Specific inhibition of CK2α from an anchor outside the active sitePaul Brear
The development of selective inhibitors of protein kinases is challenging because of the significant conservation of the ATP binding site. Here, we describe a new mechanism by which the protein kinase CK2α can be selectively inhibited using features outside the ATP site. We have identified a new binding site for small molecules on CK2α adjacent to the ATP site and behind the αD loop, termed the αD pocket. An elaborated fragment anchored in this site has been linked with a low affinity fragment binding in the ATP site, creating a novel and selective inhibitor (CAM4066) that binds CK2α with a Kd of 320 nM and shows significantly improved selectivity compared to other CK2α inhibitors. CAM4066 shows target engagement in several cell lines and similar potency to clinical trial candidate CX4945. Our data demonstrate that targeting a poorly conserved, cryptic pocket allows inhibition of CK2α via a novel mechanism, enabling the development of a new generation of selective CK2α inhibitors.
Assessment of TP53 Mutation Status in Breast Tumor Tissue using the "Ion Ampl...Thermo Fisher Scientific
TP53 mutations are found in 30% of breast tumors and are associated with poor prognosis in distinct subtypes of breast cancer. Direct sequencing is commonly used to obtain TP53 mutation status in tumor tissue, but has limitations in detection level and is time-consuming. Methods targeting hotspots is insufficient for TP53 analysis since the mutations are widely spread along the gene1. Here we describe the development of the Ion TorrentTM next-generation semiconductor sequencing and Ion AmpliSeqTM technology (Life TechnologiesTM).
Dr. Yao-Wei Huang - Here we go again? Emergence of a novel swine enteric alph...John Blue
Here we go again? Emergence of a novel swine enteric alphacoronavirus (SeACov) in Southern China - Dr. Yao-Wei Huang, Zhejiang University, from the 2017 North American PRRS/National Swine Improvement Federation Joint Meeting, December 1‐3, 2017, Chicago, Illinois, USA.
More presentations at http://www.swinecast.com/2017-north-american-prrs-nsif-joint-meeting
Identify Compounds that Rescue Disease Relevant Mutant Membrane ProteinsDiscoverX Corporation
Learn about diseases caused by protein misfolding and how you can screen for compounds, known as pharmacochaperones, that rescue misfolded proteins and could be used as therapeutics.
Effects of CTGF Overexpression on Fibrosis-Related PhenotypesAshley Kennedy
Wound healing consists of three phases: inflammation, proliferation, and remodeling. During proliferation and remodeling, new extracellular matrix (ECM) is laid down by cells called fibroblasts. ECM consists of proteins that provide structural support in tissues. ECM production and fibroblast migration and proliferation are stimulated by connective tissue growth factor (CTGF). During wound healing, CTGF is induced by transforming growth factor beta (TGF-beta) to stimulate this response. When TGF-beta and CTGF are overexpressed, excessive amounts of ECM proteins are laid down, forming scar tissue, also known as fibrosis. Fibrotic tissue in organs can impair healthy function, leading to organ failure. To better understand how CTGF functions in fibrotic tissue, cells with varying levels of CTGF expression will be examined in a cell model of wounding. We will measure gene expression and observe cells for changes in fibrosis-related phenotypes. We hypothesize that increased CTGF expression will lead to enhanced cell growth, motility, and ECM production, as compared to controls. Results will provide a foundation for further research into the effects of CTGF variations on fibrosis-related phenotypes.
Conferència a càrrec d'Enriqueta Felip. Oncòloga de l'Hospital Vall d'Hebron de Barcelona. Líder en la investigació de càncer de pulmó al VHIO. Membre de la Junta Directiva de la Societat Espanyola d'Oncologia Mèdica i de l'European Society for Medical Oncology. En el marc de la Jornada "Els nous reptes de la Medicina de Precisió" organitzada el 12 de novembre per la Societat Catalana de Gestió Sanitària
Current and Novel Immuno-Oncology Drug Evaluation Methods via Humanized Mouse...InsideScientific
Dr. Bin Xie discusses the current immuno-oncology drug development landscape, different humanized mouse models available for drug testing, and the investigation of potential mechanisms via imaging mass cytometry.
