bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coagulansin-A has beneficial effects on the development of bovine embryos in vitro via HSP70 induction
Authors: Khan Imran , Lee Kyeong-Lim , Fakruzzaman Md. , Song Seok-Hwan , Ihsan-ul-Haq  , Mirza Bushra , Yan Chang Guo , Kong Il-Keun 
Published: February 2016

Coagulansin-A (withanolide) is the steroidal lactone obtained from Withania coagulans which belong to Solanaceae family. The present study investigated the effects of coagulansin-A on bovine oocyte maturation and embryo development in vitro. All these oocytes were aspirated from the ovaries obtained from Korean Hanwoo cows at a local abattoir. To determine whether coagulansin-A has beneficial effects on bovine oocyte maturation in vitro, 355 oocytes per group (control and treated) in seven replicates were subjected with different concentrations (1, 2.5, 5, 7.5 and 10 μM) of coagulansin-A. The coagulansin-A was added in the in vitro maturation (IVM) media followed by in vitro fertilization (IVF) and then in vitro culture (IVC). Only treatment with 5 μM coagulansin-A remarkably (P&lt;0.05) improved embryos development (Day 8 blastocyst) having 27.30 and 40.01% for control and coagulansin-A treated groups respectively. Treatment with 5 μM coagulansin-A significantly induced activation of heat shock protein 70 (HSP70) (P&lt;0.05). Immunofluorescence analysis revealed that 5 μM coagulansin-A treatment also significantly inhibited oxidative stress and inflammation during bovine embryo development in vitro by decreasing 8-oxoguanosine (8-OxoG) (P&lt;0.05) and nuclear factor-κB (NF-κB) (P&lt;0.05). The expressions of HSP70 and NF-κB were also conformed through real-time PCR (RT-PCR). Additionally, the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay confirmed that coagulansin-A treatment significantly improved the embryo quality and reduced bovine embryo DNA damage (P&lt;0.05). The present study provides new information regarding the mechanisms by which coagulansin-A promotes bovine embryo development in vitro.
Mapping time-course mitochondrial adaptations in the kidney in experimental diabetes
Authors: Coughlan Melinda T. , Nguyen Tuong-Vi , Penfold Sally A. , Higgins Gavin C. , Thallas-Bonke Vicki , Tan Sih Min , Van Bergen Nicole J. , Sourris Karly C. , Harcourt Brooke E. , Thorburn David R. , Trounce Ian A. , Cooper Mark E. , Forbes Josephine M. 
Published: February 2016

Oxidative phosphorylation (OXPHOS) drives ATP production by mitochondria, which are dynamic organelles, constantly fusing and dividing to maintain kidney homoeostasis. In diabetic kidney disease (DKD), mitochondria appear dysfunctional, but the temporal development of diabetes-induced adaptations in mitochondrial structure and bioenergetics have not been previously documented. In the present study, we map the changes in mitochondrial dynamics and function in rat kidney mitochondria at 4, 8, 16 and 32 weeks of diabetes. Our data reveal that changes in mitochondrial bioenergetics and dynamics precede the development of albuminuria and renal histological changes. Specifically, in early diabetes (4 weeks), a decrease in ATP content and mitochondrial fragmentation within proximal tubule epithelial cells (PTECs) of diabetic kidneys were clearly apparent, but no changes in urinary albumin excretion or glomerular morphology were evident at this time. By 8 weeks of diabetes, there was increased capacity for mitochondrial permeability transition (mPT) by pore opening, which persisted over time and correlated with mitochondrial hydrogen peroxide (H2O2) generation and glomerular damage. Late in diabetes, by week 16, tubular damage was evident with increased urinary kidney injury molecule-1 (KIM-1) excretion, where an increase in the Complex I-linked oxygen consumption rate (OCR), in the context of a decrease in kidney ATP, indicated mitochondrial uncoupling. Taken together, these data show that changes in mitochondrial bioenergetics and dynamics may precede the development of the renal lesion in diabetes, and this supports the hypothesis that mitochondrial dysfunction is a primary cause of DKD.
Investigation into the characteristics of proton exchange membrane fuel cell‐based power system
Authors: Alrewq Mohmmad , Albarbar Alhussein 
Published: February 2016

