SNF

INTRODUCTION: The multi-subunit SWI/SNF chromatin remodeling complex is a key epigenetic regulator for many cellular processes, and several subunits are found to be mutated in human cancers. The inactivating mutations of SMARCA4, the ATPase subunit of the complex, result in cellular dependency on the paralog SMARCA2 for survival. This observed synthetic lethal relationship posits targeting SMARCA2 in SMARCA4-deficient settings as an attractive therapeutic target in oncology. AREAS COVERED: This review covers patent literature disclosed during the 2019-30 June 2023 period which claim ATPase inhibitors and PROTAC degraders that bind to the ATPase domain of SMARCA2 and/or SMARCA4...

Purpose: Lung cancer is a major cause of morbidity and mortality globally, necessitating the identification of predictive markers for effective immunotherapy. Mutations in SWI/SNF chromatin remodeling complex genes were reported sensitized human tumors to immune checkpoint inhibitors (ICIs), but the underlying mechanisms are unclear. This study aims to investigate the association between SWI/SNF gene ARID1B mutation and ICI response in non-small cell lung cancer (NSCLC) patients, to explore the functional consequences of ARID1B mutation on DNA damage response, immune microenvironment, and cGAS-STING pathway activation...

BACKGROUND: SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting (SWI/SNF) complexes and plays an essential role in oncogenesis. SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis. There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies. Programmed death 1 (PD-1) antibodies, known as immune checkpoint inhibitor antibodies, potentially play a role in treating gastrointestinal tract malignancies...

The garden pea ( Pisum sativum L.) is a significant cool-season legume, serving as crucial food sources, animal feed, and industrial raw materials. The advancement of functional genomics over the past two decades has provided substantial theoretical foundations and progress to pea breeding. Notably, the release of the pea reference genome has enhanced our understanding of plant architecture, symbiotic nitrogen fixation (SNF), flowering time, floral organ development, seed development, and stress resistance...

ATP dependent chromatin remodelers have pivotal roles in transcription, DNA replication and repair, and maintaining genome integrity. SWI/SNF remodelers were first discovered in yeast genetic screens for factors involved in mating type switching or for using alternative energy sources therefore termed SWI/SNF complex (short for SWItch/Sucrose NonFermentable). The SWI/SNF complexes utilize energy from ATP hydrolysis to disrupt histone-DNA interactions and shift, eject, or reposition nucleosomes making the underlying DNA more accessible to specific transcription factors and other regulatory proteins...

BACKGROUND: Mimosa bimucronata originates from tropical America and exhibits distinctive leaf movement characterized by a relative slow speed. Additionally, this species possesses the ability to fix nitrogen. Despite these intriguing traits, comprehensive studies have been hindered by the lack of genomic resources for M. bimucronata. RESULTS: To unravel the intricacies of leaf movement and nitrogen fixation, we successfully assembled a high-quality, haplotype-resolved, reference genome at the chromosome level, spanning 648 Mb and anchored in 13 pseudochromosomes...

PURPOSE: Older adults with Alzheimer's disease and related dementias (ADRD) are at high risk for acute medical problems and their health trajectories frequently include hospital admission and care in a skilled nursing facility (SNF). Their health trajectories after SNF discharge are poorly understood. Therefore, in the current study, we sought to describe health trajectories and factors associated with hospital read-missions for older adults with ADRD during the 30 days following SNF discharge...

INTRODUCTION: This study aims to evaluate health literacy (HL) in geriatric orthopaedic trauma patients and their families as it relates to their post-acute care (PAC) in skilled nursing facilities (SNFs) and inpatient rehabilitation facilities (IRFs). METHODS: This nonrandomized controlled clinical trial included patients aged 65 years and older treated for acute fracture at a Level 1 trauma center and discharged to either IRF or SNF. First 106 patients enrolled served as the control group and received standard discharge instructions...

Development of cancer therapies targeting chromatin modifiers and transcriptional regulatory factors is rapidly expanding to include new targets and novel targeting strategies. At the same time, basic molecular research continues to refine our understanding of the epigenetic mechanisms regulating transcription, gene expression, and oncogenesis. This mini-review focuses on cancer therapies targeting the chromatin-associated factors that recognize histone lysine acetylation. Recently reported safety and efficacy are discussed for inhibitors targeting the bromodomains of bromodomain and extraterminal domain (BET) family proteins...

Several methods have been developed to computationally predict cell-types for single cell RNA sequencing (scRNAseq) data. As methods are developed, a common problem for investigators has been identifying the best method they should apply to their specific use-case. To address this challenge, we present CHAI (consensus Clustering tHrough similArIty matrix integratIon for single cell type identification), a wisdom of crowds approach for scRNAseq clustering. CHAI presents two competing methods which aggregate the clustering results from seven state of the art clustering methods: CHAI-AvgSim and CHAI-SNF...

