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JOURNAL ARTICLE
Joseph W Galvin, Brendan M Patterson, Maria Bozoghlian, James V Nepola, Zachary T Colburn
A biorepository, also referred to as a "biobank," is a collection of biologic samples that are stored for laboratory research. With the emergence of precision medicine, the importance of leveraging individual patient biomolecular signatures to improve diagnosis, prognosis, and treatment is becoming increasingly recognized. Successful development and sustainment of a biorepository provides the potential for transformative preclinical research. Establishing a biobank requires a team approach with involvement of the institutions' research laboratory team and regulatory body...
April 17, 2024: Journal of the American Academy of Orthopaedic Surgeons
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JOURNAL ARTICLE
Cindy Im, Achal Neupane, Jessica L Baedke, Brian Lenny, Angela Delaney, Stephanie B Dixon, Eric J Chow, Sogol Mostoufi-Moab, Tianzhong Yang, Melissa A Richard, M Monica Gramatges, Philip J Lupo, Noha Sharafeldin, Smita Bhatia, Gregory T Armstrong, Melissa M Hudson, Kirsten K Ness, Leslie L Robison, Yutaka Yasui, Carmen L Wilson, Yadav Sapkota
PURPOSE: Type 2 diabetes mellitus (T2D) is a prevalent long-term complication of treatment in survivors of childhood cancer, with marked racial/ethnic differences in burden. In this study, we investigated trans-ancestral genetic risks for treatment-related T2D. PATIENTS AND METHODS: Leveraging whole-genome sequencing data from the St Jude Lifetime Cohort (N = 3,676, 304 clinically ascertained cases), we conducted ancestry-specific genome-wide association studies among survivors of African and European genetic ancestry (AFR and EUR, respectively) followed by trans-ancestry meta-analysis...
April 23, 2024: Journal of Clinical Oncology
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JOURNAL ARTICLE
Dickran Kazandjian, Benjamin Diamond, Marios Papadimitriou, Elizabeth Hill, Romanos Sklavenitis-Pistofidis, Bachisio Ziccheddu, Patrick Blaney, Monika Chojnacka, Michael Durante, Kylee Maclachlan, Ryan Young, Saad Usmani, Faith Davies, Gad Getz, Irene Ghobrial, Neha Korde, Gareth Morgan, Francesco Maura, Ola Landgren
PURPOSE: Early intervention for High-Risk Smoldering Multiple Myeloma (HR-SMM) achieves deep and prolonged responses. It is unclear if beneficial outcomes are due to treatment of less complex, susceptible disease or inaccuracy in clinical definition of cases entered. EXPERIMENTAL DESIGN: Here, we interrogated whole genome and whole exome sequencing for 54 patients across two HR-SMM interventional studies (NCT01572480, NCT02279394). RESULTS: We reveal that the genomic landscape of treated HR-SMM is generally simple as compared to Newly Diagnosed (ND)MM counterparts with less inactivation of tumor suppressor genes, RAS pathway mutations, MYC disruption, and APOBEC contribution...
April 23, 2024: Clinical Cancer Research
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JOURNAL ARTICLE
Ben Auxier, Jianhua Zhang, Francisca Reyes Marquez, Kira Senden, Joost van den Heuvel, Duur K Aanen, Eveline Snelders, Alfons J M Debets
In fungi, fusion between individuals leads to localized cell death, a phenomenon termed heterokaryon incompatibility. Generally, the genes responsible for this incompatibility are observed to be under balancing selection resulting from negative frequency-dependent selection. Here, we assess this phenomenon in Aspergillus fumigatus, a human pathogenic fungus with a very low level of linkage disequilibrium as well as an extremely high crossover rate. Using complementation of auxotrophic mutations as an assay for hyphal compatibility, we screened sexual progeny for compatibility to identify genes involved in this process, called het genes...
April 23, 2024: Molecular Biology and Evolution
#5
JOURNAL ARTICLE
Shankar C R R Chereddy, Takashi Makino
Metazoan species depict a wide spectrum of regeneration ability which calls into question the evolutionary origins of the underlying processes. Since species with high regeneration ability are widely distributed throughout metazoans, there is a possibility that the metazoan ancestor had an underlying common molecular mechanism. Early metazoans like sponges possess high regenerative ability, but, due to the large differences they have with Cnidaria and Bilateria regarding symmetry and neuronal systems it can be inferred that this regenerative ability is different...
