bluuebunny/crossref_metadata_2025 huggingface dataset:
The primate vaginal microbiome: Comparative context and implications for human health and disease
Authors: Stumpf Rebecca M. , Wilson Brenda A. , Rivera Angel , Yildirim Suleyman , Yeoman Carl J. , Polk John D. , White Bryan A. , Leigh Steven R.
Published: October 2013

The primate body hosts trillions of microbes. Interactions between primate hosts and these microbes profoundly affect primate physiology, reproduction, health, survival, and ultimately, evolution. It is increasingly clear that primate health cannot be understood fully without knowledge of host‐microbial interactions. Our goals here are to review what is known about microbiomes of the female reproductive tract and to explore several factors that influence variation within individuals, as well as within and between primate species. Much of our knowledge of microbial variation derives from studies of humans, and from microbes located in nonreproductive regions (e.g., the gut). We review work suggesting that the vaginal microbiota affects female health, fecundity, and pregnancy outcomes, demonstrating the selective potential for these agents. We explore the factors that correlate with microbial variation within species. Initial colonization by microbes depends on the manner of birth; most microbial variation is structured by estrogen levels that change with age (i.e., at puberty and menopause) and through the menstrual cycle. Microbial communities vary by location within the vagina and can depend on the sampling methods used (e.g., swab, lavage, or pap smear). Interindividual differences also exist, and while this variation is not completely understood, evidence points more to differences in estrogen levels, rather than differences in external physical environment. When comparing across species, reproductive‐age humans show distinct microbial communities, generally dominated byLactobacillus, unlike other primates. We develop evolutionary hypotheses to explain the marked differences in microbial communities. While much remains to be done to test these hypotheses, we argue that the ample variation in primate mating and reproductive behavior offers excellent opportunities to evaluate host‐microbe coevolution and adaptation. Am J Phys Anthropol 57:119–134, 2013. © 2013 Wiley Periodicals, Inc.
Secretory ranalexin produced in recombinant Pichia pastoris exhibits additive or synergistic bactericidal activity when used in combination with polymyxin B or linezolid against multi‐drug resistant bacteria
Authors: Aleinein Rasha Abou , Schäfer Holger , Wink Michael
Published: October 2013

Ranalexin, a cationic peptide from frogs, is a potent therapeutic antimicrobial peptide (AMP). Its limited availability is an obstacle for a wider application. A high‐level production of AMPs via bioengineering is possible but remains a challenging task. In the current study, we investigated the potential antibacterial properties of recombinant ranalexin, expressed in the yeast Pichia pastoris. A 78‐bp DNA fragment encoding the mature ranalexin peptide with a 6‐His tag on its C‐terminus was designed using the preferred codon usage of P. pastoris. The gene was inserted into pPICZaA and transformed into competent cells of P. pastoris strain KM71. The yield of secretory ranalexin reached up to ∼6 mg/L culture. Time‐kill curve analysis of ranalexin against both Escherichia coli and methicillin‐resistant Staphylococcus aureus (MRSA) demonstrated a concentration‐dependent rapid bactericidal activity. In checkerboard assays, the combinations of ranalexin with the established antibiotics polymyxin B or linezolid reduced the MIC additively in most tested bacteria. Time‐kill assays indicated a significant synergism in E. coli and MRSA when ranalexin was used in combination with antibiotics, even at concentrations of 1/4 MIC or 1/2 MIC of ranalexin, respectively. Thus we propose that secretory ranalexin produced in P. pastoris could be a useful tool to unravel ranalexin's biological function and for use in future in vivo studies against multi‐resistant bacterial infections.
Hierarchically Ordered Monolithic Silica with Bimodal Porosity Obtained by Hydrolysis and Condensation of 1,4‐Bis(trimethoxysilyl)arenes
Authors: von der Lehr Martin , Weidmann Christoph , Mascotto Simone , Smarsly Bernd M.
Published: October 2013

1,4‐Bis(trimethoxysilyl)benzene and 1,4‐bis((trimethoxysilyl)‐phenyl)‐dimethoxysilane were synthesized from their corresponding diarylbromides. These bis(trimethoxysilyl)arenes were used as organosilica precursors for the preparation of macro‐/mesoporous silica monoliths, using poly(ethylen glycol) as a porogen to obtain a well‐defined bicontinuous macroporosity and mesoporosity. The porosity of the prepared materials was characterized by nitrogen sorption measurements, mercury intrusion and scanning electron microscopy. The incorporation of silylarenes was studied by solid‐state 13C NMR spectroscopy, IR spectroscopy and elemental analysis.
Replication variance estimation in unequal probability sampling without replacement: One‐stage and two‐stage
Authors: Lin C. Devon , Lu Wilson W. , Rust Keith , Sitter Randy R.
Published: October 2013

Replication‐based variance estimation methods including the bootstrap, balanced repeated replication, and the Jackknife have been studied extensively. They have been applicable primarily to stratified multistage sampling designs in which the clusters within strata are sampled with replacement or the first‐stage sampling fraction is negligible with a notable exception of a two‐stage cluster sampling with equal probability and without replacement in Rao & Wu (1988). It is common practice, however, that the first‐stage sampling fraction may not be negligible, resulting in overestimation. To alleviate this practical issue, we derive the balanced repeated replication methods and the bootstrap methods for one‐ and two‐stage stratified unequal probability sampling, where the sampling fractions are not negligible. The asymptotic property of the proposed methods is studied. In addition, the methodologies are applied to a simulated population with characteristics of a real sample survey.The Canadian Journal of Statistics41: 696‐716; 2013 © 2013 Statistical Society of Canada
Ferrisilicalite‐1 Zeolite Monolith‐Based Affinitive Recognition of Intracellular Phosphorylated Protein Alteration in Tetrahymena thermophila Exposed to Photodegradates of Roxarsone and p‐Arsanilic Acid
Authors: Zhang Wenzhong , Xu Fang , Han Jingjing , Yao Jun , Wang Deju , Yang Kai , Zeng Ceng , Yang Pengyuan
Published: October 2013

