bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain
Authors: Li Zhe , Tseng Pang-Yen , Tiwari Vinod , Xu Qian , He Shao-Qiu , Wang Yan , Zheng Qin , Han Liang , Wu Zhiping , Blobaum Anna L. , Cui Yiyuan , Tiwari Vineeta , Sun Shuohao , Cheng Yingying , Huang-Lionnet Julie H. Y. , Geng Yixun , Xiao Bo , Peng Junmin , Hopkins Corey , Raja Srinivasa N. , Guan Yun , Dong Xinzhong 
Published: February 2017

Significance
Chronic pain is a major health and economic problem worldwide with an estimated prevalence reaching epidemic levels of >25% of the population. Most drugs on the market for chronic pain have undesired side effects because their targets exist both inside and outside the pain pathways. Human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target of novel pain inhibitors, mainly because of its restricted expression in primary nociceptive neurons. Our humanized mouse model expressing MRGPRX1 in native nociceptive neurons allowed us to examine physiological roles of MRGPRX1 and to develop therapeutic agents for pain treatment in patients. Our studies suggest that both agonists and positive allosteric modulators of MRGPRX1 may be promising novel drug candidates for managing persistent pain conditions.
On the shape of giant soap bubbles
Authors: Cohen Caroline , Darbois Texier Baptiste , Reyssat Etienne , Snoeijer Jacco H. , Quéré David , Clanet Christophe 
Published: February 2017

Significance
Surface tension dictates the spherical cap shape of small sessile drops, whereas gravity flattens larger drops into millimeter-thick flat puddles. In contrast with drops, soap bubbles remain spherical at much larger sizes. However, we demonstrate experimentally and theoretically that meter-sized bubbles also flatten under their weight, and we compute their shapes. We find that mechanics does not impose a maximum height for large soap bubbles, but, in practice, the physicochemical properties of surfactants limit the access to this self-similar regime where the height grows as the radius to the power 2/3. An exact analogy shows that the shape of giant soap bubbles is nevertheless realized by large inflatable structures.
Differential TOR activation and cell proliferation in
Arabidopsis
root and shoot apexes
Authors: Li Xiaojuan , Cai Wenguo , Liu Yanlin , Li Hui , Fu Liwen , Liu Zengyu , Xu Lin , Liu Hongtao , Xu Tongda , Xiong Yan 
Published: February 2017

Significance
The modulation of growth and development is central to sessile plants. Shoot and root meristems share almost identical molecular machineries but are responsible for different types of aboveground and underground organogenesis. How two such highly similar biological systems respond to different environmental cues and regulate distinct developmental programs remains largely unknown. We report that, in harmony with nature, the shoot, but not the root, demands light for the activation of cell proliferation during organogenesis. We decipher the underlying mechanism that light is necessary for continuous auxin biosynthesis only in the shoot, but not the root, to activate target of rapamycin (TOR) kinase signaling. We further elucidate an auxin-Rho-related protein 2 (ROP2)-TOR-transcription factors E2Fa,b signaling cascade that integrates different environmental signals to orchestrate plant growth and development.
Activation of contact-dependent antibacterial tRNase toxins by translation elongation factors
Authors: Jones Allison M. , Garza-Sánchez Fernando , So Jaime , Hayes Christopher S. , Low David A. 
Published: February 2017

Significance
Contact-dependent growth inhibition (CDI) systems enable cells to bind competing bacteria and deliver toxins that cleave nucleic acids or form membrane pores. Here, we characterize a CDI toxin that specifically cleaves transfer RNA (tRNA), thereby blocking protein synthesis and inhibiting bacterial growth. Remarkably, two highly conserved and essential translation factors, EF-Ts and EF-Tu, are critical for this toxic nuclease activity. The toxin binds EF-Tu with high affinity and only cleaves tRNA in complex with the translation factor. EF-Ts appears to increase the rate of tRNA turnover. The activities of two other distinct CDI toxins are also regulated by EF-Ts. We propose that the regulation of toxin activity by the protein synthesis apparatus may play a role in intercellular communication.
Imaging mRNA and protein interactions within neurons
Authors: Eliscovich Carolina , Shenoy Shailesh M. , Singer Robert H. 
Published: February 2017

Significance
Gene expression is regulated by interactions between mRNAs and RNA-binding proteins. This functionality depends on their ability to specifically recognize and bind RNAs within the cell. Thus, elucidation of RNA–protein interactions is an area of active research. Technological developments allowed the study of these associations in living cells by ensemble biochemistry approaches. However, these traditional methods to investigate RNA–protein association may report adventitious associations and importantly, lack information about cellular spatial information. In this work, we provide an approach that can integrate information from biochemical interactions with visualization of these physical contacts within neurons.
Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training
Authors: Weible Aldis P. , Piscopo Denise M. , Rothbart Mary K. , Posner Michael I. , Niell Cristopher M. 
Published: February 2017

Significance
Meditation training has been shown to reduce anxiety, lower stress hormones, improve attention and cognition, and increase rhythmic electrical activity in brain areas related to emotional control. We describe how artificially inducing rhythmic activity influenced mouse behavior. We induced rhythms in mouse anterior cingulate cortex activity for 30 min/d over 20 d, matching protocols for studying meditation in humans. Rhythmic cortical stimulation was followed by lower scores on behavioral measures of anxiety, mirroring the reductions in stress hormones and anxiety reported in human meditation studies. No effects were observed in preference for novelty. This study provides support for the use of a mouse model for studying changes in the brain following meditation and potentially other forms of human cognitive training.
Cryo-EM structure of the replisome reveals multiple interactions coordinating DNA synthesis
Authors: Kulczyk Arkadiusz W. , Moeller Arne , Meyer Peter , Sliz Piotr , Richardson Charles C. 
Published: February 2017

Significance
The antiparallel nature of the two strands in duplex DNA poses a topological problem for their simultaneous synthesis. The “trombone” model of the replication fork postulates that the lagging-strand forms a loop such that the leading- and lagging-strand replication proteins contact one another. The replisome then can move in one direction along the DNA while synthesizing both strands. Physical interactions between the replication proteins and DNA coordinate processive synthesis of the leading and lagging strands. Here, we present the structure of a functional replisome from bacteriophage T7. Our structural and biochemical analyses provide an explanation of the mechanisms governing coordination of leading- and lagging-strand synthesis.
Distinct conformations of GPCR–β-arrestin complexes mediate desensitization, signaling, and endocytosis
Authors: Cahill Thomas J. , Thomsen Alex R. B. , Tarrasch Jeffrey T. , Plouffe Bianca , Nguyen Anthony H. , Yang Fan , Huang Li-Yin , Kahsai Alem W. , Bassoni Daniel L. , Gavino Bryant J. , Lamerdin Jane E. , Triest Sarah , Shukla Arun K. , Berger Benjamin , Little John , Antar Albert , Blanc Adi , Qu Chang-Xiu , Chen Xin , Kawakami Kouki , Inoue Asuka , Aoki Junken , Steyaert Jan , Sun Jin-Peng , Bouvier Michel , Skiniotis Georgios , Lefkowitz Robert J. 
Published: February 2017

Significance
β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize G protein signaling, initiate signaling on their own, and mediate receptor endocytosis. Using a panel of GPCRs believed to couple differently to βarrs, we demonstrate how distinct conformations of GPCR–βarr complexes are specialized to perform different subsets of these cellular functions. Our results thus provide a new signaling paradigm for the understanding of GPCRs, whereby a specific GPCR–βarr conformation mediates receptor desensitization, and another drives internalization and some forms of signaling.
Survey Methods for Estimating Red Snapper Landings in a High-Effort Recreational Fishery Managed with a Small Annual Catch Limit
Authors: Sauls Beverly J. , Cody Richard P. , Strelcheck Andrew J. 
Published: February 2017

Abstract
Before the Red Snapper Lutjanus campechanus stock in the southeastern U.S. Atlantic was formally assessed, recreational harvest was permitted year-round. However, in 2010, all sectors of the fishery were closed to immediately end overfishing. In recent years, the recreational fishery for Red Snapper in the region has been managed with a substantially reduced catch limit and an annual harvest season ranging from 0 to 8 d. To obtain a precise estimate of recreational harvest over this reduced time scale, a new creel survey method was developed in Florida, where the majority of Red Snapper landings in the region occur. The fishery was intensely monitored during the short sample window when the harvest season was open, and the survey design took advantage of choke points at ocean inlets that restrict recreational boat access to offshore fishing grounds. Landings estimates from this specialized survey were more precise than the general survey that has historically been used in the region to monitor saltwater recreational fisheries over larger spatial and temporal scales. Fishing effort was highly concentrated, and the fishery was capable of reaching the small annual catch limit over the short time periods allowed. Fishing effort and landings were highest between Ponce Inlet and Cape Canaveral, and the majority of Red Snapper were harvested from shallow depths (&lt;29 m). Fish from shallow depths were approximately equally distributed among younger (1–5 years) and older age-classes. However, as fishing moved into deeper waters (≥29 m), a greater proportion of fish were older than 5 years. Precise landings estimates from the survey enabled managers to monitor the recreational fishery against a small annual catch limit, and the survey also revealed spatial patterns of effort and CPUE in the region's private boat segment of the recreational fishery, which had been poorly understood.
Received May 13, 2016; accepted November 5, 2016 Published online February 22, 2017
DNA Vaccination Partially Protects Muskellunge against Viral Hemorrhagic Septicemia Virus (VHSV-IVb)
Authors: Millard Elena V. , Bourke Ashley M. , LaPatra Scott E. , Brenden Travis O. , Fitzgerald Scott D. , Faisal Mohamed 
Published: February 2017

Abstract
A DNA vaccine containing the glycoprotein (G) gene of the North American viral hemorrhagic septicemia virus (VHSV) genotype IVb was developed to evaluate the immune response of fish following vaccination and evaluate its efficacy in protecting a susceptible species, the Muskellunge Esox masquinongy, against VHSV-IVb challenge. Seven weeks (539 degree-days) following vaccination with 10 μg of either pVHSivb-G or a control plasmid, Muskellunge were challenged by immersion with 105 plaque-forming units (pfu)/mL of VHSV-IVb. Fish vaccinated with pVHSivb-G had a relative percent survival (RPS) of 45%. Vaccinated fish also had significantly lower mean viral titers in tissues (4.2 × 102 pfu/g) and viral prevalence (4%) than fish receiving the plasmid control vaccine (3.3 × 105 pfu/g; 82%). Neutralizing antibodies were detected 28 d (308 degree-days) postchallenge (11 weeks postvaccination) in 100% of Muskellunge vaccinated with pVHSivb-G compared with only 12% of plasmid-control-vaccinated Muskellunge, suggesting robust induction of a secondary, adaptive immune response. In addition, pVHSivb-G–vaccinated Rainbow Trout Oncorhynchus mykiss challenged 7 d (100 degree-days) postvaccination with the heterologous novirhabdovirus, infectious hematopoietic necrosis virus (IHNV), experienced an RPS of 61%, compared to control fish, suggesting induction of an early and transient nonspecific antiviral immune response. This study provides an important starting point for VHSV-IVb vaccine development and useful information about the antiviral immune response elicited by DNA vaccination in a nondomesticated fish species.
Received May 1, 2016; accepted September 1, 2016
Competition, Product Safety, and Product Liability
Authors: Chen Yongmin , Hua Xinyu 
Published: February 2017

Abstract
A firm’s incentive to invest in product safety is affected by both market environment and product liability. We investigate the relationship between competition and product liability in a spatial model of oligopoly, where reputation provides a market incentive for safety investment and higher liability may distort consumers’ incentive for product care. We find that partial liability, together with reputation concerns, can motivate firms to make safety investment. Increased competition due to less product differentiation diminishes a firm’s gain from maintaining reputation and raises the socially desired product liability. On the other hand, an increase in the number of competitors reduces the benefit from maintaining reputation, but has a non-monotonic effect on the potential gain from cutting back safety investment; consequently, the optimal liability may vary non-monotonically with the number of competitors. In general, therefore, the relationship between competition and product liability is subtle, depending on how competition is measured. (JEL L13, L15, K13)
Discrimination as a Self-Fulfilling Prophecy: Evidence from French Grocery Stores*
Authors: Glover Dylan , Pallais Amanda , Pariente William 
Published: February 2017

