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Expression of the Alzheimer's disease associated polypeptide Aβ42 and the human polypeptide hormon islet amyloid polypeptide (hIAPP) and the prohormone precursor (hproIAPP) in neurons of Drosophila melanogaster leads to the formation of protein aggregates in the fat body tissue surrounding the brain. We determined the structure of these membrane-encircled protein aggregates using transmission electron microscopy (TEM) and observed the dissolution of protein aggregates after starvation. Electron tomography (ET) as an extension of transmission electron microscopy revealed that these aggregates were comprised of granular subunits having a diameter of 20 nm aligned into highly ordered structures in all three dimensions. The three dimensional (3D) lattice of hIAPP granules were constructed of two unit cells, a body centered tetragonal (BCT) and a triclinic unit cell. A 5-fold twinned structure was observed consisting of the cyclic twinning of the BCT and triclinic unit cells. The interaction between the two nearest hIAPP granules in both unit cells is not only governed by the van der Waals forces and the dipole-dipole interaction but potentially also by filament-like structures that can connect the nearest neighbors. Hence, our 3D structural analysis provides novel insight into the aggregation process of hIAPP in the fat body tissue of Drosophila melanogaster. [ABSTRACT FROM AUTHOR]

Grafting has been widely applied to melon (Cucumis melo L.) production to alleviate obstacles of continuous cropping and control soil-borne diseases. However, grafting often leads to a decline of fruit quality. For example, sometimes bitter fruits are produced on grafted plants. However, the underlying physiological mechanism still remains unclear. This study investigated the effects of different rootstocks on the taste of fruits of the Balengcui, an oriental melon cultivar, during summer production. The results showed that all grafted plants with Cucurbita maxima Duch. rootstocks produced bitter fruits, while non-grafted plants and plants grafted onto muskmelon rootstocks produced no bitter fruits. Liquid chromatography–mass spectrometry and metabonomic analysis were performed to investigate the mechanism underlying the occurrence of bitter fruits. Metabolite comparisons of fruits from plants grafted onto Ribenxuesong rootstocks both with non-grafted plants and plants grafted onto muskmelon rootstocks showed that 17 metabolites including phospholipids, cucurbitacins and flavonoids, exhibited changes. The three Cucurbitacins, Cucurbitacin O, Cucurbitacin C, and Cucurbitacin S, increased dramatically. The 10 phospholipids PS(18:1(9Z)/18:2(9Z,12Z)), PS(P-18:0/15:0), PA(18:1(11Z)/18:1(11Z)), PE(16:0/18:0), PS(O-16:0/17:2(9Z,12Z)), PI(16:0/18:2(9Z,12Z)), PA(15:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PS(P-16:0/17:2(9Z,12Z)), PS(22:0/22:1(11Z)), and PA(17:1(9Z)/0:0)) were significantly decreased, while two PA (16:0/18:2 (9Z, 12Z) and 16:0/18:1 (11Z)), two flavonoids (pelargonidin 3-(6''-malonylglucoside)-5-glucoside and malvidin 3-rutinoside) significantly increased in fruits of plants grafted onto Cucurbita maxima Duch. rootstocks. These metabolites were involved in the glycerophospholipid metabolic pathway, the mevalonate pathway, and the phenylpropanoid pathway. In summary, these results showed that the bitter fruits of grafted Balengcui were caused by Cucurbita maxima Duch. rootstocks. Phospholipids, cucurbitacins, and flavonoids were the key contributors for the occurrence of bitter fruits in Balengcui melon after grafting onto Cucurbita maxima Duch. rootstocks. [ABSTRACT FROM AUTHOR]

Conjugated linoleic acid was detected in rabbit caecotrophs, due to the presence of microbial lipid activity in rabbit cecum. However, the effect of CLA as a functional food in growing rabbit is not well established. Therefore, this study was conducted to determine the effect of CLA on production, meat quality, and its nutrigenomic effect on edible parts of rabbit carcass including skeletal muscle, liver, and adipose tissue. Therefore, seventy five weaned V-Line male rabbits, 30 days old, were randomly allocated into three dietary treatments receiving either basal control diet, diet supplemented with 0.5% (CLAL), or 1% CLA (CLAH). Total experimental period (63 d) was segmented into 7 days adaptation and 56 days experimental period. Dietary supplementation of CLA did not alter growth performance, however, the fat percentage of longissimus lumborum muscle was decreased, with an increase in protein and polyunsaturated fatty acids (PUFA) percentage. Saturated fatty acids (SFA) and mono unsaturated fatty acids (MUFA) were not increased in CLA treated groups. There was tissue specific sensing of CLA, since subcutaneous adipose tissue gene expression of PPARA was downregulated, however, CPT1A tended to be upregulated in liver of CLAL group only (P = 0.09). In skeletal muscle, FASN and PPARG were upregulated in CLAH group only (P ≤0.01). Marked cytoplasmic vacuolation was noticed in liver of CLAH group without altering hepatocyte structure. Adipocyte size was decreased in CLA fed groups, in a dose dependent manner (P <0.01). Cell proliferation determined by PCNA was lower (P <0.01) in adipose tissue of CLA groups. Our data indicate that dietary supplementation of CLA (c9,t11-CLA and t10,c12- CLA) at a dose of 0.5% in growing rabbit diet produce rabbit meat rich in PUFA and lower fat % without altering growth performance and hepatocyte structure. [ABSTRACT FROM AUTHOR]

We recently introduced a MαCD-based method to efficiently replace virtually the entire population of plasma membrane outer leaflet phospholipids and sphingolipids of cultured mammalian cells with exogenous lipids (Li et al, (2016) Proc. Natl. Acad. Sci USA 113:14025–14030). Here, we show if the lipid-to- MαCD ratio is too high or low, cells can round up and develop membrane leakiness. We found that this cell damage can be reversed/prevented if cells are allowed to recover from the exchange step by incubation in complete growth medium. After exchange and transfer to complete growth medium cell growth was similar to that of untreated cells. In some cases, cell damage was also prevented by carrying out exchange at close to room temperature (rather than at 37°C). Exchange with lipids that do (sphingomyelin) or do not (unsaturated phosphatidylcholine) support a high level of membrane order in lipid vesicles had the analogous effect on plasma membrane order, confirming exogenous lipid localization in the plasma membrane. Importantly, changes in lipid composition and plasma membrane properties after exchange and recovery persisted for several hours. Thus, it should be possible to use lipid exchange to investigate the effect of plasma membrane lipid composition upon several aspects of membrane structure and function. [ABSTRACT FROM AUTHOR]

Background and objectives: The construction of whole-body magnetic resonance (MR) imaging atlases allows to perform statistical analysis with applications in anomaly detection, longitudinal, and correlation studies. Atlas-based methods require a common coordinate system to which all the subjects are mapped through image registration. Optimisation of the reference space is an important aspect that affects the subsequent analysis of the registered data, and having a reference space that is neutral with respect to local tissue volume is valuable in correlation studies. The purpose of this work is to generate a reference space for whole-body imaging that has zero voxel-wise average volume change when mapped to a cohort. Methods: This work proposes an approach to register multiple whole-body images to a common template using volume changes to generate a synthetic reference space, starting with an initial reference and refining it by warping it with a deformation that brings the voxel-wise average volume change associated to the mappings of all the images in the cohort to zero. Results: Experiments on fat/water separated whole-body MR images show how the method effectively generates a reference space neutral with respect to volume changes, without reducing the quality of the registration nor introducing artefacts in the anatomy, while providing better alignment when compared to an implicit reference groupwise approach. Conclusions: The proposed method allows to quickly generate a reference space neutral with respect to local volume changes, that retains the registration quality of a sharp template, and that can be used for statistical analysis of voxel-wise correlations in large datasets of whole-body image data. [ABSTRACT FROM AUTHOR]

Genetic divergence is impacted by many factors, including phylogenetic history, gene flow, genetic drift, and divergent selection. Rotifers are an important component of aquatic ecosystems, and genetic variation is essential to their ongoing adaptive diversification and local adaptation. In addition to coding sequence divergence, variation in gene expression may relate to variable heat tolerance, and can impose ecological barriers within species. Temperature plays a significant role in aquatic ecosystems by affecting species abundance, spatio-temporal distribution, and habitat colonization. Recently described (formerly cryptic) species of the Brachionus calyciflorus complex exhibit different temperature tolerance both in natural and in laboratory studies, and show that B. calyciflorus sensu stricto (s.s.) is a thermotolerant species. Even within B. calyciflorus s.s., there is a tendency for further temperature specializations. Comparison of expressed genes allows us to assess the impact of stressors on both expression and sequence divergence among disparate populations within a single species. Here, we have used RNA-seq to explore expressed genetic diversity in B. calyciflorus s.s. in two mitochondrial DNA lineages with different phylogenetic histories and differences in thermotolerance. We identify a suite of candidate genes that may underlie local adaptation, with a particular focus on the response to sustained high or low temperatures. We do not find adaptive divergence in established candidate genes for thermal adaptation. Rather, we detect divergent selection among our two lineages in genes related to metabolism (lipid metabolism, metabolism of xenobiotics). [ABSTRACT FROM AUTHOR]

