bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decline and Bidecadal Oscillations of Dissolved Oxygen in the Oyashio Region and Their Propagation to the Western North Pacific
Authors: Sasano Daisuke , Takatani Yusuke , Kosugi Naohiro , Nakano Toshiya , Midorikawa Takashi , Ishii Masao 
Published: April 2018

AbstractDuring the period 1954–2014, concentrations of dissolved oxygen (O2) in the Oyashio region of the western subarctic North Pacific has been oscillating over bidecadal timescales and significantly decreasing over the isopycnal layer spanning σθ = 26.6–27.5 kg/m3. The cycles of oscillation (16.4–19.6 years) are almost consistent and synchronized within 1 year over this density layer and are probably controlled by the nodal tidal cycle of 18.6 years and/or atmospheric forcing. The mean rate of the long‐term decrease is the highest (−0.70 ± 0.06 μmol · kg−1 · year−1) in the temperature minimum layer. The O2 decline there is predominantly attributed to a reduction of ventilation in winter due to warming and freshening. On the other hand, the O2 decline in deeper layers down to the oxygen minimum layer is attributable to a reduction in ventilation in the Sea of Okhotsk associated with a reduction in sea ice formation and propagation of its impact through diapycnal mixing adjacent to the Bussol' Strait. These trends of bidecadal oscillations and decline of O2 were also found in the downstream to the east in the 165°E section at latitudes 30°N–42.5°N on σθ = 26.8 kg/m3 and with attenuated amplitudes at latitudes of 40°N–45°N in the oxygen minimum layer on σθ = 27.4 kg/m3. These results indicate that the signal of secular declines of O2, together with bidecadal oscillations, is being propagated broadly from the Oyashio source region into the interior of the Pacific Ocean.
Thermomechanical Modeling of the Formation of a Multilevel, Crustal‐Scale Magmatic System by the Yellowstone Plume
Authors: Colón D. P. , Bindeman I. N. , Gerya T. V. 
Published: April 2018

AbstractGeophysical imaging of the Yellowstone supervolcano shows a broad zone of partial melt interrupted by an amagmatic gap at depths of 15–20 km. We reproduce this structure through a series of regional‐scale magmatic‐thermomechanical forward models which assume that magmatic dikes stall at rheologic discontinuities in the crust. We find that basaltic magmas accumulate at the Moho and at the brittle‐ductile transition, which naturally forms at depths of 5–10 km. This leads to the development of a 10‐ to 15‐km thick midcrustal sill complex with a top at a depth of approximately 10 km, consistent with geophysical observations of the pre‐Yellowstone hot spot track. We show a linear relationship between melting rates in the mantle and rhyolite eruption rates along the hot spot track. Finally, melt production rates from our models suggest that the Yellowstone plume is ~175°C hotter than the surrounding mantle and that the thickness of the overlying lithosphere is ~80 km.
The transcription-repair coupling factor Mfd associates with RNA polymerase in the absence of exogenous damage
Authors: Ho Han N. , van Oijen Antoine M. , Ghodke Harshad 
Published: April 2018

AbstractDuring transcription elongation, bacterial RNA polymerase (RNAP) can pause, backtrack or stall when transcribing template DNA. Stalled transcription elongation complexes at sites of bulky lesions can be rescued by the transcription terminator Mfd. The molecular mechanisms of Mfd recruitment to transcription complexes in vivo remain to be elucidated, however. Using single-molecule live-cell imaging, we show that Mfd associates with elongation transcription complexes even in the absence of exogenous genotoxic stresses. This interaction requires an intact RNA polymerase-interacting domain of Mfd. In the presence of drugs that stall RNAP, we find that Mfd associates pervasively with RNAP. The residence time of Mfd foci reduces from 30 to 18 s in the presence of endogenous UvrA, suggesting that UvrA promotes the resolution of Mfd-RNAP complexes on DNA. Our results reveal that RNAP is frequently rescued by Mfd during normal growth and highlight a ubiquitous house-keeping role for Mfd in regulating transcription elongation.
Ancient DNA study reveals HLA susceptibility locus for leprosy in medieval Europeans
Authors: Krause-Kyora Ben , Nutsua Marcel , Boehme Lisa , Pierini Federica , Pedersen Dorthe Dangvard , Kornell Sabin-Christin , Drichel Dmitriy , Bonazzi Marion , Möbus Lena , Tarp Peter , Susat Julian , Bosse Esther , Willburger Beatrix , Schmidt Alexander H. , Sauter Jürgen , Franke Andre , Wittig Michael , Caliebe Amke , Nothnagel Michael , Schreiber Stefan , Boldsen Jesper L. , Lenz Tobias L. , Nebel Almut 
Published: April 2018

