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Social interactions among animals mediate essential behaviours, including mating, nurturing, and defence.sup.1,2. The gut microbiota contribute to social activity in mice.sup.3,4, but the gut-brain connections that regulate this complex behaviour and its underlying neural basis are unclear.sup.5,6. Here we show that the microbiome modulates neuronal activity in specific brain regions of male mice to regulate canonical stress responses and social behaviours. Social deviation in germ-free and antibiotic-treated mice is associated with elevated levels of the stress hormone corticosterone, which is primarily produced by activation of the hypothalamus-pituitary-adrenal (HPA) axis. Adrenalectomy, antagonism of glucocorticoid receptors, or pharmacological inhibition of corticosterone synthesis effectively corrects social deficits following microbiome depletion. Genetic ablation of glucocorticoid receptors in specific brain regions or chemogenetic inactivation of neurons in the paraventricular nucleus of the hypothalamus that produce corticotrophin-releasing hormone (CRH) reverse social impairments in antibiotic-treated mice. Conversely, specific activation of CRH-expressing neurons in the paraventricular nucleus induces social deficits in mice with a normal microbiome. Via microbiome profiling and in vivo selection, we identify a bacterial species, Enterococcus faecalis, that promotes social activity and reduces corticosterone levels in mice following social stress. These studies suggest that specific gut bacteria can restrain the activation of the HPA axis, and show that the microbiome can affect social behaviours through discrete neuronal circuits that mediate stress responses in the brain. The gut microbiota in mice can modulate social behaviour by influencing activity in stress-related brain areas., Author(s): Wei-Li Wu [sup.1] [sup.2] [sup.3] , Mark D. Adame [sup.1] , Chia-Wei Liou [sup.2] [sup.3] , Jacob T. Barlow [sup.1] , Tzu-Ting Lai [sup.2] , Gil Sharon [sup.1] , [...]

In Argentina's Mendoza River Basin (33° S), glaciers provide an essential supply of freshwater. They act as sensitive climate change indicators and are crucial for comprehending and evaluating changes in local and global climate. Based on Landsat remote sensing imagery from 1990 to 2020, this study aims to understand the distribution and changing patterns of glaciers in the Mendoza Basin and their influence on regional water supplies and ecosystems. It makes use of ratio threshold algorithms and manual interpretation to get glacier boundary data from seven different eras, using the Argentine National Glacier Inventory and the RGI glacier catalog. Furthermore, by integrating climate data from TerraClimate, the study examined the influence of regional climate change on glacier fluctuations and demonstrated the trajectory of climate change in this area during the study period. The findings show that: (1) The Mendoza Basin's glacier area was 134.09± 11.86 km² in 2020. The glacier area decreased considerably (p<0.01) between 1990 and 2020, totaling 86.87±21.30 km² (39.31±10.14%). The greatest rate of retreat was recorded between 2010 and 2020. (2) The majority of glaciers are more than 10 km², while the least common are less than 0.1 km². The biggest glaciers are melting the quickest. The majority of the glaciers are found on the southern slopes, with the northwest slopes having the fewest and the southeast and northeast slopes seeing the quickest rate of retreat. Their range of slopes is mostly 5° to 40°, with 50° to 55° being the quickest of retreat. With the greatest retreat rates below 4000 meters, the bulk are located at elevations between 4 200 and 5 400 meters. (3) The Mendoza region has seen a considerable increase in temperature since the late 1950s (p<0.001), with an average decadal rise in maximum and minimum temperatures of 0.53 °C and 0.29 °C, respectively. In the Mendoza Basin, glacier retreat is mostly caused by long-term increases in temperature; short-term factors include variations in precipitation. This research offers a guide for mitigating the effects of glacier fluctuations on the Mendoza Basin's water resource availability and geological calamities. [ABSTRACT FROM AUTHOR]

Two series of imperatorin analogs were synthesized based on our previous research and evaluated for their vasodilatation activities on in vitro rat mesenteric artery, basilar artery, and renal artery ring models. Target compounds were characterized by infrared, 1H NMR, and mass spectra. Most derivatives possessed significant vasodilatory activity on the mesenteric artery, and compound 3a exhibited favorable and broad vasodilatation activities on three kinds of rat artery ring models. The pharmacological results indicated that introducing nitrogen-contained ring in side chain or large steric hindrance at the distal end could increase the vasodilatory activity. Further, replacement of oxygen atom (–O–) in the skeleton of furocoumarin derivatives with nitrogen (–NH–) could cause the decrease of vasodilatory activity. The molecular docking also indicated that compound 3a showed a best affinity with α-1C receptor (PDB ID: 3G43). All these results suggested compound 3a would be a potential vasodilatory agent for hypertension. [ABSTRACT FROM AUTHOR]

Key points The inheritance of two defective alleles of SLC4A4, the gene that encodes the widely-expressed electrogenic sodium bicarbonate cotransporter NBCe1, results in the bicarbonate-wasting disease proximal renal tubular acidosis (pRTA)., In the present study, we report the first case of compound-heterozygous inheritance of pRTA (p.Arg510His/p.Gln913Arg) in an individual with low blood pH, blindness and neurological signs that resemble transient ischaemic attacks., We employ fluorescence microscopy on non-polarized (human embryonic kidney) and polarized (Madin-Darby canine kidney) renal cell lines and electrophysiology on Xenopus oocytes to characterize the mutant transporters (R510H and Q913R)., Both mutant transporters exhibit enhanced intracellular retention in renal cells, an observation that probably explains the HCO3− transport deficit in the individual., Both mutants retain a close-to-normal per molecule Na+/HCO3− cotransport activity in Xenopus oocytes, suggesting that they are suitable candidates for folding-correction therapy. However, Q913R expression is uniquely associated with a depolarizing, HCO3− independent, Cl−-conductance in oocytes that could have pathological consequences if expressed in the cells of patients., Abstract Proximal renal tubular acidosis (pRTA) is a rare, recessively-inherited disease characterized by abnormally acidic blood, blindness, as well as below average height and weight. pRTA is typically associated with homozygous mutation of the solute carrier 4 family gene SLC4A4. SLC4A4 encodes the electrogenic sodium bicarbonate cotransporter NBCe1, a membrane protein that acts to maintain intracellular and plasma pH. We present the first description of a case of compound-heterozygous inheritance of pRTA. The individual has inherited two mutations in NBCe1: p.Arg510His (R510H) and p.Gln913Arg (Q913R), one from each parent. In addition to the usual features of pRTA, the patient exhibits unusual signs, such as muscle spasms and fever. We have recreated these mutant transporters for expression in model systems. We find that both of the mutant proteins exhibit substantial intracellular retention when expressed in mammalian renal cell lines. When expressed in Xenopus oocytes, we find that the R510H and Q913R-mutant NBCe1 molecules exhibit apparently normal Na+/HCO3− cotransport activity but that Q913R is associated with an unusual HCO3− independent anion-leak. We conclude that a reduced accumulation of NBCe1 protein in the basolateral membrane of proximal-tubule epithelia is the most probable cause of pRTA in this case. We further note that the Q913R-associated anion-leak could itself be pathogenic if expressed in the plasma membrane of mammalian cells, compromising the benefit of strategies aiming to enhance mutant NBCe1 accumulation in the plasma membrane. [ABSTRACT FROM AUTHOR]