants and animals in prehistoric times. The modern field of genetic engineering began in 1973 when Herbert Boyer and Stanley Cohen accomplished the direct transfer of DNA between organisms. Since then, major breakthroughs included the discovery of restriction enzymes in 1969, the first recombinant DNA molecule in 1972, DNA sequencing in 1977, and PCR in 1983. Genetically modified foods and medicines have been commercialized since 1976. The latest developments include gene editing technologies and clinical applications of modified cells.
Both research articles discuss the role of specific proteins in human diseases. The first discusses how poor control of amyloid beta and tau proteins may be key to the progression of Alzheimer's disease. It found these proteins are less regulated in brain regions most vulnerable to the disease. The second identifies two Zika virus proteins, NS4A and NS4B, that may be responsible for microcephaly cases. Identifying these target proteins represents an important step towards potential prevention or treatment strategies for both conditions.
Both research articles discuss the role of specific proteins in human diseases. The first discusses how poor control of amyloid beta and tau proteins may be key to the progression of Alzheimer's disease. It found these proteins are less regulated in brain regions most vulnerable to the disease. The second identifies two Zika virus proteins, NS4A and NS4B, that may be responsible for microcephaly cases. Identifying these target proteins represents an important step towards potential prevention or treatment strategies for both conditions.
Zika virus can persist in the male reproductive system and negatively impact fertility. A recent study in mice found that Zika virus infected the testes, sperm, and epididymis up to 21 days after infection. This led to testicular damage, lower sperm counts, decreased testosterone production, and impaired fertility as female mice mated with infected males had lower rates of pregnancy. The study suggests Zika virus prefers cells involved in sperm formation and disrupts the function of Sertoli cells, leading to germ cell death and destruction of seminiferous tubules, indicating Zika infection has the potential to reduce male fertility in humans.
RECOMBINANT DNA TECHNOLOGY AND ITS APPLICATIONStanz Ng
Recombinant DNA technology has had widespread global impacts. It has applications in medicine like producing insulin, vaccines, and cancer treatments. In agriculture, it has led to herbicide and insect resistant crops as well as efforts to engineer nitrogen-fixing plants. It also has uses in animal husbandry such as producing transgenic animals. Additional applications include DNA fingerprinting for forensics, producing monoclonal antibodies, and developing diagnostic tests and gene therapies. While offering benefits, it also raises ethical issues that require ongoing research and regulation.
This document summarizes information about the Zika virus. It describes how the virus was originally discovered in monkeys in Uganda in 1947 and is transmitted by Aedes mosquitos. It can also be sexually transmitted. The virus causes mild symptoms like fever and rash in most cases, but infection during pregnancy is a concern as it can cause microcephaly and other birth defects in babies. Currently there is no vaccine for Zika virus but researchers are working to develop one to protect pregnant mothers and their fetuses.
Eukaryotic cells have their genetic material in the nucleus, in the other side, prokaryotes have it dispersed in the cytoplasm.
From this DNA will be synthesized RNA, which will act as an intermediary, carrying genetic information from the nucleus to the ribosomes located in the cytoplasm to carry out protein synthesis.
genetic code consists of 64 triplets (codons) of nucleotides, each codon encodes for one of the 20 amino-acids used in the synthesis of proteins.
The study of the genetic code, allow s us identify mutations in specific genes, to detect diseases or predispositions to some pathologies such as those proposed by the articles, and with tan information, implement a PREVENTIVE MEDICINE.
Knowing the sequence of genes that cause certain genetic diseases, is essential for GENE THERAPY branch. In brief it consist in introduce a correct copy of the defective gene that was visualized into the cells, by some vectors, previously studied.
With the knowledge of genetic information, can be provided counseling before and after pregnancy to future parents (Give information about the diseases to which it is susceptible and existing treatments), having always instilled an ethical principle: THE HUMAN LIFE RESPECT.
Promote investigation in medicine basic areas, such as cell biology, molecular biology, biochemistry and pharmacology, with the aim of implement humanity solutions .
