bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonclinical Safety of the Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin
Authors: Bogdanffy Matthew S. , Stachlewitz Robert F. , van Tongeren Susan , Knight Brian , Sharp Dale E. , Ku Warren , Hart Susan Emeigh , Blanchard Kerry
Published: September 2014

Empagliflozin, a selective inhibitor of the renal tubular sodium-glucose cotransporter 2, was developed for treatment of type 2 diabetes mellitus. Nonclinical safety of empagliflozin was studied in a battery of tests to support global market authorization. Safety pharmacology studies indicated no effect of empagliflozin on measures of respiratory or central nervous system function in rats or cardiovascular safety in telemeterized dogs. In CD-1 mouse, Wistar Han rat, or beagle dogs up to 13, 26, or 52 weeks of treatment, respectively, empagliflozin exhibited a toxicity profile consistent with secondary supratherapeutic pharmacology related to glucose loss and included decreased body weight and body fat, increased food consumption, diarrhea, dehydration, decreased serum glucose and increases in other serum parameters reflective of increased protein catabolism, gluconeogenesis, and electrolyte imbalances, and urinary changes such as polyuria and glucosuria. Microscopic changes were consistently observed in kidney and included tubular nephropathy and interstitial nephritis (dog), renal mineralization (rat) and tubular epithelial cell karyomegaly, single cell necrosis, cystic hyperplasia, and hypertrophy (mouse). Empagliflozin was not genotoxic. Empagliflozin was not carcinogenic in female mice or female rats. Renal adenoma and carcinoma were induced in male mice only at exposures 45 times the maximum clinical dose. These tumors were associated with a spectrum of nonneoplastic changes suggestive of a nongenotoxic, cytotoxic, and cellular proliferation-driven mechanism. In male rats, testicular interstitial cell tumors and hemangiomas of the mesenteric lymph node were observed; both tumors are common in rats and are unlikely to be relevant to humans. These studies demonstrate the nonclinical safety of empagliflozin.
Trend Analysis of Body Weight Parameters, Mortality, and Incidence of Spontaneous Tumors in Tg.rasH2 Mice
Authors: Paranjpe Madhav G. , Denton Melissa D. , Vidmar Tom , Elbekai Reem H.
Published: September 2014

Carcinogenicity studies have been performed in conventional 2-year rodent studies for at least 3 decades, whereas the short-term carcinogenicity studies in transgenic mice, such as Tg.rasH2, have only been performed over the last decade. In the 2-year conventional rodent studies, interlinked problems, such as increasing trends in the initial body weights, increased body weight gains, high incidence of spontaneous tumors, and low survival, that complicate the interpretation of findings have been well established. However, these end points have not been evaluated in the short-term carcinogenicity studies involving the Tg.rasH2 mice. In this article, we present retrospective analysis of data obtained from control groups in 26-week carcinogenicity studies conducted in Tg.rasH2 mice since 2004. Our analysis showed statistically significant decreasing trends in initial body weights of both sexes. Although the terminal body weights did not show any significant trends, there was a statistically significant increasing trend toward body weight gains, more so in males than in females, which correlated with increasing trends in the food consumption. There were no statistically significant alterations in mortality trends. In addition, the incidence of all common spontaneous tumors remained fairly constant with no statistically significant differences in trends.
PARCOACH: Combining static and dynamic validation of MPI collective communications
Authors: Saillard Emmanuelle , Carribault Patrick , Barthou Denis
Published: September 2014

Nowadays most scientific applications are parallelized based on MPI communications. Collective MPI communications have to be executed in the same order by all processes in their communicator and the same number of times, otherwise they do not conform to the standard and a deadlock or other undefined behaviour can occur. As soon as the control flow involving these collective operations becomes more complex, in particular including conditionals on process ranks, ensuring the correction of such code is error-prone. We propose in this paper a static analysis to detect when such a situation occurs, combined with a code transformation that prevents deadlocking. We focus on blocking MPI collective operations in single program multiple data applications, assuming MPI calls are not nested in multithreaded regions. We show on several benchmarks the small impact on performance and the ease of integration of our techniques in the development process.
Effect of Customer Participation on Service Outcomes
Authors: Dong Beibei , Sivakumar K. , Evans Kenneth R. , Zou Shaoming
Published: September 2014

Prior empirical evidence on the role of customer participation (CP) on service outcomes is limited and inconsistent. The authors add new insights by investigating the boundary conditions of the CP-service outcome link. Using two experiments, the article examines the moderating effect of three CP readiness factors: ability, perceived benefits of participation, and role identification. The results show that when CP readiness is high, increasing CP enhances service outcomes including customer satisfaction and perceived service quality; however, when CP readiness is low, the effect of CP on service outcomes tapers off or becomes negative. The results highlight the contingent nature of CP’s effect, demonstrate that CP could indeed be a double-edged sword, and provide managerial guidelines to enhance CP’s benefits through appropriate targeting and service design.
Multivisceral Resection for Locally Advanced Rectal Cancer: Prognostic Factors Influencing Outcome
Authors: Mañas M.J. , Espín E. , López-Cano M. , Vallribera F. , Armengol-Carrasco M.
Published: September 2014

Aims:

To assess outcome in patients with locally advanced rectal cancer undergoing multivisceral resection.

Methods:

Retrospective study of 30 consecutive patients (mean age 67.8 years) with primary locally advanced rectal cancer undergoing en bloc multivisceral resection of the organs involved with curative intent between 1998 and 2010. Overall survival, local and distal recurrence, and disease-free survival were analyzed by the Kaplan–Meier method. Risk factors for clinical outcome were obtained using a Cox multivariate model.

