bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multifunctional enzymes from reduced genomes – model proteins for simple primordial metabolism?
Authors: Seelig Burckhard 
Published: June 2017

SummaryBillions of years of evolution have yielded today's complex metabolic networks driven by efficient and highly specialized enzymes. In contrast, the metabolism of the earliest cellular life forms was likely much simpler with only a few enzymes of comparatively low activity. It has been speculated that these early enzymes had low specificities and in turn were able to perform multiple functions. In this issue of Molecular Microbiology, Ferla et al. describe examples of enzymes that catalyze chemically distinct reactions while using the same active site. Most importantly, the authors demonstrated that the comparatively weak activities of these multifunctional enzymes are each physiologically relevant. These findings contrast with simply promiscuous enzyme activities, which have been described numerous times but are not physiologically relevant. Ferla et al. elegantly combined initial bioinformatics searches for enzyme candidates with sound kinetic measurements, evolutionary considerations and even structural discussions. The phenomenon of multifunctionality appears to be a mechanism for bacteria with reduced genomes to compensate for their lack of certain enzymes. In the broader context of evolution, these organisms could be considered living model systems to study features of long‐extinct early cellular life.
Hematopoietic stem cell transplantation from unrelated donors in children with DOCK8 deficiency
Authors: Uygun Dilara Fatma K. , Uygun Vedat , Reisli İsmail , Keleş Sevgi , Özen Ahmet , Yılmaz Mustafa , Sayar Esra H. , Daloğlu Hayriye , Öztürkmen Seda I. , Çakı Suar , Karasu Gülsün T. , Yeşilipek Akif 
Published: June 2017

AbstractDIDS is a unique form of combined immune deficiency characterized by an unusual susceptibility to cutaneous viral infections, severe allergies with eosinophilia and elevated immunoglobulin E titers, autoimmunity, and cancer. HSCT is considered the standard of care for this deadly disease. We have retrospectively analyzed the outcome of allogeneic HSCT from unrelated donors in patients with DIDS. Data from four patients, with five transplants, are presented. All patients received transplants from unrelated donors' BM, except for one patient who received a cord blood transplant. The conditioning regimens were based on myeloablative protocols for BM derived transplants; a NM regimen was pursued for the patient who received a cord blood transplant, which resulted in graft rejection. Although recurrent pneumonia and skin infections resolved immediately after transplantation, all patients subsequently developed human herpesvirus infection, including cutaneous herpetic lesions, cytomegalovirus reactivation, and zona zoster, which could be attributed to the use of ATG. Despite the presence of serious morbidities prior to transplantation, all patients recovered successfully. DIDS can be successfully treated with allogeneic HSCT from unrelated donors following a myeloablative conditioning regimen, with a reasonable safety profile.
Executive function and theory of mind as predictors of socially withdrawn behavior in institutionalized children
Authors: Selcuk Bilge , Yavuz H. Melis , Etel Evren , Harma Mehmet , Ruffman Ted 
Published: June 2017

AbstractFalse‐belief understanding and executive functions are two main sociocognitive abilities reliably linked to child social competence. Although institution‐reared children are especially at risk for behavioral problems and cognitive delays, the role that executive function and false‐belief understanding might play in the social withdrawal of institutionalized children has not been examined. The current study used two‐wave data to investigate the concurrent and longitudinal relations of social withdrawal with executive function and false‐belief understanding in institutionalized children; it also allowed investigation of the directionality between executive function and false‐belief understanding. Data were collected from 66 Turkish children (T1 M = 57.83 months, SD = 9.20; T2 M = 69.58 months, SD = 8.45) residing in institutions, at two time points, approximately 1 year apart. We measured false‐belief understanding and executive function via individual assessments, and social withdrawal via care provider reports at both time points. Results showed that both executive function and false‐belief understanding increased between T1 and T2, while social withdrawal did not show a significant change. Path analysis revealed that when T1 age and language were controlled, T1 executive function predicted T2 executive function, and in turn, T2 executive function predicted lessened social withdrawal at T2. In addition, T1 executive function predicted T2 false‐belief understanding. T1 false‐belief understanding was not related to T2 false‐belief understanding, executive function, or social withdrawal. Findings suggested that executive function is an important predictor of social withdrawal in high‐risk populations.
Multicentre evaluation of the new ORTHO VISION® analyser
Authors: Lazarova E. , Scott Y. , van den Bos A. , Wantzin P. , Atugonza R. , Solkar S. , Carpio N. 
Published: June 2017

