bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic physical interactions map kinetochore regulators and regions sensitive to constitutive Cdc14 localization
Authors: Ólafsson Guðjón , Thorpe Peter H. 
Published: August 2015

Significance
The localization of proteins within the cell is assumed to be important for their function. However, we have limited understanding of protein relocalization in response to genetic changes or drug treatments and almost no understanding of the effects of protein relocation on cellular homeostasis. To address this, we have developed a method to systematically create protein fusions between a query protein and most other proteins in the cell. As proof of principle, we relocalized proteins to the kinetochore, a large protein complex essential for chromosome segregation and cell division. We identify a number of proteins that inhibit cell division via the kinetochore. One such interaction establishes a critical role for specific phosphorylation in kinetochore function.
Nectar vs. pollen loading affects the tradeoff between flight stability and maneuverability in bumblebees
Authors: Mountcastle Andrew M. , Ravi Sridhar , Combes Stacey A. 
Published: August 2015

Significance
Many insects carry substantial loads during flight. Although this behavior is often critical for survival and reproduction, few studies have examined its consequences for flight performance. Bumblebees regularly carry two types of loads in different locations: pollen on their legs or nectar in their abdomen. We found that when bees carry a pollen load rather than a nectar load, they are more stable but less maneuverable in flight, supporting the concept of a tradeoff between stability and maneuverability—a notion that is frequently suggested but has rarely been tested, particularly in flying insects. Our findings also suggest that wind conditions may influence what resources pollinators choose to collect, which would have important consequences for pollination dynamics and colony fitness.
Astrocytes phagocytose focal dystrophies from shortening myelin segments in the optic nerve of
Xenopus laevis
at metamorphosis
Authors: Mills Elizabeth A. , Davis Chung-ha O. , Bushong Eric A. , Boassa Daniela , Kim Keun-Young , Ellisman Mark H. , Marsh-Armstrong Nicholas 
Published: August 2015

Significance
Myelin segments facilitate fast conduction along axons, and thus the rapid transmission of information in the nervous system. In the absence of pathology, myelin segments are generally regarded as highly stable structures with plasticity limited to growth-related increases in myelin thickness. We discovered that existing myelin segments are also capable of rapid shortening and demonstrate that shortening involves a characteristic focal dystrophy that develops at the contact point with a phagocytic astrocyte. These astrocytes internalize large quantities of myelin from shortening segments using known phagocytic machinery in a developmentally regulated manner. This mechanism likely contributes to other instances of myelin remodeling and prevents the persistence of potentially pathological myelin dystrophies.
FXR1P is a GSK3β substrate regulating mood and emotion processing
Authors: Del’Guidice Thomas , Latapy Camille , Rampino Antonio , Khlghatyan Jivan , Lemasson Morgane , Gelao Barbara , Quarto Tiziana , Rizzo Giuseppe , Barbeau Annie , Lamarre Claude , Bertolino Alessandro , Blasi Giuseppe , Beaulieu Jean-Martin 
Published: August 2015

Significance
This study provides a cellular mechanism for the regulation of behavioral dimensions pertinent to mood disorders. Inhibition of glycogen synthase kinase 3β (GSK3β) is a shared action of drugs used for bipolar disorder. However, the substrates through which this kinase regulates mood are not known. We identified fragile X mental retardation-related protein 1 (FXR1P) as a substrate for GSK3β. Phosphorylation of FXR1P by GSK3β would lead to its down-regulation. Overexpression of FXR1P in the mouse prelimbic cortex elicits behavioral responses comparable to those of drugs inhibiting GSK3β. Furthermore, functional gene polymorphisms affecting FXR1P or GSK3β gene expression interact to regulate emotional brain responsiveness and stability in humans. These observations indicate that regulation of FXR1P by GSK3β contributes to regulating mood and emotion processing.
The genetics of human infertility by functional interrogation of SNPs in mice
Authors: Singh Priti , Schimenti John C. 
Published: August 2015

Significance
Although infertility is a highly prevalent disease with a major genetic component, the underlying genetic causes are unknown in the vast majority of patients. The complexity of sperm and egg production has confounded most efforts to address the genetics of human infertility. We have developed an experimental strategy for identifying infertility-causing mutations that exist in human populations. This strategy exploits the expanding databases of human genetic variation to computationally identify potential infertility mutations, then mimic them in mice by CRISPR/Cas genome editing technology. The mice are then evaluated for whether the human mutation renders them infertile. This technology can be used to establish a permanent resource of validated disease-causing genetic variants in infertility and other diseases.
Ubiquitination by March-I prevents MHC class II recycling and promotes MHC class II turnover in antigen-presenting cells
Authors: Cho Kyung-Jin , Walseng Even , Ishido Satoshi , Roche Paul A. 
Published: August 2015

SignificanceExpression of MHC class II–peptide complexes (pMHC-II) on the surface of antigen-presenting cells (APCs) is required for a wide variety of CD4 T-cell–dependent immunological processes. Regulation of pMHC-II biosynthesis and degradation are, therefore, essential for optimal APC function. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase March-I prevents pMHC-II recycling and targets newly synthesized pMHC-II for lysosomal degradation in resting dendritic cells and B cells. Activation of these cells terminates March-I expression, terminates pMHC-II ubiquitination, and prevents pMHC-II degradation by promoting efficient pMHC-II recycling. Our study demonstrates that rapid recycling “spares” internalized pMHC-II from degradation in activated APCs, thereby increasing the probability of efficient pMHC-II interaction with CD4 T cells.
Long-term social dynamics drive loss of function in pathogenic bacteria
Authors: Andersen Sandra Breum , Marvig Rasmus Lykke , Molin Søren , Krogh Johansen Helle , Griffin Ashleigh S. 
Published: August 2015

Significance
Laboratory experiments show that bacteria have surprisingly complex social lives: Like humans, they can cooperate but also cheat each other. Cooperation could benefit bacteria causing infection by coordinating attack and producing toxins in a collective effort. But can cheaters, exploiting the work of others, affect the outcome of infection? We show that populations of bacteria causing chronic lung infections in cystic fibrosis patients contain cheaters that freeload to the point where cooperation no longer pays off by not producing a compound that helps them steal iron from blood. Bad news for bacteria but good for us if we can find ways to meddle in their social lives.
Mapping the conformation of a client protein through the Hsp70 functional cycle
Authors: Sekhar Ashok , Rosenzweig Rina , Bouvignies Guillaume , Kay Lewis E. 
Published: August 2015

Significance
Hsp70 chaperones are key components of the cellular proteostasis network. The ATP-dependent interaction of Hsp70 with its substrates prevents aggregation and promotes their correct folding and maturation. Here we investigate the impact of Hsp70 binding on the conformation of a client substrate using nuclear magnetic resonance spectroscopy. Our experiments provide a model for Hsp70 action in which the substrate can adopt substantial amounts of secondary structure even in the globally unfolded Hsp70-bound state. Moreover, the substrate conformation does not evolve as a function of the Hsp70 nucleotide state, demonstrating that the large structural changes in Hsp70 resulting from ATP binding and hydrolysis do not perform conformational work on the bound substrate or lead to changes in client protein conformation.
New model to explain tooth wear with implications for microwear formation and diet reconstruction
Authors: Xia Jing , Zheng Jing , Huang Diaodiao , Tian Z. Ryan , Chen Lei , Zhou Zhongrong , Ungar Peter S. , Qian Linmao 
Published: August 2015

Significance
Dental microwear is among the most common proxies paleontologists use for diet reconstruction. Recent models have suggested that while quartz grit adherent to food produces wear of tooth enamel, softer particles, such as silica phytoliths found in many plants, do not. Some have therefore suggested that microwear patterns better reflect habitat than diet. This is important to paleobiologists because reconstructions of species from the earliest vertebrates to human ancestors have relied on dental microwear as a proxy for diet. Here we present an in vitro study demonstrating that softer particles produce microwear under conditions mimicking chewing. Enamel wear occurs not because an abrasive is hard but because it exceeds the binding force of proteins that hold together hydroxyapatite crystallites.
High-resolution epitope mapping by HX MS reveals the pathogenic mechanism and a possible therapy for autoimmune TTP syndrome
Authors: Casina Veronica C. , Hu Wenbing , Mao Jian-Hua , Lu Rui-Nan , Hanby Hayley A. , Pickens Brandy , Kan Zhong-Yuan , Lim Woon K. , Mayne Leland , Ostertag Eric M. , Kacir Stephen , Siegel Don L. , Englander S. Walter , Zheng X. Long 
Published: August 2015

Significance
Acquired thrombotic thrombocytopenic purpura (TTP) is primarily caused by autoantibodies that inhibit the ability of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) to proteolyze von Willebrand factor (VWF). The molecular mechanism of inhibition is not known. We used a hydrogen–deuterium exchange mass spectrometry (HX MS) method to determine at near–single-residue resolution the epitope of three monoclonal anti-ADAMTS13 autoantibodies isolated from TTP patients. Additional results show that the same autoantibody-binding epitope is responsible for ADAMTS13 binding to VWF to manage VWF proteolysis. These observations reveal the mechanism of autoimmune TTP and, together with the epitope determination, suggest a knowledge-based approach for finding a novel therapeutic.
Measuring human locomotor control using EMG and EEG: Current knowledge, limitations and future considerations
Authors: Enders Hendrik , Nigg Benno M. 
Published: August 2015

AbstractElectrical signals encoding different forms of information can be observed at multiple levels of the human nervous system. Typically, these signals have been recorded in a rather isolated fashion with little overlap between the static recordings of electroencephalography (EEG) commonly used in neuroscience and the typical surface electromyography (EMG) recordings used in biomechanics. However, within the last decade, there has been an emerging need to link the electrical activation patterns of brain areas during movement to the behavior of the musculoskeletal system. This review discusses some of the most recent studies using the EEG and/or EMG to study the neural control of movement and human locomotion as well as studies quantifying the connectivity between brain and muscles. The focus is on rhythmic locomotor‐type activities; however, results are discussed within the framework of initial work that has been done in upper and lower limbs during static and dynamic contractions. Limitations and current challenges as well as the possibility and functional interpretation of studying the connectivity between the cortex and skeletal muscles using a measure of coherence are discussed. The manuscript is geared toward scientists interested in the application of EEG in the field of locomotion, sports and exercise.
Low Adherence of HIV Providers to Practice Guidelines for Hepatocellular Carcinoma Screening in HIV/Hepatitis B Coinfection
Authors: Hearn Bevin , Chasan Rachel , Bichoupan Kian , Suprun Maria , Bagiella Emilia , Dieterich Douglas T. , Perumalswami Ponni , Branch Andrea D. , Huprikar Shirish 
Published: August 2015

Abstract
Background.  In the era of combination therapy for human immunodeficiency virus (HIV), liver disease, and hepatocellular carcinoma (HCC) are major causes of death for patients coinfected with HIV and hepatitis B virus (HBV). This study compared HIV provider and hepatologist awareness of and adherence to the American Association for the Study of Liver Diseases (AASLD) practice guidelines for chronic HBV management. The primary endpoint of HIV provider adherence to HCC screening recommendations was compared to that of hepatologists at a large metropolitan academic medical center.
Methods.  Medical record database searches by ICD-9 codes were used to identify HIV/HBV coinfected (n = 144) and HBV monoinfected (n = 225) patients who were seen at least twice over a 2-year period in outpatient clinics. Adherence to AASLD guidelines was assessed by chart review. Provider awareness was evaluated through a voluntary anonymous survey with knowledge-based questions.
Results.  Over a 2-year period, only 36.0% of HIV/HBV coinfected patients seen in HIV practices completed HCC screening compared to 81.8% of HBV monoinfected patients in hepatology practices (P &lt; .00001). Similarly, HIV providers less frequently monitored HBV viral load (P &lt; .0001), HBeAg/anti-HBe (P &lt; .00001), HBsAg/anti-HBs (P &lt; .00001) than hepatologists but screened more often for hepatitis A immunity (P = .028). Self-reported adherence and knowledge scores were similar among 19 HIV providers and 16 hepatologists.
Conclusions.  HIV providers ordered significantly fewer HCC screening and HBV monitoring tests than hepatologists within a single academic medical center. In the setting of increased reliance on quality indicators for care, both patients and providers will benefit from greater adherence to established guidelines.
Inability of Polymerase Chain Reaction, Pyrosequencing, and Culture of Infected and Uninfected Site Skin Biopsy Specimens to Identify the Cause of Cellulitis
Authors: Crisp Jonathan G. , Takhar Sukhjit S. , Moran Gregory J. , Krishnadasan Anusha , Dowd Scot E. , Finegold Sydney M. , Summanen Paula H. , Talan David A. ,   for the EMERGEncy ID Net Study Group, Abrahamian Fredrick M. , Gross Eric , Lester Laeben , Chiang William K. , Dunbar Lala M. , LoVecchio Frank , Salhi Bisan , Jui Jon , Garg Manish , Rothman Richard , Steele Mark T. , Shroff Sunil , Takhar Sukhjit S. , Crisp Jonathan G. 
Published: August 2015

