bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary changes in the Atlantic salmon Salmo salar L: characterization and impact of dietary fatty acid compositions
Authors: Dalum A , Tangen R , Falk K , Hordvik I , Rosenlund G , Torstensen B , Koppang E O
Published: November 2014

Consumption of fatty acids from fishes is widely regarded as beneficial for preventing cardiovascular disorders. Nevertheless, salmonids themselves are victims of vascular diseases. As the pathogenesis and nature of these changes are elusive, they are here addressed using novel morphological and transcriptional approaches. Coronary arteries of wild Atlantic salmon Salmo salar L., (n = 12) were investigated using histological and immunohistochemical techniques, and RT‐qPCR was employed to investigate expression of stretch‐induced genes. In an experimental trial, fish were fed diets with different fatty acids composition, and histological features of the coronary arteries (n = 36) were investigated. In addition, the heart fatty acid profile (n = 60) was analysed. There were no differences in morphological or immunological features between wild fish and groups of experimental fish. Arteriosclerotic lesions consisted of smooth muscle cells in dissimilar differential stages embedded in considerable amounts of extracellular matrix in a similar fashion to what is seen in early stages of human atherosclerosis. No fat accumulations were observed, and very few inflammatory cells were present. In affected arteries, there was an induction of stretch‐related genes, pointing to a stress‐related response. We suggest that salmon may have a natural resistance to developing atherosclerosis, which corresponds well with their high investment in lipid metabolism.
Alisporivir with peginterferon/ribavirin in patients with chronic hepatitis C genotype 1 infection who failed to respond to or relapsed after prior interferon‐based therapy: FUNDAMENTAL, a Phase II trial
Authors: Buti M. , Flisiak R. , Kao J.‐H. , Chuang W.‐L. , Streinu‐Cercel A. , Tabak F. , Calistru P. , Goeser T. , Rasenack J. , Horban A. , Davis G. L. , Alberti A. , Mazzella G. , Pol S. , Orsenigo R. , Brass C.
Published: November 2014

Alisporivir (ALV) is an oral, investigational host‐targeting agent, with pangenotypic activity against hepatitis C virus (HCV). This randomized, double‐blind, placebo‐controlled, Phase II study explored the efficacy and safety of ALV with peginterferon‐α2a/ribavirin (PR) in patients with chronic HCV genotype 1 infection in whom prior PR had failed (43% relapsers, 34% null responders and 23% partial responders). Four‐hundred‐and‐fifty‐nine patients were randomized (1:1:1:1) to ALV 600 mg once daily (QD), ALV 800 mg QD, ALV 400 twice daily (BID) or placebo plus PR for 48 weeks. When the global ALV trial programme was put on clinical hold, all patients in this study had received ≥31 weeks of randomized treatment; patients completed 48 weeks on PR alone. All ALV groups demonstrated superior rates of complete early virologic response (cEVR; primary endpoint) vs PR alone (P ≤ 0.0131), with highest cEVR rate seen with ALV 400 mg BID (74% vs 36% with PR alone; P < 0.0001). Respective SVR12 rates (key secondary endpoint) were 65% vs 26% in prior relapsers, 63% vs 5% in partial responders and 68% vs 3% in null responders. In patients who received >40 weeks of randomized treatment, the SVR12 rate was 89% for ALV 400 mg BID vs 30% for PR alone (P = 0.0053). Rates of viral breakthrough and relapse were lowest with ALV 400 mg BID. One case of pancreatitis (fully recovered) occurred with ALV/PR. Common AEs were headache, fatigue, anaemia, neutropenia and nausea. Hypertension was infrequent, but more common with ALV. ALV merits further investigation in interferon‐free regimens in combination with direct‐acting antiviral agents.
Oral anti‐CD3 immunotherapy for HCV‐nonresponders is safe, promotes regulatory T cells and decreases viral load and liver enzyme levels: results of a phase‐2a placebo‐controlled trial
Authors: Halota W. , Ferenci P. , Kozielewicz D. , Dybowska D. , Lisovoder N. , Samira S. , Shalit I. , Ellis R. , Ilan Y.
Published: November 2014

Orally administered anti‐CD3 antibodies are biologically active in the gut through induction of regulatory T cells, exert an immune‐modulatory effect, and alleviate insulin resistance and liver damage in patients with NASH. Aims: To determine the safety of oral anti‐CD3 monoclonal antibody (MAb) immunotherapy in chronic HCV patients with associated immune dysfunction. Methods: Four groups (n = 9) of chronic HCV patients who were nonresponders to interferon plus ribavirin therapy received oral placebo (group A) or anti‐CD3 MAb at one of three dosage levels for 30 days. Patients were followed for safety parameters and serum levels of liver enzymes, virus, cytokines and regulatory T cells. Results: Oral anti‐CD3 immunotherapy was safe and well tolerated; no treatment‐related adverse events were noted. The following improvements were noted relative to pretreatment levels: HCV viral load and AST and ALT levels decreased in the low‐ and high‐dose groups following 30 days of therapy. In two of the treated groups, an increase in regulatory T cells (CD4+ CD25+) was noted. The positive effects were somewhat more apparent in subjects with initially elevated liver enzyme levels. Conclusions: Oral anti‐CD3 MAb immunotherapy for nonresponder HCV patients was safe and well tolerated. Trends and statistically significant improvements were observed as reductions in viral load and liver enzyme levels, along with an increase in regulatory T‐cell levels. These data support a role for the immune system in the pathogenesis of HCV infection and suggest that this immunotherapy is worthy of evaluation in combination with HCV antiviral drugs.
Inter‐ and Intravein Differences in Cardiac Output with Cardiac Resynchronization Pacing using a Multipolar LV Pacing Lead
Authors: JONES MICHAEL A. , KHIANI RAJ , FOLEY PAUL , WEBSTER DAVID , QURESHI NORMAN , WONG KELVIN C.K. , RAJAPPAN KIM , BASHIR YAVER , BETTS TIMOTHY R.
Published: November 2014

Background

Quadripolar left ventricular pacing leads permit a variety of pacing configurations from different sites within a coronary vein. There may be advantages to selecting a specific pacing vector. This study examines whether the range of cardiac outputs obtained at cardiac resynchronization therapy (CRT) implantation is greater between different poles within a vein, or greater between two different veins.