Radiological biomarkers have been reported for multiple system atrophy and progressive supranuclear palsy, but serum/plasma biomarkers for each disorder have not been established. In this context, we performed a pilot study to identify disease-specific plasma biomarkers for multiple system atrophy and progressive supranuclear palsy. Plasma samples collected from 20 progressive supranuclear palsy patients, 16 multiple system atrophy patients and 20 controls were investigated by comprehensive metabolome analysis using capillary electrophoresis mass spectrometry and liquid chromatography mass spectrometry. Medication data were obtained from patients with multiple system atrophy and progressive supranuclear palsy, and correlations with associated metabolites were examined. Receiver operating characteristics curve analyses were used to investigate diagnostic values for each disorder. The levels of 15 and eight metabolites were significantly changed in multiple system atrophy and progressive supranuclear palsy, respectively. Multiple system atrophy was mainly characterized by elevation of long-chain fatty acids and neurosteroids, whereas progressive supranuclear palsy was characterized by changes in the level of oxidative stress-associated metabolites. Receiver operating characteristic curve analyses revealed that patients with multiple system atrophy or progressive supranuclear palsy were effectively differentiated from controls by 15 or 7 metabolites, respectively. Disease-specific metabolic changes of multiple system atrophy and progressive supranuclear palsy were identified. These biomarker sets should be replicated in a larger sample. [ABSTRACT FROM AUTHOR]

Background: Very few data are available on treatment in HIV Late presenter population that still represents a clinical challenge. Methods: Prospective, multicenter, randomized open-label, 2 arm, phase-3 trial comparing the 48-week virological response of two different regimens: abacavir/lamivudine + darunavir/r vs abacavir/lamivudine + raltegravir in antiretroviral naive with CD4+ counts < 200/mm3 and a viral load (VL)<500,000 copies/mL. The primary Endpoint was the proportion of patients with undetectable viremia (VL<50 copies/mL) after 48 weeks. The planned sample size for this trial was 350 patients. Results: In 3 years, 53 patients were screened and 46 enrolled: 22 randomized to raltegravir and 24 to darunavir/r; 7 patients were excluded, 4 because of a VL >500,000 copies/mL and 3 for HLAB5701 positivity. The snapshot analysis at 48 weeks showed a virologic success of 77.3% in raltegravir and 66.7% in darunavir/r. Time to starting treatment was 34.5 days in raltegravir and 53 days in darunavir/r. At the as treated analysis, the median CD4 counts at 48 weeks was 297 cells/μL in raltegravir and 239 cells/μL in darunavir/r. No difference in total cholesterol, while triglycerides were higher in the darunavir/r arm. No statistical analyses were performed due to the low number of patients enrolled. Conclusions: Late presenter patients are frequent but very difficult to enroll in clinical trials, especially in western countries. These regimens and the conditions of many patients could not allow the test and treat strategy. The rate of virologic success was higher than 65% in both arms with a median CD4 cell count >200/μL at week 48. Trial registration: EUDRACT number: [ABSTRACT FROM AUTHOR]

Introduction: 3D non-contact surface scanners capture highly accurate, calibrated images of surface topography for 3D structures. This study sought to establish the efficacy and accuracy of using 3D surface scanning to characterise spinal curvature and sagittal plane contour. Methods: 10 healthy female adults with a mean age of 25 years, (standard deviation: 3.6 years) underwent both MRI and 3D surface scanning (3DSS) (Artec Eva, Artec Group Inc., Luxembourg) while lying in the lateral decubitus position on a rigid substrate. Prior to 3DSS, anatomical landmarks on the spinous processes of each participant were demarcated using stickers attached to the skin surface. Following 3DSS, oil capsules (fiducial markers) were overlaid on the stickers and the subject underwent MRI. MRI stacks were processed to measure the thoracolumbar spinous process locations, providing an anatomical reference. 3D coordinates for the markers (surface stickers and MRI oil capsules) and for the spinous processes mapped the spinal column profiles and were compared to assess the quality of fit between the 3DSS and MRI marker positions. Results: The RMSE for the polynomials fit to the spinous process, fiducial and surface marker profiles ranged from 0.17–1.15mm for all subjects. The MRI fiducial marker location was well aligned with the spinous process profile in the thoracic and upper lumbar spine for nine of the subjects. Over the 10 subjects, the mean RMSE between the MRI and 3D scan sagittal profiles for all surface markers was 9.8mm (SD 4.2mm). Curvature was well matched for seven of the subjects, with two showing differing curvatures across the lumbar spine due to inconsistent subject positioning. Conclusion: Comparison of the observed trends for vertebral position measured from MRI and 3DSS, suggested the surface markers may provide a useful method for measuring internal changes in sagittal curvature or skeletal changes. [ABSTRACT FROM AUTHOR]

We identified a mouse strain, HLB444, carrying an N-ethyl-N-nitrosourea (ENU)-induced mutation in a highly conserved C2H2 zinc-finger DNA binding motif of the transcriptional regulator KLF15 that exhibits resistance to diet-induced obesity. Characterization of the HLB444 mutant model on high-fat and chow diets revealed a number of phenotypic differences compared to wild-type controls. When fed a high fat diet, HLB444 had lower body fat, resistance to hepatosteatosis, lower circulating glucose and improved insulin sensitivity compared to C57BL/6J controls. Gut microbial profiles in HLB444 generated from 16S rRNA sequencing of fecal samples differed from controls under both chow and high fat diets. HLB444 shares similar phenotypic traits with engineered full- and adipose-specific Klf15 knockout strains; however, some phenotypic differences between this mutant and the other models suggest that the Klf15 mutation in HLB444 is a hypomorphic variant. The HLB444 model will inform further annotation of transcriptional functions of KLF15, especially with respect to the role of the first zinc-finger domain. [ABSTRACT FROM AUTHOR]

Several heart rate variability (HRV) studies show abnormalities in autonomic nervous control in obese and overweight subjects. However, some of the results appear to be controversial. Here we investigate the HRV profile in seventy adult normotensive women and its association with general and visceral adiposity. Specifically, we recorded the electrocardiographic (ECG) activity in subjects during a supine resting state for five minutes in a quiet room late in the morning. Total fat mass (TFM) and visceral adipose tissue (VAT) were instead estimated using dual-energy X-ray absorptiometry (DXA). Finally, we used simple a linear regression analysis of frequency and time-domain parameters to study the relationship between HRV and adiposity. Our data showed an overall reduction of the HRV related to an increase of TFM although this regression appeared significant only for high frequencies (HF). When the linear regression was applied between HRV variables and VAT, the slope of the line increases, thus unveiling a statistically significant relation (i.e. the more VAT, the lower HRV). Finally, a control analysis showed that age does not alter the relation between HRV and VAT when used as a confounding factor in multiple regression. To conclude, these findings point to abnormal activity of the autonomic nervous system (ANS) in subjects with an excess of VAT and represent a starting point to determine a non-invasive index of cardiac wellness for clinical and nutritional application. [ABSTRACT FROM AUTHOR]

Introduction: Prader-Willi syndrome (PWS) is a complex genetic condition characterized by hyperphagia, hypotonia, low muscle mass, excess body fat, developmental delays, intellectual disability, behavioral problems, and growth hormone deficiency. This study evaluated the safety and efficacy of orally administered Diazoxide Choline Controlled-Release Tablets (DCCR) in subjects with PWS. Method: This was a single-center, Phase II study and included a 10-week Open-Label Treatment Period during which subjects were dose escalated, followed by a 4-week Double-Blind, Placebo-Controlled Treatment Period. Results: Five female and eight male overweight or obese, adolescent and adult subjects with genetically-confirmed PWS with an average age of 15.5±2.9 years were enrolled in the study. There was a statistically significant reduction in hyperphagia at the end of the Open-Label Treatment Period (-4.32, n = 11, p = 0.006). The onset of effect on hyperphagia was rapid and greater reductions in hyperphagia were seen in subjects with moderate to severe Baseline hyperphagia (-5.50, n = 6, p = 0.03), in subjects treated with the highest dose (-6.25, n = 4, p = 0.08), and in subjects with moderate to severe Baseline hyperphagia treated with the highest dose (-7.83, n = 3, p = 0.09). DCCR treatment resulted in a reduction in the number of subjects displaying aggressive behaviors (-57.1%, n = 10, p = 0.01), clinically-relevant reductions in fat mass (-1.58 kg, n = 11, p = 0.02) and increases in lean body mass (2.26 kg, n = 11, p = 0.003). There was a corresponding decrease in waist circumference, and trends for improvements in lipids and insulin resistance. The most common adverse events were peripheral edema and transient increases in glucose. Many of the adverse events were common medical complications of PWS and diazoxide. Conclusion: DCCR treatment appears to address various unmet needs associated with PWS, including hyperphagia and aggressive behaviors in this proof-of-concept study. If the results were replicated in a larger scale study, DCCR may be a preferred therapeutic option for patients with PWS. [ABSTRACT FROM AUTHOR]