Abstract
Background.  The cause of cellulitis is unclear. Streptococcus pyogenes, and to a lesser extent, Staphylococcus aureus, are presumed pathogens.
Methods.  We conducted a study of adults with acute cellulitis without drainage presenting to a US emergency department research network. Skin biopsy specimens were taken from the infected site and a comparable uninfected site on the opposite side of the body. Microbiology was evaluated using quantitative polymerase chain reaction (PCR), pyrosequencing, and standard culture techniques. To determine the cause, the prevalence and quantity of bacterial species at the infected and uninfected sites were compared.
Results.  Among 50 subjects with biopsy specimens from infected and uninfected sites, culture rarely identified a bacterium. Among 49 subjects with paired specimens from infected and uninfected sites tested with PCR, methicillin-susceptible S. aureus was identified in 20 (41%) and 17 (34%), respectively. Pyrosequencing identified abundant atypical bacteria in addition to streptococci and staphylococci. Among 49 subjects with paired specimens tested by pyrosequencing, S. aureus was identified from 11 (22%) and 15 (31%) and streptococci from 15 (31%) and 20 (41%) of the specimens, respectively. Methicillin-resistant S. aureus was not found by culture or PCR, and S. pyogenes was not identified by any technique.
Conclusions.  The bacterial cause of cellulitis cannot be determined by comparing the prevalence and quantity of pathogens from infected and uninfected skin biopsy specimens using current molecular techniques. Methicillin-susceptible S. aureus was detected but not methicillin-resistant S. aureus or S. pyogenes from cellulitis tissue specimens. For now, optimal treatment will need to be guided by clinical trials. Noninfectious causes should also be explored.
Using Immunohistochemistry to Assess the Accuracy of Histomorphologic Diagnosis of Aspergillosis and Mucormycosis
Authors: Jung Jiwon , Park Young Soo , Sung Heungsup , Song Joon Seon , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Woo Jun Hee , Kim Sung-Han 
Published: August 2015

Abstract
Background.  Data on the accuracy of conventional histomorphologic diagnosis are limited, especially in mucormycosis. We therefore investigated the accuracy of histomorphologic diagnosis of mucormycosis and aspergillosis, using immunohistochemistry (IHC) tests for mucormycosis and aspergillosis.
Methods.  Patients enrolled met the modified criteria for proven and probable mucormycosis (during a 22-year period) or invasive aspergillosis (during a 6-year period) and had formalin-fixed, paraffin-embedded tissues available. We first tested the diagnostic performance of IHC for mucormycosis and aspergillosis in proven cases. Then we determined the accuracy of histomorphologic diagnosis of probable cases, using the IHC tests.
Results.  In 7 proven cases of mucormycosis, the sensitivity and specificity of mucormycosis IHC were 100% (95% confidence interval, 65%–100%) and 100% (68%–100%), respectively. In 8 proven cases of aspergillosis, and the sensitivity and specificity of aspergillosis IHC staining were 87% (53%–98%) and 100% (65%–100%), respectively. Of 23 probable mucormycosis cases, 20 (87%) were positive with mucormycosis IHC, 2 (9%) were positive with aspergillosis IHC (including 1 positive for both), and 2 were negative with both. Of 16 probable aspergillosis cases, 10 (63%) were positive with aspergillosis IHC, 4 (25%) were positive with mucormycosis IHC, and 2 (13%) were negative with both tests.
Conclusions.  Aspergillosis and mucormycosis seem not to be correctly diagnosed morphologically, because some of the probable cases showed either test with both antibodies or failure to stain with the homologous antibody. In the absence of fungal culture results, the IHC tests seem helpful in differentiating between aspergillosis and mucormycosis.
Austerity in 2009–13
Authors: Alesina Alberto , Barbiero Omar , Favero Carlo , Giavazzi Francesco , Paradisi Matteo 
Published: August 2015