Results:

Postoperative complications occurred in 76.7% of patients and the in-hospital mortality rate was 10%. The median follow-up was 28.8 months. A total of 19 patients died at follow-up. Of the 11 patients who were alive, 7 were free of disease. In the multivariate analysis, lymph node involvement, stage II, and lymph vascular invasion were significantly associated with survival, and stage III showed a strong trend towards significance. Suture dehiscence (peritonitis and intra-abdominal abscess) showed a significant trend towards a higher local recurrence. Lymph vascular invasion was associated with a higher distant recurrence.

Conclusion:

Lymph node involvement was associated with worse survival, whereas stage II and absence of lymph vascular invasion were associated with a better survival. Lymph vascular invasion was associated with a higher distant recurrence.
Dynamic mechanical analysis of snake grass fiber-reinforced polyester composites
Authors: Sathishkumar TP
Published: September 2014

The dynamic properties of randomly oriented short snake grass fiber-reinforced polyester composites were analyzed with the functions of fiber weight fraction, length, frequency, and temperature. The storage modulus ( E ′) of the fiber-reinforced composites was enhanced compared to that of neat resin. The maximum modulus was obtained for 30% Wf of 10 mm fiber length composites. The damping peak height was reduced and the peak shifted toward higher temperature region upon gradual increase in fiber loading. By maintaining constant fiber loading (30% Wf) and upon gradually increasing the fiber length (10–50 mm), the maximum E ′ value of 30 mm fiber length was achieved. The tan δ peaks decreased by varying the fiber length. The Cole–Cole plot was used to analyze the phase behavior of the composites. Among the variations in frequencies, 1 Hz exhibits low tan δ peak. The fiber Wf in the composite increases the activation energy, which in turn reduces the relaxation process of polymer molecules in the composites. Hence, the balance of properties has been achieved for 30% Wf of fiber containing composites having 30 mm fiber length.
The power of the prize: How an emerging prize culture helped shape journalistic practice and professionalism, 1917–1960
Authors: Lanosga Gerry
Published: September 2014

This historical analysis considers the role the Pulitzer Prizes played in shaping modern journalistic practices by helping determine standards of quality for newspapers. Using entry and jury materials from the first four decades of the prizes, this study reveals a prize culture built around elite figures whose selections sent clear signals about the kinds of journalism it deemed exceptional and newspapers that responded in turn, strategically planning their coverage and nominations. In this way, the prize establishment wielded extraordinary power in the development of journalistic professionalism in the 20th century.
What’s feeling got to do with it? Decoding emotional bottlenecks in the history classroom
Authors: Middendorf Joan , Mickutė Jolanta , Saunders Tara , Najar José , Clark-Huckstep Andrew E , Pace David ,   with Keith Eberly and Nicole McGrath
Published: September 2014

The understandings and preconceptions students bring into the history classroom can interfere with student learning. Analyses of student and professor interviews in light of emotional bottlenecks revealed two different, though related, student preconceptions: procedural preconceptions about history as a field of study and pre-existing worldviews that link students’ identities to the past. With the Decoding the Disciplines method instructors can capture the students’ narratives early to better anticipate and re-channel resistance, moving students away from emotional snap judgments to more critical and historical ways of thinking.
Effects of Mutations of 3 Amino Acids on Hepatocellular Carcinoma
Authors: Lin Li Li , Wang Wei , Chang Jing , Song XuRui , Yu RuYun , Qiu Dong Min
Published: September 2014

In recent years, over 1000 reports have been published on the association between hepatic diseases and gene mutations which may result in pathogenic amino acids. Most of the studies focus on the hepatocellular carcinoma (HCC). The aim was to systematically examine the published literature on the association between the mutations of arginine, serine, and threonine and hepatic diseases, particularly HCC. The Biosciences information service database was systematically searched before July 10, 2012. Of the initially selected 471 publications, 112 articles were included in this study. Meta-analyses were conducted for 3 amino acids. Risk ratios were used to analyze the association between amino acids and liver diseases. We analyze the literature on the association between gene mutations and hepatic diseases, especially in patients with HCC. Full-text articles were analyzed by 4 independent researchers. Some amino acid mutations were found only in people with liver diseases—not in the general population. Arginine and threonine mutations occurred more frequently in patients with hepatic diseases, compared to the normal population. There is a statistically significant association between arginine mutations and the risk of HCC and serine mutations and the risk of HCC.
Smoking and Cognitive Impairment Among Older Persons in Malaysia
Authors: Momtaz Yadollah Abolfathi , Ibrahim Rahimah , Hamid Tengku Aizan , Chai Sen Tyng
Published: September 2014

Introduction:

Previous studies have shown conflicting results on the association between smoking and cognitive function. This study aims to examine the relationship of smoking with cognitive function.

Methodology:

Data for the study, consisting of 2553 older adults aged 60 years and older, were drawn from a nationwide household survey entitled “Determinants of Wellness among Older Malaysians: A Health Promotion Perspective” conducted in 2010.

Results:

Current smokers had lower rates of cognitive impairment compared to never smokers (17.4% vs 25.9%), while cognitive function in former or ex-smokers was almost similar to that of the never smokers. Findings from multiple logistic regression analysis showed that current smokers were 37% less likely to be cognitively impaired, compared to the never smokers (odds ratio [OR] = .63; 95% confidence interval [CI]: .46-.86) while controlling for potential confounders. No difference in cognitive function was observed between former smokers and never smokers (OR = .94; 95% CI: .71-1.25).