Since the first immune checkpoint blocker ipilimumab was approved by the US FDA in 2011, more drug companies have sought to develop their own immune therapy drugs. Humanized peripheral blood mononuclear cell (PBMC) reconstitution in immune deficient mice is becoming a valuable model for evaluating therapeutic antibodies, especially bispecific antibodies (BsAbs), which can mediate immune cells as well as target a tumor antigen.
However, this model has several drawbacks, including a limited dosing window due to graft-versus-host-disease and insufficient natural immune cell infiltration. This has hindered wide application of the model in the development of multiple immune checkpoint inhibitors or immune agonists.
To overcome these issues, LIDE has developed a unique human PBMC/cancer cell co-transfer model which can generate three-dimensional huPBMC-infiltrated tumor tissue for immunotherapy. This model has successfully been used to evaluate the biological function of several signaling proteins and biomarkers in multiple cancers, such as melanoma, breast cancer, and lung cancer.
In this webinar, Dr. Bin Xie discusses the current immuno-oncology drug development landscape, different humanized models available for drug testing, evaluates real-world case studies, and describes the investigation of potential mechanisms by imaging mass cytometry.
Key Topics Include:
- Introduction to immuno-oncology drug development and the importance of using humanized mouse models to address scientific questions
- Evaluation of current IO platforms and new methods from LIDE, including analysis of several case studies
- Understanding the spatiotemporal interaction between tissue-infiltrating immune cells and cancer cells via imaging mass cytometry
A quick introduction of Genomic Testing Cooperative (GTC).
We strive to offer advanced genomic testing to communities everywhere at an affordable price.
We utilize a cooperative business model that enables academic and commercial laboratories to help physicians treat patients locally with the most advanced precision medicine.
We embrace disruptive deep learning and advanced technology to create scalable efficiencies, incomparable precision, and a more personalized approach to patient care.
https://www.genomictestingcooperative.com
A choice of population-optimized GWAS imputation grids, combined with exome, loss-of-function, ADME, and eQTL markers in one high-coverage, high-value, customizable design.
Axiom® Genome-Wide LAT 1 Array World Array 4Affymetrix
Coverage-Optimized World Arrays: next-generation designs combining GWAS, replication, and fine-mapping into one array. Dense marker coverage of disease-associated SNPs, genes, and regions, plus whole-genome coverage of common and rare variants. Optimized for diverse ancestries including European, African and Native American.
A novel method for building custom ampli seq panels using optimized pcr primers Thermo Fisher Scientific
AmpliSeq™ is a next generation sequencing library preparation method for targeted re-sequencing that utilizes highly multiplexed PCR to amplify regions of interest. A key to successful AmpliSeq libraries is the primer panel used for target amplification. Until now primers have been available as pre-assembled ready-to-use panels, or as custom made-to-order panels. We describe a new process for creating customized panels consisting of optimized and verified PCR primers. The primer sets are available as whole genes (i.e., all of the primers needed to create libraries that cover the entire coding regions of genes) and are selectable on the ampliseq.com website by either uploading gene lists or choosing genes from disease research areas.
We show NGS sequencing data from 10 disease research-oriented panels, including newborn screening research and inherited cancer research, assembled from individual pre-verified gene sets. Panel performance data include coverage uniformity, reproducibility, and sensitivity and positive predictive value of variant calling. To demonstrate flexibility of panel content and performance, the coverage uniformity of the 59 genes recommended by the American College of Medical Genetics and Genomics for reporting of incidental findings (ACMG59) was evaluated by themselves and with up to 135 additional genes and shown to be ≥ 97% in all contexts. We also demonstrate the robustness of this method using a variety of sample types (fresh, frozen, and dried blood, cheek swabs) with both manual and fully automated library preparation methods. For Research use only. Not for use in diagnostic procedures.
