bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of Furan Fatty Alkyl Esters from their Bis‐Epoxide Fatty Esters
Authors: Bantchev Grigor B. , Doll Kenneth M. , Biresaw Girma , Vermillion Karl E.
Published: November 2014

Reactions of epoxidized alkyl soyate with four different alcohols: ethanol, isopropyl alcohol, 2‐ethylhexanol, benzyl alcohol, in the presence of Brønsted acid catalyst, were investigated. Products, not reported in prior studies of similar reactions, were found. These were furan fatty acid alkyl esters (FFE, mixture of alkyl 8‐(5‐hexyl‐2‐furyl) octanoate and alkyl 9‐(5‐pentyl‐2‐furyl)nonanoate) which were unambiguously identified by means of GC–MS and two‐dimensional NMR. Evidence suggests that the FFE are formed by an acid‐catalyzed rearrangement of the epoxidized linoleates. The FFE were formed in presence of all four alcohols tested and in the presence of either sulfuric acid or Amberlyst 15 catalyst. Yields of up to 13 %, as quantified by GC and NMR spectroscopies, were observed.
TALEN‐mediated mutagenesis in zebrafish reveals a role for r‐spondin 2 in fin ray and vertebral development
Authors: Tatsumi Yoshiaki , Takeda Moe , Matsuda Masaru , Suzuki Tohru , Yokoi Hayato
Published: November 2014

R‐spondin (Rspo) encodes a multi‐domain protein that modulates the Wnt‐signaling pathway. Two distinct rspo2 zebrafish mutants were generated by TALEN‐mediated mutagenesis: a null mutant, rspo2null
, lacking all functional domains, and a hypomorphic mutant, rspo2tsp
, lacking the two N‐terminal domains. Mutants were analyzed mainly for abnormalities in the skeletal system. Fin ray skeletons were formed normally in the rspo2tsp
mutants, but were absent from the rspo2null
mutants. Hypoplasia of the neural/hemal arches and ribs was observed in both mutants. Thus, the two rspo2 mutants help to identify the functions of Rspo2 in skeletogenesis, as well as functional differences among multiple Rspo2 domains.
A Rare Intra-articular Pathology of Knee Lipoma Arborescens: A Report of Two Cases Managed by Arthroscopic Synovectomy
Authors: Yee Lee Sung , Chuen Yip Sin , Hong Yuen Wai
Published: November 2014

Lipoma arborescens is a rare intra-articular condition of unknown exact aetiology. Lipoma arborescens is one of the differential diagnoses of diffuse chronic swelling of the knee and its magnetic resonance imaging (MRI) appearance is diagnostic. We present two cases of patients with recurrent knee effusion. MRI showed a frond-like fatty synovial mass and joint effusion that suggested the likelihood of lipoma arborescens. Arthroscopic synovectomy was performed and pathology confirmed the diagnosis. There was no recurrence of symptoms after synovectomy.
Intracellular metabolite levels shape sulfur isotope fractionation during microbial sulfate respiration
Authors: Wing Boswell A. , Halevy Itay
Published: November 2014

Significance

Microbes can discriminate among metabolites that differ only in the stable isotopes of the same element. This stable isotope fractionation responds systematically to environmental variables like extracellular metabolite concentrations and to physiological ones like cell-specific metabolic rates. These observable characteristics define a stable isotope phenotype, as exemplified by the rich database of experimental sulfur isotope fractionations from sulfate-respiring bacteria and archaea. We developed a quantitative model for sulfur isotope fractionation during sulfate respiration that incorporates only experimentally accessible biochemical information. With this approach, stable isotope phenotypes can be decomposed into their physiological, enzymatic, and environmental parts, potentially illuminating the relative influences of these components in natural microbial populations today, as well as how they may have varied in the deep past.
Halorhodopsin pumps Cl–and bacteriorhodopsin pumps protons by a common mechanism that uses conserved electrostatic interactions
Authors: Song Yifan , Gunner M. R.
Published: November 2014

Significance

Changing a few residues can change the function of homologous proteins. The chloride and proton affinity in the inward chloride-pumping halorhodopsin (HR) and outward proton-pumping bacteriorhodopsin (BR) are compared using classical electrostatic simulations. BR binds and releases protons from acidic residues that have been removed from HR. In the states where these acids are ionized in BR, HR binds a chloride. In the states where these acids bind a proton in BR, HR releases the chloride. Thus, BR uses static anions and mobile protons, whereas HR uses mobile ions to maintain the same charge states. The use of mobile ions makes HR more sensitive to external conditions.
Luminescence color switching of supramolecular assemblies of discrete molecular decanuclear gold(I) sulfido complexes
Authors: Hau Franky Ka-Wah , Lee Terence Kwok-Ming , Cheng Eddie Chung-Chin , Au Vonika Ka-Man , Yam Vivian Wing-Wah
Published: November 2014

Significance

Polynuclear gold(I) complexes have attracted enormous attention over the past decades owing to their intriguing luminescence behavior and their interesting structural and bonding properties, especially with regard to their propensity to form noncovalent short gold–gold contacts. Most works in polynuclear gold(I) clusters involve structural studies in the solid state, with less attention focused on supramolecular assembly in solution. Herein, discrete decanuclear gold(I) μ
3
-sulfido complexes with long alkyl chains are found to form supramolecular assemblies with different luminescence and morphologies that are tunable by solvent modulation. This has demonstrated the importance of the control and manipulation of intercluster assembly in influencing the photophysical properties and morphologies of the clusters. Such findings have not been previously reported in discrete molecular gold(I) systems.
Single-cell mass cytometry of TCR signaling: Amplification of small initial differences results in low ERK activation in NOD mice
Authors: Mingueneau Michael , Krishnaswamy Smita , Spitzer Matthew H. , Bendall Sean C. , Stone Erica L. , Hedrick Stephen M. , Pe'er Dana , Mathis Diane , Nolan Garry P. , Benoist Christophe
Published: November 2014