Conclusion:

Although the findings indicated a negative association between cigarette smoking and cognitive impairment, we are unable to conclude whether this relationship is causal or affected by other unmeasured confounding factors, especially survival bias.
Positive Psychology and Physical Health
Authors: Park Nansook , Peterson Christopher , Szvarca Daniel , Vander Molen Randy J. , Kim Eric S. , Collon Kevin
Published: September 2014

Positive psychology is the scientific study of a healthy and flourishing life. The goal of positive psychology is to complement and extend the traditional problem-focused psychology that has proliferated in recent decades. Positive psychology is concerned with positive psychological states (eg, happiness), positive psychological traits (eg, talents, interests, strengths of character), positive relationships, and positive institutions. We describe evidences of how topics of positive psychology apply to physical health. Research has shown that psychological health assets (eg, positive emotions, life satisfaction, optimism, life purpose, social support) are prospectively associated with good health measured in a variety of ways. Not yet known is whether positive psychology interventions improve physical health. Future directions for the application of positive psychology to health are discussed. We conclude that the application of positive psychology to health is promising, although much work remains to be done.
The Laughter Prescription
Authors: Louie Dexter , Brook Karolina , Frates Elizabeth
Published: September 2014

Laughter is a normal and natural physiologic response to certain stimuli with widely acknowledged psychological benefits. However, current research is beginning to show that laughter may also have serious positive physiological effects for those who engage in it on a regular basis. Providers who prescribe laughter to their patients in a structured way may be able to use these natural, free, and easily distributable positive benefits. This article reviews the current medical understanding of laughter’s physiologic effects and makes a recommendation for how physicians might best harness this natural modality for their patients.
Research on suspended microparticles’ transport driven by reflective acoustic streaming micropump
Authors: Changzhi Wei , Shoushui Wei , Chengyu Liu , Yatao Zhang , Feifei Liu
Published: September 2014

A reflective acoustic streaming micropump was designed in this study. After proposing the micropump structure model, the best driving frequency of 11,548,960 Hz was determined from modal analysis. Then the acoustic pressure field and the acoustic instantaneous intensity distribution were studied. The streaming velocity in the pump chamber was calculated and the maximum velocity reached 3 mm/s. The maximum velocity of the suspended microparticles was 1.0938 mm/s, and the influence factors on the microparticles movement were discussed. The microparticle movement was determined by acoustic streaming when microparticle diameter was less than 2 µm and the acoustic radiation force became dominated when microparticle diameter was more than 5 µm.
Anatomical and histomorphometric observations on the transfer of the anterior interosseous nerve to the deep branch of the ulnar nerve
Authors: Schenck T. L. , Stewart J. , Lin S. , Aichler M. , Machens H.-G. , Giunta R. E.
Published: September 2014

This study focuses on the anatomical and histomorphometric features of the transfer of the anterior interosseous nerve to the deep motor branch of the ulnar nerve. The transfer was carried out in 15 cadaver specimens and is described using relevant anatomical landmarks. Nerve samples of donor and target nerves were histomorphometrically analysed and compared. The superficial and the deep ulnar branches had to be separated from each other for a length of 67 mm (SD 12; range 50–85) to reach the site of coaptation. We identified a suitable site for coaptation lying proximal to the pronator quadratus muscle, 202 mm (SD 15; range 185–230) distal to the medial epicondyle of the humerus. The features of the anterior interosseous nerve included a smaller nerve diameter, smaller cross-sectional area of fascicles, fewer fascicles and axons, but a similar axon density. The histomorphometric inferiority of the anterior interosseous nerve raises a question about whether it should be transferred only to selected parts of the deep motor branch of the ulnar nerve.

Level III
The role of chronic hyperviscosity in vascular disease
Authors: Sloop Gregory , Holsworth Ralph E. , Weidman Joseph J. , St Cyr John A.
Published: September 2014

The pathogenesis of several major cardiovascular diseases, including atherosclerosis, hypertension, and the metabolic syndrome, is not widely understood because the role of blood viscosity is overlooked. Low-density lipoprotein accelerates atherosclerosis by increasing blood viscosity in areas of low flow or shear, predisposing to thrombosis. Atherosclerotic plaques are organized mural thrombi, as proposed by Duguid in the mid-twentieth century. High-density lipoprotein protects against atherosclerosis by decreasing blood viscosity in those areas. Blood viscosity, at the least, contributes to hypertension by increasing systemic vascular resistance. Because flow is inversely proportional to viscosity, hyperviscosity decreases perfusion and glucose utilization by skeletal muscle, contributing to hyperglycemia in the metabolic syndrome. Therapeutic phlebotomy reduces blood pressure and serum glucose levels in the metabolic syndrome by improving blood viscosity.
Advances in thyroid cancer treatment: latest evidence and clinical potential
Authors: Alonso-Gordoa T. , Díez J.J. , Durán M. , Grande Enrique
Published: September 2014

Advanced thyroid carcinoma is an infrequent tumor entity with limited treatment possibilities until recently. The extraordinary improvement in the comprehension of genetic and molecular alterations involving the RAS/RAF/mitogen-activated protein kinase and phosphatidylinositide 3-kinase/Akt/mammalian target of rapamycin signaling and interacting pathways that are involved in tumor survival, proliferation, differentiation, motility and angiogenesis have been the rationale for the development of new effective targeted therapies. Data coming from phase II clinical trials have confirmed the efficacy of those targeted agents against receptors in cell membrane and cytoplasmic molecules. Moreover, four of those investigational drugs, vandetanib, cabozantinib, sorafenib and lenvatinib, have reached a phase III clinical trial with favorable results in progression-free survival and overall survival in medullary thyroid carcinoma and differentiated thyroid carcinoma. Further analysis for an optimal approach has been conducted according to mutational profile and tumor subtypes. However, consistent results are still awaited and the research for adequate prognostic and predictive biomarkers is ongoing. The following report offers a comprehensive review from the rationale to the basis of targeted agents in the treatment of thyroid carcinoma. In addition, current and future therapeutic developments by the inhibition of further molecular targets are discussed in this setting.
Radiological images of keratocystoma: a rare tumor of the parotid gland
Authors: Hirata Kenji , Fujima Noriyuki , Mizumachi Takatsugu , Bandarchi Bizhan , Roesler John M
Published: September 2014

A 34-year-old man found a mildly tender preauricular mass. Ultrasonography revealed an anechoic mass in the superficial lobe of the parotid gland. Magnetic resonance imaging showed thin ring-like contrast enhancement and homogenously high intensity on T2-weighted images. The mass was resected due to its rapid growth. The cystic lesion contained keratine-like material and a stratified squamous epithelium without granular layers, which was consistent with keratocystoma.
Exhaled nitric oxide during infancy as a risk factor for asthma and airway hyperreactivity
Authors: Chang Daniel , Yao Weiguo , Tiller Christina J. , Kisling Jeffrey , Slaven James E. , Yu Zhangsheng , Kaplan Mark H. , Tepper Robert S.
Published: September 2014

Childhood asthma is often characterised by elevated exhaled nitric oxide (eNO), decreased lung function, increased airway reactivity and atopy; however, our understanding of when these phenotypic airway characteristics develop remains unclear. This study evaluated whether eNO, lung function, airway reactivity and immune characteristics during infancy are risk factors of asthma at age 5 years.

Infants with eczema, enrolled prior to wheezy illness (n=116), had eNO, spirometry, airway reactivity and allergen sensitisation assessed at entry to the study and repeated at age 5 years (n=90).

Increasing eNO at entry was associated with an increased risk of asthma (p=0.037) and increasing airway reactivity (p=0.015) at age 5 years. Children with asthma at 5 years of age had a greater increase in eNO between infancy and age 5 years compared with those without asthma (p=0.002). Egg sensitisation at entry was also associated with an increased risk of asthma (p=0.020), increasing eNO (p = 0.002) and lower forced expiratory flows (p=0.029) as a 5 year-old.

Our findings suggest that, among infants at high risk for developing asthma, eNO early in life may provide important insights into the subsequent risk of asthma and its airway characteristics.
Iloprost reverses established fibrosis in experimental right ventricular failure
Authors: Gomez-Arroyo Jose , Sakagami Masahiro , Syed Aamer A. , Farkas Laszlo , Van Tassell Benjamin , Kraskauskas Donatas , Mizuno Shiro , Abbate Antonio , Bogaard Harm J. , Byron Peter R. , Voelkel Norbert F.
Published: September 2014

Prostacyclin and its analogues improve cardiac output and functional capacity in patients with pulmonary arterial hypertension (PAH); however, the underlying mechanism is not fully understood. We hypothesised that prostanoids have load-independent beneficial effects on the right ventricle (RV).

Angio-obliterative PAH and RV failure were induced in rats with a single injection of SU5416 followed by 4 weeks of exposure to hypoxia. Upon confirmation of RV dysfunction and PAH, rats were randomised to 0.1 μg·kg−1nebulised iloprost or drug-free vehicle, three times daily for 2 weeks. RV function and treadmill running time were evaluated pre- and post-iloprost/vehicle treatment. Pulmonary artery banded rats were treated 8 weeks after surgery to allow for significant RV hypertrophy.

Inhaled iloprost significantly improved tricuspid annulus plane systolic excursion and increased exercise capacity, while mean pulmonary artery pressure and the percentage of occluded pulmonary vessels remained unchanged. Rats treated with iloprost had a striking reduction in RV collagen deposition, procollagen mRNA levels and connective tissue growth factor expression in both SU5416/hypoxia and pulmonary artery banded rats.In vitro, cardiac fibroblasts treated with iloprost showed a reduction in transforming growth factor (TGF)-β1-induced connective tissue growth factor expression, in a protein kinase A-dependent manner. Iloprost decreased TGF-β1-induced procollagen mRNA expression as well as cardiac fibroblast activation and migration. Iloprost significantly induced metalloproteinase-9 gene expression and activity and increased the expression of autophagy genes associated with collagen degradation.

Inhaled iloprost improves RV function and reverses established RV fibrosis partially by preventing collagen synthesis and by increasing collagen turnover.
Identification of novel microRNAs in the Verticillium wilt-resistant upland cotton variety KV-1 by high-throughput sequencing
Authors: He Xiaohong , Sun Quan , Jiang Huaizhong , Zhu Xiaoyan , Mo Jianchuan , Long Lu , Xiang Liuxin , Xie Yongfang , Shi Yuzhen , Yuan Youlu , Cai Yingfan
Published: September 2014

Plant microRNAs (miRNAs) play essential roles in the post-transcriptional regulation of gene expression during development, flowering, plant growth, metabolism, and stress responses. Verticillium wilt is one of the vascular disease in plants, which is caused by the Verticillium dahlia and leads to yellowing, wilting, lodging, damage to the vascular tissue, and death in cotton plants. Upland cotton varieties KV-1 have shown resistance to Verticillium wilt in multiple levels. However, the knowledge regarding the post-transcriptional regulation of the resistance is limited. Here two novel small RNA (sRNA) libraries were constructed from the seedlings of upland cotton variety KV-1, which is highly resistant to Verticillium wilts and inoculated with the V991 and D07038 Verticillium dahliae (V. dahliae) of different virulence strains. Thirty-seven novel miRNAs were identified after sequencing these two libraries by the Illumina Solexa system. According to sequence homology analysis, potential target genes of these miRNAs were predicted. With no more than three sequence mismatches between the novel miRNAs and the potential target mRNAs, we predicted 49 target mRNAs for 24 of the novel miRNAs.