Fuel cells (FCs) use hydrogen as their prime fuel source, which promotes them as one of the attractive options for clean energy generators. Though they have been around for some time, their characteristics are not yet fully understood. This study offers a thorough investigation into the characteristics of proton exchange membrane (PEM) type of FCs based power system. This study first presents a concise explanation of the working principles of the PEM electrolyser and FCs supported by novel modelling using MATLAB. The simulation results are then validated by a series of experiments carried out on operational 500 mW FC followed by detailed performance parameters of such type of FCs. Parameters affect the efficiencies of each part of the system are investigated and the total system's efficiency is then calculated. The efficiency of the electrolyser and PEM FC was found to be 85 and 60%, respectively. Polarisation curve has been used in order to evaluate FC's performance. From the polarisation curve, it is noted the efficiency of the FC increases with increasing pressure and temperature. The activation losses are reduced when the temperature increased. Moreover, the mass transfer is enhanced toward reducing the PEMFC's resistance.
Automatic method for vertebral morphometry measurements
Authors: Franchini Roberto , Conversano Francesco , Pisani Paola , Casciaro Ernesto , Peccarisi Marco , Quarta Eugenio , Grimaldi Antonella , Muratore Maurizio , Casciaro Sergio 
Published: February 2016

Aim of this study was to perform a detailed clinical validation of a novel fully automatic method for vertebral morphometry. About 80 spine lateral radiographs were evaluated both automatically, by the proposed algorithm, and manually, by an experienced radiologist. The following metrics were used for algorithm performance assessment: sensitivity and specificity in vertebra detection; errors in the localisation of characteristic points of vertebral border; errors in the measurement of six diagnostic parameters; level of agreement and correlation between manual and automatic morphometric measurements; overall accuracy of automatic diagnoses with respect to manual ones. Obtained results showed a very good performance in vertebra detection (sensitivity = 89.1% and specificity = 100.0%). Average errors in the localisation of vertebral characteristic points were always smaller than 3 mm (range 0.85–2.79 mm), causing relative errors in diagnostic parameter values ranging from −5.01 to +6.10%. Bland–Altman analysis documented a mean error in automatic measurements of diagnostic ratios of 0.01 ± 0.18 (bias ± 2 SDs), while Pearson's correlation coefficient resulted r = 0.71 (p < 0.001). Finally, an optimal diagnostic coincidence (92.8%) was found between automatic and manual diagnoses. Therefore, the adopted method has a potential for an effective employment in clinical routine for reliable diagnosis of vertebral fractures.
Chimera proteins with affinity for membranes and microtubule tips polarize in the membrane of fission yeast cells
Authors: Recouvreux Pierre , Sokolowski Thomas R. , Grammoustianou Aristea , ten Wolde Pieter Rein , Dogterom Marileen 
Published: February 2016

Significance
Cells have to spatially organize their interior to fulfill important functions. In fission yeast, this includes the concentration of polarity factors at cell ends. The molecular network that is responsible for organizing polarity factors consists of a large number of components, including proteins that travel at the ends of microtubules. In an attempt to reduce the complexity of this network, we engineered an artificial chimera protein that interacts both with microtubule ends and the membrane. As predicted by numerical simulations, this simple molecule is able to concentrate at cell ends, but the established polarity is less robust than for natural polarity factors. This finding may lead to a better understanding of the molecular mechanisms that lead to natural polarity patterns.
Subunit stoichiometry and arrangement in a heteromeric glutamate-gated chloride channel
Authors: Degani-Katzav Nurit , Gortler Revital , Gorodetzki Lilach , Paas Yoav 
Published: February 2016

Significance
Cys-loop receptors (CLRs) are transmembrane ion channels activated by neurotransmitters to mediate chemoelectric excitation or inhibition throughout the nervous system. Hence, CLRs play a key role in our day-to-day life, from coordination of motions to cognition. Impairment of CLRs’ activity leads to various pathophysiological conditions. The CLR studied here is a glutamate-gated chloride-selective receptor (GluClR). GluClRs are unique to invertebrates, yet they are pharmacologically important because they serve as targets for ivermectin, an anthelmintic drug used to treat humans suffering from filarial diseases. This study provides better understanding of the subunit arrangement and stoichiometry of Glu-binding sites in GluClRs.
Conditional cooperation and confusion in public-goods experiments
Authors: Burton-Chellew Maxwell N. , El Mouden Claire , West Stuart A. 
Published: February 2016

