bluuebunny/crossref_metadata_2025 huggingface dataset:
Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease
Authors: Marrie R. A. , Walld R. , Bolton J. M. , Sareen J. , Walker J. R. , Patten S. B. , Singer A. , Lix L. M. , Hitchon C. A. , El-Gabalawy R. , Katz A. , Fisk J. D. , Bernstein C. N. ,   for the CIHR Team in Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease
Published: November 2017

Aims.

After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population.

Methods.

Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year.

Results.

We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30–1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12–1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10–2.40).

Conclusion.

The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.
IPCC Chair Discusses Limiting Global Warming to 1.5°C
Authors: Showstack Randy
Published: November 2017

Several forthcoming reports by the Intergovernmental Panel on Climate Change examine what needs to be done to take control of our climate future.
Democrats Push NASA Nominee on Partisanship, Science Integrity
Authors: Showstack Randy
Published: November 2017

The nominee, Rep. Jim Bridenstine, tried to assure the committee of his support for science and his ability to manage NASA apolitically.
Erratum: The availability of jobs in the biopharmaceutical industry is 45-fold greater for hematology oncology than medical specialties
Authors: Kaestner V , Prasad V
Published: November 2017

Correction to: Blood Cancer Journal (2017) 7, e609; doi:10.1038/bcj.2017.91. Published online 15 September 2017 In our paper, the title refers to job advertisements (as articulated clearly in the text) and not jobs per se. The title should read ‘Job postings for biopharmaceutical industry in medicaljournals is 45-fold greater for hematology oncology than medical specialties.
Distinct Campylobacter fetus lineages adapted as livestock pathogens and human pathobionts in the intestinal microbiota
Authors: Iraola Gregorio , Forster Samuel C. , Kumar Nitin , Lehours Philippe , Bekal Sadjia , García-Peña Francisco J. , Paolicchi Fernando , Morsella Claudia , Hotzel Helmut , Hsueh Po-Ren , Vidal Ana , Lévesque Simon , Yamazaki Wataru , Balzan Claudia , Vargas Agueda , Piccirillo Alessandra , Chaban Bonnie , Hill Janet E. , Betancor Laura , Collado Luis , Truyers Isabelle , Midwinter Anne C. , Dagi Hatice T. , Mégraud Francis , Calleros Lucía , Pérez Ruben , Naya Hugo , Lawley Trevor D.
Published: November 2017

Campylobacter fetus is a venereal pathogen of cattle and sheep, and an opportunistic human pathogen. It is often assumed that C. fetus infection occurs in humans as a zoonosis through food chain transmission. Here we show that mammalian C. fetus consists of distinct evolutionary lineages, primarily associated with either human or bovine hosts. We use whole-genome phylogenetics on 182 strains from 17 countries to provide evidence that C. fetus may have originated in humans around 10,500 years ago and may have “jumped” into cattle during the livestock domestication period. We detect C. fetus genomes in 8% of healthy human fecal metagenomes, where the human-associated lineages are the dominant type (78%). Thus, our work suggests that C. fetus is an unappreciated human intestinal pathobiont likely spread by human to human transmission. This genome-based evolutionary framework will facilitate C. fetus epidemiology research and the development of improved molecular diagnostics and prevention schemes for this neglected pathogen.
Label-free automated three-dimensional imaging of whole organs by microtomy-assisted photoacoustic microscopy
Authors: Wong Terence T. W. , Zhang Ruiying , Zhang Chi , Hsu Hsun-Chia , Maslov Konstantin I. , Wang Lidai , Shi Junhui , Chen Ruimin , Shung K. Kirk , Zhou Qifa , Wang Lihong V.
Published: November 2017

Three-dimensional (3D) optical imaging of whole biological organs with microscopic resolution has remained a challenge. Most versions of such imaging techniques require special preparation of the tissue specimen. Here we demonstrate microtomy-assisted photoacoustic microscopy (mPAM) of mouse brains and other organs, which automatically acquires serial distortion-free and registration-free images with endogenous absorption contrasts. Without tissue staining or clearing, mPAM generates micrometer-resolution 3D images of paraffin- or agarose-embedded whole organs with high fidelity, achieved by label-free simultaneous sensing of DNA/RNA, hemoglobins, and lipids. mPAM provides histology-like imaging of cell nuclei, blood vessels, axons, and other anatomical structures, enabling the application of histopathological interpretation at the organelle level to analyze a whole organ. Its deep tissue imaging capability leads to less sectioning, resulting in negligible sectioning artifact. mPAM offers a new way to better understand complex biological organs.
A genome-wide association study links small-vessel ischemic stroke to autophagy
Authors: Lee Tsong-Hai , Ko Tai-Ming , Chen Chien-Hsiun , Chang Yeu-Jhy , Lu Liang-Suei , Chang Chien-Hung , Huang Kuo-Lun , Chang Ting-Yu , Lee Jiann-Der , Chang Ku-Chou , Yang Jen-Tsung , Wen Ming-Shien , Wang Chao-Yung , Chen Ying-Ting , Chen Tsai-Chuan , Chou Shu-Yu , Lee Ming-Ta Michael , Chen Yuan-Tsong , Wu Jer-Yuarn
Published: November 2017