Significance

Activation of T lymphocytes by the rearranged T-cell receptor (TCR) conditions essentially all aspects of their differentiation and function, and variations in the efficacy of signal transduction condition pathogen resistance and autoimmune deviation. We explored the defects in signal transduction downstream of the TCR in diabetes-susceptible nonobese diabetic (NOD) mice using mass cytometry and computational processing of single-cell data. We found that small initial differences in the efficacy of triggering at the apex of the cascade result in much more profound differences downstream, with the system being set to amplify the discriminating power of initial sensing to arrive at more marked response/no response decisions within T cells.
Mass spectrometry-based protein identification with accurate statistical significance assignment
Authors: Alves Gelio , Yu Yi-Kuo
Published: November 2014

Motivation: Assigning statistical significance accurately has become increasingly important as metadata of many types, often assembled in hierarchies, are constructed and combined for further biological analyses. Statistical inaccuracy of metadata at any level may propagate to downstream analyses, undermining the validity of scientific conclusions thus drawn. From the perspective of mass spectrometry-based proteomics, even though accurate statistics for peptide identification can now be achieved, accurate protein level statistics remain challenging.

Results: We have constructed a protein ID method that combines peptide evidences of a candidate protein based on a rigorous formula derived earlier; in this formula the database P-value of every peptide is weighted, prior to the final combination, according to the number of proteins it maps to. We have also shown that this protein ID method provides accurate protein level E-value, eliminating the need of using empirical post-processing methods for type-I error control. Using a known protein mixture, we find that this protein ID method, when combined with the Sorić formula, yields accurate values for the proportion of false discoveries. In terms of retrieval efficacy, the results from our method are comparable with other methods tested.

Availability and implementation: The source code, implemented in C++ on a linux system, is available for download at ftp://ftp.ncbi.nlm.nih.gov/pub/qmbp/qmbp_ms/RAId/RAId_Linux_64Bit.

Contact:  yyu@ncbi.nlm.nih.gov

Supplementary information:  Supplementary data are available at Bioinformatics online.
Arousal and locomotion make distinct contributions to cortical activity patterns and visual encoding
Authors: Vinck Martin , Batista-Brito Renata , Knoblich Ulf , Cardin Jessica A.
Published: November 2014

Spontaneous and sensory-evoked cortical activity is highly state-dependent, yet relatively little is known about transitions between distinct waking states. Patterns of activity in mouse V1 differ dramatically between quiescence and locomotion, but this difference could be explained by either motor feedback or a change in arousal levels. We recorded single cells and local field potentials from area V1 in mice head-fixed on a running wheel and monitored pupil diameter to assay arousal. Using naturally occurring and induced state transitions, we dissociated arousal and locomotion effects in V1. Arousal suppressed spontaneous firing and strongly altered the temporal patterning of population activity. Moreover, heightened arousal increased the signal-to-noise ratio of visual responses and reduced noise correlations. In contrast, increased firing in anticipation of and during movement was attributable to locomotion effects. Our findings suggest complementary roles of arousal and locomotion in promoting functional flexibility in cortical circuits.

Abbreviations

LFP

Local Field Potential

V1

primary visual cortex

PD

pupil diameter

FS

fast spiking

RS

regular spiking

FR

firing rate

L-on

locomotion onset

L-off

locomotion offset

L

locomotion

LE

early locomotion

LL

late locomotion

Q

quiescence

QE

early quiescence

QM

middle quiescence

QL

late quiescence

SNR

signal-to-noise ratio

ITI

Inter-trial-interval

LV

local coefficient of variation

ISI

inter-spike-interval

s.e.m.

standard error of the mean

SD

standard deviation

ID

Isolation Distance
Defects in a New Class of Sulfate/Anion Transporter Link Sulfur Acclimation Responses to Intracellular Glutathione Levels and Cell Cycle Control
Authors: Fang Su-Chiung , Chung Chin-Lin , Chen Chun-Han , Lopez-Paz Cristina , Umen James G.
Published: November 2014

We previously identified a mutation, suppressor of mating type locus3 15-1 (smt15-1), that partially suppresses the cell cycle defects caused by loss of the retinoblastoma tumor suppressor-related protein encoded by the MAT3 gene in Chlamydomonas reinhardtii. smt15-1 single mutants were also found to have a cell cycle defect leading to a small-cell phenotype. SMT15 belongs to a previously uncharacterized subfamily of putative membrane-localized sulfate/anion transporters that contain a sulfate transporter domain and are found in a widely distributed subset of eukaryotes and bacteria. Although we observed that smt15-1 has a defect in acclimation to sulfur-limited growth conditions, sulfur acclimation (sac) mutants, which are more severely defective for acclimation to sulfur limitation, do not have cell cycle defects and cannot suppress mat3. Moreover, we found that smt15-1, but not sac mutants, overaccumulates glutathione. In wild-type cells, glutathione fluctuated during the cell cycle, with highest levels in mid G1 phase and lower levels during S and M phases, while in smt15-1, glutathione levels remained elevated during S and M. In addition to increased total glutathione levels, smt15-1 cells had an increased reduced-to-oxidized glutathione redox ratio throughout the cell cycle. These data suggest a role for SMT15 in maintaining glutathione homeostasis that impacts the cell cycle and sulfur acclimation responses.
Experimental evidence that even minor livestock trampling has severe effects on land snail communities in forest remnants
Authors: Denmead Lisa H. , Barker Gary M. , Standish Rachel J. , Didham Raphael K.
Published: November 2014

Land‐use intensification is increasing dramatically in production systems world‐wide. Livestock production is an important component of production land use, and increases in livestock densities have had a wide range of negative consequences. The off‐site effects of livestock grazing and trampling on native vegetation adjacent to pastoral land have received less attention than on‐farm effects. Moreover, where significant ecological effects of livestock spillover have been identified, the mechanistic determinants of these effects have not typically been investigated.

