bluuebunny/crossref_metadata_2025 huggingface dataset:
HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer
Authors: Wang Can , Bao Chenchen , Liang Shujing , Zhang Lingxia , Fu Hualin , Wang Yutian , Wang Kan , Li Chao , Deng Min , Liao Qiande , Ni Jian , Cui Daxiang
Published: May 2014

The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-α-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of α-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the α-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of gastric cancer cells. In conclusion, HAI-178 antibody-conjugated fluorescent magnetic nanoparticles have a great potential in applications such as targeted imaging and simultaneous therapy of in vivo early gastric cancer cells in the near future.
Simplified ZrTiO
x
-based RRAM cell structure with rectifying characteristics by integrating Ni/n + -Si diode
Authors: Lin Chia-Chun , Wu Yung-Hsien , Chang You-Tai , Sun Cherng-En
Published: May 2014

A simplified one-diode one-resistor (1D1R) resistive switching memory cell that uses only four layers of TaN/ZrTiO
x
/Ni/n+-Si was proposed to suppress sneak current where TaN/ZrTiO
x
/Ni can be regarded as a resistive-switching random access memory (RRAM) device while Ni/n+-Si acts as an Schottky diode. This is the first RRAM cell structure that employs metal/semiconductor Schottky diode for current rectifying. The 1D1R cell exhibits bipolar switching behavior with SET/RESET voltage close to 1 V without requiring a forming process. More importantly, the cell shows tight resistance distribution for different states, significantly rectifying characteristics with forward/reverse current ratio higher than 103 and a resistance ratio larger than 103 between two states. Furthermore, the cell also displays desirable reliability performance in terms of long data retention time of up to 104 s and robust endurance of 105 cycles. Based on the promising characteristics, the four-layer 1D1R structure holds the great potential for next-generation nonvolatile memory technology.
LiFePO4 microcrystals as an efficient heterogeneous Fenton-like catalyst in degradation of rhodamine 6G
Authors: Li Zhan Jun , Ali Ghafar , Kim Hyun Jin , Yoo Seong Ho , Cho Sung Oh
Published: May 2014

We present a novel heterogeneous Fenton-like catalyst of LiFePO4 (LFP). LFP has been widely used as an electrode material of a lithium ion battery, but we observed that commercial LFP (LFP-C) could act as a good Fenton-like catalyst to decompose rhodamine 6G. The catalytic activity of LFP-C microparticles was much higher than a popular catalyst, magnetite nanoparticles. Furthermore, we found that the catalytic activity of LFP-C could be further increased by increasing the specific surface area. The reaction rate constant of the hydrothermally synthesized LFP microcrystals (LFP-H) is at least 18 times higher than that of magnetite nanoparticles even though the particle size of LFP is far larger than magnetite nanoparticles. The LFP catalysts also exhibited a good recycling behavior and high stability under an oxidizing environment. The effects of the experimental parameters such as the concentration of the catalysts, pH, and the concentration of hydrogen peroxide on the catalytic activity of LFP were also analyzed.
One-step synthesis of platinum nanoparticles loaded in alginate bubbles
Authors: Yang Chih-Hui , Wang Wei-Ting , Grumezescu Alexandru Mihai , Huang Keng-Shiang , Lin Yung-Sheng
Published: May 2014

Composite particles with multifunctions have been extensively utilized for various applications. Bubble particles can be applied for ultrasound-mediated imaging, drug delivery, absorbers, cell culture, etc. This study proposes a one-step strategy to obtain Pt nanoparticles loaded in alginate bubbles. A needle-based droplet formation was used to generate uniform alginate particles about 2 mm in diameter. The hydrolysis reaction of NaBH4 was utilized to produce gaseous hydrogen and then trapped within alginate particles to form bubbles. The Pt4+ mixed with alginate solution was dropped into the reservoir to react with reducing NaBH4 and hardening CaCl2 to form Pt nanoparticles-alginate composite bubbles. Results indicate that the size of bubbles decreases with the CaCl2 concentration (1% ~ 20%), and size of bubbles increases with the NaBH4 concentration (1 ~ 20 mM). The advantages for the present approach include low cost, easy operation, and effective production of Pt nanoparticles-alginate composite bubbles.
Efficient enumeration of monocyclic chemical graphs with given path frequencies
Authors: Suzuki Masaki , Nagamochi Hiroshi , Akutsu Tatsuya
Published: May 2014

Background

The enumeration of chemical graphs (molecular graphs) satisfying given constraints is one of the fundamental problems in chemoinformatics and bioinformatics because it leads to a variety of useful applications including structure determination and development of novel chemical compounds.

Results

We consider the problem of enumerating chemical graphs with monocyclic structure (a graph structure that contains exactly one cycle) from a given set of feature vectors, where a feature vector represents the frequency of the prescribed paths in a chemical compound to be constructed and the set is specified by a pair of upper and lower feature vectors. To enumerate all tree-like (acyclic) chemical graphs from a given set of feature vectors, Shimizu et al. and Suzuki et al. proposed efficient branch-and-bound algorithms based on a fast tree enumeration algorithm. In this study, we devise a novel method for extending these algorithms to enumeration of chemical graphs with monocyclic structure by designing a fast algorithm for testing uniqueness. The results of computational experiments reveal that the computational efficiency of the new algorithm is as good as those for enumeration of tree-like chemical compounds.