These target mRNAs corresponded to genes were found to be involved in plant–pathogen interactions, endocytosis, the mitogen-activated protein kinase (MAPK) signaling pathway, and the biosynthesis of isoquinoline alkaloid, terpenoid backbone, primary bile acid and secondary metabolites. Our results showed that some of these miRNAs and their relative gene are involved in resistance to Verticillium wilts. The identification and characterization of miRNAs from upland cotton could help further studies on the miRNA regulatory mechanisms of resistance to Verticillium wilt.
Elevated DDX21 regulates c-Jun activity and rRNA processing in human breast cancers
Authors: Zhang Yandong , Baysac Kathleen C , Yee Lian-Fai , Saporita Anthony J , Weber Jason D
Published: September 2014

Introduction

The DDX21 RNA helicase has been shown to be a nucleolar and nuclear protein involved in ribosome RNA processing and AP-1 transcription. DDX21 is highly expressed in colon cancer, lymphomas, and some breast cancers, but little is known about how DDX21 might promote tumorigenesis.

Methods

Immunohistochemistry was performed on a breast cancer tissue array of 187 patients. In order to study the subcellular localization of DDX21 in both tumor tissue and tumor cell lines, indirect immunofluorescence was applied. The effect of DDX21 knockdown was measured by cellular apoptosis, rRNA processing assays, soft agar growth and mouse xenograft imaging. AP-1 transcriptional activity was analyzed with a luciferase reporter and bioluminescence imaging, as well as qRT-PCR analysis of downstream target, cyclin D1, to determine the mechanism of action for DDX21 in breast tumorigenesis.

Results

Herein, we show that DDX21 is highly expressed in breast cancer tissues and established cell lines. A significant number of mammary tumor tissues and established breast cancer cell lines exhibit nuclear but not nucleolar localization of DDX21. The protein expression level of DDX21 correlates with cell proliferation rate and is markedly induced by EGF signaling. Mechanistically, DDX21 is required for the phosphorylation of c-Jun on Ser73 and DDX21 deficiency markedly reduces the transcriptional activity of AP-1. Additionally, DDX21 promotes rRNA processing in multiple breast cancer cell lines. Tumor cells expressing high levels of endogenous DDX21 undergo apoptosis after acute DDX21 knockdown, resulting in significant reduction of tumorigenicity in vitro and in vivo.

Conclusions

Our findings indicate that DDX21 expression in breast cancer cells can promote AP-1 activity and rRNA processing, and thus, promote tumorigenesis by two independent mechanisms. DDX21 could serve as a marker for a subset of breast cancer patients with higher proliferation potential and may be used as a therapeutic target for a subset of breast cancer patients.
Analysis of dyes in textiles from the Chehrabad salt mine in Iran
Authors: Mouri Chika , Aali Abolfazl , Zhang Xian , Laursen Richard
Published: September 2014

This study describes the analysis of dyes from three textile specimens associated with human remains found in the Chehrabad salt mine in northwestern Iran dating to 2000 ± 400 years BP. They are unique for this part of the world not only because of their age, but because they represent textiles used by common people (salt miners) as opposed to funerary garments of the wealthy. Samples of yarns from these specimens were extracted and analyzed by high performance liquid chromatography with diode array and mass spectrometric detection. The red dye was obtained from madder (specifically Rubia tinctorum L.), and the blue was from an indigo plant, probably woad (Isatis tinctoria L.), both of which are known in Iran. Two yellow, plant-derived, flavonol dyes were found. The first seems to be from a species of tamarisk (Tamarix sp.), whereas the second, found in both yellow and green yarns, is from a so-far unidentified plant. This work represents the first detailed study of these salt mine dyes, and the first evidence for the use of tamarisk as a dyestuff.
A zebrafish model of manganism reveals reversible and treatable symptoms independent of neurotoxicity
Authors: Bakthavatsalam Subha , Das Sharma Shreya , Sonawane Mahendra , Thirumalai Vatsala , Datta Ankona
Published: September 2014

Manganese (Mn) is essential for neuronal function, yet toxic at high concentrations. Environmental and occupational exposure to high concentrations of Mn causes manganism, a well-defined movement disorder in humans, with symptoms resembling Parkinson’s disease (PD). However, manganism is distinct from PD and the neural basis of its pathology is poorly understood. To address this issue, we generated a zebrafish model of manganism by incubating larvae in rearing medium containing Mn. We find that Mn-treated zebrafish larvae exhibit specific postural and locomotor defects. Larvae begin to float on their sides, show a curved spine, and swim in circles. We discovered that Mn-treatment causes postural defects by interfering with mechanotransduction at the neuromasts. Furthermore, we find that the circling locomotion could be caused by long duration bursting in the motor neurons, which can lead to long duration tail bends in the Mn-treated larvae. Mn-treated larvae also exhibited fewer startle movements. Additionally, we show that the intensity of tyrosine hydroxylase immunoreactivity is reversibly reduced after Mn-treatment. This led us to propose that reduced dopamine neuromodulation could drive the changes in startle movements. To test this, when we supplemented dopamine to Mn-treated larvae, the larvae exhibited normal number of startle swims. Taken together, these results indicate that Mn interferes with neuronal function at the sensory, motor, and modulatory levels, and open avenues for therapeutically targeted studies on the zebrafish model of manganism.
High-fat diet decreases activity of the oxidative phosphorylation complexes and causes nonalcoholic steatohepatitis in mice
Authors: García-Ruiz Inmaculada , Solís-Muñoz Pablo , Fernández-Moreira Daniel , Grau Montserrat , Colina Francisco , Muñoz-Yagüe Teresa , Solís-Herruzo José A.
Published: September 2014