Here, we tested the mechanistic drivers of livestock trampling effects on land snail communities in forest remnants using simulated trampling under field conditions. We used a factorial combination of leaf‐litter manipulation and trampling treatments to partition different causal drivers of livestock impacts on land snail communities and related them to five environmental variables that are altered by livestock.

We show that even very low frequency trampling caused severe changes to land snail communities. Land snail density, even under the lowest trampling frequency, declined by an average of 42 individuals m−2 and land snail species richness decreased by an average of 10 species per plot compared with control plots.

The underlying drivers of changes in land snail communities varied, but were primarily linked to leaf‐litter mass, rather than soil compaction.

Synthesis and applications. Overall, these results suggest that even minimal disturbance by livestock has large effects on land snail communities, but the underlying drivers of these effects require further investigation in longer duration and more intensive studies. Our results provide strong support for livestock exclusion as an important management tool for native forest remnants embedded within production landscapes.
Serum vitamin D levels are inversely related with non‐alcoholic fatty liver disease independent of visceral obesity in Chinese postmenopausal women
Authors: Lu Zhigang , Pan Xiaoping , Hu Yaqin , Hao Yaping , Luo Yuqi , Hu Xiang , Ma Xiaojing , Bao Yuqian , Jia Weiping
Published: November 2014

The aim of the present study was to investigate the association between serum vitamin D levels and both visceral adipose and with non‐alcoholic fatty liver disease (NAFLD) in Chinese postmenopausal women. Four hundred and fifty‐one postmenopausal women between 45 and 74 years of age (mean (± SD) age 57.3 ± 4.6 years) were enrolled in the study. All subjects participated in the Shanghai Obesity Study between June and August 2011 and underwent abdominal magnetic resonance imaging and an abdominal ultrasonography. Patients with a visceral fat area (VFA) ≥ 80 cm2 were classified as abdominally obese. Serum 25‐hydroxyvitamin D3 (25(OH)D3) levels were measured with an electrochemiluminescence immunoassay. The prevalence of NAFLD in the study population was 34.8% (n = 157). Women with abdominal obesity had significantly lower serum 25(OH)D3 levels than those without abdominal obesity (median (interquartile range) 11.23 (8.64–14.12) vs 12.56 (9.41–15.98) ng/mL, respectively; P < 0.01). Regardless of abdominal obesity status, serum 25(OH)D3 levels in patients with NAFLD were lower than those without non‐NAFLD (11.14 (8.63–13.81) vs 12.92 (9.48–16.37) ng/mL (P < 0.05) for those without abdominal obesity; 10.86 (8.61–13.56) vs 11.55 (8.82–16.38) ng/mL (P < 0.05) for those with abdominal obesity). Partial correlation analyses demonstrated a negative correlation between serum 25(OH)D3 levels and VFA (P < 0.05). Logistic regression analysis revealed that high serum 25(OH)D3 levels were a protective factor against NAFLD after adjusting for risk factors such as VFA. In conclusion, independent of visceral obesity, vitamin D is inversely correlated with NAFLD in Chinese postmenopausal women.
Application of microRNAs in diagnosis and treatment of cardiovascular disease
Authors: Wronska A. , Kurkowska‐Jastrzebska I. , Santulli G.
Published: November 2014

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Innovative, more stringent diagnostic and prognostic biomarkers and effective treatment options are needed to lessen its burden. In recent years, microRNAs have emerged as master regulators of gene expression – they bind to complementary sequences within the mRNAs of their target genes and inhibit their expression by either mRNA degradation or translational repression. microRNAs have been implicated in all major cellular processes, including cell cycle, differentiation and metabolism. Their unique mode of action, fine‐tuning gene expression rather than turning genes on/off, and their ability to simultaneously regulate multiple elements of relevant pathways makes them enticing potential biomarkers and therapeutic targets. Indeed, cardiovascular patients have specific patterns of circulating microRNA levels, often early in the disease process. This article provides a systematic overview of the role of microRNAs in the pathophysiology, diagnosis and treatment of CVD.
P2X receptors trigger intracellular alkalization in isolated perfused mouse medullary thick ascending limb
Authors: de Bruijn P. I. A. , Bleich M. , Praetorius H. A. , Leipziger J.
Published: November 2014

Aims

Extracellular ATP is an important regulator of renal tubular transport. Recently, we found that basolateral ATP markedly inhibits Na+ and Cl− absorption in mouse medullary thick ascending limb (mTAL) via a P2X receptor. The underlying mechanism that mediates this ATP‐dependent transport inhibition in mTAL is, however, unclear. The renal outer medullary K+ channel (ROMK) is sensitive to intracellular pH where a reduction leads to closing of ROMK. We speculated that P2X receptor stimulation in the TAL could lead to changes in pHi, leading to a reduction in NaCl transport.

Methods

To test this hypothesis, we measured pHi in single perfused mouse mTALs using the fluorescent ratiometric dye 2′,7′‐bis‐(2‐carboxyethyl)‐5‐(and‐6)‐carboxyfluorescein acetoxymethylester.

Results

Interestingly, basolateral ATP (100 μm) caused a prominent, reversible intracellular alkalization of mTAL, with an average pHi increase of 0.14 ± 0.02 (n = 14). This was completely abolished by the P2X receptor antagonist periodate‐oxidized ATP (50 μm). The P2X receptor‐mediated intracellular alkalization required the activity of the apical Na+/H+ exchanger (NHE3). Typically, Gq‐coupled receptors cause a significant acidification of tubular epithelial cells, which was confirmed in this study, by P2Y2 and Ca2+ sensing receptor stimulation.

Conclusion

This study reports that stimulation of basolateral P2X receptors causes a substantial intracellular alkalization in the isolated perfused mouse mTAL. This intracellular alkalization is mediated through an increased apical NHE3 activity, similar to what we previously observed when tubular transport is inhibited with furosemide. This increased NHE3 activity causes H+ secretion in the mTAL and provides further support that the TAL is a site of urinary acidification.
Alveolar–capillary adaptation to chronic hypoxia in the fatty lung
Authors: Yilmaz C. , Ravikumar P. , Gyawali D. , Iyer R. , Unger R. H. , Hsia C. C. W.
Published: November 2014

Aim

Obese diabetic (ZDF fa/fa) rats with genetic leptin resistance suffer chronic lipotoxicity associated with age‐related lung restriction and abnormal alveolar ultrastructure. We hypothesized that these abnormalities impair adaptation to ambient hypoxia.

Methods

Male fa/fa and lean (+/+) ZDF rats (4‐months old) were exposed to 21 or 13% O2 for 3 weeks. Lung function was measured under anaesthesia. Lung tissue was assayed for DNA damage and ultrastructure measured by morphometry.

Results

In normoxia, lung volume, compliance and diffusing capacity were lower, while blood flow was higher in fa/fa than +/+ rats. In hypoxia, fa/fa animals lost more weight, circulating hematocrit rose higher, and lung volume failed to increase compared to +/+. In fa/fa, the hypoxia‐induced increase in post‐mortem lung volume was attenuated (19%) vs. +/+ (39%). Alveolar ducts were 35% smaller in normoxia but enlarged twofold more in hypoxia compared to +/+. Hypoxia induced broad increases (90–100%) in the volumes and surface areas of alveolar septal components in +/+ lungs; these increases were moderately attenuated in fa/fa lungs (58–75%), especially that of type II epithelium volume (16 vs. 61% in +/+). In fa/fa compared to +/+ lungs, oxidative DNA damage was greater with increased hypoxia induced efflux of alveolar macrophages. Harmonic mean thickness of the diffusion barrier was higher, indicating higher structural resistance to gas transfer.

Conclusion

Chronic lipotoxicity impaired hypoxia‐induced lung expansion and compensatory alveolar growth with disproportionate effect on resident alveolar progenitor cells. The moderate structural impairment was offset by physiological adaptation primarily via a higher hematocrit.
Impact of ungulate exclusion on understorey succession in relation to forest management in the Intermountain Western United States
Authors: Pekin Burak K. , Endress Bryan A. , Wisdom Michael J. , Naylor Bridgett J. , Parks Catherine G.
Published: November 2014

Questions

Do successional trajectories in plant diversity, heterogeneity and dominance respond differently to ungulate exclusion in unmanaged forests vs managed forests that are thinned and burned? Is vegetation in recently thinned and burned stands more sensitive to changes in the grazing regime?

Location

Northeast OR, USA.

Methods

We evaluated changes in plant community composition, diversity, heterogeneity and dominance under herbivory by multiple ungulates (cattle, elk, deer) vs ungulate exclusion at sites where trees were recently thinned and a prescribed burn was applied (managed), and in sites that were not thinned or burned in over 40 yr (unmanaged). Plant species diversity was calculated with the Simpsons index and richness as the total number of plant species. We estimated changes in plant community heterogeneity using a measure of taxonomic dissimilarity. Plant dominance was measured as the relative evenness among different plant functional groups (annual and perennial forbs and graminoids, and shrubs, subshrubs and trees).

Results

As expected, managed sites displayed more early succession species, such as annual forbs and annual graminoids, while unmanaged sites were dominated by late‐succession species such as shrubs, subshrubs and trees. Species richness, particularly of annuals, was strongly reduced when ungulates were excluded from managed sites, and to a lesser extent from unmanaged sites for some perennial plant species. Species diversity decreased to a slightly greater extent with ungulate exclusion at managed sites. Species dominance was not influenced by ungulate exclusion. The effect of ungulate exclusion on plant heterogeneity also depended on forest management. Heterogeneity increased at managed sites and decreased in unmanaged sites with ungulate exclusion. Overall, the change in vegetation composition over time increased with the exclusion of ungulates, particularly at managed sites.

Conclusions

The strength and direction of specific vegetation and diversity responses to ungulate exclusion vary with forest management, and the influence of ungulate exclusion on plant succession is more pronounced in recently thinned and burned sites. Management of wild and domestic ungulates thus needs to account for forest management activities that alter vegetation seral stage and increase the sensitivity of vegetation to the ungulate grazing regime.
Spermatogenesis, sperm cell morphology and accompanying secretions from two interstitial marine mites
Authors: Pepato Almir R. , Antoniazzi Marta M. , Jared Carlos
Published: November 2014

The sperm cell morphology and spermatogenesis of Halacaroides antoniazziae Pepato Tiago and da Rocha 2011 and Acaromantis vespucioi Pepato and Tiago 2004 was investigated. Halacaroides sperm cells have a complete acrosomal complex, dense tubules crossing the cytoplasm and modified mitochondria. Mature sperm cells are surrounded by two kinds of secretions. Inside the ejaculatory duct, they lie upon a centre composed of a secretion structured as heaps of elongated bodies. Acaromantis spermatozoa are spindle shaped and lack an acrosomal complex. The plasmalemma is deeply folded; the cytoplasm is very reduced and devoid of organelles. A single kind of globular secretion was found. The sperm mass is surrounded by two layers of amorphous secretions. These species share a peripheral pattern of nuclear condensation during spermatogenesis, a possible apomorphy for most halacarids, and no special adaptation to the interstitial environment could be related to their sperm cell morphology.
High‐dose chemotherapeutics of intravesical chemotherapy rapidly induce mitochondrial dysfunction in bladder cancer‐derived spheroids
Authors: Yoshida Takahiro , Okuyama Hiroaki , Nakayama Masashi , Endo Hiroko , Nonomura Norio , Nishimura Kazuo , Inoue Masahiro
Published: November 2014

Non‐muscle invasive bladder cancer is treated with intravesical chemotherapy (IVC) after transurethral resection (TUR) to reduce the probability of recurrence. Despite improvement, the recurrence rate remains high. Intravesical chemotherapeutics at high doses are expected to ablate unresected tumors and floating cancer cells after TUR, although the fate of bladder cancer cells exposed to high‐dose chemotherapeutics remains unclear. In this study, we utilized cancer tissue‐originated spheroids (CTOS) prepared from bladder cancers or patient‐derived xenografts, which may recapitulate human tumors better than 2‐D cultures of established cell lines. We exposed CTOS to 1 mg/mL of epirubicin (EPI) or mitomycin C (MMC) for 2 h. EPI was promptly and homogeneously distributed into cancer cells in the CTOS. Two hours after exposure to MMC, the mitochondrial membrane potential decreased and the mitochondria were fragmented, while plasma membrane integrity was maintained. ATP levels rapidly decreased in CTOS after exposure to EPI or MMC. Although activation of the apoptotic pathway was confirmed by the advent of cleaved poly (ADP‐ribose) polymerase, fragmentation of DNA (a hallmark of apoptosis) was not observed in CTOS after exposure to EPI and MMC. In the CTOS prepared directly from 19 surgical specimens exposed to EPI and MMC, the decrease of ATP levels varied among patients. Further establishment of the test might help the drug selection and the prediction of recurrence for individual patients.
Intermittent chemotherapy can retain the therapeutic potential of anti‐CD137 antibody during the late tumor‐bearing state
Authors: Tongu Miki , Harashima Nanae , Tamada Koji , Chen Lieping , Harada Mamoru
Published: November 2014

Immunomodulating monoclonal antibodies (mAb) can evoke antitumor T‐cell responses, which are attenuated by regulatory T cells (Treg) and myeloid‐derived suppressor cells (MDSC). Treatment with cyclophosphamide (CP) and gemcitabine (GEM) can mitigate the immunosuppression by Treg and MDSC, respectively. In the current study, we examined the antitumor effects of a combination of local injection with anti‐CD137 mAb and intermittent low‐dose chemotherapy using CP and GEM in subcutaneously established CT26 colon carcinoma. Although a significant antitumor effect was observed when local anti‐CD137 mAb therapy (5 μg) was started early in the tumor‐bearing stage (day 10), no therapeutic efficacy was observed when the mAb therapy was started at a later tumor‐bearing stage (day 17). Analyses of the tumor‐infiltrating immune cells revealed that the number of Gr‐1high/low CD11b+ MDSC started to increase 13 days after tumor inoculation, whereas injection with low‐dose (50 mg/kg) CP and GEM mitigated this increase. In addition, although intermittent injections with low‐dose CP and GEM on days 10 and 18 suppressed tumor growth significantly, additional local injections of anti‐CD137 mAb on days 19, 21, and 23 further augmented the therapeutic efficacy. Cytotoxic T lymphocytes reactive to CT26 and a tumor antigen peptide were induced successfully from the spleen cells of tumor‐cured or tumor‐stable mice. In a bilateral tumor inoculation model, this combination therapy achieved systemic therapeutic effects and suppressed the growth of mAb‐untreated tumors. These results suggest that intermittent immunochemotherapy using CP and GEM could retain the therapeutic potential of anti‐CD137 mAb that is normally impaired during the late tumor‐bearing stage.
A cluster randomized controlled non‐inferiority trial of 5‐day Dose Adjustment for Normal Eating (DAFNE) training delivered over 1 week versus 5‐day DAFNE training delivered over 5 weeks: the DAFNE 5 × 1‐day trial
Authors: Elliott J. , Rankin D. , Jacques R. M. , Lawton J. , Emery C. J. , Campbell M. J. , Dixon S. , Heller S. R. ,   the NIHR DAFNE Research Study Group
Published: November 2014

Aims

To compare, in a randomized controlled non‐inferiority trial, the outcomes of the traditional format for Dose Adjustment for Normal Eating structured education courses; that is, one delivered over 5 consecutive days (1‐week course) with a variant of this format delivered 1 day a week for 5 consecutive weeks (5‐week course).

Methods

Adults with Type 1 diabetes, from seven UK Dose Adjustment For Normal Eating training centres, were individually randomized, stratified by centre, to receive either a 1‐week or 5‐week course. A qualitative study was embedded within the trial to explore patients’ experiences.