In this study, heteroatomic ferrisilicalite‐1 zeolite monolith (FS‐1 ZM) was developed for affinitive recognition of intracellular phosphorylated protein in Tetrahymena thermophila after exposure to organoarsenic feed additives (roxarsone, ROX; p‐arsanilic acid, PASA) and their photodegradates. ROX or PASA can be photodegradated into toxic inorganic arsenicals, which has become a public concern. After T. thermophila being exposed to ROX or PASA and their photodegradates, it is of significance to address intracellular protein phosphorylation alteration. However, it is challenging for effective capture of phosphorylated protein under the interference of arsenicals uptake. Followed by ferrisilicalite‐1 zeolite monolith based immobilization process, sodium dodecyl sulfate–polyacrylamide electrophoresis, in‐gel enzymatic digestion, and subsequent LC–MS/MS methodology, the integrated protocol was firstly attempted for identification of arsenic‐induced phosphorylated protein alteration. It was found there was little impact of ROX or PASA on intracellular phosphorylated protein distribution. Alternatively, phosphorylated 14‐3‐3ϵ was down‐regulated after the cells were exposed to photodegradates of ROX or PASA, which were similar to those following exposure to inorganic arsenicals. Overall, inorganic arsenicals present during the degradative pathways of ROX or PASA affect the signal transduction system of T. thermophila cells. The down‐regulation of phosphorylated 14‐3‐3ϵ would be further studied as potential biomarker for organoarsenicals released into the environment.
Exposure of Workers of Municipal Landfill Site to Bacterial and Fungal Aerosol
Authors: Kalwasińska Agnieszka , Burkowska Aleksandra , Swiontek Brzezinska Maria
Published: October 2013

The present research was aimed at assessing the quality of air in work environment of the municipal landfill site in Toruń. Air samples were collected in the outdoor space (operating landfill cell, technological square), and in indoor space (sorting station, weighing station, social room) using the impaction method. The microbiological air testing included determining the number of airborne mesophilic bacteria and molds. Bacterial strains were identified with appropriate API tests; molds were identified according to their macro and micro characteristics. In outdoor air, the highest average concentration of mesophilic bacteria were recorded at the operating landfill cell (1361 colony forming unit (CFU)/m3). The highest average concentrations of molds were recorded at the technological square (1179 CFU/m3). In indoor air, the highest average concentration of investigated microorganisms (bacteria: 10 707 CFU/m3, molds: 12 471 CFU/m3) were recorded in the sorting facility. The concentration of microorganisms in the outdoor air depended on the season (p < 0.05), but did not depend on the sampling site, while in the indoor air depended on the sampling site (p < 0.05) but did not depend on the season. Bioaerosol emitted in municipal facility was the source of bacterial (Bacillus subtilis, Pseudomonas aeruginosa) and fungal species (Aspergillus fumigatus, Madurella grisea, Penicillium manfferei, Scedosporium apiospermium, Cryptococcus neoformans), posing a health risk for humans. However Gram‐negative bacteria constituted only a small fraction of the isolated microorganisms. The highest risk of exposure to biological agents was determined in the sorting station. The majority of the outdoor air samples were classified as uncontaminated. The results emphasize the need for regular monitoring of microbiological tests in indoor and outdoor air of municipal landfill sites as well as for control strategies in order to protect workers at landfill.
An Approach Using Non‐Conventional Indicators for Detecting Microbial Water Pollution
Authors: Ezzat Safaa M.
Published: October 2013

The present study aims to investigate the suitability of the genus Aeromonas as a non‐conventional microbial indicator of water quality in different Egyptian water resources; River Nile, drainage wastewater, and chlorinated drinking water. Aeromonas was detected in 71.2% of examined samples, being maximum in drainage water and minimum in River Nile and drinking water. Several positive significant relationships between Aeromonas and the corresponding heterotrophic plate count, total coliforms, fecal coliforms, and fecal streptococci were recorded, particularly in drainage water and River Nile. 81.4% of presumptive Aeromonas species were identified as A. hydrophila. The effect of seasonal variation showed maximum recovery in summer (61.5%) and spring (28.9%) compared to autumn (5.8%) and winter (3.8%). The time needed to reduce the population by 90% (T90) was 55 h and the calculated decay coefficient was 0.018 h−1. The residual chlorine efficient to inactivate A. hydrophila in drinking water supplies should be maintained at levels not less than 0.7 mg L−1. Susceptibility of 72 isolates to 20 different antibiotics revealed recognizable multiple antibiotic resistance phenomenon toward eight (40%) of the tested antibiotics. Sensitivity was mostly directed to norfloxacin, ofloxacin, ceftriaxone, and cefotaxime. The study concluded that, supplementing the traditional indicators index of water quality with Aeromonas levels could be a simple, reliable, and inexpensive valid tool for better microbiological characterization of water.
Fixation effect of SurePath preservative fluids using epidermal growth factor receptor mutation‐specific antibodies for immunocytochemistry
Authors: Kawahara Akihiko , Taira Tomoki , Abe Hideyuki , Watari Kosuke , Murakami Yuichi , Fukumitsu Chihiro , Takase Yorihiko , Yamaguchi Tomohiko , Azuma Koichi , Akiba Jun , Ono Mayumi , Kage Masayoshi
Published: October 2013

BACKGROUND

Cytological diagnosis of respiratory disease has become important, not only for histological typing using immunocytochemistry (ICC) but also for molecular DNA analysis of cytological material. The aim of this study was to investigate the fixation effect of SurePath preservative fluids.