Nonalcoholic fatty liver disease (NAFLD) is the most frequent histological finding in individuals with abnormal liver-function tests in the Western countries. In previous studies, we have shown that oxidative phosphorylation (OXPHOS) is decreased in individuals with NAFLD, but the cause of this mitochondrial dysfunction remains uncertain. The aims of this study were to determine whether feeding mice a high-fat diet (HFD) induces any change in the activity of OXPHOS, and to investigate the mechanisms involved in the pathogenesis of this defect. To that end, 30 mice were distributed between five groups: control mice fed a standard diet, and mice on a HFD and treated with saline solution, melatonin (an antioxidant), MnTBAP (a superoxide dismutase analog) or uric acid (a scavenger of peroxynitrite) for 28 weeks intraperitoneously. In the liver of these mice, we studied histology, activity and assembly of OXPHOS complexes, levels of subunits of these complexes, gene expression of these subunits, oxidative and nitrosative stress, and oxidative DNA damage. In HFD-fed mice, we found nonalcoholic steatohepatitis, increased gene expression of TNFα, IFNγ, MCP-1, caspase-3, TGFβ1 and collagen α1(I), and increased levels of 3-tyrosine nitrated proteins. The activity and assembly of all OXPHOS complexes was decreased to about 50-60%. The amount of all studied OXPHOS subunits was markedly decreased, particularly the mitochondrial-DNA-encoded subunits. Gene expression of mitochondrial-DNA-encoded subunits was decreased to about 60% of control. There was oxidative damage to mitochondrial DNA but not to genomic DNA. Treatment of HFD-fed mice with melatonin, MnTBAP or uric acid prevented all changes observed in untreated HFD-fed mice. We conclude that a HFD decreased OXPHOS enzymatic activity owing to a decreased amount of fully assembled complexes caused by a reduced synthesis of their subunits. Antioxidants and antiperoxynitrites prevented all of these changes, suggesting that nitro-oxidative stress played a key role in the pathogenesis of these alterations. Treatment with these agents might prevent the development of NAFLD in humans.
Getting graduate gains
Authors: Dowling Marion
Published: September 2014

We know that the early period of a child's life is a vital time for learning and that their experiences and environments shape development, but how can we improve opportunities for the least advantaged?
Benefits of daddy play
Authors: Houghton Laura , O'Dwyer Mareesa , Foweather Lawrence , Watson Paula M , Alford Simon , Knowles Zoe
Published: September 2014

This article details research that assessed the level of fathers' engagement in play through a series of planned activities along with the resultant findings and recommendations for children's centre staff.
Let me tell you a story
Authors: Smith Michelle
Published: September 2014

There are many theories as to why girls have traditionally out performed boys when it comes to writing at an early age, many focus on biological differences, but the answer has more to do with experiences.
Cognitive dissonance
Authors: Pliakou Marianna
Published: September 2014

Do stickers really work? Extrinsic rewards are still broadly used, on the basis of ‘Operant Conditioning’. But more elaborate psychological mechanisms prove that this negatively affects intrinsic motivation.
SEND Code of Practice 2014: What it means for you
Authors: Wall Kate
Published: September 2014

The rate of change in the early years continues at pace, although it can often seem that children with additional needs get left behind. We now have a new SEND code of practice, but what will change?
Bears in the wilderness
Authors: Bunting Jane
Published: September 2014

The classic children's book, We're Going on a Bear Hunt, is 25-years-old! Celebrate this iconic story with a further selection of creative and engaging activities from independent literacy consultant, Jane Bunting.
Understanding generation through the lens of ethnic and cultural diversity
Authors: Wray Sharon , Ali Nafhesa
Published: September 2014

The notion of generation is a contested area. It has been used to denote cohort succession, age groups, kinship and historical period. This article will consider the concept of ‘generation’ through the lens of ethnic and cultural diversity. A main aim is to highlight the complex contradictions evident within the lived experience of generation for minority ethnic families and communities.
Heterotrimeric G proteins control stem cell proliferation through CLAVATA signaling in Arabidopsis
Authors: Ishida Takashi , Tabata Ryo , Yamada Masashi , Aida Mitsuhiro , Mitsumasu Kanako , Fujiwara Masayuki , Yamaguchi Katsushi , Shigenobu Shuji , Higuchi Masayuki , Tsuji Hiroyuki , Shimamoto Ko , Hasebe Mitsuyasu , Fukuda Hiroo , Sawa Shinichiro
Published: September 2014