Genome-wide association studies (GWAS) can serve as strong evidence in correlating biological pathways with human diseases. Although ischemic stroke has been found to be associated with many biological pathways, the genetic mechanism of ischemic stroke is still unclear. Here, we performed GWAS for a major subtype of stroke—small-vessel occlusion (SVO)—to identify potential genetic factors contributing to ischemic stroke. GWAS were conducted on 342 individuals with SVO stroke and 1,731 controls from a Han Chinese population residing in Taiwan. The study was replicated in an independent Han Chinese population comprising an additional 188 SVO stroke cases and 1,265 controls. Three SNPs (rs2594966, rs2594973, rs4684776) clustered at 3p25.3 in ATG7 (encoding Autophagy Related 7), with P values between 2.52 × 10−6 and 3.59 × 10−6, were identified. Imputation analysis also supported the association between ATG7 and SVO stroke. To our knowledge, this is the first GWAS to link stroke and autophagy. ATG7, which has been implicated in autophagy, could provide novel insights into the genetic basis of ischemic stroke.
Quantifying the potential for bursting bubbles to damage suspended cells
Authors: Walls Peter L. L. , McRae Oliver , Natarajan Venkatesh , Johnson Chris , Antoniou Chris , Bird James C.
Published: November 2017

Bubbles that rise to the surface of a cell suspension can damage cells when they pop. This phenomenon is particularly problematic in the biotechnology industry, as production scale bioreactors require continuous injection of oxygen bubbles to maintain cell growth. Previous studies have linked cell damage to high energy dissipation rates (EDR) and have predicted that for small bubbles the EDR could exceed values that would kill many cells used in bioreactors, including Chinese Hamster Ovary (CHO) cells. However, it’s unclear how many cells would be damaged by a particular bursting bubble, or more precisely how much volume around the bubble experiences these large energy dissipation rates. Here we quantify these volumes using numerical simulations and demonstrate that even though the volume exceeding a particular EDR increases with bubble size, on a volume-to-volume basis smaller bubbles have a more significant impact. We validate our model with high-speed experiments and present our results in a non-dimensionalized framework, enabling predictions for a variety of liquids and bubble sizes. The results are not restricted to bubbles in bioreactors and may be relevant to a variety of applications ranging from fermentation processes to characterizing the stress levels experienced by microorganisms within the sea surface microlayer.
Well-being, problematic alcohol consumption and acute subjective drug effects in past-year ayahuasca users: a large, international, self-selecting online survey
Authors: Lawn Will , Hallak Jaime E. , Crippa Jose A. , Dos Santos Rafael , Porffy Lilla , Barratt Monica J. , Ferris Jason A. , Winstock Adam R. , Morgan Celia J. A.
Published: November 2017

Ayahuasca is a natural psychedelic brew, which contains dimethyltryptamine (DMT). Its potential as a psychiatric medicine has recently been demonstrated and its non-medical use around the world appears to be growing. We aimed to investigate well-being and problematic alcohol use in ayahuasca users, and ayahuasca’s subjective effects. An online, self-selecting, global survey examining patterns of drug use was conducted in 2015 and 2016 (n = 96,901). Questions were asked about: use of ayahuasca, lysergic acid diethylamide (LSD) and magic mushrooms; demographics, current well-being and past-year problematic alcohol use of past-year ayahuasca users and comparison drug users; and subjective effects of ayahuasca and comparison drugs. Ayahuasca users (n = 527) reported greater well-being than both classic psychedelic users (n = 18,138) and non-psychedelic drug-using respondents (n = 78,236). Ayahuasca users reported less problematic drinking than classic psychedelic users, although both groups reported greater problematic drinking than the other respondents. Ayahuasca’s acute subjective effects usually lasted for six hours and were most strongly felt one hour after consumption. Within our online, self-selecting survey, ayahuasca users reported better well-being than comparison groups and less problematic drinking than classic psychedelic users. Future longitudinal studies of international samples and randomised controlled trials are needed to dissect the effects of ayahuasca on these outcomes.
New insight for pharmacogenomics studies from the transcriptional analysis of two large-scale cancer cell line panels
Authors: Sadacca Benjamin , Hamy Anne-Sophie , Laurent Cécile , Gestraud Pierre , Bonsang-Kitzis Hélène , Pinheiro Alice , Abecassis Judith , Neuvial Pierre , Reyal Fabien
Published: November 2017

One of the most challenging problems in the development of new anticancer drugs is the very high attrition rate. The so-called “drug repositioning process” propose to find new therapeutic indications to already approved drugs. For this, new analytic methods are required to optimize the information present in large-scale pharmacogenomics datasets. We analyzed data from the Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopedia studies. We focused on common cell lines (n = 471), considering the molecular information, and the drug sensitivity for common drugs screened (n = 15). We propose a novel classification based on transcriptomic profiles of cell lines, according to a biological network-driven gene selection process. Our robust molecular classification displays greater homogeneity of drug sensitivity than cancer cell line grouped based on tissue of origin. We then identified significant associations between cell line cluster and drug response robustly found between both datasets. We further demonstrate the relevance of our method using two additional external datasets and distinct sensitivity metrics. Some associations were still found robust, despite cell lines and drug responses’ variations. This study defines a robust molecular classification of cancer cell lines that could be used to find new therapeutic indications to known compounds.
Inter-individual variation in genes governing human hippocampal progenitor differentiation in vitro is associated with hippocampal volume in adulthood
Authors: Powell Timothy R. , Murphy Tytus , Lee Sang H. , Duarte Rodrigo R. R. , Lee Hyun Ah , Smeeth Demelza , Price Jack , Breen Gerome , Thuret Sandrine
Published: November 2017

