bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANCA-assoziierte Vaskulitiden – Update 2017
Authors: de Groot Kirsten 
Published: August 2017

Was ist neu?
Stratifizierung ANCA-assoziierter Vaskulitiden (AAV) Da genetische Polymorphismen bei AAV stärker mit dem ANCA-Typ (Proteinase 3 [PR3], Myeloperoxidase [MPO]) als mit dem Krankheitsphänotyp (Granulomatose mit Polyangiitis [GPA] vs. Mikroskopische Polyangiitis [MPA)) assoziiert sind, tritt die phänotypische Unterscheidung zwischen GPA und MPA in den Hintergrund. PR3- und MPO-ANCA sind außerdem prädiktiv für therapeutisches Ansprechen und Rezidivwahrscheinlichkeit.
ANCA-Immunfluoreszenztest (ANCA-IFT) Der ANCA-IFT ist zur Diagnostik von AAV zugunsten eines Festphasenimmunoassays auf die ANCA Zielantigene Proteinase 3 und Myeloperoxidase entbehrlich.
Pathogenese Bestimmte Untergruppen neutrophiler Granulozyten verstärken und unterhalten die Immunreaktion bei AAV, indem sie extrazelluläre Chromatinnetze bilden (NETs), auf denen sie PR3 und MPO präsentieren.
Management von AAV Es gibt eine aktuelle Leitlinie der europäischen rheumatologischen und nephrologischen Fachgesellschaften zum Management von Patienten mit AAV. Ein oraler Komplement-5a-Rezeptor-Inhibitor hat sich in einer Proof of Concept-Studie bei AAV als wirksam erwiesen. IL-5-Antikörper sind für die hypereosinophilen Syndrome zugelassen und damit ein neues Therapieprinzip für die refraktäre eosinophile Granulomatose mit Polyangiitis (EGPA).
Biomarker Es sind Biomarker zur Ergänzung der bislang klinischen Einschätzung von Remission, Rezidiv und therapeutischem Ansprechen in der Entwicklung, wovon der lösliche CD163-Marker im Urin eine große Trennschärfe aufweist und Marktreife erlangen dürfte.
Primäre und sekundäre arterielle Hypertonie – Update 2017
Authors: Sanner Bernd , Hausberg Martin 
Published: August 2017

Was ist neu?
Bedeutung und Epidemiologie der Hypertonie Die arterielle Hypertonie bleibt trotz aller Aufklärungsarbeit und Therapiemöglichkeiten der wichtigste Risikofaktor für eine erhöhte Sterblichkeit, für ischämische apoplektische Insulte und zerebrale Blutungen.
Obstruktive Schlafapnoe und Hypertonie Eine Störung der Atmung im REM-Schlaf hat stärkeren Einfluss auf Pathomechanismen und die Entwicklung einer arteriellen Hypertonie am Tage als obstruktive Apnoen im Non-REM-Schlaf. Möglicherweise profitieren Schlafapnoe-Patienten mit einer therapierefraktären Hypertonie von einer renalen Denervation.
Zielblutdruck Eine erneute kritische Analyse der SPRINT-Studie lässt v. a. wegen Besonderheiten der Blutdruckmesstechnik keine allgemeinen Empfehlungen zu niedrigeren Zielblutdruckwerten zu als in den europäischen Leitlinien angegeben. Auch die HOPE-3-Studie belegt weder niedrigere Zielblutdruckwerte noch einen Nutzen einer Polypill bei Patienten mit moderatem kardiovaskulärem Risiko.
Interventionelle Hochdrucktherapie Es gibt weiterhin keine Daten aus randomisierten doppelblinden Studien einschl. Schein-Intervention, die einen Zusatznutzen der renalen Denervierung belegen. Was die Barorezeptorstimulation anbetrifft, so gibt es einige interessante neue Daten bei Patienten mit therapierefraktärer Hypertonie, allerdings ebenfalls keine neuen randomisierten doppelblinden Studien mit SHAM-Intervention.
Impact of Aldosterone Synthase Inhibitor FAD286 on Steroid Hormone Profile in Human Adrenocortical Cells
Authors: Brunssen Coy , Hofmann Anja , Peitzsch Mirko , Frenzel Annika , Ziegler Christian , Brown Nicholas , Weldon Steven , Eisenhofer Graeme , Willenberg Holger , Bornstein Stefan , Morawietz Henning 
Published: July 2017