Results

In total, 213 patients were randomized and 160 completed the study procedures. In the per‐protocol analysis, the difference in HbA1c levels (95% CI) between the arms at 6 months was 0.4 mmol/mol (−2.4, 3.1) or 0.03% (−0.22, 0.28) and −0.9 mmol/mol (−3.9, 2.2) or −0.08% (−0.36, 0.20) at 12 months. All confidence limits were within the non‐inferiority margin of ± 5.5 mmol/mol (0.5%) for HbA1c%. For those patients with a baseline HbA1c of ≥ 58 mmol/mol (≥ 7.5%) the mean change (95% CI) in HbA1c was −2.2 mmol/mol (−4.0, −0.4) or −0.20% (−0.37, −0.04) at 6 months (P = 0.016), and −2.0 mmol/mol (−4.1, 0.04) or −0.18% (−0.37 to 0.004) at 12 months (P = 0.055). Episodes of severe hypoglycaemia were decreased by 82% [relative risk 0.18 (95% CI 0.03–0.936); P = 0.042], psychosocial outcomes improved significantly, and the difference between arms was not significant. Qualitative interviews showed that patients overwhelmingly favoured the format of course that they attended.

Conclusions

In summary, 5‐week and 1‐week Dose Adjustment for Normal Eating courses are equivalent in terms of biomedical and psychosocial outcomes, and we were persuaded that both course formats should be made available in routine care.
Relation of Left Atrial Stiffness to Insulin Resistance in Obese Children: Doppler Strain Imaging Study
Authors: Mahfouz Ragab A. , Gomma Abdelaziz , Goda Mohamed , Safwat Mohamed
Published: November 2014

Background

The main objective of the study was to assess the strain measures (peak systolic longitudinal strain [LAS] and stiffness index [LASt]) and their relation to insulin resistance in obese children.

Methods and results

Eighty obese children (body mass index was 28.2 ± 3.1) and 60 age‐matched healthy nonobese children were recruited. Conventional, tissue Doppler imaging LAS and LASt were measured for all children using 2D speckle tracking imaging (2DSI). Insulin resistance was assessed for obese children. Mean LAS was lower, and mean LASt was higher in obese children as compared to control group (11.3 + 2.2 vs. 38.2 + 11.6, P < 0.001, and 1.12 ± 0.23 vs. 0.21 ± 0.11, P < 0.001, respectively). LASt was significantly correlated with insulin resistance (P < 0.0001), and a value of >1.0 of LASt was the best cutoff value which can predict insulin resistance in obese children with a sensitivity of 92% and specificity of 86%.

Conclusions

LAS and LASt differed significantly in obese and nonobese children, in spite of normal left ventricular systolic and diastolic functions. LAS and LASt were associated with insulin resistance in obese children.
Host specificity testing and examination for plant pathogens reveals that the gall‐inducing psyllid Calophya latiforceps is safe to release for biological control of Brazilian peppertree
Authors: Diaz Rodrigo , Manrique Veronica , Munyaneza Joseph E. , Sengoda Venkatesan G. , Adkins Scott , Hendricks Katherine , Roberts Pamela D. , Overholt William A.
Published: November 2014

Brazilian peppertree, Schinus terebinthifolia Raddi (Anacardiaceae), is one of the worst upland exotic weeds in Florida, USA. Foreign exploration for natural enemies led to the discovery of a pit‐galling psyllid, Calophya latiforceps Burckhardt (Hemiptera: Calophyidae), in the state of Bahia, Brazil, in 2010. Crawlers of C. latiforceps stimulate the formation of galls on the leaves of S. terebinthifolia resulting in leaf discoloration and in some cases leaf abscission. To determine whether C. latiforceps is a safe candidate for biological control of S. terebinthifolia, host specificity and the presence of selected plant pathogens were examined. Adult oviposition, gall formation, and adult survival of C. latiforceps were examined on 89 plant species under no‐choice and choice conditions. We found that C. latiforceps laid eggs on plants in seven families; however, crawlers stimulated gall formation and completed development to adult only on S. terebinthifolia. All crawlers on non‐target plants died, likely due to starvation caused either by the absence of a feeding stimulus or by a hypersensitive plant response. Under no‐choice conditions, 10% of adults lived for 19 days on the target weed, but adult survival was reduced to <3 days on non‐target plants. Choice testing revealed that females preferred to oviposit on S. terebinthifolia compared to non‐target plants. Molecular methods and indicator host inoculations did not detect the presence of ‘Candidatus Liberibacter solanacearum’, ‘Ca. L. asiaticus’, ‘Ca. L. americanus’, ‘Ca. L. africanus’, or plant viruses in adult C. latiforceps. We conclude that releasing C. latiforceps in the USA will have extremely low risk to non‐target plants, and provides another tool for the management of S. terebinthifolia.
Effect of different desensitizers on inhibition of bovine dentin demineralization: micro‐computed tomography assessment
Authors: Lodha Ena , Hamba Hidenori , Nakashima Syozi , Sadr Alireza , Nikaido Toru , Tagami Junji
Published: November 2014