Conclusions

We succeed in expanding the class of chemical graphs that are able to be enumerated efficiently.
Prevalence and determinants of Campylobacter infection among under five children with acute watery diarrhea in Mwanza, North Tanzania
Authors: Deogratias Anna-Pendo , Mushi Martha F , Paterno Laurent , Tappe Dennis , Seni Jeremiah , Kabymera Rogatus , Kidenya Benson R , Mshana Stephen E
Published: May 2014

Background

Campylobacteriosis, a zoonotic bacterial disease observed world-wide, is becoming the most commonly recognized cause of bacterial gastroenteritis in humans. This study was done to determine the prevalence and determinants of Campylobacter infection among under-fives with acute watery diarrhea in Mwanza City, Tanzania.

Method

This cross-sectional hospital-based study was conducted at Bugando Medical Centre (BMC) and Sekou Toure Hospital in Mwanza City. All inpatients and outpatients under-fives who met the inclusion criteria from October 2012 to April 2013 were enrolled in the study. Demographic and clinical data were obtained using standardized data collection tools. Stool samples were collected for gram staining and culture for Campylobacter spp. on Preston selective agar media. In addition, blood slides for malaria and HIV tests were done to all patients.

Results

A total of 300 children were enrolled with a median age of 12 [interquartile range, 8–19] months. Of these, 169 (56.5%) were from BMC and 131 (43.7%) from Sekou-Toure hospital. One hundred and seventy (56.7%) of the participating children were male. Of 300 under-fives with acute watery diarrhea, 29 patients (9.7%) were found to have Campylobacter infection. A significant higher number of children with Campylobacter infection were found in Sekou Toure hospital compared to BMC [16.0% (21/29) versus 4.7% (8/29), p = 0.002)]. Age above 2 years was independently found to predict campylobacter infection (OR: 2.9, 95% CI 1.1-7.7, p = 0.0037). Of 30 patients with a positive blood slide for Plasmodium falciparum, 20.0% were also positive for Campylobacter infection (OR: 3.9, 95% CI 1.2-10.1, p = 0.021).

Conclusion

Campylobacter infection shows a comparatively low prevalence in under-fives with acute watery diarrhea in Mwanza city and is independently associated with positive slides for malaria and an age above 2 years. Further studies are needed to type the most prevalent Campylobacter species and to determine their antibiotic susceptibility pattern.
Graphical interface design for children seeking information in a digital library
Authors: Wu Ko-chiu , Tang Yun-meng , Tsai Cheng-yu
Published: May 2014

Background

Children are very curious. They like to play games but lack reading fluency. Conventional interfaces for information-seeking in digital libraries are unsuitable for children because they are rigid, text-based, and task-oriented. Thus, this study developed a customized interface for a digital library. To facilitate children in online searches, the design concepts included user-friendly target icons, icon recognition, and way-finding in a two-dimensional visualized environment.

Methods

In this study, the criteria used to develop visualization tools that children can use for information retrieval were based on theories of human perception related to graphical interfaces for information visualization systems, including iconic representations and information density on visualized displays. Databases widely used by children in the National Library of Public Information were linked to the suggested database frame. The database frame was classified into five major subject categories: Natural Sciences, Fine Arts and Music, Health and Athletics, History and Culture, and Treasure of Knowledge. The web interface was designed according to way-finding concepts and map-structure hierarchies. Information searches in the main frame, sub-frames, and linked database were designed to be simple and intuitive for use by children.

Results

Information search efficiency was measured in 104 children assigned to search the virtual environment for icons (databases) that adequately supported their studies. Statistical analyses showed that, compared to the text-lined interface, the graphical interface improved the success and speed of searches by children.

Conclusions

Incorporating theories of spatial memory and representative icons in designs for visualized retrieval systems helps children to recognize different categories of knowledge content and improves their efficiency in information retrieval. To improve database search efficiency in children, information recommendation issues require further study. However, further research is also needed to identify factors that affect patterns of information-seeking behavior in children.
Survivin family proteins as novel molecular determinants of doxorubicin resistance in organotypic human breast tumors
Authors: Faversani Alice , Vaira Valentina , Moro Giacomina P , Tosi Delfina , Lopergolo Alessia , Schultz David C , Rivadeneira Dayana , Altieri Dario C , Bosari Silvano
Published: May 2014

Introduction

The molecular determinants of breast cancer resistance to first-line anthracycline-containing chemotherapy are unknown.

Methods

We examined the response to doxorubicin of organotypic cultures of primary human breast tumors ex vivo with respect to cell proliferation, DNA damage and modulation of apoptosis. Samples were analyzed for genome-wide modulation of cell death pathways, differential activation of p53, and the role of survivin family molecules in drug resistance. Rational drug combination regimens were explored by high-throughput screening, and validated in model breast cancer cell types.