SignificanceThe finding that people vary in how they play economic games has led to the conclusion that people vary in their preference for fairness. Consequently, people have been divided into fair cooperators that make sacrifices for the good of the group and selfish free-riders that exploit the cooperation of others. This conclusion has been used to challenge evolutionary theory and economic theory and to guide social policy. We show that variation in behavior in the public-goods game is better explained by variation in understanding and that misunderstanding leads to cooperation.
Stimulus-induced visual cortical networks are recapitulated by spontaneous local and interareal synchronization
Authors: Lewis Christopher M. , Bosman Conrado A. , Womelsdorf Thilo , Fries Pascal 
Published: February 2016

Significance
The greatest proportion of brain activity is endogenously generated. The brain’s endogenous activity is highly structured and affects sensory coding, behavior, and perception. The observation of structured endogenous activity across spatial scales suggests that it plays a role in the maintenance and formation of brain networks. The correlation of spontaneous functional MRI signals has demonstrated the existence of multiple intrinsic networks, previously observed during controlled cognitive paradigms. The prevalence and reliability of intrinsic networks have generated intense interest in the functional relevance and electrophysiological basis of interareal correlations. Using multisite recordings from areas V1 and V4 of awake monkeys, we show that endogenously generated activity, both during stimulation and passive fixation, exhibits a similar pattern of local and interareal rhythmic synchronization.
Synthetic gene network restoring endogenous pituitary–thyroid feedback control in experimental Graves’ disease
Authors: Saxena Pratik , Charpin-El Hamri Ghislaine , Folcher Marc , Zulewski Henryk , Fussenegger Martin 
Published: February 2016

Significance
Graves’ disease is caused by autoantibodies that activate the thyroid-stimulating hormone (TSH) receptor and trigger a chronic increase in thyroid hormone levels. Current treatment options remain unchanged for decades and include antithyroid drugs as well as radioiodine treatment and thyroidectomy, which result in the destruction of the thyroid gland and require lifelong prescription of thyroid hormones. We designed a closed-loop gene circuit that enables engineered cells to monitor increased thyroid hormone levels and drive the expression of a validated TSH receptor antagonist that competes with TSH as well as TSH receptor autoantibodies, thereby overcoming the pathophysiological activation of the thyroid gland. Hyperthyroid animals implanted with these designer cells had thyroid hormone levels corrected by restoring the feedback control system of the hypothalamus–pituitary–thyroid axis.
SutA is a bacterial transcription factor expressed during slow growth inPseudomonas aeruginosa
Authors: Babin Brett M. , Bergkessel Megan , Sweredoski Michael J. , Moradian Annie , Hess Sonja , Newman Dianne K. , Tirrell David A. 
Published: February 2016

SignificancePathogens that are dormant or growing slowly play important roles in chronic infections, but studying how cells adapt to these conditions is difficult experimentally. This work demonstrates that time-selective analysis of cellular protein synthesis, using bioorthogonal noncanonical amino acid tagging (BONCAT), can provide the sensitivity needed to identify important factors in slow-growth physiology. We identified inPseudomonas aeruginosa, a previously uncharacterized transcriptional regulator that is expressed preferentially under slow-growth conditions, binds RNA polymerase, and has widespread effects on gene expression. This factor is one of several proteins of unknown function identified in our proteomic analysis, and our results suggest that further characterization of fundamental cellular processes under these conditions will shed light on important and understudied realms of biology.
The decadal state of the terrestrial carbon cycle: Global retrievals of terrestrial carbon allocation, pools, and residence times
Authors: Bloom A. Anthony , Exbrayat Jean-François , van der Velde Ivar R. , Feng Liang , Williams Mathew 
Published: February 2016

