Despite decades of extensive research efforts, efficacious therapies for Alzheimer's disease (AD) are lacking. The multi-factorial nature of AD neuropathology and symptomatology has taught us that a single therapeutic approach will most likely not fit all. Women constitute ~70% of the affected AD population, and pathology and rate of symptoms progression are 2-3 times higher in women than men. Epidemiological data suggest that menopausal estrogen loss may be causative of the more severe symptoms observed in AD women, however, results from clinical trials employing estrogen replacement therapy are inconsistent. AD pathological hallmarks-amyloid β (Aβ), neurofibrillary tangles (NFTs), and chronic gliosis-are laid down during a 20-year prodromal period before clinical symptoms appear, which coincides with the menopause transition (peri-menopause) in women (~45-54-years-old). Peri-menopause is marked by widely fluctuating estrogen levels resulting in periods of irregular hormone-receptor interactions. Recent studies showed that peri-menopausal women have increased indicators of AD phenotype (brain Aβ deposition and hypometabolism), and peri-menopausal women who used hormone replacement therapy (HRT) had a reduced AD risk. This suggests that neuroendocrine changes during peri-menopause may be a trigger that increases risk of AD in women. Studies on sex differences have been performed in several AD rodent models over the years. However, it has been challenging to study the menopause influence on AD due to lack of optimal models that mimic the human process. Recently, the rodent model of accelerated ovarian failure (AOF) was developed, which uniquely recapitulates human menopause, including a transitional peri-AOF period with irregular estrogen fluctuations and a post-AOF stage with low estrogen levels. This model has proven useful in hypertension and cognition studies with wild type animals. This review article will highlight the molecular mechanisms by which peri-menopause may influence the female brain vulnerability to AD and AD risk factors, such as hypertension and apolipoprotein E (APOE) genotype. Studies on these biological mechanisms together with the use of the AOF model have the potential to shed light on key molecular pathways underlying AD pathogenesis for the development of precision medicine approaches that take sex and hormonal status into account.

The negative side effects of opioid-based narcotics underscore the search for alternative non-opioid bioactive compounds that act on the peripheral nervous system to avoid central nervous system-mediated side effects. The transient receptor potential V1 ion channel (TRPV1) is a peripheral pain generator activated and sensitized by heat, capsaicin, and a variety of endogenous ligands. TRPV1 contributes to peripheral sensitization and hyperalgesia, in part, via triggering the release of proinflammatory peptides, such as calcitonin gene-related peptide (CGRP), both locally and at the dorsal horn of the spinal cord. Ultrapotent exogenous TRPV1 agonists, such as resiniferatoxin identified in the latex of the exotic Euphorbia resinifera, trigger hyperalgesia followed by long lasting, peripheral analgesia. The present study reports on the analgesic properties of Euphorbia bicolor, a relative of E. resinifera, native to the Southern United States. The study hypothesized that E. bicolor latex extract induces long-lasting, non-opioid peripheral analgesia in a rat model of inflammatory pain. Both inflamed and non-inflamed adult male and female rats were injected with the methanolic extract of E. bicolor latex into the hindpaw and changes in pain behaviors were reassessed at various time points up to 4 weeks. Primary sensory neuron cultures also were treated with the latex extract or vehicle for 15 min followed by stimulation with the TRPV1 agonist capsaicin. Results showed that E. bicolor latex extract evoked significant pain behaviors in both male and female rats at 20 min post-injection and lasting around 1-2 h. At 6 h post-injection, analgesia was observed in male rats that lasted up to 4 weeks, whereas in females the onset of analgesia was delayed to 72 h post-injection. In sensory neurons, latex extract significantly reduced capsaicin-evoked CGRP release. Blocking TRPV1, but not opioid receptors, attenuated the onset of analgesia and capsaicin-induced CGRP release. Latex was analyzed by mass spectrometry and eleven candidate compounds were identified and reported here. These findings indicate that phytochemicals in the E. bicolor latex induce hyperalgesia followed by peripheral, non-opioid analgesia in both male and female rats, which occurs in part via TRPV1 and may provide novel, non-opioid peripheral analgesics that warrant further examination.

