bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of mechanistically distinct inhibitors of HIV-1 reverse transcriptase through fragment screening
Authors: La Jennifer , Latham Catherine F. , Tinetti Ricky N. , Johnson Adam , Tyssen David , Huber Kelly D. , Sluis-Cremer Nicolas , Simpson Jamie S. , Headey Stephen J. , Chalmers David K. , Tachedjian Gilda 
Published: May 2015

Significance
In this study, we demonstrate a strategy using a combination of NMR-based binding and functional assays to screen a library of low-molecular-weight compounds known as fragments to identify new drug precursors that target HIV-1 reverse transcriptase (RT). Using this approach, we have discovered three fragments that inhibit HIV-1 RT and clinically relevant drug-resistant mutants. Enzyme assays demonstrate that at least two of these inhibitors are mechanistically distinct from HIV-1 RT drugs used clinically. One of these fragments inhibits HIV-1 replication in cell-based assays. The small size, hydrophilic nature, and excellent ligand efficiency of these fragments make them good starting points for the development of new classes of RT drugs for HIV-1 prevention or treatment.
Imperfect drug penetration leads to spatial monotherapy and rapid evolution of multidrug resistance
Authors: Moreno-Gamez Stefany , Hill Alison L. , Rosenbloom Daniel I. S. , Petrov Dmitri A. , Nowak Martin A. , Pennings Pleuni S. 
Published: May 2015

SignificanceThe evolution of drug resistance is a major health threat. In chronic infections with rapidly mutating pathogens—including HIV, tuberculosis, and hepatitis B and C viruses—multidrug resistance can cause even aggressive combination drug treatment to fail. Oftentimes, individual drugs within a combination do not penetrate equally to all infected regions of the body. Here we present a mathematical model suggesting that this imperfect penetration can dramatically increase the chance of treatment failure by creating regions where only one drug from a combination reaches a therapeutic concentration. The resulting single-drug compartments allow the pathogen to evolve resistance to each drug sequentially, rapidly causing multidrug resistance. More broadly, our model provides a quantitative framework for reasoning about trade-offs between aggressive and moderate drug therapies.
Using homology relations within a database markedly boosts protein sequence similarity search
Authors: Tong Jing , Sadreyev Ruslan I. , Pei Jimin , Kinch Lisa N. , Grishin Nick V. 
Published: May 2015

Significance
In the field of protein structure prediction, identifying homology to known folds offers the most successful and practically useful strategy to provide protein spatial structure models. For protein sequence targets without closely related structures, even very distant homologs can provide reasonable templates for modeling. Despite significant progress in the field, remote sequence similarity search is far from perfection and fresh ideas are needed to extend detection limits. In computer science, the concept of utilizing internal relations within a database to improve similarity search was key to the success of search engines such as Google. Here, we show that similar consideration of the homology network within a protein database of structure templates can dramatically improve the accuracy of homology search.
Assessing the role of static length scales behind glassy dynamics in polydisperse hard disks
Authors: Russo John , Tanaka Hajime 
Published: May 2015

Significance
The origin of dynamical slowing down toward glass transition is a fundamental unsolved problem in condensed matter physics. A crucial question is whether this slowing down has a structural origin. Recently, a method to detect hidden order within the fluid was proposed, based on the idea that freezing a fraction of the particles in a system causes a transition akin to glass transition. Here, we show that a glass former, polydisperse hard disks, has a strong increase of structural order, well correlated with slow dynamics, which goes undetected by the pinning method. This casts doubt on the order-agnostic qualities of the pinning length scale and keeps static length scales in the race for plausible explanations of the glass transition problem.
Biotic interactions mediate soil microbial feedbacks to climate change
Authors: Crowther Thomas W. , Thomas Stephen M. , Maynard Daniel S. , Baldrian Petr , Covey Kristofer , Frey Serita D. , van Diepen Linda T. A. , Bradford Mark A. 
Published: May 2015

Significance
The land carbon–climate feedback is incorporated into the earth system models that inform current Intergovernmental Panel on Climate Change projections. This feedback is driven by increases in soil microbial decomposition and carbon loss from soils under global change scenarios. The present study shows how trophic interactions in soil can mediate microbial responses to combined global change factors. As soil nitrogen deposition increases, the limitations on fungal growth are alleviated, stimulating total enzyme activity and decomposition rates. However, this process also affects the grazing activity of soil invertebrates. In the absence of nutrient limitation, top-down control by grazing isopods emerges as a dominant control, limiting any increases in fungal activity and carbon cycling.
Uncoupling protein 1 binds one nucleotide per monomer and is stabilized by tightly bound cardiolipin
Authors: Lee Yang , Willers Chrissie , Kunji Edmund R. S. , Crichton Paul G. 
Published: May 2015