Hippocampal volumes are smaller in psychiatric disorder patients and lower levels of hippocampal neurogenesis are the hypothesized cause. Understanding which molecular processes regulate hippocampal progenitor differentiation might aid in the identification of novel drug targets that can promote larger hippocampal volumes. Here we use a unique human cell line to assay genome-wide expression changes when hippocampal progenitor cells differentiate. RNA was extracted from proliferating cells versus differentiated neural cells and applied to Illumina Human HT-12 v4 Expression BeadChips. Linear regressions were used to determine the effect of differentiation on probe expression and we assessed enrichment for gene ontology (GO) terms. Genetic pathway analysis (MAGMA) was used to evaluate the relationship between hippocampal progenitor cell differentiation and adult hippocampal volume, using results from the imaging genomics consortium, ENIGMA. Downregulated transcripts were enriched for mitotic processes and upregulated transcripts were enriched for cell differentiation. Upregulated (differentiation) transcripts specifically, were also predictive of adult hippocampal volume; with Early growth response protein 2 identified as a hub transcription factor within the top GO term, and a potential drug target. Our results suggest that genes governing differentiation, rather than mitosis, have an impact on adult hippocampal volume and that these genes represent important drug targets.
Chemical and cellular oxidant production induced by naphthalene secondary organic aerosol (SOA): effect of redox-active metals and photochemical aging
Authors: Tuet Wing Y. , Chen Yunle , Fok Shierly , Gao Dong , Weber Rodney J. , Champion Julie A. , Ng Nga L.
Published: November 2017

Exposure to air pollution is a leading global health risk. Secondary organic aerosol (SOA) constitute a large portion of ambient particulate matter (PM). In this study, the water-soluble oxidative potential (OP) determined by dithiothreitol (DTT) consumption and intracellular reactive oxygen and nitrogen species (ROS/RNS) production was measured for SOA generated from the photooxidation of naphthalene in the presence of iron sulfate and ammonium sulfate seed particles. The measured intrinsic OP varied for aerosol formed using different initial naphthalene concentrations, however, no trends were observed between OP and bulk aerosol composition or seed type. For all experiments, aerosol generated in the presence of iron-containing seed induced higher ROS/RNS production compared to that formed in the presence of inorganic seed. This effect was primarily attributed to differences in aerosol carbon oxidation state $${\boldsymbol{(}}{\bar{{\bf{O}}{\bf{S}}}}_{{\bf{c}}}{\boldsymbol{)}}$$
(

O

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. In the presence of iron, radical concentrations are elevated via iron redox cycling, resulting in more oxidized species. An exponential trend was also observed between ROS/RNS and $${\boldsymbol{(}}{\bar{{\bf{O}}{\bf{S}}}}_{{\bf{c}}}{\boldsymbol{)}}$$
(

O

S

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for all naphthalene SOA, regardless of seed type or aerosol formation condition. This may have important implications as aerosol have an atmospheric lifetime of a week, over which $${\boldsymbol{(}}{\bar{{\bf{O}}{\bf{S}}}}_{{\bf{c}}}{\boldsymbol{)}}$$
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increases due to continued photochemical aging, potentially resulting in more toxic aerosol.
The lipid raft-dwelling protein US9 can be manipulated to target APP compartmentalization, APP processing, and neurodegenerative disease pathogenesis
Authors: Brandimarti Renato , Hill Gordon S. , Geiger Jonathan D. , Meucci Olimpia
Published: November 2017

The trafficking behavior of the lipid raft-dwelling US9 protein from Herpes Simplex Virus strikingly overlaps with that of the amyloid precursor protein (APP). Both US9 and APP processing machinery rely on their ability to shuttle between endosomes and plasma membranes, as well as on their lateral accumulation in lipid rafts. Therefore, repurposing US9 to track/modify these molecular events represents a valid approach to investigate pathological states including Alzheimer’s disease and HIV-associated neurocognitive disorders where APP misprocessing to amyloid beta formation has been observed. Accordingly, we investigated the cellular localization of US9-driven cargo in neurons and created a US9-driven functional assay based on the exogenous enzymatic activity of Tobacco Etch Virus Protease. Our results demonstrate that US9 can direct and control cleavage of recombinant proteins exposed on the luminal leaflet of transport vesicles. Furthermore, we confirmed that US9 is associated with lipid-rafts and can target functional enzymes to membrane microdomains where pathologic APP-processing is thought to occur. Overall, our results suggest strongly that US9 can serve as a molecular driver that targets functional cargos to the APP machinery and can be used as a tool to study the contribution of lipid rafts to neurodegenerative disease conditions where amyloidogenesis has been implicated.
Binding of mycotoxins to proteins involved in neuronal plasticity: a combined in silico/wet investigation
Authors: Scafuri Bernardina , Varriale Antonio , Facchiano Angelo , D’Auria Sabato , Raggi Maria Elisabetta , Marabotti Anna
Published: November 2017