Pancreatic cancer is an intractable malignancy associated with a dismal prognosis. Undifferentiated carcinoma, a rare subtype, poses a clinical challenge owing to a limited understanding of its molecular characteristics. In this study, we conducted genomic analysis specifically on a case of undifferentiated carcinoma of the pancreas exhibiting squamous differentiation. An 80-year-old male, previously treated for colorectal cancer, presented with a mass with central cystic degeneration in the pancreatic tail...

Mammalian switch/sucrose nonfermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, an orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients...

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Gametocyte development of the Plasmodium parasite is a key step for transmission of the parasite. Male and female gametocytes are produced from a subpopulation of asexual blood-stage parasites, but the mechanisms that regulate the differentiation of sexual stages are still under investigation. In this study, we investigated the role of PbARID, a putative subunit of a SWI/SNF chromatin remodeling complex, in transcriptional regulation during the gametocyte development of P. berghei. PbARID expression starts in early gametocytes before the manifestation of male and female-specific features, and disruption of its gene results in the complete loss of gametocytes with detectable male features and the production of abnormal female gametocytes...

Rhabdoid tumor predisposition syndrome (RTPS) is a rare disorder associated with malignant rhabdoid tumor of the kidney (RTK), atypical teratoid rhabdoid tumor (ATRT), and/or other extracranial, extrarenal rhabdoid tumors (EERT), and these pediatric malignancies are difficult to treat. Presently, most of the information regarding clinical manifestations, treatment, and outcomes of rhabdoid tumors comes from large data registries and case series. Our current understanding of treatments for patients with rhabdoid tumors may inform how we approach patients with RTPS...

INTRODUCTION: Readmissions after a traumatic brain injury (TBI) can have severe impacts on long-term health outcomes as well as rehabilitation. The aim of this descriptive study was to analyze the Nationwide Readmissions Database to determine possible risk factors associated with readmission for patients who previously sustained a TBI. METHODS: This retrospective study used data from the Nationwide Readmissions Database to explore gender, age, injury severity score, comorbidities, index admission hospital size, discharge disposition of the patient, and cause for readmission for adults admitted with a TBI...

This paper describes the methodology used to create a fuel data library comprising safeguards-relevant quantities that may be useful for verification of spent nuclear fuel (SNF) produced by simulating a concept Molten Salt Reactor (MSR). The Monte-Carlo particle transport code, Serpent2 and the calculation code SOURCES 4C were used to compile this fuel data library. The data library is based on the Compact Molten Salt Reactor (CMSR) concept being developed by Seaborg Technologies (based in Copenhagen, Denmark)...

BACKGROUND: Differences in the post-acute care (PAC) destinations among racial, ethnic, and socioeconomic groups have been documented before the COVID-19 pandemic. Yet, the pandemic's impact on these differences remains unknown. We examined the impact of the COVID-19 pandemic on PAC destinations and its variation by individual race, ethnicity, and socioeconomic status among community-dwelling older adults with Alzheimer's disease and related dementia (ADRD). METHODS: We linked 2019-2021 national data (Medicare claims, Minimum Data Set, Master Beneficiary Summary File) and several publicly available datasets, including Provider of Services File, Area Deprivation Index, Area Health Resource File, and COVID-19 infection data...

Whereas oncogenes can potentially be inhibited with small molecules, the loss of tumour suppressors is more common and is problematic because the tumour-suppressor proteins are no longer present to be targeted. Notable examples include SMARCB1-mutant cancers, which are highly lethal malignancies driven by the inactivation of a subunit of SWI/SNF (also known as BAF) chromatin-remodelling complexes. Here, to generate mechanistic insights into the consequences of SMARCB1 mutation and to identify vulnerabilities, we contributed 14 SMARCB1-mutant cell lines to a near genome-wide CRISPR screen as part of the Cancer Dependency Map Project1-3 ...

The genetic architecture of symbiotic N fixation and related traits was investigated in the field. QTLs were identified for percent N derived from the atmosphere, shoot [N] and C to N ratio. Soybean [Glycine max (L.) Merr.] is cultivated worldwide and is the most abundant source of plant-based protein. Symbiotic N2 fixation (SNF) in legumes such as soybean is of great importance; however, yields may still be limited by N in both high yielding and stressful environments. To better understand the genetic architecture of SNF and facilitate the development of high yielding cultivars and sustainable soybean production in stressful environments, a recombinant inbred line population consisting of 190 lines, developed from a cross between PI 442012A and PI 404199, was evaluated for N derived from the atmosphere (Ndfa), N concentration ([N]), and C to N ratio (C/N) in three environments...