Elucidating changes in gene expression in Tryp susceptible and resistant cattle during progression of tryp infection using Affymetrix gene expression Micro arrays
Genomic gene expression changes resulting from Trypanosomiasis: a horizontal study Examining expression changes elucidated by micro arrays in seminal tissues associated with the pathophysiology of Trypanosomiasis during disease progression
Bio380 lecture on cancer as an evolutionary process, showing descent with modification, branching evolution and natural selection; focus on genome evolution
Synonymous mutations as drivers in human cancer genomes.Fran Supek
Synonymous mutations change the sequence of a gene without directly altering the sequence of the encoded protein. Here, we present evidence that these "silent" mutations frequently contribute to human cancer. Selection on synonymous mutations in oncogenes is cancer-type specific, and although the functional consequences of cancer-associated synonymous mutations may be diverse, they recurrently alter exonic motifs that regulate splicing and are associated with changes in oncogene splicing in tumors. The p53 tumor suppressor (TP53) also has recurrent synonymous mutations, but, in contrast to those in oncogenes, these are adjacent to splice sites and inactivate them. We estimate that between one in two and one in five silent mutations in oncogenes have been selected, equating to ~6%- 8% of all selected single-nucleotide changes in these genes. In addition, our analyses suggest that dosage-sensitive oncogenes have selected mutations in their 3' UTRs.
Alpha-1 Antitrypsin (α-1 AT) deficiency is a common genetic disorder that affects 1 in 2,000 individuals in the USA. Additionally, over 20 million people have been identified as carriers for this genetic disorder. In severe cases, α-1 AT deficiency can cause substantial lung and liver damage, which if left untreated could result in death and there are no current available treatments. Alpha-1 protein is produced in the liver, travels in the bloodstream and utilized in the lungs to protect healthy lung tissue from harmful destruction by elastase. A common single amino acid substitution, located at E342K (ATZ) was identified in α-1 AT deficient humans. When this specific mutation occurs two phenotypes can result: 1) ATZ can polymerize in the liver causing cellular toxicity 2) inhibits alpha-1 antitrypsin from inhibiting elastase which can result in lung disease. Currently; little is known about the cellular mechanisms that clear the accumulated proteins in the liver. Therefore, an investigative study utilizing C. elegans model of ATZ was performed in order to help determine the cellular mechanisms that dispose of accumulated proteins. Specifically RNA interference was utilized to knockdown expression of specific genes. This investigation examined genes involved in the heat-shock pathway (HSP), unfolded protein response (UPR), and insulin signaling pathway (IS). Phenotypic analysis including: embryonic lethality, protein aggregation expression, and longevity, was completed after knockdown of genes to determine effect on ATZ accumulation. Currently with our preliminary data suggests that the heat-shack pathway may play a role in ATZ accumulation. Determining the mechanism of protein accumulation in the investigation of C. elegans may lead to possible drug targets and therefore the development of a treatment which may alleviate those diagnosed with this disorder.
Systemic analysis of data combined from genetic qtl's and gene expression dat...Laurence Dawkins-Hall
Elucidating changes in gene expression by Micro array genomic sweeps of genetic QTLs linked to Tryp resistance in WT cattle to identify putative candidates underpinning pathophysiology
Src jbbr-20-120 Dr. ihsan edan abdulkareem alsaimary PROFESSOR IN MEDICAL M...dr.Ihsan alsaimary
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
Assessment of immunomolecular_expression_and_prognostic_role_of_tlr7_among_pa...dr.Ihsan alsaimary
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
Genomic gene expression changes resulting from Trypanosomiasis: a horizontal study Examining expression changes elucidated by micro arrays in seminal tissues associated with the pathophysiology of Trypanosomiasis during disease progression
Bio380 lecture on cancer as an evolutionary process, showing descent with modification, branching evolution and natural selection; focus on genome evolution
Synonymous mutations as drivers in human cancer genomes.Fran Supek
Synonymous mutations change the sequence of a gene without directly altering the sequence of the encoded protein. Here, we present evidence that these "silent" mutations frequently contribute to human cancer. Selection on synonymous mutations in oncogenes is cancer-type specific, and although the functional consequences of cancer-associated synonymous mutations may be diverse, they recurrently alter exonic motifs that regulate splicing and are associated with changes in oncogene splicing in tumors. The p53 tumor suppressor (TP53) also has recurrent synonymous mutations, but, in contrast to those in oncogenes, these are adjacent to splice sites and inactivate them. We estimate that between one in two and one in five silent mutations in oncogenes have been selected, equating to ~6%- 8% of all selected single-nucleotide changes in these genes. In addition, our analyses suggest that dosage-sensitive oncogenes have selected mutations in their 3' UTRs.