1) The human JC virus (JCV) infects over 80% of humans and is associated with the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML).
2) JCV has the ability to transform cells in culture and induce tumors in animal models. Its major oncoprotein, T-antigen, interacts with tumor suppressors like p53 and Rb to deregulate pathways controlling cell proliferation.
3) Studies suggest T-antigen promotes tumorigenesis by interacting with cellular proteins involved in proliferation signaling like IRS-1, disrupting tumor suppressor functions and activating pathways like IGF-1 signaling.
Zika virus was first discovered in Uganda in 1947 and has since spread to many countries. It is transmitted by Aedes mosquitoes and can cause microcephaly in fetuses if the mother is infected during pregnancy. While most Zika infections cause only mild symptoms, it poses a serious threat during pregnancy due to the risk of birth defects. Diagnostic tests for Zika look for viral RNA or IgM antibodies. There is no vaccine or specific treatment, so prevention focuses on controlling mosquito populations and protecting against bites.
PharmaCon2007 Congress, Dubrovnik, Croatia "New Technologies and Trends in Pharmacy, Pharmaceutical Industry and Education" http://www.pharmacon2007.com
Abstract is available at http://www.pharmaconnectme.com
The document provides an overview of the Zika virus pandemic as of March 2016. It summarizes the epidemiology of Zika virus, describing its spread across locations in the Americas and Pacific islands since 1947. It also summarizes key aspects of Zika virus such as its transmission cycle and risk factors. The document discusses clinical manifestations of Zika virus including acute infection, complications like Guillain-Barré syndrome and microcephaly. It provides preliminary findings from Brazil linking Zika infection in pregnancy to fetal abnormalities. It concludes with a summary of a retrospective study from French Polynesia linking the 2013-2014 Zika outbreak there to cases of microcephaly.
Summary
Neurodevelopment is a complex process governed by both intrinsic and extrinsic signals. While historically studied by researching the brain, inputs from the periphery impact many neurological conditions. Indeed, emerging data suggests communication between the gut and the brain in anxiety,
depression, cognition and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut. These cues largely originate from the microbiome, the consortium of symbiotic bacteria that reside within all animals. Research over the past few years reveals that the gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brainbarrier, myelination, neurogenesis, and microglia maturation, and also modulates many aspects of animal behavior. Herein, we discuss the biological intersection of neurodevelopment and the microbiome, and explore the hypothesis that gut bacteria are integral contributors to development and function of the nervous system, and the balance between mental health and disease.
iDDNA®_HealthcareProfessional_BrochureSara Ferrari
This document discusses using a person's DNA to provide personalized anti-aging treatments. It describes iDDNA, a company that analyzes a patient's genetic code to develop individualized anti-aging programs targeting the causes of aging at a genetic level. The document outlines several Nobel Prize-winning discoveries in genetics that form the foundation of iDDNA's approach. It also discusses how environmental factors and DNA damage contribute to the aging process and how iDDNA aims to slow aging by mitigating molecular damage and supporting DNA repair mechanisms.
Zika virus causes disease in humans and other primates. It is transmitted primarily by Aedes mosquitoes, which breed in stagnant pools of water. Recent research has provided insights into Zika virus structure and how it infects human cells. Symptoms of Zika virus infection in humans are usually mild and include fever, rash, joint pain, and conjunctivitis. While Zika virus is suspected of linking to birth defects like microcephaly, more research is still needed to confirm this relationship. Ongoing studies aim to better understand Zika virus pathogenesis and develop treatments.
The Zika virus is spread primarily via mosquito bites and has led to an epidemic in Latin America and the Caribbean. Studies in 2015 detected Zika virus RNA in the amniotic fluid of pregnant women whose fetuses had microcephaly, and brain tissue from infants who died of microcephaly. The virus belongs to the Flaviviridae family and causes symptoms like rash, fever, conjunctivitis, and joint pain. Scientists are working to develop a vaccine, but in the meantime public health efforts focus on controlling mosquitoes and preventing their bites.