This study evaluated the effect of two desensitizers on inhibition of dentin demineralization, after immersion in artificial saliva using micro‐computed tomography (μCT). Dentin blocks cut from bovine incisors were treated with deionized water (DW, a negative control) or one of three desensitizers: a fluoride varnish (Duraphat, a positive control), a calcium phosphate desensitizer (Teethmate Desensitizer), and a fluoro‐alumino‐calcium silicate‐based desensitizer (Nanoseal). After each treatment, the specimens in Duraphat, Nanoseal, and Teethmate Desensitizer groups were pre‐immersed in artificial saliva (pH 6.5) for either 1 d or 1 wk. The mineral loss of the specimens after demineralization (pH 5.0, 3 h) was evaluated by μCT. The treated surface was investigated with scanning electron microscopy. Mineral loss in all treatment groups was significantly lower than that in DW. Duraphat was the most effective treatment against demineralization, followed by Nanoseal. Nanoseal showed significantly better reduction in mineral loss following immersion for 1 wk in artificial saliva than for 1 d. However, Teethmate Desensitizer and Duraphat did not exhibit enhanced inhibition of demineralization over a longer period of immersion in artificial saliva. Scanning electron microscopy images showed deposition of particles on the dentin in both Teethmate Desensitizer. The application of Teethmate Desensitizer and Nanoseal to the exposed dentin surface resulted in inhibition of demineralization, with Nanoseal resulting in improved inhibition after prolonged immersion in artificial saliva.
Effective induction of melanoma‐antigen‐specific CD8+ T cells via Vγ9γδT cell expansion by CD56high+ Interferon‐α‐induced dendritic cells
Authors: Nieda Mie , Terunuma Hiroshi , Eiraku Yuuta , Deng Xuewen , Nicol Andrew J.
Published: November 2014

Dendritic cells (DCs) can be differentiated from CD14+ monocytes in the presence of interferon‐α (IFNα) and granulocyte/macrophage‐colony stimulating factor (GM‐CSF) in vitro and are known as IFN‐DCs. Circulating blood CD56+ cells expressing high levels of CD14, HLA‐DR and CD86 have been shown to spontaneously differentiate into DC‐like cells in vitro after their isolation from blood. We show here that IFN‐DCs expressing high levels of CD56 (hereafter, CD56high+ IFN‐DCs) can be differentiated in vitro from monocytes obtained as adherent cells from healthy donors and patients with metastatic melanoma. These cells expressed high levels of CD14, HLA‐DR and CD86 and possessed many pseudopodia. These CD56high+ IFN‐DCs may be an in vitro counterpart of the circulating CD56+ CD14+ CD86+ HLA‐DR+ cells in blood. Conventional mature DCs differentiated from monocytes as adherent cells in the presence of GM‐CSF, IL‐4 and TNF‐α (hereafter, mIL‐4DCs) did not express CD56 or CD14. In contrast to mIL‐4DCs, the CD56high+ IFN‐DCs exhibited a stronger capacity to stimulate autologous CD56+ Vγ9γδT cells highly producing IFNγ in the presence of zoledronate and IL‐2. The CD56high+ IFN‐DCs possessing HLA‐A*0201 effectively induced Mart‐1‐modified melanoma peptide (A27L)‐specific CD8+ T cells through preferential expansion of CD56+ Vγ9γδT cells in the presence of A27L, zoledronate and IL‐2. Vaccination with CD56high+ IFN‐DCs copulsed with tumor antigens and zoledronate may orchestrate the induction of various CD56+ immune cells possessing high effector functions, resulting in strong immunological responses against tumor cells. This study may be relevant to the design of future clinical trials of CD56high+ IFN‐DCs‐based immunotherapies for patients with melanoma.
Dermal dendritic cells, but not Langerhans cells, are critical in murine single epicutaneous sensitization
Authors: Lee Chih‐Hung , Chen Jau‐Shiuh , Chiu Hsien‐Ching , Hong Chien‐Hui , Liu Ching‐Yi , Ta Yng‐Cun , Clausen Bjőrn E. , Ho Ji‐Chen , Wang Li‐Fang
Published: November 2014

A murine repeated protein‐patch model has been established to study epicutaneous sensitization in atopic dermatitis. This model has shown a predominant Th2 and a weak Th1 response in both BALB/c and C57BL/6 mice. However, Th responses induced in the repeated model are not consistent with the generally accepted theory that BALB/c and C57BL/6 mice are Th2 and Th1 prone and are representatives of human atopy and non‐atopy, respectively. In this study, a single protein‐patch model was established, which showed in addition to the Th2 response, a remarkable Th1 response in C57BL/6 mice, but not in BALB/c mice. Moreover, using muLangerin‐DTR mice, we demonstrated that dermal dendritic cells, but not Langerhans cells, are critical in single epicutaneous sensitization in both strains of mice.
A Pragmatist Perspective on Building Intercultural Communicative Competency: From Theory to Classroom Practice
Authors: Moeller Aleidine J. , Osborn Sarah R. Faltin
Published: November 2014

This article analyzes and synthesizes the major theoretical frameworks for building intercultural communicative competency (ICC) within the domain of the foreign language classroom. Researchers used a pragmatist orientation as a venue for the translation of theoretical models into usable, accessible guidelines for classroom teachers in order to provide a deeper understanding and clarity of ICC and its implementation in the language classroom.
A Discourse‐Based Approach to CALL Training and Professional Development
Authors: Williams Lawrence , Abraham Lee B. , Bostelmann Evan D.
Published: November 2014

Phase 1 of this study explores findings from a nationwide survey on computer‐assisted language learning (CALL) that was completed by 409 in‐service teachers of French, German, and Spanish. These results, in turn, informed specific themes that were explored in greater detail during focus group sessions with 22 in‐service K–12 foreign language teachers (Phase 2). The main theme that emerged from the survey and the focus groups was the perceived need (expressed by in‐service teachers) for future teachers to learn how to think about, analyze, and integrate new technologies into a foreign language curriculum without having to depend on tool‐specific training since prospective teachers will use a number of new technologies—many of which have not yet been developed—throughout their career. Consequently, Phase 3 of this study examines a new component of a foreign language pedagogy course in which 18 prospective teachers studied and applied a faceted classification scheme for analyzing and understanding computer‐mediated discourse as a tool‐independent approach to CALL training.
Impacts of altered precipitation regimes on soil communities and biogeochemistry in arid and semi‐arid ecosystems
Authors: Nielsen Uffe N. , Ball Becky A.
Published: November 2014