Background: Tobacco use in youths is a major public health challenge globally, and approaches to the challenge have not been sufficiently addressed. The existing policies for tobacco control are not well specified by age. Objective: Our study aims to systematically investigate existing tobacco control policies, potential impacts, and national and international challenges to control tobacco use targeting the youth. Data sources: We used the statistics of the Global Youth Tobacco Survey (GYTS), studies, and approaches of tobacco control policies targeting youth. Considering country, continent, age, and significance, PubMed, Health Inter-Network Access to Research Initiative (HINARI), Scopus, the Cochrane Library, Google, and Google Scholar were searched. The related keywords were tobacco control, youth, smoking, smoking reduction policies, prevalence of tobacco use in youth, classification of tobacco control policies, incentives to prevent young people from using tobacco, WHO Framework Convention on Tobacco Control (FTCT), etc. The search strategy was by timeline, specific and popular policies, reliability, significance, and applicability. Results: We found 122 studies related to this topic. There were 25 studies focusing on situation, significance, and theoretical aspects of tobacco control policies associated with youth; 41 studies on national population polices and challenges; and 7 studies for global challenges to overcome the youth tobacco epidemic. All national policies have been guided by WHO-MPOWER strategies. Increases in tobacco tax, warning signs on packaging, restriction of tobacco product advertisements, national law to discourage young people, and peer-based approaches to quit tobacco are popular policies. Smuggling of tobacco products by youth and ignorance of smokeless tobacco control approach are major challenges. Limitation: Our study was flexible for the standard age of youth and we were not able to include all countries in the world and most of the studies focused on smoking control rather than all smokeless tobaccos. Conclusion: The policies of tobacco control adopted by many countries are based on the WHO Framework Convention on Tobacco Control but not necessarily focused on youth. Due to the physical and economic burden of tobacco consumption by youth, this is a high priority that needs to be addressed. Youth-focused creative policies are necessary, and more priority must be given to tobacco prevention in youth. Tobacco control should be a social, public health, and quality-of-life concern rather than a business and trade issue. Implication of key findings: There is limited research on how and in what ways tobacco control policies reach young people and their engagement with these policies from physical, physiological, and psychological aspects. Analysis of these aspects, popular polices practiced in different countries, and creative strategies support the need to review current practices and future ways to discourage youth from tobacco use.

Erxian decoction (EXD), a traditional Chinese medicine formula, has been used for treatment of osteoporosis for many years. The purpose of this study was to investigate the pharmacological effect of EXD in preventing osteoblast apoptosis and the underlying mechanism of prevention. Putative targets of EXD were predicted by network pharmacology, and functional and pathway enrichment analyses were also performed. Evaluations of bone mineral density, serum estradiol level, trabecular area fraction, serum calcium levels, and tumor necrosis factor (TNF)-α levels in ovariectomized rats, as well as cell proliferation assays, apoptosis assays, and western blotting in MC3T3-E1 osteoblasts were performed for further experimental validation. Ninety-three active ingredients in the EXD formula and 259 potential targets were identified. Functional and pathway enrichment analyses indicated that EXD significantly influenced the PI3K-Akt signaling pathway. In vivo experiments indicated that EXD treatment attenuated bone loss and decreased TNF-α levels in rats with osteoporosis. In vitro experiments showed that EXD treatment increased cell viability markedly and decreased levels of caspase-3 and the rate of apoptosis. It also promoted phosphorylation of Akt, nuclear translocation of transcription factor NF-erythroid 2-related factor (Nrf2), and hemeoxygenase-1 (HO-1) expression in TNF-α-induced MC3T3-E1 cells. Our results suggest that EXD exerted profound anti-osteoporosis effects, at least partially by reducing production of TNF-α and attenuating osteoblast apoptosis via Akt/Nrf2/HO-1 signaling pathway.