METHODS

Human lung cancer PC9 and 11‐18 cell lines, and lung adenocarcinoma cells in pleural effusion, were fixed in CytoRich Blue, CytoRich Red, 15% neutral‐buffered formalin, and 95% ethanol, respectively. PC9 and 11‐18 cell lines were examined by ICC with epidermal growth factor receptor (EGFR) mutation‐specific antibodies, the EGFR mutation DNA assay, and fluorescence in situ hybridization. The effect of antigenic storage time was investigated in lung adenocarcinoma cells in pleural effusion by ICC using the lung cancer detection markers.

RESULTS

PC9 and 11‐18 cell lines in formalin‐based fixatives showed strong staining of EGFR mutation‐specific antibodies and lung cancer detection markers by ICC as compared with ethanol‐based fixatives. DNA preservation with CytoRich Blue and CytoRich Red was superior to that achieved with 95% ethanol and 15% neutral‐buffered formalin fixatives, whereas EGFR mutations by DNA assay and EGFR gene amplification by fluorescence in situ hybridization were successfully identified in all fixative samples. Although cytoplasmic antigens maintained high expression levels, expression levels in nuclear antigens fell as storage time increased.

CONCLUSIONS

These results indicate that CytoRich Red is not only suitable for ICC with EGFR mutation‐specific antibodies, but also for DNA analysis of cytological material, and is useful in molecular testing of lung cancer, for which various types of analyses will be needed in future. Cancer (Cancer Cytopathol) 2014;122:145–52. © 2013 American Cancer Society
Premature termination of treatment for anorexia nervosa: Differences between patient‐initiated and staff‐initiated discharge
Authors: Sly Richard , Mountford Victoria A. , Morgan John F. , Lacey J. Hubert
Published: October 2013

Objectives

To investigate treatment drop‐out by comparing clinical indicators of patients whose discharge was initiated by staff with those who initiated discharge themselves.

Method

Ninety participants with anorexia completed questionnaires at admission and four weeks into hospitalized treatment. Weight data was collected over this same period. At discharge, participants were categorized into completer (n = 38) or patient‐initiated (n = 36) /staff‐initiated (n = 16) premature termination groups.

Results

Significant differences between staff‐initiated and patient‐initiated discharge groups were found at admission. Staff initiated groups were on average older (p = .035), and more likely to have had prior compelled treatment (p = .039). At 4 weeks those in the patient‐initiated group had put on weight at a faster rate (p = .032) and reported a decrease in alliance (p = .017). At discharge, staff initiated discharge demonstrated greater time in treatment (p = .001), greater weight gain (p = .027), and a higher discharge BMI (p = .013). At discharge, staff‐initiated drop‐outs had comparable end‐of‐treatment outcomes to those who completed treatment as planned.

Discussion

There are key differences between those who prematurely discharge themselves from treatment, compared to those who are prematurely discharged by clinical staff. Future research into drop‐out needs to take into account and recognize these differences. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:40–46)
Incorporating topographic indices into dynamic ecosystem modelling using LPJ‐GUESS
Authors: Tang Jing , Pilesjö Petter , Miller Paul A. , Persson Andreas , Yang Zhenlin , Hanna Edward , Callaghan Terry V.
Published: October 2013

Northern high‐latitude regions could feed back strongly on global warming because of large carbon pools and the fact that those regions are predicted to experience temperature increases greater than the global average. Furthermore, ecological functioning and carbon cycling are both strongly related to the prevailing hydrological conditions. In this study, we address these issues and present a newly developed model LPJ distributed hydrology (LPJ‐DH) with distributed hydrology based on the dynamic global ecosystem and biogeochemistry model LPJ‐GUESS. The new model is an enhanced version of LPJ‐GUESS, introducing parametrizations of surface water routing and lateral water fluxes between grid cells. The newly introduced topographic variables in LPJ‐DH are extracted from digital elevation models. LPJ‐DH is tested at a 50‐m resolution in the Stordalen catchment, northern Sweden. Modelled runoff is evaluated against the measured runoff from 2007 to 2009 at six outlet points. We demonstrate that the estimated monthly runoff from LPJ‐DH agrees more closely with the measured data (adjusted R2 = 0·8713) than did the standard LPJ‐GUESS model (adjusted R2 = 0·4277). However, there are still difficulties in predicting low‐flow periods. The new model shows a possible advantage in representing the drainage network as well as topographic effects on water redistribution. The modelled birch tree line is in the range of the imagery observation, and the model captures the observed values of vegetation biomass in the region. Significant changes in biomass and carbon fluxes are also observed in the new model. Generally, the study justifies the feasibility and advantages of incorporating distributed topographic indices into the dynamic ecosystem model LPJ‐GUESS. Copyright © 2013 John Wiley & Sons, Ltd.
AKT hyperactivation confers a Th1 phenotype in thymic Treg cells deficient in TGF‐β receptor II signaling
Authors: Liu Yun , Xu Yingqian , Sun Jiabin , Ma Aihui , Zhang Feng , Xia Suhua , Xu Guiqin , Liu Yongzhong
Published: October 2013