Goat fat is one of the best sources of conjugated linoleic acid (CLA), a fatty acid which has health benefits. However, though CLA is generated in ruminants, CLA consumption is limited to meats and milk products. This study aimed to replace vegetable fat with goat milk fat enriched with CLA. From differing fat sources, four cookie recipes were developed: CVF–vegetable fat cookies; CB–butter cookies; CG–goat milk fat cookies without CLA; CGCLA–goat milk fat cookies with CLA. The cookies were evaluated using physical (color and texture), physical-chemical parameters (lipids, proteins, total sugars, fiber, ash, moisture and Aw), consumer testing (n = 123), and lipid profiles. The CGCLA presented higher values in the color parameters. The highest and the lowest scores obtained for hardness were respectively 5.54 (CB) and 2.21 (CVF). Lipids and total sugars varied inversely; the highest percentages of lipids were in the CVF and CG samples which obtained lower total sugar content. There were no differences in acceptance or preference for the four formulations. The goat cream formulations (CG and CGCLA) were as well accepted as the CFV formulation. For lipid profiles, CFV presented the highest percentage of trans-fatty acids (TFA) at 16.76%. CGCLA presented 70% more CLA than either CB or CG, certifying that CGCLA presents CLA in relevant quantities, even after cooking. The CGCLA presented higher levels of CLA, and in this study it was verified that goat milk cream enriched with CLA can be used in producing cookies, adding functional and nutritional properties, and offering another alternative(s) to produce food from goat milk fat. [ABSTRACT FROM AUTHOR]

Objectives: The association of obstructive sleep apnea (OSA) with hypothalamic pituitary adrenal (HPA) axis activation has not been fully understood from results of previous studies using hormonal assessments. We aimed to investigate the relationship between adrenal size, a potential marker reflecting HPA axis activity, and sleep parameters related to OSA. Methods: We retrospectively reviewed data on 284 consecutive adult patients aged 20 to 80 y who had undergone polysomnography and abdominal computed tomography (CT). OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 75), moderate (AHI 15 to 30, n = 80), and severe OSA (AHI ≥30, n = 129). Widths of adrenal body and limbs were measured by abdominal CT. Results: Adrenal size was greater in participants with severe OSA than in those with none/mild or moderate OSA (adrenal body width: 6.03 mm, none/mild OSA; 6.09 mm, moderate OSA; 6.78 mm, severe OSA; p <0.001; adrenal limb width: 3.75 mm, none/mild OSA; 3.95 mm, moderate OSA; 4.26 mm, severe OSA, p <0.001). Multivariate regression analysis showed that not the 3% oxygen desaturation index and time of SpO2 <90% but a higher arousal index was the only determinant factor for increased adrenal limb width (β = 0.27, p <0.001) after adjusting for other variables that could affect adrenal size. Neither the arousal index nor hypoxic parameters were associated with adrenal body width. Conclusions: Results indicated that adrenal glands may enlarge in response to longstanding sleep fragmentation, suggesting the involvement of OSA in HPA axis augmentation. [ABSTRACT FROM AUTHOR]

Background: Quantification of abdominal muscle mass by cross-sectional imaging has been increasingly used to diagnose sarcopenia; however, the technical method for quantification has not been standardized yet. We aimed to determine an optimal method to measure the abdominal muscle area. Methods: Among 50 consecutive subjects who underwent abdominal CT and MRI for possible liver donation, total abdominal muscle area (TAMA) and total psoas muscle area (TPA) at the L3 inferior endplate level were measured by two blinded readers. Inter-scan agreement between CT and MRI and inter-reader agreement between the two readers were evaluated using intraclass correlation coefficient (ICC) and within-subject coefficient of variation (WSCV). To evaluate the effect of measurement level, one reader measured TAMA and TPA at six levels from the L2 to L4 vertebral bodies. Results: TAMA was a more reliable biomarker than TPA in terms of inter-scan agreement (ICC: 0.928 vs. 0.788 for reader 1 and 0.853 vs. 0.821 for reader 2, respectively; WSCV: 8.3% vs. 23.4% for reader 1 and 10.4% vs. 22.3% for reader 2, respectively) and inter-reader agreement (ICC: 0.986 vs. 0.886 for CT and 0.865 vs. 0.669 for MRI, respectively; WSCV: 8.2% vs. 16.0% for CT and 11.6% vs. 29.7% for MRI, respectively). In terms of the measurement level, TAMA did not differ from the L2inf to L4inf levels, whereas TPA increased with a decrease in measurement level. Conclusions: TAMA is a better biomarker than TPA in terms of inter-scan and inter-reader agreement and robustness to the measurement level. CT was a more reliable imaging modality than MRI. Our results support the use of TAMA measured by CT as a standard biomarker for abdominal muscle area measurement. [ABSTRACT FROM AUTHOR]

Background: Most manufacturer manuals do not verify the use of dual energy X-ray absorptiometry for body composition analysis in subjects with a metal implant. This study aimed to quantify the effects of a spinal implant on body composition, and to determine whether unadjusted lean mass estimates are valid for patients with a spinal implant. Methods: A total of 30 healthy subjects were recruited. Three consecutive scans were performed for each participant, one with and two without extraneous spinal implant, without repositioning between scans. Lean, fat and bone estimates in the total body, trunk and limb were measured. Results: Precision errors for all total and regional body compositions were within the recommended ranges. Bone masses in the trunk and total body were significantly increased with spinal implant, and the increases exceeded the least significant change. For total and regional lean and fat estimates, the measurements between subjects with and without metal implants were in substantial to almost perfect agreement and the differences were not significant and did not exceed the least significant change. Conclusions: Spinal metal artifacts significantly increased the total body and trunk bone mass but the differences in lean- and fat-related estimates at total and regional body levels and all estimates in the extremity remained within the clinical acceptable range. Thus, a spinal implant may not compromise screening of patients for fat and lean masses using dual energy X-ray absorptiometry. Application of image reconstruction or a filtering algorithm may help reduce the effect of metallic artifacts and further study is needed. [ABSTRACT FROM AUTHOR]

High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease. [ABSTRACT FROM AUTHOR]

Zika virus infection is associated with the development of Guillain-Barré syndrome (GBS), a neurological autoimmune disorder caused by immune recognition of gangliosides and other components at nerve membranes. Using a high-throughput ELISA, we have analyzed the anti-glycolipid antibody profile, including gangliosides, of plasma samples from patients with Zika infections associated or not with GBS in Salvador, Brazil. We have observed that Zika patients that develop GBS present higher levels of anti-ganglioside antibodies when compared to Zika patients without GBS. We also observed that a broad repertoire of gangliosides was targeted by both IgM and IgG anti-self antibodies in these patients. Since Zika virus infects neurons, which contain membrane gangliosides, antigen presentation of these infected cells may trigger the observed autoimmune anti-ganglioside antibodies suggesting direct infection-induced autoantibodies as a cause leading to GBS development. Collectively, our results establish a link between anti-ganglioside antibodies and Zika-associated GBS in patients. [ABSTRACT FROM AUTHOR]

Cotton gin trash (CGT), a waste product of cotton gins, make up about 10% of each bale of cotton bolls ginned. The current study investigates high value volatile compounds in CGT to add value to this by-product. The volatile compounds in CGT and different parts of the cotton plant were extracted using various methods, identified by gas chromatography-mass spectrometry (GC-MS) or nuclear magnetic resonance (NMR) spectroscopy, and then quantified by gas chromatography-flame ionisation detection (GC-FID) against available standards. Terpenoids including monoterpenoids and sesquiterpenoids were found to be the most abundant, making up 64.66% (area under peak) of total volatiles extracted by hydro-distillation. The major extractable terpenoids in CGT were α-pinene (13.69–23.05 μg/g), β-caryophyllene (3.99–74.32 μg/g), α-humulene (2.00–25.71 μg/g), caryophyllene oxide (41.50–102.08 μg/g) and β-bisabolol (40.05–137.32 μg/g). Recoveries varied between different extraction methods. The terpenoids were found to be more abundant in the calyx (659.12 μg/g) and leaves (627.72 μg/g) than in stalks (112.97 μg/g) and stems (24.24 μg/g) of the cotton plant, indicating the possible biological origin of CGT volatiles. This study is the first to identify and quantify the different terpenoids present in CGT and significantly, β-bisabolol, an abundant compound (sesquiterpene alcohol) which may have valuable biological prospects. These findings therefore contribute to identifying alternative management strategies and uses of CGT. [ABSTRACT FROM AUTHOR]

Menopause is an endocrine-related transition that induces a number of physiological and potentially pathological changes in middle-aged and elderly women. The intention of this research was to investigate the influence of menopause on the intricate relationships between major biochemical metabolites. The study involved metabolic profiling of 186 metabolic markers measured in blood plasma collected from 120 healthy female participants. We developed a method of network analysis using differential correlation that enabled us to detect and characterize differences in metabolites and changes in inter-relationships in pre- and post-menopausal women. A topological analysis was performed on the differential network that uncovered metabolite differences in pre-and post-menopausal women. In this analysis, our method identified two key metabolites, sphingomyelins and phosphatidylcholines, which may be useful in directing further studies into menopause-specific differences in the metabolome, and how these differences may underlie the body's response to stress and disease following the transition from pre- to post-menopausal status for women. [ABSTRACT FROM AUTHOR]

Choline geranate (also described as Choline And GEranic acid, or CAGE) has been developed as a novel biocompatible antiseptic material capable of penetrating skin and aiding the transdermal delivery of co-administered antibiotics. The antibacterial properties of CAGE were analyzed against 24 and 72 hour old biofilms of 11 clinically isolated ESKAPE pathogens (defined as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter sp, respectively), including multidrug resistant (MDR) isolates. CAGE was observed to eradicate in vitro biofilms at concentrations as low as 3.56 mM (0.156% v:v) in as little as 2 hours, which represents both an improved potency and rate of biofilm eradication relative to that reported for most common standard-of-care topical antiseptics in current use. In vitro time-kill studies on 24 hour old Staphylococcus aureus biofilms indicate that CAGE exerts its antibacterial effect upon contact and a 0.1% v:v solution reduced biofilm viability by over three orders of magnitude (a 3log10 reduction) in 15 minutes. Furthermore, disruption of the protective layer of exopolymeric substances in mature biofilms of Staphylococcus aureus by CAGE (0.1% v:v) was observed in 120 minutes. Insight into the mechanism of action of CAGE was provided with molecular modeling studies alongside in vitro antibiofilm assays. The geranate ion and geranic acid components of CAGE are predicted to act in concert to integrate into bacterial membranes, affect membrane thinning and perturb membrane homeostasis. Taken together, our results show that CAGE demonstrates all properties required of an effective topical antiseptic and the data also provides insight into how its observed antibiofilm properties may manifest. [ABSTRACT FROM AUTHOR]

Magnetic Resonance Imaging (MRI) has become a valuable imaging modality in ophthalmology, especially for the diagnosis and treatment planning of patients with uveal melanoma, the most common primary intra-ocular tumor. We aim to develop and evaluate the value of silent Zero Echo Time (ZTE) MRI to image patients with ocular tumors at 7Tesla. Therefore, ZTE and different types of magnetization-prepared ZTE (FLAIR, SPIR, T2 and Saturation recovery), have been developed. After an initial validation with 7 healthy subjects, nine patients with an eye tumor have been evaluated. The ZTE scans were compared to their Cartesian equivalent in terms of contrast, motion-sensitivity, diagnostic quality and patient comfort. All volunteers and especially the patients reported a more comfortable experience during the ZTE scans, which had at least a 10 dB lower sound pressure. The image contrast in the native ZTE was poor, but in the different magnetization-prepared ZTE, the eye lens, cornea and retina were clearly discriminated. Overall the T2-prepared scan yielded the best contrast, especially between tumor and healthy tissue, and proved to be robust against eye motion. Although the intrinsic 3D nature of the ZTE-technique provides an accurate analysis of the tumor morphology, the quality of the ZTE-images is lower than their Cartesian equivalent. In conclusion, the quality of magnetization-prepared ZTE images is sufficient to assess the 3D tumor morphology, but insufficient for more detailed evaluations. As such this technique can be an option for patients who cannot comply with the sound-levels of Cartesian scans, but for other patients the conventional Cartesian scans offer a better image quality. [ABSTRACT FROM AUTHOR]

The literature lacks studies investigating the performance of supplemented replacement heifers grazing on intensively managed warm-season pasture. Our objective was to evaluate the effects of supplement composition (energetic or protein) on the performance, muscle development, thermogenisis, nutrient intake, and digestibility of replacement Holstein heifers grazing Mombaça grass. Eighteen Holstein heifers with an average age and initial body weight (BW) of 12.57 ± 2.54 mo and 218.76 ±47.6 kg, respectively, were submitted to a randomized block design, with six replicates on a rotational grazing system of Panicum maximum cv. Mombaça pasture. Treatments were: control (CON; mineral salt ad libitum); energy supplement (ENE; corn meal as supplement, 8% CP and 3.78 Mcal/kg DE); and protein supplement (PRO; corn and soybean meal, 25% CP and 3.66 Mcal/kg DE). Supplements were individually fed at 0.5% BW. The experiment lasted 120 days, subdivided into three periods. Titanium dioxide and indigestible neutral detergent fiber (iNDF) were used to estimate the intakes and digestibility of the nutrients. BW, wither height, thoracic circumference, body length, and ultrasound of ribeye fat thickness measurements were taken once per period. Body condition score (BCS) was assessed twice during the experiment. The MIXED procedure of SAS, including period as a repeated measure, was used and significance was declared at P ≤ 0.05. Dry matter intake (DMI), CP intake (CPI) and DE intake were greater in heifers fed PRO compared to CON and ENE. Heifers supplemented with ENE had the lowest DMI. Treatment affected pasture intake/BW; it was similar between PRO and CON heifers, and lower for the ENE treatment. A treatment × period interaction was observed for NDF intake (%BW), in which heifers fed PRO and CON had the greatest NDF intake and ENE had the lowest. The digestibility of DM was the greatest in PRO-supplemented heifers and the lowest in CON heifers. Heifers fed ENE had decreased CP digestibility compared to PRO and CON heifers. Average daily gain (ADG) and thoracic circumference gain were greatest in the PRO treatment. BCS was greater in PRO compared to CON and ENE heifers. Supplementing Holstein heifers at 0.5% BW using PRO supplementation resulted in better animal performance, primarily greater ADG, than feeding ENE or not supplementing (CON). In conclusion, our results indicate that dairy heifers should be fed a protein supplement when grazing intensively managed Mombaça grass pasture. [ABSTRACT FROM AUTHOR]

China’s transport sector is facing enormous challenges from soaring energy consumption and greenhouse gas (GHG) emissions. Transport electrification has been viewed as a major solution to transportation decarbonization, and electric vehicles (EVs) have attracted considerable attention from policymakers. This paper analyzes the effects of the introduction of EVs in China. A system dynamics model is developed and applied to assess the energy-saving and emission-reducing impacts of the projected penetration of EVs until the year 2030. Five types of scenarios of various EV penetration rates, electricity generation mixes, and the speed of technological improvement are discussed. Results confirm that reductions in transport GHG emissions and gasoline and diesel consumption by 3.0%–16.2%, 4.4%–16.1%, and 15.8%–34.3%, respectively, will be achieved by 2030 under China’s projected EV penetration scenarios. Results also confirm that if EV penetration is accompanied by decarbonized electricity generation, that is, the use of 55% coal by 2030, then total transport GHG emissions will be further reduced by 0.8%–4.4%. Moreover, further reductions of GHG emissions of up to 5.6% could be achieved through technological improvement. The promotion of EVs could substantially affect the reduction of transport GHG emissions in China, despite the uncertainty of the influence intensity, which is dependent on the penetration rate of EVs, the decarbonization of the power sector, and the technological improvement efficiency of EVs and internal combustion engine vehicles. [ABSTRACT FROM AUTHOR]

The voltage-gated potassium channel KCNQ1 (KV7.1) assembles with the KCNE1 accessory protein to generate the slow delayed rectifier current, IKS, which is critical for membrane repolarization as part of the cardiac action potential. Loss-of-function (LOF) mutations in KCNQ1 are the most common cause of congenital long QT syndrome (LQTS), type 1 LQTS, an inherited genetic predisposition to cardiac arrhythmia and sudden cardiac death. A detailed structural understanding of KCNQ1 is needed to elucidate the molecular basis for KCNQ1 LOF in disease and to enable structure-guided design of new anti-arrhythmic drugs. In this work, advanced structural models of human KCNQ1 in the resting/closed and activated/open states were developed by Rosetta homology modeling guided by newly available experimentally-based templates: X. leavis KCNQ1 and various resting voltage sensor structures. Using molecular dynamics (MD) simulations, the capacity of the models to describe experimentally established channel properties including state-dependent voltage sensor gating charge interactions and pore conformations, PIP2 binding sites, and voltage sensor–pore domain interactions were validated. Rosetta energy calculations were applied to assess the utility of each model in interpreting mutation-evoked KCNQ1 dysfunction by predicting the change in protein thermodynamic stability for 50 experimentally characterized KCNQ1 variants with mutations located in the voltage-sensing domain. Energetic destabilization was successfully predicted for folding-defective KCNQ1 LOF mutants whereas wild type-like mutants exhibited no significant energetic frustrations, which supports growing evidence that mutation-induced protein destabilization is an especially common cause of KCNQ1 dysfunction. The new KCNQ1 Rosetta models provide helpful tools in the study of the structural basis for KCNQ1 function and can be used to generate hypotheses to explain KCNQ1 dysfunction. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with multiple human malignancies. EBV drives B-cell proliferation, which contributes to the pathogenesis of multiple lymphomas. Yet, knowledge of how EBV subverts host biosynthetic pathways to transform resting lymphocytes into activated lymphoblasts remains incomplete. Using a temporal proteomic dataset of EBV primary human B-cell infection, we identified that cholesterol and fatty acid biosynthetic pathways were amongst the most highly EBV induced. Epstein-Barr nuclear antigen 2 (EBNA2), sterol response element binding protein (SREBP) and MYC each had important roles in cholesterol and fatty acid pathway induction. Unexpectedly, HMG-CoA reductase inhibitor chemical epistasis experiments revealed that mevalonate pathway production of geranylgeranyl pyrophosphate (GGPP), rather than cholesterol, was necessary for EBV-driven B-cell outgrowth, perhaps because EBV upregulated the low-density lipoprotein receptor in newly infected cells for cholesterol uptake. Chemical and CRISPR genetic analyses highlighted downstream GGPP roles in EBV-infected cell small G protein Rab activation. Rab13 was highly EBV-induced in an EBNA3-dependent manner and served as a chaperone critical for latent membrane protein (LMP) 1 and 2A trafficking and target gene activation in newly infected and in lymphoblastoid B-cells. Collectively, these studies identify highlight multiple potential therapeutic targets for prevention of EBV-transformed B-cell growth and survival. [ABSTRACT FROM AUTHOR]