Acetylcholine (ACh) shortens action potential duration (APD) in human atria. APD shortening facilitates atrial fibrillation (AF) by reducing the wavelength for reentry. However, the influence of ACh on electrical conduction in human atria and its contribution to AF are unclear, particularly when combined with impaired conduction from interstitial fibrosis.

Our previous research showed that CD38 played vital roles in Ang-II induced hypertrophy and high fat diet induced heart injury. However, the role of CD38 in heart aging is still unknown. In the present study, we reported that CD38 knockdown significantly protected cardiomyocytes from D-galactose (D-gal)-induced cellular senescence. Cellular senescence was evaluated by β-galactosidase staining, the expressions of genes closely related to aging including p16 and p21, and the ROS production, MDA content and the expressions of oxidant stress related genes were examined by biochemical analysis, Western blot and QPCR. Our results showed that the expression of CD38 was increased in H9c2 cells after D-gal treatment and the expressions of NAMPT and Sirt1 were downregulated in heart tissue from old mice. CD38 knockdown significantly reduced the number of SA-β-gal-positive cells and the expressions of p16 and p21 in H9c2 cells with or without D-gal treatment. The acetylation level of total protein was decreased in CD38 knockdown group, but the expression of Sirt3 was increased in CD38 knockdown group treated with D-gal. In addition, knockdown of CD38 significantly attenuated D-gal induced ROS production, MDA content and NOX4 expression in the cells. Inhibition Sirt1 partially reversed the effects of CD38 knockdown on D-gal induced senescence and oxidative stress. Furthermore, NAD+ supplementation reduced D-gal induced cellular senescence, ROS production and MDA content. The expression of SOD2 was increased and the NOX4 expression was decreased in H9c2 cells after NAD+ supplementation. Taken together, our results demonstrated that CD38 knockdown alleviated D-gal induced cell senescence and oxidative stress via NAD+/Sirt1 signaling pathway.

Recent studies show branched-chain amino acid (BCAA) catabolic pathway is defective in obese animals and humans, contributing to the pathogenesis of insulin resistance and diabetes. However, in the context of obesity, various processes including the dysfunctional lipid metabolism can affect insulin sensitivity and glycemic regulation. It remains unclear how BCAA catabolic defect may exert direct impacts on glucose metabolism without the disturbance of obesity. The current study characterized the glucose metabolism in lean mice in which the genetic deletion of PP2Cm leads to moderate BCAA catabolic defect. Interestingly, compared to the wildtype control, lean PP2Cm deficient mice showed enhanced insulin sensitivity and glucose tolerance, lower body weight, and the preference for carbohydrate over lipids utilization. Metabolomics profiling of plasma and tissues revealed significantly different metabolic patterns in the PP2Cm deficient mice, featured by the marked alterations in glucose metabolic processes, including gluconeogenesis/glycolysis, glycogen metabolism, and tricarboxylic acid cycle. The metabolic changes of glucose were predominantly observed in liver but not skeletal muscle or white adipose tissue. The elevated branched-chain keto acids (BCKAs) resulted from the BCAA catabolic defect may play a critical role in regulating the expression of key regulators of glucose metabolic processes and the activity of respiratory Complex II/succinate dehydrogenase in TCA cycle. Together, these results show BCAA catabolic defect significantly alters glucose metabolism in lean mice with some impacts different or even opposite from those in obese mice, highlighting the critical role of BCAA catabolism in glycemic regulation and the complex interplay between macronutrients in lean and obese animals.