High-Throughput Sequencing Reveals Micrornas from Plasma Exosomes as Potentia...semualkaira
As a progressive cerebrovascular disorder, moyamoya disease is a common cause of stroke in children and adults. However, search for early biomarkers and the pathogenesis of moyamoya disease remain poorly understood.
High-Throughput Sequencing Reveals Micrornas from Plasma Exosomes as Potentia...semualkaira
This study aimed to identify plasma exosomal microRNAs (miRNAs) as potential biomarkers for moyamoya disease. High-throughput sequencing of plasma exosomes from moyamoya patients and healthy controls revealed miR-574-5p was significantly upregulated in moyamoya patients. Ten miRNAs were found to be associated with sensitive and specific pathways for predicting moyamoya disease. Real-time quantitative PCR validated the expression levels of the selected miRNAs. This study provides evidence that plasma exosomal miRNAs could serve as non-invasive biomarkers for moyamoya disease diagnosis.
Science Cabaret by Dr. Rodney Dietert "How to train your super organism..via ...Kitty Gifford
This document summarizes a presentation by Rodney Dietert on training the human-microbial superorganism. It discusses how Dietert found his superorganism through research linking the microbiome to health and disease. He learned that humans are majority microbial and the microbiome helps produce our identity through volatile compounds. Microbial dysbiosis can lead to inflammation and disease. Dietert trained his own superorganism after years of antibiotics by adjusting his microbiome and diet. He provides three takeaway points on the importance of microbiome seeding at birth, co-maturation of the immune and microbial systems, and basing safety assessments on the human superorganism.
Zika virus was first isolated in 1947 in Uganda and has since spread across the Pacific and Americas. It is transmitted by Aedes mosquitoes and causes fever, rash, joint pain, and conjunctivitis. While symptoms are usually mild and short-lived, Zika can also cause microcephaly in fetuses when mothers are infected during pregnancy. The virus is diagnosed through blood and other tests and treated through symptom relief only. Prevention focuses on mosquito bite protection as there is currently no vaccine.
This document provides a summary of a student's research project on using personalised learning strategies to overcome difficulties in understanding biology topics related to pathogens and antibiotic resistance. The research project involved examining educational placement, background, aims and objectives. Effectiveness of strategies was assessed through references and an appendix providing details on case studies and educational introduction, biological introduction on pathogens and antibiotic resistance, as well as further learning sections on HIV and Ebola.
This document discusses various methods for single nucleotide polymorphism (SNP) analysis, including their principles, advantages, and disadvantages. It describes SNP genotyping techniques like RFLP-PCR, TaqMan assays, microarrays, Sanger sequencing, SNaPshot, and next-generation sequencing. The key aspects are accuracy, throughput, cost, and ability to detect both known and unknown SNPs. The document emphasizes choosing methods based on required information extraction and cost effectiveness.
Toxoplasma Gondii.
Toxoplasmosis - Congenital Toxoplasmosis
The transition between tachyzoites and bradyzoites.
T.gondii as an Epigenator.
Immune Response Pathway.
Behavior Changer by T.gondii infection.
Sex Determination definition.
Chromosomal Sex Determination.
Primary sex determination.
Secondary Sex determination.
Genetic mechanism.
Environmental Sex Determination.
Conclusion.
This document discusses RNA structure and types. It begins by describing the basic components and functions of RNA, including its role in transcription and as an intermediate molecule in protein synthesis. It then discusses the different forms and structures of RNA, including primary, secondary and tertiary structures. The main types of RNA - mRNA, tRNA, rRNA and others like miRNA and siRNA - are then summarized in terms of their roles and characteristics. Applications of RNA interference are also briefly outlined.
Nonsyndromic orofacial clefts (NSOFCs) are the most common craniofacial malformations observed
across the globe. They are classified into three types: (a) cleft palate, (b) cleft lip, and (c) cleft lip and
palate.