Significance
Uncoupling protein 1 (UCP1) is a mitochondrial carrier protein responsible for thermogenesis in brown adipose tissue, and a putative therapeutic target for the treatment of obesity and related diseases. It is widely accepted that the protein is dimeric and regulated by binding one nucleotide per dimer, and unlike other mitochondrial carriers, functions independently of the lipid cardiolipin. Here, we have developed novel methods to purify UCP1 from native sources, and demonstrate that the protein is in fact monomeric, binding nucleotide in a 1:1 stoichiometry. Each protein also binds three cardiolipin molecules, which confer stability. These findings put in place the true composition of UCP1, overturning a paradigm, which is crucial to resolve the controversial mechanism of this important membrane protein.
Selfish third parties act as peacemakers by transforming conflicts and promoting cooperation
Authors: Halevy Nir , Halali Eliran 
Published: May 2015

Significance
Six experiments show that the mere possibility of third-party intervention increases cooperation in interpersonal and intergroup interactions, that third parties often fail to increase collective gains by withholding intervention, and that reducing the risk associated with intervention significantly increases peacemaking by self-interested third parties. These findings highlight the interdependence between disputants and third parties, thereby complementing existing models that solely focus on unidirectional influence of third parties on disputants. These findings underscore the role self-interest plays in shaping third parties’ intervention decisions and demonstrate that selfish third parties can promote peaceful conflict resolution by literally changing the game disputants are playing. Overall, we explain why, how, and when self-interested third parties intervene in others’ conflicts, to everyone’s benefit.
Determining protein structures by combining semireliable data with atomistic physical models by Bayesian inference
Authors: MacCallum Justin L. , Perez Alberto , Dill Ken A. 
Published: May 2015

Significance
Modeling Employing Limited Data (MELD) is a method of integrative structural biology. It serves to determine protein structures by a Bayesian approach combining physical models with experimental data that are only semireliable, by virtue of being either too sparse, too ambiguous, or too uncertain. For eight proteins for which both the correct native structure and semireliable data were available, MELD gives excellent structures.
A survey of human brain transcriptome diversity at the single cell level
Authors: Darmanis Spyros , Sloan Steven A. , Zhang Ye , Enge Martin , Caneda Christine , Shuer Lawrence M. , Hayden Gephart Melanie G. , Barres Ben A. , Quake Stephen R. 
Published: May 2015

Significance
The brain comprises an immense number of cells and cellular connections. We describe the first, to our knowledge, single cell whole transcriptome analysis of human adult cortical samples. We have established an experimental and analytical framework with which the complexity of the human brain can be dissected on the single cell level. Using this approach, we were able to identify all major cell types of the brain and characterize subtypes of neuronal cells. We observed changes in neurons from early developmental to late differentiated stages in the adult. We found a subset of adult neurons which express major histocompatibility complex class I genes and thus are not immune privileged.
Exploring the potential impact of an expanded genetic code on protein function
Authors: Xiao Han , Nasertorabi Fariborz , Choi Sei-hyun , Han Gye Won , Reed Sean A. , Stevens Raymond C. , Schultz Peter G. 
Published: May 2015

Significance
We describe a general strategy that begins to allow us to address the question of whether an expanded genetic code provides an evolutionary advantage to an organism. A large library of β-lactamase variants with distinct noncanonical amino acids substituted randomly at single sites throughout the protein was generated and then subjected to an antibiotic growth-based screen to identify mutants with enhanced catalytic activity. We show that a unique noncanonical mutation in the enzyme β-lactamase significantly increases catalytic activity by unexpected mechanisms. These effects cannot be recapitulated by other canonical amino acids at this site, suggesting that an expanded set of building blocks beyond the canonical 20 may offer unique solutions to organisms in the evolution of new functions.
Selection and characterization of Euglena anabaena var. minor as a new candidate Euglena species for industrial application
Authors: Suzuki Kengo , Mitra Sharbanee , Iwata Osamu , Ishikawa Takahiro , Kato Sueo , Yamada Koji 
Published: May 2015

