The impact of chromosomal fusions on 3D genome folding and recombination in the germ line
The spatial folding of chromosomes inside the nucleus has regulatory effects on gene expression, yet the impact of genome reshuffling on this organization remains unclear. Here, we take advantage of chromosome conformation capture in combination with single-nucleotide polymorphism (SNP) genotyping and analysis of crossover events to study how the higher-order chromatin organization and recombination landscapes are affected by chromosomal fusions in the mammalian germ line.
We demonstrate that chromosomal fusions alter the nuclear architecture during meiosis, including an increased rate of heterologous interactions in primary spermatocytes, and alterations in both chromosome synapsis and axis length.
These disturbances in topology were associated with changes in genomic landscapes of recombination, resulting in detectable genomic footprints. Overall, we show that chromosomal fusions impact the dynamic genome topology of germ cells in two ways: (i) altering chromosomal nuclear occupancy and synapsis, and (ii) reshaping landscapes of recombination.
Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of HNSCC with or without HPV infection
Head and neck squamous cell carcinoma (HNSCC) are the sixth most common cancer type in the world. Human papillomavirus (HPV) infection is an emerging risk factor for HNSCC. Immune infiltration of HNSCC is linked to therapeutic results. This article aimed to decide whether variations in HPV status affect immune infiltration, molecular mechanism, and how these results vary in HNSCC patients.
We investigated the tumor-infiltrating immune cells (TIICs) and immune-related gene differences between HPV (+) and HPV (-) HNSCC. The gene expression quantification data of HNSCC and their clinical information were download from the TCGA database. Immune-related genes have been linked to the ImmPort platform.
After analyzed of 22 TIICs in the HNSCC tumor environment by CIBERSORT and further assessment, lower memory B cell and higher T cell regulatory were connected with better HPV (-) HNSCC outcome, higher activated memory CD4 T cell, higher T cell regulatory, and lower activated NK cell were linked with better HPV (+) result.
We finally got five forms of immune genes (CAMP, EDNRB, NTS, CXCL9, LHB) associated with HNSCC progression. Higher expressions of CAMP, EDNRB, and NTS were associated with increased overall survival in HPV (-) patients. Higher expression of CXCL9 and lower expression of LHB contributed to increased overall survival of HPV (+) patients.
There tend to be discrepancies in the cell structure of TIICs and immune-related genes in HPV (-) and HPV (+) HNSCC. These variances are typically too crucial for the therapeutic outcome of the patient and the development of the tumor. In specific, our sample established these candidate immune cells and immune-related genes as candidate reservoirs for further researches.
Multi-ancestry genome-wide association study identifies 27 loci associated with measures of hemolysis following blood storage
The evolutionary pressure of endemic malaria and other erythrocytic pathogens has shaped variation in genes encoding erythrocyte structural and functional proteins, influencing responses to hemolytic stress during transfusion and disease.
We sought to identify such genetic variants in blood donors by conducting a genome-wide association study (GWAS) of 12,353 volunteer donors, including 1,483 African Americans, 1,477 Asians, and 960 Hispanics, whose stored erythrocytes were characterized by quantitative assays of in vitro osmotic, oxidative, and cold-storage hemolysis.
GWAS revealed 27 significant loci (p<5×10-8), many in candidate genes known to modulate erythrocyte structure, metabolism, and ion channels, including SPTA1, ALDH2, ANK1, HK1, MAPKAPK5, AQP1, PIEZO1, and SLC4A1/Band 3. GWAS of oxidative hemolysis identified variants in antioxidant enzymes including GLRX, GPX4, G6PD, and a novel golgi-transport protein SEC14L4.
Genome wide significant loci were also tested for association with the severity of steady state (baseline) in vivo hemolytic anemia in patients with sickle cell disease, with confirmation of identified SNPs in HBA2, G6PD, PIEZO1, AQP1 and SEC14L4. Many of the identified variants, such as those in G6PD, have previously been shown to impair erythrocyte recovery after transfusion, associate with anemia, or cause rare Mendelian human hemolytic diseases.
Candidate SNPs in these genes, especially in polygenic combinations, may affect RBC recovery after transfusion and modulate disease severity in hemolytic diseases, such as sickle cell disease and malaria.
Incorporating Genomic and Genetic Testing into the Treatment of Metastatic Luminal Breast Cancer
Background: Treatment of patients with luminal metastatic breast cancer (MBC) has become even more complex over the last few years as molecular profiling has begun to alter disease management. It is well accepted that MBC is not curable but is treatable. Today we are able to prolong progression-free survival and partly overall survival with targeted and more individual treatment strategies adjusted according to the molecular subtype.