AbstractLeprosy, a chronic infectious disease caused by Mycobacterium leprae (M. leprae), was very common in Europe till the 16th century. Here, we perform an ancient DNA study on medieval skeletons from Denmark that show lesions specific for lepromatous leprosy (LL). First, we test the remains for M. leprae DNA to confirm the infection status of the individuals and to assess the bacterial diversity. We assemble 10 complete M. leprae genomes that all differ from each other. Second, we evaluate whether the human leukocyte antigen allele DRB1*15:01, a strong LL susceptibility factor in modern populations, also predisposed medieval Europeans to the disease. The comparison of genotype data from 69 M. leprae DNA-positive LL cases with those from contemporary and medieval controls reveals a statistically significant association in both instances. In addition, we observe that DRB1*15:01 co-occurs with DQB1*06:02 on a haplotype that is a strong risk factor for inflammatory diseases today.
Mechanically interlocked functionalization of monoclonal antibodies
Authors: Bzymek Krzysztof P. , Puckett James W. , Zer Cindy , Xie Jun , Ma Yuelong , King Jeremy D. , Goodstein Leah H. , Avery Kendra N. , Colcher David , Singh Gagandeep , Horne David A. , Williams John C. 
Published: April 2018

AbstractBecause monoclonal antibodies (mAbs) have exceptional specificity and favorable pharmacology, substantial efforts have been made to functionalize them, either with potent cytotoxins, biologics, radionuclides, or fluorescent groups for therapeutic benefit and/or use as theranostic agents. To exploit our recently discovered meditope–Fab interaction as an alternative means to efficiently functionalize mAbs, we used insights from the structure to enhance the affinity and lifetime of the interaction by four orders of magnitude. To further extend the lifetime of the complex, we created a mechanical bond by incorporating an azide on the meditope, threading the azide through the Fab, and using click chemistry to add a steric group. The mechanically interlocked, meditope–Fab complex retains antigen specificity and is capable of imaging tumors in mice. These studies indicate it is possible to “snap” functionality onto mAbs, opening the possibility of rapidly creating unique combinations of mAbs with an array of cytotoxins, biologics, and imaging agents.
Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress
Authors: van der Reest Jiska , Lilla Sergio , Zheng Liang , Zanivan Sara , Gottlieb Eyal 
Published: April 2018

AbstractReactive oxygen species (ROS) are increasingly recognised as important signalling molecules through oxidation of protein cysteine residues. Comprehensive identification of redox-regulated proteins and pathways is crucial to understand ROS-mediated events. Here, we present stable isotope cysteine labelling with iodoacetamide (SICyLIA), a mass spectrometry-based workflow to assess proteome-scale cysteine oxidation. SICyLIA does not require enrichment steps and achieves unbiased proteome-wide sensitivity. Applying SICyLIA to diverse cellular models and primary tissues provides detailed insights into thiol oxidation proteomes. Our results demonstrate that acute and chronic oxidative stress causes oxidation of distinct metabolic proteins, indicating that cysteine oxidation plays a key role in the metabolic adaptation to redox stress. Analysis of mouse kidneys identifies oxidation of proteins circulating in biofluids, through which cellular redox stress can affect whole-body physiology. Obtaining accurate peptide oxidation profiles from complex organs using SICyLIA holds promise for future analysis of patient-derived samples to study human pathologies.
Towards annotating the plant epigenome: the Arabidopsis thaliana small RNA locus map
Authors: Hardcastle Thomas J. , Müller Sebastian Y. , Baulcombe David C. 
Published: April 2018

AbstractBased on 98 public and internal small RNA high throughput sequencing libraries, we mapped small RNAs to the genome of the model organism Arabidopsis thaliana and defined loci based on their expression using an empirical Bayesian approach. The resulting loci were subsequently classified based on their genetic and epigenetic context as well as their expression properties. We present the results of this classification, which broadly conforms to previously reported divisions between transcriptional and post-transcriptional gene silencing small RNAs, and to PolIV and PolV dependencies. However, we are able to demonstrate the existence of further subdivisions in the small RNA population of functional significance. Moreover, we present a framework for similar analyses of small RNA populations in all species.
Differential contribution of cis and trans gene transcription regulatory mechanisms in amygdala and prefrontal cortex and modulation by social stress
Authors: Reuveni Eli , Getselter Dmitry , Oron Oded , Elliott Evan 
Published: April 2018

