Ten clusters were labelled by cell type according to the expression of previously described markers, and one novel population was identified according to the expression of a new set of markers. The homeostatic and mitochondrial chondrocyte populations, which were identified by the expression of the unknown markers MT1X and MT2A and MT-ND1 and MT-ATP6, were markedly expanded in KBD. The regulatory chondrocyte population, identified by the expression of CHI3L1, was markedly expanded in OA. Our study allows us to better understand the heterogeneity of chondrocytes in KBD and OA and provides new evidence of differences in the pathogenetic mechanisms between these two diseases.Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.Long term surface soil moisture (SSM) data with stable and consistent quality are critical for global environment and climate change monitoring. L band radiometers onboard the recently launched Soil Moisture Active Passive (SMAP) Mission can provide the state-of-the-art accuracy SSM, while Advanced Microwave Scanning Radiometer for EOS (AMSR-E) and AMSR2 series provide long term observational records of multi-frequency radiometers (C, X, and K bands). This study transfers the merits of SMAP to AMSR-E/2, and develops a global daily SSM dataset (named as NNsm) with stable and consistent quality at a 36 km resolution (2002-2019). The NNsm can reproduce the SMAP SSM accurately, with a global Root Mean Square Error (RMSE) of 0.029 m3/m3. NNsm also compares well with in situ SSM observations, and outperforms AMSR-E/2 standard SSM products from JAXA and LPRM. This global observation-driven dataset spans nearly two decades at present, and is extendable through the ongoing AMSR2 and upcoming AMSR3 missions for long-term studies of climate extremes, trends, and decadal variability.The real-time live fluorescent monitoring of surface AMPA receptors (AMPARs) could open new opportunities for drug discovery and phenotypic screening concerning neuropsychiatric disorders. We have developed FORTIS, a tool based on pH sensitivity capable of detecting subtle changes in surface AMPARs at a neuronal population level. The expression of SEP-GluA1 or pHuji-GluA1 recombinant AMPAR subunits in mammalian neurons cultured in 96-well plates enables surface AMPARs to be monitored with a microplate reader. Thus, FORTIS can register rapid changes in surface AMPARs induced by drugs or genetic modifications without having to rely on conventional electrophysiology or imaging. By combining FORTIS with pharmacological manipulations, basal surface AMPARs, and plasticity-like changes can be monitored. We expect that employing FORTIS to screen for changes in surface AMPARs will accelerate both neuroscience research and drug discovery.Alterations in cortical inter-areal functional connectivity, and aberrant glutamatergic signalling are implicated in the pathophysiology of schizophrenia but the relationship between the two is unclear. We used multimodal imaging to identify areas of convergence between the two systems. Two separate cohorts were examined, comprising 195 participants in total. All participants received resting state functional MRI to characterise functional brain networks and proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate concentrations in the frontal cortex. Study A investigated the relationship between frontal cortex glutamate concentrations and network connectivity in individuals with schizophrenia and healthy controls. Study B also used 1H-MRS, and scanned individuals with schizophrenia and healthy controls before and after a challenge with the glutamatergic modulator riluzole, to investigate the relationship between changes in glutamate concentrations and changes in network connectivity. In both studies the network based statistic was used to probe associations between glutamate and connectivity, and glutamate associated networks were then characterised in terms of their overlap with canonical functional networks. Puromycin ic50 Study A involved 76 individuals with schizophrenia and 82 controls, and identified a functional network negatively associated with glutamate concentrations that was concentrated within the salience network (p 0.4). Frontal cortex glutamate concentrations are associated with inter-areal functional connectivity of a network that localises to the salience network. Changes in network connectivity in response to glutamate modulation show an opposite effect compared to the relationship observed at baseline, which may complicate pharmacological attempts to simultaneously correct glutamatergic and connectivity aberrations.Many modern interactions happen in a digital space, where automated recommendations and homophily can shape the composition of groups interacting together and the knowledge that groups are able to tap into when operating online. Digital interactions are also characterized by different scales, from small interest groups to large online communities. Here, we manipulate the composition of groups based on a large multi-trait profiling space (including demographic, professional, psychological and relational variables) to explore the causal link between group composition and performance as a function of group size. We asked volunteers to search news online under time pressure and measured individual and group performance in forecasting real geo-political events. Our manipulation affected the correlation of forecasts made by people after online searches. Group composition interacted with group size so that composite diversity benefited individual and group performance proportionally to group size. Aggregating opinions of modular crowds composed of small independent groups achieved better forecasts than aggregating a similar number of forecasts from non-modular ones.Puromycin ic50
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