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Mitochondrial DNA. Part B, Resources 2024Durian, a member of the Malvaceae family, is famous for its delicious fruits, which have strong scents and are rich in nutrients. In this study, we sequenced and...
Durian, a member of the Malvaceae family, is famous for its delicious fruits, which have strong scents and are rich in nutrients. In this study, we sequenced and characterized the complete chloroplast genome of L. 1774 cultivar Ri6, a popular durian cultivar in Vietnam, using the Illumina Hiseq platform. The results showed a circular chloroplast genome composed of a large single copy of 96,115 bp, a small single copy of 20,819 bp, and two inverted repeat regions of 24,185 bp. This genome consisted of 79 protein-coding genes, 30 transfer RNA genes, and four ribosomal RNA genes. The overall GC content of this genome was 35.7%. Phylogenetic analysis inferred from 78 protein-coding regions revealed monophyly of species and a close relationship between cultivar Ri6 and cultivar Mongthong. This study provides essential information for further studies examining genetic population, breedings, and species identification among taxa and cultivars.
PubMed: 38737395
DOI: 10.1080/23802359.2024.2350619 -
Journal of Korean Medical Science May 2024This study assessed the performance of the BioFire Blood Culture Identification 2 (BCID2) panel in identifying microorganisms and antimicrobial resistance (AMR) profiles...
This study assessed the performance of the BioFire Blood Culture Identification 2 (BCID2) panel in identifying microorganisms and antimicrobial resistance (AMR) profiles in positive blood cultures (BCs) and its influence on turnaround time (TAT) compared with conventional culture methods. We obtained 117 positive BCs, of these, 102 (87.2%) were correctly identified using BCID2. The discordance was due to off-panel pathogens detected by culture (n = 13), and additional pathogens identified by BCID2 (n = 2). On-panel pathogen concordance between the conventional culture and BCID2 methods was 98.1% (102/104). The conventional method detected 19 carbapenemase-producing organisms, 14 extended-spectrum beta-lactamase-producing Enterobacterales, 18 methicillin-resistant spp., and four vancomycin-resistant . BCID2 correctly predicted 53 (96.4%) of 55 phenotypic resistance patterns by detecting AMR genes. The TAT for BCID2 was significantly lower than that for the conventional method. BCID2 rapidly identifies pathogens and AMR genes in positive BCs.
Topics: Multiplex Polymerase Chain Reaction; Blood Culture; Humans; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Bacterial Proteins; beta-Lactamases; Anti-Bacterial Agents; Enterococcus faecium; Bacteria; Vancomycin-Resistant Enterococci; Bacteremia
PubMed: 38711319
DOI: 10.3346/jkms.2024.39.e157 -
Mitochondrial DNA. Part B, Resources 2024Lour. 1790 is a precious medicinal plant species, especially for treating chronic liver diseases. Genomic data on are limited. Therefore, this current study aimed to...
Lour. 1790 is a precious medicinal plant species, especially for treating chronic liver diseases. Genomic data on are limited. Therefore, this current study aimed to characterize the chloroplast genome of and reconstruct the phylogenetic relationship among Helicteroideae taxa. Consequently, the complete chloroplast genome of was 163,404 bp in length and contained 113 unique genes (79 protein-coding genes, 30 tRNA genes, and four rRNA genes). Notably, two introns of gene of were lost in comparison to that of other Helicteroideae species. The phylogenetic tree based on chloroplast genomes of eleven Helicteroideae species revealed that was closely related to species. In conclusion, our study described the first complete chloroplast genome of , which is essential for tracing evolutionary history in the Helicteroideae subfamily.
PubMed: 38707209
DOI: 10.1080/23802359.2024.2345794 -
Characterization and identification of sources of rust resistance in Triticum militinae derivatives.Scientific Reports Apr 2024Triticum militinae (2n = 4X = 28, AAGG), belonging to the secondary gene pool of wheat, is known to carry resistance to many diseases. Though some disease...
Triticum militinae (2n = 4X = 28, AAGG), belonging to the secondary gene pool of wheat, is known to carry resistance to many diseases. Though some disease resistance genes were reported from T. timopheevii, the closest wild relative of T. militinae, there are no reports from T. militinae. Twenty-one T. militinae Derivatives (TMD lines) developed at the Division of Genetics, IARI, New Delhi, were evaluated for leaf and stripe rusts at seedling and adult plant stages. Eight TMD lines (6-4, 6-5, 11-6, 12-4, 12-8, 12-12, 13-7 and 13-9) showed seedling resistance to both leaf and stripe rusts while six TMD lines (7-5, 7-6, 11-5, 13-1, 13-3 and 13-4) showed seedling resistance to leaf rust but adult plant resistance to stripe rust and three TMD lines (9-1, 9-2 and 15) showed seedling resistance to leaf rust but susceptibility to stripe rust. Three TMD lines (2-7, 2-8 and 6-1) with adult plant resistance to leaf and stripe rusts were found to carry the known gene Lr34/Yr18. Ten TMD lines (7-5, 7-6, 9-1, 9-2, 11-5, 11-6, 12-12, 12-4, 12-8, and 15) with seedling resistance to leaf rust, showing absence of known genes Lr18 and Lr50 with linked markers requires further confirmation by the test of allelism studies. As not a single stripe rust resistance gene has been reported from T. militinae or its close relative T. timpopheevii, all the 8 TMD lines (6-4, 6-5, 11-6,12-4, 12-8, 12-12, 13-7 and 13-9) identified of carrying seedling resistance to stripe rust and 3 TMD lines (13-1, 13-3 and 13-4) identified of carrying adult plant resistance to stripe rust are expected to carry unknown genes. Also, all the TMD lines were found to be cytologically stable and thus can be used in inheritance and mapping studies.
Topics: Triticum; Disease Resistance; Plant Diseases; Basidiomycota; Seedlings; Plant Leaves; Genes, Plant
PubMed: 38658671
DOI: 10.1038/s41598-024-59902-x -
Cell Death & Disease Apr 2024Radiotherapy effectiveness in breast cancer is limited by radioresistance. Nevertheless, the mechanisms behind radioresistance are not yet fully understood. RUVBL1 and...
Radiotherapy effectiveness in breast cancer is limited by radioresistance. Nevertheless, the mechanisms behind radioresistance are not yet fully understood. RUVBL1 and RUVBL2, referred to as RUVBL1/2, are crucial AAA+ ATPases that act as co-chaperones and are connected to cancer. Our research revealed that RUVBL1, also known as pontin/TIP49, is excessively expressed in MMTV-PyMT mouse models undergoing radiotherapy, which is considered a murine spontaneous breast-tumor model. Our findings suggest that RUVBL1 enhances DNA damage repair and radioresistance in breast cancer cells both in vitro and in vivo. Mechanistically, we discovered that DTL, also known as CDT2 or DCAF2, which is a substrate adapter protein of CRL4, promotes the ubiquitination of RUVBL1 and facilitates its binding to RUVBL2 and transcription cofactor β-catenin. This interaction, in turn, attenuates its binding to acetyltransferase Tat-interacting protein 60 (TIP60), a comodulator of nuclear receptors. Subsequently, ubiquitinated RUVBL1 promotes the transcriptional regulation of RUVBL1/2-β-catenin on genes associated with the non-homologous end-joining (NHEJ) repair pathway. This process also attenuates TIP60-mediated H4K16 acetylation and the homologous recombination (HR) repair process. Expanding upon the prior study's discoveries, we exhibited that the ubiquitination of RUVBL1 by DTL advances the interosculation of RUVBL1/2-β-catenin. And, it then regulates the transcription of NHEJ repair pathway protein. Resulting in an elevated resistance of breast cancer cells to radiation therapy. From the aforementioned, it is evident that targeting DTL-RUVBL1/2-β-catenin provides a potential radiosensitization approach when treating breast cancer.
Topics: Animals; Mice; ATPases Associated with Diverse Cellular Activities; beta Catenin; DNA Helicases; Gene Expression Regulation; Mammary Neoplasms, Animal; Ubiquitin; Ubiquitination; Nuclear Proteins
PubMed: 38609375
DOI: 10.1038/s41419-024-06651-4 -
EBioMedicine May 2024Alcohol consumption is associated with numerous negative social and health outcomes. These associations may be direct consequences of drinking, or they may reflect...
BACKGROUND
Alcohol consumption is associated with numerous negative social and health outcomes. These associations may be direct consequences of drinking, or they may reflect common genetic factors that influence both alcohol consumption and other outcomes.