AbstractWhile both individual transcription factors and cis-acting sites have been studied in relation to psychiatric disorders, there is little knowledge of the relative contribution of trans-acting and cis-acting factors to gene transcription in the brain. Using an RNA-seq approach in mice bred from two evolutionary-distinct mice strains, we determined the contribution of cis and trans factors to gene expression in the prefrontal cortex and amygdala, two regions of the brain relevant to the stress response, and the contribution of cis and trans factors in the prefrontal cortex after Chronic Social Defeat (CSD) in mice. More genes were regulated by cis-regulatory factors in both brain regions, underlying the importance of cis-acting gene regulation in the brain. However, there was an increase in genes regulated by trans-regulatory mechanisms in the amygdala, compared to the prefrontal cortex. These genes were involved in synaptic functions, and were enriched for binding sites for transcription factors, including Egr1. CSD induced an increase in genes regulated by trans-regulatory mechanisms in the prefrontal cortex, and induced a pattern similar to the unstressed amygdala. Overall, we show brain site-specific patterns in cis and trans regulatory mechanisms, and show that these patterns can be modified by a psychological trigger.
The Role of Macrophage Migration Inhibitory Factor in the Function of Intestinal Barrier
Authors: Vujicic Milica , Saksida Tamara , Despotovic Sanja , Bajic Svetlana Sokovic , Lalić Ivana , Koprivica Ivan , Gajic Dragica , Golic Natasa , Tolinacki Maja , Stojanovic Ivana 
Published: April 2018

AbstractMacrophage migration inhibitory factor (MIF) is a multifunctional protein that is involved in the development of gut-related inflammation. To investigate the role of MIF in the function of the intestinal barrier, we have explored intestinal permeability and gut-associated immune response in MIF-deficient (MIF-KO) mice. The absence of MIF provoked impairment of tight and adherens epithelial junctions in the colon through the disturbance of E-cadherin, zonula occludens-1, occludin and claudin-2 expression, which lead to the increase of intestinal barrier permeability. In these circumstances the diversity and content of gut microbiota in MIF-KO mice was considerably different compared to wild type mice. This change in microbiota was accompanied by an increased intestinal IgA concentration and a higher production of pro-inflammatory cytokines TNF and IFN-γ in mesenteric lymph nodes of MIF-KO mice. The forced changes of microbiota executed by antibiotics prevented the “leakage” of the barrier in MIF-KO mice, probably through up-regulation of occludin expression and normalization of cellular pore diameters. In addition, cytokine secretion was normalized after the treatment with antibiotics. These results suggest that MIF participates in the maintenance of physiological microbiota diversity and immunosurveillance, which in turn enables the proper intestinal barrier function.
The Therapeutic Potential and Molecular Mechanism of Isoflavone Extract against Psoriasis
Authors: Li Hsin-Ju , Wu Nan-Lin , Lee Gon-Ann , Hung Chi-Feng 
Published: April 2018

AbstractPsoriasis is a common inflammatory disease. It affects 1–3% of the population worldwide and is associated with increasing medical costs every year. Typical psoriatic skin lesions are reddish, thick, scaly plaques that can occur on multiple skin sites all over the body. Topical application of imiquimod (IMQ), a toll-like receptor (TLR)7 agonist and potent immune system activator, can induce and exacerbate psoriasis. Previous studies have demonstrated that isoflavone extract has an antioxidant effect which may help decrease inflammation and inflammatory pain. Through in vivo studies in mice, we found that the topical application to the shaved back and right ear of mice of isoflavone extract prior to IMQ treatment significantly decreased trans-epidermal water loss (TEWL), erythema, blood flow speed, and ear thickness, while it increased surface skin hydration, and attenuated epidermal hyperplasia and inflammatory cell infiltration. Through in vitro experiments, we found that isoflavone extract can reduce IL-22, IL-17A, and TNF-α-induced MAPK, NF-κB, and JAK-STAT activation in normal human epidermal keratinocytes. At the mRNA level, we determined that isoflavone extract attenuated the increased response of the TNF-α-, IL-17A-, and IL-22- related pathways. These results indicate that isoflavone extract has great potential as an anti-psoriatic agent and in the treatment of other inflammatory skin diseases.
Enteric Nervous System Regulation of Intestinal Stem Cell Differentiation and Epithelial Monolayer Function
Authors: Puzan Marissa , Hosic Sanjin , Ghio Caroline , Koppes Abigail 
Published: April 2018