April 23, 2024: Genome Biology and Evolution
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JOURNAL ARTICLE
David J Anchundia, Athena W Lam, James B Henderson, Matthew H Van Dam, John P Dumbacher
Incredibly powerful whole genome studies of conservation genetics, evolution, and biogeography become possible for non-model organisms when reference genomes are available. Here, we report the sequence and assembly of the whole genome of the little vermilion flycatcher (Pyrocephalus nanus; Family Tyrannidae), which is an endemic, endangered, and declining species of the Galapagos Islands. Using PacBio HiFi reads to assemble long contigs and HiC reads for scaffolding, we assembled a genome of 1.07 gigabases comprising 267 contigs in 152 scaffolds, scaffold N50 74 M, contig N50 17...
April 23, 2024: Genome Biology and Evolution
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JOURNAL ARTICLE
Zhenghua Du, Fuquan Gao, Shuyan Wang, Shuai Sun, Chanxin Chen, Xiaxia Wang, Ruimei Wu, Xiaomin Yu
Triterpenoids from Camellia species comprise a diverse class of bioactive compounds with great therapeutic potential. However, triterpene biosynthesis in tea plants ( Camellia sinensis ) remains elusive. Here, we identified eight putative 2,3-oxidosqualene cyclase (OSC) genes ( CsOSC1-8 ) from the tea genome and characterized the functions of five through heterologous expression in yeast and tobacco and transient overexpression in tea plants. CsOSC1 was found to be a β-amyrin synthase, whereas CsOSC4, 5, and 6 exhibited multifunctional α-amyrin synthase activity...
April 23, 2024: Journal of Agricultural and Food Chemistry
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JOURNAL ARTICLE
Rajeev Ranjan, Sonali Srijan, Somaiah Balekuttira, Tina Agarwal, Melissa Ramey, Madison Dobbins, Rachel Kuhn, Xiaojin Wang, Karen Hudson, Ying Li, Kranthi Varala
Organ-specific gene expression datasets that include hundreds to thousands of experiments allow the reconstruction of organ-level gene regulatory networks (GRNs). However, creating such datasets is greatly hampered by the requirements of extensive and tedious manual curation. Here, we trained a supervised classification model that can accurately classify the organ-of-origin for a plant transcriptome. This K-Nearest Neighbor-based multiclass classifier was used to create organ-specific gene expression datasets for the leaf, root, shoot, flower, and seed in Arabidopsis thaliana ...
April 30, 2024: Proceedings of the National Academy of Sciences of the United States of America
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JOURNAL ARTICLE
Daniela Rojo, Clara E Hael, Agustina Soria, Flávio S J de Souza, Malcolm J Low, Lucía F Franchini, Marcelo Rubinstein
Food intake and energy balance are tightly regulated by a group of hypothalamic arcuate neurons expressing the proopiomelanocortin ( POMC) gene. In mammals, arcuate-specific POMC expression is driven by two cis -acting transcriptional enhancers known as nPE1 and nPE2. Because mutant mice lacking these two enhancers still showed hypothalamic Pomc mRNA, we searched for additional elements contributing to arcuate Pomc expression. By combining molecular evolution with reporter gene expression in transgenic zebrafish and mice, here, we identified a mammalian arcuate-specific Pomc enhancer that we named nPE3, carrying several binding sites also present in nPE1 and nPE2 for transcription factors known to activate neuronal Pomc expression, such as ISL1, NKX2...
April 30, 2024: Proceedings of the National Academy of Sciences of the United States of America
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JOURNAL ARTICLE
Mei Sun, Zhe Zhang, Jingjing Zhang, Juewei Zhang, Zhuqiang Jia, Lin Zhao, Xin Han, Xiaohong Sun, Junwei Zong, Ying Zhu, Shouyu Wang
BACKGROUND: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. METHOD: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels...
2024: PloS One
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JOURNAL ARTICLE
Bing Liu, Chengzhang Li, Xiang Li, Jiachen Wang, Wenhao Xie, Daniel P Woods, Weiya Li, Xiaoyu Zhu, Shuoming Yang, Aiwu Dong, Richard M Amasino
Flowering is a key developmental transition in the plant life cycle. In temperate climates, flowering often occurs in response to the perception of seasonal cues such as changes in day-length and temperature. However, the mechanisms that have evolved to control the timing of flowering in temperate grasses are not fully understood. We identified a Brachypodium distachyon mutant whose flowering is delayed under inductive long-day conditions due to a mutation in the JMJ1 gene, which encodes a Jumonji domain-containing protein...
