bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards defining the chloroviruses: a genomic journey through a genus of large DNA viruses
Authors: Jeanniard Adrien , Dunigan David D , Gurnon James R , Agarkova Irina V , Kang Ming , Vitek Jason , Duncan Garry , McClung O William , Larsen Megan , Claverie Jean-Michel , Van Etten James L , Blanc Guillaume
Published: March 2013

Background

Giant viruses in the genus Chlorovirus (family Phycodnaviridae) infect eukaryotic green microalgae. The prototype member of the genus, Paramecium bursaria chlorella virus 1, was sequenced more than 15 years ago, and to date there are only 6 fully sequenced chloroviruses in public databases. Presented here are the draft genome sequences of 35 additional chloroviruses (287 – 348 Kb/319 – 381 predicted protein encoding genes) collected across the globe; they infect one of three different green algal species. These new data allowed us to analyze the genomic landscape of 41 chloroviruses, which revealed some remarkable features about these viruses.

Results

Genome colinearity, nucleotide conservation and phylogenetic affinity were limited to chloroviruses infecting the same host, confirming the validity of the three previously known subgenera. Clues for the existence of a fourth new subgenus indicate that the boundaries of chlorovirus diversity are not completely determined. Comparison of the chlorovirus phylogeny with that of the algal hosts indicates that chloroviruses have changed hosts in their evolutionary history. Reconstruction of the ancestral genome suggests that the last common chlorovirus ancestor had a slightly more diverse protein repertoire than modern chloroviruses. However, more than half of the defined chlorovirus gene families have a potential recent origin (after Chlorovirus divergence), among which a portion shows compositional evidence for horizontal gene transfer. Only a few of the putative acquired proteins had close homologs in databases raising the question of the true donor organism(s). Phylogenomic analysis identified only seven proteins whose genes were potentially exchanged between the algal host and the chloroviruses.

Conclusion

The present evaluation of the genomic evolution pattern suggests that chloroviruses differ from that described in the related Poxviridae and Mimiviridae. Our study shows that the fixation of algal host genes has been anecdotal in the evolutionary history of chloroviruses. We finally discuss the incongruence between compositional evidence of horizontal gene transfer and lack of close relative sequences in the databases, which suggests that the recently acquired genes originate from a still largely un-sequenced reservoir of genomes, possibly other unknown viruses that infect the same hosts.
Epistatic study reveals two genetic interactions in blood pressure regulation
Authors: Ndiaye Ndeye Coumba , Said El Shamieh , Stathopoulou Maria G , Siest Gérard , Tsai Michael Y , Visvikis-Siest Sophie
Published: March 2013

Background

Although numerous candidate gene and genome-wide association studies have been performed on blood pressure, a small number of regulating genetic variants having a limited effect have been identified. This phenomenon can partially be explained by possible gene-gene/epistasis interactions that were little investigated so far.

Methods

We performed a pre-planned two-phase investigation: in phase 1, one hundred single nucleotide polymorphisms (SNPs) in 65 candidate genes were genotyped in 1,912 French unrelated adults in order to study their two-locus combined effects on blood pressure (BP) levels. In phase 2, the significant epistatic interactions observed in phase 1 were tested in an independent population gathering 1,755 unrelated European adults.

Results

Among the 9 genetic variants significantly associated with systolic and diastolic BP in phase 1, some may act through altering the corresponding protein levels: SNPs rs5742910 (Padjusted≤0.03) and rs6046 (Padjusted =0.044) in F7 and rs1800469 (Padjusted ≤0.036) in TGFB1; whereas some may be functional through altering the corresponding protein structure: rs1800590 (Padjusted =0.028, SE=0.088) in LPL and rs2228570 (Padjusted ≤9.48×10-4) in VDR. The two epistatic interactions found for systolic and diastolic BP in the discovery phase: VCAM1 (rs1041163) * APOB (rs1367117), and SCGB1A1 (rs3741240) * LPL (rs1800590), were tested in the replication population and we observed significant interactions on DBP. In silico analyses yielded putative functional properties of the SNPs involved in these epistatic interactions trough the alteration of corresponding protein structures.

Conclusions

These findings support the hypothesis that different pathways and then different genes may act synergistically in order to modify BP. This could highlight novel pathophysiologic mechanisms underlying hypertension.
Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues
Authors: Rodrigues-Peres Raquel Mary , Cadore Solange , Febraio Stefanny , Heinrich Juliana Karina , Serra Katia Piton , Derchain Sophie F M , Vassallo Jose , Sarian Luis Otavio
Published: March 2013

Background

Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels.

Methods

A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS.

Results

The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02).

Conclusions

Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next logical step is the assessment of whether the aluminum concentration is related to the key genomic abnormalities associated with breast carcinogenesis.
The prospective application of a hypoxic radiosensitizer, doranidazole to rat intracranial glioblastoma with blood brain barrier disruption
Authors: Yasui Hironobu , Asanuma Taketoshi , Kino Junichi , Yamamori Tohru , Meike Shunsuke , Nagane Masaki , Kubota Nobuo , Kuwabara Mikinori , Inanami Osamu
Published: March 2013

Background

Glioblastoma is one of the intractable cancers and is highly resistant to ionizing radiation. This radioresistance is partly due to the presence of a hypoxic region which is widely found in advanced malignant gliomas. In the present study, we evaluated the effectiveness of the hypoxic cell sensitizer doranidazole (PR-350) using the C6 rat glioblastoma model, focusing on the status of blood brain barrier (BBB).