Methods and Results

The cardiac index (CI, L/min/m2) was measured during CRT implantation using a noninvasive cardiac output monitor (NICOM™, Cheetah Medical Inc., Newton Center, MA, USA) and a quadripolar left ventricle (LV) lead, in 22 patients with sinus rhythm. CI was recorded during right atrial‐biventricular pacing at 70/min with fixed atrioventricular and ventriculo‐ventricular delay, from each LV electrode in one vein, and then from an alternate vein. Phrenic nerve stimulation (PNS) occurred in nine of 15 posterior and three of 21 anterior veins (P = 0.005). At least one electrode in each vein had no PNS. The mean (standard deviation [SD]) difference between best and worst CI within any one vein was 13.1% (±9%). The mean (SD) difference between the best CI in one vein compared to the other was 9.8% (±8%; P = 0.043). In 16 of 22 patients, the range of CI was greater between poles within one vein, rather than between two veins (best of one vein compared to best from the other). In four of 22 patients, the range was greater between veins (P = 0.0003).

Conclusion

A greater range of CI is found within a single vein than between two different veins. This finding has implications both for the approach to implant technique and postimplant programming and optimization.
A re‐assessment of sucrose signaling involved in cluster‐root formation and function in phosphate‐deficient white lupin (Lupinus albus)
Authors: Wang Zhengrui , Shen Jianbo , Ludewig Uwe , Neumann Günter
Published: November 2014

Apart from substrate functions, a signaling role of sucrose in root growth regulation is well established. This raised the question whether sucrose signals might also be involved in formation of cluster‐roots (CRs) under phosphate (Pi) limitation, mediating exudation of phosphorus (P)‐mobilizing root exudates, e.g. in Lupinus albus and members of the Proteaceae. Earlier studies demonstrated that CR formation in L. albus was mimicked to some extent by external application of high sucrose concentrations (25 mM) in the presence of extremely high P supply (1–10 mM), usually suppressing CR formation. In this study, we re‐addressed this question using an axenic hydroponic culture system with normal P supply (0.1 mM) and a range of sucrose applications (0.25–25 mM). The 2.5 mM sucrose concentration was comparable with internal sucrose levels in the zone of CR initiation in first‐order laterals of P‐deficient plants (3.4 mM) and induced the same CR morphology. Similar to earlier studies, high sucrose concentrations (25 mM) resulted in root thickening and inhibition of root elongation, associated with a 10‐fold increase of the internal sucrose level. The sucrose analog palatinose and a combination of glucose/fructose failed to stimulate CR formation under P‐sufficient conditions, demonstrating a signal function of sucrose and excluding osmotic or carbon source effects. In contrast to earlier findings, sucrose was able to induce CR formation but had no effect on CR functioning with respect to citrate exudation, in vitro activity and expression of genes encoding phosphoenolpyruvate carboxylase, secretory acid phosphatase and MATE transporters, mediating P‐mobilizing functions of CRs.
Characterization of Gambierdiscus and Coolia (Dinophyceae) isolates from Thailand based on morphology and phylogeny
Authors: Tawong Wittaya , Nishimura Tomohiro , Sakanari Hiroshi , Sato Shinya , Yamaguchi Haruo , Adachi Masao
Published: November 2014

The benthic dinoflagellates in the genus Gambierdiscus produce toxins that bioaccumulate in tropical and sub‐tropical fish causing ciguatera fish poisoning (CFP). Other co‐occurring genera such as Coolia have also been implicated in causing CFP. Little is known about the diversity of the two genera Gambierdiscus and Coolia along the Thai coasts. The results of morphological analyses based on observation under light microscopy and scanning electron microcopy showed that strains of Gambierdiscus from Thailand displayed the typical Gambierdiscus plate formula: Po, 4′, 0a, 6″, 6c,?s, 5′′′, 0p and 2′′′′. Morphological examination of Thai Gambierdiscus enabled it to be identified as Gambierdiscus caribaeus: round and anterior‐posteriorly compressed cell shape, broad 2′′′′ plate, rectangular 2′ plate, and symmetrical 3″ plate. The phylogenetic analyses based on the large subunit (LSU) rDNA D8/D10 sequences of Gambierdiscus from Thailand confirmed the morphological identification. The thecal plate formula for all of the Coolia isolates from Thailand was Po, 4′, 0a, 6″,?c,?s, 5′′′, 0p and 2′′′′. Most, but not all, of these isolates could be identified morphologically as Coolia malayensis. An LSU rDNA D1/D2 phylogenetic analysis confirmed identity of C. malayensis isolates identified morphologically. The remaining unidentified isolates fell in the C. tropicalis clade.
Adjusted Supremum Score‐Type Statistics for Evaluating Non‐Standard Hypotheses
Authors: Hsu Wei‐Wen , Todem David , Kim Kyungmann
Published: November 2014