AbstractThe Enteric Nervous System (ENS) is a complex network of neurons and glia, which regulates sensorimotor function throughout the gastroinestinal tract (GI). Here we investigated the role of the ENS and intestinal myofibroblasts in the maintenance of a primary intestinal epithelial barrier through regulation of monolayer permeability, cytokine production, and differentiation of intestinal stem cells. Utilizing a novel, in vitro, transwell-based coculture system, murine small intestinal stem cells were isolated and cultured with ENS neurons and glia or subepithelial myofibroblasts. Results show that the ENS contributes to regulation of intestinal stem cell fate, promoting differentiation into chemosensory enteroendocrine cells, with 0.9% of cells expressing chromogranin A when cultured with ENS versus 0.6% in cocultures with myofibroblasts and 0.3% in epithelial cultures alone. Additionally, enteric neurons and myofibroblasts differentially release cytokines Macrophage Inflammatory Protein 2 (MIP-2), Transforming Growth Factor beta 1 (TGF-β1), and Interleukin 10 (IL-10) when cultured with intestinal epithelial cells, with a 1.5 fold increase of IL-10 and a 3 fold increase in MIP-2 in ENS cocultures compared to coculture with myofibroblasts. These results indicate the importance of enteric populations in the regulation of intestinal barrier function.
A molecular dynamics simulation study decodes the Zika virus NS5 methyltransferase bound to SAH and RNA analogue
Authors: Chuang Chih-Hung , Chiou Shean-jaw , Cheng Tian-Lu , Wang Yeng-Tseng 
Published: April 2018

AbstractSince 2015, widespread Zika virus outbreaks in Central and South America have caused increases in microcephaly cases, and this acute problem requires urgent attention. We employed molecular dynamics and Gaussian accelerated molecular dynamics techniques to investigate the structure of Zika NS5 protein with S-adenosyl-L-homocysteine (SAH) and an RNA analogue, namely 7-methylguanosine 5′-triphosphate (m7GTP). For the binding motif of Zika virus NS5 protein and SAH, we suggest that the four Zika NS5 substructures (residue orders: 101–112, 54–86, 127–136 and 146–161) and the residues (Ser56, Gly81, Arg84, Trp87, Thr104, Gly106, Gly107, His110, Asp146, Ile147, and Gly148) might be responsible for the selectivity of the new Zika virus drugs. For the binding motif of Zika NS5 protein and m7GTP, we suggest that the three Zika NS5 substructures (residue orders: 11–31, 146–161 and 207–218) and the residues (Asn17, Phe24, Lys28, Lys29, Ser150, Arg213, and Ser215) might be responsible for the selectivity of the new Zika virus drugs.
Aufbruch in der Fastentherapie
Authors: Michalsen Andreas 
Published: April 2018

ZusammenfassungAlternierende Phasen des Nahrungsüberangebots und des Hungerns waren bei den Frühmenschen vermutlich der Regelfall. Es scheint naheliegend, dass der menschliche Körper evolutionsbedingt Phasen des Fastens sehr gut bewältigen kann und sich die genetische Ausstattung, der Körpermetabolismus und die Ernährungsphysiologie gut darauf eingestellt haben. Im Gegensatz dazu ist anzunehmen, dass die mehrmals tägliche, regelmäßige Nahrungszufuhr mit Snacks, Zwischenmahlzeiten und energiehaltigen Getränken, die Hormon- und Stoffwechselsysteme überfordert.Die günstigen metabolischen Wirkungen des Fastens sind in physiologischen Arbeiten beschrieben. Der Artikel gibt einen Überblick zu den verschiedenen Formen des Fastens und dessen mögliche Effekte.
Crataegus Special Extract WS 1442 Effects on eNOS and microRNA 155
Authors: Wang Xinwen , Liang Yan , Shi Jian , Zhu Hao-jie , Bleske Barry 
Published: April 2018