Alpha-1 Antitrypsin (α-1 AT) deficiency is a common genetic disorder that affects 1 in 2,000 individuals in the USA. Additionally, over 20 million people have been identified as carriers for this genetic disorder. In severe cases, α-1 AT deficiency can cause substantial lung and liver damage, which if left untreated could result in death and there are no current available treatments. Alpha-1 protein is produced in the liver, travels in the bloodstream and utilized in the lungs to protect healthy lung tissue from harmful destruction by elastase. A common single amino acid substitution, located at E342K (ATZ) was identified in α-1 AT deficient humans. When this specific mutation occurs two phenotypes can result: 1) ATZ can polymerize in the liver causing cellular toxicity 2) inhibits alpha-1 antitrypsin from inhibiting elastase which can result in lung disease. Currently; little is known about the cellular mechanisms that clear the accumulated proteins in the liver. Therefore, an investigative study utilizing C. elegans model of ATZ was performed in order to help determine the cellular mechanisms that dispose of accumulated proteins. Specifically RNA interference was utilized to knockdown expression of specific genes. This investigation examined genes involved in the heat-shock pathway (HSP), unfolded protein response (UPR), and insulin signaling pathway (IS). Phenotypic analysis including: embryonic lethality, protein aggregation expression, and longevity, was completed after knockdown of genes to determine effect on ATZ accumulation. Currently with our preliminary data suggests that the heat-shack pathway may play a role in ATZ accumulation. Determining the mechanism of protein accumulation in the investigation of C. elegans may lead to possible drug targets and therefore the development of a treatment which may alleviate those diagnosed with this disorder.
Systemic analysis of data combined from genetic qtl's and gene expression dat...Laurence Dawkins-Hall
Elucidating changes in gene expression by Micro array genomic sweeps of genetic QTLs linked to Tryp resistance in WT cattle to identify putative candidates underpinning pathophysiology
Src jbbr-20-120 Dr. ihsan edan abdulkareem alsaimary PROFESSOR IN MEDICAL M...dr.Ihsan alsaimary
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
Assessment of immunomolecular_expression_and_prognostic_role_of_tlr7_among_pa...dr.Ihsan alsaimary
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
A systematic, data driven approach to the combined analysis of microarray and...Laurence Dawkins-Hall
The use of gene expression data from Micro arrays coupled with WT QTL's linked to Tryp resistance phenotypes in Cattle to elucidate pertinent genetic changes underpinning phenotype in putative candidate genes
Insights into the tumor microenvironment and therapeutic T cell manufacture r...Thermo Fisher Scientific
TCRβ immune repertoire analysis by next-generation sequencing is emerging as a valuable tool for research studies of the tumor microenvironment and potential immune responses to cancer immunotherapy1-4. Here we describe a multiplex PCR-based TCRβ sequencing assay (Ion AmpliSeqTM Immune Repertoire Assay Plus – TCRβ) that leverages Ion AmpliSeq library construction chemistry and the long read capability of the Ion S5 530TM chip to provide coverage of all three CDR domains of the human TCRβ chain. We demonstrate use of the assay to evaluate tumor-infiltrating T cell repertoire features and monitor manufacture of therapeutic T cells.
Proteomic Analysis of the Serum and Excretory-Secretary proteins of Trichinel...AmalDhivaharS
The nematodes of the genus Trichinella are known to cause the pressing foodborne parasitic disease Trichinellosis and these parasites are known to complete all stages of development in one host with the enteral and parenteral phases observed during infection. Proteomics, in general, pertains to the systematic identification and quantification of the totality of proteins, which is the proteome of a biological system, at a specific point in time. The available proteomic studies have paved the way to identify and characterize Trichinella stage-specific proteins reacting with infected host-specific antibodies. Yet, very few contributions provide any information about changes in the global proteomic serum profile of Trichinella-infested individuals. Studies demonstrate that various Trichinella species and their phases of the invasion produce a characteristic proteomic pattern in the serum of experimentally infected pigs. Recent investigations have found that T. spiralis infection induced strong regulatory T cell responses through parasite excretory-secretory (ES) products, characterized by an increase of some regulatory T cells and growth factors. T. spiralis has also been reported to induce the angiogenic molecule vascular endothelial cell growth factor (VEGF) during nurse cell formation towards the induction of angiogenesis for nutrient supply and waste disposal. Herein, the various analogs considered in these studies include the serum, excretory-secretory proteins, surface proteins, immune-reactive proteins from muscle larvae (ML) and so on. Intestinal cultures, striated muscle tissues, pigs, mice, beavers, contributions from patients are some of the major models exploited for this purpose. The current analysis focuses on recapitulating the recent findings driven on this area to create a common ground for further studies and to ease any difficulty in continuing the proteomic analysis of T. spiralis using in vitro and in vivo models.
characterization of FQ Non-susceptible S. Pyogenescamilomesa22
The aim of this study was to investigate the frequency, mechanism, and epidemiological association of FQ non susceptibility in S.pyogenes during 2011 and 2016 from Shanghai, China.
identification and characterization of FQ-non-susceptable S. Pyogenescamilomesa22
The aim of this study was to investigate the frequency, mechanism, and epidemiological association of FQ non susceptibility in S.pyogenes during 2011 and 2016 from Shanghai, China.