Further characterization of essential systems in the parasitic filarial nematode Brugia malayi is needed to better understand its biology, its interaction with its hosts, and to identify critical components that can be exploited to develop novel treatments. The production of glycophosphatidylinositol-anchored proteins (GPI-APs) is essential for eukaryotic cellular and physiological function. In addition, GPI-APs perform many important roles for cells. In this study, we characterized the B. malayi GPI-anchored proteome using both computational and experimental approaches. We used bioinformatic strategies to show the presence or absence of B. malayi GPI-AP biosynthetic pathway genes and to compile a putative B. malayi GPI-AP proteome using available prediction programs. We verified these in silico analyses using proteomics to identify GPI-AP candidates prepared from the surface of intact worms and from membrane enriched extracts. Our study represents the first description of the GPI-anchored proteome in B. malayi and lays the groundwork for further exploration of this essential protein modification as a target for novel anthelmintic therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Obesity and metabolic syndrome (MetS) are associated with high risk of cardiac dysfunction and heart failure. We assessed the effect of obesity and metabolic health status on left ventricular (LV) structure and function in subjects without overt heart disease. Methods: In 789 subjects (58.8±13.0 years, 50.7% males) without overt heart disease, LV morphology and function were compared among 6 groups stratified by body mass index (BMI) (normal weight, overweight and obese) and metabolic health status (meeting ≤1 criterion of MetS excluding waist circumference defined as metabolically healthy; otherwise, metabolically unhealthy). Results: LV ejection fraction (LVEF) was not different among the 6 groups (P>0.05). However, high BMI and poor metabolic health were associated with poorer global longitudinal strain (GLS), higher LV mass index (LVMI) and higher E/e′ (P<0.001). Poor metabolic health status was associated with greater adverse changes in LV structure and function than obesity, and among MetS components, high systolic blood pressure (SBP) showed the greatest impact. Higher SBP, BMI and triglycerides were independently associated with worse GLS, and higher SBP was also associated with worse LVMI and E/e´. GLS, LVMI and E/e´ worsened in proportion to the number of MetS criteria or continuous MetS scores. Adverse myocardial changes associated with obesity were significant in the metabolically healthy group, but not in the metabolically unhealthy group. Conclusions: Obesity and poor metabolic health status were associated with subclinical decrement in LV systolic and diastolic function, and higher LV mass, but not with LVEF, in subjects without overt heart disease. [ABSTRACT FROM AUTHOR]

The ecological success of shallow water reef-building corals has been linked to the symbiosis between the coral host and its dinoflagellate symbionts (herein ‘symbionts’). As mixotrophs, symbiotic corals depend on nutrients 1) transferred from their photosynthetic symbionts (autotrophy) and 2) acquired by host feeding on particulate organic resources (heterotrophy). However, coral species differ in the extent to which they depend on heterotrophy for nutrition and these differences are typically poorly defined. Here, a multi-tracer fatty acid approach was used to evaluate the trophic strategies of three species of common reef-building coral (Galaxea fascicularis, Pachyseris speciosa, and Pocillopora verrucosa) whose trophic strategies had previously been identified using carbon stable isotopes. The composition and various indices of fatty acids were compared to examine the relative contribution of symbiont autotrophy and host heterotrophy in coral energy acquisition. A linear discriminant analysis (LDA) was used to estimate the contribution of polyunsaturated fatty acids (PUFA) derived from various potential sources to the coral hosts. The total fatty acid composition and fatty acid indices revealed differences between the more heterotrophic (P. verrucosa) and more autotrophic (P. speciosa) coral hosts, with the coral host G. fascicularis showing overlap with the other two species and greater variability overall. For the more heterotrophic P. verrucosa, the fatty acid indices and LDA results both indicated a greater proportion of copepod-derived fatty acids compared to the other coral species. Overall, the LDA estimated that PUFA derived from particulate resources (e.g., copepods and diatoms) comprised a greater proportion of coral host PUFA in contrast to the lower proportion of symbiont-derived PUFA. These estimates provide insight into the importance of heterotrophy in coral nutrition, especially in productive reef systems. The study supports carbon stable isotope results and demonstrates the utility of fatty acid analyses for exploring the trophic strategies of reef-building corals. [ABSTRACT FROM AUTHOR]

Background: Obesity is highly prevalent worldwide. More and more studies have been conducted on the relationship between H. pylori infection and obesity or overweight. But the relationship between them is controversial in the literatures and there is no comprehensive evidence for the correlation. Aim: To evaluate the prevalence of H. pylori infection in Chinese adult subjects who received routine physical examinations and the relationship between H. pylori and obesity. Methods: Literatures on H. pylori infection and obesity in Chinese population were searched in online databases. Relevant data were extracted independently by two researchers and meta-analysis was performed by using Review manager 5.3 software. Results: 22 articles were selected with a total sample size of 178033. The pooled prevalence of H. pylori was 42% (95%CI: 37% to 47%) and mean difference of BMI between subjects with and without H. pylori infection was 0.94 (95%CI: -0.04 to 1.91). 9 eligible studies with 27111 subjects were used to calculated pooled OR value because they contained obesity groups. The OR value showed that H. pylori-positive subjects tended to be obese at a risk of 1.20 (95% CI: 1.13 to 1.28). Conclusion: In China, obesity has association with H. pylori infection. H. pylori infection may be one of the risk factors for obesity. [ABSTRACT FROM AUTHOR]

Background: The continued practice of a sport linked to the unilateral predominance of the dominant side can provoke chronic asymmetric adaptations in the myotendinous structure and mechanical properties. Objectives: The main purpose was to determine whether asymmetry between the preferred and non-preferred lower limb is present in the lower limb tendon structure, muscle architecture and stiffness values of professional badminton players. Methods: Sixteen male professional badminton players (age = 24.1 ± 6.7 years; body height = 177.90 ± 7.53 cm) participated in this study. The muscle architecture of the vastus lateralis (VL), medial gastrocnemius (MG) and lateral gastrocnemius (LG) and the structure of patellar and Achilles tendons were measured in the dominant and non-dominant lower limb with ultrasonography. Stiffness was also measured at the same points with a hand-held MyotonPro. Significant differences between the dominant and non-dominant lower limb were determined using Student’s t test for related samples. Results: Bilateral differences were observed for thickness, width and cross-sectional area (CSA) in both tendons showing higher values for the dominant side: patellar tendon CSA (2.02 ± 0.64 vs. 1.51 ± 0.42 cm2; p < 0.05) and Achilles tendon CSA (1.12 ± 0.18 vs. 0.92 ± 0.28 cm2; p < 0.05). No significant differences were observed in muscle architecture and myotonic variables between the dominant and non-dominant lower limb. Conclusions: The prolonged practice of badminton caused asymmetries in the CSA, width and thickness of the patellar and Achilles tendon between the dominant and non-dominant lower limbs. No bilateral differences were found in the muscle architecture of VL, MG and LG or in the stiffness of any muscle or tendon analyzed. [ABSTRACT FROM AUTHOR]

Background: Lower birth weight is associated with diabetes although the underlying mechanisms are unclear. Muscle mass could be a modifiable link and hence a target of intervention. We assessed the associations of birth weight with muscle and fat mass observationally in a population with little socio-economic patterning of birth weight and using Mendelian randomization (MR) for validation. Methods: In the population-representative “Children of 1997” birth cohort (n = 8,327), we used multivariable linear regression to assess the adjusted associations of birth weight (kg) with muscle mass (kg) and body fat (%) at ~17.5 years. Genetically predicted birth weight (effect size) was applied to summary genetic associations with fat-free mass and fat mass (kg) from the UK Biobank (n = ~331,000) to obtain unconfounded estimates using inverse-variance weighting. Results: Observationally, birth weight was positively associated with muscle mass (3.29 kg per kg birth weight, 95% confidence interval (CI) 2.83 to 3.75) and body fat (1.09% per kg birth weight, 95% CI 0.54 to 1.65). Stronger associations with muscle mass were observed in boys than in girls (p for interaction 0.004). Using MR, birth weight was positively associated with fat-free mass (0.77 kg per birth weight z-score, 95% CI 0.22 to 1.33) and fat mass (0.58, 95% CI 0.01 to 1.15). No difference by sex was evident. Conclusion: Higher birth weight increasing muscle mass may be relevant to lower birth weight increasing the risk of diabetes and suggests post-natal muscle mass as a potential target of intervention. [ABSTRACT FROM AUTHOR]