The generation of CD4+Foxp3+ Treg cells in the thymus is crucial for immune homeostasis and self‐tolerance. Recent studies have shown Treg‐cell plasticity when Th‐related transcriptional factors and cytokines are present. However, the mechanisms that maintain the stability of Treg cells are poorly understood. Here, using mice with a T‐cell‐specific deletion of the transforming growth factor‐β receptor 2 (Tgfbr2−/− mice), we identify the restriction of AKT activation as a key event for the control of Treg‐cell stability in Th1 inflammation. AKT regulation was evident in thymic CD4+Foxp3+ Treg cells before they egressed to peripheral tissues. CD4+Foxp3+ thymocytes from mice with the Tgfbr2 deletion expressed high levels of CXCR3 and T‐bet, and produced IFN‐γ and TNF‐α. Thymic Tgfbr2−/− Treg cells also showed an increase in the activation of AKT pathway. Enhanced AKT activity induced the expression of IFN‐γ both in natural and inducible Treg cells. Inhibition of AKT activity markedly attenuated the expression of IFN‐γ and TNF‐α in thymic Tgfbr2−/− Treg cells in vivo. In addition, mixed bone marrow transplantation showed that TGF‐β signaling maintained Treg‐cell stability in an intrinsic manner. Our results demonstrate that AKT hyperactivation contributes to the conversion of Treg cells to a Th1 phenotype.
Proteomic analysis of aorta of LDLR−/− mice given omega‐3 fatty acids reveals modulation of energy metabolism and oxidative stress pathway
Authors: Joumard‐Cubizolles Laurie , Gladine Cécile , Gérard Nicolas , Chambon Christophe , Brachet Patrick , Comte Blandine , Mazur Andrzej
Published: October 2013

Long chain omega 3 polyunsaturated fatty acids (LC‐n‐3PUFAs) exert potent anti‐atherosclerotic action but the mechanisms of action at the vascular level remain unclear. The present study used a non‐targeted nutrigenomic approach to investigate the modulations of the aortic proteome in atherosclerotic prone mice following DHA supplementation. LDLR−/− male mice received an atherogenic diet (20 weeks) in parallel with daily oral gavages with either oleic acid‐rich oil (Control) or a mixture of oils providing 2% of energy as DHA. The overall protein expression was determined by a proteomic approach followed by bioinformatics analysis. In addition, protein oxidative modifications, namely 4‐hydroxynonenal (4‐HNE) protein adducts, were detected with a specific antibody followed by MS analysis of the identified spots. Nineteen differentially expressed proteins have been identified in the aorta of the DHA group. The top 5 canonical pathways analysis associated all proteins to metabolic pathways and showed that most of them were related to glucose or lipid metabolism. Up‐regulation of superoxide dismutase also suggests an impact of DHA supplementation on vascular antioxidant defenses. The analysis of 4‐HNE‐protein adducts indicated that DHA supplementation did not enhance oxidative modification of proteins with 4‐HNE. This study also identified some new proteins with 4‐HNE adducts at the aortic level. In summary, DHA supplementation induces significant modifications of aorta proteome which point out the importance of metabolic changes occurring in the vascular tissue in the presence of LC‐n‐3PUFAs.
Hormones and diet, but not body weight, control hypothalamic microglial activity
Authors: Gao Yuanqing , Ottaway Nickki , Schriever Sonja C. , Legutko Beata , García‐Cáceres Cristina , de la Fuente Esther , Mergen Clarita , Bour Susanne , Thaler Joshua P. , Seeley Randy J. , Filosa Jessica , Stern Javier E. , Perez‐Tilve Diego , Schwartz Michael W. , Tschöp Matthias H. , Yi Chun‐Xia
Published: October 2013

The arcuate nucleus (ARC) of the hypothalamus plays a key role in sensing metabolic feedback and regulating energy homeostasis. Recent studies revealed activation of microglia in mice with high‐fat diet (HFD)‐induced obesity (DIO), suggesting a potential pathophysiological role for inflammatory processes within the hypothalamus. To further investigate the metabolic causes and molecular underpinnings of such glial activation, we analyzed the microglial activity in wild‐type (WT), monogenic obese ob/ob (leptin deficient), db/db (leptin‐receptor mutation), and Type‐4 melanocortin receptor knockout (MC4R KO) mice on either a HFD or on standardized chow (SC) diet. Following HFD exposure, we observed a significant increase in the total number of ARC microglia, immunoreactivity of ionized calcium binding adaptor molecule 1 (iba1‐ir), cluster of differentiation 68 (CD68‐ir), and ramification of microglial processes. The ob/ob mice had significantly less iba1‐ir and ramifications. Leptin replacement rescued these phenomena. The db/db mice had similar iba1‐ir comparable with WT mice but had significantly lower CD68‐ir and more ramifications than WT mice. After 2 weeks of HFD, ob/ob mice showed an increase of iba1‐ir, and db/db mice showed increase of CD68‐ir. Obese MC4R KO mice fed a SC diet had comparable iba1‐ir and CD68‐ir with WT mice but had significantly more ramifications than WT mice. Intriguingly, treatment of DIO mice with glucagon‐like peptide‐1 receptor agonists reduced microglial activation independent of body weight. Our results show that diet type, adipokines, and gut signals, but not body weight, affect the presence and activity levels of hypothalamic microglia in obesity. GLIA 2013;62:17–25
High mobility group box protein‐1 promotes cerebral edema after traumatic brain injury via activation of toll‐like receptor 4
Authors: Laird Melissa D. , Shields Jessica S. , Sukumari‐Ramesh Sangeetha , Kimbler Donald E. , Fessler R. David , Shakir Basheer , Youssef Patrick , Yanasak Nathan , Vender John R. , Dhandapani Krishnan M.
Published: October 2013

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Cerebral edema, a life‐threatening medical complication, contributes to elevated intracranial pressure (ICP) and a poor clinical prognosis after TBI. Unfortunately, treatment options to reduce post‐traumatic edema remain suboptimal, due in part, to a dearth of viable therapeutic targets. Herein, we tested the hypothesis that cerebral innate immune responses contribute to edema development after TBI. Our results demonstrate that high‐mobility group box protein 1 (HMGB1) was released from necrotic neurons via a NR2B‐mediated mechanism. HMGB1 was clinically associated with elevated ICP in patients and functionally promoted cerebral edema after TBI in mice. The detrimental effects of HMGB1 were mediated, at least in part, via activation of microglial toll‐like receptor 4 (TLR4) and the subsequent expression of the astrocytic water channel, aquaporin‐4 (AQP4). Genetic or pharmacological (VGX‐1027) TLR4 inhibition attenuated the neuroinflammatory response and limited post‐traumatic edema with a delayed, clinically implementable therapeutic window. Human and rodent tissue culture studies further defined the cellular mechanisms demonstrating neuronal HMGB1 initiates the microglial release of interleukin‐6 (IL‐6) in a TLR4 dependent mechanism. In turn, microglial IL‐6 increased the astrocytic expression of AQP4. Taken together, these data implicate microglia as key mediators of post‐traumatic brain edema and suggest HMGB1‐TLR4 signaling promotes neurovascular dysfunction after TBI. GLIA 2013;62:26–38
Neuronal differences between chronic low back pain and depression regarding long‐term habituation to pain
Authors: Rodriguez‐Raecke R. , Ihle K. , Ritter C. , Muhtz C. , Otte C. , May A.
Published: October 2013

Background

Longitudinal studies of experimental pain are rare and little is known about the differences regarding sensitization and habituation over longer periods in patients with chronic pain or depression compared with controls.

Methods

We used a standardized longitudinal painful heat paradigm that was designed to induce long‐term habituation in 19 patients with chronic low back pain (CLBP), 21 patients with depression (DEP) and 21 healthy participants (controls) over a time course of eight consecutive days. We applied functional magnetic resonance imaging on the first and last day of this period and after 3 months.

Results

Although the pain paradigm was standardized, patients with DEP exhibited significantly higher pain thresholds and a trend to higher pain ratings and, in functional imaging, showed less activation of the operculum and the secondary somatosensory cortex (S2) as compared to patients with CLBP and controls. Conversely, patients with CLBP showed increased activation in the anterior insula and parietal operculum as compared to patients with DEP and controls. Within session, all participants sensitized to pain, which was associated with higher activation levels in the thalamus, amygdala, midcingulate cortex, and sensory and motor areas. However, patients with depression showed significantly less activation in midbrain and brainstem areas.

Conclusion

Given that pain and depression potentiate each other clinically, our data suggest that this may involve different cortical pain areas.
Vitamin D Does Not Increase Calcium Absorption in Young Women: A Randomized Clinical Trial
Authors: Gallagher J Christopher , Jindal Prachi S , Smith Lynette M
Published: October 2013

It is commonly said that vitamin D should be used to increase calcium absorption. We tested this statement in a dose-response study of vitamin D on calcium absorption. A total of 198 white and African American women, aged 25 to 45 years, with vitamin D insufficiency, serum 25-hydroxyvitamin D (25OHD) <20 ng/mL, were randomized in a double-blind study to vitamin D3 400, 800, 1600, 2400 IU, or placebo. A calcium supplement was given to increase mean calcium intake at baseline from 706 mg/d to 1031 mg/d. Calcium absorption was measured at baseline and after 12 months using a single isotope method with radiocalcium45 and 100 mg of calcium. Mean baseline serum 25OHD was 13.4 ng/mL (33.5 nmol/L) and increased to 40 ng/mL (100 nmol/L) on the highest dose of 2400 IU. Using a multivariate regression analysis with significant predictors, baseline absorption, calcium intake, and weight, there was no increase in 12-month calcium absorption compared with baseline on any dose of vitamin D in either whites or African Americans. There was no significant relationship between 12-month calcium absorption and final serum 25OHD. In an analysis of calcium absorption and serum 25OHD at baseline, serum 25OHD levels were divided into groups: 0 to 5, 6 to 10, 11 to 15, or 16 to 20 ng/mL. There was no evidence of a threshold decrease in calcium absorption or serum 1,25 dihydroxyvitamin D (1,25(OH)2D) amongst the lowest groups. Vitamin D doses up to 2400 IU daily did not increase calcium absorption. No threshold level of serum 25OHD for calcium absorption was found at baseline or in the longitudinal study, suggesting that active transport of calcium is saturated at very low serum 25OHD levels <5 ng/mL. There is no need to recommend vitamin D for increasing calcium absorption in normal subjects. Very efficient calcium absorption at very low levels of serum 25OHD explains why people do not develop osteomalacia provided that dietary intakes of calcium and phosphorus are adequate. © 2014 American Society for Bone and Mineral Research.
Methanosaeta dominate acetoclastic methanogenesis during high‐rate methane production in anaerobic reactors treating distillery wastewaters
Authors: van Haandel Adrianus , De Vrieze Jo , Verstraete Willy , dos Santos Vagner S.
Published: October 2013

BACKGROUND

Anaerobic treatment of vinasses wastewater can result in high methane production rates, which depends on the ability to maintain a high specific methanogenic activity in the reactor. Here, it was investigated whether methane production could be increased by optimizing (1) temperature and (2) organic loading rate. It was expected that by maintaining high residual acetate concentrations, due to systematic overloading, anaerobic sludge with higher methanogenic activity would develop.

