Summary Mossy cells (MCs) represent a major population of excitatory neurons in the adult dentate gyrus, a brain region where new neurons are generated from radial neural stem cells (rNSCs) throughout life. Little is known about the role of MCs in regulating rNSCs. Here we demonstrate that MC commissural projections structurally and functionally interact with rNSCs through both direct glutamatergic MC-rNSC pathway and indirect GABAergic MC-local interneuron-rNSC pathway. Specifically, moderate MC activation increases rNSC quiescence through dominant indirect pathway; while high MC activation increases rNSC activation through dominant direct pathway. In contrast, MC inhibition or ablation leads to a transient increase of rNSC activation, but rNSC depletion only occurs after chronic ablation of MCs. Together, our study identifies MCs as a critical stem cell niche component that dynamically controls adult NSC quiescence and maintenance under various MC activity states through a balance of direct glutamatergic and indirect GABAergic signaling onto rNSCs.

Regulation of AMPA receptor (AMPAR)-mediated synaptic transmission is a key mechanism for synaptic plasticity. In the brain, AMPARs assemble with a number of auxiliary subunits, including TARPs, CNIHs and CKAMP44, which are important for AMPAR forward trafficking to synapses. Here we report that the membrane protein GSG1L negatively regulates AMPAR-mediated synaptic transmission. Overexpression of GSG1L strongly suppresses, and GSG1L knockout (KO) enhances, AMPAR-mediated synaptic transmission. GSG1L-dependent regulation of AMPAR synaptic transmission relies on the first extracellular loop domain and its carboxyl-terminus. GSG1L also speeds up AMPAR deactivation and desensitization in hippocampal CA1 neurons, in contrast to the effects of TARPs and CNIHs. Furthermore, GSG1L association with AMPARs inhibits CNIH2-induced slowing of the receptors in heterologous cells. Finally, GSG1L KO rats have deficits in LTP and show behavioural abnormalities in object recognition tests. These data demonstrate that GSG1L represents a new class of auxiliary subunit with distinct functional properties for AMPARs.

Summary In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. While numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin2 (NL2), a synaptic cell adhesion molecule (CAM). During maturation, inhibitory synapse development requires both NL2 and Slitrk3 (ST3), another CAM. Importantly, NL2 and ST3 interact with nanomolar affinity through their extracellular domains to synergistically promote synapse development. Selective perturbation of the NL2-ST3 interaction impairs inhibitory synapse development with consequent disruptions in hippocampal network activity and increased seizure susceptibility. Our findings reveal how unique postsynaptic CAMs work in concert to control synaptogenesis and establish a general framework for GABAergic synapse development.

Exenatide treatment reduced patient body weight and BMI, improved HbA1c and the seven-point glucose profile, reduced daily mean glucose, limited glycemic excursion, and reduced oxidative stress and inflammatory markers in patients of T2DM having inadequate glucose control.

Neurogenesis occurs in discrete regions of normal brains of adult mammals including humans, and is induced in response to brain injury and neurodegenerative disease. Whether intracerebral hemorrhage can also induce neurogenesis in human brain is unknown. Specimens were obtained from patients with primary intracerebral hemorrhage undergoing surgical evacuation of an intracerebral hematoma, and evaluated by two-photon laser scanning confocal microscopy. We found that neural stem/progenitor cell-specific protein markers were expressed in cells located in the perihematomal regions of the basal ganglia and parietal lobe of the adult human brain after primary intracerebral hemorrhage (n = 5). Cells in this region also expressed cell proliferation markers, which colocalized to the same cells that expressed neural stem/progenitor cell-specific proteins. Our data suggest that intracerebral hemorrhage induces neurogenesis in the adult human brain.

BackgroundUrinary tract infections (UTIs) occur more frequently in diabetic patients. This study was conducted to investigate the prevalence, risk factors and microorganisms of UTIs in Chinese patients with type 2 diabetes (T2D).Patients and methodsA total of 3,652 Chinese inpatients with T2D were reviewed and data on their clinical characteristics, symptoms of UTIs, random blood glucose, HbA1c, glutamic acid decarboxylase antibody, insulin autoantibody, albumin excretion rate in 24-hour urine, urine culture and susceptibility to antibiotics, and so on were collected. Binary logistic analysis was performed to look for risk factors of UTIs.ResultsThere were 409 (11.2%) patients suffering from UTIs. Gender, age, random blood glucose, insulin autoantibody and albumin excretion rate in 24-hour urine were the risk factors of UTIs in diabetic patients. The percentage of positive urine cultures was higher in the asymptomatic bacteriuria patients than in symptomatic patients (P<0.001). The incidence of septicemia was considerable in the UTIs and asymptomatic bacteriuria groups. Escherichia coli was the most common pathogenic microorganism isolated in diabetic patients with UTIs, and one-half of the E. coli infections were multidrug resistant. Furthermore, meropenem was the most effective antibiotic on E. coli.ConclusionWe suggest that a routine urine analysis or urine culture should be conducted in patients with T2D diabetes who have the identified risk factors. The UTIs might affect the islet function or blood glucose control in patients with T2D. Before a doctor decides to prescribe antibiotics to a diabetic patient with UTIs, the drug sensitivity test should be performed.

Hepatic dysfunction is common in patients with GD, and elevation of TRAb may contribute to hepatic dysfunction in patients with GD.

Liquid biopsy is noninvasive and convenient to detect cancer-derived materials in blood or other body fluids. The aim of this study was to identify tRNA-derived small RNAs (tsRNAs) in plasma that could distinguish patients with breast cancer (BC) from healthy controls. Basing on high-throughput sequencing, 15 significantly upregulated tsRNAs were selected and assessed in cell supernatants and cell lines. 6 tsRNAs were identified and verified in a large cohort of 120 patients with BC and 112 healthy controls. tRF-Arg-CCT-017, tRF-Gly-CCC-001, and tiRNA-Phe-GAA-003 could serve as novel diagnostic biomarkers. Meanwhile, tRF-Arg-CCT-017 and tiRNA-Phe-GAA-003 could also act as prognostic biomarkers. Target genes of these tsRNAs were related to the development of cancers. These results suggested that specific tsRNAs in plasma might serve as diagnostic and prognostic biomarkers of BC.