Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics

Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of type 1 diabetes. Because little is known about its absorption and effects in humans, we investigated the pharmacokinetics and pharmacodynamics of GABA in healthy volunteers. Twelve subjects were subjected to an open-labeled, three-period trial involving sequential oral administration of placebo, 2 g GABA once, and 2 g GABA three times/day for 7 days, with a 7-day washout between each period. GABA was rapidly absorbed (Tmax: 0.5 ~ 1 h) with the half-life (t1/2) of 5 h. No accumulation was observed after repeated oral GABA administration for 7 days. Remarkably, GABA significantly increased circulating insulin levels in the subjects under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p \u3c 0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p \u3c 0.01). GABA also increased glucagon levels only under fasting conditions (1.3-fold, single dose, p \u3c 0.05; 1.5-fold, repeated dose, p \u3c 0.01). However, there were no significant differences in the insulin-to-glucagon ratio and no significant change in glucose levels in these healthy subjects during the study period. Importantly, GABA significantly decreased glycated albumin levels in the repeated dosing period. Subjects with repeated dosing showed an elevated incidence of minor adverse events in comparison to placebo or the single dosing period, most notably transient discomforts such as dizziness and sore throat. However, there were no serious adverse events observed throughout the study. Our data show that GABA is rapidly absorbed and tolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal secretion, suggest potential therapeutic benefits for diabetes

The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders

The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching, and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD

Large-Scale Fusion of Gray Matter and Resting-State Functional MRI Reveals Common and Distinct Biological Markers across the Psychosis Spectrum in the B-SNIP Cohort

To investigate whether aberrant interactions between brain structure and function present similarly or differently across probands with psychotic illnesses [schizophrenia (SZ), schizoaffective disorder (SAD), and bipolar I disorder with psychosis (BP)] and whether these deficits are shared with their first-degree non-psychotic relatives. A total of 1199 subjects were assessed, including 220 SZ, 147 SAD, 180 psychotic BP, 150 first-degree relatives of SZ, 126 SAD relatives, 134 BP relatives, and 242 healthy controls (1). All subjects underwent structural MRI (sMRI) and resting-state functional MRI (rs-fMRI) scanning. Joint-independent component analysis (jICA) was used to fuse sMRI gray matter and rs-fMRI amplitude of low-frequency fluctuations data to identify the relationship between the two modalities. jICA revealed two significantly fused components. The association between functional brain alteration in a prefrontal–striatal–thalamic–cerebellar network and structural abnormalities in the default mode network was found to be common across psychotic diagnoses and correlated with cognitive function, social function, and schizo-bipolar scale scores. The fused alteration in the temporal lobe was unique to SZ and SAD. The above effects were not seen in any relative group (including those with cluster-A personality). Using a multivariate-fused approach involving two widely used imaging markers, we demonstrate both shared and distinct biological traits across the psychosis spectrum. Furthermore, our results suggest that the above traits are psychosis biomarkers rather than endophenotypes

Reintroducing the Concept of Complementarity into Psychology

Central to quantum theory is the concept of complementarity. In this essay, we argue that complementarity is also central to the emerging field of quantum cognition. We review the concept, its historical roots in psychology, and its development in quantum physics and offer examples of how it can be used to understand human cognition. The concept of complementarity provides a valuable and fresh perspective for organizing human cognitive phenomena and for understanding the nature of measurements in psychology. In turn, psychology can provide valuable new evidence and theoretical ideas to enrich this important scientific concept

Comparative proteomic analysis of a membrane-enriched fraction from flag leaves reveals responses to chemical hybridization agent SQ-1 in wheat

The induction of wheat male fertile lines by using the chemical hybridizing agent SQ-1 (CHA-SQ-1) is an effective approach in the utilization of heterosis; however, the molecular basis of male fertility remains unknown. Wheat flag leaves are the initial receptors of CHA-SQ-1 and their membrane structure plays a vital role in response to CHA-SQ-1 stress. To investigate the response of wheat flag leaves to CHA-SQ-1 stress, we compared their quantitative proteomic profiles in the absence and presence of CHA-SQ-1. Our results indicated that wheat flag leaves suffered oxidative stress during CHA-SQ-1 treatments. Leaf O2-, H2O2, and malonaldehyde levels were significantly increased within 10 h after CHA-SQ-1 treatment, while the activities of major antioxidant enzymes such as superoxide dismutase, catalase, and guaiacol peroxidase were significantly reduced. Proteome profiles of membrane-enriched fraction showed a change in the abundance of a battery of membrane proteins involved in multiple biological processes. These variable proteins mainly impaired photosynthesis, ATP synthesis protein mechanisms and were involved in the response to stress. These results provide an explanation of the relationships between membrane proteomes and anther abortion and the practical application of CHA for hybrid breeding