RESULTS

A pilot‐scale experiment of 180 days showed that Methanosarcina were unable to dominate acetoclastic methanogenesis in an upflow anaerobic sludge bed (UASB) reactor, despite the favorable conditions. This could be attributed to their reduced tendency to incorporate into sludge granules. Conversion rates of 40 to 50 kg COD m−3 d−1 were obtained for vinasses in mesophilic UASB reactors.

CONCLUSION

These high methane production rates open the possibility to achieve electricity production of more than 2 kW m−3 reactor, with concomitant economic perspectives. © 2013 Society of Chemical Industry
Embryonic yolk removal affects a suite of larval salamander life history traits
Authors: Landberg Tobias
Published: October 2013

Egg size is a key life history trait affecting fitness, and it varies abundantly. The value of egg size to a mother and her offspring is often determined by a trade‐off between investing more yolk in a few large eggs or less yolk into many more, smaller eggs. Smaller eggs are generally expected to be phenotypically inferior or females could increase their fitness by making more smaller eggs. However, many females produce a mix of egg sizes and natural yolk variation induces normal developmental responses which may persist into subsequent stages of a complex life history. Since sources of phenotypic variation are easily confounded, I surgically removed yolk from embryonic spotted salamanders (Ambystoma maculatum)using a sham surgery as a control and a split‐clutch design to isolate the effects of yolk reserve variation from genetic sources of variation. Yolk removal induced early hatching, reduced developmental stage and hatchling body size. Small hatchlings stayed relatively small through the early larval period, but 17 weeks later the correlation with early larval body size was lost. When the experiment ended, larger individuals were further along in metamorphic development but mortality was independent of early larval body size. Variation in spotted salamander yolk reserves affects a suite of hatchling life history traits that persists into the larval period. Outside the laboratory, egg size effects may cascade throughout complex amphibian life histories. Applied experimentally and comparatively, this simple yolk removal technique may help identify how traits increase or decrease their response to maternal yolk investment. J. Exp. Zool. (Mol. Dev. Evol.) 322B: 45–53, 2014. © 2013 Wiley Periodicals, Inc.
An Efficient Method for the Synthesis of Naphtho[2,3‐f]pyrano[3,4‐c]quinoline Derivatives Catalyzed by Iodine
Authors: Wang W. , Zhang M.‐M. , Wang X.‐S.
Published: October 2013

A mild and efficient method for the synthesis of naphtho[2,3‐f]pyrano[3,4‐c]quinoline derivatives via three‐component reaction of aromatic aldehyde, anthracen‐2‐amine, and tetrahydropyran‐4‐one is described using iodine as catalyst. The features of this procedure are mild reaction conditions, good to high yields, and operational simplicity.
Synthesis and Structure Elucidation of New Regioisomeric 2‐Alkylamino‐6‐aryl‐8,9‐dihydropyrimido[4,5‐b][1,4]diazepin‐4(7H)‐ones
Authors: Insuasty Braulio , Orozco Fabián , Quiroga Jairo , Abonía Rodrigo , Nogueras Manuel , Cobo Justo
Published: October 2013

Novel 2‐Alkylamino‐6‐aryl‐8,9‐dihydropyrimido[4,5‐b][1,4]diazepin‐4(7H)‐ones 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5l, 5m, 5n, 5o were prepared regioselectively by the reaction of 2‐alkylamino‐5,6‐diaminopyrimidin‐4(3H)‐ones 3a, 3b, 3c and dimethylamino propiophenones (Mannich bases) 4a, 4b, 4c, 4d, 4e, 4f. The combination of conventional heating and microwave irradiation approaches provided the possibility of working with both stable and sensitive diaminopyrimidines by controlling parameters such as reaction rates, temperature, and power of irradiation. All products were fully characterized by detailed NMR measurements.
Hepatitis C virus genotype 1: How genetic variability of the core protein affects the response to pegylated‐interferon and ribavirin therapy
Authors: Alhamlan F.S. , Al‐Ahdal M.N. , Khalaf N.Z. , Abdo A.A. , Sanai F.M. , Al‐Ashgar H.I. , ElHefnawi M. , Zaid A. , Al‐Qahtani A.A.
Published: October 2013

Hepatitis C virus subgenotypes 1a and 1b are found worldwide and cause 60% of all hepatitis C cases. It has been reported recently that viral genetic variations have a critical impact on the patient treatment outcome. In particular, polymorphisms of the HCV core protein have been linked to poor treatment response. However, most of these studies were conducted on Asian populations, Japanese in particular who are infected with HCV subgenotype 1b. Hence, we aimed in this study to examine the core protein polymorphisms in Saudi patients who are infected with chronic HCV genotype 1 (1a and 1b subtypes) and its association with treatment outcome. Direct sequencing of full‐length core protein and data mining analyses were utilized. Results have shown that the response to treatment is dependent on subgenotypes. Indeed, HCV‐1b showed different point mutations that are associated with treatment outcome where the point mutations at positions 70 (Arg70Gln) and 75 (Thr75Ala) in HCV‐1b are significantly associated with PEG‐IFN/RBV treatment response. In contrast, HCV‐1a showed no significant association between core protein mutations and response to treatment. In addition, analyses of HCV‐1a core protein sequences revealed a highly conserved region especially in the responder group. This study provides a new insight in the genetic variability of full‐length core protein in HCV genotype 1 in Saudi infected patients. J. Med. Virol. 86:224–234, 2014. © 2013 Wiley Periodicals, Inc.
Therapeutic effect of human umbilical cord mesenchymal stem cells on neonatal rat hypoxic–ischemic encephalopathy
Authors: Zhang Xinhua , Zhang Qinfen , Li Wei , Nie Dekang , Chen Weiwei , Xu Chunxiang , Yi Xin , Shi Jinhong , Tian Meiling , Qin Jianbing , Jin Guohua , Tu Wenjuan
Published: October 2013