Altered precipitation patterns resulting from climate change will have particularly significant consequences in water‐limited ecosystems, such as arid to semi‐arid ecosystems, where discontinuous inputs of water control biological processes. Given that these ecosystems cover more than a third of Earth's terrestrial surface, it is important to understand how they respond to such alterations. Altered water availability may impact both aboveground and belowground communities and the interactions between these, with potential impacts on ecosystem functioning; however, most studies to date have focused exclusively on vegetation responses to altered precipitation regimes. To synthesize our understanding of potential climate change impacts on dryland ecosystems, we present here a review of current literature that reports the effects of precipitation events and altered precipitation regimes on belowground biota and biogeochemical cycling. Increased precipitation generally increases microbial biomass and fungal:bacterial ratio. Few studies report responses to reduced precipitation but the effects likely counter those of increased precipitation. Altered precipitation regimes have also been found to alter microbial community composition but broader generalizations are difficult to make. Changes in event size and frequency influences invertebrate activity and density with cascading impacts on the soil food web, which will likely impact carbon and nutrient pools. The long‐term implications for biogeochemical cycling are inconclusive but several studies suggest that increased aridity may cause decoupling of carbon and nutrient cycling. We propose a new conceptual framework that incorporates hierarchical biotic responses to individual precipitation events more explicitly, including moderation of microbial activity and biomass by invertebrate grazing, and use this framework to make some predictions on impacts of altered precipitation regimes in terms of event size and frequency as well as mean annual precipitation. While our understanding of dryland ecosystems is improving, there is still a great need for longer term in situ manipulations of precipitation regime to test our model.
Understanding the biological invasion risk posed by the global wildlife trade: propagule pressure drives the introduction and establishment of Nearctic turtles
Authors: García‐Díaz Pablo , Ross Joshua V. , Ayres César , Cassey Phillip
Published: November 2014

Biological invasions are a key component of human‐induced global change. The continuing increase in global wildlife trade has raised concerns about the parallel increase in the number of new invasive species. However, the factors that link the wildlife trade to the biological invasion process are still poorly understood. Moreover, there are analytical challenges in researching the role of global wildlife trade in biological invasions, particularly issues related to the under‐reporting of introduced and established populations in areas with reduced sampling effort. In this work, we use high‐quality data on the international trade in Nearctic turtles (1999–2009) coupled with a statistical modelling framework, which explicitly accounts for detection, to investigate the factors that influence the introduction (release, or escape into the wild) of globally traded Nearctic turtles and the establishment success (self‐sustaining exotic populations) of slider turtles (Trachemys scripta), the most frequently traded turtle species. We found that the introduction of a species was influenced by the total number of turtles exported to a jurisdiction and the age at maturity of the species, while the establishment success of slider turtles was best associated with the propagule number (number of release events), and the number of native turtles in the jurisdiction of introduction. These results indicate both a direct and indirect association between the wildlife trade and the introduction of turtles and establishment success of slider turtles, respectively. Our results highlight the existence of gaps in the number of globally recorded introduction events and established populations of slider turtles, although the expected bias is low. We emphasize the importance of researching independently the factors that affect the different stages of the invasion pathway. Critically, we observe that the number of traded individuals might not always be an adequate proxy for propagule pressure and establishment success.
Carbon sequestration potential in perennial bioenergy crops: the importance of organic matter inputs and its physical protection
Authors: Chimento Carlo , Almagro María , Amaducci Stefano
Published: November 2014

To date, only few studies have compared the soil organic carbon (SOC) sequestration potential between perennial woody and herbaceous crops. The main objective of this study was to assess the effect of perennial woody (poplar, black locust, willow) and herbaceous (giant reed, miscanthus, switchgrass) crops on SOC stock and its stabilization level after 6 years from plantation on an arable field. Seven SOC fractions related to different soil stabilization mechanisms were isolated by a combination of physical and chemical fractionation methods: unprotected (cPOM and fPOM), physically protected (iPOM), physically and chemically protected (HC‐μs + c), chemically protected (HC‐ds + c), and biochemically protected (NHC‐ds + c and NHC‐μs + c). The continuous C input to the soil and the minimal soil disturbance increased SOC stocks in the top 10 cm of soil, but not in deeper soil layers (10–30; 30–60; and 60–100 cm). In the top soil layer, greater SOC accumulation rates were observed under woody species (105 g m−2 yr‐1) than under herbaceous ones (71 g m−2 yr‐1) presumably due to a higher C input from leaf‐litter. The conversion from an arable maize monoculture to perennial bioenergy crops increased the organic C associated to the most labile organic matter (POM) fractions, which accounted for 38% of the total SOC stock across bioenergy crops, while no significant increments were observed in more recalcitrant (silt‐ and clay‐sized) fractions, highlighting that the POM fractions were the most prone to land‐use change. The iPOM fraction increased under all perennial bioenergy species compared to the arable field. In addition, the iPOM was higher under woody crops than under herbaceous ones because of the additional C inputs from leaf‐litter that occurred in the former. Conversion from arable cropping systems to perennial bioenergy crops can effectively increase the SOC stock and enlarge the SOC fraction that is physically protected within soil microaggregates.