Ideonella sakaiensis is a bacterium identified in 2016 that is capable of breaking down PET plastic. It was isolated from samples taken outside a plastic bottle recycling facility in Sakai, Osaka Prefecture, Japan. Genome sequencing of I. sakaiensis identified two key enzymes, PETase and MHETase, that allow it to break the ester bonds in PET plastic, converting it into its basic monomers. While I. sakaiensis shows promise for biodegrading PET plastic, further research is needed to improve its abilities and apply its enzymes to develop more efficient plastic recycling methods.
Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder.
PWS is relatively common with an estimated prevalence worldwide in the range of 1 in 10,000 to 30,000 individuals
Prader-Willi syndrome is due to absence of paternally expressed imprinted genes at 15q11.2-q13.
PWS was first described by Prader et al. in 1956 and it is the first recognized disorder related to genomic imprinting in humans.
PWS affects males and females with equal frequency and affects all races and ethnicities
A stop codon mutation in scn9a causes lack of pain sensationhad89
Sensation:
It is the rapid response to represent stimuli from the environment.
Essential for survival because these environmental factors may cause physical damage
There are numerous receptors, ion channel and other proteins involved in perception and transmission of painful stimuli.
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Two types of small ribonucleic acid (RNA) molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by Stamler, Verified Chapters 1 - 33, Complete Newest Version Community Health Nursing A Canadian Perspective, 5th Edition by Stamler, Verified Chapters 1 - 33, Complete Newest Version Community Health Nursing A Canadian Perspective, 5th Edition by Stamler Community Health Nursing A Canadian Perspective, 5th Edition TEST BANK by Stamler Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Pdf Chapters Download Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Pdf Download Stuvia Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Study Guide Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Ebook Download Stuvia Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Questions and Answers Quizlet Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Studocu Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Quizlet Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Pdf Chapters Download Community Health Nursing A Canadian Perspective, 5th Edition Pdf Download Course Hero Community Health Nursing A Canadian Perspective, 5th Edition Answers Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Ebook Download Course hero Community Health Nursing A Canadian Perspective, 5th Edition Questions and Answers Community Health Nursing A Canadian Perspective, 5th Edition Studocu Community Health Nursing A Canadian Perspective, 5th Edition Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Pdf Chapters Download Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Pdf Download Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Study Guide Questions and Answers Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Ebook Download Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Questions Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Studocu Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Stuvia
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
1. ZIKA VIRUS
&
EMBRYONIC DEVELOPMENT
Presented By: Hadiah Bassam Al Mahdi
PhD. Student in Genetics
Faculty of Science , King Adulaziz University
Developmental Genetics Course Bio707
2. OUTLINE
What Is Zika Virus And Its History.
Transmissions Of Zika Virus.
Congenital Zika Syndrome
Molecular Mechanism Of Microcephaly
Role of the Immune System in the Development of the CNS
Diagnosis
3. ZIKA VIRUS
Zika virus (ZIKV) is a mosquito-borne arbovirus of Flaviviridae family.
Aedes aegypti mosquito is a vector in human.
ZIKV is an enveloped virus with an approximately 10.8-kb positive-sense
RNA genome.
The genome RNA of a
+ssRNA virus contains
only the genes needed
for the infectious cycle
and is simultaneously
a messenger RNA.
(Rombi et al., 2020)
5. TRANSMISSION
Mosquito
Primarily spread by Aedes aegypti mosquito
which is active mostly in the daytime.
Sexual transmission
Zika can be transmitted from men and
women to their sexual partners; most cases
involve transmission from men to women
ZIKV can persist in semen for several
months.
Blood transfusion
Pregnancy
Zika virus can spread by vertical
transmission, during pregnancy or at
delivery.
Tissue tropism
(Rather et al., 2017)
(Gorshkov et al., 2019)
6. GENERAL SYMPTOMS
ZIKV infection frequently goes unnoticed or is asymptomatic in approximately 80%
of cases and most patients present with only mild symptoms.
(Jain et al.)
7. VERTICALLY
TRANSMITTED
ZIKV and the invasion of viral
particles through dermal
fibroblasts, epidermal
keratinocytes, and immature
dendritic cells via an infected
mosquito.
