The symbiotic microbiota profoundly affect many aspects of host physiology; however, the molecular mechanisms underlying host-microbe cross-talk are largely unknown. Here, we show that the pyrroloquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) activity of a commensal bacterium, Acetobacter pomorum, modulates insulin/insulin-like growth factor signaling (IIS) in Drosophila to regulate host homeostatic programs controlling developmental rate, body size, energy metabolism, and intestinal stem cell activity. Germ-free animals monoassociated with PQQ-ADH mutant bacteria displayed severe deregulation of developmental and metabolic homeostasis. Importantly, these defects were reversed by enhancing host IIS or by supplementing the diet with acetic acid, the metabolic product of PQQ-ADH.

All metazoan guts are subjected to immunologically unique conditions in which an efficient antimicrobial system operates to eliminate pathogens while tolerating symbiotic commensal microbiota. However, the molecular mechanisms controlling this process are only partially understood. Here, we show that bacterial-derived uracil acts as a ligand for dual oxidase (DUOX)-dependent reactive oxygen species generation in Drosophila gut and that the uracil production in bacteria causes inflammation in the gut. The acute and controlled uracil-induced immune response is required for efficient elimination of bacteria, intestinal cell repair, and host survival during infection of nonresident species. Among resident gut microbiota, uracil production is absent in symbionts, allowing harmonious colonization without DUOX activation, whereas uracil release from opportunistic pathobionts provokes chronic inflammation. These results reveal that bacteria with distinct abilities to activate uracil-induced gut inflammation, in terms of intensity and duration, act as critical factors that determine homeostasis or pathogenesis in gut-microbe interactions.

This study investigated the relationship between psychological resilience and its relevant variables by using a meta‐analytic method. The results indicated that the largest effect on resilience was found to stem from the protective factors, a medium effect from risk factors, and the smallest effect from demographic factors.

The continuous transistor down-scaling has been the key to the successful development of the current information technology. However, with Moore's law reaching its limits the development of alternative transistor architectures is urgently needed 1 . Transistors require at least 60 mV switching voltage for each 10-fold current increase, i.e. subthreshold swing (SS) 60 mV/dec. Alternative tunnel field-effect transistors (TFETs) are widely studied to achieve a sub-thermionic SS and high I 60 (current where SS becomes 60 mV/dec) 2 . Heterojunction (HJ) TFETs bear promise to deliver high I 60 , but experimental results do not meet theoretical expectations due to interface problems in the HJs constructed from different materials. Here, we report a natural HJ-TFET with spatially varying layer thickness in black phosphorus (BP) without interface problems. We achieved record-low average SS over 4-5 decades of current, SS ave_4dec ≈ 22.9 mV/dec and SS ave_5dec ≈ 26.0 mV/dec with record-high I 60 (= 0.65-1 μA/μm), paving the way for the application in low power switches.

This study is a meta-analysis of 19 relevant studies, with 95,434 participants, investigating the relationships between various types of social support and 3 dimensions of student burnout. The overall results indicate that social support is negatively correlated with student burnout. Specifically, school or teacher supports have the strongest negative relationship to student burnout. Social supports from parents and from peers also have a significant negative relationship with student burnout. Among the 3 dimensions of student burnout, inefficacy was more strongly related to social support than emotional exhaustion or cynicism. The results of a moderation analysis suggest that the type of schools (secondary school and postsecondary school) affected the relationships between the overall social support and student burnout. We discuss the implications to ameliorate student burnout.

We demonstrate highly sensitive and selective potassium ion detection against excess sodium ions in water, by modulating the interaction between the G-quadruplex-forming molecular beacon aptamer (MBA) and cationic conjugated polyelectrolyte (CPE). The K(+)-specific aptamer sequence in MBA is used as the molecular recognition element, and the high binding specificity of MBA for potassium ions offers selectivity against a range of metal ions. The hairpin-type MBA labeled with a fluorophore and quencher at both termini undergoes a conformational change (by complexation with CPEs) to either an open-chain form or a G-quadruplex in the absence or presence of K(+) ions. Conformational changes of MBA as well as fluorescence (of the fluorophore in MBA) quenching or amplification via fluorescence resonance energy transfer from CPEs provide clear signal turn-off and -on in the presence or absence of K(+). The detection limit of the K(+) assays is determined to be ~1.5 nM in the presence of 100 mM Na(+) ions, which is ~3 orders of magnitude lower than those reported previously. The successful detection of 5'-adenosine triphosphate (ATP) with the MBA containing an ATP-specific aptamer sequence is also demonstrated using the same sensor scheme. The scheme reported herein is applicable to the detection of other kinds of G-rich aptamer-binding chemicals and biomolecules.

Genetic studies in Drosophila have demonstrated that generation of microbicidal reactive oxygen species (ROS) through the NADPH dual oxidase (DUOX) is a first line of defense in the gut epithelia. Bacterial uracil acts as DUOX-activating ligand through poorly understood mechanisms. Here, we show that the Hedgehog (Hh) signaling pathway modulates uracil-induced DUOX activation. Uracil-induced Hh signaling is required for intestinal expression of the calcium-dependent cell adhesion molecule Cadherin 99C (Cad99C) and subsequent Cad99C-dependent formation of endosomes. These endosomes play essential roles in uracil-induced ROS production by acting as signaling platforms for PLCβ/PKC/Ca2+-dependent DUOX activation. Animals with impaired Hh signaling exhibit abolished Cad99C-dependent endosome formation and reduced DUOX activity, resulting in high mortality during enteric infection. Importantly, endosome formation, DUOX activation, and normal host survival are restored by genetic reintroduction of Cad99C into enterocytes, demonstrating the important role for Hh signaling in host resistance to enteric infection.

Background and Purpose-Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion. Methods-Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury. Results-Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration. Conclusions-White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia.