Explore the vast range of titles available.

Transcranial Doppler ultrasound (TCD) allows measurement of blood flow velocities in the intracranial vessels, and can be used to assess cerebral vasodilator responses to a hypercapnic stimulus. The reliability of this technique has not been established, nor is there agreement about whether the technique should be performed in sitting or lying postures. We tested the intra- and inter-rater reliability of measures of cerebrovascular reactivity (CVR) in 10 healthy adults, in sitting and lying postures. Participants underwent triplicate bilateral ultrasound assessment of flow velocities in the middle cerebral arteries whilst sitting and lying supine prior to and during inhalation of Carbogen (5% CO2, 95% O2) for 2 min. This procedure was performed twice by each of two raters for a total of four sessions. CVR was calculated as the difference between baseline and the peak blood flow velocity attained during CO2 inhalation. Intraclass correlation coefficients (ICCs) for intra-rater reliability were greater sitting than lying for both raters (e.g. Rater 1 ICC sitting = 0.822, lying = 0.734), and inter-rater reliability was also greater in sitting (e.g. sitting ICC = 0.504, lying = 0.081). These results suggest that assessment of CVR using TCD should be performed with participants sitting in order to maximise CVR measurement reliability.

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.

FOXG1 Syndrome (FS) is a devastating neurodevelopmental disorder that is caused by a heterozygous loss-of-function (LOF) mutation of the FOXG1 gene, which encodes a transcriptional regulator important for telencephalic brain development. People with FS have marked developmental delays, impaired ambulation, movement disorders, seizures, and behavior abnormalities including autistic features. Current therapeutic approaches are entirely symptomatic, however the ability to rescue phenotypes in mouse models of other genetic neurodevelopmental disorders such as Rett syndrome, Angelman syndrome, and Phelan-McDermid syndrome by postnatal expression of gene products has led to hope that similar approaches could help modify the disease course in other neurodevelopmental disorders such as FS. While FoxG1 protein function plays a critical role in embryonic brain development, the ongoing adult expression of FoxG1 and behavioral phenotypes that present when FoxG1 function is removed postnatally provides support for opportunity for improvement with postnatal treatment. Here we generated a new mouse allele of Foxg1 that disrupts protein expression and characterized the behavioral and structural brain phenotypes in heterozygous mutant animals. These mutant animals display changes in locomotor behavior, gait, anxiety, social interaction, aggression, and learning and memory compared to littermate controls. Additionally, they have structural brain abnormalities reminiscent of people with FS. This information provides a framework for future studies to evaluate the potential for post-natal expression of FoxG1 to modify the disease course in this severe neurodevelopmental disorder.

Reading disability (RD) typically consists of deficits in word reading accuracy and/or reading comprehension. While it is well known that word reading accuracy deficits lead to comprehension deficits (general reading disability, GRD), less is understood about neuropsychological profiles of children who exhibit adequate word reading accuracy but nevertheless develop specific reading comprehension deficits (S-RCD). Establishing the underlying neuropsychological processes associated with different RD types is essential for ultimately understanding core neurobiological bases of reading comprehension. To this end, the present study investigated isolated and contextual word fluency, oral language, and executive function on reading comprehension performance in 56 9- to 14-year-old children [21 typically developing (TD), 18 GRD, and 17 S-RCD]. Results indicated that TD and S-RCD participants read isolated words at a faster rate than participants with GRD; however, both RD groups had contextual word fluency and oral language weaknesses. Additionally, S-RCD participants showed prominent weaknesses in executive function. Implications for understanding the neuropsychological bases for reading comprehension are discussed.

The widespread use of protective covers in horticulture represents a novel landscape‐level change, presenting the challenges for crop pollination. Honeybees (Apis mellifera L) are pollinators of many crops, but their behavior can be affected by conditions under covers. To determine how netting crop covers can affect honeybee foraging dynamics, colony health, and pollination services, we assessed the performance of 52 nucleus honeybee colonies in five covered and six uncovered kiwifruit orchards. Colony strength was estimated pre‐ and postintroduction, and the foraging of individual bees (including pollen, nectar, and naïve foragers) was monitored in a subset of the hives fitted with RFID readers. Simultaneously, we evaluated pollination effectiveness by measuring flower visitation rates and the number of seeds produced after single honeybee visits. Honeybee colonies under cover exhibited both an acute loss of foragers and changes in the behavior of successful foragers. Under cover, bees were roughly three times less likely to return after their first trip outside the hive. Consequently, the number of adult bees in hives declined at a faster rate in these orchards, with colonies losing on average 1,057 ± 274 of their bees in under two weeks. Bees that did forage under cover completed fewer trips provisioning their colony, failing to reenter after a few short‐duration trips. These effects are likely to have implications for colony health and productivity. We also found that bee density (bees/thousand flowers) and visitation rates to flowers were lower under cover; however, we did not detect a resultant change in pollination. Our findings highlight the need for environment‐specific management techniques for pollinators. Improving honeybee orientation under covers and increasing our understanding of the effects of covers on bee nutrition and brood rearing should be primary objectives for maintaining colonies and potentially improving pollination in these systems. The widespread use of protective covers in horticulture represents a landscape‐level change that can present challenges for crop pollination. In covered kiwifruit orchards, honey bee colonies exhibited an acute loss of foragers and changes in the behavior of successful foragers. Under cover, bees were roughly three times less likely to return after their first trip outside the hive. Bees that did forage failed to reenter their colony after a few short‐duration trips. Consequently, the number of adult bees in hives declined at a faster rate in these orchards. These effects are likely to have implications for colony health and productivity.