Background: Benign osseous lesions of the spine are common but precise population prevalence estimates are lacking. Our study aimed to provide the first population-based prevalence estimates and examine association with back and neck pain. Materials and methods: We used data from the population-based Study of Health in Pomerania (SHIP). Whole-body MRI examinations (1.5 Tesla: T1, T2, and TIRM weightings) were available from 3,259 participants. Readings of the spinal MRI images were conducted according to a standardized protocol by a single reader (JS). The intra-rater reliability was greater than Kappa values of 0.98. Pain measures included the seven-day prevalence of spine pain and neck pain, and average spine pain intensity due to spine pain during the past three months. Results: We found 1,200 (36.8%) participants with at least one osseous lesion (2,080 lesions in total). Osseous lesions were less common in men than in women (35.5% vs 38.9%; P = .06). The prevalence of osseous lesions was highest at L2 in both sexes. The prevalence of osseous lesions increased with age. Up to eight osseous lesions were observed in a single subject. Hemangioma (28%), and lipoma (13%) occurred most often. Sclerosis (1.7%), aneurysmal bone cysts (0.7%), and blastoma (0.3%) were rare. Different osseous lesions occurred more often in combination with each other. The association with back or neck pain was mostly negligible. Conclusion: Osseous lesions are common in the general population but of no clinical relevance for spinal pain. The prevalence of osseous lesions varied strongly across different regions of the spine and was also associated with age and gender. Our population-based data offer new insights and assist in judging the relevance of osseous lesions observed on MRIs of patients. [ABSTRACT FROM AUTHOR]

Phosphoribosyl pyrophosphate synthetase (PRPS) is a rate-limiting enzyme whose function is important for the biosynthesis of purines, pyrimidines, and pyridines. Importantly, while missense mutations of PRPS1 have been identified in neurological disorders such as Arts syndrome, how they contribute to neuropathogenesis is still unclear. We identified the Drosophila ortholog of PRPS (dPRPS) as a direct target of RB/E2F in Drosophila, a vital cell cycle regulator, and engineered dPRPS alleles carrying patient-derived mutations. Interestingly, while they are able to develop normally, dPRPS mutant flies have a shortened lifespan and locomotive defects, common phenotypes associated with neurodegeneration. Careful analysis of the fat body revealed that patient-derived PRPS mutations result in profound defects in lipolysis, macroautophagy, and lysosome function. Significantly, we show evidence that the nervous system of dPRPS mutant flies is affected by these defects. Overall, we uncovered an unexpected link between nucleotide metabolism and autophagy/lysosome function, providing a possible mechanism by which PRPS-dysfunction contributes to neurological disorders. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is characterized by demyelinated lesions in the central nervous system. Destruction of myelin and secondary damage to axons and neurons leads to significant disability, particularly in people with progressive MS. Accumulating evidence suggests that the potential for myelin repair exists in MS, although for unclear reasons this process fails. The cells responsible for producing myelin, the oligodendrocytes, and their progenitors, oligodendrocyte precursor cells (OPCs), have been identified at the site of lesions, even in adults. Their presence suggests the possibility that endogenous remyelination without transplantation of donor stem cells may be a mechanism for myelin repair in MS. Strategies to develop novel therapies have focused on induction of signaling pathways that stimulate OPCs to mature into myelin-producing oligodendrocytes that could then possibly remyelinate lesions. We have been investigating pharmacological approaches to enhance OPC differentiation, and have identified that the combination of two agents, triiodothyronine (T3) and quetiapine, leads to an additive effect on OPC differentiation and consequent myelin production via both overlapping and distinct signaling pathways. While the ultimate production of myelin requires cholesterol biosynthesis, we identified that quetiapine enhances gene expression in this pathway more potently than T3. Two blockers of cholesterol production, betulin and simvastatin, reduced OPC differentiation into myelin producing oligodendrocytes. Elucidating the nature of agents that lead to complementary and additive effects on oligodendrocyte differentiation and myelin production may pave the way for more efficient induction of remyelination in people with MS. [ABSTRACT FROM AUTHOR]

This paper examines whether tobacco expenditure leads to the crowding out or crowding in of different expenditure items in South Africa. We apply genetic matching to expenditure quartiles of the 2010/2011 South African Income and Expenditure Survey. Genetic matching is a more appealing approach for dealing with the endogeneity of tobacco expenditure that often plagues studies using systems of demand equations. Further, genetic matching provides transparent measures of covariate balance giving the analyst objective means of assessing match success. We find that the poorest tobacco consuming households in South Africa consistently allocate smaller budget shares towards food items than non-smoking households. Specifically, we find that dairy, fruits, nuts and oils are displaced in favour of tobacco expenditure in the two poorest quartiles. Unsurprisingly, food items are never displaced for households in the top two quartiles, given these households’ greater access to resources. Like other studies in the literature, we find that tobacco expenditure consistently crowds-in alcohol across all quartiles confirming the strong complementarities between the two. [ABSTRACT FROM AUTHOR]

This study investigated the perceptions of Chinese physical therapy students on use of the Health Improvement Card (HIC) as a clinical tool to assess lifestyle and prescribe health education to others. The biometrics and health indices/attributes/lifestyles of these students were also evaluated with self-administration of the HIC. After a tutorial on the HIC and its clinical application, physical therapy students (n = 82) from two Chinese universities, completed the Chinese translation of the HIC followed by a questionnaire on students’ perceptions of it. Second, they invited a friend/relative to complete the HIC. Then, they provided feedback on the HIC’s strengths and challenges related to its administration. The data were analyzed with descriptive statistics and content thematic analysis. Response rate of self-completed HICs was 100% (n = 82) and that of questionnaires was 99% (n = 81). Participants’ age range was 20–34 years; mean body mass index (BMI) was 23.9±5.4 for men and 20.5±2.6 kg/m2 for women. Generally, participants had low-risk BMIs (82%) and blood pressures (BPs) (91%), moderate-risk dietary habits (90%), but fewer had low-risk exercise habits (41%). Of 81 friends/relatives who participated, 25% had high-risk exercise habits. Student participants concurred the HIC is useful in developing lifestyle education programs. Challenges included uncertainty about obtaining laboratory data, serving-size quantities and confidence to effect lifestyle change in others. Although students appeared receptive to assessing health and lifestyle behaviors using the HIC, they reported being unconfident to prescribe long-term effective lifestyle advice. We recommend introducing the HIC in physical therapy curricula as an effective way of sensitizing emerging physical therapists to their responsibility to assess health/attributes/lifestyle non-communicable diseases (NCDs) risk factors. Prescribing lifestyle education/counselling warrants greater curricular focus. Further research will establish how HIC data and information can be effectively used as a clinical assessment and education tool to target health and lifestyle, and track behavior change over time. [ABSTRACT FROM AUTHOR]

Freshly isolated, uncultured, autologous adipose derived regenerative cells (ADRCs) have emerged as a promising tool for regenerative cell therapy. The Transpose RT system (InGeneron, Inc., Houston, TX, USA) is a system for isolating ADRCs from adipose tissue, commercially available in Europe as a CE-marked medical device and under clinical evaluation in the United States. This system makes use of the proprietary, enzymatic Matrase Reagent for isolating cells. The present study addressed the question whether the use of Matrase Reagent influences cell yield, cell viability, live cell yield, biological characteristics, physiological functions or structural properties of the ADRCs in final cell suspension. Identical samples of subcutaneous adipose tissue from 12 subjects undergoing elective lipoplasty were processed either with or without the use of Matrase Reagent. Then, characteristics of the ADRCs in the respective final cell suspensions were evaluated. Compared to non-enzymatic isolation, enzymatic isolation resulted in approximately twelve times higher mean cell yield (i.e., numbers of viable cells/ml lipoaspirate) and approximately 16 times more colony forming units. Despite these differences, cells isolated from lipoaspirate both with and without the use of Matrase Reagent were independently able to differentiate into cells of all three germ layers. This indicates that biological characteristics, physiological functions or structural properties relevant for the intended use were not altered or induced using Matrase Reagent. A comprehensive literature review demonstrated that isolation of ADRCs from lipoaspirate using the Transpose RT system and the Matrase Reagent results in the highest viable cell yield among published data regarding isolation of ADRCs from lipoaspirate. [ABSTRACT FROM AUTHOR]

