bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative proteomics and phosphoproteomics on serial tumor biopsies from a sorafenib-treated HCC patient
Authors: Dazert Eva , Colombi Marco , Boldanova Tujana , Moes Suzette , Adametz David , Quagliata Luca , Roth Volker , Terracciano Luigi , Heim Markus H. , Jenoe Paul , Hall Michael N. 
Published: February 2016

Significance
Elucidation of evasive resistance to targeted therapies is a major challenge in cancer research. As a proof-of-concept study, we describe quantitative proteomics and phosphoproteomics on serial tumor biopsies from a sorafenib-treated hepatocellular carcinoma (HCC) patient. This approach reveals signaling pathway activity in a tumor and how it evades therapy. The described method will allow precision medicine based on phenotypic data. In particular, application of the method to a patient cohort will potentially identify new biomarkers, drug targets, and signaling pathways that mediate evasive resistance.
Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling
Authors: Li Songshan , Yang Chao , Zhang Li , Gao Xin , Wang Xuejie , Liu Wen , Wang Yuqi , Jiang Songshan , Wong Yung Hou , Zhang Yifeng , Liu Kai 
Published: February 2016

Significance
Damage to axons in the CNS typically results in permanent functional deficits. Boosting intrinsic programs such as mammalian target of rapamycin (mTOR) signaling can dramatically augment the axon regenerative capacity of injured neurons. Because certain types of neurons respond to axotomy by maintaining their mTOR activation, we hypothesized that it might be helpful to use this property to promote axon regeneration. We found that the light-responsive G protein-coupled receptor (GPCR) melanopsin could promote axonal regeneration after optic nerve crush by activating mTOR. We also showed that light, Gq/11 signaling, and neuronal activity contribute to the mechanism that underlies this effect. Activating Gq signaling through a chemogenetic approach promoted axon regeneration. Thus, we provided evidence for modulating neuronal activity through GPCR signaling in regulating intrinsic axon growth capacity.
Gene therapy blockade of dorsal striatal p11 improves motor function and dyskinesia in parkinsonian mice
Authors: Marongiu Roberta , Arango-Lievano Margarita , Francardo Veronica , Morgenstern Peter , Zhang Xiaoqun , Cenci M. Angela , Svenningsson Per , Greengard Paul , Kaplitt Michael G. 
Published: February 2016

Significance
Medications for Parkinson’s disease (PD) are designed to replace lost dopamine. Although effective, they often cause abnormal involuntary movements (AIMs), also called dyskinesias, which can be difficult to resolve without worsening PD symptoms. We report that p11, a small protein necessary for neurotransmitter receptor function, is critical to dopamine responses in a mouse PD model. Blocking p11 production in the dorsal striatum, a brain region that responds to dopamine and regulates movement, can improve forced movements and normalize spontaneous movements in parkinsonian mice while dramatically reducing AIMs after dopamine replacement therapy. Our data identify a new target for therapeutic development to both improve symptoms and reduce drug-related side effects in human PD.
X-ray structure of the MMTV-A nucleosome core
Authors: Frouws Timothy D. , Duda Sylwia C. , Richmond Timothy J. 
Published: February 2016

Significance
The DNA in eukaryotic organisms is packaged in nucleosomes, the fundamental repeating unit of chromatin. The ability of essential transcription regulatory factors to bind genomic recognition sites is contingent on the sequence-dependent conformation of DNA bound in nucleosomes. Our knowledge of the structure of nucleosome DNA is severely limited. The crystal structure of the nucleosome core particle reported here incorporating mouse mammary tumor virus promoter DNA provides new insight into the sequence-dependent structure of DNA as it exists in chromatin.
An ecocultural model predicts Neanderthal extinction through competition with modern humans
Authors: Gilpin William , Feldman Marcus W. , Aoki Kenichi 
Published: February 2016