Neuropsychiatric disorders, such as depression, bipolar disorder, schizophrenia, obsessive-compulsive disorder, and neurodevelopmental disorders such as autism spectrum disorder, are associated with significant illness burden. Accumulating evidence supports an association between these disorders and inflammation. Consequently, anti-inflammatory agents, such as the cyclooxygenase-2 inhibitors, represent a novel avenue to prevent and treat neuropsychiatric illness. In this paper, we first review the role of inflammation in psychiatric pathophysiology including inflammatory cytokines' influence on neurotransmitters, the hypothalamic-pituitary-adrenal axis, and microglial mechanisms. We then discuss how cyclooxygenase-2-inhibitors influence these pathways with potential therapeutic benefit, with a focus on celecoxib, due to its superior safety profile. A search was conducted in PubMed, Embase, and PsychINFO databases, in addition to Clinicaltrials.gov and the Stanley Medical Research Institute trial registries. The results were presented as a narrative review. Currently available outcomes for randomized controlled trials up to November 2017 are also discussed. The evidence reviewed here suggests cyclooxygenase-2 inhibitors, and in particular celecoxib, may indeed assist in treating the symptoms of neuropsychiatric disorders; however, further studies are required to assess appropriate illness stage-related indication.

Introduction: Immigration and culture change have been thought to affect various aspects of psychological well-being, including eating behaviors. This study aimed to examine the association between immigration, acculturation strategies and eating patterns. Materials and Methods: Acculturation was conceptualized and measured by acculturation strategies of integration (maintaining original culture and adopting the new culture), assimilation (adopting the new culture and leaving behind the old), separation (sticking with the original culture only) and marginalization (maintaining/adopting neither culture). Eating patterns were conceptualized by dietary restriction, eating concern, shape concern, and weight concern. Links between demographic variables, acculturation strategies, and eating patterns were also examined. Five hundred and six Georgian women took part in the study: 253 living abroad (UK and USA) and 253 living in Georgia. Measures included East Asian Acculturation Measure (EAAM) for acculturation strategies (assimilation, integration, separation, and marginalization subscales) and Eating Disorder Examination Questionnaire (EDEQ) for eating patterns (dietary restriction, eating concern, weight concern, shape concern subscales, and global score). Relevant demographic variables and Body Mass Index (BMI) were recorded. Results: Comparisons of immigrant and nonimmigrant groups using Multivariate Analysis of Covariance (MANCOVA) with BMI as a covariate found a difference in dietary restriction only, with immigrants yielding higher mean score than non-immigrants. The global EDEQ scores of immigrant and nonimmigrant groups were almost identical though. Correlations between separation and marginalization and four EDEQ scores were statistically significant and positive, while correlations between integration and two EDEQ subscales were marginally significant and negative. Regression analysis showed that separation and marginalization strategies of acculturation were significantly linked with EDEQ eating concern, shape concern, weight concern, and global scores thereby representing predictors of elevated eating outcomes. Discussion: Findings suggested that moving to Western countries increased dietary restriction among Georgian women. Furthermore, while living abroad, the lack of integration in a host culture, as a common denominator of separation and marginalization strategies of acculturation, may predict elevated eating, shape, and weight concerns among women relocated over six years ago. Acculturation conditions may also be linked with integration or well-being outcomes.

Background: Attention-deficit hyperactivity disorder (ADHD) is a typical neuropsychiatric disorder characterized by inattention, impulsivity, and hyperactivity, particularly in children. Recent studies demonstrated a close relationship between the development of ADHD and surgery under general anesthesia. However, few studies illustrated if ADHD symptoms changed after surgery. Meanwhile, whether these individuals with natural neural impairment were sensitive to postoperative neurocognitive disorder (PND) still remain unclear. Methods: Spontaneously hypertensive rats (SHR) were utilized as spontaneous ADHD animal model and Wistar-Kyoto (WKY) rats as non-ADHD animal model. We evaluated the variation of neurocognitive function and locomotor activity of the rats undergoing experimental laparotomy with general anesthesia by isoflurane. Neurocognitive function was assessed by fear conditioning test for contextual memory and Morris water maze (MWM) for spatial memory. Depressive-like behavior after surgery was detected by forced swim test, and open-field test and elevated plus maze test were utilized to evaluate locomotor activities and anxiety. Furthermore, we compared electroencephalogram (EEG) signal in ADHD and WKY rats under free-moving conditions. Afterward, c-Fos staining was also utilized to detect the excitatory activity of neurons in these rats to explore the neural mechanism. Results: Locomotor activity of SHR assessed by average speed and number of line crossings in the open-field test decreased 1 week after surgery under general anesthesia, but there was no difference concerning anxiety levels between SHR and WKY rats after surgery. This phenomenon was also paralleled with the change in EEG signal (delta band 0∼3 Hz). Surgery under general anesthesia had no effect on spatial and contextual memory, while it improved spontaneous depression in SHR. The expression of c-Fos was downregulated for at least 1 week in the nucleus accumbens (NAc) area of ADHD rats' brain after surgery. Conclusion: ADHD rats were not sensitive to PND. Surgery with general anesthesia could partly improve the hyperactivity symptom of ADHD rats. This mechanism was related to the suppression of neural activity in the cerebral NAc of ADHD rats induced by general anesthetics.