Cell‐to‐cell communication is a fundamental mechanism for coordinating developmental and physiological events in multicellular organisms. Heterotrimeric G proteins are key molecules that transmit extracellular signals; similarly, CLAVATA signaling is a crucial regulator in plant development. Here, we show that Arabidopsis thaliana Gβ mutants exhibit an enlarged stem cell region, which is similar to that of clavata mutants. Our genetic and cell biological analyses suggest that the G protein beta‐subunit1 AGB1 and RPK2, one of the major CLV3 peptide hormone receptors, work synergistically in stem cell homeostasis through their physical interactions. We propose that AGB1 and RPK2 compose a signaling module to facilitate meristem development.
N‐WASP is required for Amphiphysin‐2/BIN1‐dependent nuclear positioning and triad organization in skeletal muscle and is involved in the pathophysiology of centronuclear myopathy
Authors: Falcone Sestina , Roman William , Hnia Karim , Gache Vincent , Didier Nathalie , Lainé Jeanne , Auradé Frederic , Marty Isabelle , Nishino Ichizo , Charlet‐Berguerand Nicolas , Romero Norma Beatriz , Marazzi Giovanna , Sassoon David , Laporte Jocelyn , Gomes Edgar R
Published: September 2014

Mutations in amphiphysin‐2/BIN1, dynamin 2, and myotubularin are associated with centronuclear myopathy (CNM), a muscle disorder characterized by myofibers with atypical central nuclear positioning and abnormal triads. Mis‐splicing of amphiphysin‐2/BIN1 is also associated with myotonic dystrophy that shares histopathological hallmarks with CNM. How amphiphysin‐2 orchestrates nuclear positioning and triad organization and how CNM‐associated mutations lead to muscle dysfunction remains elusive. We find that N‐WASP interacts with amphiphysin‐2 in myofibers and that this interaction and N‐WASP distribution are disrupted by amphiphysin‐2 CNM mutations. We establish that N‐WASP functions downstream of amphiphysin‐2 to drive peripheral nuclear positioning and triad organization during myofiber formation. Peripheral nuclear positioning requires microtubule/Map7/Kif5b‐dependent distribution of nuclei along the myofiber and is driven by actin and nesprins. In adult myofibers, N‐WASP and amphiphysin‐2 are only involved in the maintenance of triad organization but not in the maintenance of peripheral nuclear positioning. Importantly, we confirmed that N‐WASP distribution is disrupted in CNM and myotonic dystrophy patients. Our results support a role for N‐WASP in amphiphysin‐2‐dependent nuclear positioning and triad organization and in CNM and myotonic dystrophy pathophysiology.
Plasma membrane H+‐ATPase regulation is required for auxin gradient formation preceding phototropic growth
Authors: Hohm Tim , Demarsy Emilie , Quan Clément , Allenbach Petrolati Laure , Preuten Tobias , Vernoux Teva , Bergmann Sven , Fankhauser Christian
Published: September 2014

Phototropism is a growth response allowing plants to align their photosynthetic organs toward incoming light and thereby to optimize photosynthetic activity. Formation of a lateral gradient of the phytohormone auxin is a key step to trigger asymmetric growth of the shoot leading to phototropic reorientation. To identify important regulators of auxin gradient formation, we developed an auxin flux model that enabled us to test in silico the impact of different morphological and biophysical parameters on gradient formation, including the contribution of the extracellular space (cell wall) or apoplast. Our model indicates that cell size, cell distributions, and apoplast thickness are all important factors affecting gradient formation. Among all tested variables, regulation of apoplastic pH was the most important to enable the formation of a lateral auxin gradient. To test this prediction, we interfered with the activity of plasma membrane H+‐ATPases that are required to control apoplastic pH. Our results show that H+‐ATPases are indeed important for the establishment of a lateral auxin gradient and phototropism. Moreover, we show that during phototropism, H+‐ATPase activity is regulated by the phototropin photoreceptors, providing a mechanism by which light influences apoplastic pH.
MAUS HÁBITOS ALIMENTARES DE ESTUDANTES DO ENSINO MÉDIO EM ESCOLAS PÚBLICAS
Authors: Sales Fábio Henrique Silva , Carvalho Wyllyane Rayana Chaves , Dos Santo Junior Joacy Montelo , Silva Darlan Costa , Santos Cláudio Mendes
Published: September 2014

O presente trabalho objetivou avaliar aspectos da alimentação dos estudantes de escolas públicas e identificar os agentes que contribuem para a gênese e permanência dos maus hábitos alimentares. Participaram da pesquisa 610 estudantes, com idades entre 15 e 19 anos, de ambos os sexos. O estudo do tipo analítico e quantitativo foi realizado por meio da aplicação de um questionário aos alunos de três escolas da rede pública na cidade de São Luís do Maranhão em 2008, que abordou os seguintes pontos: hábitos alimentares, estilo de vida, alimentos oferecidos nas lanchonetes das escolas, patologias manifestadas e participação em palestras sobre nutrição e alimentação oferecidas pelas instituições de ensino. Os dados levantados apresentaram um quadro preocupante sobre a alimentação dos estudantes entrevistados. Observou-se a escassez de palestras e intervenções de cunho educativo sobre alimentação saudável no ambiente escolar. Essa ausência de informação coopera para a continuidade de práticas alimentares inadequadas. Além disso, segundo os alunos as lanchonetes ofertam alimentos ricos em açucares, óleos e gorduras, os chamados fast food, consumidos por eles diariamente. Outra prática comum entre os adolescentes e que também foi relatada pelos entrevistados é a substituição das refeições por esses lanches rápidos, maus hábitos alimentares associados diretamente ao surgimento de patologias,como obesidade e sobrepeso.
ANÁLISE DO DESEMPENHO TÉRMICO DE UM SISTEMA DE AQUECIMENTO SOLAR DE BAIXO CUSTO NA CIDADE DE MOSSORÓ (RN)
Authors: Varella Fabiana Karla de Oliveira Martins , Guerra Maria Izabel da Silva
Published: September 2014

