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.
Description: TAO Kinase inhibitor 1 (compound 43) is a selective, ATP-competitive thousand-and-one amino acid kinases (TAOK) inhibitor with IC50s of 11 to 15 nM for TAOK1 and 2, respectively. TAO Kinase inhibitor 1 delays mitosis and induces mitotic cell death[1].
Description: Tie2 kinase inhibitor 1 (compound 5) is a potent, selective Tie2 kinase inhibitor with an IC50 of 250 nM[1]. Tie2 kinase inhibitor 1 has anti-cancer activity[2].
Description: RIP2 kinase inhibitor 1 (compound 11) is a potent and selective receptor interacting protein 2 (RIP2) kinase inhibitor with an IC50 of 0.03 μM for RIP2 FP. RIP2 kinase inhibitor 1 is used for autoinflammatory disorders[1].
Description: Tpl2 Kinase Inhibitor 1 is a 3-pyridylmethylamino analog, and is a selective Tpl2 inhibitor (IC50=50 nM). Tpl2 consists of COT kinase and MAP3K8. Tpl2 Kinase Inhibitor 1 plays an important role in the regulation of the inflammatory response and the progression of some cancers[1][2].
Description: Pim-1 kinase inhibitor 1 is a Pim-1 kinase inhibitor with an IC50 of 0.11 μM for Pim-1 kinase. Pim-1 kinase inhibitor 1 shows anticancer activity to several cancer cell lines by promotes cell apoptosis. Pim-1 kinase inhibitor 1 can be used for the research of cancer[1].
Description: PDGFRα kinase inhibitor 1 is a highly selective type II PDGFRα kinase inhibitor with IC50s of 132 nM and 6115 nM for PDGFRα and PDGFRβ, respectively[1].
Description: Protein kinase G inhibitor-1 (Compound 270) is a mycobacterial protein kinase G inhibitor, with an IC50 of 0.9 μM. Protein kinase G inhibitor-1 can be used for mycobacterial infection research[1].
Description: Pim-1 kinase inhibitor 4 (Compound 10f) is a Pim-1 kinase inhibitor (IC50: 17.01 nM). Pim-1 kinase inhibitor 4 also has antioxidant activity and inhibits DPPH. Pim-1 kinase inhibitor 4 induces apoptosis in PC-3 cell, and inhibits PC-3 cell growth with an IC50 of 16 nM. Pim-1 kinase inhibitor 4 can be used for research of prostate cancer[1].
Description: Pim-1 kinase inhibitor 5 (Compound 4c) is a Pim-1 kinase inhibitor (IC50: 0.61 μM). Pim-1 kinase inhibitor 5 shows cytotoxicity against cancer cells, with IC50s of 6.95-20.19 μM for HepG2, MCF-7, PC3, and HCT-116 cells[1].
Description: Pim-1 kinase inhibitor 6 (Compound 4d) is a potent Pim-1 kinase inhibitor with IC50 value of 0.46 μM, and has significant cytotoxic effect on cancer cells[1].
Description: Pim-1 kinase inhibitor 8 (compound 12) is a potent inhibitor of Pim-1 kinase with an IC50 of 14.3 nM. Pim-1 kinase inhibitor 8 has potent cytotoxicity against MCF-7 and HepG2 cells with IC50s of 0.5 and 5.27 μM, respectively. Pim-1 kinase inhibitor 8 can used in study breast cancer[1].
Description: Pim-1 kinase inhibitor 10 (compound 13a) is a both competitive and non-competitive inhibitor of PIM-1/2 kinase. Pim-1 kinase inhibitor 10 can induce cell apoptosis and exhibits anticancer activity. Pim-1 kinase inhibitor 10 also induces caspase 3/7 activation[1].
Description: Pim-1 kinase inhibitor 9 (compound 8b) is a selective inhibitor against Pim-1 kinase with IC50 value of 0.24 µM. Pim-1 kinase inhibitor 9 inhibits cell cycle of T47D at S phase. Pim-1 kinase inhibitor 9 reveals antitumor activity[1].
Description: Pim-1 kinase inhibitor 2 (Compound 13) is a potent inhibitor of Pim-1 kinase. Pim-1 kinase inhibitor 2 induces apoptosis. Pim-1 kinase inhibitor 2 has the potential for the research of cancer diseases[1].
Description: Pan-RAF kinase inhibitor 1 is a potent inhibitor of Pan-RAF kinase. Pan-RAF kinase inhibitor 1 regulates MAPK signaling by inhibiting RAF kinase, thereby exerting an effect on the proliferation of RAS-mutant tumor cells. Pan-RAF kinase inhibitor 1 has the potential for the research of cancer diseases (extracted from patent WO2021110141A1, compound 16B)[1].
Description: Protein kinase D inhibitor 1 (compound 17m) is a pan-PKD inhibitor, with IC50 values ranging from 17 to 35 nM. Protein kinase D inhibitor 1 inhibits PKD-dependent cortactin phosphorylation[1].
Description: EML4-ALK kinase inhibitor 1 is a potent orally active inhibitor of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), with an IC50 of 1 nM[1].
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.
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 […]
Bioinformatics evaluation and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head Background: Steroid-induced osteonecrosis of the femoral head (ONFH) is a typical hip joint illness and is troublesome to be identified early. At current, the pathogenesis of steroid-induced ONFH stays unclear, and acknowledged and efficient diagnostic biomarkers are poor. The current research […]
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 […]