SUMMARYBackgroundImplementation of fully automated analysers has become a crucial security step in the blood bank; it reduces human errors, allows standardisation and improves turnaround time (TAT).ObjectivesWe aimed at evaluating the ease of use and the efficiency of the ORTHO VISION® Analyser (VISION) in comparison to the ORTHO AutoVue® Innova System (AutoVue) in six different laboratories.MethodsAfter initial training and system configuration, VISION was used in parallel to AutoVue following the daily workload, both automates being based on ORTHO BioVue® System column agglutination technology. Each participating laboratory provided data and scored the training, system configuration, quality control, maintenance and system efficiency. A total of 1049 individual samples were run: 266 forward and reverse grouping and antibody screens with 10 urgent samples, 473 ABD forward grouping and antibody screens with 22 urgent samples, 160 ABD forward grouping, 42 antibody screens and a series of 108 specific case profiles.ResultsThe VISION instrument was more rapid than the AutoVue with a mean performing test time of 27·9 min compared to 36 min; for various test type comparisons, the TAT data obtained from VISION was shorter than that from AutoVue. Moreover, VISION analysed urgent STAT samples faster. Regarding the ease of use, VISION was intuitive and user friendly.ConclusionsVISION is a robust, reproducible system performing the most types of analytical determinations needed for pre‐transfusion testing today, thus accommodating a wide range of clinical needs. VISION brings appreciated new features that could further secure blood transfusions.
Restoration of pharyngeal dilator muscle force in dystrophin‐deficient (mdx) mice following co‐treatment with neutralizing interleukin‐6 receptor antibodies and urocortin 2
Authors: Burns David P. , Rowland Jane , Canavan Leonie , Murphy Kevin H. , Brannock Molly , O'Malley Dervla , O'Halloran Ken D. , Edge Deirdre 
Published: June 2017

New Findings
What is the central question of this study?
We previously reported impaired upper airway dilator muscle function in the mdx mouse model of Duchenne muscular dystrophy (DMD). Our aim was to assess the effect of blocking interleukin‐6 receptor signalling and stimulating corticotrophin‐releasing factor receptor 2 signalling on mdx sternohyoid muscle structure and function.

What is the main finding and its importance?
The interventional treatment had a positive inotropic effect on sternohyoid muscle force, restoring mechanical work and power to wild‐type values, reduced myofibre central nucleation and preserved the myosin heavy chain type IIb fibre complement of mdx sternohyoid muscle. These data might have implications for development of pharmacotherapies for DMD with relevance to respiratory muscle performance.

The mdx mouse model of Duchenne muscular dystrophy shows evidence of impaired pharyngeal dilator muscle function. We hypothesized that inflammatory and stress‐related factors are implicated in airway dilator muscle dysfunction. Six‐week‐old mdx (n = 26) and wild‐type (WT; n = 26) mice received either saline (0.9% w/v) or a co‐administration of neutralizing interleukin‐6 receptor antibodies (0.2 mg kg−1) and corticotrophin‐releasing factor receptor 2 agonist (urocortin 2; 30 μg kg−1) over 2 weeks. Sternohyoid muscle isometric and isotonic contractile function was examined ex vivo. Muscle fibre centronucleation and muscle cellular infiltration, collagen content, fibre‐type distribution and fibre cross‐sectional area were determined by histology and immunofluorescence. Muscle chemokine content was examined by use of a multiplex assay. Sternohyoid peak specific force at 100 Hz was significantly reduced in mdx compared with WT. Drug treatment completely restored force in mdx sternohyoid to WT levels. The percentage of centrally nucleated muscle fibres was significantly increased in mdx, and this was partly ameliorated after drug treatment. The areal density of infiltrates and collagen content were significantly increased in mdx sternohyoid; both indices were unaffected by drug treatment. The abundance of myosin heavy chain type IIb fibres was significantly decreased in mdx sternohyoid; drug treatment preserved myosin heavy chain type IIb complement in mdx muscle. The chemokines macrophage inflammatory protein 2, interferon‐γ‐induced protein 10 and macrophage inflammatory protein 3α were significantly increased in mdx sternohyoid compared with WT. Drug treatment significantly increased chemokine expression in mdx but not WT sternohyoid. Recovery of contractile function was impressive in our study, with implications for Duchenne muscular dystrophy. The precise molecular mechanisms by which the drug treatment exerts an inotropic effect on mdx sternohyoid muscle remain to be elucidated.
Draft Genome Sequences of Alloscardovia macacae UMA81211 and UMA81212, Isolated from the Feces of a Rhesus Macaque (Macaca mulatta)
Authors: Albert Korin , Sela David A. 
Published: June 2017