Supremum score test statistics are often used to evaluate hypotheses with unidentifiable nuisance parameters under the null hypothesis. Although these statistics provide an attractive framework to address non‐identifiability under the null hypothesis, little attention has been paid to their distributional properties in small to moderate sample size settings. In situations where there are identifiable nuisance parameters under the null hypothesis, these statistics may behave erratically in realistic samples as a result of a non‐negligible bias induced by substituting these nuisance parameters by their estimates under the null hypothesis. In this paper, we propose an adjustment to the supremum score statistics by subtracting the expected bias from the score processes and show that this adjustment does not alter the limiting null distribution of the supremum score statistics. Using a simple example from the class of zero‐inflated regression models for count data, we show empirically and theoretically that the adjusted tests are superior in terms of size and power. The practical utility of this methodology is illustrated using count data in HIV research.
Towards Eliminating the Displacement Bias Due to Out‐Of‐Plane Motion in 2D Inverse Problems: A Case of General Rigid‐Body Motion
Authors: Siddiqui M. Z.
Published: November 2014

This article reports an important development related to the inverse characterization of material constitutive parameters using 2D optical displacement field measurements. The out‐of‐plane motion of the specimen, which has traditionally been considered detrimental to the accuracy of these experiments, is generally of two types: (a) a global out‐of‐plane rigid‐body motion of the specimen relative to the camera and (b) out‐of‐plane deformations resulting from material heterogeneity or out‐of‐plane loads. In an earlier article, we proposed to partially relax the condition of no out‐of‐plane motion by allowing for (b) in 2D inverse procedures, in the context of finite element update method, and introduced a compensation strategy by redefining the cost function on the object plane of the acquisition system. The experimental errors due to (a) were assumed negligible. Here, we propose that the global rigid‐body motion (a) may also be recovered within the inverse procedures, hence completely waiving the condition of strictly in‐plane displacements for inverse problems. The recovery is achieved by identifying and including the possible modes of global rigid‐body motion within the cost function together with careful selection of test configuration. The effects of individual rigid‐body modes on the computed displacement fields are studied in detail and utilized as a guideline for selection of test configuration. The approach is fully demonstrated and validated by simulated as well as real experiments for determining elastic constants of isotropic and orthotropic materials using different experimental setups. Effects of improving the optimization routine, for cost function minimization, and experimental noise are also presented.
Plasma CC‐chemokine ligand 28 level is correlated with hematopoietic stem cells in human cord blood
Authors: Yoon Jong Hyun , Oh Sohee , Shin Sue , Roh Eun Youn , Lee Hye Ryun , Seo Soo Hyun , Park Hyunwoong , Song Eun Young
Published: November 2014

Background

CC‐chemokine ligand 28 (CCL28) was previously identified as a novel growth factor in vitro for hematopoietic stem cells (HSCs) from cord blood (CB). However, there is no report on the relationship between CCL28 and HSCs in a human body.

Study Design and Methods

To reveal the effect of CCL28 on hematopoietic cells in human CB at birth, we measured CCL28 in frozen CB plasma, which was preserved as a reference sample for cryopreserved CB units for HSC transplantation. We also evaluated the correlation of CCL28 level with CB components.

Results

A total of 81 cryopreserved nonconforming CB units for transplantation were selected. The level of CCL28 was 2540 ± 377 pg/mL. The CCL28 levels correlated with the number of CD34+ cells (r = 0.222, p = 0.047) and white blood cells (r = 0.254, p = 0.022) in the CB units. The CCL28 levels also correlated with hemoglobin levels (r = 0.221, p = 0.048) in fresh CB.

Conclusion

This finding of positive correlation between CCL28 level and CD34+ cell numbers in vivo, together with the previous report that CCL28 influences the proliferation of hematopoietic cells in CB in vitro, may give a clue for better understanding the variability in HSC content in CB that is cryopreserved for HSC transplantation.
A safety study on intrathecal delivery of autologous mesenchymal stromal cells in rabbits directly supporting Phase I human trials
Authors: Chen Bingkun K. , Staff Nathan P. , Knight Andrew M. , Nesbitt Jarred J. , Butler Greg W. , Padley Douglas J. , Parisi Joseph E. , Dietz Allan B. , Windebank Anthony J.
Published: November 2014

Background

There are no effective treatments that slow the progression of neurodegenerative diseases. A major challenge of treatment in neurodegenerative diseases is appropriate delivery of pharmaceuticals into the cerebrospinal fluid (CSF) of affected individuals. Mesenchymal stromal cells (MSCs—either naïve or modified) are a promising therapy in neurodegenerative diseases and may be delivered directly into the CSF where they can reside for months. In this preclinical study, we evaluated the safety of intrathecal autologous MSCs in a rabbit model.

Study Design and Methods

Autologous adipose‐derived MSCs (or artificial CSF) were delivered intrathecally, either with single or with repeated injections into the foramen magnum of healthy rabbits and monitored for 4 and 12 weeks, respectively.

Results

Rabbits tolerated injections well and no definitive MSC‐related side effects were observed apart from three rabbits that had delayed death secondary to traumatic foramen magnum puncture. Functional assessments and body weights were equivalent between groups. Gross pathology and histology did not reveal any abnormalities or tumor growth. Complete blood count data were normal and there were no differences in CSF interleukin‐6 levels in all groups tested.