Methods

Reproductive cell death in the rat C6 glioma cell line was determined by means of clonogenic assay. An intracranial C6 glioma model was established for the in vivo experiments. To investigate the status of the BBB in C6 glioma bearing brain, we performed the Evans blue extravasation test. Autoradiography with [14C]-doranidazole was performed to examine the distribution of doranidazole in the glioma tumor. T2-weighted MRI was employed to examine the effects of X-irradiation and/or doranidazole on tumor growth.

Results

Doranidazole significantly enhanced radiation-induced reproductive cell death in vitro under hypoxia, but not under normoxia. The BBB in C6-bearing brain was completely disrupted and [14C]-doranidazole specifically penetrated the tumor regions. Combined treatment with X-irradiation and doranidazole significantly inhibited the growth of C6 gliomas.

Conclusions

Our results revealed that BBB disruption in glioma enables BBB-impermeable radiosensitizers to penetrate and distribute in the target region. This study is the first to propose that in malignant glioma the administration of hydrophilic hypoxic radiosensitizers could be a potent strategy for improving the clinical outcome of radiotherapy without side effects.
Allelic expression analysis of the osteoarthritis susceptibility gene COL11A1 in human joint tissues
Authors: Raine Emma V A , Dodd Andrew W , Reynard Louise N , Loughlin John
Published: March 2013

Background

The single nucleotide polymorphism (SNP) rs2615977 is associated with osteoarthritis (OA) and is located in intron 31 ofCOL11A1, a strong candidate gene for this degenerative musculoskeletal disease. Furthermore, the common non-synonymousCOL11A1SNP rs1676486 is associated with another degenerative musculoskeletal disease, lumbar disc herniation (LDH). rs1676486 is a C-T transition mediating its affect on LDH susceptibility by modulatingCOL11A1expression. The risk T-allele of rs1676486 leads to reduced expression of theCOL11A1transcript, a phenomenon known as allelic expression imbalance (AEI). We were keen therefore to assess whether the effect that rs1676486 has onCOL11A1expression in LDH is also observed in OA and whether the rs2615977 association to OA also marked AEI.

Methods

Using RNA from OA cartilage, we assessed whether either SNP correlated withCOL11A1AEI by 1) measuringCOL11A1expression and stratifying the data by genotype at each SNP; and 2) quantifying the mRNA transcribed from each allele of the two SNPs. We also assessed whether rs1676486 was associated with OA susceptibility using a case–control cohort of over 18,000 individuals.

Results

We observed significant AEI at rs1676486 (p < 0.0001) with the T-allele correlating with reducedCOL11A1expression. This corresponded with observations in LDH but the SNP was not associated with OA. We did not observe AEI at rs2615977.

Conclusions

COL11A1is subject to AEI in OA cartilage. AEI at rs1676486 is a risk factor for LDH, but not for OA. These two diseases therefore share a common functional phenotype, namely AEI ofCOL11A1, but this appears to be a disease risk only in LDH. Other functional effects onCOL11A1presumably account for the OA susceptibility that maps to this gene.
MicroRNA-613 represses lipogenesis in HepG2 cells by downregulating LXRα
Authors: Zhong Dan , Zhang Yan , Zeng Yi-jun , Gao Min , Wu Geng-ze , Hu Chang-jiang , Huang Gang , He Feng-tian
Published: March 2013

Background

MicroRNAs (miRNAs) emerge as new important regulators of lipid homeostasis by regulating corresponding genes. MiR-613 is a newly discovered microRNA, of which the biological function is unknown. A recent report has shown that miR-613 downregulates liver X receptor α (LXRα), a ligand-activated nuclear receptor playing an important role in the regulation of lipid metabolism. The purpose of this study is to explore the effect and the molecular basis of miR-613 on lipogenesis in HepG2 cells.

Methods

HepG2 cells were transiently transfected with miR-613 mimic or control microRNA. Real time PCR, Western blot, Luciferase reporter assay and Oil Red O staining were employed to examine the expression of LXRα and its target genes involved in lipogenesis, binding site for miR-613 in 3′-untranslated region (3′-UTR) of LXRα mRNA and lipid droplet accumulation in the cells.

Results

MiR-613 dramatically suppressed the expression of LXRα and its target genes including sterol-regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), carbohydrate responsive element-binding protein (ChREBP) and acetyl-CoA carboxylase (ACC). Reporter assay showed that miR-613 directly bound to 3′-UTR of LXRα mRNA. Moreover, miR-613 significantly repressed LXRα-induced lipid droplet accumulation in HepG2 cells. Ectopic expression of LXRα without 3′-UTR markedly attenuated the miR-613-mediated downregulation of LXRα’s target genes and LXRα-induced lipid droplet accumulation.

Conclusions

MiR-613 suppresses lipogenesis by directly targeting LXRα in HepG2 cells, suggesting that miR-613 may serve as a novel target for regulating lipid homeostasis.
Mapping the EQ-5D index by UPDRS and PDQ-8 in patients with Parkinson’s disease
Authors: Dams Judith , Klotsche Jens , Bornschein Bernhard , Reese Jens P , Balzer-Geldsetzer Monika , Winter Yaroslav , Schrag Anette , Siderowf Andrew , Oertel Wolfgang H , Deuschl Günther , Siebert Uwe , Dodel Richard
Published: March 2013

Background

Clinical studies employ the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure the severity of Parkinson’s disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates.

Methods

Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson’s disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson’s disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R2, the root mean square error (RMS), the Bayesian information criterion, and Pregibon’s link test. Three independent data sets validated the models.

Results

The regression analyses resulted in a single best prediction model (R2: 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2of 0.60 and 0.67. The independent data confirmed the prediction models.

Conclusion

The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use.
Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors
Authors: Diaz Claudia Marcela , Chiappori Alberto , Aurisicchio Luigi , Bagchi Ansuman , Clark Jason , Dubey Sheri , Fridman Arthur , Fabregas Jesus C , Marshall John , Scarselli Elisa , La Monica Nicola , Ciliberto Gennaro , Montero Alberto J
Published: March 2013

Background

DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols. We report the results of 2 multicenter phase 1 trials involving adult cancer patients (n=33) with stage II-IV disease.

Methods

Patients were vaccinated with V930 alone, a DNA vaccine containing equal amounts of plasmids expressing the extracellular and trans-membrane domains of human HER2, and a plasmid expressing CEA fused to the B subunit of Escherichia coli heat labile toxin (Study 1), or a heterologous prime-boost vaccination approach with V930 followed by V932, a dicistronic adenovirus subtype-6 viral vector vaccine coding for the same antigens (Study 2).

Results

The use of the V930 vaccination with electroporation alone or in combination with V932 was well-tolerated without any serious adverse events. In both studies, the most common vaccine-related side effects were injection site reactions and arthralgias. No measurable cell-mediated immune response (CMI) to CEA or HER2 was detected in patients by ELISPOT; however, a significant increase of both cell-mediated immunity and antibody titer against the bacterial heat labile toxin were observed upon vaccination.

Conclusion

V930 vaccination alone or in combination with V932 was well tolerated without any vaccine-related serious adverse effects, and was able to induce measurable immune responses against bacterial antigen. However, the prime-boost strategy did not appear to augment any detectable CMI responses against either CEA or HER2.

Trial registration

Study 1 – ClinicalTrials.gov, NCT00250419; Study 2 – ClinicalTrials.gov, NCT00647114.
A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior
Authors: Morris Gerwyn , Anderson George , Galecki Piotr , Berk Michael , Maes Michael
Published: March 2013

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions.
Management of a female with recurrence of fibromatosis of the chest wall adjacent to the breast: a case report
Authors: Shen Cheng , Zhou Yubin , Che Guowei
Published: March 2013

Extra-abdominal desmoid tumor is a rare soft tissue tumor that is histologically benign, but may behave aggressively. This case report specifically describes the clinical, radiographic, and pathologic features of 27 year-old female who experienced a post-surgical recurrence of fibromatosis of the chest wall over a two-year period of time secondary to previous inadequate excision. The fibromatosis was found to be involving the lower-inner quadrant of her right breast and causing worsening pain. A surgical management strategy was successfully undertaken.
Molecular identification of microorganisms associated with the brine shrimp Artemia franciscana
Authors: Riddle Misty R , Baxter Bonnie K , Avery Brian J
Published: March 2013

Background

Prior research on the microorganisms associated with the brine shrimp, Artemia franciscana, has mainly been limited to culture-based identification techniques or feeding studies for aquaculture. Our objective was to identify bacteria and archaea associated with Artemia adults and encysted embryos to understand the role of microbes in the Artemia life cycle and, therefore, their importance in a hypersaline food chain.

Results

We used small subunit (SSU) 16S ribosomal RNA gene sequencing to identify bacteria and archaea associated with adults and encysted Artemia embryos from one of their natural environments – Great Salt Lake (GSL), Utah, USA. We found that bacterial sequences most closely related to the genera Halomonas and Vibrio were commonly extracted from GSL adult Artemia, while bacterial sequences most similar to the genera Halomonas, Psychroflexus and Alkalilimnicola dominate in GSL water. Encysted embryos (cysts) yielded bacterial sequences from the genera Idiomarina and Salinivibrio, which were absent from adults and water. Common archaeal sequences in adults were most closely related to the genera Haloterrigena and Haloarcula, while all of the archaeal sequences from GSL water were most similar to the genus Halogeometricum. Cyst derived archaeal sequences were most closely related to the genera Halorubrum and Haloarcula.

Conclusions

In addition to identifying microbial rRNA sequences that are specific to different stages of the Artemia life cycle, we observed striking differences in the sequences associated with the adult Artemia population in samples collected from GSL at different times and locations. While our study was limited in scope and the sample was small, our findings provide a foundation for future research into how the bacteria and archaea associated with Artemia influence the Artemia life cycle, and GSL food web.
Attitudes among healthcare professionals to the reporting of adverse drug reactions in Nepal
Authors: KC Santosh , Tragulpiankit Pramote , Gorsanan Sarun , Edwards I Ralph
Published: March 2013

Background

Healthcare professional’s knowledge and attitudes to adverse drug reaction (ADR) and ADR reporting play vital role to report any cases of ADR. Positive attitudes may favour ADR reporting by healthcare professionals. This study was aimed to investigate the attitudes towards and ways to improve adverse drug reaction (ADR) reporting among healthcare professionals working at four Regional Pharmacovigilance Centres (RPCs) of Nepal.

