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In contrast, BD patients showed a less integrated network topology but no disturbances in connectivity strength. No differences in outcome measures were found between SCP and SCZ, or between BD patients that used antipsychotic medication or lithium and those that did not. We conclude that functional networks in patients prone to psychosis have different signatures for chronic SCZ patients and SCP compared to euthymic BD patients, with a limited role for medication. Connectivity strength effects may have confounded previous studies, as no functional network alterations were found in SCZ after strict correction for connectivity strength.The Earth's biota is changing over time in complex ways. A critical challenge is to test whether specific biomes, taxa or types of species benefit or suffer in a time of accelerating global change. We analysed nearly 10,000 abundance time series from over 2000 vertebrate species part of the Living Planet Database. We integrated abundance data with information on geographic range, habitat preference, taxonomic and phylogenetic relationships, and IUCN Red List Categories and threats. We find that 15% of populations declined, 18% increased, and 67% showed no net changes over time. Against a backdrop of no biogeographic and phylogenetic patterning in population change, we uncover a distinct taxonomic signal. Amphibians were the only taxa that experienced net declines in the analysed data, while birds, mammals and reptiles experienced net increases. Population trends were poorly captured by species' rarity and global-scale threats. Incorporation of the full spectrum of population change will improve conservation efforts to protect global biodiversity.The glymphatic system is a network of perivascular spaces that promotes movement of cerebrospinal fluid (CSF) into the brain and clearance of metabolic waste. This fluid transport system is supported by the water channel aquaporin-4 (AQP4) localized to vascular endfeet of astrocytes. The glymphatic system is more effective during sleep, but whether sleep timing promotes glymphatic function remains unknown. We here show glymphatic influx and clearance exhibit endogenous, circadian rhythms peaking during the mid-rest phase of mice. Drainage of CSF from the cisterna magna to the lymph nodes exhibits daily variation opposite to glymphatic influx, suggesting distribution of CSF throughout the animal depends on time-of-day. The perivascular polarization of AQP4 is highest during the rest phase and loss of AQP4 eliminates the day-night difference in both glymphatic influx and drainage to the lymph nodes. We conclude that CSF distribution is under circadian control and that AQP4 supports this rhythm.Bacteriophage genomes rapidly evolve via mutation and horizontal gene transfer to counter evolving bacterial host defenses; such arms race dynamics should lead to divergence between phages from similar, geographically isolated ecosystems. However, near-identical phage genomes can reoccur over large geographical distances and several years apart, conversely suggesting many are stably maintained. Here, we show that phages with near-identical core genomes in distant, discrete aquatic ecosystems maintain diversity by possession of numerous flexible gene modules, where homologous genes present in the pan-genome interchange to create new phage variants. By repeatedly reconstructing the core and flexible regions of phage genomes from different metagenomes, we show a pool of homologous gene variants co-exist for each module in each location, however, the dominant variant shuffles independently in each module. These results suggest that in a natural community, recombination is the largest contributor to phage diversity, allowing a variety of host recognition receptors and genes to counter bacterial defenses to co-exist for each phage.Understanding extreme weather impacts on staple crops such as wheat is vital for creating adaptation strategies and increasing food security, especially in dryland cropping systems across Southern Africa. This study analyses heat impacts on wheat using daily weather information and a dryland wheat dataset for 71 cultivars across 17 locations in South Africa from 1998 to 2014. We estimate temperature impacts on yields in extensive regression models, finding that extreme heat drives wheat yield losses, with an additional 24 h of exposure to temperatures above 30 °C associated with a 12.5% yield reduction. Results from a uniform warming scenario of +1 °C show an average wheat yield reduction of 8.5%, which increases to 18.4% and 28.5% under +2 and +3 °C scenarios. We also find evidence of differences in heat effects across cultivars, which suggests warming impacts may be reduced through the sharing of gene pools amongst wheat breeding programs.The hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell-specific and genetically targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide-expressing SCN (SCNVIP) neurons, including their molecular clock, in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCNVIP neurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCNVIP neurons may regulate LMA rhythms. In vivo photometry revealed that while SCNVIP neurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNA-sequencing revealed that SCNVIP neurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Altogether, our work establishes necessity of SCNVIP neurons for the LMA circadian rhythm, elucidates organization of circadian outflow from and modulatory input to SCNVIP cells, and demonstrates a subpopulation-level molecular heterogeneity that suggests distinct functions for specific SCNVIP subtypes.In gastric cancer (GC), hypoxia is one of the greatest obstacles to cancer therapy. In this present study, we report that SH003, an herbal formulation, induces ER stress via PERK-ATF4-CHOP signaling in GC. SH003-mediated ER stress inhibits G9a, a histone methyltransferase, by reducing STAT3 phosphorylation and activates autophagy, indicating to the dissociation of Beclin-1 and autophagy initiation from Bcl-2/Beclin-1 complex. learn more However, the inhibition of PERK and CHOP inhibited SH003-induced cell death and autophagy activation. Moreover, targeting autophagy using specific siRNAs of LC3B or p62 or the autophagy inhibitor 3-MA also inhibited SH003-induced cell death in GC. Interestingly, SH003 induces BNIP3-mediated autophagic cell death under hypoxia than normoxia in GC. These findings reveal that SH003-induced ER stress regulates BNIP3-induced autophagic cell death via inhibition of STAT3-G9a axis under hypoxia in GC. Therefore, SH003 may an important tumor therapeutic strategy under hypoxia-mediated chemo-resistance.

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