Red Blood Cells from Individuals with Abdominal Obesity or Metabolic Abnormalities Exhibit Less Deformability upon Entering a Constriction.

Abdominal obesity and metabolic syndrome (MS) are multifactorial conditions associated with increased risk of cardiovascular disease and type II diabetes mellitus. Previous work has demonstrated that the hemorheological profile is altered in patients with abdominal obesity and MS, as evidenced for example by increased whole blood viscosity. To date, however, no studies have examined red blood cell (RBC) deformability of blood from individuals with obesity or metabolic abnormalities under typical physiological flow conditions. In this study, we pumped RBCs through a constriction in a microfluidic device and used high speed video to visualize and track the mechanical behavior of ~8,000 RBCs obtained from either healthy individuals (n = 5) or obese participants with metabolic abnormalities (OMA) (n = 4). We demonstrate that the OMA+ cells stretched on average about 25% less than the healthy controls. Furthermore, we examined the effects of ingesting a high-fat meal on RBC mechanical dynamics, and found that the postprandial period has only a weak effect on the stretching dynamics exhibited by OMA+ cells. The results suggest that chronic rigidification of RBCs plays a key role in the increased blood pressure and increased whole blood viscosity observed in OMA individuals and was independent of an acute response triggered by consumption of a high-fat meal

Matterport3D: Learning from RGB-D Data in Indoor Environments

Access to large, diverse RGB-D datasets is critical for training RGB-D scene understanding algorithms. However, existing datasets still cover only a limited number of views or a restricted scale of spaces. In this paper, we introduce Matterport3D, a large-scale RGB-D dataset containing 10,800 panoramic views from 194,400 RGB-D images of 90 building-scale scenes. Annotations are provided with surface reconstructions, camera poses, and 2D and 3D semantic segmentations. The precise global alignment and comprehensive, diverse panoramic set of views over entire buildings enable a variety of supervised and self-supervised computer vision tasks, including keypoint matching, view overlap prediction, normal prediction from color, semantic segmentation, and region classification

Scalable control of mounting and attack by Esr1^+ neurons in the ventromedial hypothalamus

Social behaviours, such as aggression or mating, proceed through a series of appetitive and consummatory phases that are associated with increasing levels of arousal. How such escalation is encoded in the brain, and linked to behavioural action selection, remains an unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male–male and male–female social encounters. Non-cell-type-specific optogenetic activation of this region elicited attack behaviour, but not mounting. We have identified a subset of VMHvl neurons marked by the oestrogen receptor 1 (Esr1), and investigated their role in male social behaviour. Optogenetic manipulations indicated that Esr1^+ (but not Esr1^−) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behaviour. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behaviour, rather than attack, towards both males and females, as well as sniffing and close investigation. Increasing photostimulation intensity could promote a transition from close investigation and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1^+ neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1^+ neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population

Development of quantitative metabolomics for Pichia pastoris

Accurate, reliable and reproducible measurement of intracellular metabolite levels has become important for metabolic studies of microbial cell factories. A first critical step for metabolomic studies is the establishment of an adequate quenching and washing protocol, which ensures effective arrest of all metabolic activity and removal of extracellular metabolites, without causing leakage of metabolites from the cells. Five different procedures based on cold methanol quenching and cell separation by filtration were tested for metabolomics of Pichia pastoris regarding methanol content and temperature of the quenching solution as key parameters. Quantitative evaluation of these protocols was carried out through mass balance analysis, based on metabolite measurements in all sample fractions, those are whole broth, quenched and washed cells, culture filtrate and quenching and washing solution. Finally, the optimal method was used to study the time profiles of free amino acid and central carbon metabolism intermediates in glucose-limited chemostat cultures. Acceptable recoveries (>90%) were obtained for all quenching procedures tested. However, quenching at −27°C in 60% v/v methanol performed slightly better in terms of leakage minimization. We could demonstrate that five residence times under glucose limitation are enough to reach stable intracellular metabolite pools. Moreover, when comparing P. pastoris and S. cerevisiae metabolomes, under the same cultivation conditions, similar metabolite fingerprints were found in both yeasts, except for the lower glycolysis, where the levels of these metabolites in P. pastoris suggested an enzymatic capacity limitation in that part of the metabolism

Somatic Mitochondrial DNA Mutations in Diffuse Large B-Cell Ly

Diffuse Large B-Cell Lymphoma (DLBCL) is an aggressive hematological cancer for which mitochondrial metabolism may play an important role. Mitochondrial DNA (mtDNA) encodes crucial mitochondrial proteins, yet the relationship between mtDNA and DLBCL remains unclear. We analyzed the functional consequences and mutational spectra of mtDNA somatic mutations and private constitutional variants in 40 DLBCL tumour-normal pairs. While private constitutional variants occurred frequently in the D-Loop, somatic mutations were randomly distributed across the mitochondrial genome. Heteroplasmic constitutional variants showed a trend towards loss of heteroplasmy in the corresponding tumour regardless of whether the reference or variant allele was being lost, suggesting that these variants are selectively neutral. The mtDNA mutational spectrum showed minimal support for ROS damage and revealed strand asymmetry with increased C > T and A > G transitions on the heavy strand, consistent with a replication-associated mode of mutagenesis. These heavy strand transitions carried higher proportions of amino acid changes – which were also more pathogenic – than equivalent substitutions on the light strand. Taken together, endogenous replication-associated events underlie mtDNA mutagenesis in DLBCL and preferentially generate functionally consequential mutations. Yet mtDNA somatic mutations remain selectively neutral, suggesting that mtDNA-encoded mitochondrial functions may not play an important role in DLBCL

Effectiveness of Online Mindfulness-Based Interventions on Psychological Distress and the Mediating Role of Emotion Regulation

Online mindfulness-based intervention as a feasible and acceptable approach has received mounting attention in recent years, yet more evidence is needed to demonstrate its effectiveness. The primary objective of this study was to examine the effects of online mindfulness-based programs on psychological distress (depression and anxiety). The randomized controlled intervention design consisted of four conditions: group mindfulness-based intervention (GMBI), self-direct mindfulness-based intervention (SDMBI), discussion group (DG) and blank control group (BCG). The program lasted 8 weeks and a total of 76 participants completed the pre- and post-test. Results showed that participants in GMBI and SDMBI had significant pre- and post-test differences on mindfulness, emotion regulation difficulties, and psychological distress, with medium to large effect sizes. In addition, ANCOVA results indicated significant effects of group membership on post-test scores of mindfulness, depression and anxiety when controlling the pretest scores, with medium to large effect sizes. The GMBI appeared to exert the greatest effects on outcome variables in comparison with other groups. In addition, changes in emotion regulation difficulties across groups could mediate the relationship between changes in mindfulness dimensions (Observing and Describing) and changes in psychological distress across groups. These results provided encouraging evidence for the effectiveness of online mindfulness-based interventions in reducing psychological distress, and the possible mediating role of emotion regulation, while also underlining the importance of group discussion in online mindfulness-based interventions