Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants

Background: Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study. Methods: This study included cross-sectional data from 48 170 white European adults, aged 37–73 years, participating on the UK Biobank. Interactions between GPRS-obesity, and macronutrient intake (including total energy, protein, fat, carbohydrate and dietary fibre intake) and its effects on BMI and WC were investigated. Results: The 93-SNPs genetic profile risk score was associated with a higher BMI (β:0.57 kg.m−2 per standard deviation (s.d.) increase in GPRS, [95%CI:0.53–0.60]; P=1.9 × 10−183) independent of major confounding factors. There was a significant interaction between GPRS and total fat intake (P[interaction]=0.007). Among high fat intake individuals, BMI was higher by 0.60 [0.52, 0.67] kg.m−2 per s.d. increase in GPRS-obesity; the change in BMI with GPRS was lower among low fat intake individuals (β:0.50 [0.44, 0.57] kg.m-2). Significant interactions with similar patterns were observed for saturated fat intake (High β:0.66 [0.59, 0.73] versus Low β:0.49 [0.42, 0.55] kg.m-2, P-interaction=2 × 10-4), and total energy intake (High β:0.58 [0.51, 0.64] versus Low β:0.49 [0.42, 0.56] kg.m−2, P-interaction=0.019), but not for protein intake, carbohydrate intake and fiber intake (P-interaction >0.05). The findings were broadly similar using WC as the outcome. Conclusions: These data suggest that the benefits of reducing the intake of fats and total energy intake, may be more important in individuals with high genetic risk for obesity

CrRLK1L receptor‐like kinases HERK1 and ANJEA are female determinants of pollen tube reception

Communication between the gametophytes is vital for angiosperm fertilisation. Multiple CrRLK1L‐type receptor kinases prevent premature pollen tube burst, while another CrRLK1L protein, FERONIA (FER), is required for pollen tube reception in the female gametophyte. We report here the identification of two additional CrRLK1L homologues, HERCULES RECEPTOR KINASE 1 (HERK1) and ANJEA (ANJ), which act redundantly to promote pollen tube growth arrest at the synergid cells. HERK1 and ANJ localise to the filiform apparatus of the synergid cells in unfertilised ovules, and in herk1 anj mutants, a majority of ovules remain unfertilised due to pollen tube overgrowth, together indicating that HERK1 and ANJ act as female determinants for fertilisation. As in fer mutants, the synergid cell‐specific, endomembrane protein NORTIA (NTA) is not relocalised after pollen tube reception; however, unlike fer mutants, reactive oxygen species levels are unaffected in herk1 anj double mutants. Both ANJ and HERK1 associate with FER and its proposed co‐receptor LORELEI (LRE) in planta. Together, our data indicate that HERK1 and ANJ act with FER to mediate female–male gametophyte interactions during plant fertilisation

Thirty Years of Cometary Spectroscopy from McDonald Observatory

We report on the results of a spectroscopic survey of 130 comets that was conducted at McDonald observatory from 1980 through 2008. Some of the comets were observed on only one night, while others were observed repeatedly. For 20 of these comets, no molecules were detected. For the remaining 110 comets, some emission from CN, OH, NH, C$_{3}$, C$_{2}$, CH, and NH$_{2}$ molecules were observed on at least one occasion. We converted the observed molecular column densities to production rates using a Haser (1957) model. We defined a restricted data set of comets that had at least 3 nights of observations. The restricted data set consists of 59 comets. We used ratios of production rates to study the trends in the data. We find two classes of comets: typical and carbon-chain depleted comets. Using a very strict definition of depleted comets, requiring C$_{2}$ \underline{and} C$_{3}$ to both be depleted, we find 9% of our restricted data set comets to be depleted. Using a more relaxed definition that requires only C$_{2}$ to be below a threshold (similar to other researchers), we find 25% of the comets are depleted. Two-thirds of the depleted comets are Jupiter Family comets, while one-third are Long Period comets. 37% of the Jupiter Family comets are depleted, while 18.5% of the Long Period comets are depleted. We compare our results with other studies and find good agreement.Comment: Accepted for Icarus; 15 figures, 9 tables (some multi-page and in landscape mode

