bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue inflammation
Authors: Shin Kyung Cheul , Hwang Injae , Choe Sung Sik , Park Jeu , Ji Yul , Kim Jong In , Lee Gha Young , Choi Sung Hee , Ching Jianhong , Kovalik Jean-Paul , Kim Jae Bum 
Published: October 2017

AbstractObesity is closely associated with increased adipose tissue macrophages (ATMs), which contribute to systemic insulin resistance and altered lipid metabolism by creating a pro-inflammatory environment. Very low-density lipoprotein receptor (VLDLR) is involved in lipoprotein uptake and storage. However, whether lipid uptake via VLDLR in macrophages affects obesity-induced inflammatory responses and insulin resistance is not well understood. Here we show that elevated VLDLR expression in ATMs promotes adipose tissue inflammation and glucose intolerance in obese mice. In macrophages, VLDL treatment upregulates intracellular levels of C16:0 ceramides in a VLDLR-dependent manner, which potentiates pro-inflammatory responses and promotes M1-like macrophage polarization. Adoptive transfer of VLDLR knockout bone marrow to wild-type mice relieves adipose tissue inflammation and improves insulin resistance in diet-induced obese mice. These findings suggest that increased VLDL-VLDLR signaling in ATMs aggravates adipose tissue inflammation and insulin resistance in obesity.
Immunosenescence patterns differ between populations but not between sexes in a long-lived mammal
Authors: Cheynel L. , Lemaître J.-F. , Gaillard J.-M. , Rey B. , Bourgoin G. , Ferté H. , Jégo M. , Débias F. , Pellerin M. , Jacob L. , Gilot-Fromont E. 
Published: October 2017

AbstractIn animals, physiological mechanisms underlying reproductive and actuarial senescence remain poorly understood. Immunosenescence, the decline in the ability to display an efficient immune response with increasing age, is likely to influence both reproductive and actuarial senescence through increased risk of disease. Evidence for such a link has been reported from laboratory animal models but has been poorly investigated in the wild, where variation in resource acquisitions usually drives life-history trade-offs. We investigated immunosenescence patterns over 7 years in both sexes of two contrasting roe deer populations (Capreolus capreolus). We first measured twelve immune markers to obtain a thorough identification of innate and adaptive components of immunity and assessed, from the same individuals, the age-dependent variation observed in parasitic infections. Although the level of innate traits was maintained at old age, the functional innate immune traits declined with increasing age in one of two populations. In both populations, the production of inflammatory markers increased with advancing age. Finally, the adaptive response declined in late adulthood. The increasing parasite burden with age we reported suggests the effective existence of immunosenescence. Age-specific patterns differed between populations but not between sexes, which indicate that habitat quality could shape age-dependent immune phenotype in the wild.
Focal Spot and Wavefront Sensing of an X-Ray Free Electron laser using Ronchi shearing interferometry
Authors: Nagler Bob , Aquila Andrew , Boutet Sébastien , Galtier Eric C. , Hashim Akel , S. Hunter Mark , Liang Mengning , Sakdinawat Anne E. , Schroer Christian G. , Schropp Andreas , Seaberg Matthew H. , Seiboth Frank , van Driel Tim , Xing Zhou , Liu Yanwei , Lee Hae Ja 
Published: October 2017

AbstractThe Linac Coherent Light Source (LCLS) is an X-ray source of unmatched brilliance, that is advancing many scientific fields at a rapid pace. The highest peak intensities that are routinely produced at LCLS take place at the Coherent X-ray Imaging (CXI) instrument, which can produce spotsize at the order of 100 nm, and such spotsizes and intensities are crucial for experiments ranging from coherent diffractive imaging, non-linear x-ray optics and high field physics, and single molecule imaging. Nevertheless, a full characterisation of this beam has up to now not been performed. In this paper we for the first time characterise this nanofocused beam in both phase and intensity using a Ronchi Shearing Interferometric technique. The method is fast, in-situ, uses a straightforward optimization algoritm, and is insensitive to spatial jitter.
Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet and relationship to metabolic syndrome
Authors: Pallister Tess , Jackson Matthew A. , Martin Tiphaine C. , Zierer Jonas , Jennings Amy , Mohney Robert P. , MacGregor Alexander , Steves Claire J. , Cassidy Aedin , Spector Tim D. , Menni Cristina 
Published: October 2017