Methods

A cross sectional study was done by survey using a self-administered structured questionnaire. The questionnaire was distributed to 450 healthcare professionals working at four RPCs.

Results

The overall response rate was 74.0%. There were 74.8% of healthcare professionals who had seen patient experiencing an ADR; however, only 20.1% had reported. Reporting form not available (48.1%) and other colleagues not reporting ADR cases (46.9%) would significantly discourage the ADR reporting among healthcare professionals working at four RPCs. Healthcare professionals perceived that seriousness of the reaction (75.6%); unusual reaction (64.6%); reaction to new product (71.2%); new reaction to existing product (70.2%); and confidence in diagnosis of ADR (60.8%) were important factors on the decision to report ADR. Awareness among healthcare professionals (85.9%), training (76.0%), collaboration (67.0%), and involve pharmacist for ADR reporting (63.1%) were mostly recognized ways to improve reporting. Regular newsletter on current awareness in drug safety (71.2%), information on new ADR (65.8%), and international drug safety information (64.0%) were the identified feedbacks they would like to receive from the Nepal pharmacovigilance programme.

Conclusion

Healthcare professionals working at four RPCs of Nepal have positive attitudes towards ADR reporting. Awareness among healthcare professionals, training and collaboration would likely improve reporting provided they would receive appropriate feedback from the national pharamcovigilance programme.
Electrospun eri silk fibroin scaffold coated with hydroxyapatite for bone tissue engineering applications
Authors: Andiappan Muthumanickkam , Sundaramoorthy Subramanian , Panda Niladrinath , Meiyazhaban Gowri , Winfred Sofi Beaula , Venkataraman Ganesh , Krishna Pramanik
Published: March 2013

Natural biomaterials such as collagen, silk fibroin, and chitosan, and synthetic biopolymers such as polylactic acid, polycaprolactone, polyglycolic acid, and their copolymers are being used as scaffold for tissue engineering applications. In the present work, a fibrous mat was electrospun from eri silk fibroin (ESF). A composite of hydroxyapatite (Hap) and the ESF scaffold was prepared by soaking the ESF scaffold in a solution of calcium chloride and then in sodium diammonium phosphate. The average tensile stress of the pure ESF and hydroxyapatite-coated ESF scaffold (ESF-Hap) was found to be 1.84 and 0.378 MPa, respectively. Pure ESF and ESF-Hap scaffolds were evaluated for their characteristics by a themogravimetric analyzer and Fourier transform infrared spectroscope. The crystallinity and thermal stability of the ESF-Hap scaffold were found to be more than that of uncoated eri silk nanofiber scaffold. The water uptake of the pure ESF and ESF-Hap scaffolds was found to be 69% and 340%, respectively, in distilled water as well as phosphate buffer saline. The hemolysis percentage of both scaffolds was less than 5%, which indicate their good blood compatibility. The cytocompatibility studied by 3-(4,5-dimethyl) thiazol-2-yl-2,5-dimethyl tetrazolium bromide assay showed that the scaffold is biocompatible. To assess cell attachment and growth on the scaffold, human mesenchymal stem cells were cultured on the scaffolds. The results from scanning electron microscopy and fluorescent microscopy showed a notable cellular growth and favorable morphological features. Hence, the ESF-Hap scaffold is better suited for cell growth than the pure ESF scaffold.
Conditional Mutagenesis of Gata6 in SF1-Positive Cells Causes Gonadal-Like Differentiation in the Adrenal Cortex of Mice
Authors: Pihlajoki Marjut , Gretzinger Elisabeth , Cochran Rebecca , Kyrönlahti Antti , Schrade Anja , Hiller Theresa , Sullivan Laura , Shoykhet Michael , Schoeller Erica L. , Brooks Michael D. , Heikinheimo Markku , Wilson David B.
Published: March 2013

Transcription factor GATA6 is expressed in the fetal and adult adrenal cortex and has been implicated in steroidogenesis. To characterize the role of transcription factor GATA6 in adrenocortical development and function, we generated mice in which Gata6 was conditionally deleted using Cre-LoxP recombination with Sf1-cre. The adrenal glands of adult Gata6 conditional knockout (cKO) mice were small and had a thin cortex. Cytomegalic changes were evident in fetal and adult cKO adrenal glands, and chromaffin cells were ectopically located at the periphery of the glands. Corticosterone secretion in response to exogenous ACTH was blunted in cKO mice. Spindle-shaped cells expressing Gata4, a marker of gonadal stroma, accumulated in the adrenal subcapsule of Gata6 cKO mice. RNA analysis demonstrated the concomitant upregulation of other gonadal-like markers, including Amhr2, in the cKO adrenal glands, suggesting that GATA6 inhibits the spontaneous differentiation of adrenocortical stem/progenitor cells into gonadal-like cells. Lhcgr and Cyp17 were overexpressed in the adrenal glands of gonadectomized cKO vs control mice, implying that GATA6 also limits sex steroidogenic cell differentiation in response to the hormonal changes that accompany gonadectomy. Nulliparous female and orchiectomized male Gata6 cKO mice lacked an adrenal X-zone. Microarray hybridization identified Pik3c2g as a novel X-zone marker that is downregulated in the adrenal glands of these mice. Our findings offer genetic proof that GATA6 regulates the differentiation of steroidogenic progenitors into adrenocortical cells.
Exendin-4 Protects Hypoxic Islets From Oxidative Stress and Improves Islet Transplantation Outcome
Authors: Padmasekar M. , Lingwal N. , Samikannu B. , Chen C. , Sauer H. , Linn T.
Published: March 2013

