Metastases to the brain are rare in prostate cancer. Here, we describe a patient with two treatment-emergent metastatic lesions, one to the brain with neuroendocrine prostate cancer (NEPC) histology and one to the dural membrane of adenocarcinoma histology. We performed genomic, transcriptomic, and proteomic characterization of these lesions and the primary tumor to investigate molecular features promoting these metastases.
View Article and Find Full Text PDFADP-ribosylation is a highly dynamic and fully reversible post-translational modification performed by poly(ADP-ribose) polymerases (PARPs) that modulates protein function, abundance, localization and turnover. Here we show that influenza A virus infection causes a rapid and dramatic upregulation of global ADP-ribosylation that inhibits viral replication. Mass spectrometry defined for the first time the global ADP-ribosylome during infection, creating an infection-specific profile with almost 4,300 modification sites on ~1,080 host proteins, as well as over 100 modification sites on viral proteins.
View Article and Find Full Text PDFNull hypothesis significance testing is a statistical tool commonly employed throughout laboratory animal research. When experimental results are reported, the reproducibility of the results is of utmost importance. Establishing standard, robust, and adequately powered statistical methodology in the analysis of laboratory animal data is critical to ensure reproducible and valid results.
View Article and Find Full Text PDFThe theory and practice of statistics comprises two main schools of thought: frequentist statistics and Bayesian statistics. Frequentist methods are most commonly used to analyze animal-based laboratory data, while Bayesian statistical methods have been implemented less widely and may be relatively unfamiliar to practitioners in experimental science. This paper provides a high-level overview of Bayesian statistics and how they compare with frequentist methods.
View Article and Find Full Text PDFObjectives: This study aims to compare the efficacy of remote versus in-person training strategies to teach ultrasound guided knee arthrocentesis using formalin embalmed cadavers.
Methods: 30 first-year medical student participants were randomly assigned to remote or in-person training groups. Pre- and post- training surveys were used to evaluate participant's self-confidence in their ability to perform the procedure.
Livestock guarding dogs (LGDs) have been used to protect livestock for millennia. While previous works suggested a single origin of modern LGDs, the degree and source of shared ancestry have not been tested. To address this, we generated genome-wide SNP data from 304 LGDs and combined it with public genomic data from 2,183 modern and 22 ancient dogs.
View Article and Find Full Text PDFThe multi-millenia long history between dogs and humans has placed them at the forefront of archeological and genomic research. Despite ongoing efforts including the analysis of ancient dog and wolf genomes, many questions remain regarding their geographic and temporal origins, and the microevolutionary processes that led to the diversity of breeds today. Although ancient genomes provide valuable information, their use is hindered by low depth of coverage and post-mortem damage, which inhibits confident genotype calling.
View Article and Find Full Text PDFThe southern Mendoza province, located in the northern region of Patagonia, was inhabited by hunter-gatherer groups until historic times. Previous archaeological studies have reported canid remains among faunal assemblages, which were assumed to be part of the human diet. However, the taxonomic identification and significance of these canids within human groups have raised questions.
View Article and Find Full Text PDFHuman noroviruses, globally the main cause of viral gastroenteritis, show strain specific affinity for histo-blood group antigens (HBGA) and can successfully be propagated ex vivo in human intestinal enteroids (HIEs). HIEs established from jejunal stem cells of individuals with different ABO, Lewis and secretor geno- and phenotypes, show varying susceptibility to such infections. Using bottom-up glycoproteomic approaches we have defined and compared the N-linked glycans of glycoproteins of seven jejunal HIEs.
View Article and Find Full Text PDFThe brain is thought to be among the first human organs to decompose after death. The discovery of brains preserved in the archaeological record is therefore regarded as unusual. Although mechanisms such as dehydration, freezing, saponification, and tanning are known to allow for the preservation of the brain on short time scales in association with other soft tissues (≲4000 years), discoveries of older brains, especially in the absence of other soft tissues, are rare.
View Article and Find Full Text PDFBackground: Studies are increasingly examining the relationship between the neighborhood environment and cognitive decline; yet, few have investigated associations between multiple neighborhood features and Alzheimer's disease and related dementias (ADRD).
Objective: We investigated the relationship between neighborhood features and ADRD cumulative incidence from 2010 to 2014 in the South Carolina Alzheimer's Disease Registry (SCADR).