Significance
Ecocultural niche modeling and radiocarbon dating suggest a causal role for interspecific competition in the extinction of Neanderthals. Most archaeologists argue that the advantage to modern humans lay in a higher culture level (a sizable minority dispute this view). Competition between the two species may have occurred when a modern human propagule entered a region occupied by a larger Neanderthal population. We present a model for this replacement, stressing the importance of the founder effect. Our findings shed light on the disappearance of the Neanderthals, showing that endogenous factors such as relative culture level, rather than such extrinsic factors as epidemics or climate change, could have caused the eventual exclusion of a comparatively larger population by an initially smaller one.
Multiscale model of light harvesting by photosystem II in plants
Authors: Amarnath Kapil , Bennett Doran I. G. , Schneider Anna R. , Fleming Graham R. 
Published: February 2016

Significance
Plants thrive in natural sunlight in part because photosystem II (PSII) flexibly captures sunlight. PSII is composed of pigment–protein complexes that densely pack the thylakoid membrane in chloroplasts. We explain the mechanisms underlying the high quantum efficiency of PSII light harvesting in ideal conditions using a quantum mechanical model of excitation energy transport in the membrane. We show that the diffusion length of excitation energy determines the way in which modifications to the membrane affect PSII’s, and ultimately a plant’s, photosynthetic efficiency. The model could be useful for developing artificial light-harvesting materials that are robust to the fluctuations inherent in natural sunlight and rationally engineered crops that achieve higher yields in adverse environments.
S1PR1-mediated IFNAR1 degradation modulates plasmacytoid dendritic cell interferon-α autoamplification
Authors: Teijaro John R. , Studer Sean , Leaf Nora , Kiosses William B. , Nguyen Nhan , Matsuki Kosuke , Negishi Hideo , Taniguchi Tadatsugu , Oldstone Michael B. A. , Rosen Hugh 
Published: February 2016

Significance
The sphingosine 1-phosphate receptor (S1PR1) is known to act by multiple mechanisms: limiting lymphocyte egress from secondary lymphoid organs, suppressing proinflammatory endothelial cell function, and acting directly on neurons and astrocytes. Here, we report that sphingosine 1-phosphate (S1P)-S1PR1 signaling in plasmacytoid dendritic cells (pDCs) directly inhibits IFN-α autoamplification by induced degradation of the interferon alpha receptor 1 (IFNAR1) receptor and suppression of signal transducer and activator of transcription 1 (STAT1) signaling. An endosomal regulatory interaction of a lipid G-protein coupled receptor (GPCR) and IFNAR1 balances effective and detrimental components of immune responses and provides a previously unidentified pathway that contributes to significant and unexpected efficacy in clinical trials in multiple sclerosis, ulcerative colitis, psoriasis, and likely other diseases with aberrant IFN-α signatures.
Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes
Authors: Romero Maritza J. , Lucas Rudolf , Dou Huijuan , Sridhar Supriya , Czikora Istvan , Mosieri Eby M. , Rick Ferenc G. , Block Norman L. , Sridhar Subbaramiah , Fulton David , Weintraub Neal L. , Bagi Zsolt , Schally Andrew V. 
Published: February 2016

Significance
Growth hormone-releasing hormone (GHRH) antagonist MIA-602 reduces hyperlipidemia in rats with type 1 diabetes (T1D). Elevated triglyceride-rich lipoprotein (TRL) and LDL levels correlate with renal and cardiovascular disease in T1D. Activity of GLP-1 in the intestine to lower TRL, glucagon, and postprandial glucose levels is impaired in T1D subjects. Expression of GHRH receptor was upregulated in the small intestine, involved in chylomicron synthesis in T1D rats. MIA-602 restored GLP-1 actions on hyperlipidemia and hyperglucagonemia in T1D rats and reduced generation of Apo-B48 induced by oleic acid in intestinal epithelial cells in vitro in a GLP-1–dependent manner. MIA-602 significantly improved proteinuria and vasorelaxation capacity in T1D rats. These findings unravel a previously unidentified pathway in T1D mediated by GHRH associated with impaired GLP-1 signaling and hyperlipidemia.
Myotubes derived from human-induced pluripotent stem cells mirror in vivo insulin resistance
Authors: Iovino Salvatore , Burkart Alison M. , Warren Laura , Patti Mary Elizabeth , Kahn C. Ronald 
Published: February 2016

Significance
In this manuscript, we have exploited induced pluripotent stem cells (iPS cells) to generate an in vitro model of human skeletal muscle insulin resistance using cells from patients affected by a monogenic form of insulin resistance (Donohue syndrome/leprechaunism). Following differentiation into skeletal muscle cells, these cells show dramatic defects in insulin signaling, glucose uptake, and glycogen accumulation, as well as insulin-regulated gene expression. To our knowledge, this represents the first use of human iPS cells differentiated into muscle to study diabetes and demonstrates that these cells can robustly reproduce insulin resistance in vitro.
miR-H28 and miR-H29 expressed late in productive infection are exported and restrict HSV-1 replication and spread in recipient cells
Authors: Han Zhiyuan , Liu Xianjie , Chen Xiaoqing , Zhou Xusha , Du Te , Roizman Bernard , Zhou Guoying 
Published: February 2016

Significance
Herpes simplex virus-1 (HSV-1) is transmitted by contact between the infected tissues of a transmitter and those of an uninfected recipient. Effective spread requires that the lesions be small and not repulsive in appearance. For successful transmission HSV must control both its replication and its spread from infected to uninfected cells. Here we report that two HSV microRNAs (miRNAs) made late in productive infection are exported in exosomes. Ectopic expression in transfected cells before infection reduces the synthesis of viral gene products and the spread from infected to uninfected cells. The miRNAs accumulate in neurons after latent virus is induced to reactivate. The miRNAs conform to the expectations of gene products that control viral replication and spread.
Global informatics and physical property selection in protein sequences
Authors: Scheraga Harold A. , Rackovsky S. 
Published: February 2016

Significance
Many bioinformatic investigations of protein sequence–structure relationships are based on preselected sets of amino acid physical properties. We investigate the extent to which such preselection is justified on information–theoretical grounds. It is shown that neither sequence-dependent nor -averaged properties can be identified as informatically negligible and that no physical properties can be identified that carry sufficient information about other variables to act as surrogates. This result implies that knowledge-based studies of proteins must be based on complete, nonredundant physical property sets.
Robust and Defensible Mark–Recapture Methodologies for Salmonid Escapement: Modernizing the Use of Data and Resources
Authors: Vélez-Espino L. Antonio , Irvine James R. , Winther Ivan , Dunlop Roger , Mullins Geoff , Singer Kristin , Trouton Nicole 
Published: February 2016

Abstract
Estimates of population size, required for most ecological investigations, are often achieved by mark–recapture experiments, frequently by applying pooled or stratified Petersen estimators. Unfortunately, the closure assumption required by Petersen estimators is frequently violated in the estimation of salmonid escapement, even though the consequences of this violation have been known for decades. We illustrate how biologists and analysts can and should make better use of statistical, mathematical, and computational advances in their analysis of mark–recapture data. Modern, easily applied approaches address and minimize the effects of violations to the model assumptions on which abundance estimators are based. Using examples from research estimating the numbers of Chinook Salmon Oncorhynchus tshawytscha escaping fisheries to spawn, this study demonstrates and provides evidence in support of the use of a robust and defensible approach to salmonid escapement estimation based on the analysis of individual encounter histories. The main attributes of the approach include (1) testing for demographic closure, (2) allowing different hypotheses about the demographic attributes and capture history of the studied population to be expressed within a model selection framework, encompassing suites of open- or closed-population approaches, and (3) optimizing the use of information by embracing the opportunities that mark–recapture experiments generate to increase our knowledge of salmonid ecology and hence improve both future study designs and management decisions. This study also demonstrates that discrepancies (positive) in abundance estimates produced with the Petersen estimator relative to those produced by the “best models” from robust estimators are inversely proportional to sampling rates.
Received May 20, 2015; accepted October 22, 2015
Public Incentives, Private Investment, and Outlooks for Hybrid Rice in Bangladesh and India
Authors: Spielman David J. , Ward Patrick S. , Kolady Deepthi E. , Ar‐Rashid Harun 
Published: February 2016

AbstractThe governments of Bangladesh and India have set impressive targets to expand hybrid rice cultivation as part of their national food security strategies for the next decade. Although hybrid rice offers significant yield improvements over varietal rice, adoption by farmers remains low and unstable. This paper analyzes the technical challenges, market opportunities, and policy constraints associated with hybrid rice in both countries. It argues that while many of the technical constraints can be addressed through continued investment in breeding, significant challenges remain relating to product development, marketing, and economic policy. Solutions require new insight into relationships between industry structure, business strategies, and public policy incentives.
Miltefosine for Mucosal and Complicated Cutaneous Old World Leishmaniasis: A Case Series and Review of the Literature
Authors: Mosimann Vincent , Blazek Claudia , Grob Heini , Chaney Matthew , Neumayr Andreas , Blum Johannes 
Published: February 2016

Abstract
Complicated Old World cutaneous leishmaniasis (OWCL) and Old World mucosal leishmaniasis (OWML) constitute an indication for systemic treatment. To date, there no controlled clinical studies that compare treatment options for these diseases. We compiled a case series of 24 cases successfully treated with miltefosine. We conclude that oral miltefosine is an effective treatment option for both OWCL and OWML.
Suzaku observation of a high-entropy cluster Abell 548W
Authors: Nakazawa Kazuhiro , Kato Yuichi , Gu Liyi , Kawaharada Madoka , Takizawa Motokazu , Fujita Yutaka , Makishima Kazuo 
Published: February 2016

Abstract
Abell 548W, one of the galaxy clusters located in the Abell 548 region, has about an order of magnitude lower X-ray luminosity compared to ordinal clusters in view of the well-known intracluster medium (ICM) temperature vs. X-ray luminosity (kT–LX) relation. The cluster hosts a pair of diffuse radio sources to the northwest and north, both about 10′ apart from the cluster center. They are candidate radio relics, frequently associated with merging clusters. A Suzaku deep observation with exposure of 84.4 ks was performed to search for signatures of merging in this cluster. The XIS detectors successfully detected the ICM emission out to 16′ from the cluster center. The temperature is ∼ 3.6 keV around its center, and ∼ 2 keV at the outermost regions. The hot region (∼ 6 keV) beside the relic candidates shifted to the cluster center reported by XMM-Newton was not seen in the Suzaku data, although its temperature of 3.6 keV itself is higher than the average temperature of 2.5 keV around the radio sources. In addition, the signature of a cool (kT ∼ 0.9 keV) component was found around the northwest source. A marginal temperature jump at its outer edge was also found, consistent with the canonical idea of the shock acceleration origin of the radio relics. The cluster has among the highest central entropy of ∼ 400 keV cm2 and is one of the so-called low surface brightness clusters. Taking into account the fact that its shape itself is relatively circular and smooth and also that its temperature structure is nearly flat, possible scenarios for merging are discussed.
Patient physiological status during emergency care and rapid response team or cardiac arrest team activation during early hospital admission
Authors: Considine Julie , Jones Daryl , Pilcher David , Currey Judy 
Published: February 2016

Objectives
The objective of this study was to examine the relationship between rapid response team (RRT) or cardiac arrest team (CAT) activation within 72 h of emergency admission and (i) physiological status in the emergency department (ED) and (ii) risk for ICU admission and in-hospital mortality.

Methods
A retrospective matched cohort study was conducted in three hospitals in Melbourne, Australia. The exposed cohort (n=660) included randomly selected adults admitted to the medical or surgical ward through the ED who had RRT or CAT activation within 72 h of admission. Unexposed matched controls (n=1320) did not have RRT or CAT activation.

Results
The exposed cohort was more likely to have physiological abnormalities fulfilling hospital RRT activation criteria during ED care (36.7 vs. 23.8%, P<0.001). After adjusting for confounders, tachypnoea (adjusted odds ratio=1.92, 95% confidence interval: 1.38–2.67) or hypotension (AOR=1.43, 95% confidence interval: 1.00–2.03), fulfilling RRT activation criteria during ED care, was associated with RRT or CAT activation within 72 h of admission. The exposed cohort had more in-hospital deaths (16.5 vs. 3.6%, P<0.001), more unexpected in-hospital deaths (2.05 vs. 0.2%, P<0.001), more ICU admissions (11.8 vs. 0.7%, P<0.001) and longer lengths of hospital stay (median=8 vs. 5 days, P<0.001).

Conclusion
CAT/RRT activations within 72 h of emergency admission are associated with higher mortality and increased length of stay. Factors associated with CAT/RRT activation in the wards are often identifiable when patients are in the ED. Further studies are required to determine whether early identification and intervention in patients at risk for RRT or CAT activation can improve their eventual outcomes.
Paediatric Crohn Disease
Authors: De Greef Elisabeth , Hoffman Ilse , Smets Francoise , Van Biervliet Stephanie , Bontems Patrick , Hauser Bruno , Paquot Isabelle , Alliet Philippe , Arts Wim , Dewit Olivier , De Vos Martine , Baert Filip , Bossuyt Peter , Rahier Jean‐Francois , Franchimont Denis , Vermeire Severine , Fontaine Fernand , Louis Edouard , Coche J.C. , Veereman Gigi ,   IBD working group of BESPGHAN, BIRD
Published: February 2016

ABSTRACTObjective:The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth.Methods:Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow‐up.Results:At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals’ initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from −0.97 (range −5.5–2.1) to 0.11 (range −3.4–2) and median height z score from −0.15 (range −3.4–1.6) to 0.12 (range −2.3–2.3) at M36. None of the variables mentioned above influenced growth over time.Conclusions:Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36.
Plasma Cytokeratin‐18 Level As a Novel Biomarker for Liver Fibrosis in Children With Nonalcoholic Fatty Liver Disease
Authors: Mandelia Chetan , Collyer Elizabeth , Mansoor Sana , Lopez Rocio , Lappe Sara , Nobili Valerio , Alkhouri Naim 
Published: February 2016

ABSTRACTObjectives:Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the obesity epidemic and affects approximately 10% of children in the US. The presence of hepatic fibrosis may be the most important factor in determining the prognosis of NAFLD. Noninvasive methods to identify the presence of fibrosis in children with NAFLD are greatly needed. Hepatocyte apoptosis activates hepatic stellate cells and plays a central role in fibrosis progression in NAFLD. The aim of the present study was to evaluate the use of plasma cytokeratin‐18 (CK18) fragment levels, a marker of hepatocyte apoptosis, as a noninvasive biomarker in detecting liver fibrosis in pediatric NAFLD.Methods:Consecutive children with biopsy‐proven NAFLD were included and blood samples and anthropometric measurements were collected at the time of the biopsy. NAFLD activity score was calculated (0–8) and fibrosis stage was scored (0–4). We measured plasma CK18 levels using the M30‐Apoptosense enzyme‐linked immunosorbent assay kit.Results:A total of 201 subjects were enrolled in the study. The mean age was 10.7 ± 2.5 years, and 37 % were boys. Sixty‐eight percent of the patients had any fibrosis, with 56% having F1, 6% having F2, and 6 % having F3. CK18 levels were found to be significantly higher in subjects with any fibrosis compared with those without fibrosis (304.6 ± 124.8 vs 210.4 ± 70.9, P < 0.001). CK18 level revealed good accuracy for prediction of any fibrosis (F1‐F3) with AUROC of 0.75. Multivariate logistic regression was performed to assess whether CK18 in combination with another clinical factor could improve accuracy of prediction of fibrosis. Together, CK18 with waist circumference percentile generated an area under the receiver operating characteristics curve of 0.842 for prediction of any fibrosis.Conclusions:CK18 is a promising noninvasive biomarker for fibrosis in NAFLD in children. A fibrosis prediction model that includes CK18 and waist circumference percentile should be validated in other populations.