Abstract
Examining the performance of cashiers in a French grocery store chain, we find that manager bias negatively affects minority job performance. In the stores studied, cashiers work with different managers on different days and their schedules are determined quasi-randomly. When minority cashiers, but not majority cashiers, are scheduled to work with managers who are biased (as determined by an implicit association test), they are absent more often, spend less time at work, scan items more slowly, and take more time between customers. This appears to be because biased managers interact less with minorities, leading minorities to exert less effort. Manager bias has consequences for the average performance of minority workers: while on average minority and majority workers perform equivalently, on days where managers are unbiased, minorities perform significantly better than do majority workers. The findings are consistent with statistical discrimination in hiring whereby because minorities underperform when assigned to biased managers, the firm sets a higher hiring standard for minorities to get similar average performance from minority and nonminority workers.
An update on the pharmacologic management and treatment of neuropathic pain
Authors: Wright Megan E. , Rizzolo Denise 
Published: February 2017

ABSTRACT
Neuropathic pain results directly from a lesion or disease of the somatosensory nervous system and can be central or peripheral in origin. Epidemiologic research suggests that 7% to 10% of the general population suffers from neuropathic pain, although the prevalence may be underestimated. Patients with neuropathic pain may experience anxiety, depression, insomnia, disability, and reduced quality of life. Treatment remains suboptimal because traditional drugs provide only modest pain relief. This article reviews the causes of neuropathic pain, patient presentation, diagnosis, and management strategies.
Which dosing of furosemide is better in acute decompensated heart failure?
Authors: Jalaba Stephanie , Palermo Jennifer , Budavari Adriane I. 
Published: February 2017

ABSTRACT
Continuous versus bolus dosing of furosemide has been a longstanding debate for clinicians treating patients with acute decompensated heart failure. This article discusses the efficacy and safety of both options, and reviews several meta-analyses examining this topic.
Early introduction of peanuts
Authors: Rickman Shelley , Duby Desiree , Peters Michelle , Freigeh Carla , Archambault Mark E. 
Published: February 2017

ABSTRACT
Peanut allergy is the most common food allergy and the leading cause of anaphylaxis and death due to food allergy. Despite previous guidelines created by the American Academy of Pediatrics in 2003, peanut allergy has continued to significantly increase over the past decade. Therefore, further research has been done to help clinicians provide more evidence-based recommendations about the timing of introduction of peanuts. The LEAP study, published in February 2015, demonstrated the value of much earlier introduction of peanuts to nonallergic patients than previously suggested. These findings have altered current practice, and recommendations supported by the American Academy of Pediatrics now allow the introduction of peanuts as early as age 4 months to reduce the likelihood of developing peanut allergy.
Building school health partnerships to improve pediatric asthma care: the School-based Asthma Management Program
Authors: Kakumanu Sujani , Antos Nicholas , Szefler Stanley J. , Lemanske Robert F. 
Published: February 2017

Purpose of review
Children with asthma require care that is seamlessly coordinated so that asthma symptoms are recognized and managed at home and at school. The purpose of this review is to discuss recent consensus recommendations in school-based asthma care.

Recent findings
The School-based Asthma Management Program (SAMPRO) provides a widely endorsed framework to coordinate care with schools and consists of four components: establishing a circle of support around the child with asthma; facilitating bidirectional communication between clinicians and schools; comprehensive asthma education for schools; and assessment and remediation of environmental asthma triggers at school. SAMPRO standardizes recommendations for school-based asthma care coordination and provides a toolkit with websites and resources useful for the care of children with asthma in the school setting.

Summary
The review will discuss the need for coordinated school asthma partnerships, the inception and development of SAMPRO, and its vision to improve pediatric asthma care coordination within the circle of support, comprising clinicians, school nurses, families, and communities.
Progress with Structure–Activity Relationship modelling of occupational chemical respiratory sensitizers
Authors: Seed Martin J. , Agius Raymond M. 
Published: February 2017

Purpose of review
This appraises currently available computer-based (‘in silico’) models relating the molecular structure of low molecular weight compounds to their respiratory sensitization hazard. The present review places focus on the two main applications of such structure--activity relationship (SAR) models: hypotheses on disease mechanisms and toxicological prediction.