The infected mother to the
fetus by infecting placental
trophoblasts and
macrophages (Hofbauer
cells) and crossing the
placental barrier.
(Faizan et al., 2016)
8. ZIKV as TERATOGENS
Teratogens are
substances or other
factors that can cause
congenital
abnormalities, which
are also called birth
defects.
Usually abnormalities arise in
the third to eighth weeks of
pregnancy, when the major
organ systems are forming
(Wen et al., 2017)
(Gilbert, 2000)
9. CONGENITAL ZIKA SYNDROME
The first trimester of pregnancy is crucial
for neurological development
It characterized with 5 distinctive features that focus on brain development
abnormalities (microcephaly and brain calcifications), retinal manifestations, and
defects on extremities including congenital contractures and hypertonia.
(Musso et al., 2019)
10. ZIKA VIRUS INDUCE
MICROCEPHELY
o Microcephaly is a congenital defect in which the head size is
smaller than normal.
o Two types of microcephaly are recognized.
The first : the brain fails to grow into appropriate size during
pregnancy at around 32 weeks of the gestation period
The second: caused by a gradual decrease in the neuron
production.
(CDC, 2018)
11. WHY ARE NEURONS
SUSCEPTIBLE TO ZIKA VIRUS
Axl receptor mediates ZIKA Virus entry
in Human progenitor cell (hNPCs) and
Modulates Innate Immune Responses.
MSI1 an RNA-binding protein called
Musashi-1 (MSI1), which is highly
expressed in neural progenitor cells and
binds to 3′UTR Zika's RNA genome
(Meertens et al., 2017)
(Griffin, 2017)
13. RECEPTOR TYROSINE KINASE
MEDIATING INFLAMMATORY
PROCESSES
STAT2 to inhibit
type I interferon
signaling
The Akt-mTOR
signalling pathway
to regulate various
processes in
NPCs
Inhibit RIG-I-like
receptor
signalling,
supressing type I
IFN induction
(Wen et al., 2017)
14. ROLE OF THE IMMUNE SYSTEM IN
THE DEVELOPMENT OF THE CNS
The central nervous system (CNS) and the immune system are both
intricate and highly organized systems that regulate the entire body,
with both sharing certain common features in developmental
mechanisms and operational modes.
The innate immunity-related molecules, such as cytokines, toll-like
receptors, the complement family, and acquired immunity-related
molecules are also expressed in the brain and play important roles in
brain development.
The brain has been regarded as an immune-privileged site, it is
known to contain lymphatic vessels. Not only microglia but also
lymphocytes regulate cognition and play a vital role in the formation of
neuronal circuits.
List of sharing genes and their functions
15. MOLECULAR MECHANISM OF
MICROCEPHALY IN NPCS
MCPH1 and CDK6 (MCPH12) are
an association genes with Congenital
Microcephaly.
MSI1-expressing cell, Zika
virus competes for available
MSI1, decreasing MSI1
interaction with its normal
targets.
Targets include messenger
RNAs (mRNAs) encoding
proteins that promote the
expression of microcephalin
(MCPH1) for fetal brain
development and cyclin-
dependent kinase 6 (CDK6)
for cell division cycle.
(Chavali et al., 2017)
19. REFERENCES
o CHAVALI, P. L., STOJIC, L., MEREDITH, L. W., JOSEPH, N., NAHORSKI, M. S.,
SANFORD, T. J., SWEENEY, T. R., KRISHNA, B. A., HOSMILLO, M. & FIRTH, A. E.
2017. Neurodevelopmental protein Musashi-1 interacts with the Zika genome and
promotes viral replication. Science, 357, 83-88.
o FAIZAN, M. I., ABDULLAH, M., ALI, S., NAQVI, I. H., AHMED, A. & PARVEEN, S.
2016. Zika virus-induced microcephaly and its possible molecular mechanism.
Intervirology, 59, 152-158.
o GHARBARAN, R. & SOMENARAIN, L. 2017. Insights into the molecular roles of Zika
virus in human reproductive complications and congenital neuropathologies.