Results

Doxorubicin treatment segregated organotypic human breast tumors into distinct Responder or Non Responder groups, characterized by differential proliferative index, stabilization of p53, and induction of apoptosis. Conversely, tumor histotype, hormone receptor or human epidermal growth factor receptor-2 (HER2) status did not influence chemotherapy sensitivity. Global analysis of cell death pathways identified survivin and its alternatively spliced form, survivin-ΔEx3 as uniquely overexpressed in Non Responder breast tumors. Forced expression of survivin-ΔEx3 preserved cell viability and prevented doxorubicin-induced apoptosis in breast cancer cell types. High-throughput pharmacologic targeting of survivin family proteins with a small-molecule survivin suppressant currently in the clinic (YM155) selectively potentiated the effect of doxorubicin, but not other chemotherapeutics in breast cancer cell types, and induced tumor cell apoptosis.

Conclusions

Survivin family proteins are novel effectors of doxorubicin resistance in chemotherapy-naive breast cancer. The incorporation of survivin antagonist(s) in anthracycline-containing regimens may have improved clinical activity in these patients.
A new alternative in plant retrograde signaling
Authors: Jung Hou-Sung , Mockler Todd C
Published: May 2014

The reduced or oxidized state of plastoquinone in chloroplasts regulates splicing in the nucleus to control nuclear gene expression in response to changing environmental conditions.
Gene expression profiles associated with acute myocardial infarction and risk of cardiovascular death
Authors: Kim Jinhee , Ghasemzadeh Nima , Eapen Danny J , Chung Neo Christopher , Storey John D , Quyyumi Arshed A , Gibson Greg
Published: May 2014

Background

Genetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death.

Methods

Peripheral blood samples from 338 subjects aged 62 ± 11 years with coronary artery disease (CAD) were analyzed in two phases (discovery N = 175, and replication N = 163), and followed for a mean 2.4 years for cardiovascular death. Gene expression was measured on Illumina HT-12 microarrays with two different normalization procedures to control technical and biological covariates. Whole genome genotyping was used to support comparative genome-wide association studies of gene expression. Analysis of variance was combined with receiver operating curve and survival analysis to define a transcriptional signature of cardiovascular death.

Results

In both phases, there was significant differential expression between healthy and AMI groups with overall down-regulation of genes involved in T-lymphocyte signaling and up-regulation of inflammatory genes. Expression quantitative trait loci analysis provided evidence for altered local genetic regulation of transcript abundance in AMI samples. On follow-up there were 31 cardiovascular deaths. A principal component (PC1) score capturing covariance of 238 genes that were differentially expressed between deceased and survivors in the discovery phase significantly predicted risk of cardiovascular death in the replication and combined samples (hazard ratio = 8.5, P < 0.0001) and improved the C-statistic (area under the curve 0.82 to 0.91, P = 0.03) after adjustment for traditional covariates.

Conclusions

A specific blood gene expression profile is associated with a significant risk of death in Caucasian subjects with CAD. This comprises a subset of transcripts that are also altered in expression during acute myocardial infarction.
Estradiol Modulates Translocator Protein (TSPO) and Steroid Acute Regulatory Protein (StAR) via Protein Kinase A (PKA) Signaling in Hypothalamic Astrocytes
Authors: Chen Claire , Kuo John , Wong Angela , Micevych Paul
Published: May 2014

The ability of the central nervous system to synthesize steroid hormones has wide-ranging implications for physiology and pathology. Among the proposed roles of neurosteroids is the regulation of the LH surge. This involvement in the estrogen-positive feedback demonstrates the integration of peripheral steroids with neurosteroids. Within the female hypothalamus, estradiol from developing follicles stimulates progesterone synthesis in astrocytes, which activate neural circuits regulating gonadotropin (GnRH) neurons. Estradiol acts at membrane estrogen receptor-α to activate cellular signaling that results in the release of inositol trisphosphate-sensitive calcium stores that are sufficient to induce neuroprogesterone synthesis. The purpose of the present studies was to characterize the estradiol-induced signaling leading to activation of steroid acute regulatory protein (StAR) and transporter protein (TSPO), which mediate the rate-limiting step in steroidogenesis, ie, the transport of cholesterol into the mitochondrion. Treatment of primary cultures of adult female rat hypothalamic astrocytes with estradiol induced a cascade of phosphorylation that resulted in the activation of a calcium-dependent adenylyl cyclase, AC1, elevation of cAMP, and activation of both StAR and TSPO. Blocking protein kinase A activation with H-89 abrogated the estradiol-induced neuroprogesterone synthesis. Thus, together with previous results, these experiments completed the characterization of how estradiol action at the membrane leads to the augmentation of neuroprogesterone synthesis through increasing cAMP, activation of protein kinase A, and the phosphorylation of TSPO and StAR in hypothalamic astrocytes.
Loss of Follicle-Stimulating Hormone Receptor Function Causes Masculinization and Suppression of Ovarian Development in Genetically Female Medaka
Authors: Murozumi Norikazu , Nakashima Ryo , Hirai Toshiaki , Kamei Yasuhiro , Ishikawa-Fujiwara Tomoko , Todo Takeshi , Kitano Takeshi
Published: May 2014