ABSTRACT

Here, we provide the draft genome sequences of two isolates identified as
Alloscardovia macacae
. These bacteria originated from the feces of a rhesus macaque. The draft genomes of both
Alloscardovia macacae
isolates are ~1.8 Mb in length, with a G+C content of 56.1%.
Kinetics of Corneal Antigen Presenting Cells in Experimental Dry Eye Disease
Authors: Lee Hyun Soo , Amouzegar Afsaneh , Dana Reza 
Published: June 2017

ObjectiveTo evaluate dry eye disease (DED)-induced alterations in subsets of corneal antigen presenting cells (APCs) in a mouse model of experimental DED.Methods and AnalysisSeven to 8-week-old female C57BL/6 mice were housed in a controlled environment chamber and were treated with subcutaneous scopolamine to induce DED. Normal mice were used as controls. The frequencies of different subsets of dendritic cells (DCs) and macrophages in the cornea were evaluated using immunohistochemistry and flow cytometry at days 2, 7 and 14 after DED induction. Real-time PCR was used to assess the functional phenotype of macrophages in the cornea of DED mice.ResultsOur results demonstrated significant corneal infiltration of CD11b+and CD11c+cells on days 7 and 14. Further analysis of different DC subsets revealed non-significant changes in the frequencies of total CD11b+CD11c+cells at different time points. However, frequencies of CD11c+CD11b-DCs, CD11c+Langerin (CD207)+DCs and macrophages were significantly increased on both days 7 and 14 after DED induction. Real-time PCR data demonstrated increased expression of M1 macrophage markers, iNOS and TNF-α, and reduced expression of M2 macrophage markers, Arg1 and IL-10, by corneal F4/80+macrophages at day 7.ConclusionAlthough the frequencies of total CD11b+CD11c+cells do not significantly change in the course of DED, CD11c+CD11b-DCs and Langerin+DCs do show a significant increase. Interestingly, macrophages exhibit a predominant inflammatory M1 phenotype and suppressed anti-inflammatory M2 phenotype early after induction of DED, which are restored to near baseline levels in later stages of the disease.
Challenging current views on bile acid diarrhoea and malabsorption
Authors: Kurien Matthew , Thurgar Elizabeth , Davies Ashley , Akehurst Ron , Andreyev Jervoise 
Published: June 2017

BackgroundIn 2012, the National Institute for Health and Care Excellence (NICE) assessed guidance (DG7) on the use of tauroselcholic (75selenium) acid (also known as SeHCAT) for the investigation of diarrhoea due to bile acid malabsorption (BAM) in patients with IBS-D and in patients with Crohn’s disease who have not had an ileal resection. NICE concluded that tauroselcholic (75selenium) acid was recommended for use in research only. NICE will be reviewing the decision to update the guidance for tauroselcholic (75selenium) acid, for these populations, in March 2017.AimOur aim is to summarise advances in BAM, also known as bile acid diarrhoea (BAD), and encourage clinicians to re-evaluate their understanding of this disorder.ApproachWe review the prevalence, diagnosis and treatment of BAD/BAM. We describe the new evidence available since the original NICE review in 2012, and discuss the economic issues associated with failure to diagnose or to treat BAD/BAM accurately.Evidence updateThere is new and compelling evidence available since DG7, which shows that tauroselcholic (75selenium) acid scanning is a powerful tool in the diagnosis of BAD/BAM. We summarise published prevalence data (approximately 1% prevalence in the UK, as suggested by clinical practice diagnosis rates), and highlight that the true prevalence of BAD/BAM could be far greater than this.ConclusionWe present evidence that challenges current opinion about this disorder, and we commend both clinicians and health technology assessment (HTA) agencies for being open to arguments and new evidence in any future HTAs.
A high value care curriculum for interns: a description of curricular design, implementation and housestaff feedback
Authors: Hom Jason , Kumar Andre , Evans Kambria H , Svec David , Richman Ilana , Fang Daniel , Smeraglio Andrea , Holubar Marisa , Johnson Tyler , Shah Neil , Renault Cybele , Ahuja Neera , Witteles Ronald , Harman Stephanie , Shieh Lisa 
Published: June 2017