Recent findings
Analyses of the chemical structures of low molecular weight organic compounds known to have caused occupational asthma has led to the development of mechanistic alerts usually based on electrophilic reaction chemistry and protein cross-linking potential. Protein cross-linking potential has also been found to be a consistent feature of chemicals that have caused human cases of hypersensitivity pneumonitis. Stepwise iteration of quantitative SAR (QSAR) modelling has shown appreciable improvements in predictivity for occupational asthma hazard and useful prospects for practical application. A good case has also been made for the potential use of structural alert-based mechanistic SARs in predictive toxicology.

Summary
Further understanding of the molecular interactions between chemical respiratory sensitizers and components of human proteins have been obtained from in-vitro and in-silico techniques. There have been developments in both qualitative (mechanistic) SARs and QSARs, which offer potential for use in a predictive algorithm for the toxicological screening of industrial chemicals for respiratory sensitization potential.
It Is Time to Cancel Medicine’s Social Contract Metaphor
Authors: Harris John M. 
Published: February 2017

There is agreement that the complex relationship between medicine and society is best described as a metaphorical social contract and that professionalism is the medical profession’s contribution to this contract. Metaphors can help clarify abstract concepts, but they can also be abused if the counterfactual attributes of a metaphor become attributed to its subject. This seems to be happening with medical professionalism, which has sometimes been reduced to a contracted deliverable and a bargaining chip. The undesirable attributes of the social contract metaphor may be hindering efforts to understand and teach medical professionalism.
Despite its theoretical weaknesses, the social contract metaphor has historical credibility because of its alleged association with the 1847 Code of Medical Ethics and the subsequent ascension of regular (allopathic) medicine in the early 20th century. However, the record does not support an argument that the intended purpose of the 1847 Code was to create a social contract or that one ever arose. The alternative account that a contract did arise, but physicians were poor partners, is neither satisfying nor explanatory.
As now used, medicine’s social contract metaphor has serious theoretical and historic weaknesses. Medical educators should remove this narrow and overworked metaphor from their discussions of professionalism. By doing this, educators and the profession in general would only lose the ability to threaten themselves with the cancellation of their social contract. In return they would open the door to a more complex and fruitful consideration of medical professionalism and medicine’s relationship with society.
Beyond Selection: The Use of Situational Judgement Tests in the Teaching and Assessment of Professionalism
Authors: Goss Barbara D. , Ryan Anna T. , Waring Joshua , Judd Terry , Chiavaroli Neville G. , O’Brien Richard Charles , Trumble Stephen C. , McColl Geoffrey J. 
Published: February 2017

Problem
Professionalism is a critical attribute of medical graduates. Its measurement is challenging. The authors sought to assess final-year medical students’ knowledge of appropriate professional behavior across a broad range of workplace situations.

Approach
Situational judgement tests (SJTs) are used widely in applicant selection to assess judgement or decision making in work-related settings as well as attributes such as empathy, integrity, and resilience. In 2014, the authors developed three 40-item SJTs with scenarios relevant to interns (first-year junior doctors) and delivered the tests to final-year medical students to assess aspects of professionalism. As preparation, students discussed SJT-style scenarios; after the tests they completed an evaluation. The authors applied the Angoff method for the standard-setting process, delivered electronic individualized feedback reports to students post test, and provided remediation for students failing to meet the cut score.

Outcomes
Evaluation revealed that the tests positively affected students’ learning and that students accepted them as an assessment tool. Validity and reliability were acceptable. Implementation costs were initially high but will be recouped over time.

Next Steps
Recent improvements include changes to pass requirements, question revision based on reliability testing, and provision of detailed item-level feedback. Work is currently under way to expand the item bank and to introduce tests earlier in the course. Future research will explore correlation of SJT performance with other measures of professionalism and focus on the impact of SJTs on professionalism and interns’ ability to deal with challenging workplace situations.