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic AnalysisGolden Helix
In the rapidly evolving field of genomic analysis, staying current with the latest research, data sources, and test advancements is crucial. In this webinar, we review how VarSeq addresses the needs to stay on top of the latest with the release of VarSeq 2.6.0.
This release features an exome-optimized workflow for LOH and CNV calling as well as the introduction of VSPGx to produce pharmacogenomic reports for gene panels as well as exomes and genomes. With the recent release of gnomAD v4, we have had many requests for the integration of this large update to the most population frequency source. With VarSeq 2.6.0, the latest version of gnomAD has been integrated into VSClinical and the updated tracks spans beyond variants to cover CNVs and gene scores to update all your workflows to the latest data.
In this webcast, we will cover.
Improved VS-CNV performance and updated exome analysis workflows.
Pharmacogenomics in action: Utilizing VSPGx for exome and genome assessments.
gnomAD v4 in practice: Updated automated and manual variant interpretation workflows.
Join us for an insightful session on the latest VarSeq 2.6.0 features, bringing you the most up-to-date data and workflows for your genomic analysis.
Specific inhibition of CK2α from an anchor outside the active sitePaul Brear
The development of selective inhibitors of protein kinases is challenging because of the significant conservation of the ATP binding site. Here, we describe a new mechanism by which the protein kinase CK2α can be selectively inhibited using features outside the ATP site. We have identified a new binding site for small molecules on CK2α adjacent to the ATP site and behind the αD loop, termed the αD pocket. An elaborated fragment anchored in this site has been linked with a low affinity fragment binding in the ATP site, creating a novel and selective inhibitor (CAM4066) that binds CK2α with a Kd of 320 nM and shows significantly improved selectivity compared to other CK2α inhibitors. CAM4066 shows target engagement in several cell lines and similar potency to clinical trial candidate CX4945. Our data demonstrate that targeting a poorly conserved, cryptic pocket allows inhibition of CK2α via a novel mechanism, enabling the development of a new generation of selective CK2α inhibitors.
Assessment of TP53 Mutation Status in Breast Tumor Tissue using the "Ion Ampl...Thermo Fisher Scientific
TP53 mutations are found in 30% of breast tumors and are associated with poor prognosis in distinct subtypes of breast cancer. Direct sequencing is commonly used to obtain TP53 mutation status in tumor tissue, but has limitations in detection level and is time-consuming. Methods targeting hotspots is insufficient for TP53 analysis since the mutations are widely spread along the gene1. Here we describe the development of the Ion TorrentTM next-generation semiconductor sequencing and Ion AmpliSeqTM technology (Life TechnologiesTM).
Dr. Yao-Wei Huang - Here we go again? Emergence of a novel swine enteric alph...John Blue
Here we go again? Emergence of a novel swine enteric alphacoronavirus (SeACov) in Southern China - Dr. Yao-Wei Huang, Zhejiang University, from the 2017 North American PRRS/National Swine Improvement Federation Joint Meeting, December 1‐3, 2017, Chicago, Illinois, USA.
More presentations at http://www.swinecast.com/2017-north-american-prrs-nsif-joint-meeting
Identify Compounds that Rescue Disease Relevant Mutant Membrane ProteinsDiscoverX Corporation
Learn about diseases caused by protein misfolding and how you can screen for compounds, known as pharmacochaperones, that rescue misfolded proteins and could be used as therapeutics.
Effects of CTGF Overexpression on Fibrosis-Related PhenotypesAshley Kennedy
Wound healing consists of three phases: inflammation, proliferation, and remodeling. During proliferation and remodeling, new extracellular matrix (ECM) is laid down by cells called fibroblasts. ECM consists of proteins that provide structural support in tissues. ECM production and fibroblast migration and proliferation are stimulated by connective tissue growth factor (CTGF). During wound healing, CTGF is induced by transforming growth factor beta (TGF-beta) to stimulate this response. When TGF-beta and CTGF are overexpressed, excessive amounts of ECM proteins are laid down, forming scar tissue, also known as fibrosis. Fibrotic tissue in organs can impair healthy function, leading to organ failure. To better understand how CTGF functions in fibrotic tissue, cells with varying levels of CTGF expression will be examined in a cell model of wounding. We will measure gene expression and observe cells for changes in fibrosis-related phenotypes. We hypothesize that increased CTGF expression will lead to enhanced cell growth, motility, and ECM production, as compared to controls. Results will provide a foundation for further research into the effects of CTGF variations on fibrosis-related phenotypes.
