Crosbyjensen0586

Statistical modeling suggests that the capacity for siderophore uptake is endemic to remote ocean regions where atmospheric iron fluxes are the smallest, especially at deep chlorophyll maximum and primary nitrite maximum layers. We argue that abundant siderophore consumers at these two common oceanographic features could be a symptom of wider community iron stress, consistent with prior hypotheses. Our results provide a clear example of iron as a selective force driving the evolution of marine picocyanobacteria.

Disrupted leptin signaling in vagal afferent neurons contributes to hyperphagia and obesity. Thus, we tested the hypothesis that intrinsic negative regulators of leptin signaling, suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) underlie dysfunctional leptin-mediated vagal afferent satiety signaling during obesity.

Experiments were performed on standard chow-fed control mice, high-fat fed (HFF), or low-fat fed (LFF) mice. SOCS3 and PTP1B expression were quantified using western blot and quantitative PCR. Nodose ganglion neuronal excitability and jejunal afferent sensitivity were measured by patch clamp and extracellular afferent recordings, respectively.

Increased expression of SOCS3 and PTP1B were observed in the jejunum of HFF mice. Prolonged incubation with leptin attenuated nodose ganglion neuronal excitability, and this effect was reversed by inhibition of SOCS3. Leptin potentiated jejunal afferent nerve responses to CCK in LFF mice but decreased them in HFF mice. Inhibition of SOCS3 restored impaired vagal afferent neuronal excitability and afferent nerve responses to satiety mediators during obesity. Two-pore domain K

channel (K

) conductance and nitric oxide (NO) production that we previously demonstrated were elevated during obesity were decreased by inhibitions of SOCS3 or PTP1B.

This study suggests that obesity impairs vagal afferent sensitivity via SOCS3 and PTP1B, likely as a consequence of obesity-induced hyperleptinemia. The mechanisms underlying leptin resistance appear also to cause a more global impairment of satiety-related vagal afferent responsiveness.