We have applied a combined computational procedure based on inverse and direct docking in order to identify putative protein targets of a panel of mycotoxins and xenobiotic compounds that can contaminate food and that are known to have several detrimental effects on human health. This procedure allowed us to identify a panel of human proteins as possible targets for aflatoxins, gliotoxin, ochratoxin A and deoxynivalenol. Steady-state fluorescence and microscale thermophoresis experiments allowed us to confirm the binding of some of these mycotoxins to acetylcholinesterase and X-linked neuroligin 4, two proteins involved in synapse activity and, particularly for the second protein, neuronal plasticity and development. Considering the possible involvement of X-linked neuroligin 4 in the etiopathogenesis of autism spectrum syndrome, this finding opens up a new avenue to explore the hypothetical role of these xenobiotic compounds in the onset of this pathology.
IL-6/IL-12 Cytokine Receptor Shuffling of Extra- and Intracellular Domains Reveals Canonical STAT Activation via Synthetic IL-35 and IL-39 Signaling
Authors: Floss D. M. , Schönberg M. , Franke M. , Horstmeier F. C. , Engelowski E. , Schneider A. , Rosenfeldt E. M. , Scheller J.
Published: November 2017

IL-35 and IL-39 are recently discovered shared members of the IL-6- and IL-12–type cytokine family with immune-suppressive capacity. IL-35 has been reported to induce the formation of four different receptor complexes: gp130:IL-12β2, gp130:gp130, IL-12β2:IL-12β2, and IL-12β2:WSX-1. IL-39 was proposed to form a gp130:IL-23R receptor complex. IL-35, but not IL-39, has been reported to activate non-conventional STAT signaling, depending on the receptor complex and target cell. Analyses of IL-35 and IL-39 are, however, hampered by the lack of biologically active recombinant IL-35 and IL-39 proteins. Therefore, we engineered chimeric cytokine receptors to accomplish synthetic IL-35 and IL- 39 signaling by shuffling the extra- and intracellular domains of IL-6/IL-12–type cytokine receptors, resulting in biological activity for all previously described IL-35 receptor complexes. Moreover, we found that the proposed IL-39 receptor complex is biologically active and discovered two additional biologically active synthetic receptor combinations, gp130/IL-12Rβ1 and IL-23R/IL-12Rβ2. Surprisingly, synthetic IL-35 activation led to more canonical STAT signaling of all receptor complexes. In summary, our receptor shuffling approach highlights an interchangeable, modular domain structure among IL-6- and IL-12–type cytokine receptors and enabled synthetic IL-35 and IL-39 signaling.
The biomechanical coordination during oropharyngeal swallowing: an evaluation with a non-invasive sensing system
Authors: Li Qiang , Minagi Yoshitomo , Ono Takahiro , Chen Yongjin , Hori Kazuhiro , Fujiwara Shigehiro , Maeda Yoshinobu
Published: November 2017

Swallowing is a very important and complex physiological behaviour. The dynamic of swallowing has created great interest as any procedural abnormality will result in dysphagia and even lower quality of life. However, a non-invasive evaluation of biomechanical coordination during oropharyngeal swallowing, which includes the activities of the tongue, the hyoid and swallowing-related muscles, has not yet been achieved. In the present study, we recruited fifteen subjects, and a non-invasive sensing system composed of a pressure sensor, a bend sensor, surface electrodes and a microphone was created to simultaneously monitor tongue pressure, hyoid motion, and surface EMG of swallowing-related muscles, as well as take sound recordings, when the subjects swallowed 5 ml of water. In addition to obtaining the durations of certain motor events, the considerable time (beginning, peak and ending time) of tongue pressure production, suprahyoid and infrahyoid muscle activity and hyoid motion were successfully measured. Moreover, the significant correlations between swallowing-related muscles, tongue pressure, and the hyoid were confirmed. These findings suggest that the non-invasive sensing system has potential as a good candidate for monitoring and evaluating the oropharyngeal process of swallowing, which may be useful in clinical work involving dysphagia evaluation and rehabilitation.
Ordered and Disordered Phases in Mo1−xWxS2 Monolayer
Authors: Tan Wei , Wei Zhipeng , Liu Xiaomin , Liu Jialin , Fang Xuan , Fang Dan , Wang Xiaohua , Wang Dengkui , Tang Jilong , Fan Xiaofeng
Published: November 2017

With special quasirandom structure approach and cluster expansion method combined with first-principle calculations, we explore the structure and electronic properties of monolayer Mo1−xWxS2 alloy with disordered phase and ordered phase. The phase transition from ordered phase to disordered phase is found to happen at 41 K and 43 K for x = 1/3 and x = 2/3, respectively. The band edge of VBM is just related with the composition x, while the band edge of CBM is sensitive to the degree of order, besides the concentration of W. Near the CBM band edge, there are two bands with the Mo-character and W-character, respectively. It is found that in disordered phase the Mo-character band is mixed with the W-character band, while the opposite happens in ordered phase. This result leads to that the splitting of two bands near CBM in ordered phase is larger than in disordered phase and gives rise to the smaller band gap in ordered phase compared to the disordered phase. The electron effective mass in ordered phase is smaller than in disordered phase, while the heavy hole effective mass in ordered phase is larger than that in disordered phase.
A common neonicotinoid pesticide, thiamethoxam, alters honey bee activity, motor functions, and movement to light
Authors: Tosi S. , Nieh J. C.
Published: November 2017