METHODS
We performed exploratory phenome-wide association studies (PheWAS) of three of the best studied protective single nucleotide polymorphisms (SNPs) in genes encoding ethanol metabolising enzymes (ADH1B: rs1229984-T, rs2066702-A; ADH1C: rs698-T) using up to 1109 health outcomes across 28 phenotypic categories (e.g., substance-use, mental health, sleep, immune, cardiovascular, metabolic) from a diverse 23andMe cohort, including European (N ≤ 2,619,939), Latin American (N ≤ 446,646) and African American (N ≤ 146,776) populations to uncover new and perhaps unexpected associations. These SNPs have been consistently implicated by both candidate gene studies and genome-wide association studies of alcohol-related behaviours but have not been investigated in detail for other relevant phenotypes in a hypothesis-free approach in such a large cohort of multiple ancestries. To provide insight into potential causal effects of alcohol consumption on the outcomes significant in the PheWAS, we performed univariable two-sample and one-sample Mendelian randomisation (MR) analyses.
FINDINGS
The minor allele rs1229984-T, which is protective against alcohol behaviours, showed the highest number of PheWAS associations across the three cohorts (N = 232, European; N = 29, Latin American; N = 7, African American). rs1229984-T influenced multiple domains of health. We replicated associations with alcohol-related behaviours, mental and sleep conditions, and cardio-metabolic health. We also found associations with understudied traits related to neurological (migraines, epilepsy), immune (allergies), musculoskeletal (fibromyalgia), and reproductive health (preeclampsia). MR analyses identified evidence of causal effects of alcohol consumption on liability for 35 of these outcomes in the European cohort.
INTERPRETATION
Our work demonstrates that polymorphisms in genes encoding alcohol metabolising enzymes affect multiple domains of health beyond alcohol-related behaviours. Understanding the underlying mechanisms of these effects could have implications for treatments and preventative medicine.
FUNDING
MVJ, NCK, SBB, SSR and AAP were supported by T32IR5226 and 28IR-0070. SSR was also supported by NIDA DP1DA054394. NCK and RBC were also supported by R25MH081482. ASH was supported by funds from NIAAA K01AA030083. JLMO was supported by VA 1IK2CX002095. JLMO and JJMM were also supported by NIDA R21DA050160. JJMM was also supported by the Kavli Postdoctoral Award for Academic Diversity. EGA was supported by K01MH121659 from the NIMH/NIH, the Caroline Wiess Law Fund for Research in Molecular Medicine and the ARCO Foundation Young Teacher-Investigator Fund at Baylor College of Medicine. MSA was supported by the Instituto de Salud Carlos III and co-funded by the European Union Found: Fondo Social Europeo Plus (FSE+) (P19/01224, PI22/00464 and CP22/00128).
Topics: Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Alcohol Drinking; Genome-Wide Association Study; Phenotype; Female; Cohort Studies; Male; Phenomics; Genetic Predisposition to Disease; Alcohol Dehydrogenase; Genotype; Alleles
PubMed: 38580523
DOI: 10.1016/j.ebiom.2024.105086 -
Journal of Medicinal Chemistry Apr 2024BRD4 is associated with a variety of human diseases, including breast cancer. The crucial roles of amino-terminal bromodomains (BDs) of BRD4 in binding with acetylated...
BRD4 is associated with a variety of human diseases, including breast cancer. The crucial roles of amino-terminal bromodomains (BDs) of BRD4 in binding with acetylated histones to regulate oncogene expression make them promising drug targets. However, adverse events impede the development of the BD inhibitors. BRD4 adopts an extraterminal (ET) domain, which recruits proteins to drive oncogene expression. We discovered a peptide inhibitor PiET targeting the ET domain to disrupt BRD4/JMJD6 interaction, a protein complex critical in oncogene expression and breast cancer. The cell-permeable form of PiET, TAT-PiET, and PROTAC-modified TAT-PiET, TAT-PiET-PROTAC, potently inhibits the expression of BRD4/JMJD6 target genes and breast cancer cell growth. Combination therapy with TAT-PiET/TAT-PiET-PROTAC and JQ1, iJMJD6, or Fulvestrant exhibits synergistic effects. TAT-PiET or TAT-PiET-PROTAC treatment overcomes endocrine therapy resistance in ERα-positive breast cancer cells. Taken together, we demonstrated that targeting the ET domain is effective in suppressing breast cancer, providing a therapeutic avenue in the clinic.