Wearable sensors have the potential to enable measurement of sweat chloride outside the clinic. Here we assess the feasibility of mild exercise as an alternative to pilocarpine iontophoresis for sweat generation. The results from this proof-of-concept study suggest that mild exercise could be a feasible approach to obtain reliable measurements of sweat chloride concentration within 20–30 min using a wearable sensor.

Differential gene expression regulates tissue morphogenesis. The embryonic gonad is a good example, where the developmental decision to become an ovary or testis is governed by female- or male-specific gene expression. A number of genes have now been identified that control gonadal sex differentiation. However, the potential role of microRNAs (miRNAs) in ovarian and testicular pathways is unknown. In this review, we summarise our current understanding of gonadal differentiation and the possible involvement of miRNAs, using the chicken embryo as a model system. Chickens and other birds have a ZZ/ZW sex chromosome system, in which the female, ZW, is the heterogametic sex, and the male, ZZ, is homogametic (opposite to mammals). The Z-linked DMRT1 gene is thought to direct testis differentiation during embryonic life via a dosage-based mechanism. The conserved SOX9 gene is also likely to play a key role in testis formation. No master ovary determinant has yet been defined, but the autosomal FOXL2 and Aromatase genes are considered central. No miRNAs have been definitively shown to play a role in embryonic gonadal development in chickens or any other vertebrate species. Using next generation sequencing, we carried out an expression-based screen for miRNAs expressed in embryonic chicken gonads at the time of sexual differentiation. A number of miRNAs were identified, including several that showed sexually dimorphic expression. We validated a subset of miRNAs by qRT-PCR, and prediction algorithms were used to identify potential targets. We discuss the possible roles for these miRNAs in gonadal development and how these roles might be tested in the avian model.

Variation in nutrient allocation can influence the timing of breeding and ultimately reproductive output. Time and space constraints might exist, however, if fewer food resources are available to meet the costs of reproduction early during the reproductive season. Here, for the first time, we test whether nutrient‐allocation strategies for reproduction in a shrub‐dependent avian species differ with timing of breeding in different ecoregions: a high‐elevation landscape, containing spatially complex vegetation (Rocky Mountains) vs. a low‐elevation, more homogenous landscape (Great Plains). We analyzed data collected from radio‐telemetry and stable isotopes to assess the degree to which endogenous (body) reserves are used for reproduction and whether variation in allocation strategies was associated with time of year, ecoregion, habitat quality (including sagebrush type and plant greenness), or maternal characteristics. Using a Bayesian statistical framework, we found that females relied on a similar amount of endogenous reserves for reproduction in first nesting and renesting attempts. Additionally, endogenous contributions declined more rapidly throughout the nesting season in the Rocky Mountains than in the Great Plains. Individuals in high‐ and intermediate‐elevation sagebrush types in the Rocky Mountains used similar amounts of endogenous reserves, whereas females nesting in low‐elevation sagebrush used less. Females nesting at intermediate elevations, which experience the greatest flush of new green vegetation during the nesting season, switched their reliance from endogenous‐to‐exogenous sources for reproduction as green vegetation became available during spring. Our study highlights adaptations of a nutrient‐allocation strategy across areas with varying levels of resources in time and space in a habitat specialist bird. Nutrient allocation by individuals residing in high‐elevation areas favors a strategy that mainly uses nutrients gained from wintering habitats, whereas individuals residing in low‐elevation areas mainly use exogenous sources for reproduction.

Recently published data indicated that cigarette smoking causes acquired CFTR dysfunction, manifested by increased sweat chloride (2), altered sweat rate (3), and reduced CFTR activity in the upper (4) and lower respiratory tracts (5) measured by nasal and lower airway potential difference, respectively, in subjects with chronic obstructive pulmonary disease (COPD) and smokers without fixed airflow obstruction. Recent studies suggested that CFTR potentiators can reverse acquired CFTR abnormalities in vitro (2, 4, 21, 22) and that ivacaftor may restore CFTR function and improve symptoms in patients with COPD with chronic bronchitis (22). [...]these results have potential therapeutic implications, given that CFTR potentiators used for treatment of CF may also restore CFTR activity in patients with COPD (22). The Genetic Epidemiology of COPD (COPDGene) study is funded by the National Heart, Lung, and Blood Institute (grants R01 HL089897 and R01 HL089856) and by the COPD Foundation through contributions made to an industry advisory board comprised of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion. The cystic fibrosis transmembrane conductance regulator potentiator ivacaftor augments mucociliary clearance abrogating cystic fibrosis transmembrane conductance regulator inhibition by cigarette smoke.

Dyslexia is a developmental disorder in reading that exhibits varied patterns of expression across children. Here we examined the degree to which different kinds of reading disabilities (defined as profiles or patterns of reading problems) contribute to brain morphology results in Jacobian determinant images that represent local brain shape and volume. A matched-pair brain morphometry approach was used to control for confounding from brain size and research site effects in this retrospective multi-site study of 134 children from eight different research sites. Parietal operculum, corona radiata, and internal capsule differences between cases and controls were consistently observed across children with evidence of classic dyslexia, specific comprehension deficit, and language learning disability. Thus, there can be common brain morphology findings across children with quite varied reading disability profiles that we hypothesize compound the developmental difficulties of children with unique reading disability profiles and reasons for their reading disability.