Honey bees provide key ecosystem services. To pollinate and to sustain the colony, workers must walk, climb, and use phototaxis as they move inside and outside the nest. Phototaxis, orientation to light, is linked to sucrose responsiveness and the transition of work from inside to outside the nest, and is also a key component of division of labour. However, the sublethal effects of pesticides on locomotion and movement to light are relatively poorly understood. Thiamethoxam (TMX) is a common neonicotinoid pesticide that bees can consume in nectar and pollen. We used a vertical arena illuminated from the top to test the effects of acute and chronic sublethal exposures to TMX. Acute consumption (1.34 ng/bee) impaired locomotion, caused hyperactivity (velocity: +109%; time moving: +44%) shortly after exposure (30 min), and impaired motor functions (falls: +83%; time top: −43%; time bottom: +93%; abnormal behaviours: +138%; inability to ascend: +280%) over a longer period (60 min). A 2-day chronic exposure (field-relevant daily intakes of 1.42–3.48 ng/bee/day) impaired bee ability to ascend. TMX increased movement to light after acute and chronic exposure. Thus, TMX could reduce colony health by harming worker locomotion and, potentially, alter division of labour if bees move outside or remain outdoors.
Neural-specific deletion of mitochondrial p32/C1qbp leads to leukoencephalopathy due to undifferentiated oligodendrocyte and axon degeneration
Authors: Yagi Mikako , Uchiumi Takeshi , Sagata Noriaki , Setoyama Daiki , Amamoto Rie , Matsushima Yuichi , Kang Dongchon
Published: November 2017

Mitochondrial dysfunction is a critical step in the pathogenesis of many neurodegenerative diseases. The p32/ C1qbp gene functions as an essential RNA and protein chaperone in mitochondrial translation, and is indispensable for embryonic development. However, little is known about the consequences of mitochondrial dysfunction of p32 deletion in the brain development. Here, we found that mice lacking p32 in the central nervous system (p32cKO mice) showed white matter degeneration accompanied by progressive oligodendrocyte loss, axon degeneration and vacuolation in the mid brain and brain stem regions. Furthermore, p32cKO mice died within 8 weeks of birth. We also found that p32-deficient oligodendrocytes and neurons showed reduced oligodendrocyte differentiation and axon degeneration in primary culture. We show that mitochondrial disruption activates an adaptive program known as the integrated stress response (ISR). Mitochondrial respiratory chain function in oligodendrocytes and neurons is, therefore, essential for myelination and axon maintenance, respectively, suggesting that mitochondrial respiratory chain dysfunction in the central nervous system contributes to leukoencephalopathy.
Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans
Authors: Laker R. C. , Garde C. , Camera D. M. , Smiles W. J. , Zierath J. R. , Hawley J. A. , Barrès R.
Published: November 2017

High fat feeding impairs skeletal muscle metabolic flexibility and induces insulin resistance, whereas exercise training exerts positive effects on substrate handling and improves insulin sensitivity. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression and DNA methylation. HFD markedly induced expression of immune and inflammatory genes, which was not attenuated by Ex. Conversely, Ex markedly remodelled expression of genes associated with muscle growth and structure. We detected marked DNA methylation changes following HFD alone and in combination with Ex. Among the genes that showed a significant association between DNA methylation and gene expression changes were PYGM, which was epigenetically regulated in both groups, and ANGPTL4, which was regulated only following Ex. In conclusion, while short-term Ex did not prevent a HFD-induced inflammatory response, it provoked a genomic response that may protect skeletal muscle from atrophy. These epigenetic adaptations provide mechanistic insight into the gene-specific regulation of inflammatory and metabolic processes in human skeletal muscle.
Plasmonic Chromatic Electrode with Low Resistivity
Authors: Moon Young Gyu , Do Yun Seon , Lee Min Ho , Hwang Bo Yeon , Jeong Dong Jun , Ju Byeong-Kwon , Choi Kyung Cheol
Published: November 2017

We report on the optical and electrical properties of a novel plasmonic chromatic electrode (PCE). The PCE was composed of a metallic nano-hole array and ITO layer as a dielectric for electrical property. The structure design was optimized to obtain the matched condition between surface plasmon modes at the top and bottom metal-dielectric interfaces for high transmittance. The fabricated PCEs have high transmittance of 25~40% and low resistivity (level of 10−5 Ωcm) compared to conventional electrodes. Due to the multi-functionality and simple structure of PCEs, we predict the PCEs can be applied for advanced industrial use such as, high resolution, flexible, and stretchable devices.
Influence of Precipitation and Crop Germination on Resource Selection by Mule Deer (Odocoileus hemionus) in Southwest Colorado
Authors: Carrollo Emily M. , Johnson Heather E. , Fischer Justin W. , Hammond Matthew , Dorsey Patricia D. , Anderson Charles , Vercauteren Kurt C. , Walter W. David
Published: November 2017

Mule deer (Odocoileus hemionus) populations in the western United States provide many benefits to local economies but can also cause considerable damage to agriculture, particularly damage to lucrative crops. Limited information exists to understand resource selection of mule deer in response to annual variation in crop rotation and climatic conditions. We tested the hypothesis that mule deer select certain crops, and in particular sunflower, based on annual climatic variability. Our objective was to use movements, estimates of home range, and resource selection analysis to identify resources selected by mule deer. We used annually-derived crop-specific datasets along with Global Positioning System collars to monitor 14 mule deer in an agricultural area near public lands in southwestern Colorado, USA. We estimated home ranges for two winter seasons that ranged between 7.68 and 9.88 km2, and for two summer seasons that ranged between 5.51 and 6.24 km2. Mule deer selected areas closer to forest and alfalfa for most periods during 2012, but selected areas closer to sunflower in a majority of periods during 2013. Considerable annual variation in climate patterns and precipitation levels appeared to influence selection by mule deer because of variability in crop rotation and success of germination of specific crops.
Synergistic combinations of short high-voltage pulses and long low-voltage pulses enhance irreversible electroporation efficacy
Authors: Yao Chenguo , Lv Yanpeng , Zhao Yajun , Dong Shoulong , Liu Hongmei , Ma Jianhao
Published: November 2017