ABSTRACTPurposeMost residency programmes do not have a formal high value care curriculum. Our goal was to design and implement a multidisciplinary high value care curriculum specifically targeted at interns.DesignOur curriculum was designed with multidisciplinary input from attendings, fellows and residents at Stanford. Curricular topics were inspired by the American Board of Internal Medicine’s Choosing Wisely campaign, Alliance for Academic Internal Medicine, American College of Physicians and Society of Hospital Medicine. Our topics were as follows: introduction to value-based care; telemetry utilisation; lab ordering; optimal approach to thrombophilia work-ups and fresh frozen plasma use; optimal approach to palliative care referrals; antibiotic stewardship; and optimal approach to imaging for low back pain. Our curriculum was implemented at the Stanford Internal Medicine residency programme over the course of two academic years (2014 and 2015), during which 100 interns participated in our high value care curriculum. After each high value care session, interns were offered the opportunity to complete surveys regarding feedback on the curriculum, self-reported improvements in knowledge, skills and attitudinal module objectives, and quiz-based knowledge assessments.ResultsThe overall survey response rate was 67.1%. Overall, the material was rated as highly useful on a 5-point Likert scale (mean 4.4, SD 0.6). On average, interns reported a significant improvement in their self-rated knowledge, skills and attitudes after the six seminars (mean improvement 1.6 points, SD 0.4 (95% CI 1.5 to 1.7), p&lt;0.001).ConclusionsWe successfully implemented a novel high value care curriculum that specifically targets intern physicians.
Extended Features of Task Models for Specifying Cooperative Activities
Authors: Buchholz Gregor , Forbrig Peter 
Published: June 2017

In this paper, an extended version of task models is discussed that allows detailed specifications of cooperative activities. Within the presented specification CoTaL (Cooperative Task Language), there exist two complementary types of task models called role model and team model. One or more instances of each role model describe the specific activities of actors. The team model represents joined activities and reflects progression in cooperation between role instances. For each scenario there exists one instance of the team model. Preconditions and events can be assigned to tasks and refer to one or all running instances of a role model. An event can be a starting or finishing trigger and is activated as result of task executions. Additionally, variables can be defined. They are bound within the specified context during runtime and get the value of the identifier of a certain role instance. In this way, communication and collaboration between different actors can be specified. Tasks of a team model cannot be performed directly but present the result of the execution of other (role) models only. However, a team model can restrict the execution of role model instances.
It is shown how such models can be used to specify the activities in a smart meeting room. Snapshots of their simulation in CoTaSE (Cooperative Task Specification Environment) are presented. Additionally to the local implementation there exists an implementation in a cloud. It allows real cooperative executions of tasks.
Glucose Transporter 3 Potentiates Degranulation and Is Required for Platelet Activation
Authors: Fidler Trevor P. , Middleton Elizabeth A. , Rowley Jesse W. , Boudreau Luc H. , Campbell Robert A. , Souvenir Rhonda , Funari Trevor , Tessandier Nicolas , Boilard Eric , Weyrich Andrew S. , Abel E. Dale 
Published: June 2017

Objective—
On activation, platelets increase glucose uptake, glycolysis, and glucose oxidation and consume stored glycogen. This correlation between glucose metabolism and platelet function is not well understood and even less is known about the role of glucose metabolism on platelet function in vivo. For glucose to enter a cell, it must be transported through glucose transporters. Here we evaluate the contribution of GLUT3 (glucose transporter 3) to platelet function to better understand glucose metabolism in platelets.