The 'omics' revolution: How will it improve our understanding of infections a...WAidid
This slideset explains the ‘Omics’ technology and its role in the study of infections and vaccination. It is a revolution as it offers powerful tools to interrogate the animal / human immune response to vaccines and infections.
Shigella flexneri serotype 1c derived from serotype 1a by acquisition of gtrI...Swee Seong TANG
Background
Shigella spp. are the primary causative agents of bacillary dysentery. Since its emergence in the late 1980s, the S. flexneri serotype 1c remains poorly understood, particularly with regard to its origin and genetic evolution. This article provides a molecular insight into this novel serotype and the gtrIC gene cluster that determines its unique immune recognition.
Results
A PCR of the gtrIC cluster showed that serotype 1c isolates from different geographical origins were genetically conserved. An analysis of sequences flanking the gtrIC cluster revealed remnants of a prophage genome, in particular integrase and tRNAPro genes. Meanwhile, Southern blot analyses on serotype 1c, 1a and 1b strains indicated that all the tested serotype 1c strains may have had a common origin that has since remained distinct from the closely related 1a and 1b serotypes. The identification of prophage genes upstream of the gtrIC cluster is consistent with the notion of bacteriophage-mediated integration of the gtrIC cluster into a pre-existing serotype.
Conclusions
This is the first study to show that serotype 1c isolates from different geographical origins share an identical pattern of genetic arrangement, suggesting that serotype 1c strains may have originated from a single parental strain. Analysis of the sequence around the gtrIC cluster revealed a new site for the integration of the serotype converting phages of S. flexneri. Understanding the origin of new pathogenic serotypes and the molecular basis of serotype conversion in S. flexneri would provide information for developing cross-reactive Shigella vaccines.
Keywords
Shigella flexneri, Bacillary dysentery, Serotype-conversion , Evolutionary origin, Glucosyltransferase, Serotype 1c
Female mammals achieve dosage compensation by inactivating one of their two X chromosomes
during development, a process entirely dependent on Xist, an X-linked long noncoding
RNA (lncRNA). At the onset of X chromosome inactivation (XCI), Xist is up-regulated
and spreads along the future inactive X chromosome. Contextually, it recruits repressive
histone and DNA modifiers that transcriptionally silence the X chromosome. Xist regulation is
tightly coupled to differentiation and its expression is under the control of both pluripotency
and epigenetic factors. Recent evidence has suggested that chromatin remodelers accumulate
at the X Inactivation Center (XIC) and here we demonstrate a new role for Chd8 in Xist
regulation in differentiating ES cells, linked to its control and prevention of spurious
transcription factor interactions occurring within Xist regulatory regions. Our findings have a
broader relevance, in the context of complex, developmentally-regulated gene expression.
An evaluation of methods used to sequence pGEM template within core facilitie...Laurence Dawkins-Hall
A horizontal study by ABRF designed to investigate & collate cycle sequencing methods for the pGEM template and subsequent data output on automated sequencing platforms (cf. AB 3700 & AB 3100)
Optimising parameters associated with a high through put FRET assay for identifying Tryp REL 1 antagonists, viz.
1. Ligation conditions, cf. buffer composition e.g. pH; ligation time etc
2. Mixing and matching fluorophores to maximise S:N and hence assay sensitivity
1. more work at optimising expression and purification of rREL 1 for incorporation into a high throughput FRET assay for compound library screens to identify REL 1 antagonists
2. Regression analysis of titrants of compounds identified as demonstrating REL 1 inhibition by radiomimetic assay; quantification of efficacy by means of IC50
Lab talk 020410 inducing rel 1 to set up ht fret assay_progressLaurence Dawkins-Hall
Outlining procedural pipeline for expressing and purifying active rREL 1 for incorporation into high throughput fluorescent (FRET) screening assay for identifying antagonistic hits of REL 1
Lab talk 190210 efficacy studies on radioligand hits_beginnings of fret assay...Laurence Dawkins-Hall
1. Titration of REL 1 antagonist hits identified by radio mimetic assay to quantify efficacy (IC50)
2. Exposition of HT FRET assay principles for large scale compound library screens to empirically identify REL 1 antagonist hits
Lab talk 020710 comparing bac r_rel 1 with e coli rrel 1 for use in fret assayLaurence Dawkins-Hall
Comparing activity of baculovirus and E Coli expressed rREL 1 fractions in context of HT FRET assay for screening compound libraries to identify REL1 antagonist hits
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Salas, V. (2024) "John of St. Thomas (Poinsot) on the Science of Sacred Theol...Studia Poinsotiana
I Introduction
II Subalternation and Theology
III Theology and Dogmatic Declarations
IV The Mixed Principles of Theology
V Virtual Revelation: The Unity of Theology
VI Theology as a Natural Science
VII Theology’s Certitude
VIII Conclusion
Notes
Bibliography
All the contents are fully attributable to the author, Doctor Victor Salas. Should you wish to get this text republished, get in touch with the author or the editorial committee of the Studia Poinsotiana. Insofar as possible, we will be happy to broker your contact.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
PRESENTATION ABOUT PRINCIPLE OF COSMATIC EVALUATION
Genomic approaches to trypanosome resistance
1. BIG DIFFERENCES BETWEEN GENOTYPES AND OVER TIME. Between 600 and 750 probes were differently expressed
between infected and uninfected cattle. Principle component analysis of the expression data clearly shows genome-wide
differences between the transcriptomes of tolerant (×) and susceptible ( ) cattle (Top Right, PCA component 3) and some of these
differences are associated with the presence and progression of trypanosome infection (Top left, PCA component 1).
