A germline exome analysis reveals harmful POT1 variants in multiple myeloma patients and families

Peer reviewe

Enrichment of cancer-predisposing germline variants in adult and pediatric patients with acute lymphoblastic leukemia

Despite recent progress in acute lymphoblastic leukemia (ALL) therapies, a significant subset of adult and pediatric ALL patients has a dismal prognosis. Better understanding of leukemogenesis and recognition of germline genetic changes may provide new tools for treating patients. Given that hematopoietic stem cell transplantation, often from a family member, is a major form of treatment in ALL, acknowledging the possibility of hereditary predisposition is of special importance. Reports of comprehensive germline analyses performed in adult ALL patients are scarce. Aiming at fulfilling this gap of knowledge, we investigated variants in 93 genes predisposing to hematologic malignancies and 70 other cancer-predisposing genes from exome data obtained from 61 adult and 87 pediatric ALL patients. Our results show that pathogenic (P) or likely pathogenic (LP) germline variants in genes associated with predisposition to ALL or other cancers are prevalent in ALL patients: 8% of adults and 11% of children. Comparison of P/LP germline variants in patients to population-matched controls (gnomAD Finns) revealed a 2.6-fold enrichment in ALL cases (CI 95% 1.5-4.2, p = 0.00071). Acknowledging inherited factors is crucial, especially when considering hematopoietic stem cell transplantation and planning post-therapy follow-up. Harmful germline variants may also predispose patients to excessive toxicity potentially compromising the outcome. We propose integrating germline genetics into precise ALL patient care and providing families genetic counseling.Peer reviewe

Social network and dominance hierarchy analyses at Chimpanzee Sanctuary Northwest

Different aspects of sociality bear considerable weight on the individual- and group-level welfare of captive nonhuman primates. Social Network Analysis (SNA) is a useful tool for gaining a holistic understanding of the dynamic social relationships of captive primate groups. Gaining a greater understanding of captive chimpanzees through investigations of centrality, preferred and avoided relationships, dominance hierarchy, and social network diagrams can be useful in advising current management practices in sanctuaries and other captive settings. In this study, we investigated the dyadic social relationships, group-level social networks, and dominance hierarchy of seven chimpanzees (Pan troglodytes) at Chimpanzee Sanctuary Northwest. We used focal-animal and instantaneous scan sampling to collect 106.75 total hours of associative, affiliative, and agonistic data from June to September 2016. We analyzed our data using SOCPROG to derive dominance hierarchies and network statistics, and we diagrammed the group\u27s social networks in NetDraw. Three individuals were most central in the grooming network, while two others had little connection. Through agonistic networks, we found that group members reciprocally exhibited agonism, and the group\u27s dominance hierarchy was statistically non-linear. One chimpanzee emerged as the most dominant through agonism but was least connected to other group members across affiliative networks. Our results indicate that the conventional methods used to calculate individuals\u27 dominance rank may be inadequate to wholly depict a group\u27s social relationships in captive sanctuary populations. Our results have an applied component that can aid sanctuary staff in a variety of ways to best ensure the improvement of group welfare

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

More Than Meets the Eye: The Merging of Perceptual and Conceptual Knowledge in the Anterior Temporal Face Area

An emerging body of research has supported the existence of a small face sensitive region in the ventral anterior temporal lobe (ATL), referred to here as the “anterior temporal face area”. The contribution of this region in the greater face-processing network remains poorly understood. The goal of the present study was to test the relative sensitivity of this region to perceptual as well as conceptual information about people and objects. We contrasted the sensitivity of this region to that of two highly-studied face-sensitive regions, the fusiform face area (FFA) and the occipital face area (OFA), as well as a control region in early visual cortex (EVC). Our findings revealed that multivoxel activity patterns in the anterior temporal face area contain information about facial identity, as well as conceptual attributes such as one’s occupation. The sensitivity of this region to the conceptual attributes of people was greater than that of posterior face processing regions. In addition, the anterior temporal face area overlaps with voxels that contain information about the conceptual attributes of concrete objects, supporting a generalized role of the ventral ATLs in the identification and conceptual processing of multiple stimulus classes

Rare variants in complement system genes associate with endothelial damage after pediatric allogeneic hematopoietic stem cell transplantation

Peer reviewe

Progression of type 1 diabetes from latency to symptomatic disease is predicted by distinct autoimmune trajectories

Abstract Development of islet autoimmunity precedes the onset of type 1 diabetes in children, however, the presence of autoantibodies does not necessarily lead to manifest disease and the onset of clinical symptoms is hard to predict. Here we show, by longitudinal sampling of islet autoantibodies (IAb) to insulin, glutamic acid decarboxylase and islet antigen-2 that disease progression follows distinct trajectories. Of the combined Type 1 Data Intelligence cohort of 24662 participants, 2172 individuals fulfill the criteria of two or more follow-up visits and IAb positivity at least once, with 652 progressing to type 1 diabetes during the 15 years course of the study. Our Continuous-Time Hidden Markov Models, that are developed to discover and visualize latent states based on the collected data and clinical characteristics of the patients, show that the health state of participants progresses from 11 distinct latent states as per three trajectories (TR1, TR2 and TR3), with associated 5-year cumulative diabetes-free survival of 40% (95% confidence interval [CI], 35% to 47%), 62% (95% CI, 57% to 67%), and 88% (95% CI, 85% to 91%), respectively (p < 0.0001). Age, sex, and HLA-DR status further refine the progression rates within trajectories, enabling clinically useful prediction of disease onset