Conferència a càrrec d'Enriqueta Felip. Oncòloga de l'Hospital Vall d'Hebron de Barcelona. Líder en la investigació de càncer de pulmó al VHIO. Membre de la Junta Directiva de la Societat Espanyola d'Oncologia Mèdica i de l'European Society for Medical Oncology. En el marc de la Jornada "Els nous reptes de la Medicina de Precisió" organitzada el 12 de novembre per la Societat Catalana de Gestió Sanitària
Current and Novel Immuno-Oncology Drug Evaluation Methods via Humanized Mouse...InsideScientific
Dr. Bin Xie discusses the current immuno-oncology drug development landscape, different humanized mouse models available for drug testing, and the investigation of potential mechanisms via imaging mass cytometry.
Since the first immune checkpoint blocker ipilimumab was approved by the US FDA in 2011, more drug companies have sought to develop their own immune therapy drugs. Humanized peripheral blood mononuclear cell (PBMC) reconstitution in immune deficient mice is becoming a valuable model for evaluating therapeutic antibodies, especially bispecific antibodies (BsAbs), which can mediate immune cells as well as target a tumor antigen.
However, this model has several drawbacks, including a limited dosing window due to graft-versus-host-disease and insufficient natural immune cell infiltration. This has hindered wide application of the model in the development of multiple immune checkpoint inhibitors or immune agonists.
To overcome these issues, LIDE has developed a unique human PBMC/cancer cell co-transfer model which can generate three-dimensional huPBMC-infiltrated tumor tissue for immunotherapy. This model has successfully been used to evaluate the biological function of several signaling proteins and biomarkers in multiple cancers, such as melanoma, breast cancer, and lung cancer.
In this webinar, Dr. Bin Xie discusses the current immuno-oncology drug development landscape, different humanized models available for drug testing, evaluates real-world case studies, and describes the investigation of potential mechanisms by imaging mass cytometry.
Key Topics Include:
- Introduction to immuno-oncology drug development and the importance of using humanized mouse models to address scientific questions
- Evaluation of current IO platforms and new methods from LIDE, including analysis of several case studies
- Understanding the spatiotemporal interaction between tissue-infiltrating immune cells and cancer cells via imaging mass cytometry
A quick introduction of Genomic Testing Cooperative (GTC).
We strive to offer advanced genomic testing to communities everywhere at an affordable price.
We utilize a cooperative business model that enables academic and commercial laboratories to help physicians treat patients locally with the most advanced precision medicine.
We embrace disruptive deep learning and advanced technology to create scalable efficiencies, incomparable precision, and a more personalized approach to patient care.
https://www.genomictestingcooperative.com
A choice of population-optimized GWAS imputation grids, combined with exome, loss-of-function, ADME, and eQTL markers in one high-coverage, high-value, customizable design.
Axiom® Genome-Wide LAT 1 Array World Array 4Affymetrix
Coverage-Optimized World Arrays: next-generation designs combining GWAS, replication, and fine-mapping into one array. Dense marker coverage of disease-associated SNPs, genes, and regions, plus whole-genome coverage of common and rare variants. Optimized for diverse ancestries including European, African and Native American.
A novel method for building custom ampli seq panels using optimized pcr primers Thermo Fisher Scientific
AmpliSeq™ is a next generation sequencing library preparation method for targeted re-sequencing that utilizes highly multiplexed PCR to amplify regions of interest. A key to successful AmpliSeq libraries is the primer panel used for target amplification. Until now primers have been available as pre-assembled ready-to-use panels, or as custom made-to-order panels. We describe a new process for creating customized panels consisting of optimized and verified PCR primers. The primer sets are available as whole genes (i.e., all of the primers needed to create libraries that cover the entire coding regions of genes) and are selectable on the ampliseq.com website by either uploading gene lists or choosing genes from disease research areas.