O presente trabalho estuda a possibilidade de instalação e utilização de um Sistema de Aquecimento Solar de Água Não Convencional e de Baixo Custo (SASncbc) na cidade de Mossoró/RN. Para isso, foi analisado o desempenho térmico de cada elemento que compõe o sistema de aquecimento solar separadamente, a fim de analisar o comportamento que os mesmos apresentaram na cidade em estudo. O SASncbc é composto por um coletor solar plano e um reservatório térmico, e o funcionamento desse sistema é realizado através do regime de convecção natural, também conhecido como termossifão. Foi determinado que o coletor solar não convencional e de baixo custo confeccionado apresenta boas temperaturas de saída, apesar do seu baixo rendimento, entretanto, não é adequado para ser utilizado na cidade de Mossoró/RN, pois atingiu ou ultrapassou, em alguns momentos da pesquisa, os níveis críticos de temperatura para início da degradação térmica de alguns dos materiais utilizados. Por outro lado, o reservatório térmico não convencional e de baixo custo construído apresentou bons resultados, podendo inclusive ser utilizado em outros sistemas de aquecimento de água alternativos ou não convencionais.
IDENTIFICAÇÃO DA FLORA ESPONTÂNEA EM ÁREA DE CULTIVO COM Arachis hypogeae L.
Authors: Ferreira Thiago , Cunha Ana Lúcia Araújo , Oliveira Leandro Andrade
Published: September 2014

O Arachis hypogeae L. (Fabales: Fabaceae) é uma leguminosa-oleaginosa de porte baixo, que suas sementes são apreciadas pelo seu sabor agradável, e seus cultivos sofrem bastante com a competição com as ervas. Sendo assim o objetivo deste trabalho foi estudar a composição florística de uma área de cultivo de amendoim no município de Lagoa Seca-PB. Esta identificação ocorreu coma utilização de coleta in loco, dentro de quadrículas pré-determinadas, da parte aérea dos vegetais, futura catalogação das ervas, segundo bibliografia especializada. Foi descrita uma flora de quinze espécies e gêneros diferentes, pertencentes a doze diferentes famílias vegetativas, com maior relevância a família Poaceae.
PROPOSTA DE METODOLOGIA DE ADEQUAÇÃO AO NOVO ACORDO ORTOGRÁFICO DA LÍNGUA PORTUGUESA PARA ESTUDANTES DO CURSO DE LICENCIATURA EM QUÍMICA DO IFRN- CURRAIS NOVOS
Authors: Pereira Luiz Fernando , Matias-Ferreira, Jr. Tito
Published: September 2014

Este trabalho tem o intuito de dissertar sobre a importância de adequação ao novo acordo ortográfico da língua portuguesa para estudantes do curso de Licenciatura em Química do Instituto Federal do Rio Grande do Norte- Campus Currais Novos. Neste sentido, busca-se fazer um levantamento bibliográfico sobre este acordo, considerando suas características e importância para os estudantes e profissionais da área de educação. Objetiva-se ainda diagnosticar o nível de conhecimento sobre o tema que os discentes julgam possuir, bem como a importância que estes atribuem, e ainda, propor possíveis soluções de adequação ao acordo.
BEHAVIOURAL DESCRIPTION OF Sapajus nigritus (GOLDFUSS, 1809) RAISED IN CAPTIVITY AT IPATINGA, MG
Authors: Machado Felipe Santana , Costa Claudia Guimarães , Ribeiro Alan Loures
Published: September 2014

The maintenance of animals in captivity is one of the many ways of species preservation and allows studies that are often unattainable under natural conditions. Primate’s behavior and ecology studies supply tools for the development of conservation and management strategies. Consequently, the current research aimed to describe the patterns of behavior of a capuchin monkey, Sapajus nigritus, group raised in captivity at the Biodiversity Center of Associação Esportiva e Recreativa at Ipatinga, MG, Brazil. The Scan Sample was used with five minutes intervals. Ad libitum and Focal Animal were the complementary sampling. Twenty-three behavioral categories were recorded; this is considered average when compared to other ethograms. The behavioral class with greater prominence was foraging, however the different categories of behavior suggest a complex capacity of intra-specific interaction. The information serves as basic tools for the formulation of conservation strategies, management and to the comprehension of ecological interactions.
TERRAS RARAS: CONSIDERAÇÕES SOBRE O PLANALTO DE POÇOS DE CALDAS, MG NO NOVO CENÁRIO MUNDIAL
Authors: Vicente Gouvea Almir Donizette , Navarro Fabiano Cabañas , Roveri Carolina Del
Published: September 2014

A importância dos minerais de terras raras, considerados “materiais da terceira onda”, se deve a sua relação com o desenvolvimento tecnológico. A China por muito tempo dominou a produção e vendas no mercado mundial, adotando nos últimos anos severas medidas protecionistas que acabaram por forçar diversos países a optar por outras formas de suprimento para suas demandas. A necessidade de procurar novas fontes de minerais estratégicos levou ao desenvolvimento ou retomada de programas de exploração em diversas áreas. Dentre essas, destaca-se o Planalto de Poços de Caldas – MG, que corresponde a um depósito laterítico desenvolvido sobre um complexo alcalino intrusivo em domínios de embasamento cristalino. Nesse contexto geológico observam-se comportamentos distintos quanto aos processos de laterização e/ou oxidação que ocasionam a lixiviação de certos elementos e enriquecimento residual dos menores móveis, podendo formar um depósito econômico dependendo das condições locais. São apresentados dados oriundos de extensa revisão bibliográfica acerca do potencial geológico deste depósito e propõe-se a aplicação de técnicas de baixo custo para os trabalhos prospectivos no maciço.