Approach and Results—
Platelet-specific knockout of GLUT3 was generated by crossing mice harboring GLUT3 floxed allele to a PF4 (platelet factor 4)-driven Cre recombinase. In platelets, GLUT3 is localized primarily on α-granule membranes and under basal conditions facilitates glucose uptake into α-granules to be used for glycolysis. After activation, platelets degranulate and GLUT3 translocates to the plasma membrane, which is responsible for activation-mediated increased glucose uptake. In vivo, loss of GLUT3 in platelets increased survival in a collagen/epinephrine model of pulmonary embolism, and in a K/BxN model of autoimmune inflammatory disease, platelet-specific GLUT3 knockout mice display decreased disease progression. Mechanistically, loss of GLUT3 decreased platelet degranulation, spreading, and clot retraction. Decreased α-granule degranulation is due in part to an impaired ability of GLUT3 to potentiate exocytosis.

Conclusions—
GLUT3-mediated glucose utilization and glycogenolysis in platelets promotes α-granule release, platelet activation, and postactivation functions.
Numerical Study of Nocturnal Low-Level Jets over Gently Sloping Terrain
Authors: Fedorovich Evgeni , Gibbs Jeremy A. , Shapiro Alan 
Published: June 2017

AbstractNocturnal low-level jets (LLJs) over gently sloping terrain typical of the U.S. Great Plains are investigated by means of direct numerical simulation. Such LLJs develop in a tilted atmospheric boundary layer as a result of inertia–gravity oscillations initiated by a change of the surface thermal forcing during the evening transition. External parameters are the free-atmospheric geostrophic wind, ambient atmospheric stratification, surface buoyancy forcing, and slope angle. The governing momentum and buoyancy balance equations are written in slope-following coordinates, and solved numerically in the Boussinesq approximation. The surface forcing is prescribed in a form of surface buoyancy or buoyancy flux, both of which are slope-uniform but change in time. LLJs over slopes are contrasted with LLJs over flat terrain.Slope-induced effects essentially modify the entire structure of nocturnal LLJs. The shape of the LLJ wind profile over a slope is characterized by a sharper and larger-magnitude maximum. The presence of the slope causes the along-slope advection of environmental potential temperature during the night. This advection can reignite static instability in the LLJ flow developing after the evening transition. The resulting turbulence leads to a complete or partial remix of the boundary layer flow and drastically changes the appearance of the LLJ in terms of its shape and vertical position. A pronounced nighttime jet can also develop from the daytime convective boundary layer in the absence of any free-atmospheric geostrophic forcing. The daytime flow preconditioning, an important precursor of the nocturnal LLJ development, plays an especially important role in LLJs over a slope.
Preconditioning of the Weddell Sea Polynya by the Ocean Mesoscale and Dense Water Overflows
Authors: Dufour Carolina O. , Morrison Adele K. , Griffies Stephen M. , Frenger Ivy , Zanowski Hannah , Winton Michael 
Published: June 2017

Abstract
The Weddell Sea polynya is a large opening in the open-ocean sea ice cover associated with intense deep convection in the ocean. A necessary condition to form and maintain a polynya is the presence of a strong subsurface heat reservoir. This study investigates the processes that control the stratification and hence the buildup of the subsurface heat reservoir in the Weddell Sea. To do so, a climate model run for 200 years under preindustrial forcing with two eddying resolutions in the ocean (0.25° CM2.5 and 0.10° CM2.6) is investigated. Over the course of the simulation, CM2.6 develops two polynyas in the Weddell Sea, while CM2.5 exhibits quasi-continuous deep convection but no polynyas, exemplifying that deep convection is not a sufficient condition for a polynya to occur. CM2.5 features a weaker subsurface heat reservoir than CM2.6 owing to weak stratification associated with episodes of gravitational instability and enhanced vertical mixing of heat, resulting in an erosion of the reservoir. In contrast, in CM2.6, the water column is more stably stratified, allowing the subsurface heat reservoir to build up. The enhanced stratification in CM2.6 arises from its refined horizontal grid spacing and resolution of topography, which allows, in particular, a better representation of the restratifying effect by transient mesoscale eddies and of the overflows of dense waters along the continental slope.