Identification of a novel gene regulating amygdala-mediated fear extinction.

Recent years have seen advances in our understanding of the neural circuits associated with trauma-related disorders, and the development of relevant assays for these behaviors in rodents. Although inherited factors are known to influence individual differences in risk for these disorders, it has been difficult to identify specific genes that moderate circuit functions to affect trauma-related behaviors. Here, we exploited robust inbred mouse strain differences in Pavlovian fear extinction to uncover quantitative trait loci (QTL) associated with this trait. We found these strain differences to be resistant to developmental cross-fostering and associated with anatomical variation in basolateral amygdala (BLA) perineuronal nets, which are developmentally implicated in extinction. Next, by profiling extinction-driven BLA expression of QTL-linked genes, we nominated Ppid (peptidylprolyl isomerase D, a member of the tetratricopeptide repeat (TPR) protein family) as an extinction-related candidate gene. We then showed that Ppid was enriched in excitatory and inhibitory BLA neuronal populations, but at lower levels in the extinction-impaired mouse strain. Using a virus-based approach to directly regulate Ppid function, we demonstrated that downregulating BLA-Ppid impaired extinction, while upregulating BLA-Ppid facilitated extinction and altered in vivo neuronal extinction encoding. Next, we showed that Ppid colocalized with the glucocorticoid receptor (GR) in BLA neurons and found that the extinction-facilitating effects of Ppid upregulation were blocked by a GR antagonist. Collectively, our results identify Ppid as a novel gene involved in regulating extinction via functional actions in the BLA, with possible implications for understanding genetic and pathophysiological mechanisms underlying risk for trauma-related disorders

Transmitted/Founder and Chronic Subtype C HIV-1 Use CD4 and CCR5 Receptors with Equal Efficiency and Are Not Inhibited by Blocking the Integrin α4β7

Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently

Left and right ventricle assessment with Cardiac CT: validation study vs. Cardiac MR

Objectives To compare Magnetic Resonance (MR) and Computed Tomography (CT) for the assessment of left (LV) and right (RV) ventricular functional parameters. Methods Seventy nine patients underwent both Cardiac CT and Cardiac MR. Images were acquired using short axis (SAX) reconstructions for CT and 2D cine b-SSFP (balanced- steady state free precession) SAX sequence for MR, and evaluated using dedicated software. Results CT and MR images showed good agreement: LV EF (Ejection Fraction) (52±14% for CT vs. 52±14% for MR; r0 0.73; p>0.05); RV EF (47±12% for CT vs. 47±12% for MR; r00.74; p>0.05); LV EDV (End Diastolic Volume) (74± 21 ml/m 2 for CT vs. 76±25 ml/m 2 for MR; r00.59; p>0.05); RV EDV (84±25 ml/m 2 for CT vs. 80±23 ml/m 2 for MR; r0 0.58; p>0.05); LV ESV (End Systolic Volume)(37±19 ml/m 2 for CT vs. 38±23 ml/m 2 for MR; r00.76; p>0.05); RV ESV (46±21 ml/m 2 for CT vs. 43±18 ml/m 2 for MR; r00.70; p>0.05). Intra- and inter-observer variability were good, and the performance of CT was maintained for different EF subgroups. Conclusions Cardiac CT provides accurate and reproducible LVand RV volume parameters compared with MR, and can be considered as a reliable alternative for patients who are not suitable to undergo MR. Key Points • Cardiac-CT is able to provide Left and Right Ventricular function. • Cardiac-CT is accurate as MR for LV and RV volume assessment. • Cardiac-CT can provide accurate evaluation of coronary arteries and LV and RV function

Logging Affects Fledgling Sex Ratios and Baseline Corticosterone in a Forest Songbird

Silviculture (logging) creates a disturbance to forested environments. The degree to which forests are modified depends on the logging prescription and forest stand characteristics. In this study we compared the effects of two methods of group-selection (“moderate” and “heavy”) silviculture (GSS) and undisturbed reference stands on stress and offspring sex ratios of a forest interior species, the Ovenbird (Seiurus aurocapilla), in Algonquin Provincial Park, Canada. Blood samples were taken from nestlings for corticosterone and molecular sexing. We found that logging creates a disturbance that is stressful for nestling Ovenbirds, as illustrated by elevated baseline corticosterone in cut sites. Ovenbirds nesting in undisturbed reference forest produce fewer male offspring per brood (proportion male = 30%) while logging with progressively greater forest disturbance, shifted the offspring sex ratio towards males (proportion male: moderate = 50%, heavy = 70%). If Ovenbirds in undisturbed forests usually produce female-biased broods, then the production of males as a result of logging may disrupt population viability. We recommend a broad examination of nestling sex ratios in response to anthropogenic disturbance to determine the generality of our findings

Best practice approaches to outpatient management of people living with Parkinson's disease during the COVID-19 pandemic

The prevalence of Parkinson's disease (PD) is rising, rendering it one of the most common neurodegenerative diseases. Treatment and monitoring of patients require regular specialized in- and outpatient care. Patients with PD are more likely to have a complicated disease course if they become infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Regular in-hospital appointments place these patients at risk of exposure to SARS-CoV-2 due to travel and contact with other patients and staff. However, guidelines for the management of outpatients with PD during times of increased risk of infection are currently lacking. These are urgently needed to conduct risk-benefit evaluations to recommend the best medical treatment. This article discusses best practice approaches based on the current literature, as suggested by the multidisciplinary Network of University Medicine (NUM) in Germany. These include measures such as mask-wearing, hand hygiene, social distancing measures, and appropriate testing strategies in outpatient settings, which can minimize the risk of exposure. Furthermore, the urgency of appointments should be considered. Visits of low urgency may be conducted by general practitioners or via telemedicine consultations, whereas in-person presentation is required in case of moderate and high urgency visits. Classification of urgency should be carried out by skilled medical staff, and telemedicine (telephone or video consultations) may be a useful tool in this situation. The currently approved vaccines against SARS-CoV-2 are safe and effective for patients with PD and play a key role in minimizing infection risk for patients with PD

Where Brain, Body and World Collide

The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y| < 0.8) in the transverse momentum range 1 < pt < 8 Gev/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy sqrt{s} = 7 TeV using an integrated luminosity of 2.2 nb^{-1}. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark-antiquark pairs

Short Communication: Dried Blood Spots Stored at Room Temperature Should Not Be Used for HIV Incidence Testing

The limiting antigen (LAg)-avidity assay is a serologic assay used for cross-sectional HIV incidence testing. We compared the results obtained with the LAg-avidity assay using dried blood spot (DBS) samples stored at room temperature (18°C-25°C) or stored frozen at -80°C with results obtained from matched plasma samples. Matched DBS and plasma samples (306 paired samples) were collected in the HIV Prevention Trials Network (HPTN) 068 trial in South Africa (2012-2014). The DBS were stored at room temperature before testing. Matched DBS and plasma samples (100 paired samples) from the Consortium for the Evaluation and Performance of HIV Incidence Assays (CEPHIA) were collected in 2016 and were stored at -80°C. All DBS testing was performed in 2017. Differences in normalized optical density (ODn) were compared between matched DBS and plasma samples. For DBS samples stored at room temperature (HPTN 068), the average difference in ODn values for plasma versus DBS was 1.49 (95% confidence intervals [CI]: 1.36-1.62). In contrast, when DBS samples were stored at -80°C (CEPHIA), the average difference in ODn values for plasma versus DBS was -0.22 (95% CI: -0.32 to -0.13). DBS samples stored at room temperature should not be used for cross-sectional HIV incidence testing with the LAg-avidity assay