FSH, a glycoprotein hormone, is circulated from the pituitary and functions by binding to a specific FSH receptor (FSHR). FSHR is a G protein-coupled, seven-transmembrane receptor linked to the adenylyl cyclase or other pathways and is expressed in gonadal somatic cells. In some nonmammalian species, fshr expression is much higher in the ovary than in the testis during gonadal sex differentiation, suggesting that FSHR is involved in ovarian development in nonmammalian vertebrates. However, little is known of FSHR knockout phenotypes in these species. Here we screened for fshr mutations by a medaka (Oryzias latipes) target-induced local lesion in the genomes and identified one nonsense mutation located in the BXXBB motif, which is involved in G protein activation. Next, we used an in vitro reporter gene assay to demonstrate that this mutation prevents FSHR function. We then analyzed the phenotypes of fshr mutant medaka. The fshr mutant male medaka displayed normal testes and were fertile, whereas the mutant female fish displayed small ovaries and were infertile because vitellogenesis was inhibited. The mutant females also have suppressed expression of ovary-type aromatase (cyp19a1a), a steroidogenic enzyme responsible for the conversion of androgens to estrogens, resulting in decreased 17β-estradiol levels. Moreover, loss of FSHR function caused female-to-male sex reversal in some cases. In addition, the transgenic overexpression of fshr in fshr mutants rescued FSHR function. These findings strongly suggest that in the medaka, FSH regulates the ovarian development and the maintenance mainly by the elevation of estrogen levels. We present the first FSHR knockout phenotype in a nonmammalian species.
Parathyroid Hormone Receptor Signaling Induces Bone Resorption in the Adult Skeleton by Directly Regulating the RANKL Gene in Osteocytes
Authors: Ben-awadh Abdullah N. , Delgado-Calle Jesus , Tu Xiaolin , Kuhlenschmidt Kali , Allen Matthew R. , Plotkin Lilian I. , Bellido Teresita
Published: May 2014

PTH upregulates the expression of the receptor activator of nuclear factor κB ligand (Rankl) in cells of the osteoblastic lineage, but the precise differentiation stage of the PTH target cell responsible for RANKL-mediated stimulation of bone resorption remains undefined. We report that constitutive activation of PTH receptor signaling only in osteocytes in transgenic mice (DMP1-caPTHR1) was sufficient to increase Rankl expression and bone resorption. Resorption in DMP1-caPTHR1 mice crossed with mice lacking the distal control region regulated by PTH in the Rankl gene (DCR−/−) was similar to DMP1-caPTHR1 mice at 1 month of age, but progressively declined to reach values undistinguishable from wild-type (WT) mice at 5 months of age. Moreover, DMP1-caPTHR1 mice exhibited low tissue material density and increased serum alkaline phosphatase activity at 5 month of age, and these indices of high remodeling were partially and totally corrected in compound DMP1-caPTHR1;DCR−/− male mice, and less affected in female mice. Rankl expression in bones from DMP1-caPTHR1 mice was elevated at both 1 and 5 months of age, whereas it was high, similar to DMP1-caPTHR1 mice at 1 month, but low, similar to WT levels at 5 months in compound mice. Moreover, PTH increased Rankl and decreased Sost and Opg expression in ex vivo bone organ cultures established from WT mice, but only regulated Sost and Opg expression in cultures from DCR−/− mice. PTH also increased RANKL expression in osteocyte-containing primary cultures of calvarial cells, in isolated murine osteocytes, and in WT but not in DCR−/− osteocyte-enriched bones. Thus, PTH upregulates Rankl expression in osteocytes in vitro, ex vivo and in vivo, and resorption induced by PTH receptor signaling in the adult skeleton requires direct regulation of the Rankl gene in osteocytes.
Loss of Ntrk2/Kiss1r Signaling in Oocytes Causes Premature Ovarian Failure
Authors: Dorfman Mauricio D. , Garcia-Rudaz Cecilia , Alderman Zefora , Kerr Bredford , Lomniczi Alejandro , Dissen Gregory A. , Castellano Juan Manuel , Garcia-Galiano David , Gaytan Francisco , Xu Baoji , Tena-Sempere Manuel , Ojeda Sergio R.
Published: May 2014