AbstractInhibition of aldosterone synthase (CYP11B2) is an alternative treatment option to mineralocorticoid receptor antagonism to prevent harmful aldosterone effects. FAD286 is the best characterized aldosterone synthase inhibitor. However, to date, no study has used sensitive liquid chromatography-tandem mass spectrometry to characterize in detail the effect of FAD286 on the secreted steroid hormone profile of adrenocortical cells. Basal aldosterone production in NCI-H295R cells was detectable and 9-fold elevated after stimulation with angiotensin II. FAD286 inhibited this increase, showing a maximal effect at 10 nmol/l. Higher concentrations of FAD286 did not further reduce aldosterone concentrations, but showed a parallel reduction in corticosterone, cortisol and cortisone levels, reflecting additional inhibition of steroid-11β-hydroxylase (CYP11B1). Pregnenolone, progesterone and 17-OH-progesterone levels remained unaffected. In conclusion, the aldosterone synthase inhibitor FAD286 lowers angiotensin II-induced aldosterone concentrations in adrenocortical cells but the relative lack of selectivity over CYP11B1 is evident at higher FAD286 concentrations.
Subsequent Injuries and Early Recurrent Diagnoses in elite Rugby Union Players
Authors: Williams Sean , Trewartha Grant , Kemp Simon , Cross Matthew , Brooks John , Fuller Colin , Taylor Aileen , Stokes Keith 
Published: July 2017

AbstractAn eight-season (2005/06–2012/13) prospective cohort design was used to record time-loss injuries in 15 English Premiership teams. Data pertaining to a total of 1 556 players and 9 597 injuries (8 180 subsequent) were included in the analysis. Injuries subsequent to an index injury were classified as (1) New: different site; (2) Local: same site (and different type); or (3) Recurrent: same site and type. The severity of subsequent injuries (days missed) was compared with their related index injury. The proportions of early (<2 months), late (2–12 months) and delayed (>12 months) subsequent injuries were compared across injury classifications and diagnosis groupings. The majority of subsequent injuries (70%) were classified as new injuries, with 14% local and 16% recurrent. A large proportion of recurrent subsequent injuries (42%) occurred within two months of return-to-play. Subsequent injuries were not more severe than their corresponding index injury (effect sizes <0.20). Specific local and recurrent subsequent injury diagnoses with the highest risk of occurring within two months of return-to-play were: ‘neck muscle strain’, ‘ankle joint capsule sprain’, and ‘cervical nerve root’ injuries. These findings may be used to drive targeted secondary prevention efforts, such as reconsideration of return-to-play protocols for neck muscle strain injuries.
Irisin and Testosterone in Men with Metabolic Syndrome
Authors: Kamenov Zdravko , Assyov Yavor , Angelova Petya , Gateva Antoaneta , Tsakova Adelina 
Published: July 2017

AbstractThe beneficial effects of testosterone on the metabolism and body composition of men are well established but the exact mechanisms of these effects are not clearly understood. A potential explanation might lie in the hormones, secreted from skeletal muscles, named “myokines”. One such myokine, irisin, has been shown to also have potential beneficial metabolic effects. The aim of this pilot study was to evaluate the association of serum testosterone with circulating serum irisin levels in men with metabolic syndrome. A total 128 men with metabolic syndrome (MS) based on the IDF criteria participated in the study. Irisin serum concentration was determined by means of ELISA. Mean age±SD of the study participants was 51.8±8.3 years. Seventy percent of the subjects had type 2 diabetes mellitus. Circulating irisin was inversely associated with serum testosterone (r=−0.279, p<0.01) and was significantly higher in subjects with hypogonadism – mean±SD 252.0±147.1 vs.172.9±92.2 ng/ml (p=0.002). ROC analysis of serum irisin value was determined for distinguishing subjects with hypogonadism (AUC=0.670). In a multiple linear regression model with BMI, FPG, age, and irisin, only BMI (β=−0.228, p=0.004) and irisin (β=−0.170, p=0.045) were variables independently associated with testosterone concentrations. Irisin is negatively associated with serum testosterone in our population sample of men with MS. This might suggest a possible involvement of myokines and testosterone with regards to the human metabolism. As no such data on this association has been reported in the literature thus far, further prospective studies are required to elucidate this correlation.
3.6.16 Gold-Catalyzed Cycloaddition Reactions
Authors: Qian D. , Zhang J. 
Published: August 2017

AbstractSince about 2000, a “gold rush” has resulted in the development of numerous gold-catalyzed cycloaddition reactions. Such cycloadditions have now become a powerful and privileged method for the construction of carbo- and heterocycles, in particular those complex polycyclic structures featured in diverse natural products. This chapter is organized according to the key reactive gold intermediate that formally participates in the cycloaddition.
34.1.4.1 Synthesis of Fluoroalkanes by Substitution of a Halogen
Authors: Lequeux T. P. 
Published: August 2017

AbstractThis chapter is a revision of the earlier Science of Synthesis contribution describing methods for the synthesis of fluoroalkanes by substitution of a halogen atom. It includes additional methods published up until 2016. Newer approaches involve the use of fluoride complex reagents and the use of solvent effects to avoid competitive elimination reactions.
34.7.4 Allylic Fluorides (Update 2017)
Authors: Pitts C. R. , Lectka T. 
Published: August 2017

AbstractThis chapter is an update to the earlier Science of Synthesis contribution (Section 34.7) regarding the synthesis of allylic monofluorides. Herein, literature from 2005–2015 is discussed. Advancements during this time period include the employment of milder fluorinating reagents, methods that favor alkene migration or retention, tactics for catalytic and asymmetric reactions, and the introduction of a creative array of functional-group interconversions.
40.1.6.2 Azetidines (Update 2017)
Authors: Couty F. 
Published: August 2017

AbstractThis chapter is an update to the earlier Science of Synthesis contribution (Section 40.1.6) describing methods for the synthesis of azetidines. This review focuses on contributions in this field published between 2008 and 2015 (with some exceptions of papers published as early as 2006, which were not covered in the earlier review). This period has witnessed an impressive breakthrough of pharmaceutical agents bearing an azetidine ring in medicinal chemistry and the first examples of organocatalyzed enantioselective syntheses of nonracemic azetidines.
Distinct functions of diaphanous-related formins regulate HIV-1 uncoating and transport
Authors: Delaney Michael Keegan , Malikov Viacheslav , Chai Qingqing , Zhao Guangyuan , Naghavi Mojgan H. 
Published: August 2017

Significance
Viruses are adept at exploiting the host cytoskeleton to facilitate various aspects of their replication. Among host cytoskeletal regulators, diaphanous-related formins (DRFs) coordinate actin nucleation and microtubule (MT) stabilization in response to various environmental signals. Here, we uncover a function of DRFs and show that human immunodeficiency virus type 1 (HIV-1) exploits DRFs to coordinate the disassembly of the viral capsid shell, or “uncoating,” with induction of MT stabilization and virus transport. These two functions of DRFs during HIV-1 infection were genetically separable and independent of actin. Our findings suggest that HIV-1 coopts discrete functions of DRFs to coordinately control uncoating and MT-based virus transport, mimicking how DRFs naturally function to coordinate host actin and MT dynamics.
Two interacting PPR proteins are major Arabidopsis editing factors in plastid and mitochondria
Authors: Guillaumot Damien , Lopez-Obando Mauricio , Baudry Kevin , Avon Alexandra , Rigaill Guillem , Falcon de Longevialle Andéol , Broche Benjamin , Takenaka Mizuki , Berthomé Richard , De Jaeger Geert , Delannoy Etienne , Lurin Claire 
Published: August 2017

Significance
Breaking the “central dogma” of molecular biology, RNA editing is a specific posttranscriptional modification of RNA sequences. In seed plant organelle editosomes, each editable cytidine is identified by a specific pentatricopeptide repeat (PPR) protein. Some of these sequence-specific proteins contain an additional C-terminal “DYW” domain, which is supposed to carry the catalytic activity for editing. However, many PPR editing factors lack this domain. In this article, we show that a subfamily of about 60 Arabidopsis proteins might all require two additional PPR proteins for the editing of their sites. One of them, DYW2, is a specific cofactor containing a DYW domain, supporting the hypothesis that this domain might bring the cytidine deaminase activity to these editosomes.
Toll-like receptor 4 deficiency alters nucleus accumbens synaptic physiology and drug reward behavior
Authors: Kashima Daniel T. , Grueter Brad A. 
Published: August 2017

Significance
Substance use disorders affect >8% of the US adult population. Mitigating this problem requires a better understanding of how these substances alter reward system structures such as the nucleus accumbens (NAc). Although classically studied in a neuron-centric manner, the immune system contributes to synaptic and behavioral changes associated with drug experience. We report that the pattern recognition molecule toll-like receptor 4 (TLR4) plays a role in NAc synaptic physiology and drug reward. We show NAc subregion-specific differences in basal synaptic properties consistent with alterations in induction of NMDA receptor-dependent synaptic plasticity in TLR4 knockout (TLR4.KO) animals. Furthermore, we show that TLR4.KO animals exhibit deficits in drug reward learning and confirm microglia as the primary cell type expressing TLR4.
Homeostatic enhancement of sensory transduction
Authors: Milewski Andrew R. , Ó Maoiléidigh Dáibhid , Salvi Joshua D. , Hudspeth A. J. 
Published: August 2017

Significance
How do biological systems ensure robustness of function despite developmental and environmental variation? Although the operation of some systems appears to require precise control over parameter values, we describe how the function of the ear might instead be made robust to parameter perturbation. The sensory hair cells of the cochlea are physiologically vulnerable, yet most ears remain highly sensitive despite differences in their physical properties. We propose that slow homeostatic feedback allows hair cells to detect weak acoustic signals over a wide span of parameter values. Homeostasis also ensures that hair cells exhibit sharp frequency selectivity and a broad dynamic range. This homeostatic strategy constitutes a general principle by which many biological systems might ensure robustness of function.
Poly(ADP-ribose) polymerase 1 escorts XPC to UV-induced DNA lesions during nucleotide excision repair
Authors: Robu Mihaela , Shah Rashmi G. , Purohit Nupur K. , Zhou Pengbo , Naegeli Hanspeter , Shah Girish M. 
Published: August 2017

Significance
Repair of the majority of UV-induced DNA damage in mammalian cells by the nucleotide excision repair pathway starts with rapid recruitment of Xeroderma pigmentosum C (XPC) protein to the lesion. However, rapidity of XPC recruitment to the lesion site in a genomic context cannot be fully explained by the known properties of XPC or its partner protein DDB2. Here, we show that the DNA damage-detecting nuclear protein PARP1 forms a stable complex with XPC before DNA damage and transfers it very rapidly to the DNA lesion site if other repair conditions are present. Since PARP1 is known to interact with many proteins under steady-state conditions, our results reveal a paradigm that an association with PARP1 could confer a functional advantage to these proteins.
Structural basis of subunit selectivity for competitive NMDA receptor antagonists with preference for GluN2A over GluN2B subunits
Authors: Lind Genevieve E. , Mou Tung-Chung , Tamborini Lucia , Pomper Martin G. , De Micheli Carlo , Conti Paola , Pinto Andrea , Hansen Kasper B. 
Published: August 2017

Significance
Despite decades of studies, the development of competitive glutamate-site antagonists that can distinguish between NMDA receptor subtypes based on GluN2 subunits has been unsuccessful. The resulting lack of subunit-selective NMDA receptor ligands has led to the widespread use of competitive antagonists with only modest subunit preference in neurophysiological and behavioral studies. This study describes competitive glutamate-site antagonists with a binding mode in the GluN2A agonist binding domain that enables indirect engagement between ligands and nonconserved residues to achieve preferential binding to GluN1/2A over GluN1/2B. These findings are required for rational drug design and suggest that glutamate-site competitive antagonists with considerable subunit selectivity can be developed, despite the highly conserved nature of the glutamate binding site.
Exploiting conformational plasticity in the AAA+ protein VCP/p97 to modify function
Authors: Schütz Anne Kathrin , Rennella Enrico , Kay Lewis E. 
Published: August 2017

Significance
Cdc48/TERA/p97/VCP is an enzyme that utilizes energy stored in ATP to coordinate protein degradation and recycling in eukaryotic cells. Point mutations in p97 cause a degenerative disease in humans that affects the central nervous system, bone, and muscle. These mutations deregulate the structure and dynamics of p97 with implications for binding of a cofactor that recruits p97 to the lysosomal degradation pathway. Here we probe the plasticity of p97, searching for hotspots in this enzyme to revert the effect of disease mutations. We demonstrate that mutations at secondary sites can shift the dynamics and structure toward wild type, highlighting the potential of exploiting the plasticity of p97 in the rational design of compounds that restore function in disease mutants.
Cdk5-dependent phosphorylation of liprinα1 mediates neuronal activity-dependent synapse development
Authors: Huang Huiqian , Lin Xiaochen , Liang Zhuoyi , Zhao Teng , Du Shengwang , Loy Michael M. T. , Lai Kwok-On , Fu Amy K. Y. , Ip Nancy Y. 
Published: August 2017

