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Among the six SNPs tested, five SNPs (rs2236337, rs2236338, rs11539752, rs10909625, and rs8192917) showed significant association with NSV susceptibility. Among them, rs2236338, rs11539752, rs10909625, and rs8192917 remained a statistically significant association following multiple correction test. The five SNPs were located within a block of linkage disequilibrium. Haplotypes T-A-G-T-T and C-G-C-C-C consisting of rs2236337, rs2236338, rs11539752, rs10909625, and rs8192917 demonstrated significant association with NSV. Our results suggest that GZMB polymorphisms are associated with the development of NSV.Humans exhibit changes in postural control when confronted with threats to stability. This study used a prolonged threat exposure protocol to manipulate emotional state within a threatening context to determine if any threat-induced standing behaviours are employed independent of emotional state. Retention of balance adaptations was also explored. Thirty-seven adults completed a series of 90-s standing trials at two surface heights (LOW 0.8 m above ground, away from edge; HIGH 3.2 m above ground, at edge) on two visits 2-4 weeks apart. Psychological and autonomic state was assessed using self-report and electrodermal measures. Balance control was assessed using centre of pressure (COP) and lower limb electromyographic recordings. Upon initial threat exposure, individuals leaned backward, reduced low-frequency centre of pressure (COP) power, and increased high-frequency COP power and plantar/dorsiflexor coactivation. Following repeated exposure, the psychological and autonomic response to threat was substantially reduced, yet only high-frequency COP power and plantar/dorsiflexor coactivation habituated. Upon re-exposure after 2-4 weeks, there was partial recovery of the emotional response to threat and few standing balance adaptations were retained. This study suggests that some threat-induced standing behaviours are coupled with the psychological and autonomic state changes induced by threat, while others may reflect context-appropriate adaptations resistant to habituation.Species diversification in ancient lakes has enabled essential insights into evolutionary theory as they embody an evolutionary microcosm compared to continental terrestrial habitats. We have studied the high-altitude amphipods of the Andes Altiplano using mitogenomic, nuclear ribosomal and single-copy nuclear gene sequences obtained from 36 Hyalella genomic libraries, focusing on species of the Lake Titicaca and other water bodies of the Altiplano northern plateau. Results show that early Miocene South American lineages have recently (late Pliocene or early Pleistocene) diversified in the Andes with a striking morphological convergence among lineages. This pattern is consistent with the ecological opportunities (access to unoccupied resources, initial relaxed selection on ecologically-significant traits and low competition) offered by the lacustrine habitats established after the Andean uplift.Changing patterns in aerosol concentrations over the Asian region is well documented with a concurrent increase over India and a marked reduction over China. However, aerosol vertical distribution in the changing climate is not fully understood. By combining long-term satellite observations from MODIS and CALIOP, here we show rapid changes in the aerosol vertical distribution over the South and East Asia covering India and China. A statistically significant decreasing (increasing) trend in the boundary layer (free troposphere) aerosol concentrations is noticed over India. ERA-Interim reanalysis model suggests that this increase in free tropospheric aerosol concentrations are due to the lifting of boundary layer pollutants through an increase in convection (and vertical velocity) in a changing climate. In contrast, a consistent decreasing trend is observed over China irrespective of the altitude. Interestingly, a decreasing trend in Aerosol Optical Depth is observed over the northwest India and we relate this to an observed increase in precipitation leading to increase in the vegetation. It is also found that long-term oscillations like QBO, ENSO and solar cycle significantly affect the aerosol concentrations. Thus, it is prudent to conclude that background meteorology and dynamics play an important role in changing patterns of aerosol vertical distribution.The tissue microenvironment in chronic lymphocytic leukaemia (CLL) plays a key role in the pathogenesis of CLL, but the complex blood microenvironment in CLL has not yet been fully characterised. Therefore, immunophenotyping of circulating immune cells in 244 CLL patients and 52 healthy controls was performed using flow cytometry and analysed by multivariate Patient Similarity Networks (PSNs). Our study revealed high inter-individual heterogeneity in the distribution and activation of bystander immune cells in CLL, depending on the bulk of the CLL cells. High CLL counts were associated with low activation on circulating monocytes and T cells and vice versa. The highest activation of immune cells, particularly of intermediate and non-classical monocytes, was evident in patients treated with novel agents. PSNs revealed a low activation of immune cells in CLL progression, irrespective of IgHV status, Binet stage and TP53 disruption. Patients with high intermediate monocytes (> 5.4%) with low activation were 2.5 times more likely (95% confidence interval 1.421-4.403, P = 0.002) to had shorter time-to-treatment than those with low monocyte counts. Our study demonstrated the association between the activation of circulating immune cells and the bulk of CLL cells. The highest activation of bystander immune cells was detected in patients with slow disease course and in those treated with novel agents. The subset of intermediate monocytes showed predictive value for time-to-treatment in CLL.Single-cell level analysis is powerful tool to assess the heterogeneity of cellular components in tumor microenvironments (TME). In this study, we investigated immune-profiles using the single-cell analyses of endoscopically- or surgically-resected