Neurotrophins (NTs), once believed to be neural-specific trophic factors, are now known to also provide developmental cues to non-neural cells. In the ovary, NTs contribute to both the formation and development of follicles. Here we show that oocyte-specific deletion of the Ntrk2 gene that encodes the NTRK2 receptor (NTRK2) for neurotrophin-4/5 and brain-derived neurotrophic factor (BDNF) results in post-pubertal oocyte death, loss of follicular organization, and early adulthood infertility. Oocytes lacking NTRK2 do not respond to gonadotropins with activation of phosphatidylinositol 3-kinase (PI3K)-AKT-mediated signaling. Before puberty, oocytes only express a truncated NTRK2 form (NTRK2.T1), but at puberty full-length (NTRK2.FL) receptors are rapidly induced by the preovulatory gonadotropin surge. A cell line expressing both NTRK2.T1 and the kisspeptin receptor (KISS1R) responds to BDNF stimulation with activation of Ntrk2 expression only if kisspeptin is present. This suggests that BDNF and kisspeptin that are produced by granulosa cells (GCs) of periovulatory follicles act in concert to mediate the effect of gonadotropins on Ntrk2 expression in oocytes. In keeping with this finding, the oocytes of NTRK2-intact mice fail to respond to gonadotropins with increased Ntrk2 expression in the absence of KISS1R. Our results demonstrate that the preovulatory gonadotropin surge promotes oocyte survival at the onset of reproductive cyclicity by inducing oocyte expression of NTRK2.FL receptors that set in motion an AKT-mediated survival pathway. They also suggest that gonadotropins activate NTRK2.FL expression via a dual communication pathway involving BDNF and kisspeptin produced in GCs and their respective receptors NTRK2.T1 and KISS1R expressed in oocytes.
Hindbrain Oxytocin Receptors Contribute to the Effects of Circulating Oxytocin on Food Intake in Male Rats
Authors: Ho Jacqueline M. , Anekonda Vishwanath T. , Thompson Benjamin W. , Zhu Mingyan , Curry Robert W. , Hwang Bang H. , Morton Gregory J. , Schwartz Michael W. , Baskin Denis G. , Appleyard Suzanne M. , Blevins James E.
Published: May 2014

Oxytocin (OT)-elicited hypophagia has been linked to neural activity in the nucleus of the solitary tract (NTS). Because plasma OT levels increase after a meal, we hypothesized that circulating OT acts at both peripheral and hindbrain OT receptors (OTRs) to limit food intake. To initially determine whether circulating OT inhibits food intake by acting at hindbrain OTRs, we pretreated rats with an OTR antagonist administered into the fourth ventricle (4V) followed by either central or systemic OT administration. Administration of the OTR antagonist into the 4V blocked anorexia induced by either 4V or ip injection of OT. However, blockade of peripheral OTRs also weakened the anorectic response to ip OT. Our data suggest a predominant role for hindbrain OTRs in the hypophagic response to peripheral OT administration. To elucidate central mechanisms of OT hypophagia, we tested whether OT activates NTS catecholaminergic neurons. OT (ip) increased the number of NTS cells expressing c-Fos, of which 10%–15% were catecholaminergic. Furthermore, electrophysiological studies in mice revealed that OT stimulated 47% (8 of 17) of NTS catecholamine neurons through a presynaptic mechanism. However, OT-elicited hypophagia did not appear to require activation of α1-adrenoceptors, and blockade of glucagon-like peptide-1 receptors similarly did not attenuate anorexia induced by OT. These findings demonstrate that OT elicits satiety through both central and peripheral OTRs and that although catecholamine neurons are a downstream target of OT signaling in the NTS, the hypophagic effect is mediated independently of α1-adrenoceptor signaling.
Circadian Dynamics of the Cone-Rod Homeobox (CRX) Transcription Factor in the Rat Pineal Gland and Its Role in Regulation of Arylalkylamine N-Acetyltransferase (AANAT)
Authors: Rohde Kristian , Rovsing Louise , Ho Anthony K. , Møller Morten , Rath Martin F.
Published: May 2014

The cone-rod homeobox (Crx) gene encodes a transcription factor in the retina and pineal gland. Crx deficiency influences the pineal transcriptome, including a reduced expression of arylalkylamine N-acetyltransferase (Aanat), a key enzyme in nocturnal pineal melatonin production. However, previous functional studies on pineal Crx have been performed in melatonin-deficient mice. In this study, we have investigated the role of Crx in the melatonin-proficient rat pineal gland. The current study shows that pineal Crx transcript levels exhibit a circadian rhythm with a peak in the middle of the night, which is transferred into daily changes in CRX protein. The study further shows that the sympathetic innervation of the pineal gland controls the Crx rhythm. By use of adenovirus-mediated short hairpin RNA gene knockdown targeting Crx mRNA in primary rat pinealocyte cell culture, we here show that intact levels of Crx mRNA are required to obtain high levels of Aanat expression, whereas overexpression of Crx induces Aanat transcription in vitro. This regulatory function of Crx is further supported by circadian analysis of Aanat in the pineal gland of the Crx-knockout mouse. Our data indicate that the rhythmic nature of pineal CRX protein may directly modulate the daily profile of Aanat expression by inducing nighttime expression of this enzyme, thus facilitating nocturnal melatonin synthesis in addition to its role in ensuring a correct tissue distribution of Aanat expression.
Genome-Wide Analyses of ChIP-Seq Derived FOXA2 DNA Occupancy in Liver Points to Genetic Networks Underpinning Multiple Complex Traits
Authors: Johnson Matthew E. , Schug Jonathan , Wells Andrew D. , Kaestner Klaus H. , Grant Struan F. A.
Published: May 2014

Background:

Forkhead Box A2 (FOXA2) exerts an influence on glucose homeostasis via activity in the liver. In addition, a key genome-wide association study (GWAS) recently demonstrated that genetic variation, namely rs6048205, at the FOXA2 locus is robustly associated with fasting glucose levels. Our hypothesis was that this DNA-binding protein regulates the expression of a set of molecular pathways critical to endocrine traits.