This image cannot currently be displayed.
This image cannot currently be displayed.
Genomics approaches to trypanosomiasis resistance
Breeds of cattle which are resistant and susceptible to pathology following Trypanosoma congolense infection, show
differences in gene expression following challenge. Examination of the networks of genes responding most
differently between these genotypes provides insights into the biology of the response to infection.
Where differentially used networks include genes within QTL for resistance, those genes become functional
candidates irrespective of whether they are differentially expressed themselves. The diversity of cattle and disease
challenge across Africa provides a unique natural experiment which can be used to evaluate these genes for
evidence of a functional role in trypanosome resistance.
The responding networks provide new ways of examining the pathology, raising hypotheses and suggesting novel
interventions which may be unrelated to the present diversity represented by the QTL.
GeneGo was used to identify networks amongst the
genes that were differentially expressed. The figure
(right) shows the largest network of connected genes that
were differently expressed by trypanosome infected
resistant (N’Dama) and susceptible (Boran) cattle.
STAT3 and c-Fos have the most connectivity. STAT3 is a
transcription factor which is activated in response to the
IL-6 family of cytokines and is involved in the acute
phase response in the liver
Interestingly, STAT3 is modulated by RAC1 which is in
turn controlled by VAV1 and ARHGAP15 which are both
located in the QTLs controlling trypanotolerance.
Different cattle genotypes show differences in gene expression before and during trypanosome infection.
Trypanosome infection induces profound changes in the steady state level of many genes.
Network-based analysis reveals some highly concordantly responding networks
Genes that are within QTL and also within highly connected networks are strong candidates for QTL genes
Some differentially expressed genes are highly connected to many other differentially expressed genes. These are key points
for intervention.
Twenty N’Dama (tolerant) cattle and 20 Boran (susceptible) cattle were challenged with a lethal dose of T. congolense. Liver
biopsy samples were taken from each individual in specified days prior to and post infection such that at each time point there
were samples from at least 5 Boran and 5 N’Dama.
The mRNA profiles were assayed using the Affymetrix 24K probe sets (B). The gene data were fed into an analysis workflow (C)
that integrates the expression measures, gene ontology, QTL information, and gene pathways data.
Agaba M1
Anderson S4
Archibald A4
Brass A2
Gibson J5
Hall L4
Hanotte O1
Hulme H2
Kemp SJ1,3
Mwakaya J1
Noyes, HA3
Ogugo M1
Rennie C3
Addresses
1International Livestock
Research Institute,
Box 30709 - 00100, Nairobi
Kenya
2The University of
Manchester
LF8 Kilburn Bldg, Oxford Rd
Manchester M13 9PL
UK
3School of Biological
Sciences,
University of Liverpool,
Liverpool, L69 7ZB, UK
4Roslin Institute,
Roslin,
Midlothian, EH25 9PS, UK
5The Institute for Genetics &
Bioinformatics, Hawkins
Homestead, University of
New England, Armidale,
NSW 2351, Australia
Acknowledgements:
We thank all the staff at the
ILRI large animal facility and
all colleagues in the
Welcome Trust Consortium
This work was supported by
the Wellcome Trust.
QTL with p<0.0043 FDR(10%)
PCV
Body weight
Parasitaemia
Hanotte et al PNAS 2003 7443-7448
-15
-10
-5
0
5
10
15
N’Dama (tolerant)
-15
-10
-5
0
5
10
15
Boran (susceptible)
A cross between relatively
susceptible Boran and resistant
N’dama has shown that each
breed carries 5 different QTL for
resistance, and these have been
mapped in an F2 cross.