Conclusion

Our data suggest that intrathecal delivery of autologous MSCs is safe in a rabbit model. Data from this study have supported two successful investigational new drug applications to the Food and Drug Administration, resulting in the initiation of two clinical trials using autologous MSCs in amyotrophic lateral sclerosis and multiple system atrophy.
RHD variants in Flanders, Belgium
Authors: Van Sandt Vicky S.T. , Gassner Christoph , Emonds Marie‐Paule , Legler Tobias J. , Mahieu Sarah , Körmöczi Günther F.
Published: November 2014

Background

D antigen variants may be grouped into partial D, weak D, and DEL types. Cumulative phenotype frequencies of these D variants may approach 1% in certain European regions. Unambiguous and quick identification of D variants is of immediate clinical relevance, with implications for transfusion strategy.

Study Design and Methods

A total of 628 samples with ambiguous serologic results from different immunohematology laboratories throughout the Flanders region, Belgium, were genotyped using a commercially available weak D typing approach. After exclusion of detectable weak D types, molecular RHD exon scanning was performed for the remaining samples, and RHD sequencing was performed in two particular cases.

Results

Of all samples investigated, 424 (67.5%) were positive for weak D Type 1, 2, or 3, and 22 cases (3.5%) typed weak D Type 4.0/4.1/4.3, 4.2, 5, 11, 15, or 17. Another 49 (7.8%) samples were partial D variants, with a major proportion being category DVI types (n = 27). One RHD(S103P) sample was identified as high‐grade partial D, with DIII‐like phenotype and anti‐D and anti‐C immunization. Additionally, a novel DVI Type 3 (A399T) variant was found. Of the remaining 133 samples mainly tested because of ambiguous serologic D typing results due to recent transfusion, 32 (5.1%) were negative for RHD, and 101 (16.1%) were indistinguishable from wild‐type RHD and not investigated further.

Conclusion

Despite the enormous diversity of RHD alleles, first‐line weak D genotyping was remarkably informative, allowing for rapid classification of most samples with conspicuous RhD phenotype in Flanders. The clinical implications are discussed.
Synthesis, Characterization, and ECAP Consolidation of Carbon Nanotube Reinforced AA 4032 Nanocrystalline Composites Produced by High Energy Ball Milling
Authors: Senthil Saravanan M. S. , Kumaresh Babu S. P.
Published: November 2014

In the present work, multiwalled carbon nanotubes (MWNTs) were synthesized by electric arc discharge method in open air atmosphere. The synthesized nanotubes were subjected to multistep purification followed by characterization using Raman spectroscopy and transmission electron microscopy (TEM). These carbon nanotubes (CNTs) have inner and outer diameters of the order of 3.5 nm and 16 nm with an aspect ratio of 63. AA 4032 nanocomposites reinforced with MWNTs were produced by high energy ball milling using elemental powder mixtures. X-ray diffraction (XRD) and scanning electron microscope (SEM) studies showed different phases of composite with and without CNTs. The crystallite size and lattice strain were calculated using an anisotropic model of Williamson–Hall peak broadening analysis, which showed in decreased crystallite size with increasing milling time. TEM studies reveal that the MWNTs were uniformly distributed in the matrix. Thermal stability of the nanocrystalline powders was studied using a differential thermal analyzer (DTA). The mechanically alloyed powders were consolidated using a novel method called equal channel angular pressing (ECAP) at room temperature. The consolidated samples were sintered at 480 °C in argon atmosphere for 90 min. ECAP method was investigated as an alternative to conventionally sintered powder composites. CNT addition has shown significant improvement in the hardness of the system, even though the observed density is relatively low compared with a base alloy. Thus, the results show that ECAP enables sufficient shear deformation results in good metallurgical bonds between particles at lower compaction pressures. Hence, it is proven that ECAP can be effectively used as one of the consolidation technique especially for powders that are difficult to consolidate by other means.
Forelimbs of Tyrannosaurus Rex: A pathetic vestigial organ or an integral part of a fearsome predator?
Authors: Lee Scott A. , Thomas Joshua D.
Published: November 2014

In this paper, we examine a first-year torque and angular acceleration problem to address a possible use of the forelimbs of Tyrannosaurus rex. A 1/40th-scale model (see Fig. 1) is brought to the classroom to introduce the students to the quandary: given that the forelimbs of T. rex were too short to reach its mouth, what function did the forelimbs serve? This issue crosses several scientific disciplines including paleontology, ecology, and physics, making it a great starting point for thinking “outside the box.” Noted paleontologist Kenneth Carpenter has suggested that the forelimbs of T. rex were an integral part of its predatory behavior. Given the large teeth of T. rex, it is assumed that they killed with their teeth. Lipkin and Carpenter1 have suggested that the forelimbs were used to hold a struggling victim (which had not been dispatched with the first bite) while the final, lethal bite was applied. If that is the case, then the forelimbs must be capable of large angular accelerations α in order to grab the animal attempting to escape. The concepts of the typical first-year physics course are sufficient to test this hypothesis by solving α=τ/I. Naturally, students love solving any problem related to Tyrannosaurus rex!
“Hearing“ Electromagnetic Waves
Authors: Rojo Marta , Muñoz Juan
Published: November 2014

In this work, an educational experience is described in which a microwave communication link is used to make students aware that all electromagnetic waves have the same physical nature and properties. Experimental demonstrations are linked to theoretical concepts to increase comprehension of the physical principles underlying electromagnetic waves. Moreover, students learn about the importance and historical development of communication systems, the basic principles of communication links, and the procedure to send information through an electromagnetic wave.1,2
Delivering Engaging Content for Online Education: Key Principles and Solutions
Authors: Gilson Todd A. , Jung Jinhong
Published: November 2014