Methods:

Drawing on our laboratory and bioinformatic experience with chromatin immunoprecipitation followed by massively parallel sequencing, we analyzed our existing FOXA2 chromatin immunoprecipitation followed by massively parallel sequencing data generated in human liver, using the algorithm hypergeometric optimization of motif enrichment, to gain insight into its global genomic binding pattern from a disease perspective.

Results:

We performed a pathway analysis of the gene list using the gene set enrichment analysis algorithm, which yielded a number of significant annotations. Motivated by the fact that the FOXA2 locus has been implicated by GWAS, we cross-referenced the occupancy sites with the National Institutes of Health GWAS catalog and found strong evidence for the enrichment of loci implicated in endocrine, neuropsychiatric, cardiovascular, and cancer trait categories, but interestingly there was no evidence for enrichment for inflammation related traits. Intriguingly, a FOXA2 occupancy site coincided with rs6048205, suggesting that this variant confers its effect, at least partially, via a perturbation of a FOXA2 feedback mechanism.

Conclusion:

Our data strongly suggest that FOXA2 is acting as a master regulator of key pathways that are enriched for loci implicated by GWAS for most trait categories, with the clear exception of inflammation, suggesting that this factor exerts its effect in this context via noninflammatory processes.
Teprotumumab, an IGF-1R Blocking Monoclonal Antibody Inhibits TSH and IGF-1 Action in Fibrocytes
Authors: Chen Hong , Mester Tünde , Raychaudhuri Nupur , Kauh Courtney Y. , Gupta Shivani , Smith Terry J. , Douglas Raymond S.
Published: May 2014

Context:

Thyroid-associated ophthalmopathy (TAO) is the component of Graves' disease characterized by orbital inflammation and connective tissue remodeling. The IGF-1 receptor (IGF-1R) and TSH receptor (TSHR) form a physical and functional complex in orbital fibroblasts. A subset of these fibroblasts is derived from infiltrating CD34+ fibrocytes. Teprotumumab (RV 001, R1507) is a human monoclonal anti-IGF-1R blocking antibody currently undergoing a phase 2 clinical trial in patients with active TAO.

Objective:

To determine whether teprotumumab inhibits the induction by TSH of IL-6 and IL-8 in fibrocytes.

Design:

Fibrocytes were treated without or with teprotumumab in combination with IGF-1 or TSH.

Main Outcome Measures:

IL-6 and IL-8 mRNA expression and protein production were analyzed by real-time PCR and Luminex, respectively. Phosphorylated Akt (S473) levels were analyzed by Western blot. TSHR and IGF-1R display was assessed by flow cytometry.

Results:

Fibrocyte display of IGF-1R and TSHR was reduced with teprotumumab, as were IGF-1- and TSH-dependent phosphorylated Akt levels. TSH induction of IL-6 and IL-8 mRNA and protein was also reduced by the monoclonal antibody.

Conclusions:

Teprotumumab attenuates the actions of both IGF-1 and TSH in fibrocytes. Specifically, it blocks the induction of proinflammatory cytokines by TSH. These results provide, at least in part, the molecular rationale for interrogating the therapeutic efficacy of this antibody in TAO.
Raising Gays
Authors: Jacobs Jason
Published: May 2014

Taking critical aim at an emergent cultural demand for family “acceptance” of queer youth and at the trope of parental love offered “no matter what,” this essay resists the occlusion of long-standing traditions of queer pedagogy and acculturation in contemporary “pro-LGBT” discourses. Via an analysis of the musical sitcom Glee, the essay tracks how an insistence on parental acceptance displaces the knowledge, experience, and instruction of other gay people, as well as the cultural practices and traditions that have long sustained queer lives. Focusing on the coming out of gay boy Kurt Hummel and the outing of girl-loving cheerleader Santana Lopez, I highlight the aesthetic and discursive strategies that permit young queers to resist the demands associated with parental acceptance or at least manage and survive its inadequacies.
Queering China
Authors: Chiang Howard
Published: May 2014

Four recent books attest to how much remains to be understood about queer Chinese cultures, both historically and in the contemporary period, especially in relation to their wider global contexts. While varying by discipline and approach, these books converge around a common set of analytical agendas: casting light on the importance of language and its discursive reach in popular understandings of same-sex desire, overturning the problem of long-standing heteronormative biases in area studies, grappling with the ghost of Western concepts of gender and sexuality, and jostling with the tensions between the global and the regional in diasporic China's queer formations. Yet despite their virtues, and in spite of their unanimous refusal to include the label “queer” in their titles, these books, to varying degrees, risk losing sight of the genealogical historicism that has methodologically grounded more global syntheses of queer scholarship.
Bällchen is required for self-renewal of germline stem cells in Drosophila melanogaster
Authors: Herzig Bettina , Yakulov Toma A. , Klinge Kathrin , Günesdogan Ufuk , Jäckle Herbert , Herzig Alf
Published: May 2014

