bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial protease uses distinct thermodynamic signatures for substrate recognition
Authors: Bezerra Gustavo Arruda , Ohara-Nemoto Yuko , Cornaciu Irina , Fedosyuk Sofiya , Hoffmann Guillaume , Round Adam , Márquez José A. , Nemoto Takayuki K. , Djinović-Carugo Kristina 
Published: May 2017

AbstractPorphyromonas gingivalis and Porphyromonas endodontalis are important bacteria related to periodontitis, the most common chronic inflammatory disease in humans worldwide. Its comorbidity with systemic diseases, such as type 2 diabetes, oral cancers and cardiovascular diseases, continues to generate considerable interest. Surprisingly, these two microorganisms do not ferment carbohydrates; rather they use proteinaceous substrates as carbon and energy sources. However, the underlying biochemical mechanisms of their energy metabolism remain unknown. Here, we show that dipeptidyl peptidase 11 (DPP11), a central metabolic enzyme in these bacteria, undergoes a conformational change upon peptide binding to distinguish substrates from end products. It binds substrates through an entropy-driven process and end products in an enthalpy-driven fashion. We show that increase in protein conformational entropy is the main-driving force for substrate binding via the unfolding of specific regions of the enzyme (“entropy reservoirs”). The relationship between our structural and thermodynamics data yields a distinct model for protein-protein interactions where protein conformational entropy modulates the binding free-energy. Further, our findings provide a framework for the structure-based design of specific DPP11 inhibitors.
Structure distribution and turbulence in self-consistently supernova-driven ISM of multiphase magnetized galactic discs
Authors: Iffrig Olivier , Hennebelle Patrick 
Published: May 2017

Context. Galaxy evolution and star formation are two multi-scale problems tightly linked to each other.
Aims. We aim to describe simultaneously the large-scale evolution widely induced by the feedback processes and the details of the gas dynamics that controls the star formation process through gravitational collapse. This is a necessary step in understanding the interstellar cycle, which triggers galaxy evolution.
Methods. We performed a set of three-dimensional high-resolution numerical simulations of a turbulent, self-gravitating and magnetized interstellar medium within a 1 kpc stratified box with supernova feedback correlated with star-forming regions. In particular, we focussed on the role played by the magnetic field and the feedback on the galactic vertical structure, the star formation rate (SFR) and the flow dynamics. For this purpose we have varied their respective intensities. We extracted properties of the dense clouds arising from the turbulent motions and compute power spectra of various quantities.
Results. Using a distribution of supernovae sufficiently correlated with the dense gas, we find that supernova explosions can reproduce the observed SFR, particularly if the magnetic field is on the order of a few μG. The vertical structure, which results from a dynamical and an energy equilibrium is well reproduced by a simple analytical model, which allows us to roughly estimate the efficiency of the supernovae in driving the turbulence in the disc to be rather low, of the order of 1.5%. Strong magnetic fields may help to increase this efficiency by a factor of between two and three. To characterize the flow we compute the power spectra of various quantities in 3D but also in 2D in order to account for the stratification of the galactic disc. We find that within our setup, the compressive modes tend to dominate in the equatorial plane, while at about one scale height above it, solenoidal modes become dominant. We measured the angle between the magnetic and velocity fields and we conclude that they tend to be well aligned particularly at high magnetization and lower feedback. Finally, the dense structures present scaling relations that are reminiscent of the observational ones. The virial parameter is typically larger than 10 and shows a large spread of masses below 1000 M⊙. For masses larger than 104M⊙, its value tends to a few.
Conclusions. Using a relatively simple scheme for the supernova feedback, which is self-consistently proportional to the SFR and spatially correlated to the star formation process, we reproduce a stratified galactic disc that presents reasonable scale height, SFR as well as a cloud distribution with characteristics close to the observed ones.
The Human Gut Microbiome in Liver Diseases
Authors: Davis Brian , Bajaj Jasmohan 
Published: May 2017

AbstractRecent advances in culture-independent laboratory techniques and bioinformatics have contributed to enriched characterizations of the gut microbiota and microbiome in chronic liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease, primary sclerosing cholangitis, primary biliary cholangitis, and cirrhosis. In this review, the authors focus on studies characterizing and modulating the gut microbiota and microbiome in humans. The majority of studies that characterized microbiota involved a small number of patients using 16S ribosomal RNA genetic sequencing. Few studies applied whole-genome shotgun sequencing and metagenomics analyses. The majority of clinical trials on modulating the microbiome have focused on probiotics or antibiotics in small groups of patients with cirrhosis versus healthy controls. Several trials are underway using fecal microbial transplantation in alcoholic liver disease, nonalcoholic fatty liver disease, primary sclerosing cholangitis, and cirrhosis. Future research is needed on understanding the viral and fungal microbiome and developing user-friendly microbiome tools.
Speech-evoked Brainstem Auditory Responses and Auditory Processing Skills: A Correlation in Adults with Hearing Loss
Authors: Sanguebuche Taissane , Peixe Bruna , Bruno Rúbia , Biaggio Eliara , Garcia Michele 
Published: May 2017

Introduction The auditory system consists of sensory structures and central connections. The evaluation of the auditory pathway at a central level can be performed through behavioral and electrophysiological tests, because they are complementary to each other and provide important information about comprehension.
Objective To correlate the findings of speech brainstem-evoked response audiometry with the behavioral tests Random Gap Detection Test and Masking Level Difference in adults with hearing loss.
Methods All patients were submitted to a basic audiological evaluation, to the aforementioned behavioral tests, and to an electrophysiological assessment, by means of click-evoked and speech-evoked brainstem response audiometry.
Results There were no statistically significant values among the electrophysiological test and the behavioral tests. However, there was a significant correlation between the V and A waves, as well as the D and F waves, of the speech-evoked brainstem response audiometry peaks. Such correlations are positive, indicating that the increase of a variable implies an increase in another and vice versa.
Conclusion It was possible to correlate the findings of the speech-evoked brainstem response audiometry with those of the behavioral tests Random Gap Detection and Masking Level Difference. However, there was no statistically significant correlation between them. This shows that the electrophysiological evaluation does not depend uniquely on the behavioral skills of temporal resolution and selective attention.
Diagnostik und Behandlung der schwangerschaftsassoziierten Thromboembolie – aktuelle Empfehlungen
Authors: Linnemann Birgit 
Published: May 2017

Was ist neu?
Diagnostik in der Schwangerschaft Studien belegen den hohen Stellenwert der Kompressionssonografie der Beinvenen plus Duplexsonografie der Beckenvenen in der Diagnostik der Becken- und Beinvenenthrombose auch bei Schwangeren. Perfusionsszintigrafie und CT-Angiografie der Pulmonalarterien sind bei vergleichbarer fötaler Strahlenbelastung gleich aussagekräftig. Aufgrund der mütterlichen Strahlenbelastung favorisieren aktuelle Leitlinien bei fehlender struktureller Lungenerkrankung die Perfusionsszintigrafie als primäre Bildgebung. Es gibt keinen Grund, einer Schwangeren mit Lungenembolieverdacht eine notwendige radiologische Diagnosesicherung vorzuenthalten.
Antikoagulation in der Schwangerschaft Heparine bleiben Antikoagulans der 1. Wahl bei der Behandlung der venöses Thromboembolien (VTE) in der Schwangerschaft. Neue orale Antikoagulantien (NOAK) sind aufgrund ihrer geringen Molekülgröße plazentagängig und daher in der Schwangerschaft kontraindiziert.
Peripartales Vorgehen Zur Minimierung des postpartalen Blutungsrisikos vor der Geburt ist in den letzten Wochen vor der Geburt eine Aufteilung der NMH-Injektion auf 2 Tagesdosen sinnvoll. Bei der Entbindung ist eine interdisziplinäre Abstimmung wichtig. Postpartal kann eine NMH-Therapie fortgesetzt oder Warfarin eingesetzt werden (Kein Phenprocoumon, da es in die Muttermilch übergeht).
Akute Nierenschädigung (ANS) – Aktuelles zu (Früh)diagnostik und konservativer Therapie
Authors: Patschan Daniel , Müller Gerhard 
Published: May 2017

Was ist neu?
Epidemiologie Die Häufigkeit der akuten Nierenschädigung (ANS) nimmt auf gesamteuropäischer Ebene zu. Dabei lässt sich weltweit keine signifikante Verbesserung der Prognose feststellen.
ANS-Diagnosekriterien und neue Indikatoren der ANS Trotz intensiver Bemühungen konnte bislang kein Marker identifiziert werden, welcher die Serumkreatininkonzentration als ANS-Indikator ersetzen könnte. Mutmaßlich ist eher mit der Etablierung eines diagnostisch-prognostischen Marker-Panels bei ANS zu rechnen.
Konservative Maßnahmen mit gesichertem Nutzen Die derzeit verfügbaren konservativen Therapieempfehlungen sind in den letzten Jahren kaum durch neue Maßnahmen ergänzt worden. Kristalloide Volumenpräparate sind kolloidalen Lösungen meist vorzuziehen. Zudem sind balancierte Elektrolytlösungen Chlorid-reichen Präparationen bei drohender/manifester ANS wahrscheinlich überlegen. Im Rahmen einer jeden Volumentherapie ist eine Hyperhydratation betroffener Patienten jedoch zu vermeiden.
Das Dunkelfeld intentional lebensbeendender Handlungen durch Ärzte und Pflegekräfte
Authors: Beine Karl , Schubert Torben 
Published: May 2017

Zusammenfassung
Einleitung Intentional lebensbeendende Handlungen (LH), darunter Tötung auf Verlangen und Tötung ohne explizite Willensäußerung, sind in Deutschland verboten und wenig erforscht. In einer Pilotstudie wurde das Dunkelfeld der Anwendung von LH durch Ärzte und Pflegekräfte im deutschen Gesundheitswesen untersucht.
Methoden Alle 2015 in Deutschland eingetragenen Kliniken und Altenheime (n = 13 393) wurden per Post oder E-mail angeschrieben. Ärztliche und pflegerische Mitarbeiter wurden um Bearbeitung des anonymen Online-Fragebogens oder der mitgesandten identischen Paper-Pencil-Version gebeten. 4629 Personen beantworteten Fragen zu LH am eigenen Arbeitsplatz, Bitten um aktive Sterbehilfe und selbst durchgeführte LH, darunter befanden sich Ärzte (n = 356), Krankenpfleger (n = 3121) und Altenpfleger (n = 1152) aus vorrangig stationären Arbeitsbereichen..
Ergebnisse 2,25 – 4,01 % (172 Personen) der Befragten gaben an, in den vergangenen 12 Monaten von LH am eigenen Arbeitsplatz gehört zu haben und 1,42 – 3,39 % (77 Personen) gaben an, LH jemals selbst durchgeführt zu haben. LH wurde häufiger von Männern, Ärzten und auf Intensivstationen durchgeführt. Mehr als ein Drittel der Personen, die LH durchgeführt hatten (38,10 – 41,67 %), waren nie darum gebeten worden.
Diskussion Unsere Erhebung lässt vermuten, dass neben legalen Formen der passiven und indirekten Sterbehilfe auch strafbare intentional lebensbeendende Handlungen durch Ärzte und Pflegekräfte in allen erhobenen Bereichen des Gesundheitssystems angewandt werden.
Viral and cellular mRNA-specific activators harness PABP and eIF4G to promote translation initiation downstream of cap binding
Authors: Smith Richard W. P. , Anderson Ross C. , Larralde Osmany , Smith Joel W. S. , Gorgoni Barbara , Richardson William A. , Malik Poonam , Graham Sheila V. , Gray Nicola K. 
Published: May 2017

Significance
The majority of genes are controlled at the level of mRNA translation, with accurate regulation being critical to cellular function and health. The repression or activation of subsets of mRNAs, so-called “mRNA-specific” regulation, is often mediated by RNA-binding proteins. However, the mechanisms underlying mRNA-specific activation have only been determined in a very few cases. Here, we uncover a mechanism of mRNA-specific activation used by viral and cellular proteins, which share no sequence similarity, suggesting that it may represent a widespread mechanism. Importantly, in so doing, we also expand our knowledge of how two key translation factors, poly(A)-binding protein (PABP) and eukaryotic initiation factor 4G (eIF4G), function during translation initiation, showing they have pleiotropic effects on small ribosomal subunit recruitment.
Disparate foundations of scientists’ policy positions on contentious biomedical research
Authors: Edelmann Achim , Moody James , Light Ryan 
Published: May 2017

SignificanceWhat drives scientists’ public support for contentious policy issues? We examined associations between peer exposure and academic specialization on public declarations about research involving potentially pandemic pathogens. Although we found significant peer associations for everyone, they are strongest among the opposition. Conversely, specializing in fields directly related to gain-of-function research predicts support better than specializing in fields related to epidemic risks predicts opposition. These findings suggest that different social processes, rooted in differing social networks and expertise, underlie support or opposition. Identifying the sources of policy support might help parties better understand the different, but legitimate, foundations of each other’s positions, providing additional information to inform decision making and thereby help to maintain science’s role as an objective arbiter for policy.
Early 20th-century Arctic warming intensified by Pacific and Atlantic multidecadal variability
Authors: Tokinaga Hiroki , Xie Shang-Ping , Mukougawa Hitoshi 
Published: May 2017