The present state of higher education is in a period of transition as alternative forms of content dissemination via blended learning and exclusively online class models continue to expand. In addition, traditional universities face increased pressure to deliver content “on-demand” for the learner from an increasing number of nonprofit and for-profit organizations. In this article, key principles for creating and distributing content for online education are discussed. Furthermore, solutions used by the authors in their own teaching are shared as an additional resource for the reader. Finally, the benefits and drawbacks of two widely known software platforms are explored as they relate to the functionality of delivering content online to students.
Agriculture facilitated permanent human occupation of the Tibetan Plateau after 3600 B.P.
Authors: Chen F. H. , Dong G. H. , Zhang D. J. , Liu X. Y. , Jia X. , An C. B. , Ma M. M. , Xie Y. W. , Barton L. , Ren X. Y. , Zhao Z. J. , Wu X. H. , Jones M. K.
Published: November 2014

Colonizing the roof of the world

Humans only settled permanently on the Tibetan plateau about 3600 years ago. Chen
et al.
examined archaeological crop remains unearthed in northeastern Tibet, which elucidate the timing of agricultural settlement. Although much earlier traces of humans in Tibet have been dated to 20,000 years ago, year-round presence at the highest altitudes appears to have been impossible until the advent of suitable crops, such as barley. Surprisingly, these prehistoric farming communities expanded onto the plateau at the same time as climate was cooling.

Science
, this issue p.
248
Nanomole-scale high-throughput chemistry for the synthesis of complex molecules
Authors: Buitrago Santanilla Alexander , Regalado Erik L. , Pereira Tony , Shevlin Michael , Bateman Kevin , Campeau Louis-Charles , Schneeweis Jonathan , Berritt Simon , Shi Zhi-Cai , Nantermet Philippe , Liu Yong , Helmy Roy , Welch Christopher J. , Vachal Petr , Davies Ian W. , Cernak Tim , Dreher Spencer D.
Published: November 2014

Breaking through the milligram floor

When chemists synthesize compounds, the threshold for success is at least a milligram of product. This has been true for decades—even though biochemical assays have long since descended into microgram territory—and results in part from the constraints of characterization methods. Buitrago Santanilla
et al.
present an automated dosing and characterization protocol for optimizing chemical reaction conditions on the microgram scale. This allowed them to screen numerous base and ligand combinations for catalytic C-N bond-forming reactions between complex pairs of compounds, in short supply, that resisted standard coupling conditions.

Science
, this issue p.
49
Finished Genome Sequence of the Laboratory Strain Escherichia coli K-12 RV308 (ATCC 31608)
Authors: Krempl Peter M. , Mairhofer Juergen , Striedner Gerald , Thallinger Gerhard G.
Published: November 2014

Escherichia coli
strain K-12 substrain RV308 is an engineered descendant of the K-12 wild-type strain. Like its ancestor, it is an important organism in biotechnological research and is heavily used for the expression of single-chain variable fragments. Here, we report the complete genome sequence of
E. coli
K-12 RV308 (ATCC 31608).
Draft Genome Sequence of the Halophilic and Highly Halotolerant
Gammaproteobacteria
Strain MFB021
Authors: Joseph Toms C. , Baby Anju , Reghunathan Dinesh , Varghese Aswathy Mary , Murugadas V. , Lalitha K. V.
Published: November 2014

We report the 4.25-Mbp first draft sequence of
Gammaproteobacteria
strain MFB021, a moderate halophile isolated from petroleum-contaminated soil in Cochin, India. The genome of the strain MFB021 was sequenced to understand the mechanism of hydrocarbon degradation and the halophilicity of the bacterium.
Complete Genome Sequence of Streptococcus pyogenes M/
emm44
Strain STAB901, Isolated in a Clonal Outbreak in French Brittany
Authors: Soriano Nicolas , Vincent Pascal , Piau Caroline , Moullec Séverine , Gautier Philippe , Lagente Vincent , Faili Ahmad , Kayal Samer
Published: November 2014

We report the complete genome sequence of an invasive isolate of
Streptococcus pyogenes
M/
emm44
, belonging to a clonal outbreak that occurred in French Brittany. The genome is composed of 1,795,608 bp, with a GC content of 38.5%, has 1,358 identified coding sequences (CDSs), and harbors a novel Tn916-like transposon (Tn6253).
Seven Strains of Enterovirus D68 Detected in the United States during the 2014 Severe Respiratory Disease Outbreak
Authors: Brown B. A. , Nix W. A. , Sheth M. , Frace M. , Oberste M. S.
Published: November 2014

Clusters of severe respiratory disease in the United States were reported to the CDC beginning in August 2014. Enterovirus D68 (EV-D68) was identified from 83% (30/36) of initial severe cases. Investigations in August and September found severe EV-D68 cases to be widespread across the United States. We report seven EV-D68 genomes from the outbreak.
First Draft Genome Sequence of a Member of the Genus
Mangrovibacter
, Isolated from an Aquaculture Farm in India
Authors: Joseph Toms C. , Varghese Aswathy Mary , Baby Anju , Reghunathan Dinesh , Murugadas V. , Lalitha K. V.
Published: November 2014

Mangrovibacter
sp. MFB070, a Gram-negative, facultatively anaerobic, nitrogen-fixing bacterium, was isolated from an aquaculture farm in Cochin, India. Here, we report the first draft genome sequence of a member of the genus
Mangrovibacter
, which may help us to elucidate the evolutionary status of this genus. The draft genome sequence of the
Mangrovibacter
sp. consists of 5,361,682 bp, encoding 4,971 predicted coding sequences in 57 contigs.
Health in overweight children: 2-year follow-up of Finnmark Activity School—a randomised trial
Authors: Kokkvoll Ane , Grimsgaard Sameline , Steinsbekk Silje , Flægstad Trond , Njølstad Inger
Published: November 2014

Objective

To compare a comprehensive lifestyle intervention for overweight children performed in groups of families with a conventional single-family treatment. Two-year follow-up data on anthropometric and psychological outcome are presented.