Summary: Genetic and genomic testing has become therapeutically relevant in luminal MBC and is therefore an integral component within the treatment spectrum. By now, germline testing of BRCABRCAPIK3CA mutations are inevitable elements in disease management and the current state of the art in luminal MBC patients.
Furthermore, testing of ESR1 resistance mutation, ERBB2 mutation, microsatellite instability, and neurotrophic tyrosine receptor kinase (NTRK) gene fusion (mainly in secretory breast cancer) has recently gained increasing attention. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities. The following review summarizes current developments in genetic and genomic testing in luminal MBC.
Key messages: In luminal MBC genomics have become an integral component within the spectrum of oncological treatment establishing novel therapeutic facilities. Further developments in treatment personalization adjusted according to the molecular subtype should become increasingly important in order to enhance the progress of de-escalation of chemotherapy in luminal MBC. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities.
Description: Recombinant HIV p24 protein (NCBI accession number ABO61536, AA35-265, L40I) produced in HEK293 cells. Protein carries a C-terminal His-tag.. Protein was purified by immobilised metal affinity and ion exchange chromatography from the pellet of transfected cells.
Human Immunodeficiency Virus p24 Protein [HIV-1/Clade B]
Description: Recombinant HIV p24 protein (NCBI accession number ABO61536, AA35-265, L40I) produced in HEK293 cells. Protein carries a C-terminal His-tag.. Protein was purified by immobilised metal affinity and ion exchange chromatography from the pellet of transfected cells.
Description: HIV-1 p24 Antibody: The human immunodeficiency virus type 1 (HIV-1) particle consists of an envelope, a core and the region between the two termed matrix. The HIV-1 Gag protein is a late structural protein that contains four proteins: matrix (p17), capsid (p24), nucleocapsid (p7) and the p6 protein. The p24 is the major capsid protein of the virus and has been used in clinical trials as one of the components of the HIV-1 vaccine because of the high degree of sequence conservation between different strains.
Description: HIV-1 p24 Antibody: The human immunodeficiency virus type 1 (HIV-1) particle consists of an envelope, a core and the region between the two termed matrix. The HIV-1 Gag protein is a late structural protein that contains four proteins: matrix (p17), capsid (p24), nucleocapsid (p7) and the p6 protein. The p24 is the major capsid protein of the virus and has been used in clinical trials as one of the components of the HIV-1 vaccine because of the high degree of sequence conservation between different strains.
Description: Harvested bacteria are washed and detergent solubilized to produce a cytoplasmic extract enriched with lipoproteins and outer surface proteins (OSPs). The antigen is presented in phosphate buffered saline containing 1 % n-octyl-β-D-glucopyranoside.
Description: Harvested bacteria are washed and detergent solubilized to produce a cytoplasmic extract enriched with lipoproteins and outer surface proteins (OSPs). The antigen is presented in phosphate buffered saline containing 1 % n-octyl-β-D-glucopyranoside.
Description: Harvested bacteria are washed and detergent solubilized to produce a cytoplasmic extract enriched with lipoproteins and outer surface proteins (OSPs). The antigen is presented in phosphate buffered saline containing 1 % n-octyl-β-D-glucopyranoside.
Description: Harvested bacteria are washed and detergent solubilized to produce a cytoplasmic extract enriched with lipoproteins and outer surface proteins (OSPs). The antigen is presented in phosphate buffered saline containing 1 % n-octyl-β-D-glucopyranoside.
Description: Candida albicans is grown on solid medium, washed, disrupted and subjected to an extraction process. The antigen consists of cytoplasmic and cell wall components.
Description: Candida albicans is grown on solid medium, washed, disrupted and subjected to an extraction process. The antigen consists of cytoplasmic and cell wall components.
Description: Bacteria are cultured on solid medium, harvested, washed and solubilised. The antigen is partially purified by detergent extraction and centrifugation.
Description: Bacteria are cultured on solid medium, harvested, washed and solubilised. The antigen is partially purified by detergent extraction and centrifugation.
Description: Campylobacter jejuni is cultured on solid medium. This antigen is a partially purified detergent extract of the membrane fraction. The main component is an outer membrane protein, approximately 45 kDa in SDS-PAGE.
Description: Campylobacter jejuni is cultured on solid medium. This antigen is a partially purified detergent extract of the membrane fraction. The main component is an outer membrane protein, approximately 45 kDa in SDS-PAGE.