SignificanceThe activity-dependent organization of synaptic components occurs during brain development in response to experience, and involves the precise regulation of the localization of synaptic proteins. However, the molecular mechanisms underlying activity-dependent organization of synaptic proteins remain unclear. We found that inhibition of the phosphorylation of the scaffold protein liprinα1 by neuronal activity promotes the synaptic localization of a major postsynaptic organizer, PSD-95, through increased liprinα1–PSD-95 interaction. This suggests that the phosphorylation status of liprinα1 functions as a molecular control for the activity-dependent localization of PSD-95 and hence postsynaptic organization and synapse maturation. Dysregulation of this posttranslational process may lead to impaired synapse development.
On pronouns that drop (out of German)
Authors: Falk Ylva 
Published: July 2017

Abstract
The null-subject parameter (NSP) is a well-studied syntactic feature within the field of L3 learning. The present study explores whether the L2 status factor (e.g., Bardel & Falk, 2012) exerts such a strong impact that the NSP from a non-typologically close or even similar L2 (Spanish/Italian) can be transferred into the L3. Data were recorded from two absolute beginners of L3 German (L1 Swedish, L2 English, French, Spanish, Italian) during a semester. The results show that both participants transferred the NSP from their weakest L2 into German. These results are discussed in relation to theories about transfer in L3 learning: the L1 transfer hypothesis, the L2 status factor, and the Typological Proximity Model. The results support the L2 status factor.
L3 morphosyntactic effects on L1 vs. L2 systems
Authors: Amaro Jennifer Cabrelli 
Published: July 2017

Abstract
This study investigates the extent to which L1 versus adult L2 syntactic systems resist influence from a third language (L3) via observation of the effect of Brazilian Portuguese (BP) on Spanish in L1 Spanish/L2 English and L1 English/L2 Spanish bilinguals that are advanced L3 BP speakers. We examine the phenomenon of raising across a dative experiencer out of a TP complement (TPExp), which is acceptable in BP and English but not Spanish. Spanish data from an acceptability judgment task indicate that although both experimental groups rate TPExp higher than the Spanish control, L2 Spanish speakers are more accepting of TPExp than L1 Spanish speakers and Spanish controls. We take these results to support our hypothesis of differential stability conditioned by age of acquisition.
How flat is flat in random interface growth?
Authors: Quastel Jeremy , Remenik Daniel 
Published: August 2017

Domains of attraction are identified for the universality classes of one-point asymptotic fluctuations for the Kardar-Parisi-Zhang (KPZ) equation with general initial data. The criterion is based on a large deviation rate function for the rescaled initial data, which arises naturally from the Hopf-Cole transformation. This allows us, in particular, to distinguish the domains of attraction of curved, flat, and Brownian initial data and to identify the boundary between the curved and flat domains of attraction, which turns out to correspond to square root initial data.

The distribution of the asymptotic one-point fluctuations is characterized by means of a variational formula written in terms of certain limiting processes (arising as subsequential limits of the spatial fluctuations of the KPZ equation with narrow wedge initial data, as shown in Probab. Theory Related Fields 166 (2016), pp. 67–185) which are widely believed to coincide with the Airy

2

_2

process. In order to identify these distributions for general initial data, we extend earlier results on continuum statistics of the Airy

2

_2

process to probabilities involving the process on the entire line. In particular, this allows us to write an explicit Fredholm determinant formula for the case of square root initial data.
DelPhiForce web server: electrostatic forces and energy calculations and visualization
Authors: Li Lin , Jia Zhe , Peng Yunhui , Chakravorty Arghya , Sun Lexuan , Alexov Emil 
Published: August 2017

Abstract

Summary
Electrostatic force is an essential component of the total force acting between atoms and macromolecules. Therefore, accurate calculations of electrostatic forces are crucial for revealing the mechanisms of many biological processes. We developed a DelPhiForce web server to calculate and visualize the electrostatic forces at molecular level. DelPhiForce web server enables modeling of electrostatic forces on individual atoms, residues, domains and molecules, and generates an output that can be visualized by VMD software. Here we demonstrate the usage of the server for various biological problems including protein–cofactor, domain–domain, protein–protein, protein–DNA and protein–RNA interactions.

Availability and implementation
The DelPhiForce web server is available at: http://compbio.clemson.edu/delphi-force.

Supplementary information
Supplementary data are available at Bioinformatics online.