Self-renewing stem cells are pools of undifferentiated cells, which are maintained in cellular niche environments by distinct tissue-specific signalling pathways. In Drosophila melanogaster, female germline stem cells (GSCs) are maintained in a somatic niche of the gonads by BMP signalling. Here we report a novel function of the Drosophila kinase Bällchen (BALL), showing that its cell autonomous role is to maintain the self-renewing capacity of female GSCs independent of BMP signalling. ball mutant GSCs are eliminated from the niche and subsequently differentiate into mature eggs, indicating that BALL is largely dispensable for differentiation. Similar to female GSCs, BALL is required to maintain self-renewal of male GSCs, suggesting a tissue independent requirement of BALL for self-renewal of germline stem cells.
Fission yeast arrestin-related trafficking adaptor, Arn1/Any1, is ubiquitinated by Pub1 E3 ligase and regulates endocytosis of Cat1 amino acid transporter
Authors: Nakashima Akio , Kamada Shinji , Tamanoi Fuyuhiko , Kikkawa Ushio
Published: May 2014

The Tsc1–Tsc2 complex homologous to human tuberous sclerosis complex proteins governs amino acid uptake by regulating the expression and intracellular distribution of amino acid transporters in Schizosaccharomyces pombe. Here, we performed a genetic screening for molecules that are involved in amino acid uptake and found Arn1 (also known as Any1). Arn1 is homologous to ART1, an arrestin-related trafficking adaptor (ART) in Saccharomyces cerevisiae, and contains a conserved arrestin motif, a ubiquitination site, and two PY motifs. Overexpression of arn1+ confers canavanine resistance on cells, whereas its disruption causes hypersensitivity to canavanine. We also show that Arn1 regulates endocytosis of the Cat1 amino acid transporter. Furthermore, deletion of arn1+ suppresses a defect of amino acid uptake and the aberrant Cat1 localization in tsc2Δ. Arn1 interacts with and is ubiquitinated by the Pub1 ubiquitin ligase, which is necessary to regulate Cat1 endocytosis. Cat1 undergoes ubiquitinations on lysine residues within the N-terminus, which are mediated, in part, by Arn1 to determine Cat1 localization. Correctively, Arn1 is an ART in S. pombe and contributes to amino acid uptake through regulating Cat1 endocytosis in which Tsc2 is involved.
Cenp-meta is required for sustained spindle checkpoint
Authors: Rubin Thomas , Karess Roger E. , Rahmani Zohra
Published: May 2014

Cenp-E is a kinesin-like motor protein required for efficient end-on attachment of kinetochores to the spindle microtubules. Cenp-E immunodepletion in Xenopus mitotic extracts results in the loss of mitotic arrest and massive chromosome missegregation, whereas its depletion in mammalian cells leads to chromosome segregation defects despite the presence of a functional spindle assembly checkpoint (SAC). Cenp-meta has previously been reported to be the Drosophila homolog of vertebrate Cenp-E. In this study, we show that cenp-metaΔ mutant neuroblasts arrest in mitosis when treated with colchicine. cenp-metaΔ mutant cells display a mitotic delay. Yet, despite the persistence of the two checkpoint proteins Mad2 and BubR1 on unattached kinetochores, these cells eventually enter anaphase and give rise to highly aneuploid daughter cells. Indeed, we find that cenp-metaΔ mutant cells display a slow but continuous degradation of cyclin B, which eventually triggers the mitotic exit observed. Thus, our data provide evidence for a role of Cenp-meta in sustaining the SAC response.
Cdk5 activity in the brain – multiple paths of regulation
Authors: Shah Kavita , Lahiri Debomoy K.
Published: May 2014

Cyclin dependent kinase-5 (Cdk5), a family member of the cyclin-dependent kinases, plays a pivotal role in the central nervous system. During embryogenesis, Cdk5 is indispensable for brain development and, in the adult brain, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation. However, Cdk5 activity becomes deregulated in several neurological disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, which leads to neurotoxicity. Therefore, precise control over Cdk5 activity is essential for its physiological functions. This Commentary covers the various mechanisms of Cdk5 regulation, including several recently identified protein activators and inhibitors of Cdk5 that control its activity in normal and diseased brains. We also discuss the autoregulatory activity of Cdk5 and its regulation at the transcriptional, post-transcriptional and post-translational levels. We finally highlight physiological and pathological roles of Cdk5 in the brain. Specific modulation of these protein regulators is expected to provide alternative strategies for the development of effective therapeutic interventions that are triggered by deregulation of Cdk5.
A Tight 2-Approximation for Preemptive Stochastic Scheduling
Authors: Megow Nicole , Vredeveld Tjark
Published: May 2014

We consider dynamic stochastic scheduling of preemptive jobs with processing times that follow independent discrete probability distributions. We derive a policy with a guaranteed performance ratio of 2 for the problem of minimizing the sum of weighted completion times on identical parallel machines subject to release dates. The analysis is tight. Our policy as well as their analysis applies also to the more general model of stochastic online scheduling.