Significance
Quantitative knowledge of terrestrial carbon pathways and processes is fundamental for understanding the biosphere’s response to a changing climate. Carbon allocation, stocks, and residence times together define the dynamic state of the terrestrial carbon cycle. These quantities are difficult to measure and remain poorly quantified on a global scale. Here, we retrieve global 1° × 1° carbon state and process variables by combining a carbon balance model with satellite observations of biomass and leaf area (where and when available) and global soil carbon data. Our results reveal emergent continental-scale patterns and relationships between carbon states and processes. We find that conventional land cover types cannot capture continental-scale variations of retrieved carbon variables; this mismatch has strong implications for terrestrial carbon cycle predictions.
Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies
Authors: Jackson Nicholas J. , Isen Joshua D. , Khoddam Rubin , Irons Daniel , Tuvblad Catherine , Iacono William G. , McGue Matt , Raine Adrian , Baker Laura A. 
Published: February 2016

Significance
Marijuana is the most commonly used recreational drug in the United States. Some studies suggest that marijuana use in adolescence is linked to declines in intellectual functioning. Because of the infeasibility of studying this phenomenon experimentally, it is unclear whether the association can be causally attributed to marijuana use itself or is instead the result of confounding factors. We approach this issue quasiexperimentally using longitudinal samples of adolescent twins. Among twin pairs discordant for marijuana use, we assessed intelligence quotient (IQ) score changes while adjusting for the effects of genetic influences and other factors shared by members of the same twin pair. Results suggest that familial confounds underlie the association between adolescent marijuana use and declining IQ scores.
Marine mixotrophy increases trophic transfer efficiency, mean organism size, and vertical carbon flux
Authors: Ward Ben A. , Follows Michael J. 
Published: February 2016

SignificanceMarine plankton commonly combine the autotrophic use of light and inorganic resources with the heterotrophic ingestion of prey. These mixotrophs blur the strict boundary between producers and consumers and allow energy and biomass to enter the food web across multiple trophic levels. Incorporating this flexibility into a global simulation of the surface ocean food web reveals that mixotrophy enhances the transfer of biomass to larger organisms at higher trophic levels, which in turn increases the efficiency of oceanic carbon storage through the production of larger, faster-sinking, and carbon-enriched organic detritus.
Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes
Authors: Grigoryev Sergei A. , Bascom Gavin , Buckwalter Jenna M. , Schubert Michael B. , Woodcock Christopher L. , Schlick Tamar 
Published: February 2016

Significance
Though the two-start zigzag geometry of a nucleosome chain is dominant in chromatin fibers in vitro, it remains unknown whether it is preserved in living cells. Our combined nucleosome interaction capture technique and mesoscale modeling reveal that the zigzag motif is persistent in interphase and metaphase chromatin. For metaphase chromosomes, we observe a striking increase in occurrence of long-range internucleosome interactions, inconsistent with hierarchical coiling or a liquid melt. Instead, the data point to a new mechanism for higher-order folding, via hierarchical looping, similar to rope flaking used in mountaineering. This mechanism brings together distant DNA elements in a manner that can be controlled by linker histones and histone modifications. Implications for genomic accessibility and epigenetic functions naturally arise.
Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers
Authors: Mehine Miika , Kaasinen Eevi , Heinonen Hanna-Riikka , Mäkinen Netta , Kämpjärvi Kati , Sarvilinna Nanna , Aavikko Mervi , Vähärautio Anna , Pasanen Annukka , Bützow Ralf , Heikinheimo Oskari , Sjöberg Jari , Pitkänen Esa , Vahteristo Pia , Aaltonen Lauri A. 
Published: February 2016

Significance
The clinical and scientific community widely regards uterine leiomyomas as a single entity, although evidence of genetic heterogeneity exists. The aim of this study was to explore transcriptional differences between leiomyomas harboring different genetic alterations, including high mobility group AT-hook 2 rearrangements, mediator complex subunit 12 mutations, biallelic inactivation of fumarate hydratase, and collagen, type IV, alpha 5-collagen, type IV, alpha 6 deletions. The evidence presented herein strongly suggests that specific driver mutations are the major determinants of expression changes in leiomyomas. Here we highlight subtype-specific expression differences in key driver pathways and emphasize the utility of stratification in leiomyoma research. Finally, we offer a set of candidate biomarkers that will facilitate the molecular classification of leiomyomas.
Folding and assembly of the large molecular machine Hsp90 studied in single-molecule experiments
Authors: Jahn Markus , Buchner Johannes , Hugel Thorsten , Rief Matthias 
Published: February 2016