Flavodoxins are small electron transfer proteins containing flavin mononucleotide (FMN) as a prosthetic group, which play an important role during oxidative stress or iron limitation. The aims of this study were the identification and characterization of flavodoxins in the model aromatic-degrader Paraburkholderia xenovorans LB400 and the analyses of their protective effects during oxidative stress induced by paraquat and H2O2. Two genes (BxeA0278 and BxeB0391) encoding flavodoxins (hereafter referred to as fldX for avooxin from P. enovorans), were identified at the LB400 major and minor chromosome. Genomic context of the flavodoxin-encoding genes showed genes encoding membrane proteins, transporters, and proteins involved in redox processes and biosynthesis of macromolecules. A secondary structure prediction of both LB400 flavodoxins showed the characteristic flavodoxin structure of five ß-sheets intercalated with five α-helices. FldX1 contains a loop intercalated in the fifth β-strand, which indicates that it belongs to the long-chain flavodoxins, whereas FldX2 is a short-chain flavodoxin. A phylogenetic analysis of 73 flavodoxins from 43 bacterial genera revealed eight clusters (I-VIII), while FldX1 and FldX2 grouped separately within a long-chain and a short-chain flavodoxin clades. FldX1 and FldX2 were overexpressed in P. xenovorans. Interestingly, the strain overexpressing the long-chain flavodoxin FldX1 (p2-fldX1) showed a faster growth in glucose than the control strain. The recombinant strain overexpressing the long-chain flavodoxin FldX1 (p2-fldx1) exposed to paraquat (20 mM) possessed lower susceptibility to growth inhibition on plates and higher survival in liquid medium than the control strain. The strains overexpressing the flavodoxins FldX1 and FldX2 showed higher survival during exposure to 1 mM paraquat (>95%) than the control strain (68%). Compared to the control strain, strains overexpressing FldX1 and FldX2 showed lower lipid peroxidation (>20%) after exposure to 1 mM paraquat and a lower protein carbonylation (~30%) after exposure to 1 mM H2O2 was observed. During exposure to paraquat, strain p2-fldx1 downregulated the katG4, hpf, trxB1 and ohr genes (> 2-fold), whereas strain p2-fldx2 upregulated the oxyR and ahpC1 genes (> 2-fold). In conclusion, the flavodoxins FldX1 and FldX2 of P. xenovorans LB400 conferred protection to cells exposed to the oxidizing agents paraquat and H2O2. [ABSTRACT FROM AUTHOR]

Flavodoxins are small electron transfer proteins containing flavin mononucleotide (FMN) as a prosthetic group, which play an important role during oxidative stress or iron limitation. The aims of this study were the identification and characterization of flavodoxins in the model aromatic-degrader Paraburkholderia xenovorans LB400 and the analyses of their protective effects during oxidative stress induced by paraquat and H2O2. Two genes (BxeA0278 and BxeB0391) encoding flavodoxins (hereafter referred to as fldX for avooxin from P. enovorans), were identified at the LB400 major and minor chromosome. Genomic context of the flavodoxin-encoding genes showed genes encoding membrane proteins, transporters, and proteins involved in redox processes and biosynthesis of macromolecules. A secondary structure prediction of both LB400 flavodoxins showed the characteristic flavodoxin structure of five ß-sheets intercalated with five α-helices. FldX1 contains a loop intercalated in the fifth β-strand, which indicates that it belongs to the long-chain flavodoxins, whereas FldX2 is a short-chain flavodoxin. A phylogenetic analysis of 73 flavodoxins from 43 bacterial genera revealed eight clusters (I-VIII), while FldX1 and FldX2 grouped separately within a long-chain and a short-chain flavodoxin clades. FldX1 and FldX2 were overexpressed in P. xenovorans. Interestingly, the strain overexpressing the long-chain flavodoxin FldX1 (p2-fldX1) showed a faster growth in glucose than the control strain. The recombinant strain overexpressing the long-chain flavodoxin FldX1 (p2-fldx1) exposed to paraquat (20 mM) possessed lower susceptibility to growth inhibition on plates and higher survival in liquid medium than the control strain. The strains overexpressing the flavodoxins FldX1 and FldX2 showed higher survival during exposure to 1 mM paraquat (>95%) than the control strain (68%). Compared to the control strain, strains overexpressing FldX1 and FldX2 showed lower lipid peroxidation (>20%) after exposure to 1 mM paraquat and a lower protein carbonylation (~30%) after exposure to 1 mM H2O2 was observed. During exposure to paraquat, strain p2-fldx1 downregulated the katG4, hpf, trxB1 and ohr genes (> 2-fold), whereas strain p2-fldx2 upregulated the oxyR and ahpC1 genes (> 2-fold). In conclusion, the flavodoxins FldX1 and FldX2 of P. xenovorans LB400 conferred protection to cells exposed to the oxidizing agents paraquat and H2O2. [ABSTRACT FROM AUTHOR]

TLQP-21, a peptide encoded by the highly conserved vgf gene, is expressed in neuroendocrine cells and has been the most prominent VGF-derived peptide studied in relation to control of energy balance. The recent discovery that TLQP-21 is the natural agonist for the complement 3a receptor 1 (C3aR1) has revived interest in this peptide as a potential drug target for obesity. We have investigated its function in Siberian hamsters (Phodopus sungorus), a rodent that displays natural seasonal changes in body weight and adiposity as an adaptation to survive winter. We have previously shown that intracerebroventricular administration of TLQP-21 reduced food intake and body weight in hamsters in their long-day fat state. The aim of our current study was to determine the systemic actions of TLQP-21 on food intake, energy expenditure and body weight, and to establish whether adiposity affected these responses. Peripheral infusion of TLQP-21 (1mg/kg/day for 7 days) in lean hamsters exposed to short photoperiods (SP) reduced cumulative food intake in the home cage (p<0.05), and intake when measured in metabolic cages (P<0.01). Energy expenditure was significantly increased (p<0.001) by TLQP-21 infusion, this was associated with a significant increase in uncoupling protein 1 mRNA in brown adipose tissue (BAT) (p<0.05), and body weight was significantly reduced (p<0.05). These effects of systemic TLQP-21 treatment were not observed in hamsters exposed to long photoperiod (LP) with a fat phenotype. C3aR1 mRNA and protein were abundantly expressed in the hypothalamus, brown and white adipose tissue in hamsters, but changes in expression cannot explain the differential response to TLQP-21 in lean and fat hamsters. [ABSTRACT FROM AUTHOR]

Characterization of milk fat globule (MFG) was performed to investigate the difference in MFG membrane (MFGM) between fresh and mastitis Holstein Friesian cow milk. Lipid distribution investigated by exogenous phospholipids using microscopy showed higher phospholipid content in fresh compared to mastitic MFGM. Xanthine oxidase assay indicative of membrane impairment revealed lower activity in mastitic samples compared to fresh globules. Of note, significantly higher roughness of globule surface and zeta potential was observed in mastitis compared to fresh globules. Influence of globule membrane on the interaction with L. fermentum demonstrated preferential adhesion of bacteria to fresh compared to mastitic globules including enhanced extent of binding. Results of the present study provides an insight of the interfacial changes occurring at the globule surface as well as highlighting the importance of selective bacterial interaction with milk components for the potential development of functional food with relevance to human health. [ABSTRACT FROM AUTHOR]

Water deficit induces reactive oxygen species (ROS) overproduction, which in turn inhibits plant growth and development. High concentrations of ROS disrupt the osmotic balance in plant cells and alter membrane integrity. Chromosomes carrying structural or regulatory genes must be detected to better understand plant response mechanisms to stress. The aim of our study was to identify Triticum aestivum L. chromosomes involved in early responses to short-term water-deficit stress (1, 3 and 6 h). In the present study, intervarietal substitution lines of drought-tolerant 'Saratovskaya 29' and sensitive 'Janetzkis Probat' wheat cultivars were examined. We studied the biochemical plant response system and conducted an analysis of catalase, ascorbate peroxidase and guaiacol peroxidase activities, levels of lipid peroxidation and changes in relative water content. Our results determined that the first reaction was a significant increase in guaiacol peroxidase (GPX) activity. However, the strongest impact on plant responses was found for catalase (CAT), which caused a significant decrease in lipid peroxidation (LPO) levels. Our findings indicate that chromosomes 5A, 4B, 6B and 7D are associated with early responses to short-term osmotic stress in wheat. [ABSTRACT FROM AUTHOR]

The objective was to determine the effects of sleep or lying deprivation on the behavior of dairy cows. Data were collected from 8 multi- and 4 primiparous cows (DIM = 199 ± 44 (mean ± SD); days pregnant = 77 ± 30). Using a crossover design, each cow experienced: 1) sleep deprivation implemented by noise or physical contact when their posture suggested sleep, and 2) lying deprivation imposed by a grid placed on the pen floor. One day before treatment (baseline), and treatment day (treatment) were followed by a 12-d washout period (with the first 7 d used to evaluate recovery). Study days were organized from 2100 to 2059. During habituation (d -3 and -2 before treatment), baseline (d -1), and trt (d 0), housing was individual boxstalls (mattress with no bedding). After treatment, cows returned to sand-bedded freestalls for a 7-d recovery period (d 1 to 7) where data on lying behaviors were collected. Following the recovery period, an additional 5-d period was provided to allow the cows a 12-d period between exposures to treatments. Daily lying time, number lying bouts, bout duration, and number of steps were recorded by dataloggers attached to the hind leg of cows throughout the study period. Data were analyzed using a mixed model including fixed effects of treatment (sleep deprivation vs. sleep and lying deprivation), day, and their interaction with significant main effects separated using a PDIFF statement (P ≤ 0.05). Interactions between treatment and day were detected for daily lying time and the number of bouts. Lying time was lower for both treatments during the treatment period compared to baseline. Lying time increased during the recovery period for both lying and sleep deprived cows. However, it took 4 d for the lying deprived cows to fully recover their lying time after treatment, whereas it took the sleep deprived cows 2 d for their lying time to return to baseline levels. Results suggest that both sleep and lying deprivation can have impact cow behavior. Management factors that limit freestall access likely reduce lying time and sleep, causing negative welfare implications for dairy cows. [ABSTRACT FROM AUTHOR]