The therapeutic potential of umbilical cord blood mesenchymal stem cells has been studied in several diseases. However, the possibility that human umbilical cord Wharton's jelly‐derived mesenchymal stem cells (hUCMSCs) can be used to treat neonatal hypoxic–ischemic encephalopathy (HIE) has not yet been investigated. This study focuses on the potential therapeutic effect of hUCMSC transplantation in a rat model of HIE. Dermal fibroblasts served as cell controls. HIE was induced in neonatal rats aged 7 days. hUCMSCs labeled with Dil were then transplanted into the models 24 hr or 72 hr post‐HIE through the peritoneal cavity or the jugular vein. Behavioral testing revealed that hUCMSC transplantation but not the dermal fibroblast improved significantly the locomotor function vs. vehicle controls. Animals receiving cell grafts 24 hr after surgery showed a more significant improvement than at 72 hr. More hUCMSCs homed to the ischemic frontal cortex following intravenous administration than after intraperitoneal injection. Differentiation of engrafted cells into neurons was observed in and around the infarct region. Gliosis in ischemic regions was significantly reduced after hUCMSC transplantation. Administration of ganglioside (GM1) enhanced the behavioral recovery on the base of hUCMSC treatment. These results demonstrate that intravenous transplantation of hUCMSCs at an early stage after HIE can improve the behavior of hypoxic–ischemic rats and decrease gliosis. Ganglioside treatment further enhanced the recovery of neurological function following hUCMSC transplantation. © 2013 Wiley Periodicals, Inc.
Downregulation of UBE2Q1 is associated with neuronal apoptosis in rat brain cortex following traumatic brain injury
Authors: Wan Chunhua , Chen Jian , Hu Baoying , Zou Huifei , Li Aihong , Guo Aihang , Jiang Junkang
Published: October 2013

Aberrant functionality of the ubiquitin proteasome system (UPS) has been implicated in the pathology of various neurological disorders. Although it has been reported that the expressions of various UPS components were altered significantly following traumatic brain injury (TBI), detailed information on the subject remains largely unclear. In the study, using microarray assay, we identified a gene encoding ubiquitin‐conjugating enzyme E2Q1 (UBE2Q1) that was significantly downregulated during TBI. Western blot and immunohistochemical analyses verified the reduced expression of UBE2Q1 in ipsilateral brain cortex adjacent to the lesion site compared with the contralateral and sham‐operated ones. Double‐immunofluorescence staining indicated that UBE2Q1 was expressed mainly in the nucleus of neurons, with a minority in astrocytes in normal cortex. In addition, we observed a remarkable reduction in the number of UBE2Q1‐positive neurons following brain trauma. Furthermore, we showed that TBI resulted in a significant increase in the levels of p53, bax, p21 and active caspase 3 in brain cortex, which was correlated with decreased expression of UBE2Q1. We also found that knockdown of UBE2Q1 apparently increased the level of p53, whereas overexpressing UBE2Q1 attenuated cellular p53 level in PC12 neuronal cells. Accordingly, interference with UBE2Q1 augmented H2O2‐induced apoptosis of PC12 cells. Taken together, our findings indicate that UBE2Q1 might play an important role in the neuropathological process of TBI through modulating p53 signaling. © 2013 Wiley Periodicals, Inc.
A Network Perspective for a Borderless International Structure: The Experience of an Italian Entrepreneurial SME in Morocco
Authors: Zardini Alessandro , Rossignoli Cecilia , Soliman Marco
Published: October 2013

Going global has become more than just a strategy; it is essential to ensuring revenues and firm survival, especially for organizations that function in saturated, highly competitive markets. Because small firms often lack the internal resources, competencies, information, capital, and managerial experience needed to expand globally, they tend to rely on resources held by other, partner firms. Thus, a network view that encourages resource and information sharing among participants can help smaller firms overcome any limitations stemming from a lack of internal resources. The experience of an Italian manufacturer with operations in Morocco reflects a new approach to network formation that focuses particularly on the learning process and acquisition of knowledge in local markets. © 2013 Wiley Periodicals, Inc.
Slow Growth or Rapid Internationalization in Emerging Markets: The Case of Maybank Berhad
Authors: Ahmad Syed Zamberi
Published: October 2013

Theories on the internationalization of multinational banks are largely based on companies from developed countries. Their application has not yet been studied in depth among firms based in developing nations, however. The international expansion of Maybank Berhad and its transformation from a medium‐sized Malaysian national bank to one of the most profitable regional banks in Asia offers a template for other growing organizations in emerging markets. By building on its strong capabilities at home, creating growth in nearby markets that share its cultural outlook, and simultaneously leapfrogging over some early stages of international expansion through the acquisition of competitors in the international arena, Maybank has contradicted the notion of gradual development that is an essential aspect of the stage‐model perspective of internationalization. © 2013 Wiley Periodicals, Inc.
Electrochemotherapy for the management of cutaneous and subcutaneous metastasis: A series of 39 patients treated with palliative intent
Authors: Solari Nicola , Spagnolo Francesco , Ponte Erica , Quaglia Alberto , Lillini Roberto , Battista Michela , Queirolo Paola , Cafiero Ferdinando
Published: October 2013

Background and Objectives

Electrochemotherapy (ECT) is technique for local control of skin metastasis. This study is primarily aimed at assessing the clinical activity of ECT in a prospective cohort of patients, and evaluating the association between primary tumor histology, number of metastatic lesions and size of tumor deposits and objective response rate.