This study suggests that obesity impairs vagal afferent sensitivity via SOCS3 and PTP1B, likely as a consequence of obesity-induced hyperleptinemia. The mechanisms underlying leptin resistance appear also to cause a more global impairment of satiety-related vagal afferent responsiveness.Complications of portal hypertension can be treated with transjugular intrahepatic portosystemic shunt (TIPS) in selected patients. TIPS dysfunction is a relevant clinical problem. This study investigated the prognostic value of two-dimensional (2D) TIPS geometry for the development of TIPS dysfunction. Three hundred and seven patients undergoing TIPS procedure between 2014 and 2019 were analyzed in this monocentric retrospective study. 2D angiograms from the patients with and without TIPS dysfunction were reviewed to determine geometric characteristics including insertion and curve angles and the location of the stent. Primary outcome was the development of TIPS dysfunction. A total of 70 patients developed TIPS dysfunction and were compared to the dysfunction-free (n = 237) patients. The position of the cranial stent end in the hepatic vein and the persistence of spontaneous portosystemic shunts were significantly associated with the development of TIPS dysfunction. Among significant parameters in univariable regression analysis (portal vein-pressure after TIPS, Child-Pugh Score before TIPS, MELD before TIPS and white blood cell count before TIPS), multivariable models showed cranial stent position (p = 0.027, HR 2.300, 95% CI 1.101-4.806) and SPSS embolization (p = 0.006, HR 0.319, 95% CI 0.140-0.725) as the only predictors of TIPS dysfunction. This monocentric study demonstrates that the position of the cranial stent end is independently associated with the development of TIPS dysfunction. The distance of the cranial stent end to the IVC at the time of TIPS placement should be less than 1 cm in 2D angiography.In this study, sunset glow fundus was evaluated in patients with Vogt-Koyanagi-Harada (VKH) disease using polarization-sensitive optical coherence tomography (PS-OCT). We evaluated 40 VKH eyes (20 patients) and 59 healthy eyes (59 age-matched controls). VKH eyes were divided into three groups according to color fundus images sunset (17 eyes), potential sunset (13 eyes), and non-sunset (10 eyes). Choroidal melanin thickness (ChMeT) and the choroidal melanin thickness ratio (ChMeTratio) were calculated based on the degree of polarization uniformity from PS-OCT. ChMeT was significantly lower in sunset eyes than in non-sunset or control eyes (P = 0.003). The ChMeTratios of sunset or potential sunset eyes were significantly lower than those of non-sunset or control eyes (P = 0.04). Regional evaluation of ChMeT and the ChMeTratio showed that choroidal depigmentation predominantly occurred in the macula's outer ring area (P = 0.002). The areas under receiver operating characteristic curves discriminating combined sunset (sunset and potential sunset) from non-sunset eyes were 0.983 and 0.997 for ChMeT and the ChMeTratio, respectively. Time course evaluation of 12 eyes from disease onset showed that ChMeT and the ChMeTratio significantly decreased over time. PS-OCT may be useful for objectively evaluating choroidal depigmentation in patients with VKH disease.Posttraumatic stress disorder (PTSD) is a psychiatric disorder that may arise in response to severe traumatic event and is diagnosed based on three main symptom clusters (reexperiencing, avoidance, and hyperarousal) per the Diagnostic Manual of Mental Disorders (version DSM-IV-TR). In this study, we characterized the biological heterogeneity of PTSD symptom clusters by performing a multi-omics investigation integrating genetically regulated gene, splicing, and protein expression in dorsolateral prefrontal cortex tissue within a sample of US veterans enrolled in the Million Veteran Program (N total = 186,689). We identified 30 genes in 19 regions across the three PTSD symptom clusters. We found nine genes to have cell-type specific expression, and over-representation of miRNA-families - miR-148, 30, and 8. Gene-drug target prioritization approach highlighted cyclooxygenase and acetylcholine compounds. Next, we tested molecular-profile based phenome-wide impact of identified genes with respect to 1678 phenotypes derived from the Electronic Health Records of the Vanderbilt University biorepository (N = 70,439). Lastly, we tested for local genetic correlation across PTSD symptom clusters which highlighted metabolic (e.g., obesity, diabetes, vascular health) and laboratory traits (e.g., neutrophil, eosinophil, tau protein, creatinine kinase). Overall, this study finds comprehensive genomic evidence including clinical and regulatory profiles between PTSD, hematologic and cardiometabolic traits, that support comorbidities observed in epidemiologic studies of PTSD.Adverse childhood experiences (ACEs) are associated with depression and systemic inflammation in adults. However, limited longitudinal research has tested these relationships in children and young people, and it is unclear whether inflammation is an underlying mechanism through which ACEs influence depression. We examined the longitudinal associations of several ACEs across different early-life periods with longitudinal patterns of early-life inflammation and depression in young adulthood and assessed the mediating role of inflammation. The data came from the Avon Longitudinal Study of Parents and Children (N = 3931). ACEs from the prenatal period through to adolescence were operationalised using cumulative scores, single adversities, and dimensions derived through factor analysis. Inflammation (C-reactive protein) was measured on three occasions (9-18 years) and depressive symptoms were ascertained on four occasions (18-23 years). Latent class growth analysis was employed to delineate group-based trajectories of inflammation and depression. XL092 mouse The associations between ACEs and the inflammation/depression trajectories were tested using multinomial logistic regression analysis. Most types of ACEs across all early-life periods were associated with elevated depression trajectories, with larger associations for threat-related adversities compared with other ACEs. Bullying victimisation and sexual abuse in late childhood/adolescence were associated with elevated CRP trajectories, while other ACEs were unrelated to inflammation. Inflammation was also unrelated to depression and did not mediate the associations with ACEs. These results suggest that ACEs are consistently associated with depression, whereas the associations of inflammation with ACEs and depression are weak in young people. Interventions targeting inflammation in this population might not offer protection against depression.Drug treatment against liver cancer has limited efficacy due to heterogeneous response among liver cancer subtypes. In addition, the functional biophysical phenotypes which arise from this heterogeneity and contribute to aggressive invasive behavior remain poorly understood. This study interrogated how heterogeneity in liver cancer subtypes contributes to differences in invasive phenotypes and drug response. Utilizing histological analysis, quantitative 2D invasion metrics, reconstituted 3D hydrogels, and bioinformatics, our study linked cytoskeletal dynamics to differential invasion profiles and drug resistance in liver cancer subtypes. We investigated cytoskeletal regulation in 2D and 3D culture environments using two liver cancer cell lines, SNU-475 and HepG2, chosen for their distinct cytoskeletal features and invasion profiles. For SNU-475 cells, a model for aggressive liver cancer, many cytoskeletal inhibitors abrogated 2D migration but only some suppressed 3D migration. For HepG2 cells, cytoskeletal inhibition did not significantly affect 3D migration but did affect proliferative capabilities and spheroid core growth. This study highlights cytoskeleton driven phenotypic variation, their consequences and coexistence within the same tumor, as well as efficacy of targeting biophysical phenotypes that may be masked in traditional screens against tumor growth.High-throughput detection of neutralizing antibodies against SARS-CoV-2 presents a valuable tool for vaccine trials or investigations of population immunity. We evaluate the performance of the first commercial surrogate virus neutralization test (sVNT, GenScript Biotech) against SARS-CoV-2 plaque reduction neutralization test (PRNT) in convalescent and vaccinated individuals. We compare it to five other ELISAs, two of which are designed to detect neutralizing antibodies. In 491 pre-vaccination serum samples, sVNT missed 23.6% of PRNT-positive samples when using the manufacturer-recommended cutoff of 30% binding inhibition. Introducing an equivocal area between 15 and 35% maximized sensitivity and specificity against PRNT to 72.8-93.1% and 73.5-97.6%, respectively. The overall diagnostic performance of the other ELISAs for neutralizing antibodies was below that of sVNT. Vaccinated individuals exhibited higher antibody titers by PRNT (median 119.8, IQR 56.7-160) and binding inhibition by sVNT (median 95.7, IQR 88.