Noradrenergic pathways have been implicated in eating pathologies. These experiments sought to examine how dietary-induced binge eating influences the neuronal activity of the locus coeruleus (LC)-norepinephrine (NE) system. Young adult female Sprague Dawley rats (7-8 weeks old) were exposed to a repeated intermittent (twice weekly) cycle of 30-min access to a highly palatable sweetened fat (i.e., vegetable shortening with 10% sucrose) with or without intermittent (24 h) calorie restriction (Restrict Binge or Binge groups, respectively). Age- and weight-matched female control rats were exposed to standard chow feeding (Naive group) or intermittent chow feeding (Restrict group). The Binge and Restrict Binge groups demonstrated an escalation in sweet-fat food intake after 2.5 weeks. On week 3, in vivo single-unit LC electrophysiological activity was recorded under isoflurane anesthesia. Restrict Binge (20 cells from six rats) and Binge (27 cells from six rats) had significantly reduced (approximate 20% and 26%, respectively) evoked LC discharge rates compared with naive rats (22 cells, seven rats). Spontaneous and tonic discharge rates were not different among the groups. Signal-to-noise ratio was reduced in the groups with intermittent sweetened fat exposure. In order to investigate the neuropeptide alterations as a consequence of dietary binge eating, relative gene expression of neuropeptide Y (NPY), glucagon-like peptide 1 receptor (GLP-1r), prodynorphin, and related genes were measured in LC and hypothalamic arcuate (Arc) regions. Glp-1r, Npy2r, and Pdyn in LC region were reduced with repeated intermittent restriction. Npy1r was reduced by approximately 27% in ARC of Restrict compared with Naive group. Such data indicate that dietary-induced binge eating alters the neural response of LC neurons to sensory stimuli and dampens the neural stress response.

Previous research has reliably found that self-control strength moderates the anxiety-performance relationship for cognitive and perceptual-motor tasks that involve executive functioning. In the present preregistered experiment (N = 200; https://aspredicted.org/a775h.pdf), we investigated whether the interaction of anxiety and self-control also predicts creative flexibility performance. According to the Attentional Control Theory, anxiety can impair executive functioning. In the case that creative flexibility relies on executive functions, anxiety should therefore interfere with creative flexibility performance. However, self-control strength has been demonstrated to serve as a buffer against the negative effects of anxiety on executive functioning. Therefore, we assumed that there will be a negative relationship between anxiety and creative flexibility performance, and that this negative relationship would be more pronounced for participants who are low compared to high in momentary self-control strength. Analogous to the previous studies, we manipulated the participants' self-control strength (ego depletion vs. no depletion) and subsequently induced a potentially threatening test situation. The participants then completed a measure of their state anxiety and a standardized test of creative flexibility. Contrary to our expectation, self-control strength, state anxiety, and their interaction did not predict creative flexibility performance. Complementary Bayesian hypothesis testing revealed strong support for the null hypothesis. Therefore, we conclude that, at least under certain conditions, creative flexibility performance may be unrelated to resource-dependent executive functions.

