Polymorphisms in the circadian expressed genes PER3 and ARNTL2 are associated with diurnal preference and GNβ3 with sleep measures

Sleep and circadian rhythms are intrinsically linked, with several sleep traits, including sleep timing and duration, influenced by both sleep homeostasis and the circadian phase. Genetic variation in several circadian genes has been associated with diurnal preference (preference in timing of sleep), although there has been limited research on whether they are associated with other sleep measurements. We investigated whether these genetic variations were associated with diurnal preference (Morningness-Eveningness Questionnaire) and various sleep measures, including: the global Pittsburgh Sleep Quality index score; sleep duration; and sleep latency and sleep quality. We genotyped 10 polymorphisms in genes with circadian expression in participants from the G1219 sample (n = 966), a British longitudinal population sample of young adults. We conducted linear regressions using dominant, additive and recessive models of inheritance to test for associations between these polymorphisms and the sleep measures. We found a significant association between diurnal preference and a polymorphism in period homologue 3 (PER3) (P < 0.005, recessive model) and a novel nominally significant association between diurnal preference and a polymorphism in aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) (P < 0.05, additive model). We found that a polymorphism in guanine nucleotide binding protein beta 3 (GNβ3) was associated significantly with global sleep quality (P < 0.005, recessive model), and that a rare polymorphism in period homologue 2 (PER2) was associated significantly with both sleep duration and quality (P < 0.0005, recessive model). These findings suggest that genes with circadian expression may play a role in regulating both the circadian clock and sleep homeostasis, and highlight the importance of further studies aimed at dissecting the specific roles that circadian genes play in these two interrelated but unique behaviours

In vitro and in cellulo anti-diabetic activity of AuI- and AuIII-isothiourea complexes

Authors are grateful to the Higher Education Commission (HEC), Pakistan, for providing financial support under the Indigenous Ph. D. Fellowship for 5000 Scholars Phase-II program for providing financial support.About 100 million people worldwide have type II diabetes (T2D), making it one of the most common metabolic disease. DPP-IV inhibitors are new class of anti-diabetic drug. Gold complexes are known for diverse biological activities. Considering these precedents, and growing interest in developing metal-based enzyme inhibitors, we report here the dipeptidyl peptidase-IV (DPP-IV) inhibitory potential of cationic, and neutral chiral gold (I), and gold (III) isothiourea complexes. Colorimetric assay with recombinant DPP-IV enzyme was employed for initial screening. Kinetic based mechanistic studies were also performed for most active complexes. Efficiency of identified inhibitors in biological environment was assessed in in cellulo assay, using Caco-2 cell line. These complexes showed a good to moderate inhibition of DPP-IV with IC50 values in the range of 22.0 – 99.0 µM, as compared to standard inhibitor, sitagliptin (IC50 = 0.033 ± 0.04 µM). It was observed that steric, and electronic properties of the isothiourea ligands have profound effect on the DPP-IV inhibitory activity of these complexes. To the best of our knowledge this study reports for the first time isothiourea based gold complexes as inhibitors of DPP-IV enzyme. These results thus provide an approach for exploring new insights into the development of effective agents against diabetes using incretin-based therapy.PostprintPeer reviewe

A Northern Survey of Gamma-Ray Blazar Candidates

In preparation for GLAST, we have compiled a sample of blazar candidates to increase the pool of well studied AGN from which GLAST counterparts will be drawn. Sources were selected with our Figure of Merit (FoM) ranking; thus, they have radio and X-ray properties very similar to the EGRET blazars. Spectroscopic confirmation of these candidates is in progress, and more than 70% of these objects have been identified as flat spectrum radio quasars and BL Lac objects. We present ~250 new optical blazar identifications based on McDonald Observatory spectroscopy, 224 with redshifts. Of these, 167 are in our FoM-selected set. To motivate the Gamma-ray nature of these objects, we analyzed the current release of the EGRET data for possible point sources at their radio positions. We develop two distinct methods to combine multiple EGRET observations of a sky position into a single detection significance. We report a detection of the signal of the set of blazar candidates in the EGRET data at the > 3 sigma level by both techniques. We predict that the majority of these blazar candidates will be found by GLAST due to its increased sensitivity, duty cycle and resolving power.Comment: ApJ Accepted (to appear 10 June 2005

