Whole-brain monosynaptic inputs to lateral periaqueductal gray glutamatergic neurons in mice.

OBJECTIVE: The lateral periaqueductal gray (LPAG), which mainly contains glutamatergic neurons, plays an important role in social responses, pain, and offensive and defensive behaviors. Currently, the whole-brain monosynaptic inputs to LPAG glutamatergic neurons are unknown. This study aims to explore the structural framework of the underlying neural mechanisms of LPAG glutamatergic neurons. METHODS: This study used retrograde tracing systems based on the rabies virus, Cre-LoxP technology, and immunofluorescence analysis. RESULTS: We found that 59 nuclei projected monosynaptic inputs to the LPAG glutamatergic neurons. In addition, seven hypothalamic nuclei, namely the lateral hypothalamic area (LH), lateral preoptic area (LPO), substantia innominata (SI), medial preoptic area, ventral pallidum, posterior hypothalamic area, and lateral globus pallidus, projected most densely to the LPAG glutamatergic neurons. Notably, we discovered through further immunofluorescence analysis that the inputs to the LPAG glutamatergic neurons were colocalized with several markers related to important neurological functions associated with physiological behaviors. CONCLUSION: The LPAG glutamatergic neurons received dense projections from the hypothalamus, especially nuclei such as LH, LPO, and SI. The input neurons were colocalized with several markers of physiological behaviors, which show the pivotal role of glutamatergic neurons in the physiological behaviors regulation by LPAG.

Spatial-temporal expression analysis of lineage-restricted shell matrix proteins reveals shell field regionalization and distinct cell populations in the slipper snail Crepidula atrasolea.

Molluscs are one of the most morphologically diverse clades of metazoans, exhibiting an immense diversification of calcium carbonate structures, such as the shell. Biomineralization of the calcified shell is dependent on shell matrix proteins (SMPs). While SMP diversity is hypothesized to drive molluscan shell diversity, we are just starting to unravel SMP evolutionary history and biology. Here we leveraged two complementary model mollusc systems, Crepidula fornicata and Crepidula atrasolea , to determine the lineage-specificity of 185 Crepidula SMPs. We found that 95% of the adult C. fornicata shell proteome belongs to conserved metazoan and molluscan orthogroups, with molluscan-restricted orthogroups containing half of all SMPs in the shell proteome. The low number of C. fornicata -restricted SMPs contradicts the generally-held notion that an animal’s biomineralization toolkit is dominated by mostly novel genes. Next, we selected a subset of lineage-restricted SMPs for spatial-temporal analysis using in situ hybridization chain reaction (HCR) during larval stages in C. atrasolea . We found that 12 out of 18 SMPs analyzed are expressed in the shell field. Notably, these genes are present in 5 expression patterns, which define at least three distinct cell populations within the shell field. These results represent the most comprehensive analysis of gastropod SMP evolutionary age and shell field expression patterns to date. Collectively, these data lay the foundation for future work to interrogate the molecular mechanisms and cell fate decisions underlying molluscan mantle specification and diversification.

Role of Dorsomedial Hypothalamus GABAergic Neurons in Sleep-Wake States in Response to Changes in Ambient Temperature in Mice.

Good sleep quality is essential for maintaining the body's attention during wakefulness, which is easily affected by external factors such as an ambient temperature. However, the mechanism by which an ambient temperature influences sleep-wake behaviors remains unclear. The dorsomedial hypothalamus (DMH) has been reported to be involved in thermoregulation. It also receives projection from the preoptic area, which is an important region for sleep and energy homeostasis and the suprachiasmatic nucleus-a main control area of the clock rhythm. Therefore, we hypothesized that the DMH plays an important role in the regulation of sleep related to ambient temperatures. In this study, we found that cold exposure (24/20/16/12 °C) increased wakefulness and decreased non-rapid eye movement (NREM) sleep, while warm exposure (32/36/40/44 °C) increased NREM sleep and decreased wakefulness compared to 28 °C conditions in wild-type mice. Then, using non-specific and specific apoptosis, we found that lesions of whole DMH neurons and DMH γ-aminobutyric acid (GABA)-ergic neurons induced by caspase-3 virus aggravated the fluctuation of core body temperature after warm exposure and attenuated the change in sleep-wake behaviors during cold and warm exposure. However, chemogenetic activation or inhibition of DMH GABAergic neurons did not affect the sleep-wake cycle. Collectively, our findings reveal an essential role of DMH GABAergic neurons in the regulation of sleep-wake behaviors elicited by a change in ambient temperature.

Qinghua Fang inhibits high-fat diet-induced non-alcoholic fatty liver disease by modulating gut microbiota.

BACKGROUND: Disturbance of the gut microbiota may play a critical role in the progression of nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet (HFD). Changes in gut microbiota were analyzed in a rat HFD-induced NAFLD model following treatment with Qinghua Fang (QHF), a Chinese herbal formula currently used in the clinical practice of traditional Chinese medicine. METHODS: Sixty Wistar rats were randomly divided into 6 groups (n=10): blank group [normal chow (NC) group], model group (HFD group), control group (BG group), Qinghua Fang high-dose group [QHF(H) group], QHF mid-dose group [QHF(M) group], QHF low-dose group [QHF(L) group]. The high, medium and low doses of QHF were used to intervene in the H, M, and L groups; the BG group was given berberine; the NC and HFD groups were given distilled water for 10 weeks. H&E staining, determination of serum liver function and blood lipid levels, and changes in the structure of rat intestinal flora through 16S rDNA denaturing gradient gel electrophoresis sequencing technology and ERIC-PCR fingerprinting were performed. RESULTS: The liver function and blood lipid levels of the rats in the HFD group were higher than those in the NC group; the alanine aminotransferase levels in the QHF-H group, QFH-M group and QHF-L group were lower than in the HFD group (P<0.05); the liver pathology of the QHF-M group and QHF-H group showed a small amount of fatty cell infiltration, but was significantly less than the hepatocyte inflammation and necrosis in the HFD group. The ERIC-PCR fingerprint and diversity analysis found that the composition of the intestinal flora of rats in the QHF-H group was significantly different from that of the NC and HFD groups. The flora of the QHF and NC groups was more diverse and richer than in the HFD group (P<0.05). CONCLUSIONS: QHF alleviated the liver dysfunction and increased blood lipid levels of NAFLD rats induced by HFD. It also effectively reduced the degree of liver steatosis and adjusted the number and structure of intestinal flora. Treatment with QHF had a significant effect on NAFLD.

Brain Functional Specialization Is Enhanced Among Tai Chi Chuan Practitioners.

OBJECTIVE: To investigate the effect of long-term Tai Chi Chuan (TCC) practice on practitioners' brain functional specialization compare with the TCC novices. DESIGN: A cross-sectional study. SETTING: A psychology Institute. PARTICIPANTS: TCC practitioners (N=22) (52.4±6.8y; 7 men; educated years: 12.18±3.03y) and 18 healthy adults (54.8±6.8y; 8 men; education years: 11.78±2.90y) matched by age, sex, and education were enrolled. MAIN OUTCOME MEASURES: Participants underwent functional magnetic resonance imaging scanning and cognitive test to measure the differences in functional specialization and cognitive function. Functional specialization was evaluated by voxel-mirrored homotopic connectivity (VMHC) method. RESULTS: Lower middle frontal gyrus VMHC in TCC practitioners compared to controls. For TCC practitioners, the longer they practice, the lower their VMHC in precentral and precuneus. TCC practitioners showed better cognition performance. CONCLUSIONS: Changed VMHC indicated that TCC practice could enhance functional specialization in the middle frontal cortex of practitioners, which may be associated with higher-order cognitive ability.

Peri-conception maternal lipid profiles predict pregnancy outcomes.