We show NGS sequencing data from 10 disease research-oriented panels, including newborn screening research and inherited cancer research, assembled from individual pre-verified gene sets. Panel performance data include coverage uniformity, reproducibility, and sensitivity and positive predictive value of variant calling. To demonstrate flexibility of panel content and performance, the coverage uniformity of the 59 genes recommended by the American College of Medical Genetics and Genomics for reporting of incidental findings (ACMG59) was evaluated by themselves and with up to 135 additional genes and shown to be ≥ 97% in all contexts. We also demonstrate the robustness of this method using a variety of sample types (fresh, frozen, and dried blood, cheek swabs) with both manual and fully automated library preparation methods. For Research use only. Not for use in diagnostic procedures.
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic AnalysisGolden Helix
In the rapidly evolving field of genomic analysis, staying current with the latest research, data sources, and test advancements is crucial. In this webinar, we review how VarSeq addresses the needs to stay on top of the latest with the release of VarSeq 2.6.0.
This release features an exome-optimized workflow for LOH and CNV calling as well as the introduction of VSPGx to produce pharmacogenomic reports for gene panels as well as exomes and genomes. With the recent release of gnomAD v4, we have had many requests for the integration of this large update to the most population frequency source. With VarSeq 2.6.0, the latest version of gnomAD has been integrated into VSClinical and the updated tracks spans beyond variants to cover CNVs and gene scores to update all your workflows to the latest data.
In this webcast, we will cover.
Improved VS-CNV performance and updated exome analysis workflows.
Pharmacogenomics in action: Utilizing VSPGx for exome and genome assessments.
gnomAD v4 in practice: Updated automated and manual variant interpretation workflows.
Join us for an insightful session on the latest VarSeq 2.6.0 features, bringing you the most up-to-date data and workflows for your genomic analysis.
Development of a high-throughput high-density SNP genotyping array for bovineAffymetrix
Ali Pirani, Bioinformatics, Affymetrix.Our bioinformatics team first developed a workflow for validating de novo SNPs in animals. They have since applied this successfully in multiple plant species.
A next generation sequencing based sample-to-result pharmacogenomics research...Thermo Fisher Scientific
Pharmacogenomics (PGx) is the study of genetic variations in terms of their response to drugs. Variations in gene sequence or copy numbers may result in complete loss of function, partial decrease or increase in enzyme activity, or an altered affinity for substrates, which may in turn significantly impact drug efficacy. PGx studies are becoming increasingly important for precision medicine. We have developed a next generation sequencing (NGS) PGx research solution with increased flexibility on the assay targets and combined detection of SNP/INDEL genotyping and CNV using Ion AmpliSeq™ technology for low to medium throughput laboratories. With this highly multiplexed PGx research panel we can profile a set of 136 genetic markers in 40 known PGx related genes (Table 1) and determine CYP2D6 copy number variation (CNV, Figure 1) in a single reaction using Ion Torrent™ semiconductor sequencing.
Alzheimer’s disease (AD) is a devastating neurodegenerative disease that is genetically complex. Although great progress has been made in identifying fully penetrant mutations in genes that cause early-onset AD, these still represent a very small percentage of AD cases. Large-scale, genome-wide association studies (GWAS) have identified at least 20 additional genetic risk loci for the more common form: late-onset AD. However, the identified SNPs are typically not the actual risk variants, but are in linkage disequilibrium with the presumed causative variants [1].
To help identify causative genetic variants, we have combined highly accurate, long-read sequencing with hybrid-capture technology. In this collaborative webinar*, we present this method and show how combining IDT xGen® Lockdown® Probes with PacBio SMRT® Sequencing allows targeting and sequencing of candidate genes from genomic DNA and corresponding transcripts from cDNA. Using a panel of target capture probes for 35 AD candidate genes, we demonstrate the power of this approach by looking at data for two individuals with AD. Some additional benefits of this method include the ability to leverage long reads, phase heterozygous variants, and link corresponding transcript isoforms to their respective alleles.