Methods: Diagnosed ADRD cases of age were ascertained from the SCADR by ZIP code and census tract.
Biochem Biophys Res Commun
April 2024
Utilizing RNA sequence (RNA-Seq) splice junction data from a cohort of 1841 B-cell acute lymphoblastic leukemia (B-ALL) patients we define transcriptionally distinct isoforms of ARID5B, a risk-associated gene identified in genome wide association studies (GWAS), which associate with disease survival. Short (S) and long (L) ARID5B transcripts, which differ in an encoded BAH-like chromatin interaction domain, show remarkable correlation to the isoform splicing pattern. Testing of the ARID5B proximal promoter of the S & L isoforms indicated that both are functionally independent in luciferase reporter assays.
View Article and Find Full Text PDFUnlabelled: Resistance to androgen-deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform into emergent aggressive variant prostate cancer (AVPC), which has neuroendocrine (NE)-like features. In this work, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflect and retain key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins.
View Article and Find Full Text PDFComp Biochem Physiol A Mol Integr Physiol
May 2024
Birds have the highest blood glucose among vertebrates. Several mechanisms may explain this including the lack of a functional insulin-responsive glucose transport protein, high glucagon concentrations, and reliance on lipid oxidation resulting in the production of gluconeogenic precursors. The hypothesis was that interruption of gluconeogenesis using the diabetes medication metformin would lower glucose concentrations in wild-caught birds.
View Article and Find Full Text PDFInfluenza A virus (IAV) pandemics result from interspecies transmission events within the avian reservoir and further into mammals including humans. Receptor incompatibility due to differently expressed glycan structures between species has been suggested to limit zoonotic IAV transmission from the wild bird reservoir as well as between different bird species. Using glycoproteomics, we have studied the repertoires of expressed glycan structures with focus on putative sialic acid-containing glycan receptors for IAV in mallard, chicken and tufted duck; three bird species with different roles in the zoonotic ecology of IAV.
View Article and Find Full Text PDFThe pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example, Marek's disease virus (MDV), which causes lymphoid tumors in chickens, has experienced a marked increase in virulence over the past century. Today, MDV infections kill >90% of unvaccinated birds, and controlling it costs more than US$1 billion annually.
View Article and Find Full Text PDFAncestral Coast Salish societies in the Pacific Northwest kept long-haired "woolly dogs" that were bred and cared for over millennia. However, the dog wool-weaving tradition declined during the 19th century, and the population was lost. In this study, we analyzed genomic and isotopic data from a preserved woolly dog pelt from "Mutton," collected in 1859.
View Article and Find Full Text PDFThe European wildcat population in Scotland is considered critically endangered as a result of hybridization with introduced domestic cats, though the time frame over which this gene flow has taken place is unknown. Here, using genome data from modern, museum, and ancient samples, we reconstructed the trajectory and dated the decline of the local wildcat population from viable to severely hybridized. We demonstrate that although domestic cats have been present in Britain for over 2,000 years, the onset of hybridization was only within the last 70 years.
View Article and Find Full Text PDFDomestic cats were derived from the Near Eastern wildcat (Felis lybica), after which they dispersed with people into Europe. As they did so, it is possible that they interbred with the indigenous population of European wildcats (Felis silvestris). Gene flow between incoming domestic animals and closely related indigenous wild species has been previously demonstrated in other taxa, including pigs, sheep, goats, bees, chickens, and cattle.
View Article and Find Full Text PDFDosS is a heme-containing histidine kinase that triggers dormancy transformation in. Sequence comparison of the catalytic ATP-binding (CA) domain of DosS to other well-studied histidine kinases reveals a short ATP-lid. This feature has been thought to block binding of ATP to DosS's CA domain in the absence of interactions with DosS's dimerization and histidine phospho-transfer (DHp) domain.
View Article and Find Full Text PDFIntroduction: Neurogenesis within the dentate gyrus is thought to play an important role in cognitive processes such as reversal learning and pattern separation. The α7 nicotinic acetylcholine receptor (α7 nAChR) is expressed early in newly formed granule cells of the dentate gyrus, though its role in neurogenesis and related cognitive function is not fully understood.
Methods: To better characterize relevant function of α7 nAChRs, we performed unbiased stereology to quantify hippocampal granule cells, pyramidal cells, and total volume and used a touchscreen operant spatial discrimination/reversal task to test pattern separation in a global α7 nAChR knockout mouse line.