In this study we examine the effectiveness and far transfer effects of a training that was found to be effective in promoting Executive Function (EF) in a sample of 5-year-old children (Traverso et al., 2015). By contrast with Traverso et al. (2015), the intervention was administered by regular teachers to verify its ecological validity. Far transfer was assessed by evaluating the training effects on pre-academic skills. 126 children attending the last year of Italian preschool educational services took part in the study (mainly 5-year-old children). Pre- and post-test assessments were conducted using a large EF and pre-academic skill task battery. The results indicate that the experimental group outperformed the control group in an interference suppression composite score. Moreover, significant far transfer effects to pre-academic skills in literacy domain were found. In addition, we found that the improvement in the pre academic skills (in both literacy and math domains) was mediated by the improvement in the interference suppression score. The results suggest the possibility that this intervention, which may be easily implemented in the context of educational services, can promote EF during the preschool period before entry to primary school.

Adolescence is an especially risky phase for the appearance of antisocial behaviors. Antisocial behavior produces significant individual and social harms, so it is important to provide keys for prevention and treatment. To do that, it is essential to identify the main predictors. The objective of this study is to analyze the effect of family (affection and communication, behavioral control) and friends (antisocial friendships) on adolescent antisocial behavior, as well as the mediating role of adolescent impulsivity and empathy on these relationships. Previously validated questionnaires measuring parental affection and communication, and behavioral control, as well as adolescent impulsivity, empathy, antisocial friendships, and antisocial behavior were applied to 3199 adolescents in Asturias (Spain), aged between 11 and 18 (M = 14.03; SD = 1.39). Descriptive, correlational, and structural equation analysis were performed. Antisocial friendships were a risk factor for antisocial behavior in adolescence, with a moderate effect size. The effect is mostly direct, although it is also indirect through the positive relationship with adolescent impulsivity and low empathy. The two analyzed parenting style dimensions (affection and communication, and behavioral control) demonstrate a protective effect, albeit small, on adolescent antisocial behavior. There is a direct protective effect, but it is mostly indirect through the negative relationship with antisocial friendships and low adolescent empathy. Parental behavioral control can be a risk factor for antisocial behavior, through the positive relationship with adolescent impulsivity. This study helps to clarify the causal mechanisms of antisocial behavior in adolescence, as a basis for its prevention and treatment.

Freezing of gait (FOG) is often experienced in advanced stages of Parkinson's disease (PD) and can lead to an increased risk of falls. Although spatiotemporal characteristics of FOG are well-described, their underlying neuromuscular mechanisms remain poorly understood. Several studies have demonstrated an abnormal activation of distal muscles of the lower limb and coordination impairments during gait in people with PD (pwPD). However, few have investigated how various characteristics of electromyograms (EMGs) change before, during and after a freezing episode (FE). Our objective was to quantify changes in proximal and distal leg muscle activity associated with FEs. In this study, 12 pwPD, confirmed as freezers, performed a repetitive stepping-in-place task used to elicit FE. Surface EMGs were collected from proximal [rectus femoris and biceps femoris (BF)] and distal [tibialis anterior (TA) and gastrocnemius medialis (GM)] muscles. Data epochs of 500 ms were extracted from EMG time series at four different periods: baseline, 2 s before a FE, during a FE, and 2 s after a FE. For each epoch, EMG amplitude [root-mean-square (RMS)], variability [coefficient of variation (CoV)], and inter-muscle functional connectivity (mutual information) were quantified. Results from the analysis of 21 FEs show a significant main effect of Period for EMG amplitude in bilateral TA and in the least affected GM (p < 0.01), with decreased activation before freezing that remained low during and after the FE. On the other hand, a main effect of Period was also found in bilateral BF muscles (p < 0.01) but with increased activation before freezing that was generally sustained during and after FE. Main effects of Period were also found for all measures of variability, except for the least affected GM, showing reduced variability during the FE that returned to baseline in all muscles except both TA. Moreover, an increase in functional connectivity between the least affected distal muscles was seen before the FE. Our findings confirm that many characteristics of EMG patterns of both distal and proximal leg muscles change throughout periods of a FE, suggesting both impairment and adaptive strategies from proximal muscles.