Reference: 1. Van Cauwenberghe C, Van Broeckhoven C, Sleegers K. (2016) The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med, 18(5):421–430.
* This presentation represents a collaboration between Pacific Biosciences and Integrated DNA Technologies. The individual opinions expressed may not reflect shared opinions of Pacific Biosciences and Integrated DNA Technologies.
Automating the ACMG Guidelines with VSClinicalGolden Helix
Clinical Genetic testing requires a complex analysis using the totality of our knowledge about the clinical relevance of a variant and a gene. This includes bioinformatic evidence as well as clinical evidence. The ACMG Guidelines provided a framework in which to score variants based on this evidence, and while some of those scoring criteria require close consultation of the clinical context for a given patient, much of it can be automated.
In this webcast, we review how VSClinical automates the ACMG scoring guidelines while integrating the collective lab expertise from previously classified variants and preferences about genes. We will cover:
Using the ACMG Auto Classifier as part the filtering strategy for gene panels and trio workflows
How gene preferences such as the default transcript, inheritance model, and disorder are updated and saved from VSClinical and used in all future analysis
How the per-variant recommendation engine builds on the auto-classification with descriptive reasons for answering each criterion yes or no
Using the auto-interpretation to present the evidence for all scored criteria in a human-readable paragraph
Working with VSClinical’s self-learning knowledgebase that incorporates previously classified variants and genes inform the interpretation of new variants!
Cancer is a disease characterized by uncontrolled cell growth and proliferation. Recent advances in molecular medicine and cancer biology have changed the way research clinicians evaluate and consider treatment. Selected tumor biomarkers have been utilized as targets for drug therapy leading to better more effective treatment. Gene expression profiling has been used for identifying new biomarkers for tumor classification and driving decision making for better patient outcome in different tumor types. DNA microarrays have become a key method to acquire a comparative snapshot of the gene expression profile from test samples in a high throughput manner. Quantitative PCR and newer sequencing techniques are popular research alternatives offering highly accurate gene expression measurements, but with limitations due to cost, complex instrumentation and analysis needs. RNA extracted from formalin fixed paraffin embedded tissue (FFPE) creates considerable additional challenges in acquiring accurate gene expression measurements due to the highly fragmented and compromised integrity of FFPE RNA due to the fixation process.
SNP genotyping using the Affymetrix® Axiom® Genome-Wide Pan-African (PanAFR) ...Affymetrix
Affymetrix Research and Development Scientists Many GWAS arrays are optimized for European populations but significantly compromise study power when used in non-European cohorts. Read about the design strategy of the Axiom Pan-African Array, our leading solution for optimized whole-genome studies of African ancestries.
A SNP array for human population genetics studiesAffymetrix
Yontao Lu, Teri Genschoreck, Swapan Mallick, Amy Ollmann, Nick Patterson, Yiping Zhan, Teresa Webster, David Reich Overview of the Human Origins Array, the first array developed with leading geneticists to enable rigorous population genetics studies.
Statistical methods for off-target variant genotyping on Affymetrix' Axiom Ar...Affymetrix
Teresa Webster, Bioinformatics, Affymetrix.Automated clustering and calling of ""Off-Target Variants,"" atypical cluster patterns caused by secondary variants in the probe hybridization region.
Allopolyploid Genotyping Algorithm on Affymetrix' Axiom ArraysAffymetrix
Hong Gao, Bioinformatics, Affymetrix.An automated algorithm that reduces genotype analysis to ~1 hour is described and applied to hexaploid wheat data.
SNP genotyping of markers with nearby secondary polymorphisms using Affymetri...Affymetrix
Laurent Bellon, Product Development, Affymetrix.Axiom® Genotyping Solution is uniquely suited to genotyping of highly polymorphic genomes as it is permissive to secondary variants as close as 10 bp from the target variant.