Do physical activity, commuting mode, cardiorespiratory fitness and sedentary behaviours modify the genetic predisposition to higher BMI? Findings from a UK Biobank study

Objective: To investigate whether the association between a genetic profile risk score for obesity (GPRS-obesity) (based on 93 SNPs) and body mass index (BMI) was modified by physical activity (PA), cardiorespiratory fitness, commuting mode, walking pace and sedentary behaviours. Methods: For the analyses we used cross-sectional baseline data from 310,652 participants in the UK Biobank study. We investigated interaction effects of GPRS-obesity with objectively measured and self-reported PA, cardiorespiratory fitness, commuting mode, walking pace, TV viewing, playing computer games, PC-screen time and total sedentary behaviour on BMI. Body mass index (BMI) was the main outcome measure. Results: GPRS-obesity was associated with BMI (β:0.54 kg.m−2 per standard deviation (SD) increase in GPRS, [95% CI: 0.53; 0.56]; P = 2.1 × 10−241). There was a significant interaction between GPRS-obesity and objectively measured PA (P[interaction] = 3.3 × 10−11): among inactive individuals, BMI was higher by 0.58 kg.m−2 per SD increase in GPRS-obesity (p = 1.3 × 10−70) whereas among active individuals the relevant BMI difference was less (β:0.33 kg.m−2, p = 6.4 × 10−41). We observed similar patterns for fitness (Unfit β:0.72 versus Fit β:0.36 kg.m−2, P[interaction] = 1.4 × 10−11), walking pace (Slow β:0.91 versus Brisk β:0.38 kg.m−2, P[interaction] = 8.1 × 10−27), discretionary sedentary behaviour (High β:0.64 versus Low β:0.48 kg.m−2, P[interaction] = 9.1 × 10−12), TV viewing (High β:0.62 versus Low β:0.47 kg.m−2, P[interaction] = 1.7 × 10−11), PC-screen time (High β:0.82 versus Low β:0.54 kg.m−2, P[interaction] = 0.0004) and playing computer games (Often β:0.69 versus Low β:0.52 kg.m−2, P[interaction] = 8.9 × 10−10). No significant interactions were found for commuting mode (car, public transport, active commuters). Conclusions: Physical activity, sedentary behaviours and fitness modify the extent to which a set of the most important known adiposity variants affect BMI. This suggests that the adiposity benefits of high PA and low sedentary behaviour may be particularly important in individuals with high genetic risk for obesity

A Review of the fossil record of turtles of the clade Baenidae

The fossil record of the turtle clade Baenidae ranges from the Early Cretaceous (Aptian—Albian) to the Eocene. The group is present throughout North America during the Early Cretaceous, but is restricted to the western portions of the continents in the Late Cretaceous and Paleogene. No credible remains of the clade have been reported outside of North America to date. Baenids were warmadapted freshwater aquatic turtles that supported high levels of diversity at times through niche partitioning, particularly by adapting to a broad range of dietary preferences ranging from omnivorous to molluscivorous. Current phylogenies place Baenidae near the split of crown-group Testudines. Within Baenidae three more inclusive, named clades are recognized: Baenodda, Palatobaeninae and Eubaeninae. A taxonomic review of the group concludes that of 49 named taxa, 30 are nomina valida, 12 are nomina invalida and 7 are nomina dubia

The combination of physical activity and sedentary behaviors modifies the genetic predisposition to obesity

Objective: This study aimed to investigate whether the association between a validated genetic profile risk score for BMI (GPRS‐BMI) (based on 93 single‐nucleotide polymorphisms) and phenotypic obesity (BMI) was modified by the combined categories of physical activity (PA) and sedentary behaviors in a large population‐based study. Methods: This study included cross‐sectional baseline data from 338,216 white European adult men and women aged 37 to 73 years. Interaction effects of GPRS‐BMI with the combined categories of PA and sedentary behaviors on BMI were investigated. Results: There was a significant interaction between GPRS‐BMI and the combined categories of objectively measured PA and total sedentary behavior (P[interaction]  =  3.5 × 10−6); among physically inactive and highly sedentary individuals, BMI was higher by 0.60 kg/m2 per 1‐SD increase in GPRS‐obesity (P  =  8.9 × 10−50), whereas the relevant BMI difference was 38% lower among physically active individuals and those with low sedentary time (β: 0.37 kg/m2; P  =  2.3 × 10−51). A similar pattern was observed for the combined categories of objective PA and TV viewing (inactive/high TV viewing β: 0.60 vs. active/low TV viewing β: 0.40 kg/m2; P[interaction]  =  2.9 × 10−6). Conclusions: This study provides evidence that combined categories of PA and sedentary behaviors modify the extent to which genetic predisposition to obesity results in higher BMI