Oxidative stress produced during pancreatic islet isolation leads to significant β-cell damage. Homeostatic cytokines secreted subsequently to islet transplantation damage β-cells by generating oxygen free radicals. In this study, exendin-4, a glucagon-like peptide-1 analog improved islet transplantation outcome by increasing the survival of diabetic recipient mice from 58% to 100%. We hypothesized that this beneficial effect was due to the ability of exendin-4 to reduce oxidative stress. Further experiments showed that it significantly reduced the apoptotic rate of cultured β-cells subjected to hypoxia or to IL-1β. Reduction of apoptotic events was confirmed in pancreatic islet grafts of exendin-4–treated mice. Exendin-4 enhanced Akt phosphorylation of β-cells and insulin released from them. It even augmented insulin secretion from islets cultivated at hypoxic conditions. Exposure to hypoxia led to a decrease in the activation of Akt, which was reversed when β-cells were pretreated with exendin-4. Moreover, exendin-4 increased the activity of redox enzymes in a hypoxia-treated β-cell line and reduced reactive oxygen species production in isolated pancreatic islets. Recovery from diabetes in mice transplanted with hypoxic islets was more efficient when they received exendin-4. In conclusion, exendin-4 rescued islets from oxidative stress caused by hypoxia or due to cytokine exposure. It improved the outcome of syngenic and xenogenic islet transplantation.
High-Fat Diet-Mediated Lipotoxicity and Insulin Resistance Is Related to Impaired Lipase Expression in Mouse Skeletal Muscle
Authors: Badin Pierre-Marie , Vila Isabelle K. , Louche Katie , Mairal Aline , Marques Marie-Adeline , Bourlier Virginie , Tavernier Geneviève , Langin Dominique , Moro Cedric
Published: March 2013

Elevated expression/activity of adipose triglyceride lipase (ATGL) and/or reduced activity of hormone-sensitive lipase (HSL) in skeletal muscle are causally linked to insulin resistance in vitro. We investigated here the effect of high-fat feeding on skeletal muscle lipolytic proteins, lipotoxicity, and insulin signaling in vivo. Five-week-old C3H mice were fed normal chow diet (NCD) or 45% kcal high-fat diet (HFD) for 4 weeks. Wild-type and HSL knockout mice fed NCD were also studied. Whole-body and muscle insulin sensitivity, as well as lipolytic protein expression, lipid levels, and insulin signaling in skeletal muscle, were measured. HFD induced whole-body insulin resistance and glucose intolerance and reduced skeletal muscle glucose uptake compared with NCD. HFD increased skeletal muscle total diacylglycerol (DAG) content, protein kinase Cθ and protein kinase Cϵ membrane translocation, and impaired insulin signaling as reflected by a robust increase of basal Ser1101 insulin receptor substrate 1 phosphorylation (2.8-fold, P < .05) and a decrease of insulin-stimulated v-Akt murine thymoma viral oncogene homolog Ser473 (−37%, P < .05) and AS160 Thr642 (−47%, P <.01) phosphorylation. We next showed that HFD strongly reduced HSL phosphorylation at Ser660. HFD significantly up-regulated the muscle protein content of the ATGL coactivator comparative gene identification 58 and triacylglycerol hydrolase activity, despite a lower ATGL protein content. We further show a defective skeletal muscle insulin signaling and DAG accumulation in HSL knockout compared with wild-type mice. Together, these data suggest a pathophysiological link between altered skeletal muscle lipase expression and DAG-mediated insulin resistance in mice.
Part 1: Why I Am Not a Postsecularist
Authors: Cooper Melinda
Published: March 2013

This article questions the culturalist and civilizational taxonomies of postsecular theory by redirecting attention toward the practical consequences of public theology in the realm of neoliberal welfare reform. Tracing the simultaneous rise of faith-based welfare and the religious Right in the United Kingdom, the United States, the Middle East, and India, it argues that the postsecular posture of anticapitalist critique testifies at best to a misunderstanding of the constitutive relationship between the neoliberal and the neopaternal. Returning to Marx, the essay posits (contra Polanyi) that capital demands the constant reassertion of fundamental value, even while it works to undermine all historically specific instances of foundation.
The Echo Chamber of Freedom: The Muslim Woman and the Pretext of Agency
Authors: Abbas Sadia
Published: March 2013

This essay argues that notions of the subject, individualism, freedom, agency, change, and history (in other words, the ideas that are used to mark the boundaries of the West, and that generate the most sensitized aporias of modernity) have come to cluster around the figure of the Muslim woman (for whom the metonym is increasingly the veil): object of imperial rescue, justification for imperial warfare, Orientalist cipher, target of jihadist violence, and increasingly the discursive site upon which is worked out the central preoccupation of our time: How do you free yourself from freedom?
Is the Postcolonial Also Postsecular?
Authors: Robbins Bruce
Published: March 2013