Orbits of Near-Earth Asteroid Triples 2001 SN263 and 1994 CC: Properties, Origin, and Evolution

Three-body model fits to Arecibo and Goldstone radar data reveal the nature of two near-Earth asteroid triples. Triple-asteroid system 2001 SN263 is characterized by a primary of ~10^13 kg, an inner satellite ~1% as massive orbiting at ~3 primary radii in ~0.7 days, and an outer satellite ~2.5% as massive orbiting at ~13 primary radii in ~6.2 days. 1994 CC is a smaller system with a primary of mass ~2.6 \times 10^11 kg and two satellites ~2% and ~1% as massive orbiting at distances of ~5.5 and ~19.5 primary radii. Their orbital periods are ~1.2 and ~8.4 days. Examination of resonant arguments shows that the satellites are not currently in a mean-motion resonance. Precession of the apses and nodes are detected in both systems (2001 SN263 inner body: d{\varpi}/dt ~1.1 deg/day, 1994 CC inner body: d{\varpi}/dt ~ -0.2 deg/day), which is in agreement with analytical predictions of the secular evolution due to mutually interacting orbits and primary oblateness. Nonzero mutual inclinations between the orbital planes of the satellites provide the best fits to the data in both systems (2001 SN263: ~14 degrees, 1994 CC: ~16 degrees). Our best-fit orbits are consistent with nearly circular motion, except for 1994 CC's outer satellite which has an eccentric orbit of e ~ 0.19. We examine several processes that can generate the observed eccentricity and inclinations, including the Kozai and evection resonances, past mean-motion resonance crossings, and close encounters with terrestrial planets. In particular, we find that close planetary encounters can easily excite the eccentricities and mutual inclinations of the satellites' orbits to the currently observed values.Comment: 17 pages, accepted to Astronomical Journa

Neurological, Cognitive, and Psychological Findings Among Survivors of Ebola Virus Disease From the 1995 Ebola Outbreak in Kikwit, Democratic Republic of Congo: A Cross-sectional Study.

BackgroundClinical sequelae of Ebola virus disease (EVD) have not been described more than 3 years postoutbreak. We examined survivors and close contacts from the 1995 Ebola outbreak in Kikwit, Democratic Republic of Congo (DRC), and determined prevalence of abnormal neurological, cognitive, and psychological findings and their association with EVD survivorship.MethodsFrom August to September 2017, we conducted a cross-sectional study in Kikwit, DRC. Over 2 decades after the EVD outbreak, we recruited EVD survivors and close contacts from the outbreak to undergo physical examination and culturally adapted versions of the Folstein mini-mental status exam (MMSE) and Goldberg anxiety and depression scale (GADS). We estimated the strength of relationships between EVD survivorship and health outcomes using linear regression models by comparing survivors versus close contacts, adjusting for age, sex, educational level, marital status, and healthcare worker status.ResultsWe enrolled 20 EVD survivors and 187 close contacts. Among the 20 EVD survivors, 4 (20%) reported at least 1 abnormal neurological symptom, and 3 (15%) had an abnormal neurological examination. Among the 187 close contacts, 14 (11%) reported at least 1 abnormal neurologic symptom, and 9 (5%) had an abnormal neurological examination. EVD survivors had lower mean MMSE and higher mean GADS scores as compared to close contacts (MMSE: adjusted coefficient: -1.85; 95% confidence interval [CI]: -3.63, -0.07; GADS: adjusted coefficient: 3.91; 95% CI: 1.76, 6.04).ConclusionsEVD survivors can have lower cognitive scores and more symptoms of depression and anxiety than close contacts more than 2 decades after Ebola virus outbreaks

Merkuriuksen pohjoisnapaesiintymien paikallisen kokoluokan heterogeenisyyksien luonnehdinta Arecibon S-kaistan tutkalla

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