AbstractReduced gut microbiome diversity is associated with multiple disorders including metabolic syndrome (MetS) features, though metabolomic markers have not been investigated. Our objective was to identify blood metabolite markers of gut microbiome diversity, and explore their relationship with dietary intake and MetS. We examined associations between Shannon diversity and 292 metabolites profiled by the untargeted metabolomics provider Metabolon Inc. in 1529 females from TwinsUK using linear regressions adjusting for confounders and multiple testing (Bonferroni: P < 1.71 × 10−4). We replicated the top results in an independent sample of 420 individuals as well as discordant identical twin pairs and explored associations with self-reported intakes of 20 food groups. Longitudinal changes in circulating levels of the top metabolite, were examined for their association with food intake at baseline and with MetS at endpoint. Five metabolites were associated with microbiome diversity and replicated in the independent sample. Higher intakes of fruit and whole grains were associated with higher levels of hippurate cross-sectionally and longitudinally. An increasing hippurate trend was associated with reduced odds of having MetS (OR: 0.795[0.082]; P = 0.026). These data add further weight to the key role of the microbiome as a potential mediator of the impact of dietary intake on metabolic status and health.
Distinct retinoic acid receptor (RAR) isotypes control differentiation of embryonal carcinoma cells to dopaminergic or striatopallidal medium spiny neurons
Authors: Podleśny-Drabiniok Anna , Sobska Joanna , de Lera Angel R. , Gołembiowska Krystyna , Kamińska Katarzyna , Dollé Pascal , Cebrat Małgorzata , Krężel Wojciech 
Published: October 2017

AbstractEmbryonal carcinoma (EC) cells are pluripotent stem cells extensively used for studies of cell differentiation. Although retinoic acid (RA) is a powerful inducer of neurogenesis in EC cells, it is not clear what specific neuronal subtypes are generated and whether different RAR isotypes may contribute to such neuronal diversification. Here we show that RA treatment during EC embryoid body formation is a highly robust protocol for generation of striatal-like GABAergic neurons which display molecular characteristics of striatopallidal medium spiny neurons (MSNs), including expression of functional dopamine D2 receptor. By using RARα, β and γ selective agonists we show that RARγ is the functionally dominant RAR in mediating RA control of early molecular determinants of MSNs leading to formation of striatopallidal-like neurons. In contrast, activation of RARα is less efficient in generation of this class of neurons, but is essential for differentiation of functional dopaminergic neurons, which may correspond to a subpopulation of inhibitory dopaminergic neurons expressing glutamic acid decarboxylasein vivo.
Multi-modal sexual displays in Australian humpback dolphins
Authors: Allen S. J. , King S. L. , Krützen M. , Brown A. M. 
Published: October 2017

AbstractSexual displays enriched by object carrying serve to increase individual male fitness, yet are uncommon phenomena in the animal kingdom. While they have been documented in a variety of taxa, primarily birds, they are rare outside non-human mammals. Here, we document marine sponge presenting associated with visual and acoustic posturing found in several, geographically widespread populations of Australian humpback dolphins (Sousa sahulensis) over ten years of observation. Only adult males presented marine sponges, typically doing so in the presence of sexually mature females, although social groups predominantly consisted of mixed age and sex classes. Male humpback dolphins appear to be using sponges for signalling purposes in multi-modal sexual displays. Further, based on limited behavioural and genetic data, we hypothesise that pairs of adult male Sousa form at least temporary coalitions or alliances. The use of objects in sexual displays by non-human mammals is rare and, moreover, cooperation between males in the pursuit of an indivisible resource is an evolutionary hurdle relatively few species have overcome. These findings suggest a hitherto unrecognised level of social complexity in humpback dolphins.
Breast-Lesion Characterization using Textural Features of Quantitative Ultrasound Parametric Maps
Authors: Sadeghi-Naini Ali , Suraweera Harini , Tran William Tyler , Hadizad Farnoosh , Bruni Giancarlo , Rastegar Rashin Fallah , Curpen Belinda , Czarnota Gregory J. 
Published: October 2017