In this study, healthy women and those at high-risk of adverse pregnancy outcomes (pre-eclampsia, fetal growth restriction, gestational diabetes) were selected to assess the effect of fatty acid supplementation. The purpose of this paper is to report two novel findings (i) at recruitment the receiver operating characteristic (ROC) for erythrocyte oleic acid predicted spontaneous delivery at 34 weeks gestation (ROC=0.926 n=296) for all women entering the study. Further analysis revealed oleic and all monounsaturated fatty acids were similarly predictive with or without a supplement during the pregnancy. (ii) At delivery, we observed a biomagnification of saturated fatty acids from mother to fetus with the reverse for monounsaturates. The major conclusions are (i) the status of the mother in the months prior to conception is a stronger predictor of preterm delivery than the events during the pregnancy. (ii) Saturated fats may be playing an important function in supporting fetal membrane growth.

New European Food Safety Authority recommendation for infant formulae contradicts the physiology of human milk and infant development.

The European Food Safety Authority (EFSA) has concluded from a limited review of the literature that although docosahexaenoic acid (DHA) was required for infant formula, arachidonic acid was not 'even in the presence of DHA'. The EFSA report mistakes a nutrient ubiquitous in the diets of infants, and with wide-ranging effects, for an optional drug targeted to a particular outcome that is properly excluded when no benefit is found for that particular outcome. The EFSA's conclusion is not evidence-based. Its conclusions are grounded in trials which tested functionality of DHA, not arachidonic acid. Arachidonic acid has very different biological functions, for instance, in the vasculature and in specific aspects of immunity. None of the trials cited tested any property specific to arachidonic acid. The test of time through natural selection and human evolution has resulted in milk composition in which arachidonic acid and its long-chain polyenoic family members are conserved and occupy a prominent position. As DHA suppresses arachidonic acid, an infant formula with DHA and no arachidonic acid runs the risk of cardio- and cerebrovascular morbidity through suppression of the favourable eicosanoid derivatives of arachidonic acid and cell structural integrity. The EFSA recommendation should be rejected forthwith as unsafe and risking lifelong disability.

Effects of chromium picolinate on glucose uptake in insulin-resistant 3T3-L1 adipocytes involve activation of p38 MAPK.

Chromium picolinate (CrPic) has been discovered as a supplemental or alternative medication for type 2 diabetes, but its mechanism of action is not well understood. The purpose of this study was to explore the possible anti-diabetic mechanisms of CrPic in insulin-resistant 3T3-L1 adipocytes; the insulin resistance was induced by treatment with high glucose and insulin for 24 h. The effects of CrPic on glucose metabolism and the glucose uptake-inducing activity of CrPic were investigated. Meanwhile, the effects of CrPic on glucose transporter 4 (GLUT4) translocation were visualized by immonofluorescence microscopy. In addition, its effects on insulin signaling pathways and mitogen-activated protein kinase (MAPK) signaling cascades were assessed by immunoblotting analysis and real-time PCR. The results showed that CrPic induced glucose metabolism and uptake, as well as GLUT4 translocation to plasma membrane (PM) in both control and insulin-resistant 3T3-L1 adipocytes without any changes in insulin receptor beta (IR-beta), protein kinase B (AKt), c-Cbl, extracellular signal-regulated kinase (ERK), c-Jun phosphorylation and c-Cbl-associated protein (CAP) mRNA levels. Interestingly, CrPic was able to increase the basal and insulin-stimulated levels of p38 MAPK activation in the control and insulin-resistant cells. Pretreatment with the specific p38 MAPK inhibitor SB203580 partially inhibited the CrPic-induced glucose transport, but CrPic-activated translocation of GLUT4 was not inhibited by SB203580. This study provides an experimental evidence of the effects of CrPic on glucose uptake through the activation of p38 MAPK and it is independent of the effect on GLUT4 translocation. The findings also suggest exciting new insights into the role of p38 MAPK in glucose uptake and GLUT4 translocation.