Abstract
Euglena gracilis is a microalgae used as a model organism. Recently, mass cultivation of this species has been achieved for industrial applications. The genus Euglena includes more than 200 species that share common useful features, but the potential industrial applications of other Euglena species have not been evaluated. Thus, we conducted a pilot screening study to identify other species that proliferate at a sufficiently rapid rate to be used for mass cultivation; we found that Euglena anabaena var. minor had a rapid growth rate. In addition, its cells accumulated more than 40% weight of carbohydrate, most of which is considered to be a euglenoid specific type of beta-1-3-glucan, paramylon. Carbohydrate is stored in E. anabaena var. minor cells during normal culture, whereas E. gracilis requires nitrogen limitation to facilitate paramylon accumulation. These results suggest the potential industrial application of E. anabaena var. minor.
Identification of matrix metalloproteinase inhibitors by chemical arrays
Authors: Kawatani Makoto , Fukushima Yukako , Kondoh Yasumitsu , Honda Kaori , Sekine Tomomi , Yamaguchi Yoshiki , Taniguchi Naoyuki , Osada Hiroyuki 
Published: May 2015

AbstractMatrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade many extracellular matrix components and that have been implicated in the pathogenesis of various human diseases including cancer metastasis. Here, we screened MMP-9 inhibitors using photo-cross-linked chemical arrays, which can detect small-molecule ligand–protein interactions on a chip in a high-throughput manner. The array slides were probed sequentially with His-MMP-9, anti-His antibody, and a Cy5-labeled secondary antibody and then scanned with a microarray scanner. We obtained 27 hits among 24,275 compounds from the NPDepo library; 2 of the identified compounds (isoxazole compound 1 and naphthofluorescein) inhibited MMP-9 enzyme activity in vitro. We further explored 17 analogs of 1 and found that compound 18 had the strongest inhibitory activity. Compound 18 also inhibited other MMPs, including MMP-2, MMP-12, and MMP-13 and significantly inhibited cell migration in human fibrosarcoma HT1080 cells. These results suggest that 18 is a broad-spectrum MMP inhibitor.
Seeing Feeling: Queer Voyeurism in
À la recherche du temps perdu
Authors: Soldin Adeline 
Published: May 2015

Abstract

This article examines the constitutive pattern created by the Proustian narrator's repeated performance as a peeping Tom. Drawing on psychoanalysis, queer studies, visual culture, and affect and performance theories, this study expands the repertoire that has heretofore been limited to homosexual primal scenes by focusing on queer elements linking a number of voyeuristic moments in
À la recherche du temps perdu
. As unconventional primal scenes, these passages serve to break down heterosexual/homosexual and man/woman dichotomies through the inclusion of multiple participants of all genders and sexualities. That is, the repetition and authorization of such scenarios function as a performative discourse that advocates for queer sexualities in the novel. In addition to analysis dedicated to the implications of these erotic performances, significant attention is given to the protagonist's role as voyeur. By highlighting the pleasure that the narrator experiences as a peeping Tom, this article argues that, rather than endeavour to label the Proustian narrator as homosexual or heterosexual, a more productive approach would be to avoid such strict binaries and focus more on his erotic experiences; namely, to view his voyeurism of men and women of various sexual leanings as representative of his sexual preferences.
Contribution of Esophagram to the Evaluation of Complicated Pediatric Eosinophilic Esophagitis
Authors: Menard‐Katcher Calies , Swerdlow Mathew P. , Mehta Pooja , Furuta Glenn T. , Fenton Laura Z. 
Published: May 2015

ABSTRACTObjectives:In contrast to peptic strictures, clinically significant strictures in patients with eosinophilic esophagitis (EoE) may be subtle and go unrecognized at the time of endoscopy. We aimed to identify how often stricture was identified by endoscopy as compared with contrast esophagram.Methods:We retrospectively reviewed esophagram and endoscopy examinations of all of the patients with EoE with esophageal stricture seen at a tertiary care pediatric hospital over a 6‐year period who had both procedures completed within a 3‐month time frame. Medical charts were reviewed for clinicopathologic information including age, duration of symptoms, histology, and treatment.Results:Twenty‐two children with EoE‐associated stricture completed both esophagram and endoscopic assessments. Esophageal strictures were identified by esophagram, and not endoscopy, in 55% of these children. Patients with stricture identified at esophagram alone had a shorter duration of symptoms (2.1 years duration vs 5.4 years duration, P = 0.03) than the group identified by endoscopy. Preoperative radiographic identification of a stricture was associated with dilation more often being performed.Conclusions:Esophagram is a valuable test to assess esophageal anatomy in children with complicated EoE. Esophagram may be able to detect subtle fibrostenosis earlier in the natural history of the disease than endoscopy.
Electrolyte and Mineral Homeostasis After Optimizing Early Macronutrient Intakes in VLBW Infants on Parenteral Nutrition
Authors: Senterre Thibault , Abu Zahirah Ibrahim , Pieltain Catherine , de Halleux Virginie , Rigo Jacques 
Published: May 2015