Development of a novel AAV gene therapy cassette with improved safety features and efficacy in a mouse model of Rett syndrome

Rett syndrome (RTT), caused by loss-of-function mutations in the MECP2 gene, is a neurological disorder characterized by severe impairment of motor and cognitive functions. The aim of this study was to investigate the impact of vector design, dosage and delivery route on the efficacy and safety of gene augmentation therapy in mouse models of RTT. Our results show that AAV-mediated delivery of MECP2 to Mecp2-null mice by systemic administration, and utilizing a minimal endogenous promoter, was associated with a narrow therapeutic window and resulted in liver toxicity at higher doses. Lower doses of this vector significantly extended survival of mice lacking MeCP2 or expressing a mutant T158M allele but had no impact on RTT-like neurological phenotypes. Modifying vector design by incorporating an extended Mecp2 promoter and additional regulatory 3’-UTR elements significantly reduced hepatic toxicity after systemic administration. Moreover, direct cerebroventricular injection of this vector into neonatal Mecp2-null mice resulted in high brain transduction efficiency, increased survival and bodyweight and an amelioration of RTT-like phenotypes. Our results show that controlling levels of MeCP2 expression in the liver is achievable through modification of the expression cassette. However, it also highlights the importance of achieving high brain transduction to impact the RTT-like phenotypes

Convex hull approach for determining rock representative elementary volume for multiple petrophysical parameters using pore-scale imaging and Lattice-Boltzmann modelling

In the last decade, the study of fluid flow in porous media has developed considerably due to the combination of X-ray Micro Computed Tomography (micro-CT) and advances in computational methods for solving complex fluid flow equations directly or indirectly on reconstructed three-dimensional pore space images. In this study, we calculate porosity and single phase permeability using micro-CT imaging and Lattice Boltzmann (LB) simulations for 8 different porous media: beadpacks (with bead sizes 50 µm and 350 µm), sandpacks (LV60 and HST95), sandstones (Berea, Clashach and Doddington) and a carbonate (Ketton). Combining the observed porosity and calculated single phase permeability, we shed new light on the existence and size of the Representative Element of Volume (REV) capturing the different scales of heterogeneity from the pore-scale imaging. Our study applies the concept of the ‘Convex Hull’ to calculate the REV by considering the two main macroscopic petrophysical parameters, porosity and single phase permeability, simultaneously. The shape of the hull can be used to identify strong correlation between the parameters or greatly differing convergence rates. To further enhance computational efficiency we note that the area of the convex hull (for well-chosen parameters such as the log of the permeability and the porosity) decays exponentially with sub-sample size so that only a few small simulations are needed to determine the system size needed to calculate the parameters to high accuracy (small convex hull area). Finally we propose using a characteristic length such as the pore size to choose an efficient absolute voxel size for the numerical rock

Analysis of LIGO data for gravitational waves from binary neutron stars

We report on a search for gravitational waves from coalescing compact binary systems in the Milky Way and the Magellanic Clouds. The analysis uses data taken by two of the three LIGO interferometers during the first LIGO science run and illustrates a method of setting upper limits on inspiral event rates using interferometer data. The analysis pipeline is described with particular attention to data selection and coincidence between the two interferometers. We establish an observational upper limit of $\mathcal{R}<$1.7 \times 10^{2}$per year per Milky Way Equivalent Galaxy (MWEG), with 90coalescence rate of binary systems in which each component has a mass in the range 1--3$M_\odot$.Comment: 17 pages, 9 figure