Effects of Trapping and Subsequent Short-Term Confinement Stress on Plasma Corticosterone in the Brown Treesnake (\u3ci\u3eBoiga irregularis\u3c/i\u3e) on Guam

The effects of capture in a live trap and subsequent handling stress on plasma concentrations of corticosterone and other sex steroids were examined in wild male and female brown treesnakes (Boiga irregularis), an introduced species on Guam that has been implicated in the extirpation or decline of many of that island\u27s vertebrate species. Males and females that spent 1 night in a trap had plasma levels of corticosterone about four and two times higher, respectively, than those of the respective free-ranging controls. Mean plasma levels of corticosterone of snakes that had spent 3 nights in a trap were intermediate between, but not significantly different from, those of snakes that had spent 1 night in a trap and free-ranging snakes, suggesting that some acclimation to capture occurred during this period. Snakes that were taken from traps and held in collecting bags for 10 min and 2 h prior to blood sampling had levels of corticosterone about two and three times higher, respectively, than those of control snakes that were taken from traps and bled immediately. Concentrations of plasma corticosterone in free-ranging females were about two times higher than those of males but were well within the range of basal levels observed in other reptiles. Few snakes of potential reproductive size were reproductive (males: 1 of 35; females: 2 of 33), and plasma concentrations of testosterone and progesterone in nonreproductive males and females, respectively, were accordingly low. The possible relationship between corticosterone and these sex steroids, therefore, could not be adequately assessed, although there was a positive relationship between plasma progesterone and corticosterone in the nonreproductive females. Nonetheless, as a prerequisite for studies on the seasonal hormonal cycles of this species on Guam, our observations raise the possibility that the stress caused by trapping could affect the levels of other sex steroids and that, therefore, such studies should use free-ranging individuals

Effects of Trapping and Subsequent Short-Term Confinement Stress on Plasma Corticosterone in the Brown Treesnake (\u3ci\u3eBoiga irregularis\u3c/i\u3e) on Guam

The effects of capture in a live trap and subsequent handling stress on plasma concentrations of corticosterone and other sex steroids were examined in wild male and female brown treesnakes (Boiga irregularis), an introduced species on Guam that has been implicated in the extirpation or decline of many of that island\u27s vertebrate species. Males and females that spent 1 night in a trap had plasma levels of corticosterone about four and two times higher, respectively, than those of the respective free-ranging controls. Mean plasma levels of corticosterone of snakes that had spent 3 nights in a trap were intermediate between, but not significantly different from, those of snakes that had spent 1 night in a trap and free-ranging snakes, suggesting that some acclimation to capture occurred during this period. Snakes that were taken from traps and held in collecting bags for 10 min and 2 h prior to blood sampling had levels of corticosterone about two and three times higher, respectively, than those of control snakes that were taken from traps and bled immediately. Concentrations of plasma corticosterone in free-ranging females were about two times higher than those of males but were well within the range of basal levels observed in other reptiles. Few snakes of potential reproductive size were reproductive (males: 1 of 35; females: 2 of 33), and plasma concentrations of testosterone and progesterone in nonreproductive males and females, respectively, were accordingly low. The possible relationship between corticosterone and these sex steroids, therefore, could not be adequately assessed, although there was a positive relationship between plasma progesterone and corticosterone in the nonreproductive females. Nonetheless, as a prerequisite for studies on the seasonal hormonal cycles of this species on Guam, our observations raise the possibility that the stress caused by trapping could affect the levels of other sex steroids and that, therefore, such studies should use free-ranging individuals

Blood Levels of S-100 Calcium-Binding Protein B, High-Sensitivity C-Reactive Protein, and Interleukin-6 for Changes in Depressive Symptom Severity after Coronary Artery Bypass Grafting: Prospective Cohort Nested within a Randomized, Controlled Trial

Background: Cross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood–brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calcium- binding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge. Methods: Fifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and six-month follow-up using the Beck Depression Inventory II (BDI-II). The primary outcome of the present biomarker study was acute change in depressive symptom severity, defined as the intra-subject difference between baseline and discharge BDI-II scores. Blood biomarker levels were determined at baseline and 2 days postoperative. Results: Changes in S-100B levels correlated positively with acute changes in depressive symptom severity (Spearman r, 0.62; P=0.0004) and accounted for about one-fourth of their observed variance (R2, 0.23; P=0.0105). This association remained statistically significant after adjusting for baseline S-100B levels, age, weight, body-mass index, or b-blocker use, but not baseline BDI-II scores (P = 0.064). There was no statistically significant association between the primary outcome and baseline S-100B levels, baseline high-sensitivity C-reactive protein or interleukin-6 levels, or changes in high-sensitivity C- reactive protein or interleukin-6 levels. Among most participants, levels of all three biomarkers were normal at baseline and markedly elevated at 2 days postoperative. Conclusions: Acute changes in depressive symptom severity were specifically associated with incremental changes in S- 100B blood levels, largely independent of covariates associated with either. These findings support the hypothesis that glial activation and injury and blood–brain barrier disruption can be mechanistically linked to acute exacerbation of depressive symptoms in some individuals

Variations in Hip Shape Are Associated with Radiographic Knee Osteoarthritis : Cross-sectional and Longitudinal Analyses of the Johnston County Osteoarthritis Project

Acknowledgment We thank our funding sources, as well as the staff and participants in the Johnston County Osteoarthritis Project, without whom this work would not be possible. Funding was provided in part by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) K23 AR061406 (Nelson); US National Institutes of Health (NIH)/NIAMS P60AR30701 (Jordan/Renner/Schwartz); US Centers for Disease Control/Association of Schools of Public Health S043 and S3486 (Jordan/Renner); K24-AR04884, P50-AR063043, and P50-AR060752 (Lane); and NIH/National Center for Advancing Translational Sciences KL2TR001109 (Golightly).Peer reviewedPostprin

Incident symptomatic hip osteoarthritis is associated with differences in hip shape by active shape modeling: The Johnston County Osteoarthritis Project

To investigate hip shape by active shape modeling (ASM) as a potential predictor of incident radiographic and symptomatic hip OA (rHOA and srHOA)

Inhibiting ACK1-mediated phosphorylation of C-terminal Src kinase counteracts prostate cancer immune checkpoint blockade resistance

Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p < 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

Anatomical patterns of recurrence following biochemical relapse after post‐prostatectomy salvage radiation therapy: a multi‐institutional study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138303/1/bju13792.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138303/2/bju13792_am.pd

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin