spacodiR: structuring of phylogenetic diversity in ecological communities

Motivation: spacodiR is a cross-platform package, written for the R environment, for studying partitioning of diversity among natural communities in space and time. Complementing and extending existing software, spacodiR allows for hypothesis testing and parameter estimation in studying spatial structuring of species-, phylogenetic- and trait diversities. Availability: Integrated with other software in the R environment and with well documented and demonstrated functions, spacodiR is an open-source package and available at http://cran.r-project.org. Contact: [email protected]; [email protected]

Dynamic glucose disposal is driven by reduced endogenous glucose production in response to voluntary wheel running: A stable isotope approach

© 2020 the American Physiological Society. Dynamic glucose disposal is driven by reduced endogenous glucose production in response to voluntary wheel running: A stable isotope approach. Am J Physiol Endocrinol Metab 319: E2-E10, 2020. First published April 28, 2020; doi:10.1152/ajpendo.00450.2019.-To resolve both the systems level and molecular mechanisms responsible for exerciseinduced improvements in glucose tolerance, we sought to test the effect of voluntary wheel running exercise on postprandial glucose dynamics. We utilized a stable isotope-labeled oral glucose tolerance test (SI-OGTT) incorporating complementary deuterium glucose tracers at a 1:1 ratio (2-2H-glucose and 6-6 2H-glucose; 2g/kg lean body mass) to distinguish between endogenous glucose production (EGP) and whole-body glucose disposal. SI-OGTT was performed in C57BL/6J mice after 8 wk on a high-fat diet (HFD; 45% fat). Mice were then randomized to either a wheel-running cage (n = 13, HFD Ex) or a normal cage (n = 13, HFD Sed) while maintaining the HFD for 4 wk before performing a SI-OGTT. HFD Ex mice demonstrated improvements in whole blood glucose total area under the curve (AUC) that was attributed primarily to a reduction in EGP AUC. Serum insulin levels measured at 0 and 15 min post-glucose gavage were significantly elevated in the HFD Sed mice, whereas HFD Ex mice demonstrated the expected reduction in insulin at both time points. Overall, exercise improved hepatic insulin sensitivity by reducing postprandial EGP, but also increased whole-body glucose disposal. Finally, these results demonstrate the benefits of exercise on hepatic insulin sensitivity by combining a more physiological route of glucose administration (oral glucose) with the resolution of stable isotope tracers. These novel observations clearly demonstrate that SI-OGTT is a sensitive and cost-effective method to measure exercise adaptations in obese mice with as little as 2 μl of tail blood

Influences on consumption of soft drinks and fast foods in adolescents

Soft drink and fast food are energy dense foodstuffs that are heavily marketed to adolescents, and are likely to be important in terms of risk of obesity. This study sought to examine the influences on soft drink and fast food consumption among adolescents as part of a cross-sectional survey of 2,719 adolescents (aged 11-16) from 93 randomly selected schools in New South Wales, Australia. Students provided information on soft drink and fast food consumption, and responded to statements examining influences over consumption. Over half of the boys and more than one third of the girls reported drinking soft drink daily, and consumption peaked in Grade 8 students. A quarter of students reported choosing soft drinks instead of water or milk, and around 40% agreed that soft drink was usually available in their homes. Availability in the home and drinking soft drinks with meals was most strongly associated with consumption in all age groups. Fast food consumption was higher among boys than girls in all age groups. Convenience and value for money yielded the strongest associations with fast foodconsumption in boys, while preferring fast food to meals at home and preferring to &ldquo;upsize&rdquo; meals were most strongly associated with consumption in girls. Interventions to reduce consumption of soft drinks should target availability in both the home and school environment by removing soft drinks and replacing them with more nutritive beverages. Fast food outlets should be encouraged to provide a greater range of healthy and competitively priced options in reasonable portions.<br /

Diffusion MR Characteristics Following Concurrent Radiochemotherapy Predicts Progression-Free and Overall Survival in Newly Diagnosed Glioblastoma.

The standard of care for newly diagnosed glioblastoma (GBM) is surgery, then radiotherapy (RT) with concurrent temozolomide (TMZ), followed by adjuvant TMZ. We hypothesized patients with low diffusivity measured using apparent diffusion coefficient (ADC) histogram analysis evaluated after RT+TMZ, prior to adjuvant TMZ, would have a significantly shorter progression-free (PFS) and overall survival (OS). To test this hypothesis we evaluated 120 patients with newly diagnosed GBM receiving RT+TMZ followed by adjuvant TMZ. MRI was performed after completion of RT+TMZ, prior to initiation of adjuvant TMZ. A double Gaussian mixed model was used to describe the ADC histograms within the enhancing tumor, where ADCL and ADCH were defined as the mean ADC value of the lower and higher Gaussian distribution, respectively. An ADCL value of 1.0 um2/ms and ADCH value of 1.6 um2/ms were used to stratify patients into high and low risk categories. Results suggest patients with low ADCL had significantly shorter PFS (Cox Hazard Ratio = 0.12, P = 0.0006). OS was significantly shorter with low ADCL tumors, showing a median OS of 407 vs. 644 days (Cox Hazard Ratio = 0.31, P = 0.047). ADCH was not predictive of PFS or OS when accounting for age and ADCL. In summary, newly diagnosed glioblastoma patients with low ADCL after completion of RT+TMZ are likely to progress and die earlier than patients with higher ADCL. Results suggest ADC histogram analysis may be useful for patient risk stratification following completion of RT+TMZ

Assessment of musculoskeletal abnormalities in children with mucopolysaccharidoses using pGALS

Background - Children with mucopolysaccharidoses (MPS) often have musculoskeletal (MSK) abnormalities. Paediatric Gait, Arms, Legs, and Spine (pGALS), is a simple MSK assessment validated in school-age children to detect abnormal joints. We aimed to identify MSK abnormalities in children with MPS performing pGALS. Methods - Videos of children with a spectrum of MPS performing pGALS were analysed. A piloted proforma to record abnormalities for each pGALS manoeuvre observed in the videos (scored as normal/abnormal/not assessable) was used by three observers blinded to MPS subtype. Videos were scored independently and rescored for intra- and inter-observer consistency. Data were pooled and analysed. Results - Eighteen videos of children [12 boys, 6 girls, median age 11 years (4–19)] with MPS (13 type I [5 Hurler, 8 attenuated type I]; 4 type II; 1 mannosidosis) were assessed. The most common abnormalities detected using pGALS were restrictions of the shoulder, elbow, wrist, jaw (>75% cases), and fingers (2/3 cases). Mean intra-observer Κ 0.74 (range 0.65–0.88) and inter-observer Κ 0.62 (range 0.51–0.77). Hip manoeuvres were not clearly demonstrated in the videos. Conclusions - In this observational study, pGALS identifies MSK abnormalities in children with MPS. Restricted joint movement (especially upper limb) was a consistent finding. Future work includes pGALS assessment of the hip and testing pGALS in further children with attenuated MPS type I. The use of pGALS and awareness of patterns of joint involvement may be a useful adjunct to facilitate earlier recognition of these rare conditions and ultimately access to specialist care

Associations between insulin and glucose concentrations and anthropometric measures of fat mass in Australian adolescents

Background One of the most serious, yet common co-morbidities of obesity is insulin resistance, which if untreated may progress to type 2 diabetes. This paper describes the insulin and glucose concentration distributions, the prevalence of elevated insulin, the associations between insulin and body mass index (BMI), waist circumference, waist-to-height ratio (WHtR) and fat mass index in a representative sample of Australian adolescents. Methods Cross-sectional population-based study of adolescent boys and girls (N = 496, mean age 15.3 years) attending schools in metropolitan Sydney, Australia. Fasting venous blood collected and analysed for insulin and glucose concentrations. Height, weight, waist circumference measured, BMI and waist-to-height ratio calculated. Pubertal status self-reported. Results Glucose concentrations were normally distributed and were not associated with adiposity. Insulin concentrations were distributed logarithmically, were higher among girls than boys overall and within the same ranges of BMI and waist circumference, but were lower among girls than boys within the same ranges of fat mass adjusted for height. The prevalence of elevated insulin concentration (defined as \u3e 100 pmol/L) was 15.9% and 17.1% among boys and girls, respectively. Correlations between insulin concentration and BMI, waist circumference, WHtR and fat mass adjusted for height were 0.53, 0.49, 0.51 and 0.55, among boys, respectively, and 0.35, 0.40, 0.42 and 0.34, among girls, respectively. Conclusions Elevated insulin is highly correlated with adiposity in adolescents. BMI and WHtR are simple measures that can be used to identify young people who should be screened for insulin resistance and other co-morbidities

New insight into the role of the β3 subunit of the GABAA-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout

<p>Abstract</p> <p>Background</p> <p>The β3 subunit of the γ-aminobutyric acid type A receptor (GABA_A-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p> <p>Results</p> <p>Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p> <p>Conclusion</p> <p>Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA_A-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p