April 23, 2024: Plant Cell
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JOURNAL ARTICLE
Soo Heon Kwak, Ryan B Hernandez-Cancela, Daniel A DiCorpo, David E Condon, Jordi Merino, Peitao Wu, Jennifer A Brody, Jie Yao, Xiuqing Guo, Fariba Ahmadizar, Mariah Meyer, Murat Sincan, Josep M Mercader, Sujin Lee, Jeffrey Haessler, Ha My T Vy, Zhaotong Lin, Nicole D Armstrong, Shaopeng Gu, Noah L Tsao, Leslie A Lange, Ningyuan Wang, Kerri L Wiggins, Stella Trompet, Simin Liu, Ruth J F Loos, Renae Judy, Philip H Schroeder, Natalie R Hasbani, Maxime M Bos, Alanna C Morrison, Rebecca D Jackson, Alexander P Reiner, JoAnn E Manson, Ninad S Chaudhary, Lynn K Carmichael, Yii-Der Ida Chen, Kent D Taylor, Mohsen Ghanbari, Joyce van Meurs, Achilleas N Pitsillides, Bruce M Psaty, Raymond Noordam, Ron Do, Kyong Soo Park, J Wouter Jukema, Maryam Kavousi, Adolfo Correa, Stephen S Rich, Scott M Damrauer, Catherine Hajek, Nam H Cho, Marguerite R Irvin, James S Pankow, Girish N Nadkarni, Robert Sladek, Mark O Goodarzi, Jose C Florez, Daniel I Chasman, Susan R Heckbert, Charles Kooperberg, Josée Dupuis, Rajeev Malhotra, Paul S de Vries, Ching-Ti Liu, Jerome I Rotter, James B Meigs
OBJECTIVE: To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association with incident CVD. RESULTS: Among 49,230 participants with T2D, 8,956 had incident CVD events (event rate 18...
April 23, 2024: Diabetes Care
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JOURNAL ARTICLE
Yim Ling Cheng, Matei A Banu, Wenting Zhao, Steven S Rosenfeld, Peter Canoll, Peter A Sims
Glioblastoma (GBM) is a deadly brain tumor, and the kinesin motor KIF11 is an attractive therapeutic target with roles in proliferation and invasion. Resistance to KIF11 inhibitors, which has mainly been studied in animal models, presents significant challenges. We use lineage-tracing barcodes and single-cell RNA sequencing to analyze resistance in patient-derived GBM neurospheres treated with ispinesib, a potent KIF11 inhibitor. Similar to GBM progression in patients, untreated cells lose their neural lineage identity and become mesenchymal, which is associated with poor prognosis...
April 21, 2024: Cell Reports
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JOURNAL ARTICLE
Jonathan Parkinson, Wei Wang
MOTIVATION: Antibody therapeutic candidates must exhibit not only tight binding to their target but also good developability properties, especially low risk of immunogenicity. RESULTS: In this work, we fit a simple generative model, SAM, to sixty million human heavy and seventy million human light chains. We show that the probability of a sequence calculated by the model distinguishes human sequences from other species with the same or better accuracy on a variety of benchmark datasets containing >400 million sequences than any other model in the literature, outperforming large language models (LLMs) by large margins...
April 23, 2024: Bioinformatics
#15
JOURNAL ARTICLE
Yuki Hitomi, Kazuko Ueno, Yoshihiro Aiba, Nao Nishida, Michihiro Kono, Mitsuki Sugihara, Yosuke Kawai, Minae Kawashima, Seik-Soon Khor, Kazuhiro Sugi, Hirotaka Kouno, Hiroshi Kouno, Atsushi Naganuma, Satoru Iwamoto, Shinji Katsushima, Kiyoshi Furuta, Toshiki Nikami, Tomohiko Mannami, Tsutomu Yamashita, Keisuke Ario, Tatsuji Komatsu, Fujio Makita, Masaaki Shimada, Noboru Hirashima, Shiro Yokohama, Hideo Nishimura, Rie Sugimoto, Takuya Komura, Hajime Ota, Motoyuki Kojima, Makoto Nakamuta, Naoyuki Fujimori, Kaname Yoshizawa, Yutaka Mano, Hironao Takahashi, Kana Hirooka, Satoru Tsuruta, Takeaki Sato, Kazumi Yamasaki, Yuki Kugiyama, Yasuhide Motoyoshi, Tomoyuki Suehiro, Akira Saeki, Kosuke Matsumoto, Shinya Nagaoka, Seigo Abiru, Hiroshi Yatsuhashi, Masahiro Ito, Kazuhito Kawata, Akinobu Takaki, Kuniaki Arai, Teruko Arinaga, Masanori Abe, Masaru Harada, Makiko Taniai, Mikio Zeniya, Hiromasa Ohira, Shinji Shimoda, Atsumasa Komori, Atsushi Tanaka, Kazuyoshi Ishigaki, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura
BACKGROUND AIMS: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-non-specific) and non-shared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC...