Pathology, 49, 707-714.
o GILBERT, S. F. 2000. An Introduction to Early Developmental Processes.
Developmental Biology. 6th edition. Sinauer Associates.
o GORSHKOV, K., SHIRYAEV, S. A., FERTEL, S., LIN, Y.-W., HUANG, C.-T., PINTO,
A., FARHY, C., STRONGIN, A. Y., ZHENG, W. & TERSKIKH, A. V. 2019. Zika virus:
origins, pathological action, and treatment strategies. Frontiers in Microbiology, 9,
3252.
o GRIFFIN, D. E. 2017. Why are neurons susceptible to Zika virus? Science, 357, 33-
34.
20. o JAIN, H., PATEL, K., RAJPUT, Z., JANI, P. & TANDEL, H. ZIKA VIRUS
INFECTION: THREAT TO HUMAN LIFE.
o MEERTENS, L., LABEAU, A., DEJARNAC, O., CIPRIANI, S., SINIGAGLIA, L.,
BONNET-MADIN, L., LE CHARPENTIER, T., HAFIRASSOU, M. L., ZAMBORLINI,
A. & CAO-LORMEAU, V.-M. 2017. Axl mediates ZIKA virus entry in human glial
cells and modulates innate immune responses. Cell reports, 18, 324-333.
o MUSSO, D. & GUBLER, D. J. 2016. Zika virus. Clinical microbiology reviews, 29,
487-524.
o MUSSO, D., KO, A. I. & BAUD, D. 2019. Zika virus infection—after the pandemic.
New England Journal of Medicine, 381, 1444-1457.
o RATHER, I. A., KUMAR, S., BAJPAI, V. K., LIM, J. & PARK, Y.-H. 2017. Prevention
and control strategies to counter ZIKA epidemic. Frontiers in microbiology, 8, 305.
o ROMBI, F., BAYLISS, R., TUPLIN, A. & YEOH, S. 2020. The journey of Zika to the
developing brain. Molecular Biology Reports, 1-19.
o WEN, Z., SONG, H. & MING, G.-L. 2017. How does Zika virus cause
microcephaly? Genes & development, 31, 849-861.
REFERENCES
Editor's Notes
https://link.springer.com/article/10.1007/s11033-020-05349-y
https://jvi.asm.org/content/90/10/4864
The genome RNA of a +ssRNA virus contains only the genes needed for the infectious cycle and is simultaneously a messenger RNA
The genome of ZIKV encodes a single polyprotein that is post-translationally cleaved by host and viral proteases into three structural proteins (capsid [C], premembrane [prM], and envelope [E]) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5)
https://www.youtube.com/watch?v=0rPJS32ir2I
https://www.researchgate.net/figure/ZIKA-transmission-cycle-in-humans_fig3_314112380
https://www.frontiersin.org/articles/10.3389/fmicb.2018.03252/full
https://www.nejm.org/doi/full/10.1056/nejmcibr1605445
ZIKV is most commonly transmitted from the bite of a mosquito, where initial infection most likely occurs in human skin cells directly affecting permissive human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells
Tissue tropism is the cells and tissues of a host which support growth of a particular virus or bacteria.
/https://doi.org/10.1159/000452950
[VII] A diagrammatic representation of hNPCs showing the proposed molecular mechanism of microcephaly.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458753/
vertically transmitted from the infected mother to the fetus by infecting placental trophoblasts and macrophages (Hofbauer cells) and crossing the placental barrier
trophoblast combines with the maternal endometrium to form the placenta in eutherian mammals. Blastocyst: The blastocyst possesses an inner cell mass from which the embryo will develop, and an outer layer of cells, called the trophoblast, which will eventually form the placenta
كتاب GILLBIRT
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392600/
Chart shows the gestational timing of maternal infection and fetal phenotype. Based on current knowledge,(18,21,22,64) if vertical transmission of Zika infection occurs, the possible risks to the pregnancy and fetus associated with a particular gestational timing of the maternal infection are summarised. The absolute risks to the fetus during each of these window periods remain to be determined, but overall, they are believed to be relatively low, with the highest risk in the first(19) and early second trimesters.(53) The light grey boxes indicate the timing of maternal infection (in gestational weeks), while the dark grey boxes show the resultant anomalies for each time period. The text in italics represents retrospective information on the presumed timing of the maternal infection, which is less accurate.(48) CNS: central nervous system.