ABSTRACTObjectives:The aim of the present study was to evaluate electrolyte and mineral homeostasis in very‐low‐birth‐weight (VLBW) infants who received high protein and energy intakes with a unique standardized parenteral nutrition solution containing electrolytes and minerals from birth onward.Methods:Prospective cohort study in 102 infants with birth weight <1250 g. The evolution of plasma biochemical parameters was described during the first 2 weeks of life.Results:During the first 3 days of life, mean parenteral intakes were 51 ± 8 kcal · kg−1 · day−1 with 2.7 ± 0.4 g · kg−1 · day−1 of protein, 1.1 ± 0.2 mmol · kg−1 · day−1 of sodium and potassium, and 1.3 ± 0.2 mmol · kg−1 · day−1 of calcium and phosphorus. Afterwards, most nutritional intakes (parenteral and enteral) met growth requirements. No infant developed a hyperkalemia >7 mmol/L, and a hypernatremia >150 mmol/L occurred only in 15.7% of the infants. In contrast, hyponatremia <130 mmol/L and hypokalemia <3 mmol/L occurred in 30.4% and 8.8% of the infants, respectively. The initial neonatal metabolic acidosis rapidly resolved in most infants and only 2.0% developed a base deficit >10 mmol/L after day 3 of life. Early hypocalcemia <1.8 mmol/L occurred in 13.7% of the infants. In contrast, hypophosphatemia <1.6 mmol/L occurred in 37.3% and hypercalcemia >2.8 mmol/L occurred in 12.7% of the infants.Conclusions:Increasing early protein and energy intakes in VLBW infants in the first week of life improves electrolyte homeostasis. It also increases the phosphorus requirements with a calcium‐to‐phosphorus ratio ≤1.0 (mmol/mmol) and the potassium and sodium requirements to avoid the development of a refeeding‐like syndrome. These data suggest that the parenteral nutrition guidelines for VLBW infants for the first week of life need to be revised.
Effects of Maternal Ω‐3 Supplementation on Fatty Acids and on Visual and Cognitive Development
Authors: Hurtado Jose A. , Iznaola Carmen , Peña Manuela , Ruíz Josefa , Peña‐Quintana Luis , Kajarabille Naroa , Rodriguez‐Santana Yessica , Sanjurjo Pablo , Aldámiz‐Echevarría Luis , Ochoa Julio , Lara‐Villoslada Federico ,   NUGELA Group
Published: May 2015

ABSTRACTObjectives:The aim of the present study was to elucidate whether a dairy drink enriched with ω‐3 long‐chain polyunsaturated fatty acid (LC‐PUFA) could have an impact on the lipid profile of the mother and the newborn, and also whether this intervention could affect the newborns’ visual and cognitive development.Methods:A total of 110 pregnant women were randomly assigned to one of the following intervention groups: control group (n = 54), taking 400 mL/day of the control dairy drink, and supplemented group (fish oil [FO]) (n = 56), taking 400 mL/day of the fish oil–enriched dairy drink (including ~400 mg eicosapentaenoic acid–docosahexaenoic acid [DHA]/day). During the study, the mothers’ diets were supervised by a nutritionist to encourage compliance with present recommendations of FA intake. Blood fatty acid profiles were determined in the mother's (at enrollment, at delivery, and at 2.5 and 4 months) and newborn (at delivery and at 2.5 months) placenta and breast milk (colostrum and at 1, 2, and 4 months). Pattern reversal visual evoked potentials (VEPs) (at 2.5 and 7.5 months) and Bayley test (at 12 months) were recorded.Results:DHA percentage was higher in plasma, erythrocyte membranes, and breast milk samples from the FO group. The ratio of nervonic acid was also higher in plasma and erythrocyte lipids of the mother and newborn's blood samples from the FO group. No differences were observed in the Bayley test. No differences were observed in VEPs between both groups. We observed a shorter latency, however, in the lower visual angle (7.5′) in the boys of the supplemented group.Conclusions:Omega‐3 LC‐PUFA dietary supplement during pregnancy and lactation influenced the mother and newborn's fatty acid profile and nervonic acid content but did not show effects on visual and cognitive/psychomotor development.
Short Sleep Duration Is Related to Emerging Cardiovascular Risk Factors in Obese Children
Authors: Navarro‐Solera María , Carrasco‐Luna Joaquín , Pin‐Arboledas Gonzalo , González‐Carrascosa Rebeca , Soriano José M. , Codoñer‐Franch Pilar 
Published: May 2015

