Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder

BackgroundGastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBR(T + tf/j) (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile.FindingsJuvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10-14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals.ConclusionsResults indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model

Nonlinear Flight Dynamics of Very Flexible Aircraft

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77147/1/AIAA-27606-989.pd

Attraction of the Invasive Halyomorpha halys (Hemiptera: Pentatomidae) to Traps Baited with Semiochemical Stimuli Across the United States

A recent identification of the two-component aggregation pheromone of the invasive stink bug species, Halyomorpha halys (Stål), in association with a synergist, has greatly improved the ability to accurately monitor the seasonal abundance and distribution of this destructive pest. We evaluated the attraction of H. halys to black pyramid traps baited with lures containing the pheromone alone, the synergist methyl (2E,4E,6Z)-decatrienoate (MDT) alone, and the two lures in combination. Traps were deployed around areas of agricultural production including fruit orchards, vegetables, ornamentals, or row crops in Delaware, Maryland, North Carolina, New Jersey, New York, Ohio, Oregon, Pennsylvania, Virginia, and West Virginia from mid-April to mid-October, 2012 and 2013. We confirmed that H. halys adults and nymphs are attracted to the aggregation pheromone season long, but that attraction is significantly increased with the addition of the synergist MDT. H. halys adults were detected in April with peak captures of overwintering adults in mid- to late May. The largest adult captures were late in the summer, typically in early September. Nymphal captures began in late May and continued season long. Total captures declined rapidly in autumn and ceased by mid-October. Captures were greatest at locations in the Eastern Inland region, followed by those in the Eastern Coastal Plain and Pacific Northwest. Importantly, regardless of location in the United States, all mobile life stages of H. halys consistently responded to the combination of H. halys aggregation pheromone and the synergist throughout the entire season, suggesting that these stimuli will be useful tools to monitor for H. halys in managed system

Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of Human Blood Mononuclear Cells

Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an ‘immature’ neonatal to a ‘mature’ adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation

Monitoring of post-match fatigue in professional soccer: Welcome to the real world

Participation in soccer match-play leads to acute and transient subjective, biochemical, metabolic and physical disturbances in players over subsequent hours and days. Inadequate time for rest and regeneration between matches can expose players to the risk of training and competing whilst not entirely recovered. In professional soccer, contemporary competitive schedules can require teams to compete in-excess of 60 matches over the course of the season while periods of fixture congestion occur prompting much attention from researchers and practitioners to the monitoring of fatigue and readiness to play. A comprehensive body of research has investigated post-match acute and residual fatigue responses. Yet the relevance of the research for professional soccer contexts is debatable notably in relation to the study populations and designs employed. Monitoring can indeed be invasive, expensive, time-inefficient and difficult to perform routinely and simultaneously in a large squad of regularly competing players. Uncertainty also exists regarding the meaningfulness and interpretation of changes in fatigue response values and their functional relevance, and practical applicability in the field. The real-world need and cost-benefit of monitoring must be carefully weighed up. In relation to professional soccer contexts, this opinion paper intends to: 1) debate the need for PMF monitoring, 2) critique the real-world relevance of the current research literature, 3) discuss the practical burden relating to measurement tools and protocols and the collection, interpretation and application of data in the field, and, 4) propose future research perspectives

Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy

Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability

Alfalfa Seed Decontamination in Salmonella Outbreak

Based on in vitro data, the U.S. Food and Drug Administration recommends chemical disinfection of raw sprout seeds to reduce enteric pathogens contaminating the seed coats. However, little is known about the effectiveness of decontamination at preventing human disease. In 1999, an outbreak of Salmonella enterica serotype Mbandaka occurred in Oregon, Washington, Idaho, and California. Based on epidemiologic and pulsed-field gel electrophoresis evidence from 87 confirmed cases, the outbreak was linked to contaminated alfalfa seeds grown in California’s Imperial Valley. Trace-back and trace-forward investigations identified a single lot of seeds used by five sprout growers during the outbreak period. Cases of salmonellosis were linked with two sprout growers who had not employed chemical disinfection; no cases were linked to three sprout growers who used disinfection. This natural experiment provides empiric evidence that chemical disinfection can reduce the human risk for disease posed by contaminated seed sprouts

A gonadotropin-releasing hormone type neuropeptide with a high affinity binding site for copper(ii) and nickel(ii).

In vertebrates gonadotropin-releasing hormone I (GnRH-I) is a key regulator of reproductive development and function. The receptor-binding activity of human GnRH-I can be modified by the presence of divalent copper. Thus, copper binding to N-terminal amino acids in GnRH-I induces structural changes that influence receptor interactions and downstream intracellular signalling cascades. It is not known if copper-binding is restricted to human GnRH-I or if it is also a feature of GnRH-type peptides that have been identified in other taxa. To investigate this, we have characterised copper binding to a recently discovered GnRH-type peptide from the starfish Asterias rubens (ArGnRH). Using a range of spectroscopic and biophysical techniques we show that this peptide can bind copper(ii) and nickel(ii). Copper(ii) is bound in a square-planar, high-affinity (Kd ∼ 10-12 M) site incorporating four nitrogen donor atoms from a histidine imidazole group, two amides and the N-terminal amine group. The ArGnRH copper affinity and geometry are quite different to GnRH-I suggesting the copper sites have evolved to suit the environment the peptides are exposed to. By comparing the copper binding sites in ArGnRH and human GnRH-I and conducting a phylogenetic analysis of GnRH-type peptide sequences from a range of species, we predict that copper-binding is an evolutionarily ancient feature of GnRH-type peptides that has been retained, modified or lost in different lineages

Long-term follow-up of IPEX syndrome patients after different therapeutic strategies : an international multicenter retrospective study

Background: Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n 5 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term.disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen