bluuebunny/crossref_metadata_2025_split huggingface dataset:
β2-Adrenergic receptor-dependent chemokine receptor 2 expression regulates leukocyte recruitment to the heart following acute injury
Authors: Grisanti Laurel A. , Traynham Christopher J. , Repas Ashley A. , Gao Erhe , Koch Walter J. , Tilley Douglas G. 
Published: December 2016

SignificanceThe sympathetic nervous system influences various immune cell functions, in particular via β2-adrenergic receptor (β2AR) signaling. Although immune cell recruitment is critical for cardiac repair following ischemia, the impact of β2AR on this process is unclear. We describe how immune cell-specific β2AR depletion ablates chemokine receptor 2 (CCR2) expression and leukocyte recruitment to the heart postischemia. Reciprocally, β2AR activation increases CCR2 expression and responsiveness in a β-arrestin–dependent manner, and expression of a β-arrestin–biased β2AR in β2AR-depleted immune cells restores CCR2 levels and leukocyte recruitment to the postischemic heart. These results highlight the potential utility of next-generation β-arrestin–biased β2AR ligands to selectively modulate leukocyte responsiveness, and suggest that β-blockers, used commonly in peri/postischemic patients, may impact leukocyte-mediated repair mechanisms.
Phosphorylation of the Mdm2 oncoprotein by the c-Abl tyrosine kinase regulates p53 tumor suppression and the radiosensitivity of mice
Authors: Carr Michael I. , Roderick Justine E. , Zhang Hong , Woda Bruce A. , Kelliher Michelle A. , Jones Stephen N. 
Published: December 2016

Significance
The p53 transcription factor is stabilized in response to cellular stress and regulates the expression of genes involved in numerous biological activities, thereby suppressing tumorigenesis. DNA damage and other stress signals upregulate p53, in part, by freeing p53 from negative regulation imposed by the Mdm2 and MdmX (Mdm4) oncoproteins. MDM proteins are subject to posttranslational modification, and accumulating evidence indicates that phosphorylation of Mdm2 by different stress-activated kinases such as ATM or c-Abl alters Mdm2-p53 signaling and profoundly affects p53 function. A better understanding of the in vivo effects of Mdm2 phosphorylation may facilitate the development of novel therapeutics capable of stimulating p53 antitumor activity or alleviating p53-dependent toxicities in nonmalignant tissues.
Neutrophils induce proangiogenic T cells with a regulatory phenotype in pregnancy
Authors: Nadkarni Suchita , Smith Joanne , Sferruzzi-Perri Amanda N. , Ledwozyw Agata , Kishore Madhav , Haas Robert , Mauro Claudio , Williams David J. , Farsky Sandra H. P. , Marelli-Berg Federica M. , Perretti Mauro 
Published: December 2016

Significance
Neutrophils are typically known as short-lived cells that act as the first line of defense in response to pathogens. However, emerging data indicate that neutrophils have wider implications in the immune system and have a direct influence on the ensuing immune response. Establishment of successful pregnancy requires immune tolerance at the maternal–fetal interface. Aberrations in normal placental development can lead to complications, including preeclampsia. In this study, we examined a role for maternal neutrophils in maintaining normal pregnancy through their interactions with T cells, resulting in a population of T cells that are both regulatory and proangiogenic and are required for normal placental development. Such interactions are absent in patients with preeclampsia, suggesting a potential therapeutic target for pregnancy-related pathologies.
Mutant p53 promotes tumor progression and metastasis by the endoplasmic reticulum UDPase ENTPD5
Authors: Vogiatzi Fotini , Brandt Dominique T. , Schneikert Jean , Fuchs Jeannette , Grikscheit Katharina , Wanzel Michael , Pavlakis Evangelos , Charles Joël P. , Timofeev Oleg , Nist Andrea , Mernberger Marco , Kantelhardt Eva J. , Siebolts Udo , Bartel Frank , Jacob Ralf , Rath Ariane , Moll Roland , Grosse Robert , Stiewe Thorsten 
Published: December 2016

Significance
p53 mutations are the most frequent genetic alteration in cancer and are often indicative of poor patient survival prognosis. The most prevalent missense mutations lead to a “gain of function” (GOF) that actively drives tumor progression, metastasis, and therapy resistance. Our study links the mutant p53 (mutp53) GOF to enhanced N-glycoprotein folding via ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5) in the calnexin/calreticulin cycle of the endoplasmic reticulum. Mutp53 thus increases expression of prometastatic cell surface proteins, such as receptors and integrins, not only quantitatively but also qualitatively, with respect to N-glycosylation state. Our study reveals N-glycoprotein quality control in the endoplasmic reticulum as an indispensable mechanism underlying the progression of tumors with GOF mutp53 that could provide new possibilities for treating prognostically challenging p53-mutated cancers.
Low-stringency selection of TEM1 for BLIP shows interface plasticity and selection for faster binders
Authors: Cohen-Khait Ruth , Schreiber Gideon 
Published: December 2016

Significance
The ability of proteins to interact quickly and specifically is fundamental for most living activities. For a protein interaction to be formed, the corresponding surfaces need a high degree of chemical and structural complementarity. Here we investigated the level of plasticity of composition of a protein–protein interface without affecting the high-affinity binding. Using directed evolution and mild selection, we show that most interface residues can be exchanged without a loss in binding affinity. Conversely, many of the buried residues were highly conserved. Interestingly, the selection process resulted in sequences promoting faster binding kinetics. Selection of faster binders was further promoted by drastically shortening the incubation time, resulting in preequilibrium selection, which provides a path for evolution of fast-binding complexes.
Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice
Authors: Sozmen Elif G. , Rosenzweig Shira , Llorente Irene L. , DiTullio David J. , Machnicki Michal , Vinters Harry V. , Havton Lief A. , Giger Roman J. , Hinman Jason D. , Carmichael S. Thomas 
Published: December 2016

Significance
White matter stroke is a common clinical problem that leads to widespread cognitive and sensorimotor deficits. The incidence of white matter stroke is sharply age-associated; imaging studies indicate that, over age 80, virtually all of us will have white matter strokes. Little is known of the repair processes after white matter stroke. Here, we report the tissue repair processes after white matter stroke and identify Nogo receptor 1 (NgR1) ligands as inhibitors. We show that white matter repair and functional recovery are indeed possible in aged brains when an engineered NgR1 decoy receptor is systemically administered after white matter stroke, even at chronic periods in this disease.
Brief treatment with a highly selective immunoproteasome inhibitor promotes long-term cardiac allograft acceptance in mice
Authors: Sula Karreci Esilida , Fan Hao , Uehara Mayuko , Mihali Albana B. , Singh Pradeep K. , Kurdi Ahmed T. , Solhjou Zhabiz , Riella Leonardo V. , Ghobrial Irene , Laragione Teresina , Routray Sujit , Assaker Jean Pierre , Wang Rong , Sukenick George , Shi Lei , Barrat Franck J. , Nathan Carl F. , Lin Gang , Azzi Jamil 
Published: December 2016

Significance
The potential of proteasome inhibitors to prevent transplant rejection and to treat other immune disorders is hindered by mechanism-based toxicity from inhibition of constitutive proteasomes. Here, we demonstrate that briefly, reversibly, and selectively inhibiting the immunoproteasome prolonged the survival of transplanted hearts in mice and allowed long-term survival when combined with single-dose CTLA4-Ig. Immunoproteasome inhibition noncytotoxically reduced T-cell proliferation and the numbers of effector T cells in the allograft and draining nodes while increasing T-cell expression of exhaustion markers. The immunoproteasome thus appears to play a role in suppressing induction of T-cell exhaustion. Selective inhibition of the immunoproteasome may be a potential treatment option for the management of transplant rejection.
VarMatch: robust matching of small variant datasets using flexible scoring schemes
Authors: Sun Chen , Medvedev Paul 
Published: December 2016

Abstract

Motivation
Small variant calling is an important component of many analyses, and, in many instances, it is important to determine the set of variants which appear in multiple callsets. Variant matching is complicated by variants that have multiple equivalent representations. Normalization and decomposition algorithms have been proposed, but are not robust to different representation of complex variants. Variant matching is also usually done to maximize the number of matches, as opposed to other optimization criteria.

Results
We present the VarMatch algorithm for the variant matching problem. Our algorithm is based on a theoretical result which allows us to partition the input into smaller subproblems without sacrificing accuracy. VarMatch is robust to different representation of complex variants and is particularly effective in low complexity regions or those dense in variants. VarMatch is able to detect more matches than either the normalization or decomposition algorithms on tested datasets. It also implements different optimization criteria, such as edit distance, that can improve robustness to different variant representations. Finally, the VarMatch software provides summary statistics, annotations and visualizations that are useful for understanding callers’ performance.

Availability and Implementation
VarMatch is freely available at: https://github.com/medvedevgroup/varmatch

Supplementary information
Supplementary data are available at Bioinformatics online.
High-throughput interpretation of gene structure changes in human and nonhuman resequencing data, using ACE
Authors: Majoros William H , Campbell Michael S , Holt Carson , DeNardo Erin K , Ware Doreen , Allen Andrew S , Yandell Mark , Reddy Timothy E 
Published: December 2016

AbstractMotivationThe accurate interpretation of genetic variants is critical for characterizing genotype–phenotype associations. Because the effects of genetic variants can depend strongly on their local genomic context, accurate genome annotations are essential. Furthermore, as some variants have the potential to disrupt or alter gene structure, variant interpretation efforts stand to gain from the use of individualized annotations that account for differences in gene structure between individuals or strains.ResultsWe describe a suite of software tools for identifying possible functional changes in gene structure that may result from sequence variants. ACE (‘Assessing Changes to Exons’) converts phased genotype calls to a collection of explicit haplotype sequences, maps transcript annotations onto them, detects gene-structure changes and their possible repercussions, and identifies several classes of possible loss of function. Novel transcripts predicted by ACE are commonly supported by spliced RNA-seq reads, and can be used to improve read alignment and transcript quantification when an individual-specific genome sequence is available. Using publicly available RNA-seq data, we show that ACE predictions confirm earlier results regarding the quantitative effects of nonsense-mediated decay, and we show that predicted loss-of-function events are highly concordant with patterns of intolerance to mutations across the human population. ACE can be readily applied to diverse species including animals and plants, making it a broadly useful tool for use in eukaryotic population-based resequencing projects, particularly for assessing the joint impact of all variants at a locus.Availability and ImplementationACE is written in open-source C ++ and Perl and is available from geneprediction.org/ACESupplementary informationSupplementary information is available at Bioinformatics online.
cBinderDB: a covalent binding agent database
Authors: Du Jiewen , Yan Xin , Liu Zhihong , Cui Lu , Ding Peng , Tan Xiaoqing , Li Xiuming , Zhou Huihao , Gu Qiong , Xu Jun 
Published: December 2016

Abstract

Motivation
Small molecule drug candidates with attractive toxicity profiles that modulate target proteins through non-covalent interactions are usually favored by scientists and pharmaceutical industry. In the past decades, many non-covalent binding agents have been developed for different diseases. However, an increasing attention has been paid to covalent binding agents in pharmaceutical fields during recent years. Many covalent binding agents entered clinical trials and exerted significant advantages for diseases such as infection, cancers, gastrointestinal disorders, central nervous system or cardiovascular diseases. It has been recognized that covalent binding ligands can be attractive drug candidates. But, there is lack of resource to support covalent ligand discovery.

Results
Hence, we initiated a covalent binder database (cBinderDB). To our best knowledge, it is the first online database that provides information on covalent binding compound structures, chemotypes, targets, covalent binding types and other biological properties. The covalent binding targets are annotated with biological functions, protein family and domains, gene information, modulators and receptor–ligand complex structure. The data in the database were collected from scientific publications by combining a text mining method and manual inspection processes. cBinderDB covers covalent binder’s data up to September 2016.

Availability and Implementation
cBinderDB is freely available at www.rcdd.org.cn/cbinderdb/

Supplementary information
Supplementary data are available at Bioinformatics online.
Occupational HIV Infection in a Research Laboratory With Unknown Mode of Transmission: A Case Report
Authors: Soria Alessandro , Alteri Claudia , Scarlatti Gabriella , Bertoli Ada , Tolazzi Monica , Balestra Emanuela , Bellocchi Maria Concetta , Continenza Fabio , Carioti Luca , Biasin Mara , Trabattoni Daria , Bandera Alessandra , Ceccherini-Silberstein Francesca , Perno Carlo Federico , Gori Andrea 
Published: December 2016

Abstract
A laboratory worker was infected with human immunodeficiency virus (HIV) type 1 in a biosafety level 2 containment facility, without any apparent breach. Through full-genome sequencing and phylogenetic analyses, we could identify the source of infection in a replication-competent clone that unknowingly contaminated a safe experiment. Mode of transmission remains unclear. Caution is warranted when handling HIV-derived constructs.
A hadronic minute-scale GeV flare from quasar 3C 279?
Authors: Petropoulou M. , Nalewajko K. , Hayashida M. , Mastichiadis A. 
Published: December 2016

Abstract
The flat spectrum radio quasar 3C 279 is a known γ-ray variable source that has recently exhibited minute-scale variability at energies &gt;100 MeV. One-zone leptonic models for blazar emission are severely constrained by the short time-scale variability that implies a very compact emission region at a distance of hundreds of Schwarzschild radii from the central black hole. Here, we investigate a hadronic scenario where GeV γ-rays are produced via proton synchrotron radiation. We also take into account the effects of the hadronically initiated electromagnetic cascades (EMC). For a γ-ray emitting region in rough equipartition between particles and kG magnetic fields, located within the broad-line region (BLR), the development of EMC redistributes the γ-ray luminosity to softer energy bands and eventually leads to broad-band spectra that differ from the observed ones. Suppression of EMC and energy equipartition are still possible, if the γ-ray emitting region is located beyond the BLR, is fast moving with Doppler factor (&gt;70) and contains strong magnetic fields (&gt;100 G). Yet, these conditions cannot be easily met in parsec-scale jets, thus disfavouring a proton synchrotron origin of the Fermi-LAT flare.
Stem cell toxicology: a powerful tool to assess pollution effects on human health
Authors: Yao Xinglei , Yin Nuoya , Faiola Francesco 
Published: December 2016

AbstractEnvironmental pollution is a global problem; the lack of comprehensive toxicological assessments may lead to increased health risks. To fully understand the health effects of pollution, it is paramount to implement fast, efficient and specific toxicity screening that relies on human models rather than on time-consuming, expensive and often inaccurate tests involving live animals. Human stem cell toxicology represents a valid alternative to traditional toxicity assays because it takes advantage of the ability of stem cells to differentiate into multiple cell types and tissues of the human body. Thus, this branch of toxicology provides a possibility to assess cellular, embryonic, developmental, reproductive and functional toxicity in vitro within a single system highly relevant to human physiology. In this review, we describe the development, performance and future perspectives of stem cell toxicology, with an emphasis on how it can meet the increasing challenges posed by environmental pollution in the modern world.
Global environmental health: an interview with Sally Perreault Darney
Authors: Xu By Li , Zhao Bin 
Published: December 2016

Abstract
Pollution-induced health problems are of concern across the world. In China, the recent and rapid surge of economic development has been associated with public health problems as well as environmental degradation. We recently spoke with Sally Perreault Darney, Ph.D., the Editor-in-Chief of Environmental Health Perspectives (EHP), the foremost journal about environmental health. Published by the National Institute of Environmental Health Sciences (NIEHS), a part of the US National Institutes of Health, this fully open-access journal publishes peer-reviewed research and commentary, as well news and opinion across the many disciplines that contribute to the field of environmental health, including toxicology, epidemiology, risk assessment and exposure science. We wanted to learn her perspectives on the role that research plays in defining and solving environmental health problems in today's world. Dr. Darney holds a Ph.D. in Biomedical Science and enjoyed a productive research career in the US Environmental Protection Agency (EPA)'s Office of Research and Development, before joining NIEHS in 2015.
Breast cancer: updates and advances in 2016
Authors: Giordano Sara B. , Gradishar William 
Published: December 2016

Purpose of review
Approximately 1 in 8 US women (12%) will develop invasive breast cancer over the course of her lifetime. In 2016, an estimated 246,660 new cases of invasive breast cancer are expected to be diagnosed and approximately 40,450 would die as a result of it. The global burden of breast cancer exceeds all other cancers and the incidence is increasing. The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. This review focuses on the recent advances in breast cancer therapy including hormonal treatment of metastatic breast cancer, targeting cyclin-dependent kinases (CDK) 4/6 in breast cancer, updates in targeting human epidermal growth factor receptor 2 (HER2) positive breast cancer, adaptive randomization trial design and cancer genetic risk assessment.

Recent findings
Breast cancer is a heterogeneous disease and targeted therapy is improving the outcomes of women. The use of cyclin-dependent kinase inhibitors (CDK) 4/6 have demonstrated a substantial improvement in progression-free survival in the first line setting of metastatic hormone receptor positive breast cancer. And newer agents directed at HER2 continue to revolutionize HER2-positive breast cancer treatment.

Summary
This review highlights the recent updates in breast cancer treatment, new concepts in clinical trial design and provides a current overview of cancer genetic risk assessment.
The Utility of Low-Dose Aripiprazole for the Treatment of Bipolar II and Bipolar NOS Depression
Authors: Kelly Tammas , Lieberman Daniel Z. 
Published: December 2016

Abstract

Background
Despite initial reports of efficacy in bipolar depression, multicenter trials did not show aripiprazole to be better than placebo, possibly because the doses used were too high, leading to lower efficacy and high dropout rates. This study evaluated the effects of low-dose aripiprazole. Extensive clinical experience has suggested that doses beyond 5 mg are rarely efficacious.

Methods
Data were gathered from patients with bipolar II or bipolar not otherwise specified depression using a retrospective chart review. Efficacy was assessed with the Clinical Global Impression-Improvement score. Patients who had at least 2 trials of aripiprazole were included in a retrospective off-on-off-on experimental design. All patients were on other medications when aripiprazole was started. Patients were treated with doses of 1 to 5 mg.

Findings
On average, patients were rated improved or very much improved compared with baseline. Sixteen of 211 patients worsened or experienced no change. Forty-four patients (21%) discontinued due to adverse effects. The group of patients who underwent off-on-off-on trials experienced statistically significant improvement when they started and restarted aripiprazole, and statistically significant worsening when they discontinued it.

Conclusions
When treating bipolar II or bipolar not otherwise specified depression, low doses of aripiprazole, 5 mg or less, may be more effective and better tolerated than higher ones. Clinicians should start treatment with a very low dose and give patients time to respond.
Therapeutic Effects of Nurse Telephone Follow-up for Lung Cancer Patients in Turkey
Authors: Hintistan Sevilay , Nural Nesrin , Cilingir Dilek , Gursoy Ayla 
Published: December 2016

Background:
Patients with lung cancer can encounter many difficulties as they adjust to the side effects of chemotherapy treatments.

Objective:
The aim of this study is to determine the therapeutic effects of nurse telephone follow-up for lung cancer patients.

Methods:
In this quasi-experimental study, the sample consisted of 60 patients with lung cancer assigned to an intervention group (n = 30) and a control group (n = 30). The control group participants were sequentially enrolled first and then the intervention group participants were enrolled. The data were collected using the Patient Information Form, Eastern Cooperative Oncology Group Performance Status, the Edmonton Symptom Assessment Scale, and the Functional Living Index–Cancer. The Nursing Care Guide was created by the nurse researchers’ team and given to both the intervention and control groups. Telephone follow-up calls were conducted with intervention patients within the first week after their chemotherapy session. The Kolmogorov-Smirnov, Pearson χ
2, Fisher exact, Mann-Whitney U, and Friedman test and descriptive statistics were used to evaluate the data.

Results:
Patients in the intervention group demonstrated significantly better adjustment to the symptoms secondary to chemotherapy and higher social functioning quality of life scores compared with reported scores in the control group.

Conclusion:
Nurse telephone follow-up can reduce chemotherapy-related symptoms for lung cancer patients and improve participants’ social functioning.

Implications for Practice:
Nurse telephone follow-up is an acceptable and feasible form of patient contact and is a convenient and efficient way to offer patients the support and continuity of care they need.