Significance
Arctic amplification is a robust feature of climate response to global warming, with large impacts on ecosystems and societies. A long-standing mystery is that a pronounced Arctic warming occurred during the early 20th century when the rate of interdecadal change in radiative forcing was much weaker than at present. Here, using observations and model experiments, we show that the combined effect of internally generated Pacific and Atlantic interdecadal variabilities intensified the Arctic land warming in the early 20th century. The synchronized Pacific–Atlantic warming drastically alters planetary-scale atmospheric circulations over the Northern Hemisphere that transport warm air into the Arctic. Our results highlight the importance of regional sea surface temperature changes for Arctic climate and constrain model projections in this important region.
miR-183/96 plays a pivotal regulatory role in mouse photoreceptor maturation and maintenance
Authors: Xiang Lue , Chen Xue-Jiao , Wu Kun-Chao , Zhang Chang-Jun , Zhou Gao-Hui , Lv Ji-Neng , Sun Lan-Fang , Cheng Fei-Fei , Cai Xue-Bi , Jin Zi-Bing 
Published: May 2017

Significance
The polycistronic miR-183/96/182 cluster is highly expressed in various types of terminally differentiating sensory neurons, including photoreceptors. Although miR-182 single-knockout mice do not exhibit significant retinal architecture alterations in photoreceptors, deletion of miR-183 and miR-96 gives rise to severe defects in cone maturation. Long-term follow-up analysis reveals that miR-183/96 ablation results in progressive photoreceptor degeneration. Mechanistic studies demonstrate that miR-183 and miR-96 directly regulate the expression of the taurine transporter Slc6a6. The expression levels of photoreceptor-specific genes change in accordance with the knockdown or overexpression of Slc6a6 in vivo. In both cases, the mouse scotopic electroretinography responses are compromised. Our findings reveal that the epigenetic regulation of miR-183/96 via Slc6a6 is essential for mouse photoreceptor formation and functionalization.
The POTRA domains of Toc75 exhibit chaperone-like function to facilitate import into chloroplasts
Authors: O’Neil Patrick K. , Richardson Lynn G. L. , Paila Yamuna D. , Piszczek Grzegorz , Chakravarthy Srinivas , Noinaj Nicholas , Schnell Danny 
Published: May 2017

Significance
Nearly all proteins found within chloroplasts are synthesized in the cytoplasm as preproteins and then imported and trafficked to their final destination. The initial steps in importation are orchestrated by the TOC complex, which includes Toc75, serving as the translocation channel, and Toc33 and Toc159, both containing GTPase domains, which help drive substrate selection and importation. Aside from the soluble domain of Toc33/34, structural information for the TOC complex is lacking, hindering our ability to form mechanistic models for function. Here we report a structure of Toc75 consisting of three tandem POTRA domains. Our findings indicate that the POTRA domains may help facilitate preprotein import by directly binding preproteins and orchestrating handoff to the TIC complex.
Antimalarials inhibit hematin crystallization by unique drug–surface site interactions
Authors: Olafson Katy N. , Nguyen Tam Q. , Rimer Jeffrey D. , Vekilov Peter G. 
Published: May 2017

Significance
Approximately 3.2 billion people are at risk for malaria. The resistance of malaria parasites to current advanced multidrug treatments, recently recorded to spread out of Southeast Asia, has raised concerns of dire public health consequences. We demonstrate that antimalarial drugs suppress heme detoxification in the malaria parasites in a manner that is counter to the prevailing hypothesis in the field. We find that quinoline-class drugs work by specific interactions with β-hematin crystals, which are the by-product of heme detoxification within the digestive vacuole of the parasites. We also identify specific drug adsorption sites on crystal surfaces. These insights may potentially spur development of antimalarial drugs that overcome parasite resistance through a rational approach, far superior to currently used combinatorial methods.
Structural basis for ligand binding to an enzyme by a conformational selection pathway
Authors: Kovermann Michael , Grundström Christin , Sauer-Eriksson A. Elisabeth , Sauer Uwe H. , Wolf-Watz Magnus 
Published: May 2017

