G-protein-coupled receptors for free fatty acids: nutritional and therapeutic targets

It is becoming evident that nutrients and metabolic intermediates derived from such nutrients regulate cellular function by activating a number of cell-surface G-protein coupled receptors (GPCRs). Until now, members of the GPCR family have largely been considered as the molecular targets that communicate cellular signals initiated by hormones and neurotransmitters. Recently, based on tissue expression patterns of these receptors and the concept that they may elicit the production of a range of appetite- and hunger-regulating peptides, such nutrient sensing GPCRs are attracting considerable attention due to their potential to modulate satiety, improve glucose homeostasis and supress the production of various pro-inflammatory mediators. Despite the developing interests in these nutrients sensing GPCR both as sensors of nutritional status, and targets for limiting the development of metabolic diseases, major challenges remain to exploit their potential for therapeutic purposes. Mostly, this is due to limited characterisation and validation of these receptors because of paucity of selective and high-potency/affinity pharmacological agents to define the detailed function and regulation of these receptors. However, ongoing clinical trials of agonists of free fatty acid receptor 1 suggest that this receptor and other receptors for free fatty acids may provide a successful strategy for controlling hyperglycaemia and providing novel approaches to treat diabetes. Receptors responsive to free fatty acid have been of particular interest, and some aspects of these are considered herein

A comparison of the galaxy peculiar velocity field with the PSCz gravity field-- A Bayesian hyper-parameter method

We constructed a Bayesian hyper-parameter statistical method to quantify the difference between predicted velocities derived from the observed galaxy distribution in the \textit{IRAS}-PSC$z$ redshift survey and peculiar velocities measured using different distance indicators. In our analysis we find that the model--data comparison becomes unreliable beyond 70 \hmpc because of the inadequate sampling by \textit{IRAS} survey of prominent, distant superclusters, like the Shapley Concentration. On the other hand, the analysis of the velocity residuals show that the PSC$z$ gravity field provides an adequate model to the local, \le 70 \hmpc, peculiar velocity field. The hyper-parameter combination of ENEAR, SN, A1SN and SFI++ catalogues in the Bayesian framework constrains the amplitude of the linear flow to be $\beta=0.53 \pm 0.014$. For an rms density fluctuations in the PSC$z$ galaxy number density $\sigma_8^{\rm gal}=0.42\pm0.03$, we obtain an estimate of the growth rate of density fluctuations $f\sigma_{8}(z\sim0) = 0.42 \pm 0.033$, which is in excellent agreement with independent estimates based on different techniques.Comment: 14 pages, 32 figures, MNRAS in press, matched the MNRAS published versio

Rapid acceleration of electrons in the magnetosphere by fast-mode MHD waves

During major megnetic storms, enhanced flux of relativistic electrons in the inner magnetosphere have been observed to correleated with ULF waves. The enhancements can take place over a period of several hours. In order to account for such a rapid generation of relativistic electrons, we examine the mechanism of transit-time acceleration of electrons by low-frequency fast-mode MHD waves, here the assumed form of ULF waves. Calcaulations of the acceleration timescales in the model show that fast-mode waves in the Pc4 to Pc5 frequency range, with typically observed wave amplitudes 10--20 nT, can accelerate the seed electrons to energies of order MeV in a period of a few hours.Comment: 9 pages, 3 figures, Accepted to J. Geophys. Re

Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease and cancer : a systematic review and meta-analysis

We thank Associate Professor Andrew Grey for helping to resolve discrepancies in data extraction and interpretation for cardiovascular events and cancer events. We thank trialists from 16 studies for clarifying or providing additional information for this review [Andrews 2011, Aveyard 2016, Bennett 2012, de Vos 2014, Finnish Diabetes Prevention Study 2009, Goodwin 2014, Green 2015, Horie 2016, Hunt (FFIT) 2014, Katula 2013, Li (Da Qing) 2014, Logue 2005, Ma 2013, O’Neil 2016, Rejeski (CLIP) 2011, Uusitupa 1993] and also others who provided information, but their trials were later found not to fulfil our inclusion criteria. Funding: The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.Peer reviewedPublisher PD

Measuring the dark flow with public X-ray cluster data

We present new results on the "dark flow" from a measurement of the dipole in the distribution of peculiar velocities of galaxy clusters, applying the methodology proposed and developed by us earlier. Our latest measurement is conducted using new, low-noise 7-yr WMAP data as well as an all-sky sample of X-ray selected galaxy clusters compiled exclusively from published catalogs. Our analysis of the CMB signature of the kinematic Sunyaev-Zeldovich (SZ) effect finds a statistically significant dipole at the location of galaxy clusters. The residual dipole outside the cluster regions is small, rendering our overall measurement 3-4 sigma significant. The amplitude of the dipole correlates with cluster properties, being larger for the most X-ray luminous clusters, as required if the signal is produced by the SZ effect. Since it is measured at zero monopole, the dipole can not be due to the thermal SZ effect. Our results are consistent with those obtained earlier by us from 5-yr WMAP data and using a proprietary cluster catalog. In addition, they are robust to quadrupole removal, demonstrating that quadrupole leakage contributes negligibly to the signal. The lower noise of the 7-yr WMAP also allows us, for the first time, to obtain tentative empirical confirmation of our earlier conjecture that the adopted filtering flips the sign of the KSZ effect for realistic clusters and thus of the deduced direction of the flow. The latter is consistent with our earlier measurement in both the amplitude and direction. Assuming the filtering indeed flips the sign of the KSZ effect from the clusters, the direction agrees well also with the results of independent work using galaxies as tracers at lower distances. We make all maps and cluster templates derived by us from public data available to the scientific community to allow independent tests of our method and findings.Comment: ApJ, in press. Replaced with accepted version. The data needed for these results are at http://www.kashlinsky.info/bulkflows/data_publi