SNP genotyping using Affymetrix' Axiom Genotyping SolutionAffymetrix
Michael Shapero, Product Development, Affymetrix.Outline of the development and performance of the new Axiom® 384 high-throughput format for low-cost genotyping of up to 50,000 SNPs.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
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.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Richard's entangled aventures in wonderlandRichard 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.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
1. Axiom®
Genome-Wide CHB 1 & CHB 2 Array Plate Set
The highest coverage of rare and common variants for association studies in Han Chinese populations
Highlights
n 1.2 million SNPs selected from GWAS in Han
Chinese populations
n Comprehensive genotype-tested SNPs including
maximized rare and common allele coverage
n Focus on SNPs with strong disease associations
and functional relevance
n Cost- and analysis-efficient design using only highly
informative CHB markers to avoid redundancy
n Fully automatable with quick assay turnaround time
n Low running costs enable highly powered studies
n Flexible, automation-friendly data analysis software
for simplified data management
Array design/SNP selection
All of the content for Axiom®
Genome-Wide (GW) CHB 1
& CHB 2 Array Plate Set was selected from Axiom®
Genomic
Database, which contains genotype-tested markers derived
from various public sources, including the International HapMap
Project, the Single Nucleotide Polymorphism Database (dbSNP),
and the 1000 Genomes Project. Each marker was tested
extensively to ensure robust detection of the minor allele
with stringent performance criteria in the Axiom®
Assay.
Our genotype testing program gives us uniquely detailed
data on population-specific linkage disequilibrium and
haplotypes. This allows us to be highly efficient when selecting
tagging SNPs for high genomic coverage. By avoiding marker
redundancy and uninformative markers, we minimize the
numbers of SNPs needed to achieve genomic coverage.
SNPs were selected to provide maximum genome-wide
coverage including: chromosomes X and Y, mitochondrial
SNPs, cSNPs (coding SNPs), and indels (see Table 1).
Also included on the array are SNPs within functionally
relevant coding and untranslated regions (UTR) including
markers for ADME and disease-associated SNPs. SNPs
were selected from disease annotation databases such as
Gene Ontology (GO) for the cardiovascular system, Sanger
Cancer Gene Census, PharmaADME, SNPs within the Major
Histocompatibility Complex (MHC) region on chromosome
6, and SNPs originating from the National Human Genome
Research Institute (NHGRI) Catalog of Published Genome-
Wide Association Studies (see Table 1).
Comprehensive genomic coverage
The 1.2 million SNPs in Axiom Genome-Wide CHB 1 & CHB 2
Array Plate Set were chosen to deliver comprehensive coverage
of rare and common alleles in Han Chinese populations.
Axiom®
Genome-Wide (GW) CHB 1 Array Plate was designed
for high genomic coverage of common alleles, while Axiom®
Genome-wide (GW) CHB 2 Array Plate focuses on rare variants.
Axiom GW CHB 2 Array Plate was specifically designed to
supplement the content of the Axiom GW CHB 1 Array Plate.
This complementary nature is shown in Table 2.
Data Sheet
Table 1: Breakdown of SNPs by biological relevance.
Biological category
No. SNPs
Axiom
GW CHB 1
Array Plate
No. SNPs
Axiom GW
CHB 1 & CHB 2
Array Plate Set
cSNPs-nonsynonymous 4,225 10,560
cSNPs-synonymous 3,243 8,422
Splicing and UTR 7,641 20,538
Chromosome X 12,545 36,841
Chromosome Y 1,613 2,460
Indels 3,112 3,826
Mitochondrial 217 304
ADME 3,723 7,886
Genic 277,429 552,684
Inflammation and
immunity pathways
4,387 12,009
MHC 1,873 4,229
Cardiovascular N/A 14,293
NHGRI
disease-associated
2,114 2,424
Sanger Cancer
Gene Census
N/A 16,781
Total SNPs 640,674 1,282,446