Early postcolonial critics were at worst ambivalent about secularism, and more likely either uninterested or, like Edward Said, extremely enthusiastic. What is the meaning of the recent turn against secularism by critics in and around the field Said did so much to establish? This essay weighs both Said’s militant commitment, finding it more complex than it appears, and the critiques of Said and secularism by such figures as Talal Asad and Gil Anidjar. Accusing the latter thinkers of a religious essentialism on the embarrassing model of Samuel Huntington’s clash of civilizations, the essay answers its title question with a resounding “no,” proposes a withdrawal from the easy identification of secularism, modernity, and the state, and ends with a counsel of disciplinary modesty.
“The Balance Wheel”: William Allen White, the Kansas Industrial Court, and the Progressive Approach to the Labor Question, 1914–1925
Authors: Delgadillo Charles
Published: March 2013

In this article, Charles Delgadillo addresses the fate of the Progressive approach to the labor question, which sought to eliminate socially costly industrial strikes through quasi-judicial measures that envisioned government as a neutral adjudicator between warring labor and capital. The Kansas Industrial Relations Act of 1920 epitomized this strategy by replacing strikes and lockouts with a system of compulsory adjudication called the industrial court. William Allen White, the celebrated Kansas newspaper editor, played a key role in advancing the industrial court as a civilized substitute for industrial warfare that was especially fair to labor. The Great Railroad Strike of 1922 dispelled White's Progressive illusions after the law was used to break the strike by crushing civil liberties. White finally understood the working class's wariness toward the state, and he realized that strikes were labor's only means of obtaining justice. The failure of the Kansas Industrial Court freed Progressives such as White to accept the necessity of conflict in resolving industrial disputes, which formed the basis of New Deal labor policy.
Loss of integration is associated with reduced resistance to oxidative stress
Authors: Costantini David , Monaghan Patricia , Metcalfe Neil
Published: March 2013

One cellular mechanism thought to be particularly important as a constraint on lifespan and life-history strategies is oxidative stress. Susceptibility to oxidative stress is influenced by a number of antioxidant defences, whose effectiveness depends on the synergistic and competitive interactions among them (biochemical integration). It is generally assumed that exposure to oxidative stress is detrimental, but it is also possible that low level oxidative stress has a positive effect on integration, and therefore carries some benefits. Using three experimental groups of zebra finches (control, mild and high flight activity), we tested whether exercise-induced oxidative stress altered the integration of the pro-oxidant/antioxidant system by manipulating levels of flight activity, known to generate oxidative stress in birds. We show for the first time that a short-term high level of physical activity leads to a reduction in integration among components of the blood antioxidant defences, associated with a reduced resistance to oxidative stress. We found no evidence of improved integration in the antioxidant defences at low levels of oxidative stress exposure, suggesting that improved integration is not the route whereby any benefits of low level stress exposure occur. These findings point to a reduction in biochemical integration as a potential mechanism explaining a reduced resistance to oxidative stress induced by short-term stressors.
An Expeditious and Solvent-Free Synthesis of Substituted Pyrroles Using Sulfated Anatase-Titania as a Solid Acid Catalyst
Authors: Ravi Krishnaswamy , Krishnakumar Balu , Swaminathan Meenakshisundaram
Published: March 2013

Sulfated anatase-titania (TiO2–SO42−) has been used as a solid acid catalyst for the synthesis of substituted pyrroles from γ-diketone and aromatic/aliphatic (acyclic and cyclic) primary amines by simple physical grinding. This sulfated titania gives an excellent yield with less reaction time and is an inexpensive, easily recyclable nanocatalytic material for this reaction. Higher catalytic activity of TiO2–SO42− is due to its increased Brønsted acidity.
Studies of Composite Cathode Material LiFePO4–Li3V2(PO4)3 and It’s Precursor FeVO4·xH2O
Authors: Zheng Jun-chao , Zhang Bao , Yang Zhan-hong , Ou Xing , Zhang Jia-feng
Published: March 2013

As both iron and vanadium sources, the spherical amorphous FeVO4·xH2O powders are synthesized through an aqueous precipitation method by using Fe(NO3)3, NH4VO3, and ammonia water as starting materials. The effects of pH value of precursor solution on the Fe/V molar ratio is studied, it is found that when the pH is 4, the Fe/V molar ration is 1.004, it is close to 1. The FeVO4·xH2O powders are preheat treated at 600 °C for 12 h in air to obtain triclinic FeVO4. The FeVO4 powders are homogeneously mixed with Li2CO3, NH4H2PO4, and oxalic acid with stoichiometric ratio, and then sinter at 750 °C for 12 h in argon atmosphere to obtain LiFePO4–Li3V2(PO4)3 composite material. The structural properties, particle morphology, and electrochemical performance of composite cathode material LiFePO4–Li3V2(PO4)3 were studied. The FeVO4 not only plays as the main reactant to form LiFePO4 and Li3V2(PO4)3, but also as the dopants doping LiFePO4–Li3V2(PO4)3. The LiFePO4–Li3V2(PO4)3 composite cathode shows good electrochemical performance, and its discharge capacity is about 138.7 mA h g−1 at 1 C rate after 100 cycles, which retains 93.3% of it’s theoretical capacity (148.6 mA h g−1) for composite cathode material LiFePO4–Li3V2(PO4)3 in the voltage range of 2.5–4.5 V.
Odd–Even Effect in the Surface Structure of Alkyloxy-Substituted Anthraquinone on HOPG Observed by Scanning Tunneling Microscope
Authors: Tamaki Yoshinori , Muto Kosuke , Miyamura Kazuo
Published: March 2013