Irreversible electroporation (IRE) uses ~100 μs pulsed electric fields to disrupt cell membranes for solid tumor ablation. Although IRE has achieved exciting preliminary clinical results, implementing IRE could be challenging because of volumetric limitations at the ablation region. Combining short high-voltage (SHV: 1600V, 2 μs, 1 Hz, 20 pulses) pulses with long low-voltage (LLV: 240–480 V, 100 μs, 1 Hz, 60–80 pulses) pulses induces a synergistic effect that enhances IRE efficacy. Here, cell cytotoxicity and tissue ablation were investigated. The results show that combining SHV pulses with LLV pulses induced SKOV3 cell death more effectively, and compared to either SHV pulses or LLV pulses applied alone, the combination significantly enhanced the ablation region. Particularly, prolonging the lag time (100 s) between SHV and LLV pulses further reduced cell viability and enhanced the ablation area. However, the sequence of SHV and LLV pulses was important, and the LLV + SHV combination was not as effective as the SHV + LLV combination. We offer a hypothesis to explain the synergistic effect behind enhanced cell cytotoxicity and enlarged ablation area. This work shows that combining SHV pulses with LLV pulses could be used as a focal therapy and merits investigation in larger pre-clinical models and microscopic mechanisms.
Detecting abnormality in heart dynamics from multifractal analysis of ECG signals
Authors: Shekatkar Snehal M. , Kotriwar Yamini , Harikrishnan K. P. , Ambika G.
Published: November 2017

The characterization of heart dynamics with a view to distinguish abnormal from normal behavior is an interesting topic in clinical sciences. Here we present an analysis of the Electro-cardiogram (ECG) signals from several healthy and unhealthy subjects using the framework of dynamical systems approach to multifractal analysis. Our analysis differs from the conventional nonlinear analysis in that the information contained in the amplitude variations of the signal is being extracted and quantified. The results thus obtained reveal that the attractor underlying the dynamics of the heart has multifractal structure and the variations in the resultant multifractal spectra can clearly separate healthy subjects from unhealthy ones. We use supervised machine learning approach to build a model that predicts the group label of a new subject with very high accuracy on the basis of the multifractal parameters. By comparing the computed indices in the multifractal spectra with that of beat replicated data from the same ECG, we show how each ECG can be checked for variations within itself. The increased variability observed in the measures for the unhealthy cases can be a clinically meaningful index for detecting the abnormal dynamics of the heart.
Measuring the Conformational Distance of GPCR-related Proteins Using a Joint-based Descriptor
Authors: Thangappan Jayaraman , Madan Bharat , Wu Sangwook , Lee Sun-Gu
Published: November 2017

Joint-based descriptor is a new level of macroscopic descriptor for protein structure using joints of secondary structures as a basic element. Here, we propose how the joint-based descriptor can be applied to examine the conformational distances or differences of transmembrane (TM) proteins. Specifically, we performed three independent studies that measured the global and conformational distances between GPCR A family and its related structures. First, the conformational distances of GPCR A family and other 7TM proteins were evaluated. This provided the information on the distant and close families or superfamilies to GPCR A family and permitted the identification of conserved local conformations. Second, computational models of GPCR A family proteins were validated, which enabled us to estimate how much they reproduce the native conformation of GPCR A proteins at global and local conformational level. Finally, the conformational distances between active and inactive states of GPCR proteins were estimated, which identified the difference of local conformation. The proposed macroscopic joint-based approach is expected to allow us to investigate structural features, evolutionary relationships, computational models and conformational changes of TM proteins in a more simplistic manner.
Identification of selection signals by large-scale whole-genome resequencing of cashmere goats
Authors: Li Xiaokai , Su Rui , Wan Wenting , Zhang Wenguang , Jiang Huaizhi , Qiao Xian , Fan Yixing , Zhang Yanjun , Wang Ruijun , Liu Zhihong , Wang Zhiying , Liu Bin , Ma Yuehui , Zhang Hongping , Zhao Qianjun , Zhong Tao , Di Ran , Jiang Yu , Chen Wei , Wang Wen , Dong Yang , Li Jinquan
Published: November 2017