Design

Overweight and obese children aged 6–12 years with body mass index (BMI) corresponding to ≥27.5 kg/m2 in adults were randomised to multiple-family (n=48) or single-family intervention (n=49) in a parallel design. Multiple-family intervention comprised an inpatient programme with other families and a multidisciplinary team, follow-up visits in their hometown, weekly physical activity and a family camp. Single-family intervention included counselling by paediatric nurse, paediatric consultant and nutritionist at the hospital and follow-up by a community public health nurse. Primary outcome measures were change in BMI kg/m2 and BMI SD score after 2 years.

Results

BMI increased by 1.29 kg/m2 in the multiple-family intervention compared with 2.02 kg/m2 in the single-family intervention (p=0.075). BMI SD score decreased by 0.20 units in the multiple-family group and 0.08 units in the single-family intervention group (p=0.046). A between-group difference of 2.4 cm in waist circumference (p=0.038) was detected. Pooled data from both treatment groups showed a significant decrease in BMI SD score of 0.14 units and a significant decrease in parent-reported and self-reported Strength and Difficulty Questionnaire total score of 1.9 units.

Conclusions

Two-year outcome showed no between-group difference in BMI. A small between-group effect in BMI SD score and waist circumference favouring multiple-family intervention was detected. Pooled data showed an overall improvement in psychological outcome measures and BMI SD score.

Trial registration number

NCT00872807, http://www.clinicaltrials.gov.
A core outcome set for clinical trials in acute diarrhoea
Authors: Karas Jacek , Ashkenazi Shai , Guarino Alfredo , Lo Vecchio Andrea , Shamir Raanan , Vandenplas Yvan , Szajewska Hania
Published: November 2014

Objective

Core outcome sets are the baseline for what should be measured in clinical research and, thus, should serve as a guide for what should be collected and reported. The Consensus Group on Outcome Measures Made in Pediatric Enteral Nutrition Clinical Trials, established in 2012, agreed that consensus on a core set of outcomes with agreed-upon definitions that should be measured and reported in clinical trials was needed. To achieve this goal, six working groups (WGs) were setup, including WG on acute diarrhoea, whose main goal was to develop a core outcome set for trials in acute diarrhoea.

Methods

The first step identified how published outcomes related to acute diarrhoea were reported. The second focused on the methodology for determining which outcomes to measure in clinical trials. The third employed a two-phase questionnaire study using the Delphi technique to define clinically important outcomes to clinicians and parents.

Results

For therapeutic studies, the five most important outcome measures were diarrhoea duration, degree of dehydration, need for hospitalisation (or duration of hospitalisation for inpatients), the proportion of patients recovered by 48 h and adverse effects. The prophylactic core outcome set included prevention of diarrhoea, prevention of dehydration, prevention of hospitalisation and adverse effects.

Conclusions

The outcome sets for therapy and prevention can be recommended for use in future trials of patients with gastroenteritis. Their envisioned goal is to decrease study heterogeneity and to ease the comparability of studies. WG's next step is to determine how to measure the outcomes included in the core set.
Barriers to uptake and use of pre-exposure prophylaxis (PrEP) among communities most affected by HIV in the UK: findings from a qualitative study in Scotland
Authors: Young Ingrid , Flowers Paul , McDaid Lisa M
Published: November 2014

Objectives

To explore the acceptability of pre-exposure prophylaxis (PrEP) among gay, bisexual and men who have sex with men (MSM) and migrant African communities in Scotland, UK.

Design

Consecutive mixed qualitative methods consisting of focus groups (FGs) and in-depth interviews (IDIs) explored PrEP acceptability. Data were digitally recorded, transcribed and analysed thematically to identify anticipated and emerging themes.

Setting

Participants were recruited through community sexual health and outreach support services, and from non-sexual health settings across Scotland.

Participants

Inclusion criteria included identification as either MSM and/or from migrant African communities; 18 years and older; living in Scotland at the time of participation. 7 FGs were conducted (n=33): 5 with MSM (n=22) and 2 mixed-sex groups with African participants (n=11, women=8), aged 18–75 years. 34 IDIs were conducted with MSM (n=20) and African participants (n=14, women=10), aged 19–60 years. The sample included participants who were HIV-positive and HIV-negative or untested (HIV-positive FG participants, n=22; HIV-positive IDI participants, n=17).

Results

Understandings of PrEP effectiveness and concerns about maintaining regular adherence were identified as barriers to potential PrEP uptake and use. Low perception of HIV risk due to existing risk management strategies meant few participants saw themselves as PrEP candidates. Participants identified risk of other sexually transmitted infections and pregnancy as a concern which PrEP did not address for either themselves or their sexual partners. PrEP emerged as a contentious issue because of the potentially negative implications it had for HIV prevention. Many participants viewed PrEP as problematic because they perceived thatotherswould stop using condoms if PrEP was to become available.

