The effect of the GLP-1 analogue Exenatide on functional connectivity within an NTS-based network in women with and without obesity.

ObjectiveThe differential effect of GLP-1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite-related behaviours was investigated in women with normal weight compared with women with obesity.MethodsFollowing an 8-h fast, 19 female subjects (11 lean, 8 obese) participated in a 2-d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30-min post subcutaneous injection of 5 μg of Exenatide or placebo. Functional connectivity was examined with the NTS. Drug-induced functional connectivity changes within and between groups and correlations with appetite measures were examined in a region of interest approach focusing on the thalamus and hypothalamus.ResultsWomen with obesity reported less hunger after drug injection. Exenatide administration increased functional connectivity of the left NTS with the left thalamus and hypothalamus in the obese group only and increased the correlation between NTS functional connectivity and hunger scores in all subjects, but more so in the obese.ConclusionsObesity can impact the effects of Exenatide on brain connectivity, specifically in the NTS and is linked to changes in appetite control. This has implications for the use of GLP-1 analogues in therapeutic interventions

Altered functional connectivity within the central reward network in overweight and obese women.

Background/objectivesNeuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network.Subjects/methodsFifty healthy, premenopausal women, 19 overweight and obese (high BMI=26-38 kg m(-2)) and 31 lean (BMI=19-25 kg m(-2)) were selected from the University of California Los Angeles' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined.ResultsGMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects with high BMI had greater connectivity of the left NAcc with bilateral ACC (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03) in a high frequency band.ConclusionsOverweight and obese women in the absence of food-related stimuli show significant structural and functional alterations within regions of reward-related brain networks, which may have a role in altered ingestive behaviors

History of early life adversity is associated with increased food addiction and sex-specific alterations in reward network connectivity in obesity.

Background:Neuroimaging studies have identified obesity-related differences in the brain's resting state activity. An imbalance between homeostatic and reward aspects of ingestive behaviour may contribute to obesity and food addiction. The interactions between early life adversity (ELA), the reward network and food addiction were investigated to identify obesity and sex-related differences, which may drive obesity and food addiction. Methods:Functional resting state magnetic resonance imaging was acquired in 186 participants (high body mass index [BMI]: ≥25: 53 women and 54 men; normal BMI: 18.50-24.99: 49 women and 30 men). Participants completed questionnaires to assess ELA (Early Traumatic Inventory) and food addiction (Yale Food Addiction Scale). A tripartite network analysis based on graph theory was used to investigate the interaction between ELA, brain connectivity and food addiction. Interactions were determined by computing Spearman rank correlations, thresholded at q < 0.05 corrected for multiple comparisons. Results:Participants with high BMI demonstrate an association between ELA and food addiction, with reward regions playing a role in this interaction. Among women with high BMI, increased ELA was associated with increased centrality of reward and emotion regulation regions. Men with high BMI showed associations between ELA and food addiction with somatosensory regions playing a role in this interaction. Conclusions:The findings suggest that ELA may alter brain networks, leading to increased vulnerability for food addiction and obesity later in life. These alterations are sex specific and involve brain regions influenced by dopaminergic or serotonergic signalling

A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

© 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

Improving "color rendering" of LED lighting for the growth of lettuce

Light plays a vital role on the growth and development of plant. On the base of white light with high color rendering to the benefit of human survival and life, we proposed to improve “color rendering” of LED lighting for accelerating the growth of lettuce. Seven spectral LED lights were adopted to irradiate the lettuces under 150 μmol·m−2·s−1 for a 16 hd−1 photoperiod. The leaf area and number profiles, plant biomass, and photosynthetic rate under the as-prepared LED light treatments were investigated. We let the absorption spectrum of fresh leaf be the emission spectrum of ideal light and then evaluate the “color rendering” of as-prepared LED lights by the Pearson product-moment correlation coefficient and CIE chromaticity coordinates. Under the irradiation of red-yellow-blue light with high correlation coefficient of 0.587, the dry weights and leaf growth rate are 2-3 times as high as the sharp red-blue light. The optimized LED light for lettuce growth can be presumed to be limited to the angle (about 75°) between the vectors passed through the ideal light in the CIE chromaticity coordinates. These findings open up a new idea to assess and find the optimized LED light for plant growth

Landscape structure affects the prevalence and distribution of a tick-borne zoonotic pathogen

Background Landscape structure can affect pathogen prevalence and persistence with consequences for human and animal health. Few studies have examined how reservoir host species traits may interact with landscape structure to alter pathogen communities and dynamics. Using a landscape of islands and mainland sites we investigated how natural landscape fragmentation affects the prevalence and persistence of the zoonotic tick-borne pathogen complex Borrelia burgdorferi(sensu lato), which causes Lyme borreliosis. We hypothesized that the prevalence of B. burgdorferi (s.l.) would be lower on islands compared to the mainland and B. afzelii, a small mammal specialist genospecies, would be more affected by isolation than bird-associated B. garinii and B. valaisiana and the generalist B. burgdorferi (sensu stricto). Methods Questing (host-seeking) nymphal I. Ricinus ticks (n = 6567) were collected from 12 island and 6 mainland sites in 2011, 2013 and 2015 and tested for B. burgdorferi(s.l.). Deer abundance was estimated using dung transects. Results The prevalence of B. burgdorferi (s.l.) was significantly higher on the mainland (2.5%, 47/1891) compared to island sites (0.9%, 44/4673) (P < 0.01). While all four genospecies of B. burgdorferi (s.l.) were detected on the mainland, bird-associated species B. garinii and B. valaisiana and the generalist genospecies B. burgdorferi(s.s.) predominated on islands. Conclusion We found that landscape structure influenced the prevalence of a zoonotic pathogen, with a lower prevalence detected among island sites compared to the mainland. This was mainly due to the significantly lower prevalence of small mammal-associated B. afzelii. Deer abundance was not related to pathogen prevalence, suggesting that the structure and dynamics of the reservoir host community underpins the observed prevalence patterns, with the higher mobility of bird hosts compared to small mammal hosts leading to a relative predominance of the bird-associated genospecies B. garinii and generalist genospecies B. burgdorferi (s.s.) on islands. In contrast, the lower prevalence of B. afzelii on islands may be due to small mammal populations there exhibiting lower densities, less immigration and stronger population fluctuations. This study suggests that landscape fragmentation can influence the prevalence of a zoonotic pathogen, dependent on the biology of the reservoir host

Structural diversity of supercoiled DNA

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA min icircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Chronic nonpuerperal uterine inversion and necrosis: a case report

<p>Abstract</p> <p><b>Introduction</b></p> <p>Inversion of the non-pregnant uterus is rare.</p> <p><b>Case presentation</b></p> <p>A 56-year-old African American woman presented to our emergency center with complaints of a mass protruding from her vagina. She subsequently underwent vaginal myomectomy, abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathologic examination revealed a necrotic fibroid and endometrium. At the time of laparotomy an inverted uterus was diagnosed when a 3 cm dimple containing bilateral round ligaments, infundibulopelvic ligaments and bladder was observed.</p> <p>Conclusion</p> <p>Chronic nonpuerperal inversion of the uterus is rare. Infection should be suspected and appropriate broad spectrum antibiotics begun while planning surgery. An attempt at vaginal restoration and removal is difficult. Abdominal hysterectomy may be necessary taking care to locate the distal urinary collecting system.</p

A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a “candidate interactome” (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms