bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beclin 1 regulates recycling endosome and is required for skin development in mice
Authors: Noguchi Saori , Honda Shinya , Saitoh Tatsuya , Matsumura Hiroyuki , Nishimura Emi , Akira Shizuo , Shimizu Shigeomi 
Published: January 2019

AbstractBeclin 1 is a key regulator of autophagy and endocytosis. However, its autophagy-independent functions remain poorly understood. Here, we report that Beclin 1 regulates recycling endosome and is required for skin development in vivo. We first established keratinocyte-specific Beclin 1-knockout mice and found that these mutant mice died owing to severe impairment of epidermal barrier. Beclin 1 plays a role in autophagy and the endocytic pathway in cooperation with Atg14 and UVRAG, respectively, and keratinocyte-specific Atg14-knockout mice do not show any abnormal phenotypes, suggesting that Beclin 1 has a role in skin development via the endocytic pathway. Furthermore, we found that Beclin 1 deficiency causes mislocalization of integrins via a defect of recycling endosome, abnormal cell detachment of basal cells and their immature differentiation, and abnormal skin development. These results provide the first genetic evidence showing the roles of Beclin 1 in recycling endosome and skin development.
Enhanced dynamics of conformationally heterogeneous T7 bacteriophage lysozyme native state attenuates its stability and activity
Authors: Sharma Meenakshi , Jaiswal Nancy , Kumar Dinesh , Poluri Krishna Mohan 
Published: January 2019

Abstract
Proteins are dynamic in nature and exist in a set of equilibrium conformations on various timescale motions. The flexibility of proteins governs various biological functions, and therefore elucidation of such functional dynamics is essential. In this context, we have studied the structure–dynamics–stability–activity relationship of bacteriophage T7 lysozyme/endolysin (T7L) native-state ensemble in the pH range of 6–8. Our studies established that T7L native state is conformationally heterogeneous, as several residues of its C-terminal half are present in two conformations (major and minor) in the slow exchange time scale of nuclear magnetic resonance (NMR). Structural and dynamic studies suggested that the residues belonging to minor conformations do exhibit native-like structural and dynamic features. Furthermore, the NMR relaxation experiments unraveled that the native state is highly dynamic and the dynamic behavior is regulated by the pH, as the pH 6 conformation exhibited enhanced dynamics compared with pH 7 and 8. The stability measurements and cell-based activity studies on T7L indicated that the native protein at pH 6 is ∼2 kcal less stable and is ∼50% less active than those of pH 7 and 8. A comprehensive analysis of the T7L active site, unfolding initiation sites and the residues with altered dynamics outlined that the attenuation of stability and activity is a resultant of its enhanced dynamic properties, which, in turn, can be attributed to the protonation/deprotonation of its partially buried His residues. Our study on T7L structure–dynamics–activity paradigm could assist in engineering novel amidase-based endolysins with enhanced activity and stability over a broad pH range.
„Lithium in der Behandlung der Altersdepression. Was spricht dafür, was dagegen?“
Authors: Stühler Sina , Quante Arnim 
Published: January 2019

Zusammenfassung
Anliegen Die Lithiumaugmentation ist eine der Behandlungsoptionen bei therapieresistenter Depression. In diesem Review soll die Studienlage zu der Anwendung von Lithium im höheren Lebensalter bei unipolarer Depression zusammengefasst werden.
Methode Es wurde eine selektive Literaturrecherche in PubMed durchgeführt. Es konnten insgesamt 15 relevante Artikel (Plazebokontrollierte Studien und Übersichtsarbeiten) miteinbezogen werden. Ergebnisse: Sowohl die klinischen Studien als auch die Reviews sprechen sich positiv für die Lithiumaugmentation im Alter aus. Die Remissionsraten und das Ansprechen auf das Lithium allgemein sind sehr hoch. Nierenschäden als gefürchtete Nebenwirkungen treten nur selten auf. Auch über längere Anwendung hinaus zeigt sich das Lithium als wirksam und verträglich, wobei Laborkontrollen engmaschiger durchgeführt werden sollten.
Schlussfolgerung Lithium präsentiert sich als wirksames Medikament bei therapieresistenter unipolaren Altersdepression. Im klinischen Alltag ist der Einsatz bei fehlender Kontraindikation zu empfehlen.
Advancements in Visible-Light-Enabled Radical C(sp)2–H Alkylation of (Hetero)arenes
Authors: Sun Alexandra , McAtee Rory , McClain Edward , Stephenson Corey 
Published: January 2019

The Minisci reaction, which encompasses the radical C–H alkylation of heteroarenes, has undergone revolutionary development in recent years. The application of photoredox catalysis to alkyl radical generation has given rise to a multitude of methods that feature enhanced functional group tolerance, generality, and operational simplicity. The intent of this short review is to bring readers up to date on this rapidly expanding field. Specifically, we will highlight key examples of visible-light-driven Minisci alkylation strategies that represent key advancements in this area of research. The scope and limitations of these transformations will be discussed, with a focus on examining the underlying pathways for alkyl radical generation. Our goal is to make this short review a stepping stone for further synthetic research development. Sections are organized based on alkyl radical precursor reagents.1	Introduction2	Alkyl Carboxylic Acids and Carboxylic Acid Derivatives3	Alkylboronic Acids4	Potassium Alkyl- and Alkoxymethyltrifluoroborates5	Alkyl Halides6	Alcohols and Ethers7	Conclusion
Anatomie des oberflächlichen Venensystems des
Beines
Authors: Brenner E. 
Published: January 2019

ZusammenfassungDas oberflächliche Venensystem des Beines beginnt mit den epifaszialen Venen, das sind
die diversen Venennetze der Subkutis, die Vv. saphenae accessoriae, die V. epigastica
superficialis, die V. circumflexa ilium superficialis und die Vv. pudendae externae. Diese
münden in die beiden intrafaszialen Venen, die V. saphena magna und die V. saphena parva
ein. Diese wiederum münden in das tiefe Ve-nensystem ein, die V. saphena magna konstant im
Hiatus saphenus, die V. saphena parva in etwas mehr als zwei Dritteln der Fälle in der
Fossa poplitea. Zudem bestehen zahlreiche Verbindungen zwischen oberflächlichem und tiefem
Venensystem über die Vv. perforantes. Die oberflächlichen Venen stehen untereinander über
Vv. communicantes in Verbindung. In den oberflächlichen Venen finden sich zahlreiche
parietale Klappen, zumeist mit zwei, in kleineren und kleinsten Venen auch mit nur einem
Klappensegel. An der Mündung der V. saphena magna kann sich zudem eine ostiale Klappe,
Astklappe, befinden. Die Wand der oberflächlichen Venen besitzt den typischen
dreischichtigen Aufbau mit einer Tunica intima, einer Tunica media und einer Tunica
externa. Die Tunica intima besitzt, zumindest in der V. saphena magna nachgewiesen, eine
Membrana elastica interna. In der Tunica media finden sich innen longitudinal angeordnete
Bündel glatter Muskulatur, nach außen gefolgt von dichten Bündeln zirkulär angeordneter
glatter Muskulatur. In der Tunica externa können ebenfalls noch längsgerichtete
Muskelfaserbündel zu finden sein. Sowohl die V. saphena magna als auch die V. spahena
parva liegen in einer eigenen Faszienhülle, deren Boden von der Fascia cruris bzw. der
Fascia lata und deren oberflächliches Blatt von der jeweiligen Fascia saphena gebildet
wird. Innerhalb dieser „Saphenous Compartments” werden die jeweiligen Venen durch
Ligamenta saphena seitlich verankert. Etwa 60 großvolumige, klinisch bedeutende Vv.
perforantes verbinden das oberflächliche mit dem tiefen Venensystem. Zumindest eine Klappe
in einer V. perforans verhindert dabei einen Rückstrom aus dem tiefen Venensystem.
Efficacy of an over-the-scope clip for preventing adverse events after duodenal endoscopic submucosal dissection: a prospective interventional study
Authors: Tashima Tomoaki , Ohata Ken , Sakai Eiji , Misumi Yoshitsugu , Takita Maiko , Minato Yohei , Matsuyama Yasushi , Muramoto Takashi , Satodate Hitoshi , Horiuchi Hajime , Matsuhashi Nobuyuki , Nonaka Kouichi , Ryozawa Shomei 
Published: January 2019