Chemical perturbation of redox states alters developmental programming causing malformation.
https://www.sciencedirect.com/science/article/abs/pii/S0890623812002985
The first trimester of pregnancy is crucial for neurological development. Zika viral infection in the mother during this period is more likely to affect the central nervous system
A congenital Zika syndrome (CZS) has been characterized with 5 distinctive features that focus on brain development abnormalities (including microcephaly and brain calcifications), retinal manifestations, and defects on extremities including congenital contractures and hypertonia.
The other relates to a normal brain size at birth but failure to grow subsequently due to the loss of dendritic connections.
Brain and Nervous System
A study by Nayak et al 2016 using mouse models identified radial glial cells, a type of neural progenitor cells as the primary target of ZIKV in fetal mouse brains. In this study the Asian ZIKV strain was injected into immunosupprescent mice and the effects were observed. Upon injection ZIKV was shown to target neural progenitor cells. They were also shown to prevent the proliferation and differentiation of cortical neural progenitor cells. Although genes that regulate organ development were shown to be downregulated, a gene analysis also showed that genes involved in apoptosis pathways and immune response such as cytokine production were upregulated. This study demonstrated the persistent replication of ZIKV up to twenty eight days after the initial infection (Nayak et al 2016). An infected cell is characterised by rounding, pyknosis and caspase activation. Several molecular pathways have been put together to explain the mechanisms of ZIKV infection one of which includes the cytokine receptor AXL which has been shown to mediate ZIKV infection. Most cells in the body are enriched with AXL kinases especially the cells along the pathway of ZIKV infection which includes the skin, the lymph node, micro-capillaries, microglial and cortical astrocytes. This enables the rapid expansion of ZIKV. ZIkV then signals the upregulation of AXL kinases resulting in reduced neural cell proliferation and cell death. ZIKV has also been shown to upregulate genes associated with autophagy and apoptosis such as Bmf1, Casp6 and can activate toll-like receptor 3 (TLR3) in human embryonic stem cell derived organoids which leads to the disregulation of genes involved in neurogenesis and apoptotic pathways resulting in the manifestation of clinical neurological symptoms (Nayak et al 2016).
https://www.sciencedirect.com/science/article/pii/S2211124716317521
https://science.sciencemag.org/content/357/6346/33?rss%253D1=
Binding of viral particles with the hNPCs via the AXL receptor facilitates viral entry with the formation of the endosome.
Neural progenitors are cells that are capable of dividing a limited number of times and have the capacity to differentiate into a restricted repertoire of neuronal and glial cell types
Neural stem cells (NSCs) are a group of ectodermal progenitor cells
Interaction between the Zika virus RNA genome and an RNA-binding protein (MSI1) that is highly expressed in neural progenitor cells may explain why infection leads to fewer neural precursors and microcephaly
Notch signaling promotes proliferative signaling during neurogenesis, and its activity is inhibited by Numb to promote neural differentiation. It plays a major role in the regulation of embryonic development
Mechanisms underlying impaired brain development upon ZIKV infection. ZIKV directly targets NPCs in the developing brain and activates innate immune response, which could lead to dysregulation of genes involved in cell cycle, neurogenesis, and apoptosis, resulting in increased cell death, disrupted cell cycle progression, reduced proliferation, and premature differentiation. On the other hand, infection of ZIKV in placenta and glial cells, including astrocytes and microglia, could lead to placental insufficiency and activation of immune response (inflammation), which may elicit non-cell-autonomous effects on NPCs, neurons, and vasculature, resulting in impaired neurogenesis and microcephaly.