Significance
Understanding protein folding is, as yet, an unsolved question in the life sciences that has relevance for many diseases. While the folding of simple and small protein domains is well studied, for large proteins, the abundance of pathways and intermediate states makes them difficult to characterize using standard protein folding experiments. With single-molecule optical tweezers experiments, we can overcome these limitations. We observe in real time the folding of a dimeric, three-domain protein from the fully unfolded chain to the biologically active, quaternary structure. The likelihood of the folding process being hindered by misfolded intermediates increases with chain length. These misfolded states can slow down folding significantly and may lead to aggregation in vivo.
C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation
Authors: Harris Samantha P. , Belknap Betty , Van Sciver Robert E. , White Howard D. , Galkin Vitold E. 
Published: February 2016

Significance
Cardiac myosin binding protein C (cMyBP-C) is a regulatory protein that modulates the strength and speed of heart contractions. cMyBP-C is required for normal heart function, and mutations in the gene encoding cMyBP-C are the most common cause of hypertrophic cardiomyopathy, a disease affecting an estimated 1 in 500 people. Here we used an integrated structure–function approach to determine how C0 and C1, the first two domains of cMyBP-C, interact with muscle thin filaments (composed of F-actin and regulatory proteins) to influence their ability to interact with myosin, the force-generating protein of muscle. Results reveal that C0 and C1 both bind to actin at multiple, distinct sites and that C0 and C1 exert different effects on heart muscle contraction.
Decision-related perturbations of decision-irrelevant eye movements
Authors: Joo Sung Jun , Katz Leor N. , Huk Alexander C. 
Published: February 2016

Significance
Studies using limb movements to probe cognitive states have suggested an interactive model of cognition and motor action. Despite ample evidence showing that the neural activity in oculomotor brain circuits is correlated with the formation of decisions about where to move the eyes, it is not known whether there are interactions between such decision-related activity and decision-irrelevant oculomotor processing. By probing the oculomotor system with a decision-irrelevant saccadic eye movement during decision formation, we found that saccade metrics are affected by the strength and direction of motion evidence. Our results suggest that decision signals continuously flow into the oculomotor system during decision making, and further extend the interactive model of cognition and action into the oculomotor system.
Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8
+
T-cell axis
Authors: Brackett Craig M. , Kojouharov Bojidar , Veith Jean , Greene Kellee F. , Burdelya Lyudmila G. , Gollnick Sandra O. , Abrams Scott I. , Gudkov Andrei V. 
Published: February 2016

Significance
Innate immune modulators can generate a potent antitumor T-cell response and are thus a desirable approach to immunotherapy. However, their use is limited by the risk of induction of acute inflammation. In this regard, bacterial flagellin is unique among other innate immune modulators because of a significantly safer cytokine profile induced upon activation by its target, Toll-like receptor 5 (TLR5). We show here that systemic administration of entolimod, a pharmacologically optimized flagellin derivative, induces a cascade of cell–cell signaling resulting in mobilization to the liver of various components of innate and adaptive immunity, followed by suppression of liver metastases and development of long-term antitumor immune memory. Thus, TLR5 agonists can be considered as an organ-specific immunotherapy for the treatment and prevention of metastases.
Redundant function of DNA ligase 1 and 3 in alternative end-joining during immunoglobulin class switch recombination
Authors: Masani Shahnaz , Han Li , Meek Katheryn , Yu Kefei 
Published: February 2016

Significance
DNA ligase IV (Lig4) is essential for nonhomologous end-joining (NHEJ), the major pathway for repairing DNA double-strand breaks in mammalian cells. An ill-defined alternative end-joining (A-EJ) pathway can also mediate end-joining in cells deficient in NHEJ, although A-EJ is kinetically slower and less accurate than NHEJ. Here, we report that either Lig1 or Lig3 can mediate alternative end-joining in Lig4 knockout cells. Cells having only one ligase (Lig1 or nuclear Lig3) are capable of DNA replication and DNA repair after exposure to a wide range of genotoxins. These results demonstrate the remarkable (and unexpected) plasticity of DNA ligases in mammalian cells.