Abstract
Background Duodenal endoscopic submucosal dissection (ESD) remains technically challenging, with a high risk of severe adverse events. Because exposure of the duodenal post-ESD mucosal defect to pancreatic juice and bile acid reportedly induces delayed perforation and bleeding, we examined whether defect closure using an over-the-scope clip (OTSC) system was useful for preventing postoperative adverse events.
Methods From April 2016 to February 2017, a total of 50 consecutive patients with superficial non-ampullary duodenal epithelial tumors (SNADETs) larger than 10 mm, with no more than semi-circumferential spread, were prospectively enrolled in this study. All of the lesions were treated by experienced ESD operators and the post-ESD mucosal defect was closed using OTSCs.
Results All of the SNADETs were completely removed by ESD, with an R0 resection rate of 88.0 %. The mean procedure and closure times were 67.3 ± 58.8 minutes and 9.8 ± 7.2 minutes, respectively. Although complete defect closure was achieved in 94.0 % of the patients (47/50), two patients required surgical conversion. Delayed perforation occurred in only one patient (2.1 %), who did not have successful closure of the defect, as misplacement of the OTSC exposed the muscle layer. Meanwhile, delayed bleeding occurred in three patients (6.3 %); however, the bleeding was easily controlled using endoscopic coagulation. The mean duration of postoperative hospitalization was 5.5 ± 7.2 days.
Conclusions Prophylactic defect closure using OTSCs may be effective in reducing severe adverse events after duodenal ESD.
Genetically modified hematopoietic stem/progenitor cells that produce IL-10–secreting regulatory T cells
Authors: Ng Sze-Ling , Leno-Duran Ester , Samanta Dibyendu , Almo Steven C. , Strominger Jack L. 
Published: January 2019

SignificanceAmino acid copolymers that are used in the treatment of experimental autoimmune encephalomyelitis (EAE) in mice or multiple sclerosis (MS) in humans result in the induction of immunosuppressive IL-10–secreting regulatory T cells. The TCRs of these T cells have previously been isolated and sequenced. Introduction of these TCR into a retroviral vector was used to transduce murine hematopoietic stem/progenitor cells (HSC/HPC). These genetically modified HSC/HPC were then transplanted to create retrogenic mice. Splenocytes or T cells of these retrogenic mice produced high levels of IL-10 on appropriate stimulation, and strongly suggests that the TCR itself encodes information for IL-10 secretion. Moreover, these retrogenic mice were resistant to induction of EAE, suggesting an approach to therapy for progressive MS using genetically modified HSC/HPC for transplantation.
Realizing the potential of dielectric elastomer artificial muscles
Authors: Duduta Mihai , Hajiesmaili Ehsan , Zhao Huichan , Wood Robert J. , Clarke David R. 
Published: January 2019

Significance
To build new robots that can safely interact with people, while completing complex tasks, we need artificial muscles. Ideally, these devices would be completely soft, as strong as natural muscles, and powered by electricity for easy integration with the rest of the robot. We found a materials solution that relies on an established technology, a dielectric elastomer soft capacitor, which deforms when an electric field is applied. By using a unique combination of nanoscale conductive particles and soft elastomers, we can apply high electric fields and reach contraction forces on par with natural muscles. Potential uses include novel surgical tools, prosthetics and artificial limbs, haptic devices, and more capable soft robots for exploration.
Actuation of magnetoelastic membranes in precessing magnetic fields
Authors: Brisbois Chase Austyn , Tasinkevych Mykola , Vázquez-Montejo Pablo , Olvera de la Cruz Monica 
Published: January 2019

Significance
Understanding the properties of elastic membranes with superparamagnetic particles advances the design of autonomous, soft robots. Magnetic fields readily penetrate most materials and can be used remotely to induce rapid and precise changes in membrane shape. Here, we compare analytical and numerical models to molecular dynamics simulations to explain how rapidly precessing biaxial magnetic fields can be used to control the forces on magnetoelastic membranes. These forces are closely linked to its actuating behavior and its potential applications in micromechanics.
Canonical Wnt is inhibited by targeting one-carbon metabolism through methotrexate or methionine deprivation
Authors: Albrecht Lauren V. , Bui Maggie H. , De Robertis Edward M. 
Published: January 2019

SignificanceMetabolism, one of the most conserved features across all domains of life, is interwoven with cellular signaling networks and the posttranslational modification state of proteins. Methionine is an essential amino acid in one-carbon metabolism that serves as the substrate for S-adenosylmethionine, the universal methyl donor for cellular methylation. Here we report that the use of methionine-depleted medium inhibits Wnt-induced endolysosomal formation and canonical Wnt/β-catenin signaling. Use of methotrexate, a folate cycle inhibitor used in cancer chemotherapy, prevented PRMT1 and GSK3 vesicular sequestration, decreased Wnt-driven endolysosomal activity, and reduced canonical Wnt β-catenin luciferase signaling. In sum, these results imply a role for one-carbon metabolism in the regulation of Wnt signaling and endolysosomal biology.
Instant messaging, digital writing and spelling production quality in French
Authors: Simoës-Perlant Aurélie , Lanchantin Tonia , Gunnarsson-Largy Cecilia , Largy Pierre 
Published: January 2019

Abstract
The increased use of digital writing led to the appearance of written content that may differ from the standards
of spelling. Writing instant messages leads to the production of two different types of written forms that differ from standard
spelling: (a) those that can be confused with misspellings and (b) those that cannot. We showed that the production of the second
type of modifications has no effect on spelling production. Our research protocol allowed comparing two corpora (written in 1974
and 2012). These results showed that when a modification has no orthographic equivalent, its use cannot damage the quality of
spelling production. When it does, the effect on spelling may be negative.
Calculation of accurate interatomic contact surface areas for the quantitative analysis of non-bonded molecular interactions
Authors: Ribeiro Judemir , Ríos-Vera Carlos , Melo Francisco , Schüller Andreas 
Published: January 2019

Abstract

Summary
Intra- and intermolecular contact surfaces are routinely calculated for a large array of applications in bioinformatics but are typically approximated from differential solvent accessible surface area calculations and not calculated directly. These approximations do not properly take the effects of neighboring atoms into account and tend to deviate considerably from the true contact surface. We implemented an extension of the original Shrake-Rupley algorithm to accurately estimate interatomic contact surface areas of molecular structures and complexes. Our extended algorithm is able to calculate the contact area of an atom to all nearby atoms by directly calculating overlapping surface patches, taking into account the possible shielding effects of neighboring atoms. Here, we present a versatile software tool and web server for the calculation of contact surface areas, as well as buried surface areas and solvent accessible surface areas (SASA) for different types of biomolecules, such as proteins, nucleic acids and small organic molecules. Detailed results are provided in tab-separated values format for analysis and Protein Databank files for visualization. Direct contact surface area calculation resulted in improved accuracy in a benchmark with a non-redundant set of 245 protein–DNA complexes. SASA-based approximations underestimated protein–DNA contact surfaces on average by 40%. This software tool may be useful for surface-based intra- and intermolecular interaction analyses and scoring function development.

Availability and implementation
A web server, stand-alone binaries for Linux, MacOS and Windows and C++ source code are freely available from http://schuellerlab.org/dr_sasa/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Aligning optical maps to de Bruijn graphs
Authors: Mukherjee Kingshuk , Alipanahi Bahar , Kahveci Tamer , Salmela Leena , Boucher Christina 
Published: January 2019

AbstractMotivationOptical maps are high-resolution restriction maps (Rmaps) that give a unique numeric representation to a genome. Used in concert with sequence reads, they provide a useful tool for genome assembly and for discovering structural variations and rearrangements. Although they have been a regular feature of modern genome assembly projects, optical maps have been mainly used in post-processing step and not in the genome assembly process itself. Several methods have been proposed for pairwise alignment of single molecule optical maps—called Rmaps, or for aligning optical maps to assembled reads. However, the problem of aligning an Rmap to a graph representing the sequence data of the same genome has not been studied before. Such an alignment provides a mapping between two sets of data: optical maps and sequence data which will facilitate the usage of optical maps in the sequence assembly step itself.ResultsWe define the problem of aligning an Rmap to a de Bruijn graph and present the first algorithm for solving this problem which is based on a seed-and-extend approach. We demonstrate that our method is capable of aligning 73% of Rmaps generated from the Escherichia coli genome to the de Bruijn graph constructed from short reads generated from the same genome. We validate the alignments and show that our method achieves an accuracy of 99.6%. We also show that our method scales to larger genomes. In particular, we show that 76% of Rmaps can be aligned to the de Bruijn graph in the case of human data.Availability and implementationThe software for aligning optical maps to de Bruijn graph, omGraph is written in C++ and is publicly available under GNU General Public License at https://github.com/kingufl/omGraph.Supplementary informationSupplementary data are available at Bioinformatics online.
P860 Evaluation of the probiotic features of two different multi-strain probiotic preparations from two different manufacturers
Authors: Colombo S , Sagheddu V , Elli M , Mora D 
Published: January 2019

Abstract

Background
The aim of this work was to compare the probiotic adhesion features and immunomodulatory properties of 2 probiotic products characterised by the same bacterial content but manufactured in different places (Italy and USA).