Self-assembled adlayers of a series of anthraquinone derivatives, 2-alkoxyanthraquinone (n-ant, n = 14, 15, 16, 17, 18, 20, and 22) where n stands for the alkyl (CnH2n+1) chain length, on highly oriented pyrolytic graphite (HOPG) surface are investigated by scanning tunneling microscope (STM). Anthraquinone derivatives are found to form C–H···O hydrogen-bonded dimers. However, the self-assembled 2D pattern of monolayer depends on the parity (odd/even) of carbon atoms and the length of the alkyl chains. When n is even in number, the aggregating structure in the monolayer is interdigitated lamellar structure. The specific feature of these lamellae is the propagation of dislocations. The frequency of dislocation increased as the alkyl chain elongated. However, when n is odd in number, molecules adopt different conformation (type B) and the aggregating structure changes drastically. This indicates that the orientation of the terminal methyl of the alkyl group induces the surface structural change, i.e., the odd–even effect.
Dissecting the role of TRPV1 in detecting multiple trigeminal irritants in three behavioral assays for sensory irritation
Authors: Saunders CJ , Li Winston Y , Patel Tulsi D , Muday Jeffrey A , Silver Wayne L
Published: March 2013

Polymodal neurons of the trigeminal nerve innervate the nasal cavity, nasopharynx, oral cavity and cornea. Trigeminal nociceptive fibers express a diverse collection of receptors and are stimulated by a wide variety of chemicals. However, the mechanism of stimulation is known only for relatively few of these compounds. Capsaicin, for example, activates transient receptor potential vanilloid 1 (TRPV1) channels. In the present study, wildtype (C57Bl/6J) and TRPV1 knockout mice were tested in three behavioral assays for irritation to determine if TRPV1 is necessary to detect trigeminal irritants in addition to capsaicin. In one assay mice were presented with a chemical via a cotton swab and their response scored on a 5 level scale. In another assay, a modified two bottle preference test, which avoids the confound of mixing irritants with the animal’s drinking water, was used to assess aversion. In the final assay, an air dilution olfactometer was used to administer volatile compounds to mice restrained in a double-chambered plethysmograph where respiratory reflexes were monitored. TRPV1 knockouts showed deficiencies in the detection of benzaldehyde, cyclohexanone and eugenol in at least one assay. However, cyclohexanone was the only substance tested that appears to act solely through TRPV1.
The Atiyah–Patodi–Singer signature formula for measured foliations
Authors: Antonini Paolo
Published: March 2013

Given a compact manifold with boundary X
0 endowed with a foliation

ℱ
0

${\mathcal {F}_0}$

transverse to the boundary, and which
admits a holonomy invariant transverse measure Λ,
we define three types of signature for the pair (foliation, boundary foliation): the analytic signature, denoted by

σ

Λ
,
an

(

X
0

,
∂

X
0

)

${\sigma _{\Lambda ,\operatorname{an}}(X_0,\partial X_0)}$

, is the leafwise L2
-Λ-index of the signature operator on the extended manifold X obtained by attaching cylindrical ends to the boundary; the Hodge signature

σ

Λ
,
Hodge

(

X
0

,
∂

X
0

)

${\sigma _{\Lambda ,\operatorname{Hodge}}(X_0,\partial X_0)}$

is defined using the natural representation of the Borel groupoid

ℛ

${\mathcal {R}}$

of X on the field of square integrable harmonic forms on the leaves; and
the de Rham signature,

σ

Λ
,
dR

(

X
0

,
∂

X
0

)

${\sigma _{\Lambda ,\operatorname{dR}}(X_0,\partial X_0)}$

, defined using the natural representation
of the Borel groupoid

ℛ
0

${\mathcal {R}_0}$

of X
0 on the field of the L2
-relative de Rham spaces of the leaves. We prove that
these three signatures coincide

σ

Λ
,
an

(

X
0

,
∂

X
0

)

=

σ

Λ
,
Hodge

(

X
0

,
∂

X
0

)

=

σ

Λ
,
dR

(

X
0

,
∂

X
0

)

.

$ \sigma _{\Lambda , \operatorname{an}}(X_0,\partial X_0)=
\sigma _{\Lambda ,\operatorname{Hodge}}(X_0,\partial X_0)=\sigma _{\Lambda ,\operatorname{dR}}(X_0,\partial X_0). $

As a consequence of the index formula we proved in [Bull. Sci. Math. (2010), DOI 10.1016/
j.bulsci.2010.10.003], we finally obtain the Atiyah–Patodi–Singer
signature formula for measured foliations:

σ

Λ
,
dR

(

X
0

,
∂

X
0

)

=

〈
L

(
T

ℱ
0

)

,

C
Λ

〉

+
1
/
2

[

η
Λ

(

D

ℱ
∂

)

]

.