Purpose: We have developed a diagnostic technique to evaluate hepatic steatosis using the attenuation coefficient (ATT) in ultrasound B mode imaging. A controlled attenuation parameter (CAP) by vibration-controlled transient elastography (VCTE) has also been used to evaluate hepatic steatosis. As that method uses ultrasound A mode, visualizing the liver in real time is difficult. We designed this clinical study to evaluate the diagnostic advantage of our technique using ATT compared to CAP. Materials and methods: The study group included 94 patients with chronic liver disease who had undergone both ATT and CAP assessment at the time of liver biopsy. The M-probe and XL-probe were used for CAP measurement. Data for ATT and CAP were compared as a function of the steatosis grade. Results: The area under the receiver operating characteristic curve (AUC-ROCs) for ATT and PAC as a function of the steatosis grade were as follows: grade 1, 0.74 and 0.81; grade 2, 0.80 and 0.85; and grade 3, 0.96 and 0.98, respectively. Conclusion: The accuracy of steatosis grade diagnosis using ATT was the same as that using CAP, with no significant differences and with the added advantage of B mode ultrasound being more convenient and rapid, compared to A mode ultrasound, particularly for patients with subcutaneous fat thickness ≥2 cm. [ABSTRACT FROM AUTHOR]

Objective: Nonalcoholic fatty liver disease (NAFLD) is a well-recognized hepatic manifestation of metabolic disease in adults and has been associated with the development of gestational diabetes (GDM). Hepatic insulin resistance can result in increased release of glucose (from gluconeogenesis) and free fatty acids (due to enhanced lipolysis), which can lead in turn to fetal overgrowth. However, the relationship between maternal metabolic factors (such as circulating levels of triglycerides, free fatty acids [FFA], or adipokines) and excessive fetal birthweight in NAFLD has not been carefully examined. In this study, we evaluated the relationship between NAFLD and the subsequent risk of large-for-gestational-age (LGA) birthweight. Method: Singleton nondiabetic pregnant women were evaluated for the presence of fatty liver at 10–14 weeks of gestation by abdominal ultrasound. The degree of fatty liver was classified as Grade 0–3 steatosis. At the time of liver ultrasound, maternal blood was taken after fasting and measured for adiponectin and FFA. LGA was defined as birthweight >90th percentile for gestational age. Results: A total of 623 women were included in the analysis. The frequency of LGA was 10.9% (68/623), and the frequency of NAFLD was 18.9%. The risk of LGA increased significantly in patients with Grade 2–3 steatosis in the first trimester. The relationship between Grade 2–3 steatosis and LGA remained significant after adjustment for maternal age, pre-pregnancy BMI, GDM, and maternal serum triglyceride levels. The concentration of maternal blood adiponectin at 10–14 weeks was significantly lower in cases with LGA than non-LGA, but the maternal blood FFA concentrations were not different between the groups. Conclusion: The presence of Grade 2–3 steatosis on ultrasound in early pregnancy was associated with the increased risk of delivering an LGA infant, even after adjustment for multiple confounding factors including GDM. Adiponectin may be the linking biomarker between NAFLD and LGA. [ABSTRACT FROM AUTHOR]

The prevalence of metabolic syndrome (MetSyn) has risen 35% since 2012 and over two-thirds of Americans exhibit features characterizing this condition (obesity, dyslipidemia, hyperglycemia, insulin resistance and/or endothelial dysfunction). The aim of this study was to evaluate the effects of a novel dietary supplemental organic mineral complex (OMC) on these risk factors in a rodent model of MetSyn. Six-week old male Sprague-Dawley rats were fed either standard chow or a high-fat diet (HFD) composed of 60% kcal from fat for 10 weeks. Rats were also treated with OMC in their drinking water at either 0 mg/mL (control), 0.6 mg/mL, or 3.0 mg/mL. The HFD-treated rats exhibited significantly increased body mass (p<0.05), epididymal fat pad mass (p<0.001), waist circumference (p = 0.010), in addition to elevations in plasma endotoxins (p<0.001), ALT activity (p<0.001), fasting serum glucose (p = 0.025) and insulin concentrations (p = 0.009). OMC did not affect body weight or adiposity induced by the HFD. At the higher dose OMC significantly blunted HFD-induced hyperglycemia (p = 0.021), whereas both low and high doses of OMC prevented HFD-induced endotoxemia (p = 0.002 and <0.001, respectively) and hepatocyte injury (ALT activity, p<0.01). Despite evidence of oxidative stress (elevated urinary H2O2 p = 0.032) in HFD-fed rats, OMC exhibited no demonstrable antioxidative effect. Consistent with prior studies, mesenteric arteries from HFD rats had more uncoupled eNOS (p = 0.006) and iNOS protein expression (p = 0.027) in addition to impaired endothelium-dependent vasodilation that was abrogated by the high dose of OMC (p<0.05). This effect of OMC may be attributed to the high nitrate content of the supplement. These findings suggest that the OMC supplement, particularly at the higher dose, ameliorated several risk factors associated with MetSyn via a non-antioxidant-dependent mechanism. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis and is an attractive therapeutic target for combating obesity and related diseases. Human BAT activity has been evaluated by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) under acute cold exposure, but the method has some serious limitations, including radiation exposure. Infrared thermography (IRT) may be a simple and less-invasive alternative to evaluate BAT activity. In the present study, to establish an optimal condition for IRT, using a thermal imaging camera, skin temperature was measured in the supraclavicular region close to BAT depots (Tscv) and the control chest region (Tc) in 24 young healthy volunteers. Their BAT activity was assessed as the maximal standardized uptake value (SUVmax) by 18FDG-PET/CT. Under a warm condition at 24–27°C, no significant correlation was found between the IRT parameters (Tscv, Tc,, and the difference between Tscv and Tc,, Δtemp) and SUVmax, but 30–120 min after cold exposure at 19°C, Tscv and Δtemp were significantly correlated with SUVmax (r = 0.40–0.48 and r = 0.68–0.76). Δtemp after cold exposure was not affected by mean body temperature, body fatness, and skin blood flow. A lower correlation (r = 0.43) of Δtemp with SUVmax was also obtained when the participant’s hands were immersed in water at 18°C for 5 min. Receiver operating characteristic analysis revealed that Δtemp after 30–60 min cold exposure can be used as an index for BAT evaluation with 74% sensitivity, 92% specificity, and 79% diagnostic accuracy. Thus, IRT may be useful as a simple and less-invasive method for evaluating BAT, particularly for large-scale screening and longitudinal repeat studies. [ABSTRACT FROM AUTHOR]

Hepatic iron overload, a hallmark of hereditary hemochromatosis, triggers progressive liver disease. There is also increasing evidence for a pathogenic role of iron in non-alcoholic fatty liver disease (NAFLD), which may progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular cancer. Mouse models of hereditary hemochromatosis and NAFLD can be used to explore potential interactions between iron and lipid metabolic pathways. Hfe-/- mice, a model of moderate iron overload, were reported to develop early liver fibrosis in response to a high fat diet. However, this was not the case with Hjv-/- mice, a model of severe iron overload. These data raised the possibility that the Hfe gene may protect against liver injury independently of its iron regulatory function. Herein, we addressed this hypothesis in a comparative study utilizing wild type, Hfe-/-, Hjv-/- and double Hfe-/-Hjv-/- mice. The animals, all in C57BL/6J background, were fed with high fat diets for 14 weeks and developed hepatic steatosis, associated with iron overload. Hfe co-ablation did not sensitize steatotic Hjv-deficient mice to liver injury. Moreover, we did not observe any signs of liver inflammation or fibrosis even in single steatotic Hfe-/- mice. Ultrastructural studies revealed a reduced lipid and glycogen content in Hjv-/- hepatocytes, indicative of a metabolic defect. Interestingly, glycogen levels were restored in double Hfe-/-Hjv-/- mice, which is consistent with a metabolic function of Hfe. We conclude that hepatocellular iron excess does not aggravate diet-induced steatosis to steatohepatitis or early liver fibrosis in mouse models of hereditary hemochromatosis, irrespectively of the presence or lack of Hfe. [ABSTRACT FROM AUTHOR]

Gene set analysis (GSA) has become the common methodology for analyzing transcriptomics data. However, self-contained GSA techniques are rarely, if ever, used for proteomics data analysis. Here we present a self-contained proteome level GSA of four consensus molecular subtypes (CMSs) previously established by transcriptome dissection of colon carcinoma specimens. Despite notable difference in structure of proteomics and transcriptomics data, many pathway-wide characteristic features of CMSs found at the mRNA level were reproduced at the protein level. In particular, CMS1 features show heavy involvement of immune system as well as the pathways related to mismatch repair, DNA replication and functioning of proteasome, while CMS4 tumors upregulate complement pathway and proteins participating in epithelial-to-mesenchymal transition (EMT). In addition, protein level GSA yielded a set of novel observations visible at the proteome, but not at the transcriptome level, including possible involvement of major histocompatibility complex II (MHC-II) antigens in the known immunogenicity of CMS1 and a connection between cholesterol trafficking and the regulation of Integrin-linked kinase (ILK) in CMS3. Overall, this study proves utility of self-contained GSA approaches as a critical tool for analyzing proteomics data in general and dissecting protein-level molecular portraits of human tumors in particular. [ABSTRACT FROM AUTHOR]