Field-based evidence for consistent responses of bacterial communities to copper contamination in two contrasting agricultural soils

Copper contamination on China’s arable land could pose severe economic, ecological and healthy consequences in the coming decades. As the drivers in maintaining ecosystem functioning, the responses of soil microorganisms to long-term copper contamination in different soil ecosystems are still debated. This study investigated the impacts of copper gradients on soil bacterial communities in two agricultural fields with contrasting soil properties. Our results revealed consistent reduction in soil microbial biomass carbon (SMBC) with increasing copper levels in both soils, coupled by significant declines in bacterial abundance in most cases. Despite of contrasting bacterial community structures between the two soils, the bacterial diversity in the copper-contaminated soils showed considerably decreasing patterns when copper levels elevated. High-throughput sequencing revealed copper selection for major bacterial guilds, in particular, Actinobacteria showed tolerance, while Acidobacteria and Chloroflexi were highly sensitive to copper. The thresholds that bacterial communities changed sharply were 800 and 200 added copper mg kg-1 in the fluvo-aquic soil and red soil, respectively, which were similar to the toxicity thresholds (EC50 values) characterized by SMBC. Structural equation model (SEM) analysis ascertained that the shifts of bacterial community composition and diversity were closely related with the changes of SMBC in both soils. Our results provide field-based evidence that copper contamination exhibits consistently negative impacts on soil bacterial communities, and the shifts of bacterial communities could have largely determined the variations of the microbial biomass

Similar responses of circulating microRNAs to acute high-intensity interval exercise and vigorous-intensity continuous exercise

AbstractHigh-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than low-to-moderate exercise intensity. Recently, it is becoming increasingly evident that circulating miRNAs (c-miRNAs) may distinguish between specific stress signals imposed by variations in the duration, modality, and type of exercise. The aim of this study is to investigate whether or not HIIE is superior to vigorous-intensity continuous exercise (VICE), which is contributing to develop effective fitness assessment. Twenty-six young males were enrolled, and plasma samples were collected prior to exercise and immediately after HIIE or distance-matched VICE. The miRNA level profiles in HIIE were initially determined using TaqMan Low Density Array (TLDA). And the differentially miRNAs levels were validated by stem-loop quantitative reverse-transcription PCR (RT-qPCR). Furthermore, these selective c-miRNAs were measured for VICE. Our results showed that some muscle-related miRNAs levels in the plasma, such as miR-1, miR-133a, miR-133b, and miR-206 significantly increased following HIIE or VICE compared to those at rest (P 0.05). In addition, some tissue-related or unknown original miRNA levels, such as miR-485-5p, miR-509-5p, miR-517a, miR-518f, miR-520f, miR-522, miR-553, and miR-888, also significantly increased (P 0.05). Overall, endurance exercise assessed in this study both led to significant increases in selective c-miRNAs of comparable magnitude, suggesting that both types of endurance exercise have general stress processes. Accordingly, the similar responses to both acute exercises likely indicate both exercises can be used interchangeably. Further work is needed to reveal the functional significance and signaling mechanisms behind changes in c-miRNA turnover during exercise

Development and identification of SSR markers associated with starch properties and β-carotene content in the storage root of sweet potato (Ipomoea batatas L.)