Abstract
The conventional wisdom is (i) that fiscal austerity was the main culprit for the recessions experienced by many countries, especially in Europe, since 2010 and (ii) that this round of fiscal consolidation was much more costly than past ones. The contribution of this paper is a clarification of the first point and, if not a clear rejection, at least it raises doubts on the second. In order to obtain these results we construct a new detailed “narrative” dataset which documents the size and composition of the fiscal plans implemented by several countries over 2009–13. Out of sample simulations, that project output growth conditional only upon the fiscal plans implemented since 2009, do reasonably well in predicting the total output fluctuations of the countries in our sample over the years 2010–13 and are also capable of explaining some of the cross-country heterogeneity in this variable. Fiscal adjustments based on cuts in spending appear to have been much less costly, in terms of output losses, than those based on tax increases. Our results, however, are mute on the question whether the countries we study did the right thing implementing fiscal austerity at the time they did, that is 2009–13.
Pliny the Elder
Authors: Doody Aude 
Published: August 2015

Gaius Plinius Secundus or Pliny the Elder (b. 23/4–d. 79 ce) is famous for two things: his monumental Natural History (Historia naturalis), which describes the world in thirty-seven volumes, and his death in the eruption of Vesuvius, which was carefully described by his nephew, Pliny the Younger, in one of two letters about his uncle that have survived to us (Plin. Ep. 6.16). In the second of these letters, Pliny the Elder is described as a man who read insatiably and the author of a large number of lost works, including histories of the German Wars and of the later Julio-Claudian period, as well as a treatise on how to throw a javelin from a horse (Plin. Ep. 3.5). Born in Novum Comum in the Transpadane regions, Pliny the Elder served in Germany alongside the future emperor Titus, practiced law at Rome under Nero, and went on to a prominent career as an equestrian administrator under the Flavians, holding a series of important procuratorships, including that of Hispania Tarraconensis, and serving as commander of the fleet at Misenum. The Natural History is dedicated to Titus, and Pliny’s closeness to both Vespasian and Titus seems reflected in his political views in the work, most obviously in his animosity toward Nero and his court. The Natural History is a key document in the history of science and scholarship in Europe. In this encyclopedic text, Pliny gathers together and arranges data from his reading and from his experience to present an account of nature that has Roman concerns at its heart. Pliny is not particularly concerned with philosophical schools, though he is usually seen as influenced by Stoicism. Nature is knowable through a succession of itemized facts that he puts at the disposal of his readers, to encourage them to marvel at the wonderful and unexpected inventiveness of the natural world. The burden of his text can be seen as a moral or a political one: Pliny promotes a return to old Roman values and a renewed spirit of intellectual inquiry in the rhetorical passages of the text, and the work as a whole is dependent on, and produced in the service of, Roman imperial interests. The work is organized in thirty-seven volumes. The first contains the preface and—unusually—a list of the contents and sources for each of the ensuing volumes. The following thirty-six deal with the heavens (Book 2); geography (Books 3–6); humans and other living creatures (Books 7–11); plants (Books 12–19); medicines from plants (Books 20–27); medicines from living creatures (Books 28–32); and an account of metals, minerals, and gemstones and the art that has been produced from them (Books 33–37).