Conclusions

PrEP implementation needs to identify appropriate communication methods in the context of diverse HIV literacy; address risk-reduction concerns and; demonstrate how PrEP can be part of a safe and comprehensive risk management strategy.
Monitoring sheep andCulicoidesmidges in Montana for evidence of Bunyamwera serogroup virus infection
Authors: Johnson Gregory D. , Bahnson Charlie S. , Ishii Patricia , Cochrane Zachary N. , Hokit D. Grant , Plummer Paul J. , Bartholomay Lyric C. , Blitvich Bradley J.
Published: November 2014

Introduction

A serological and entomological investigation was performed to monitor for potential Bunyamwera (BUN) serogroup virus activity in Montana.

Results

To facilitate the serological investigation, sera were collected from 104 sheep in 2013 and 2014 and assayed by plaque reduction neutralization test using all six BUN serogroup viruses known to occur in the United States: Cache Valley virus (CVV), Lokern virus (LOKV), Main Drain virus (MDV), Northway virus, Potosi virus and Tensaw virus. BUN serogroup virus‐specific antibodies were detected in 41 (39%) sheep. Of these, three were seropositive for MDV, one was seropositive for CVV, one was seropositive for LOKV and 36 had antibodies to an undetermined BUN serogroup virus. Additionally, 30,606 Culicoides sonorensis were collected in 2013 using Centers for Disease Control and Prevention (CDC) light traps and assayed for cytopathic virus by virus isolation in African Green Monkey kidney (Vero) cells. All midges were negative. Almost one‐third of the midges were further tested by reverse transcription‐polymerase chain reaction using BUN serogroup virus‐reactive primers and all were negative.

Conclusions

We provide evidence of BUN serogroup virus infection in sheep but not C. sonorensis in Montana in 2013‐2014. This study also provides the first evidence of CVV, MDV and LOKV activity in Montana.
Transition-state structure for the hydronium-ion-promoted hydrolysis of α-d-glucopyranosyl fluoride
Authors: Chan Jefferson , Tang Ariel , Bennet Andrew J.
Published: November 2014

The transition state for the hydronium-ion-promoted hydrolysis of α-d-glucopyranosyl fluoride in water has been characterized by combining multiple kinetic isotope effect measurements with theoretical modelling. The measured kinetic isotope effects for the C1-deuterium, C2-deuterium, C5-deuterium, anomeric carbon-13, and ring oxygen-18 are 1.219 ± 0.021, 1.099 ± 0.024, 0.976 ± 0.014, 1.014 ± 0.005, and 0.991 ± 0.013, respectively. The transition state for the hydronium ion reaction is late with respect to both C–F bond cleavage and proton transfer.
Melanogenic actinomycetes from rhizosphere soil — antagonistic activity against Xanthomonas oryzae and plant-growth-promoting traits
Authors: Muangham Supattra , Pathom-aree Wasu , Duangmal Kannika
Published: November 2014

A total of 210 melanogenic actinomycetes were isolated from 75 rhizospheric soils using ISP6 and ISP7 agar supplemented with antifungal and antibacterial agents. Their morphological characteristics and the presence of ll-diaminopimelic acid in whole-cell hydrolyzates revealed that all isolates belonged to the genus Streptomyces. Their ability to inhibit the growth of 2 pathogenic rice bacteria, Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola, was observed using the agar overlay method. The results indicated that 61.9% of the isolates could inhibit at least one of the tested rice pathogens. Among these, isolate TY68-3 showed the highest antibacterial activity and siderophore production. The 16S rRNA gene sequence analysis of 46 representative isolates revealed that isolates with high similarity to Streptomyces bungoensis were frequently found. The present study indicated the potential of melanogenic actinomycetes for use as biocontrol agents against X. oryzae as well as their diversity in rhizospheric soils.
Oral administration ofBifidobacterim bifidumfor modulating microflora, acid and bile resistance, and physiological indices in mice
Authors: Wang Bao-gui , Xu Hai-bo , Wei Hua , Zeng Zhe-ling , Xu Feng
Published: November 2014

Bifidobacteria are generally acknowledged as major gut microflora used as probiotics, which promote human health. In this study, the effects of the administration of Bifidobacterim bifidum on modulating gastrointestinal (GI) tract microflora, acid and bile resistance, and physiological indices in BALB/c mice were investigated. Results showed that B. bifidum can significantly improve the ecosystem of the GI tract by increasing the amount of probiotics and reducing the populations of pathogenic bacteria, as measured by plate count and real-time PCR. After exposure to simulated GI tract conditions, the growth of gut microflora in the B. bifidum group was higher than that in the control group when incubated for 12 h in MRS or nutrient broth adjusted to pH 2.0 or 3.0 or in the presence of a concentration of bile salt (0.45% m/v). The blood biochemical index was examined, and the physiological effect of the cell-free extract of gut microflora was evaluated by measuring the activity of various enzymes, including α-glucosidases, esterase, and lactate dehydrogenase. This study suggested that a B. bifidum strain can stabilize blood sugar, lower cholesterol levels in serum, and improve metabolic activity. Moreover, B. bifidum was a promising enhancer of microbial diversity in mouse intestine and played a vital role in human physiological processes, which can benefit the health of a host.
Factors influencing the seasonal diet selection by woodland caribou (Rangifer tarandus tarandus) in boreal forests in Ontario
Authors: Thompson Ian D. , Wiebe Philip A. , Mallon Erin , Rodgers Arthur R. , Fryxell John M. , Baker James A. , Reid Douglas
Published: November 2014