Methods and Results

Thirty‐nine patients with skin metastases from melanoma and other tumors underwent intravenous bleomycin ECT with palliative intent. No serious adverse events (SAE) or CTC grade 3 or 4 were observed. Overall response rate (ORR) was 66.6%. Response rate significantly correlated at univariate analysis both with the number (< or >10) and the size (< or >2 cm) of metastases. No relationship was observed for the histology of primary tumor. At multivariate analysis the size of the nodules under 2 cm was associated with a positive response and the correlation was statistically significant.

Conclusions

ORR was 66.6% and all patients obtained a subjective clinical benefit from the treatment with minimal side effects. The most suitable patients were the ones with nodules <2 cm. J. Surg. Oncol. 2014 109:270–274. © 2013 Wiley Periodicals, Inc.
Topology Evolution in Polymer Modification
Authors: Kryven Ivan , Iedema Piet D.
Published: October 2013

A recent numerical method has opened new opportunities in multidimensional population balance modeling. Here, this method is applied to a full three‐dimensional population balance model (PBM) describing branching topology evolution driven by chain end to backbone coupling. This process is typical for polymer modification reactions, e.g., in polyethylene, where initially linear polymer chains undergo hydrogen abstraction, and subsequent branching or scission. Topologies are distinguished by chain ends, number of branches, and number of reactive ends. The resulting time dependent trivariate distribution is utilized to extract various distributive properties of the polymer. The results exhibit excellent agreement with data from Monte Carlo simulations.
Canonical and non‐canonical EcfG sigma factors control the general stress response in Rhizobium etli
Authors: Jans Ann , Vercruysse Maarten , Gao Shanjun , Engelen Kristof , Lambrichts Ivo , Fauvart Maarten , Michiels Jan
Published: October 2013

A core component of the α‐proteobacterial general stress response (GSR) is the extracytoplasmic function (ECF) sigma factor EcfG, exclusively present in this taxonomic class. Half of the completed α‐proteobacterial genome sequences contain two or more copies of genes encoding σEcfG‐like sigma factors, with the primary copy typically located adjacent to genes coding for a cognate anti‐sigma factor (NepR) and two‐component response regulator (PhyR). So far, the widespread occurrence of additional, non‐canonical σEcfG copies has not satisfactorily been explained. This study explores the hierarchical relation between Rhizobium etli σEcfG1 and σEcfG2, canonical and non‐canonical σEcfG proteins, respectively. Contrary to reports in other species, we find that σEcfG1 and σEcfG2 act in parallel, as nodes of a complex regulatory network, rather than in series, as elements of a linear regulatory cascade. We demonstrate that both sigma factors control unique yet also shared target genes, corroborating phenotypic evidence. σEcfG1 drives expression of rpoH2, explaining the increased heat sensitivity of an ecfG1 mutant, while katG is under control of σEcfG2, accounting for reduced oxidative stress resistance of an ecfG2 mutant. We also identify non‐coding RNA genes as novel σEcfG targets. We propose a modified model for GSR regulation in R. etli, in which σEcfG1 and σEcfG2 function largely independently. Based on a phylogenetic analysis and considering the prevalence of α‐proteobacterial genomes with multiple σEcfG copies, this model may also be applicable to numerous other species.
Slice accelerated gradient‐echo spin‐echo dynamic susceptibility contrast imaging with blipped CAIPI for increased slice coverage
Authors: Eichner Cornelius , Jafari‐Khouzani Kourosh , Cauley Stephen , Bhat Himanshu , Polaskova Pavlina , Andronesi Ovidiu C. , Rapalino Otto , Turner Robert , Wald Lawrence L. , Stufflebeam Steven , Setsompop Kawin
Published: October 2013

Purpose

To improve slice coverage of gradient echo spin echo (GESE) sequences for dynamic susceptibility contrast (DSC) MRI using a simultaneous‐multiple‐slice (SMS) method.

Methods

Data were acquired on 3 Tesla (T) MR scanners with a 32‐channel head coil. To evaluate use of SMS for DSC, an SMS GESE sequence with two‐fold slice coverage and same temporal sampling was compared with a standard GESE sequence, both with 2× in‐plane acceleration. A signal to noise ratio (SNR) comparison was performed on one healthy subject. Additionally, data with Gadolinium injection were collected on three patients with glioblastoma using both sequences, and perfusion analysis was performed on healthy tissues as well as on tumor.

Results

Retained SNR of SMS DSC is 90% for a gradient echo (GE) and 99% for a spin echo (SE) acquisition, compared with a standard acquisition without slice acceleration. Comparing cerebral blood volume maps, it was observed that the results of standard and SMS acquisitions are comparable for both GE and SE images.

Conclusion

Two‐fold slice accelerated DSC MRI achieves similar SNR and perfusion metrics as a standard acquisition, while allowing a significant increase in slice coverage of the brain. The results also point to a possibility to improve temporal sampling rate, while retaining the same slice coverage. Magn Reson Med 72:770–778, 2014. © 2013 Wiley Periodicals, Inc.