tumors, and peripheral blood mononuclear cells from gastric cancer patients. Furthermore, we technically characterized two distinct platforms of the single-cell analysis; RNA-seq-based analysis (scRNA-seq), and mass cytometry-based analysis (CyTOF), both of which are broadly embraced technologies. Our study revealed that the scRNA-seq analysis could cover a broader range of immune cells of TME in the biopsy-resected small samples of tumors, detecting even small subgroups of B cells or Treg cells in the tumors, although CyTOF could distinguish the specific populations in more depth. These findings demonstrate that scRNA-seq analysis is a highly-feasible platform for elucidating the complexity of TME in small biopsy tumors, which would provide a novel strategies to overcome a therapeutic difficulties against cancer heterogeneity in TME.The brain-expressed ubiquilins, UBQLNs 1, 2 and 4, are highly homologous proteins that participate in multiple aspects of protein homeostasis and are implicated in neurodegenerative diseases. Studies have established that UBQLN2 forms liquid-like condensates and accumulates in pathogenic aggregates, much like other proteins linked to neurodegenerative diseases. However, the relative condensate and aggregate formation of the three brain-expressed ubiquilins is unknown. Here we report that the three ubiquilins differ in aggregation propensity, revealed by in-vitro experiments, cellular models, and analysis of human brain tissue. UBQLN4 displays heightened aggregation propensity over the other ubiquilins and, like amyloids, UBQLN4 forms ThioflavinT-positive fibrils in vitro. Measuring fluorescence recovery after photobleaching (FRAP) of puncta in cells, we report that all three ubiquilins undergo liquid-liquid phase transition. UBQLN2 and 4 exhibit slower recovery than UBQLN1, suggesting the condensates formed by these brain-expressed ubiquilins have different compositions and undergo distinct internal rearrangements. We conclude that while all brain-expressed ubiquilins exhibit self-association behavior manifesting as condensates, they follow distinct courses of phase-separation and aggregation. We suggest that this variability among ubiquilins along the continuum from liquid-like to solid informs both the normal ubiquitin-linked functions of ubiquilins and their accumulation and potential contribution to toxicity in neurodegenerative diseases.Fibrosis is a key pathological feature in muscle disorders, but its quantification mainly relies on histological and biochemical assays. Muscle fibrosis most frequently is entangled with other pathological processes, as cell membrane lesions, inflammation, necrosis, regeneration, or fatty infiltration, making in vivo assessment difficult. Here, we (1) describe a novel mouse model with variable levels of induced skeletal muscle fibrosis displaying minimal inflammation and no fat infiltration, and (2) report how fibrosis affects non-invasive metrics derived from nuclear magnetic resonance (NMR) and ultrasound shear-wave elastography (SWE) associated with a passive biomechanical assay. Our findings show that collagen fraction correlates with multiple non-invasive metrics. Among them, muscle stiffness as measured by SWE, T2, and extracellular volume (ECV) as measured by NMR have the strongest correlations with histology. We also report that combining metrics in a multi-modality index allowed better discrimination between fibrotic and normal skeletal muscles. This study demonstrates that skeletal muscle fibrosis leads to alterations that can be assessed in vivo with multiple imaging parameters. Furthermore, combining NMR and SWE passive biomechanical assay improves the non-invasive evaluation of skeletal muscle fibrosis and may allow disentangling it from co-occurring pathological alterations in more complex scenarios, such as muscular dystrophies.The experimental dataset presented was collected in an 18 m long and 1 m wide laboratory flume. Low to high flood flows through an urbanized floodplain were modelled. The floodplain bed is rough, modelled with dense artificial grass. A square cylinder array, representing house models, was set on the rough bed. The cylinder immersion rate was varied cylinders are emerged for three flow cases and slightly submerged for one case. The experimental dataset comprises water levels, measured using an ultrasonic transit time probe, velocities across the channel measured using an Acoustic Doppler Velocimetry with a side looking probe, and velocities in longitudinal-vertical planes measured using Particle Image Velocimetry. These data could help understanding the physical processes associated with high flood flows through urbanized floodplains, with a focus on the transition from emerged to submerged obstacles. They could also be used as benchmark data to assess the ability of numerical models from one to three-dimensions to estimate the flood hazard (water depth, velocity) over a wide range of flood event magnitudes.Hearing aid and cochlear implant (CI) users often struggle to locate and segregate sounds. The dominant sound-localisation cues are time and intensity differences across the ears. A recent study showed that CI users locate sounds substantially better when these cues are provided through haptic stimulation on each wrist. However, the sensitivity of the wrists to these cues and the robustness of this sensitivity to aging is unknown. The current study showed that time difference sensitivity is much poorer across the wrists than across the ears and declines with age. In contrast, high sensitivity to across-wrist intensity differences was found that was robust to aging. This high sensitivity was observed across a range of stimulation intensities for both amplitude modulated and unmodulated sinusoids and matched across-ear intensity difference sensitivity for normal-hearing individuals. Furthermore, the usable dynamic range for haptic stimulation on the wrists was found to be around four times larger than for CIs. These findings suggest that high-precision haptic sound-localisation can be achieved, which could aid many hearing-impaired listeners.
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