We used remote video cameras to assess seasonal diet composition of woodland caribou (Rangifer tarandus tarandus (L., 1758)) at three areas across the boreal forest of Ontario. Caribou consume lichens in winter, but we expected they would significantly reduce lichen consumption in favour of higher protein levels in green plants in summer. We sampled videos from 23 caribou, from 2 years, to derive seasonal diet composition. Diet differed among seasons and study areas, except in winter when lichens dominated. Diet breadth doubled from winter to summer, but overlap between seasons was still >60%. Green plants were less commonly eaten than we expected, only three genera were preferred, and few species constituted more than 2% of the diet. Preferred foods varied by land-cover types. Diet differed between managed and unmanaged landscapes but did not result from use of plant species found in successional habitats. Caribou selected a nonoptimal diet in the snow-free seasons, especially with respect to protein, suggesting factors other than nutrition influenced diet choice, and indicating the possibility of bottom-up limitation on production.
Differential Neuritogenic Activities of Two Edible Brown Macroalgae,Undaria pinnatifidaandSaccharina japonica
Authors: Hannan Md. Abdul , Mohibbullah Md. , Hwang Seon-Yeong , Lee Kyungyong , Kim Yang-Chun , Hong Yong-Ki , Moon Il Soo
Published: November 2014

Undaria pinnatifida (Harvey) Suringar and Saccharina japonica Areschoug are two common seaweeds, and both are known to have numerous pharmacological properties that include neuroprotective effects. In a previous study, we found that the ethanol extracts of U. pinnatifida (UPE) and S. japonica (SJE) had neurite promoting activities on developing hippocampal neurons. In the present study, we studied and compared the effects of UPE and SJE on neuronal maturation. Both UPE and SJE promoted neurite outgrowth in a dose-dependent manner with optimal concentrations of 5 and 15 μg/mL, respectively. Initial neuronal differentiation was significantly promoted by UPE and SJE. Subsequently, treatment with both increased indices of axonal and dendritic cytoarchitecture, such as, the numbers and lengths of primary processes, although only UPE had a significant effect on branching frequencies. In addition, UPE and SJE showed no evidence of cytotoxicity, rather they protected neurons from naturally occurring death in vitro. These results indicate that UPE and SJE promote axodendritic maturation and neuronal survival and suggest that these algal extracts, especially UPE, have beneficial effects on the nervous system.
Signatures of primordial black hole dark matter
Authors: Belotsky K. M. , Dmitriev A. E. , Esipova E. A. , Gani V. A. , Grobov A. V. , Khlopov M. Yu. , Kirillov A. A. , Rubin S. G. , Svadkovsky I. V.
Published: November 2014

The nonbaryonic dark matter of the Universe is assumed to consist of new stable forms of matter. Their stability reflects symmetry of micro-world and mechanisms of its symmetry breaking. In the early Universe heavy metastable particles can dominate, leaving primordial black holes (PBHs) after their decay, as well as the structure of particle symmetry breaking gives rise to cosmological phase transitions, from which massive black holes (BHs) and/or their clusters can originate. PBHs can be formed in such transitions within a narrow interval of masses about 1017 g and, avoiding severe observational constraints on PBHs, can be a candidate for the dominant form of dark matter. PBHs in this range of mass can give solution of the problem of reionization in the Universe at the redshift z~5–10. Clusters of massive PBHs can serve as a nonlinear seeds for galaxy formation, while PBHs evaporating in such clusters can provide an interesting interpretation for the observations of point-like gamma-ray sources. Analysis of possible PBH signatures represents a universal probe for super-high energy physics in the early Universe in studies of indirect effects of the dark matter.
Loss of hepatocyte EGFR has no effect alone but exacerbates carbon tetrachloride-induced liver injury and impairs regeneration in hepatocyte Met-deficient mice
Authors: Scheving Lawrence A. , Zhang Xiuqi , Stevenson Mary C. , Threadgill David W. , Russell William E.
Published: November 2014

The role(s) of the epidermal growth factor receptor (EGFR) in hepatocytes is unknown. We generated a murine hepatocyte specific-EGFR knockout (KO) model to evaluate how loss of hepatocellular EGFR expression affects processes such as EGF clearance, circulating EGF concentrations, and liver regeneration following 70% resection or CCl4-induced centrilobular injury. We were able to disrupt EGFR expression effectively in hepatocytes and showed that the ability of EGF and heregulin (HRG) to phosphorylate EGFR and ERBB3, respectively, required EGFR. Loss of hepatocellular EGFR impaired clearance of exogenous EGF from the portal circulation but paradoxically resulted in reduced circulating levels of endogenous EGF. This was associated with decreased submandibular salivary gland production of EGF. EGFR disruption did not result in increased expression of other ERBB proteins or Met, except in neonatal mice. Liver regeneration following 70% hepatectomy revealed a mild phenotype, with no change in cyclin D1 expression and slight differences in cyclin A expression compared with controls. Peak 5-bromo-2′-deoxyuridine labeling was shifted from 36 to 48 h. Centrilobular damage and regenerative response induced by carbon tetrachloride (CCl4) were identical in the KO and wild-type mice. In contrast, loss of Met increased CCl4-induced necrosis and delayed regeneration. Although loss of hepatocellular EGFR alone did not have an effect in this model, EGFR-Met double KOs displayed enhanced necrosis and delayed liver regeneration compared with Met KOs alone. This suggests that EGFR and Met may partially compensate for the loss of the other, although other compensatory mechanisms can be envisioned.