The wide diversity in gut microbiota that is found among individuals is affected by factors including environment, genetics, dietary habits, and lifestyle after birth. The gastrointestinal tract, the largest and most complicated in vivo ecosystem, is a natural habitat for microbe colonization. Gut microbiota acts as "metabolic organ" that interacts with the human host symbiotically and performs an important role in maintaining health. In addition to the above factors, microbiota distributions/proportions are affected by exercise and other forms of physical activity. However, diet, lifestyle, and nutritional supplementation may impede the actual analytic relationship in practice. Therefore, the purpose of this study is to understand the effects of several microbiota on physical fitness, exercise performance, energy metabolism, and biochemistries using the concept of gnotobiote based on a germ-free model. The microbes Eubacterium rectale, Lactobacillus plantarum TWK10, and Clostridium coccoides were separately inoculated into gnotobiotic animal models. Fecal analysis was regularly done for the entire duration of the experiment. The exercise capacities were measured repeatedly with and without aerobic exercise training using an exhaustive swimming test. Various fatigue-associated biochemical variables, including lactate, ammonia, glucose, lactic dehydrogenase (LDH), and creatine kinase (CK) were also measured to assess physiological adaption. In addition, metabolic phenotype was applied to record basal metabolic rate, diet, behavior, and activities. Body composition, glycogen content, and histopathology were further evaluated to assess the gnotobiotic effects. E. rectale engendered capacities, physiological adaption, and physical activities that were significantly better than other two microbes, possible due to energy regulation and bioavailability. In addition, L. plantarum TWK10 and C. coccoides were found to significantly increase the basal metabolic rate and to alter the body compositions, although no exercise capacity benefit was found in the gnotobiotic models. The E. rectale and L. plantarum gnotobiotic animals all showed normal histological observations with the exception of the C. coccoides gnotobiote, which showed the pathological observation of hepatic necrosis. The gnotobiotic model directly demonstrates the interactions between microbes and hosts, which are especially relevant and applicable to the field of sports science. This study supports the development of beneficial microbiota for application to exercise and fitness, which is an emerging area of health promotion.

Earth's temperature is rising, and with this increase, fungal communities are responding and affecting soil carbon processes. At a long-term soil-warming experiment in a boreal forest in interior Alaska, warming and warming-associated drying alters the function of microbes, and thus, decomposition of carbon. But what genetic mechanisms and resource allocation strategies are behind these community shifts and soil carbon changes? Here, we evaluate fungal resource allocation efforts under long-term experimental warming (including associated drying) using soil metatranscriptomics. We profiled resource allocation efforts toward decomposition and cell metabolic maintenance, and we characterized community composition. We found that under the warming treatment, fungi allocate resources to cell metabolic maintenance at the expense of allocating resources to decomposition. In addition, we found that fungal orders that house taxa with stress-tolerant traits were more abundant under the warmed treatment compared to control conditions. Our results suggest that the warming treatment elicits an ecological tradeoff in resource allocation in the fungal communities, with potential to change ecosystem-scale carbon dynamics. Fungi preferentially invest in mechanisms that will ensure survival under warming and drying, such as cell metabolic maintenance, rather than in decomposition. Through metatranscriptomes, we provide mechanistic insight behind the response of fungi to climate change and consequences to soil carbon processes.