Association Between Khat (Catha edulis) Chewing and Infection with Helicobacter pylori: A Case Control Study in Nairobi County

Background: Khat (Catha edulis) is a psycho-stimulant substance grown and widely chewed in East Africa. The use of Khat leads to a number of health complications however its adverse effects and prevalence are not well studied.Objective: To compare the prevalence of Khat chewing among H. Pylori infected cases and controls.Design: Individual matched case control studySetting: KEMRI’s Centre for Clinical Research (CCR) and St. Michael’s Digestive Disease and Medical Care.Subjects: Ninety three cases were selected using Rome III criteria for functional dyspepsia, and the controls (n=93) were matched on age and gender.Results: Khat Chewing was associated with infection with H. Pylori. Of the 93 cases, 58.1% were H. Pylori positive with a majority being Khat chewers 67.2% (41/61) and 32.8% (20/61) non-Khat chewers; the two groups were significantly different (p-value=0.007). Functional dyspepsia was associated with H. Pylori. Therefore, participants with functional dyspepsia were twice more likely of being diagnosed with H. Pylori (OR 2.1, 95% CI: 1.2,3.9).Conclusion: The prevalence of H. Pylori infection was found to be higher among khat chewers, indicating that Khat chewing could be a predisposing factor to H. Pylori infection and to gastrointestinal disorders. Community-based awareness creation about the adverse effect of Khat use is thus recommended

Khat (Catha edulis) Use is Associated with the Development of Gastritis among Adults in Nairobi County, Kenya

Background: Khat (Catha edulis) chewing leads to a number of health related problems in the gastro-intestinal tract (GIT). Few studies have examined the effects of regular Khat chewing in relation to gastritis. Experimental studies with animals have shown that an association exists between Khat chewing and the incidence of gastritis.Objective: To compare the prevalence of Khat chewing among cases with gastritis cases and cases without gastritis.Design: Individual matched case control study.Setting: Kenya Medical Research Institute's Centre for Clinical Research (CCR) and St. Michael’s Digestive Disease and Medical Care.Subjects: Ninety three cases were selected using Rome III criteria for functional dyspepsia, and the controls (n=93) were matched on age and gender.Results: Among the 93 dyspepsia cases, 64.5% were Khat chewers and 35.5% were nonchewers. Khat chewing was associated with the presence of functional dyspepsia (OR 3.8, 95% CI 1.6- 9.4). Of the 60 Khat chewers, 60% (36/60) had erosions in the upper GIT. Chewing Khat was associated with upper GIT erosions (OR 4.095% CI: 1.6, 10.1) It was determined that Khat chewers are four times more likely to have upper GIT erosions than non-chewers.. Khat chewers are 5.5 times (OR 5.5 95% CI: 1.9, 22.0)) more likely to have OGD (Oesophagitis, Gastritis and Duodenitis) compared to non-chewers. Among cases and controls, smoker  (p-value<0.001) and non-smoker (p-value<0.001) Khat chewers were significantly different. The prevalence of H. pylori among Khat chewers was significantly found to be higher (62.9%, p = 0.042); the two groups (Khatchewers and non-chewers) showed significant differenceConclusion: These results reveal that regular Khat chewing is positively associated with gastritis, which is consistent with previous experimental studies on animals

The Complete Mitogenome of the Mountain Chicken Frog, Leptodactylus fallax

The mountain chicken frog (Leptodactylus fallax) is a critically endangered frog native to the Caribbean islands of Dominica and Montserrat. Over the past 25 years their populations have declined by over 85%, largely due to a chytridiomycosis outbreak that nearly wiped out the Montserratian population. Within the context of developing tools that can aid in the conservation of the mountain chicken frog, we assembled its complete mitochondrial genome, contributing the first complete mitogenome of the genus Leptodactylus (Genbank Accession number MW260634). The circular genome is 18,669 bp long and contains 37 genes. A phylogenetic analysis reveals that L. fallax forms a clade with Leptodactylus melanonotus, highlighting the close relationship of Leptodactylus spp. relative to other species from the superfamily Hyloidea included in the analysis

The Complete Mitogenome of the Mountain Chicken Frog, Leptodactylus fallax

The mountain chicken frog (Leptodactylus fallax) is a critically endangered frog native to the Caribbean islands of Dominica and Montserrat. Over the past 25 years their populations have declined by over 85%, largely due to a chytridiomycosis outbreak that nearly wiped out the Montserratian population. Within the context of developing tools that can aid in the conservation of the mountain chicken frog, we assembled its complete mitochondrial genome, contributing the first complete mitogenome of the genus Leptodactylus (Genbank Accession number MW260634). The circular genome is 18,669 bp long and contains 37 genes. A phylogenetic analysis reveals that L. fallax forms a clade with Leptodactylus melanonotus, highlighting the close relationship of Leptodactylus spp. relative to other species from the superfamily Hyloidea included in the analysis

Franck-Condon Factors and Radiative Lifetime of the A^{2}\Pi_{1/2} - X^{2}\Sigma^{+} Transition of Ytterbium Monoflouride, YbF

The fluorescence spectrum resulting from laser excitation of the A^{2}\Pi_{1/2} - X^{2}\Sigma^{+} (0,0) band of ytterbium monofluoride, YbF, has been recorded and analyzed to determine the Franck-Condon factors. The measured values are compared with those predicted from Rydberg-Klein-Rees (RKR) potential energy curves. From the fluorescence decay curve the radiative lifetime of the A^{2}\Pi_{1/2} state is measured to be 28\pm2 ns, and the corresponding transition dipole moment is 4.39\pm0.16 D. The implications for laser cooling YbF are discussed.Comment: 5 pages, 5 figure