Description: Proprietary recombinant antigen expressed in E. coli and purified by chromatography. Individually pooled antigens shown to react with QC serum panel (multiple negative, borderline and positive sera) within defined reactivity range in Coxsackie-/Echovirus
Description: Proprietary recombinant antigen expressed in E. coli and purified by chromatography. Individually pooled antigens shown to react with QC serum panel (multiple negative, borderline and positive sera) within defined reactivity range in Coxsackie-/Echovirus
Description: Proprietary recombinant antigen expressed in E. coli and purified by chromatography. Individually pooled antigens shown to react with QC serum panel (multiple negative, borderline and positive sera) within defined reactivity range in Coxsackie-/Echovirus IgA, IgG and IgM ELISA.
Description: Proprietary recombinant antigen expressed in E. coli and purified by chromatography. Individually pooled antigens shown to react with QC serum panel (multiple negative, borderline and positive sera) within defined reactivity range in Coxsackie-/Echovirus IgA, IgG and IgM ELISA.
Description: Yersinia pestis V antigen (LcrV antigen, capsule protein fraction 1, type III secretion system needle tip protein). The protein is produced as an N-terminal GST fusion, with GST being cleaved by thrombin and is not present in the final product.
Description: Yersinia pestis V antigen (LcrV antigen, capsule protein fraction 1, type III secretion system needle tip protein). The protein is produced as an N-terminal GST fusion, with GST being cleaved by thrombin and is not present in the final product.
Description: HIV-1 p24 Monoclonal Antibody: The human immunodeficiency virus type 1 (HIV-1) particle consists of an envelope, a core and the region between the two termed matrix (1). The HIV-1 Gag protein is a late structural protein that contains four proteins: matrix (p17), capsid (p24), nucleocapsid (p7) and the p6 protein (2). The p24 constitutes the major core component of the virus and shows high degree of sequence conservation among HIV isolates. The Gag p24 has been used as an integral part of multicomponent HIV-1 vaccines (3).
Description: HIV-1 p24 Monoclonal Antibody: The human immunodeficiency virus type 1 (HIV-1) particle consists of an envelope, a core and the region between the two termed matrix (1). The HIV-1 Gag protein is a late structural protein that contains four proteins: matrix (p17), capsid (p24), nucleocapsid (p7) and the p6 protein (2). The p24 constitutes the major core component of the virus and shows high degree of sequence conservation among HIV isolates. The Gag p24 has been used as an integral part of multicomponent HIV-1 vaccines (3).
Description: HIV-1 p24 Monoclonal Antibody: The human immunodeficiency virus type 1 (HIV-1) particle consists of an envelope, a core and the region between the two termed matrix (1). The HIV-1 Gag protein is a late structural protein that contains four proteins: matrix (p17), capsid (p24), nucleocapsid (p7) and the p6 protein (2). The p24 constitutes the major core component of the virus and shows high degree of sequence conservation among HIV isolates. The Gag p24 has been used as an integral part of multicomponent HIV-1 vaccines (3).
Description: HIV-1 p24 Monoclonal Antibody: The human immunodeficiency virus type 1 (HIV-1) particle consists of an envelope, a core and the region between the two termed matrix (1). The HIV-1 Gag protein is a late structural protein that contains four proteins: matrix (p17), capsid (p24), nucleocapsid (p7) and the p6 protein (2). The p24 constitutes the major core component of the virus and shows high degree of sequence conservation among HIV isolates. The Gag p24 has been used as an integral part of multicomponent HIV-1 vaccines (3).
The influence of cross-kingdom molecular forensics on genetic privateness Latest advances in metagenomic expertise and computational prediction could inadvertently weaken a person’s cheap expectation of privateness. By way of cross-kingdom genetic and metagenomic forensics, we will already predict at the very least a dozen human phenotypes with various levels of accuracy. There’s additionally rising potential to […]
digIS: in direction of detecting distant and putative novel insertion sequence components in prokaryotic genomes Background: The insertion sequence components (IS components) symbolize the smallest and probably the most plentiful cell components in prokaryotic genomes. It has been proven that they play a big position in genome group and evolution. To higher perceive their perform within the […]
Identification of key gene modules and pathways of human platelet transcriptome in acute myocardial infarction sufferers by way of co-expression community Acute myocardial infarction (AMI) critically threatens human life. On this examine we aimed to systemically analyze the perform of key gene modules in human platelets in AMI. We used weighted gene co-expression community evaluation (WGCNA) […]