Protein phosphorylation is a key post-translational modification required for many cellular functions of the bacterial cell. Recently, we identified a new protein-kinase, named UbK, in Bacillus subtilis that belongs to a new family of protein-kinases widespread in bacteria. In this study, we analyze the function of UbK in Streptococcus pneumoniae. We show that UbK displays a tyrosine-kinase activity and autophosphorylates on a unique tyrosine in vivo. To get insights into its cellular role, we constructed a set of pneumococcal ubk mutants. Using conventional and electron microscopy, we show that the ubk deficient strain, as well as an ubk catalytic dead mutant, display both severe cell-growth and cell-morphology defects. The same defects are observed with a mutant mimicking permanent phosphorylation of UbK whereas they are not detected for a mutant mimicking defective autophosphorylation of UbK. Moreover, we find that UbK phosphorylation promotes its ability to hydrolyze ATP. These observations show that the hydrolysis of ATP by UbK serves not only for its autophosphorylation but also for a distinct purpose essential for the optimal cell growth and cell-morphogenesis of the pneumococcus. We thus propose a model in which the autophosphorylation/dephosphorylation of UbK regulates its cellular function through a negative feedback loop.

The crustal subseafloor is the least explored and largest biome on Earth. Interrogating crustal life is difficult due to habitat inaccessibility, low-biomass and contamination challenges. Subseafloor observatories have facilitated the study of planktonic life in crustal aquifers, however, studies of life in crust-attached biofilms are rare. Here, we investigate biofilms grown on various minerals at different temperatures over 1-6 years at subseafloor observatories in the Eastern Pacific. To mitigate potential sequence contamination, we developed a new bioinformatics tool - TaxonSluice. We explore ecological factors driving community structure and potential function of biofilms by comparing our sequence data to previous amplicon and metagenomic surveys of this habitat. We reveal that biofilm community structure is driven by temperature rather than minerology, and that rare planktonic lineages colonize the crustal biofilms. Based on 16S rRNA gene overlap, we partition metagenome assembled genomes into planktonic and biofilm fractions and suggest that there are functional differences between these community types, emphasizing the need to separately examine each to accurately describe subseafloor microbe-rock-fluid processes. Lastly, we report that some rare lineages present in our warm and anoxic study site are also found in cold and oxic crustal fluids in the Mid-Atlantic Ridge, suggesting global crustal biogeography patterns.

We performed a study to (i) investigate efficacy of an Escherichia coli/Salmonella spp./Listeria monocytogenes-targeting bacteriophage cocktail (tentatively named F.O.P.) to reduce a human pathogenic E. coli strain O157:H7 in experimentally infected mice, and (ii) determine how bacteriophages impact the normal gut microbiota when compared with antibiotic therapy. A total of 85 mice were inoculated with E. coli O157:H7 strain Ec231 [nalidixic acid resistant (NalAcR)] via oral gavage, and were randomized into six groups separated into three categories: 1st category received PBS or No phage/No PBS (control), 2nd category received either F.O.P., F.O.P. at 1:10 dilution, or only the E. coli phage component of F.O.P. (EcoShield PXTM), and 3rd category received the antibiotic ampicillin. All therapies were administered twice daily for four consecutive days including before and after bacterial challenge; except ampicillin which was administered only before and after bacterial challenge on day 0. Fecal samples were collected at Days 0, 1, 2, 3, 5, and 10. Samples were homogenized and plated on LB plates supplemented with NalAc to determine viable Ec231 counts. Body weights were measured at every fecal sample collection point. qPCR was performed using specific E. coli O157:H7 primers to quantify the number of E. coli O157:H7 genome copies. Microbiota community profiles were analyzed using Denature Gradient Gel Electrophoresis (DGGE) and 16S rRNA sequencing. F.O.P. significantly (P < 0.05) reduced E. coli O157:H7 pathogen counts by 54%. Ampicillin therapy significantly (P < 0.05) reduced E. coli O157:H7 pathogen counts by 79%. Greater initial weight-loss occurred in mice treated with ampicillin (-5.44%) compared to other treatment groups. No notable changes in the gut microbiota profiles were observed for control and F.O.P. groups. In contrast, the antibiotic group displayed noticeable distortion of the gut microbiota composition, only partially returning to normal by Day 10. In conclusion, we found that F.O.P. administration was effective in reducing viable E. coli O157:H7 in infected mice with a similar efficacy to ampicillin therapy. However, the F.O.P. bacteriophage preparation had less impact on the gut microbiota compared to ampicillin.