Autography : is the natural, regulated mechanism of the cell that removes unnecessary or dysfunctional components
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458753/
https://link.springer.com/article/10.1007/s11033-020-05349-y
https://www.pathologyjournal.rcpa.edu.au/article/S0031-3025(17)30098-3/abstract
second pic)
Third
https://link.springer.com/article/10.1007/s11033-020-05349-y
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458753/
Study of ZIKV infection in multiple cell types indicated that ZIKV gains entry into host cells through the interaction of the virus envelope glycoprotein with cell surface receptors DC-SIGN, AXL, TYRO3, and TIM-1 and that AXL, a receptor tyrosine kinase mediating inflammatory processes, appears to play a major role
here are both cell-autonomous and non-cell-autonomous effects
The Akt-mTOR signalling pathway plays a crucial role in regulating various processes in NPCs, including cellular development, proliferation, survival and inhibition of autophagy
https://link.springer.com/article/10.1007/s11033-020-05349-y
The viral envelope degrades due to a decrease in pH and release of virion into the cytoplasm.
Some viral RNA released in the cytoplasm replicates and forms the viral proteins using the host cell machinery. The viral RNA and proteins form progeny virions which are released from the host cell. The viral RNA also binds to the TLR3 receptors present on the surface of the endosome. Hyperactivation of TLR3-mediated innate immune response occurs with the binding of viral RNA. Subsequent dysregulation in transcription occurs due to downregulation of about 41 specific genes responsible for NPC differentiation. This leads to impaired neurogenesis and activation of the proapoptotic pathway. Consequently, the downregulation of neurogenesis and upregulation of apoptosis leads to impaired brain growth culminating in microcephaly
The central nervous system (CNS) and the immune system are both intricate and highly organized systems that regulate the entire body, with both sharing certain common features in developmental mechanisms and operational modes. It is known that innate immunity-related molecules, such as cytokines, toll-like receptors, the complement family, and acquired immunity-related molecules, such as the major histocompatibility complex and antibody receptors, are also expressed in the brain and play important roles in brain development. Moreover, although the brain has previously been regarded as an immune-privileged site, it is known to contain lymphatic vessels. Not only microglia but also lymphocytes regulate cognition and play a vital role in the formation of neuronal circuits. This review provides an overview of the function of immune cells and immune molecules in the CNS, with particular emphasis on their effect on neural developmental processes.
Certain sites of the human body have immune privilege, meaning they are able to tolerate the introduction of antigens without eliciting an inflammatory immune response.
https://www.frontiersin.org/articles/10.3389/fnins.2019.00916/full
Zika's RNA genome binds to an RNA-binding protein called Musashi-1 (MSI1), which is highly expressed in neural progenitor cells. These progenitors are precursors for neurons and astrocytes (2), cells required for cortical development. The interaction between Zika viral RNA and MSI1 may explain why these precursor cells are targets for infection.
binds to the of Zika viral RNA and promotes its translation into the polyprotein that then facilitates viral replication. In an MSI1-expressing cell, Zika virus competes for available MSI1, decreasing MSI1 interaction with its normal targets. These targets include messenger RNAs (mRNAs) encoding proteins that promote the expression of microcephalin (MCPH1) and cyclin-dependent kinase 6 (CDK6).
In an MSI1-expressing cell, Zika virus competes for available MSI1, decreasing MSI1 interaction with its normal targets. These targets include messenger RNAs (mRNAs) encoding proteins that promote the expression of microcephalin (MCPH1) and cyclin-dependent kinase 6 (CDK6). MCPH1 is expressed during human fetal brain development, and mutations in the encoding gene can cause microcephaly, a smaller brain size. CDK6 is a serine-threonine kinase that controls the cell division cycle, and thus, cell proliferation. MSI1 also represses the translation of mRNAs encoding the proteins Numb and p21, both of which maintain proliferation of neural precursors and cortical development
https://www.researchgate.net/publication/317590663_Neurodevelopmental_protein_Musashi_1_interacts_with_the_Zika_genome_and_promotes_viral_replication
https://science.sciencemag.org/content/357/6346/33