Inner Mongolia and Liaoning cashmere goats are two outstanding Chinese multipurpose breeds that adapt well to the semi-arid temperate grassland. These two breeds are characterized by their soft cashmere fibers, thus making them great models to identify genomic regions that are associated with cashmere fiber traits. Whole-genome sequencing of 70 cashmere goats produced more than 5.52 million single-nucleotide polymorphisms and 710,600 short insertions and deletions. Further analysis of these genetic variants showed some population-specific molecular markers for the two cashmere goat breeds that are otherwise phenotypically similar. By analyzing FST and θπ outlier values, we identified 135 genomic regions that were associated with cashmere fiber traits within the cashmere goat populations. These selected genomic regions contained genes, which are potential involved in the production of cashmere fiber, such as FGF5, SGK3, IGFBP7, OXTR, and ROCK1. Gene ontology enrichment analysis of identified short insertions and deletions also showed enrichment in keratinocyte differentiation and epidermal cell differentiation. These findings demonstrate that this genomic resource will facilitate the breeding of cashmere goat and other Capra species in future.
The independent effects of vitamin D deficiency and house dust mite exposure on lung function are sex-specific
Authors: Nuñez Nailê K. , Bennett Ellen , Chen Ling , Pitrez Paulo Márcio , Zosky Graeme R.
Published: November 2017

Vitamin D deficiency is increasing around the world and has been associated with the development of asthma. This study aims to evaluate the effect of dietary vitamin D deficiency at different life stages on lung function using a murine model of allergic airways disease. BALB/c mice were challenged intranasally with HDM or saline alone for 10 days. Twenty four hours after the last challenge, mice were anesthetized and lung function was measured using the forced oscillation technique (FOT). Mice were euthanized for assessment of inflammation in the bronchoalveolar lavage (BAL) and total collagen content in lung homogenates by ELISA. Vitamin D deficiency impaired lung function in both male and female mice, increasing tissue damping and elastance, however had no effect on HDM induced inflammation. The impact of vitamin D deficiency was more evident in females. HDM also decreased airway distensibility, but only in females and this response was not altered by vitamin D deficiency. Our data suggest that vitamin D deficiency and HDM exposure have independent effects on lung mechanics and that females are more susceptible to these effects. Vitamin D deficiency may exacerbate lung function deficits by having a direct, but independent, effect on parenchymal mechanics.
Insecticidal effects of dsRNA targeting the Diap1 gene in dipteran pests
Authors: Powell Michelle , Pyati Prashant , Cao Min , Bell Howard , Gatehouse John A. , Fitches Elaine
Published: November 2017

The Drosophila melanogaster (fruit fly) gene Diap1 encodes a protein referred to as DIAP1 (DrosophilaInhibitor of Apoptosis Protein 1) that acts to supress apoptosis in “normal” cells in the fly. In this study we investigate the use of RNA interference (RNAi) to control two dipteran pests, Musca domestica and Delia radicum, by disrupting the control of apoptosis. Larval injections of 125–500 ng of Diap1 dsRNA resulted in dose-dependent mortality which was shown to be attributable to down-regulation of target mRNA. Insects injected with Diap1 dsRNA have approx. 1.5-2-fold higher levels of caspase activity than controls 24 hours post injection, providing biochemical evidence that inhibition of apoptotic activity by the Diap1 gene product has been decreased. By contrast adults were insensitive to injected dsRNA. Oral delivery failed to induce RNAi effects and we suggest this is attributable to degradation of ingested dsRNA by intra and extracellular RNAses. Non-target effects were demonstrated via mortality and down-regulation of Diap1 mRNA levels in M. domestica larvae injected with D. radicum Diap1 dsRNA, despite the absence of 21 bp identical sequence regions in the dsRNA. Here we show that identical 15 bp regions in dsRNA are sufficient to trigger non-target RNAi effects.
Net primary productivity and its partitioning in response to precipitation gradient in an alpine meadow
Authors: Zhang Fangyue , Quan Quan , Song Bing , Sun Jian , Chen Youjun , Zhou Qingping , Niu Shuli
Published: November 2017

The dynamics of net primary productivity (NPP) and its partitioning to the aboveground versus belowground are of fundamental importance to understand carbon cycling and its feedback to climate change. However, the responses of NPP and its partitioning to precipitation gradient are poorly understood. We conducted a manipulative field experiment with six precipitation treatments (1/12 P, 1/4 P, 1/2 P, 3/4 P, P, and 5/4 P, P is annual precipitation) in an alpine meadow to examine aboveground and belowground NPP (ANPP and BNPP) in response to precipitation gradient in 2015 and 2016. We found that changes in precipitation had no significant impact on ANPP or belowground biomass in 2015. Compared with control, only the extremely drought treatment (1/12 P) significantly reduced ANPP by 37.68% and increased BNPP at the depth of 20–40 cm by 80.59% in 2016. Across the gradient, ANPP showed a nonlinear response to precipitation amount in 2016. Neither BNPP nor NPP had significant relationship with precipitation changes. The variance in ANPP were mostly due to forbs production, which was ultimately caused by altering soil water content and soil inorganic nitrogen concentration. The nonlinear precipitation-ANPP relationship indicates that future precipitation changes especially extreme drought will dramatically decrease ANPP and push this ecosystem beyond threshold.
Enamel Resistance to Demineralization After Bracket Debonding Using Fluoride Varnish
Authors: Vicente Ascensión , Ortiz Ruiz Antonio José , García López Miriam , Martínez Beneyto Yolanda , Bravo-González Luis-Alberto
Published: November 2017