Sweet potato (Ipomoea batatas L.) is a nutritious food crop and, based on the high starch content of its storage root, a potential bioethanol feedstock. Enhancing the nutritional value and starch quantity of storage roots are important goals of sweet potato breeding programs aimed at developing improved varieties for direct consumption, processing, and industrial uses. However, developing improved lines of sweet potato is challenging due to the genetic complexity of this plant and the lack of genome information. Short sequence repeat (SSR) markers are powerful molecular tools for tracking important loci in crops and for molecular-based breeding strategies; however, few SSR markers and marker-trait associations have hitherto been identified in sweet potato. In this study, we identified 1,824 SSRs by using a de novo assembly of publicly available ESTs and mRNAs in sweet potato, and designed 1,476 primer pairs based on SSR-containing sequences. We mapped 214 pairs of primers in a natural population comprised of 239 germplasms, and identified 1,278 alleles with an average of 5.972 alleles per locus and a major allele frequency of 0.7702. Population structure analysis revealed two subpopulations in this panel of germplasms, and phenotypic characterization demonstrated that this panel is suitable for association mapping of starch-related traits. We identified 32, 16, and 17 SSR markers associated with starch content, β-carotene content, and starch composition in the storage root, respectively, using association analysis and further evaluation of a subset of sweet potato genotypes with various characteristics. The SSR markers identified here can be used to select varieties with desired traits and to investigate the genetic mechanism underlying starch and carotenoid formation in the starchy roots of sweet potato

Genome-wide Transcriptional Excavation of Dipsacus asperoides Unmasked both Cryptic Asperosaponin Biosynthetic Genes and SSR Markers

Background: Dipsacus asperoides is a traditional Chinese medicinal crop. The root is generally used as a medicine and is frequently prescribed by Chinese doctors for the treatment of back pain, limb paralysis, flutter trauma, tendon injuries and fractures. With the rapid development of bioinformatics, research has been focused on this species at the gene or molecular level. For purpose of fleshing out genome information about Dipsacus asperoides, in this paper we conducted transcriptome analysis of this species.Principal Findings: To date, many genes encoding enzymes involved in the biosynthesis of triterpenoid saponins in D.asperoides have not been elucidated. Illumina paired-end sequencing was employed to probe Dipsacus asperoides’s various enzymes associated with the relevant mesostate. A total of 30, 832,805 clean reads and de novo spliced 43,243 unigenes were obtained. Of all unigenes, only 8.27% (3578) were successfully annotated in total of seven public databases: Nr, Nt, Swiss-Prot, GO, KOG, KEGG and Pfam, which might be attributed to the poor studies on D. asperoides. The candidate genes encoding enzymes involved in triterpenoid saponin biosynthesis were identified and experimentally verified by reverse transcription qPCR, encompassing nine cytochrome P450s and seventeen UDP - glucosyltransferases. Specifically, unearthly putative genes involved in the glycosylation of hederagenin were acquired. Simultaneously, 4490 SSRs from 43,243 examined sequences were determined via bioinformatics analysis.Conclusion: This study represents the first report on the use of the Illumina sequence platform on this crop at the transcriptome level. Our findings of candidate genes encoding enzymes involved in Dipsacus saponin VI biosynthesis provide novel information in efforts to further understand the triterpenoid metabolic pathway on this species. The initial genetics resources in this study will contribute significantly to the genetic breeding program of Dipsacus asperoides, and are beneficial for clinical diagnosis and treatment

Continuing Reassortant of H5N6 Subtype Highly Pathogenic Avian Influenza Virus in Guangdong

First identified in May 2014 in China’s Sichuan Province, initial cases of H5N6 avian influenza virus (AIV) infection in humans raised great concerns about the virus’s prevalence, origin, and development. To evaluate both AIV contamination in live poultry markets (LPMs) and the risk of AIV infection in humans, we have conducted surveillance of LPMs in Guangdong Province since 2013 as part of environmental sampling programs. With environmental samples associated with these LPMs, we performed genetic and phylogenetic analyses of 10 H5N6 AIVs isolated from different cities of Guangdong Province from different years. Results revealed that the H5N6 viruses were reassortants with hemagglutinin (HA) genes derived from clade 2.3.4.4 of H5-subtype AIV, yet neuraminidase (NA) genes derived from H6N6 AIV. Unlike the other seven H5N6 viruses isolated in first 7 months of 2014, all of which shared remarkable sequence similarity with the H5N1 AIV in all internal genes, the PB2 genes of GZ693, GZ670, and ZS558 more closely related to H6N6 AIV and the PB1 gene of GZ693 to the H3-subtype AIV. Phylogenetic analyses revealed that the environmental H5N6 AIV related closely to human H5N6 AIVs isolated in Guangdong. These results thus suggest that continued reassortment has enabled the emergence of a novel H5N6 virus in Guangdong, as well as highlight the potential risk of highly pathogenic H5N6 AIVs in the province