ABSTRACTObjective:The aim of the present study was to evaluate the influence of sleep duration on cardiovascular risk factors in obese children.Methods:Cross‐sectional analysis of 90 obese children ages 7 to 16 years. Anthropometric and clinical evaluation with specification of dietary and lifestyle habits was carried out during an office visit. Sleep duration was evaluated by the BEARS (B = bedtime issues, E = excessive daytime sleepiness, A = night awakening, R = regularity and duration of sleep, S = snoring) questionnaire on children's sleep characteristics. Sleep time adequacy by age was assessed according to the criteria of the National Sleep Foundation. Biochemical blood variables indicative of metabolic risk (glucose, lipid profile, and insulin) were obtained. Emergent new factors of metabolic risk, including high‐sensitive C‐reactive protein, γ‐glutamyltranspeptidase, homocysteine, retinol‐binding protein 4 (RBP4), thyroid‐stimulating hormone (TSH), inflammatory markers, and the adipokines leptin, adiponectin, and ghrelin were also evaluated. The relations between the duration of sleep and these variables were analyzed by general lineal model analysis. Significant variables were introduced in logistic regression analysis to determine the odds ratio (OR) and 95% confidence interval (CI) of cardiometabolic factors with respect to sleep.Results:Children who slept for short duration were significantly more at risk of severe central obesity. In the regression model, the mean arterial pressure (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02–1.17, P = 0.008), homocysteine (OR 1.41, 95% CI 1.08–1.84, P = 0.013), RBP4 (OR 1.78, 95% CI 1.15–2.78, P = 0.010), and TSH (OR 2.01, 95% CI 1.21–3.34, P = 0.007) remain as significant independent predictors related to short sleep duration. We did not find any association between sleep duration and inflammatory markers or adipokines.Conclusions:Short sleep duration increases the severity of obesity and is related to cardiovascular risk factors in children.
Statistical correlation properties of the SHIBOR interbank lending market
Authors: Luo Yong , Xiong Jie , Dong Lie Gang , Tang Yong 
Published: May 2015

Purpose
– The purpose of this paper is to investigate the statistical correlation properties of the Shanghai Interbank Offered Rate (SHIBOR) interbank lending market.

Design/methodology/approach
– The authors apply methods of correlation analysis, random matrix theory (RMT) and minimum spanning tree (MST) to investigate the correlation properties of Chinese interbank lending market and analyze how the SHIBOR panel banks behave in different market periods.

Findings
– First, the largest eigenvalue λ
1 is the index to describe the market mode of the whole market when all banks behavior collectively and λ
1/N is a good estimator of the average correlation <C> of the correlation matrix. Second, notably, the authors find the “market mode” is weakened in two crises periods of 2008 stock market crash and 2009 Global Financial Crisis. This is significantly different from other market where the “market mode” is normally strengthened in crises periods. Third, the authors subtract the contribution of λ
1, the second and third eigenvalue, λ
2 and λ
3, will fall outside of the predicted interval. And both λ
2 and λ
3 are getting times larger in the crises periods than in “Non-Crisis” period. Fourth, and in the MST analysis, the authors find again that the average distances of the MST are the times larger in crises periods than in “Non-Crisis” period and the second largest eigenvalue is a good estimator of the average distance of the MST.

Originality/value
– According to the best knowledge, this paper is the first work on the study of the statistical properties of an interbank lending market using quotation level data of panel banks, which allows us to analyze the properties of the interest rate formation and how all panel banks behavior in different periods. This work is also the first study on the SHIBOR market using econophysics methods of correlation analysis, RMT and MST.