AbstractIncreased expression of microRNA 155 (miR-155) results in a decrease in endothelial nitric oxide synthase (eNOS) expression and impaired endothelial function. Factors that have been shown to increase expression of miR-155 may be mitigated by WS 1442, an extract of hawthorn leaves and flowers (Crataegus special extract) that contains a range of pharmacologically active substances including oligomeric proanthocyanidins and flavonoids. The purpose of this study is to determine the effect of WS 1442 on the expression of miR-155 and eNOS in the presence of tumor necrosis factor (TNF-α). Human umbilical vein endothelial cells (HUVECs) were studied after the exposure to TNF-α, with or without simvastatin (positive control) and WS 1442. The expression levels of eNOS, phosphorylated eNOS, and miR-155 in the different HUVEC treatment groups were determined by western blot and quantitative real-time polymerase chain reaction, respectively. To evaluate the effect of WS 1442 on the eNOS activity, the medium and intracellular nitrate/nitrite (NO) concentrations were also analyzed using a colorimetric Griess assay kit. The results demonstrated that TNF-α upregulated miR-155 expression and decreased eNOS expression and NO concentrations. WS 1442 also increased miR-155 expression and decreased eNOS expression but, unlike TNF-α, increased phosphorylated eNOS expression and NO concentrations. Surprisingly, WS 1442 increased miR-155 expression; however, WS 1442 mitigated the overall negative effect of miR-155 on decreasing eNOS expression by increasing expression of phosphorylated eNOS and resulting in an increase in NO concentrations. In the setting where miR-155 may be expressed, WS 1442 may offer vascular protection by increasing the expression of phosphorylated eNOS.
Optimal Timing of Delivery in Women with Higher Order Cesareans: A Cohort Study
Authors: Nielsen Chloe , Zafman Kelly , Fox Nathan , Miller Emily 
Published: April 2018

Objective To evaluate whether a planned early term delivery or a planned 39-week delivery is associated with differences in perinatal outcomes in women undergoing a higher order cesarean (HOC).
Study Design This cohort study included women with singleton gestations with a history of three or more prior cesareans who delivered at one of two urban tertiary care hospitals. One center routinely delivered HOC at 39 weeks' gestation and the other at 37 weeks. Maternal and neonatal morbidities were compared using bivariable and multivariable analyses.
Results The policy of 37-week delivery was associated with a decrease in unscheduled deliveries (15.3 vs. 41.1%; p < 0.001). Planned delivery at 37 weeks was associated with a decreased incidence of composite maternal morbidity (1.6 vs. 7.9%; p = 0.002) and 5-minute Apgar score less than 7 (0.4 vs. 6.4%; p < 0.001), but these differences were not significant after controlling for potential confounders (adjusted odds ratio [aOR]: 0.30, 95% confidence interval [CI]: 0.08–1.17; aOR: 0.13, 95% CI: 0.01–1.30, respectively). There were no other differences in perinatal outcomes.
Conclusion Compared with planned delivery at 39 weeks, a policy of planned delivery at 37 weeks was associated with a reduction in unscheduled deliveries, but there were no measured differences in perinatal outcomes.
Antimicrobial Peptidomimetics for Recurrent Septicemia Infections: In Vitro Study for Immuno Compromised Disease Target
Authors: Sharma Priyanka , Nagarajan Kandasamy , Panda Bihu 
Published: April 2018

AbstractThe frequency of Bacillus subtilis infection such as pneumonia pan-opthalmitis, visceral abscess or musculoskeletal infection etc. complications following bacteremia, meningitis in children & the infection associated with majority of motor vehicle accidents associated with trauma & gun shoot injury. Antibiotics which appear especially useful in the treatment of Bacillus. infection are clindamycin and vancomycin to which vast majority of strains are susceptible in vitro. Our objective is to test the synthesized peptidomimetics with the efforts mainly directed towards the identification of antibacterial compounds against recurrent septicemia infection. Six peptidomimetics namely G-A-L-D (C60-soot Glu-ala-leu-Asp), D-P-F (C60-soot Asp-pro-Phe), I-R (C60-soot Ile-Arg), L-R (C60-soot leu-Arg), E-R (C60-soot Glu-Arg), D-E (C60-soot Asp-Glu), the column eluted compounds were tested for disc diffusion using gram positive Bacillus Subtilis strains at different concentrations predicted by pH and inhibitory concentrations. I-R (C60-soot Ile-Arg), & D-E (C60-soot Asp-Glu) was found to be very effective along with 5 compounds against Bacillus Subtilis strain tested. Maximum activity 100 µg/ml for synthesized peptidomimetics with the corresponding zonal inhibition diameter (11 mm; 11 mm; 14 mm; 11 mm; 11 mm; 14 mm) against Bacillus subtilis strain. This is the first evidence based report that proves I-R (C60-soot Ile-Arg) & D-E (C60-soot Asp-Glu) has shown antibacterial action against gram positive strains of Bacillus Subtilis against recurrent septicemia infection