The aim of this study was to evaluate the elemental content and morphology of enamel subjected to demineralization cycles after bracket debonding, adhesive remnant removal, and application of a fluoride varnish. 125 bovine teeth were divided into five groups (n = 25): 1) Intact enamel; 2) Intact enamel + demineralization cycles (DC); 3) Enamel after adhesive removal; 4)Enamel after adhesive removal + DC; 5) Enamel after adhesive removal + Profluorid + DC. The weight percentages of calcium (Ca), phosphorous (P) and fluoride (F) were calculated using energy dispersive X-ray spectroscopy (EDX). Samples were observed under scanning electron microscopy (SEM). Data were analyzed using Kruskal-Wallis and Mann-Whitney test. The weight percentages of Ca and P in Group 1 were significantly higher than Groups 2, 4, and 5. The weight percentages of Ca and P in Group 2 were significantly higher than Groups 4 and 5. Group 3 presented significantly higher percentages of Ca and P than Group 4. Group 5 showed a significantly higher percentage of Ca than Group 4. The presence of F was detected in Group 5. SEM images showed more signs of demineralization in Group 4 than Group 5. Fluoride varnish application may protect enamel from demineralization after bracket debonding.
Engineering ‘cell robots’ for parallel and highly sensitive screening of biomolecules under in vivo conditions
Authors: Song Lifu , Zeng An-Ping
Published: November 2017

Cells are capable of rapid replication and performing tasks adaptively and ultra-sensitively and can be considered as cheap “biological-robots”. Here we propose to engineer cells for screening biomolecules in parallel and with high sensitivity. Specifically, we place the biomolecule variants (library) on the bacterial phage M13. We then design cells to screen the library based on cell-phage interactions mediated by a specific intracellular signal change caused by the biomolecule of interest. For proof of concept, we used intracellular lysine concentration in E. coli as a signal to successfully screen variants of functional aspartate kinase III (AK-III) under in vivo conditions, a key enzyme in L-lysine biosynthesis which is strictly inhibited by L-lysine. Comparative studies with flow cytometry method failed to distinguish the wild-type from lysine resistance variants of AK-III, confirming a higher sensitivity of the method. It opens up a new and effective way of in vivo high-throughput screening for functional molecules and can be easily implemented at low costs.
Specific Light-Up System for Protein and Metabolite Targets Triggered by Initiation Complex Formation
Authors: Fujita Hiroto , Kataoka Yuka , Nagano Remi , Nakajima Yasuyo , Yamada Masanobu , Sugimoto Naoki , Kuwahara Masayasu
Published: November 2017

Gene regulation systems are mimicked by simple quantitative detection of non-nucleic acid molecular targets such as protein and metabolite. Here, we describe a one-tube, one-step real-time quantitative detection methodology for isothermal signal amplification of those targets. Using this system, real-time quantitative detection of thrombin and streptomycin, which were used as examples for protein and metabolite targets, was successfully demonstrated with detection limits of at most 50 pM and 75 nM, respectively. Notably, the dynamic range of target concentrations could be obtained for over four orders of magnitude. Thus, our method is expected to serve as a point-of-care or on-site test for medical diagnosis and food and environmental hygiene.
Ion mobility-resolved collision-induced dissociation and electron transfer dissociation of N-glycopeptides: gathering orthogonal connectivity information from a single mass-selected precursor ion population
Authors: Kolli Venkata , Schumacher Katherine N. , Dodds Eric D.
Published: November 2017

One packet of N-glycopeptide precursors can be successively probed by CID and ETD, with fragmentation spectra deconvoluted via IM.
A lysosome-locating and acidic pH-activatable fluorescent probe for visualizing endogenous H2O2 in lysosomes
Authors: Liu Jun , Zhou Shunqing , Ren Jing , Wu Chuanliu , Zhao Yibing
Published: November 2017

We developed a lysosome-locating and acid-activatable fluorescent probe consisting of a H2O2-responsive boronate unit, a lysosome-locating morpholine group, and a pH-activatable benzorhodol fluorophore for the detection and visualization of H2O2 in lysosomes.
An ionic liquid-magnetic graphene composite for magnet dispersive solid-phase extraction of triazine herbicides in surface water followed by high performance liquid chromatography
Authors: Zhang Hua , Yuan Yanan , Sun Yunyun , Niu Can , Qiao Fengxia , Yan Hongyuan
Published: November 2017

A new ionic liquid-magnetic graphene composite was synthesized by a time-saving one-pot strategy for the extraction of triazine herbicides from surface water.
Towards single egg toxicity screening using microcoil NMR
Authors: Fugariu I. , Soong R. , Lane D. , Fey M. , Maas W. , Vincent F. , Beck A. , Schmidig D. , Treanor B. , Simpson A. J.
Published: November 2017

Planar NMR microcoils are evaluated, their application to single eggs is demonstrated, and their potential for studying smaller single cells is discussed.
Electrokinetically operated microfluidic devices for integrated immunoaffinity monolith extraction and electrophoretic separation of preterm birth biomarkers
Authors: Sonker Mukul , Parker Ellen K. , Nielsen Anna V. , Sahore Vishal , Woolley Adam T.
Published: November 2017

An integrated immunoaffinity extraction and separation device for analysis of preterm birth biomarkers in a human blood serum matrix.
Water-soluble Au nanoclusters for multiplexed mass spectrometry imaging
Authors: Li Jinan , Liu Jing , Liu Zheyi , Tan Yuan , Liu Xiaoyan , Wang Fangjun
Published: November 2017

Homogeneous Au nanoclusters were utilized for enhancing the detection sensitivity and lateral resolution of multiplexed mass spectrometry imaging due to their high ultraviolet adsorption, high water solubility, and high biocompatibility.