Significance
Cellular chemical reactions are slow, and to make them compatible with biological life, enzymes have evolved to accelerate their associated rate constants. Enzymatic catalysis is a complex process where the increase of rate constants predominantly depends on a reduction of the free energy barrier for product formation. It is now established that transient, so-called high-energy, enzyme states are indispensable entities that contribute to lowering of free energy barriers. Such states are inherently difficult to study. Here, we have been able to arrest a catalytically indispensable high-energy state of the enzyme adenylate kinase. A detailed characterization of its structure, dynamics, and function has revealed several aspects that together increase the understanding of how enzymes can perform their spectacular function.
Contacts between the endoplasmic reticulum and other membranes in neurons
Authors: Wu Yumei , Whiteus Christina , Xu C. Shan , Hayworth Kenneth J. , Weinberg Richard J. , Hess Harald F. , De Camilli Pietro 
Published: May 2017

Significance
The cytoplasm of eukaryotic cells is compartmentalized by intracellular membranes that define subcellular organelles. One of these organelles, the endoplasmic reticulum, forms a continuous network of tubules and cisternae that extends throughout all cell compartments, including neuronal dendrites and axons. This network communicates with most other organelles by vesicular transport, and also by contacts that do not lead to fusion but allow cross-talk between adjacent bilayers. Though these membrane contacts have previously been observed in neurons, their distribution and abundance has not been systematically analyzed. Here, we have carried out such analysis. Our studies reveal new aspects of the internal structure of neurons and provide a critical complement to information about interorganelle communication emerging from functional and biochemical studies.
Input timing for spatial processing is precisely tuned via constant synaptic delays and myelination patterns in the auditory brainstem
Authors: Stange-Marten Annette , Nabel Alisha L. , Sinclair James L. , Fischl Matthew , Alexandrova Olga , Wohlfrom Hilde , Kopp-Scheinpflug Conny , Pecka Michael , Grothe Benedikt 
Published: May 2017

Significance
Neural computation depends on precisely timed synaptic inputs, but the way that the timing of inputs is tuned to match postsynaptic processing requirements is not well understood. Here, we studied the same brainstem sound localization pathway in two species with dissimilar temporal processing requirements. Two factors that limit precise timing are synaptic delay and axonal conduction time. In gerbils, which depend on precise timing for sound localization, synaptic delays in fast conducting axons are stable across activity level, and axon myelination is adapted to minimize conduction delays. In mice, which do not depend on precise timing, these specializations are absent. Our results suggest that both axonal and synaptic properties are optimized to the specific functional requirements of neural computation, advancing our understanding of the mechanisms that optimize neural circuits.
Superresolution microscopy reveals the three-dimensional organization of meiotic chromosome axes in intact
Caenorhabditis elegans
tissue
Authors: Köhler Simone , Wojcik Michal , Xu Ke , Dernburg Abby F. 
Published: May 2017

Significance
Meiosis is the essential cell division process that generates haploid gametes from diploid precursor cells. It relies on a dramatic reorganization of chromosomes around a central axis, which establishes a platform for homologous pairing and its subsequent stabilization by the formation of a proteinaceous structure, the synaptonemal complex, and by physical linkages resulting from crossover recombination events. Despite their central role in regulating key meiotic events, little is known about the organization of the chromosome axes. Here, we use superresolution microscopy, combined with CRISPR/Cas9 genome editing, to build a three-dimensional model of the synapsed chromosome axis. Our data link axis structure to its functions in synapsis and regulation of partner choice during meiotic double-strand break repair.
RNA-seq reveals conservation of function among the yolk sacs of human, mouse, and chicken
Authors: Cindrova-Davies Tereza , Jauniaux Eric , Elliot Michael G. , Gong Sungsam , Burton Graham J. , Charnock-Jones D. Stephen 
Published: May 2017

Significance
The human yolk sac is often considered vestigial. Here, we report RNA-sequencing analysis of the human and murine yolk sacs and compare with that of the chicken. We relate the human RNA-sequencing data to coelomic fluid proteomic data. Conservation of transcripts across the species indicates the human secondary yolk sac likely performs key functions early in development, particularly uptake and processing of macro- and micronutrients, many of which are found in coelomic fluid. More generally, our findings shed light on evolutionary mechanisms giving rise to complex structures such as the placenta. We propose that although a choriovitelline placenta is never established physically in the human, the placental villi, exocoelomic cavity, and secondary yolk sac function together as a physiological equivalent.