$ \sigma _{\Lambda ,\operatorname{dR}}(X_0,\partial X_0)=\langle L(T\mathcal {F}_0),C_{\Lambda }\rangle +1/2[\eta _{\Lambda }(D^{\mathcal {F}_{\partial }})]. $
Heat kernel for fractional diffusion operators with perturbations
Authors: Wang Feng-Yu , Zhang Xi-Cheng
Published: March 2013

Let L be an elliptic differential operator on a complete connected Riemannian manifold M such that the associated heat kernel has two-sided Gaussian
bounds as well as a Gaussian type gradient estimate. Let

L

(
α
)

${L^{(\alpha )}}$

be the α-stable subordination of L for

α
∈
(
1
,
2
)

${\alpha \in (1,2)}$

. We
found some classes

𝕂

α

γ
,
β

(
β
,
γ
∈

[
0
,
α
)

)

${\mathbb {K}_{\alpha }^{\gamma ,\beta } (\beta ,\gamma \in [0,\alpha ))}$

of
time-space functions containing the Kato class, such that for any
measurable functions

b
:
[
0
,
∞
)
×
M
→
T
M

${b: [0,\infty )\times M\rightarrow TM}$

and

c
:
[
0
,
∞
)
×
M
→
M

${c: [0,\infty )\times M\rightarrow M}$

with

|
b
|
,
c

∈

𝕂

α

1
,
1

${|b|, c\in \mathbb {K}_{\alpha }^{1,1}}$

, the operator

L

b
,
c

(
α
)

(
t
,
x
)

:
=

L

(
α
)

(
x
)

+

〈
b

(
t
,
x
)

,
∇
·

〉

+
c

(
t
,
x
)

,

(
t
,
x
)

∈

[
0
,
∞
)

×
M
,

$
L_{b,c}^{(\alpha )}(t,x):= L^{(\alpha )}(x)+ \langle b(t,x),\nabla \cdot \,\rangle +c(t,x),\quad (t,x)\in [0,\infty )\times M,\vspace*{-1.42262pt}
$

has a unique heat kernel

p

b
,
c

(
α
)

(
t
,
x
;
s
,
y
)

${p_{b,c}^{(\alpha )}(t,x;s,y)}$

,

0
≤
s
<
t

${0\le s<t}$

,

x
,
y
∈
M

${x,y\in M}$

, which is jointly continuous and satisfies

t
-
s

C

{
ρ

(
x
,
y
)

∨

(
t
-
s
)

1
α

}

d
+
α

≤

p

b
,
c

(
α
)

(
t
,
x
;
s
,
y
)

≤

C
(
t
-
s
)

{
ρ

(
x
,
y
)

∨

(
t
-
s
)

1
α

}

d
+
α

$
\frac{t-s}{C\lbrace \rho (x,y)\vee (t-s)^{\frac{1}{\alpha }}\rbrace ^{d+\alpha }}\le p_{b,c}^{(\alpha )}(t,x;s,y)\le \frac{C(t-s)}{\lbrace \rho (x,y)\vee (t-s)^{\frac{1}{\alpha }}\rbrace ^{d+\alpha }}\vspace*{-1.42262pt}
$

and

|

∇
x

p

b
,
c

(
α
)

(
t
,
x
;
s
,
y
)

|
≤

C

(
t
-
s
)

α
-
1

α

{
ρ

(
x
,
y
)

∨

(
t
-
s
)

1
α

}

d
+
α

,

0
≤
s
<
t
,

x
,
y
∈
M
,

$ \big |\nabla _x p_{b,c}^{(\alpha )}(t,x; s,y)\big |\le \frac{C(t-s)^{\frac{\alpha -1}{\alpha }}}{\lbrace \rho (x,y)\vee (t-s)^{\frac{1}{\alpha }}\rbrace ^{d+\alpha }},\quad 0\le s<t,\; x,y\in M,\vspace*{-1.42262pt}
$

for some constant C > 1, where ρ is the Riemannian distance. The estimate of

∇
y

p

b
,
c

(
α
)

${\nabla _yp^{(\alpha )}_{b,c}}$

and the Hölder continuity of

∇
x

p

b
,
c

(
α
)

${\nabla _x p_{b,c}^{(\alpha )}}$

are also considered. The resulting estimates of the gradient and its Hölder continuity are new even in the standard case where

L
=
Δ

${L=\Delta }$

on ℝ
d
and b, c are time-independent.
Block-diagonal characterization of locally finite simple groups of p-type
Authors: Delcroix Stefaan
Published: March 2013

In this paper, we prove the following characterization of LFS-groups of

Let

(i)

(ii) there exists

(a)

(b)

(c) for

where

Then

We use this theorem to construct a general family of LFS-groups of
Wear Evaluation of Pack Boronized AISI 1060 Steel
Authors: Fernandes F. A. P. , Heck S. C. , Totten G. E. , Casteletti L. C.
Published: March 2013

Boronizing is used to obtain very high hardness and wear resistance on ferrous and non-ferrous materials and some super alloys. The process can be carried out in solid, liquid, or gaseous medium. In this work, samples of AISI 1060 steel were treated by the pack boriding method during 2 and 4 h at 900 and 1000°C. Optical microscopy, x-ray diffraction, and micro-hardness analyses were conducted and wear tests were performed using a micro-wear machine with a fixed-ball configuration. The pack boriding resulted in the formation of layers with high hardness and wear resistance. All the borided layers presented top hardness around 2000 HV (Vickers pyramid number). Raising time and temperature of treatment increased the layer thickness. X-ray diffraction patterns showed the presence of only Fe2B for samples treated at 900°C for 2 and 4 h. The samples borided at 1000°C for 2 and 4 h presented layers composed by a mixture of Fe2B and FeB. The wear resistance of the samples borided at 1000°C was higher than that borided at 900°C, probably because of the difference in chemical composition.