Methods
The multi-strain probiotic products under investigation were composed by a mixture of 8 different strains. The two products were manufactured in Italy (VSL#3 - Lot 710061 expiry date 10/2019) and in US (Vivomixx - Lot 1708702 expiry date 31/03/2019). The cell viability in each lot was assessed by flow cytometry. The adhesive abilities of probiotics were evaluated on three different eukaryotic intestinal cell lines (Caco-2, HT-29 and mucus-producing HT29-MTX).
For the evaluation of immune-modulatory activity, human Dendritic Cells (hDCs) obtained from blood mononuclear cells were exposed for 6 days to cytokines cocktail (IL-4 20 ng/ml + GM-CSF 50 ng/ml) and then to both probiotic mixtures for 2 h with MOI 1:10. A positive inflammatory condition was obtained by incubating washed hDCs in fresh medium containing Salmonella sp. for additional two h. Finally, hDCs were then cultured for 23 h in complete medium with antibiotics for the final analysis of soluble and surface molecules with ELISA or cytofluorimetric analysis method, respectively.

Results
The two products showed a comparable amount of live cells, 2.2 1011 (FU/g) and 2.4 1011 (FU/g), respectively, for the VSL#3 and Vivomixx. The two tested products showed similar adhesive capacity to the 3 cell lines considered, with adhesion values in the range 67–71%. No significant differences were observed in the percentage of adhesiveness expressed by the two mixtures according to the type of cell line considered. Regarding the immune-modulatory ability of the two tested products, results showed that they have the same behaviours. The exposure of the probiotic mixtures to hDCs resulted in a meaningful reduction of the expression of IL-12 following Salmonella induction. We observed that both products slightly increase the proportion of HLA-DR+/CD11+ and CD80+/CD11+ hDCs. Moreover, both mixtures significantly reduce Salmonella-induced HLA-DR+/CD11+ and CD80+/CD11+ hDCs. Both probiotic products did not significantly induce TNF-α production by hDCs at basal condition, and they did not result in further TNF-α production if compared with that induced by Salmonella sp. alone even if the response of the two products was almost identical.

Conclusions
Investigative activities described in this work demonstrated a comparable adhesive performances and interesting immunomodulatory activity against inflammation induced by Salmonella sp. for both VSL#3 and Vivomixx showing same behaviours irrespective of the manufacturer.
Changes in Physiological Functioning in Loblolly Pine Trees Undergoing Bark Beetle Simulated Mortality
Authors: Hornslein Nicole J , Siegert Courtney M , Renninger Heidi J 
Published: January 2019

AbstractThe southeastern United States contains extensive loblolly pine (Pinus taeda L.) plantations at risk from bark beetle damage that can change ecosystem biogeochemical cycling. Functional changes in tree physiology have the potential to occur before visual evidence of mortality making them difficult to incorporate into ecosystem models. Therefore, we girdled loblolly pines to simulate bark beetle damage and measured physiological processes including sapflow rates, photosynthesis, litterfall, and needle nitrogen concentrations to determine the physiological changes occurring in trees undergoing mortality. We found that the girdling treatment took 5 months to significantly reduce sapflow rates but visual crown mortality occurred more than one year after girdling. Girdled pines had approximately 2.5 times lower water use than control pines and exhibited greater susceptibility to atmospheric water stress. Girdled and control pines had similar needle nitrogen concentrations and photosynthetic rates measured during the mortality year. However, more litterfall with higher nitrogen concentrations occurred in the mortality year than in the previous year, resulting in redistribution of carbon and nitrogen in the ecosystem. Overall, these data allow for better quantification of the effects of background disturbance levels and individual tree mortality on water, carbon, and nitrogen cycling within a loblolly pine ecosystem.