Topics: Humans; Breast Neoplasms; Female; Transcription Factors; Cell Cycle Proteins; Antineoplastic Agents; Animals; Cell Proliferation; Peptides; Cell Line, Tumor; Mice; Protein Domains; Mice, Nude; Nuclear Proteins; Bromodomain Containing Proteins
PubMed: 38569135
DOI: 10.1021/acs.jmedchem.4c00141 -
Life Science Alliance Jun 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), pose significant... (Meta-Analysis)
Meta-Analysis
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), pose significant risks of severe fibrosis, cirrhosis, and hepatocellular carcinoma. Despite their widespread prevalence, the molecular mechanisms underlying the development and progression of these common chronic hepatic conditions are not fully understood. Here, we conducted the most extensive meta-analysis of hepatic gene expression datasets from liver biopsy samples to date, integrating 10 RNA-sequencing and microarray datasets (1,058 samples). Using a random-effects meta-analysis model, we compared over 12,000 shared genes across datasets. We identified 685 genes differentially expressed in MASLD versus normal liver, 1,870 in MASH versus normal liver, and 3,284 in MASLD versus MASH. Integrating these results with genome-wide association studies and coexpression networks, we identified two functionally relevant, validated coexpression modules mainly driven by SMOC2, ITGBL1, LOXL1, MGP, SOD3, and TAT, HGD, SLC25A15, respectively, the latter not previously associated with MASLD and MASH. Our findings provide a comprehensive and robust analysis of hepatic gene expression alterations associated with MASLD and MASH and identify novel key drivers of MASLD progression.
Topics: Humans; Genome-Wide Association Study; Transcriptome; Fatty Liver; Carcinoma, Hepatocellular; Liver Neoplasms; Integrin beta1
PubMed: 38565287
DOI: 10.26508/lsa.202302517 -
International Journal of Molecular... Mar 2024Viruses provide vital insights into gene expression control. Viral transactivators, with other viral and cellular proteins, regulate expression of self, other viruses,...
Viruses provide vital insights into gene expression control. Viral transactivators, with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to transacting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the replication-transcription complex might, therefore, transactivate viral and cellular RNAs in the transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution. Here, we show, by using primary and secondary structural comparisons, that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3. The coronaviral nucleocapsid C-terminal domains harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain, as do lentiviral Tat proteins. Although SARS-CoV-1 nucleocapsid transactivated gene expression in a replicon-based study, further experimental evidence for coronaviral transactivation and its possible implications is warranted.
Topics: Humans; HIV-1; SARS-CoV-2; Transcriptional Activation; HIV Long Terminal Repeat; COVID-19; Gene Products, tat; Lentivirus; Gene Expression; tat Gene Products, Human Immunodeficiency Virus; RNA, Viral
PubMed: 38542351
DOI: 10.3390/ijms25063378 -
BioRxiv : the Preprint Server For... Mar 2024The complex and heterogeneous genetic architecture of schizophrenia inspires us to look beyond individual risk genes for therapeutic strategies and target their...
The complex and heterogeneous genetic architecture of schizophrenia inspires us to look beyond individual risk genes for therapeutic strategies and target their interactive dynamics and convergence. Postsynaptic NMDA receptor (NMDAR) complexes are a site of such convergence. Src kinase is a molecular hub of NMDAR function, and its protein interaction subnetwork is enriched for risk-genes and altered protein associations in schizophrenia. Previously, Src activity was found to be decreased in post-mortem studies of schizophrenia, contributing to NMDAR hypofunction. PSD-95 suppresses Src via interacting with its SH2 domain. Here, we devised a strategy to suppress the inhibition of Src by PSD-95 via employing a cell penetrating and Src activating PSD-95 inhibitory peptide (TAT-SAPIP). TAT-SAPIP selectively increased post-synaptic Src activity in humans and mice, and enhanced synaptic NMDAR currents in mice. Chronic ICV injection of TAT-SAPIP rescued deficits in trace fear conditioning in Src hypomorphic mice. We propose blockade of the Src-PSD-95 interaction as a proof of concept for the use of interfering peptides as a therapeutic strategy to reverse NMDAR hypofunction in schizophrenia and other illnesses.
PubMed: 38496466
DOI: 10.1101/2024.03.08.584132