AbstractThis study evaluated, for the first time, the efficacy of quantitative ultrasound (QUS) spectral parametric maps in conjunction with texture-analysis techniques to differentiate non-invasively benign versus malignant breast lesions. Ultrasound B-mode images and radiofrequency data were acquired from 78 patients with suspicious breast lesions. QUS spectral-analysis techniques were performed on radiofrequency data to generate parametric maps of mid-band fit, spectral slope, spectral intercept, spacing among scatterers, average scatterer diameter, and average acoustic concentration. Texture-analysis techniques were applied to determine imaging biomarkers consisting of mean, contrast, correlation, energy and homogeneity features of parametric maps. These biomarkers were utilized to classify benign versus malignant lesions with leave-one-patient-out cross-validation. Results were compared to histopathology findings from biopsy specimens and radiology reports on MR images to evaluate the accuracy of technique. Among the biomarkers investigated, one mean-value parameter and 14 textural features demonstrated statistically significant differences (p < 0.05) between the two lesion types. A hybrid biomarker developed using a stepwise feature selection method could classify the legions with a sensitivity of 96%, a specificity of 84%, and an AUC of 0.97. Findings from this study pave the way towards adapting novel QUS-based frameworks for breast cancer screening and rapid diagnosis in clinic.
Engineering a short-chain dehydrogenase/reductase for the stereoselective production of (2S,3R,4S)-4-hydroxyisoleucine with three asymmetric centers
Authors: Shi Xuan , Miyakawa Takuya , Nakamura Akira , Hou Feng , Hibi Makoto , Ogawa Jun , Kwon Yeondae , Tanokura Masaru 
Published: October 2017

AbstractFenugreek is a dietary supplement for anti-aging and human health. (2S,3R,4S)-4-hydroxyisoleucine (4-HIL), which is extracted from fenugreek seeds, is expected to be a promising orally active drug for diabetes and diabetic nephropathy because of its insulinotropic effect. Although several chemical synthesis methods of 4-HIL have been proposed, these methods require multistep reactions to control the stereochemistry of 4-HIL. In this study, we modified the key enzyme 4-HIL dehydrogenase (HILDH) to overcome the biggest limitation in commercial-scale production of 4-HIL. As a result, an effective one-step carbonyl reduction to produce (2S,3R,4S)-4-HIL was successfully accomplished with strict stereoselectivity (>99% de). Mass production of (2S,3R,4S)-4-HIL by our synthetic method could have a significant contribution to the prevention of diabetes, dyslipidemia, and Alzheimer’s disease. (120 words/200 words)
Cyclobutane-1,3-Diacid (CBDA): A Semi-Rigid Building Block Prepared by [2+2] Photocyclization for Polymeric Materials
Authors: Wang Zhihan , Miller Benjamin , Mabin Micah , Shahni Rahul , Wang Zijun D. , Ugrinov Angel , Chu Qianli R. 
Published: October 2017

AbstractA previously overlooked building block, cyclobutane-1,3-diacid (CBDA), is introduced to materials synthesis due to its great potentials. As an example of CBDA, α-truxillic acid or 2,4-diphenylcyclobutane-1,3-dicarboxylic acid, was readily synthesized from commercially available trans-cinnamic acid. This CBDA showed outstanding stability both in sunlight and upon heating. While its two carboxylic acid groups can be readily utilized in connecting with other molecules to form new materials, the cyclobutane ring was able to tolerate acid and base treatments showing good chemical stability. A series of cyclobutane-containing polymers (CBPs), namely poly-α-truxillates, were obtained by condensation between α-truxillic acid and diols including ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,5-petanediol, and 1,6-hexanediol. The structures of these poly-α-truxillates were analyzed by NMR, FT-IR, and HRMS. Powder X-ray diffraction results of the poly-α-truxillates indicated that they are semi-crystalline materials. Preliminary thermal, chemical, and photochemical tests showed that the poly-α-truxillates exhibited comparable stabilities to PET.
Photosensing and Thermosensing by Phytochrome B Require Both Proximal and Distal Allosteric Features within the Dimeric Photoreceptor
Authors: Burgie E. Sethe , Bussell Adam N. , Lye Shu-Hui , Wang Tong , Hu Weiming , McLoughlin Katrice E. , Weber Erin L. , Li Huilin , Vierstra Richard D. 
Published: October 2017

AbstractPhytochromes (Phys) encompass a diverse collection of bilin-containing photoreceptors that help plants and microorganisms perceive light through photointerconversion between red light (Pr) and far-red light (Pfr)-absorbing states. In addition, Pfr reverts thermally back to Pr via a highly enthalpic process that enables temperature sensation in plants and possibly other organisms. Through domain analysis of the Arabidopsis PhyB isoform assembled recombinantly, coupled with measurements of solution size, photoconversion, and thermal reversion, we identified both proximal and distal features that influence all three metrics. Included are the downstream C-terminal histidine kinase-related domain known to promote dimerization and a conserved patch just upstream of an N-terminal Period/Arnt/Sim (PAS) domain, which upon removal dramatically accelerates thermal reversion. We also discovered that the nature of the bilin strongly influences Pfr stability. Whereas incorporation of the native bilin phytochromobilin into PhyB confers robust Pfr → Pr thermal reversion, that assembled with the cyanobacterial version phycocyanobilin, often used for optogenetics, has a dramatically stabilized Pfr state. Taken together, we conclude that Pfr acquisition and stability are impacted by a collection of opposing allosteric features that inhibit or promote photoconversion and reversion of Pfr back to Pr, thus allowing Phys to dynamically measure light, temperature, and possibly time.
Deterioration of the Hanson Logboat: chemical and imaging assessment with removal of polyethylene glycol conserving agent
Authors: Pinder Adam P. , Panter Ian , Abbott Geoffrey D. , Keely Brendan J. 
Published: October 2017

AbstractThe state of preservation of wood in two samples from the Hanson Logboat, currently on display in Derby Museum and Art Gallery, was analysed using elemental analysis (EA), pyrolysis–gas chromatography/flame ionisation detection (Py-GC/FID), pyrolysis–gas chromatography/mass spectrometry (Py–GC/MS) and scanning electron microscopy (SEM). The samples were collected in 2003, after the boat had undergone conservation, and in 2011 after the condition of the boat began to deteriorate. Solvent extraction enabled removal of polyethylene glycol, with which the wood had been impregnated during conservation, allowing the degradation of the cellulose and lignin polymeric components of the woods to be assessed. Elemental compositions (C, H, N, O, S), Py–GC/FID, Py-GC/MS and SEM imaging reveal extensive degradation of the wood polymers during the eight year period since conservation.
Controlling the Overfitting of Heritability in Genomic Selection through Cross Validation
Authors: Jia Zhenyu 
Published: October 2017

AbstractIn genomic selection (GS), all the markers across the entire genome are used to conduct marker-assisted selection such that each quantitative trait locus of complex trait is in linkage disequilibrium with at least one marker. Although GS improves estimated breeding values and genetic gain, in most GS models genetic variance is estimated from training samples with many trait-irrelevant markers, which leads to severe overfitting in the calculation of trait heritability. In this study, we demonstrated overfitting heritability due to the inclusion of trait-irrelevant markers using a series of simulations, and such overfitting can be effectively controlled by cross validation experiment. In the proposed method, the genetic variance is simply the variance of the genetic values predicted through cross validation, the residual variance is the variance of the differences between the observed phenotypic values and the predicted genetic values, and these two resultant variance components are used for calculating the unbiased heritability. We also demonstrated that the heritability calculated through cross validation is equivalent to trait predictability, which objectively reflects the applicability of the GS models. The proposed method can be implemented with the Mixed Procedure in SAS or with our R package “GSMX” which is publically available at https://cran.r-project.org/web/packages/GSMX/index.html.
HIV-1 sequences in the epidemic suggest an alternative pathway for the generation of the Long Terminal Repeats
Authors: Cappy Pierre , Moisan Alice , De Oliveira Fabienne , Plantier Jean-Christophe , Negroni Matteo 
Published: October 2017

AbstractTo generate the long-terminal repeats (LTR) that border the integrated viral genome, two-strand transfer steps must occur during reverse transcription. Analysis of the genetic polymorphisms that are present in the LTR of HIV-1 heterozygous virions in single infection cycle studies has revealed which of the two copies of genomic RNAs is used for each transfer event. Thus, the first event of strand transfer has been described to be either intra- or intermolecular, while the second event is generally intramolecular. Here, we repeated these analyses using sequences from HIV databases and extended the study to the regions surrounding the LTR. We observed a striking correlation between the pattern of recombination in the LTR and the phylogenetic origin of the surrounding sequences. This correlation suggests that the second-strand transfer can be either intra- or intermolecular and, interestingly, could reflect an effect of proximity between nucleic acids that would guide this transfer. This factor could be particularly relevant for heterozygous viruses containing highly divergent genomic RNAs, such as those considered in the present study.
Mast cell involvement in glucose tolerance impairment caused by chronic mild stress with sleep disturbance
Authors: Chikahisa Sachiko , Harada Saki , Shimizu Noriyuki , Shiuchi Tetsuya , Otsuka Airi , Nishino Seiji , Séi Hiroyoshi 
Published: October 2017

AbstractWe have developed a chronic mild stress (MS) mouse model by simply rearing mice on a wire net for 3 weeks and investigated the effects of MS on glucose homeostasis and sleep. MS mice showed impaired glucose tolerance and disturbed sleep. One-week treatment with a histamine H1 receptor antagonist (H1RA) ameliorated the glucose intolerance and improved sleep quality in MS mice. MS mice showed an increased number of mast cells in both adipose tissue and the brain. Inhibition of mast cell function ameliorated the impairment in both glucose tolerance and sleep. Together, these findings indicate that mast cells may represent an important pathophysiological mediator in sleep and energy homeostasis.
ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells
Authors: Guerra Fabiana Sélos , Oliveira Ramon Guerra de , Fraga Carlos Alberto Manssour , Mermelstein Claudia dos Santos , Fernandes Patricia Dias 
Published: October 2017

AbstractTumor aggressiveness is usually associated with metastasis. MDA-MB 231, a triple-negative breast cancer (TNBC), is an aggressive type of breast cancer and associated with early metastasis. The Rho/ROCK pathway is a key regulator of cell motility involving cytoskeleton regulation through stabilization of actin filaments and stress fiber formation. In this study we show that Fasudil, a ROCK inhibitor, inhibited the migration of MDA-MB 231 and A549 cells, without altering the viability of these cells at the concentration of 10 μM, modified tumor cell morphology, with disorganization of stress fibers and promotes activation of the canonical-Wnt/beta-catenin pathway. Therefore, Fasudil present a promising approach to the prevention of breast cancer metastasis through a different mechanism of action from the well-known one.
Paternal Diet and Obesity: Effects on Reproduction
Authors: Polotsky Alex , Aly Jasmine 
Published: October 2017

AbstractAlthough most research has focused on maternal obesity, there is growing data to indicate that obesity in the father can affect reproduction. Supporting data come from both mouse and human studies. Murine studies found that obese male mice exhibited decreased motility and reduced hyperactivated progression versus lean mice. Obese mice also exhibited sperm with increased levels of intracellular and mitochondrial levels of reactive oxygen species, increased sperm damage, and lower levels of capacitation, which has been shown to be associated with poor fertilization rates following in vitro fertilization, defective preimplantation embryonic development, and high rates of miscarriage and morbidity in the offspring. Furthermore, diet-induced paternal obesity was found to initiate intergenerational transmission of obesity and insulin resistance in two generations of murine offspring. Meta-analysis from human studies found obese males were more likely to demonstrate sperm DNA fragmentation, infertility, decreased live birth per cycle of assisted reproduction technology, and increased absolute risk of pregnancy nonviability, with no consistent effect on conventional semen parameters. There is a need for future studies to expound on the mechanisms of sperm DNA damage and the impact of weight loss in reversing this damage.
Pharmacologic Treatment of Polycystic Ovary Syndrome: Alternate and Future Paths
Authors: Legro Richard , Duguech Luciana 
Published: October 2017

AbstractPolycystic ovary syndrome (PCOS) is a complex disorder which interacts with other genetic and environmental factors to cause dysregulation of steroidogenesis and anovulation as well as insulin resistance. Treatments which address the long-term effects of this unique combination of reproductive and metabolic dysfunction are needed. Over the past decade, new insights into the genetic factors of PCOS and biotechnological advances have led to potential treatments for women with PCOS. These treatments include both new potent pharmaceutical compounds and repurposed drugs which target different steps in metabolic-reproductive pathways to improve long-term health of women with PCOS. These new therapies target key enzymes involved in steroidogenesis, regulatory pathways of gonadotropin secretion, or lower oxidative stress. We review in this article the current common treatments of PCOS, recent developments in the field, and current information on the mode of action, efficacy, and safety of emerging therapeutic compounds.