April 23, 2024: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
#16
JOURNAL ARTICLE
Nicole M A Blijlevens, Björn Reijnders, Eva Molendijk
PURPOSE OF REVIEW: Gastrointestinal mucositis (GIM) is a significant complication of cancer therapy. Whilst inflammation is a central feature of GIM, studies attempting to mitigate mucosal damage via this mechanism are scarce. This review describes the relation between GIM, local and systemic inflammation, and the microbiome and its metabolites, and explores recent research on therapeutics that target this relationship. RECENT FINDINGS: Recent literature underscores the pivotal role of inflammation in GIM, elucidating its bidirectional relation with disturbance of the gut microbiota composition and intestinal permeability...
April 23, 2024: Current Opinion in Supportive and Palliative Care
#17
JOURNAL ARTICLE
Nantia Leonidou, Lisa Ostyn, Tom Coenye, Aurélie Crabbé, Andreas Dräger
Cystic fibrosis (CF), an inherited genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, results in sticky and thick mucosal fluids. This environment facilitates the colonization of various microorganisms, some of which can cause acute and chronic lung infections, while others may positively impact the disease. Rothia mucilaginosa , an oral commensal, is relatively abundant in the lungs of CF patients. Recent studies have unveiled its anti-inflammatory properties using in vitro three-dimensional lung epithelial cell cultures and in vivo mouse models relevant to chronic lung diseases...
April 23, 2024: Microbiology Spectrum
#18
JOURNAL ARTICLE
Zhi Zhang, Guoshuai Zhang, Xinke Zhang, Huihui Zhang, Junbo Xie, Rui Zeng, Baolin Guo, Linfang Huang
Eomecon chionantha Hance, an endemic species in China, has a long medical history in Chinese ethnic minority medicine and is known for its anti-inflammatory and analgesic effects. However, studies of E. chionantha are lacking. In this study, we investigated the characteristics of the E. chionantha chloroplast genome and determined the taxonomic position of E. chionantha in Papaveraceae via phylogenetic analysis. In addition, we determined molecular markers to identify E. chionantha at the molecular level by comparing the chloroplast genomes of E...
April 23, 2024: Journal of Plant Research
#19
JOURNAL ARTICLE
Ivana Djordjevic, Nemanja Garai, Stojan Peric, Jelena Karanovic, Jovan Pesovic, Milos Brkusanin, Dragana Lavrnic, Slobodan Apostolski, Dusanka Savic-Pavicevic, Ivana Basta
Genome-wide association studies (GWAS) have provided strong evidence that early- and late-onset MG have different genetic backgrounds. Recent in silico analysis based on GWAS results revealed rs231735 and rs231770 variants within CTLA-4 locus as possible MG causative genetic factors. We aimed to explore the association of rs231735 and rs231770 with MG in a representative cohort of Serbian patients. We conducted an age-, sex-, and ethnicity-matched case-control study. Using TaqMan allele discrimination assays, the frequency of rs231735 and rs231770 genetic variants was examined in 447 AChR-MG patients and 447 matched controls...
April 23, 2024: Molecular Neurobiology
#20
JOURNAL ARTICLE
Aastha Ranjan, Shiloo Raj, Kamlesh Kumar Soni, Vivek Verma
We have identified and analyzed 28 SUMO-pathway proteins from pigeonpea. Enhanced transcripts of pathway genes and increased SUMO conjugation under drought signifies the role of SUMO in regulating stress. Being a protein-rich and nutrient-dense legume crop, pigeonpea (Cajanus cajan) holds a vital position in a vegetarian meal. It is a resilient crop capable of striving in harsh climates and provides a means of subsistence to small-holding farmers. Nevertheless, extremes of water scarcity and drought conditions, especially during seedling and reproductive stages, remains a major issue severely impacting the growth and overall productivity of pigeonpea...
April 23, 2024: Plant Cell Reports
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