In contrast to previous results for nonpreemptive stochastic scheduling, our preemptive policy yields an approximation guarantee that is independent of the processing time distributions. However, our policy extensively utilizes information on the distributions other than the first (and second) moments. We also introduce a new nontrivial lower bound on the expected value of an unknown optimal policy. It relies on a relaxation to the basic problem on a single machine without release dates, which is known to be solved optimally by the Gittins index priority rule. This dynamic priority index is crucial to the analysis and also inspires the design of our policy.
Revisiting Fixation and Embedding Techniques for Optimal Detection of Dendritic Cell Subsets in Tissues
Authors: Accart Nathalie , Sergi Florinda , Rooke Ronald
Published: May 2014

Organ-specific cell types are maintained by tissue homeostasis and may vary in nature and/or frequency in pathological situations. Moreover, within a cell lineage, some sub-populations, defined by combinations of cell-surface markers, may have specific functions. Dendritic cells are the epitome of such a population as they may be subdivided into discrete sub-groups with defined functions in specific compartments of various organs. Technically, to study the distribution of DC sub-populations, it involves performing multiparametric immunofluorescence on well-conserved organ structures. However, immunodetection may be impacted by protein cross-linking and antigenic epitope masking by the use of 10% neutral-buffered formalin. To circumvent this and to preserve a good morphological tissue structure, we evaluated alternative fixatives such as Periodate Lysine Paraformaldehyde or Tris Zinc fixatives in combination with other embedding techniques. The cryosection protocols were adapted for optimal antigen detection but offered a poor morphological preservation. We therefore developed a new methodology based on Tris Zinc fixative, gelatin-sucrose embedding and freezing. Using multiple DC markers, we demonstrate that this treatment is an optimal protocol for cell-surface marker detection on high-quality tissue sections.
Mobile phone and adolescents- addiction a mindful check in!
Authors: Sumesh Kumar Sudhen
Published: May 2014

Mobile phones, one of the greatest inventions in the late 20th century, now have become the newest addiction in the world. Even though it has given us convenient and comfort, it doesn’t mean it has no adverse effect. It is something that is going to affect everyone on day to day basis. The concept and ideas of the adolescents with mobile phone use and mental health generated a possible pathway for personnel dependency and also for the direct sources of stress, depression, sleep disturbances, aggression, and to a list of risky behaviors. However, studies on the association between problematic mobile phone use and psychological problems have been relatively few until now. The impact of mobile phone in adolescents in different domains of mental health should be considered for epidemiological and interventional studies.   Keywords: Adolescents, Cell Phone Use [CPU], Mobile Phone, Mobile Phone Use [MPU], Psychological Problems.
Predicting post-deployment family adaptation in U.S. Navy families
Authors: Scott Micah , Condon Esther , Montgomery Arlene , Baker Spencer
Published: May 2014

Background: Although military families worldwide face changes that include adapting to peace and wartime deployments, few studies have explored how military families adapt to the post-deployment return of a service member. Objectives: To identify variables that predicted post-deployment adaptation of U.S. Navy families. Methods: A mixed method study guided by the Roy Adaptation Model included a convenience sample of 142 spouses of service members recently returned from deployment. The degree to which length of deployment, prior deployments, and years married, number of children, participation in religious and family support groups, communication, race, and interdependence predicted post-deployment family adaptation was tested. Multiple regression analysis and content analysis were used to analyze quantitative and qualitative data to better understand post- deployment adaptation of military families. Results: Post-deployment family adaptation was significantly predicted by having been previously deployed and by scores measuring family interdependence. Content analysis of qualitative responses from 10 spouses indicated that 90% experienced integrated adaptive responses. Conclusions: Family interdependence and prior deployments predicted levels of post-deployment family adaptation. Families who “give time” to adjust, communicate, and resume family routines experienced levels of adaptive response. Keywords: Deployment, Family, Family Nursing, Military Families, Spouse.
Parametric optimization of wire cut electrical discharge machining
Authors: Durairaj M. , Ansari A.K.S. , Gauthamkumar M. H.
Published: May 2014

Wire Electrical Discharge Machining is a manufacturing process whereby a desired shape is obtained using electrical discharges (or) by repetitive spark cycle. Precision and intricate machining are the strengths. Machining parameters tables provided by the machine tool manufacturers often do not meet the operator requirements. Selection of optimum machining and machining parameters combinations is needed for obtaining higher cutting efficiency and accuracy. In this present study, machining is done using Wire-Cut EDM and optimization of surface roughness is done using Taguchis design of experiments. Experimentation was planned as per Taguchis L16 orthogonal array. Each experiment has been performed under different cutting conditions of gap voltage, pulse ON time, and pulse OFF time and Wire feed. Dielectric fluid pressure, wire speed, wire tension, resistance and cutting length are taken as fixed parameters. Inconel 800 was selected as a work material to conduct the experiments. From experimental results, the surface roughness was determined for each machining performance criteria. Signal to noise ratio was applied to measure the performance characteristics deviating from the actual value. Finally, experimental confirmation was carried out to identify the effectiveness of this proposed method. Keywords: Optimization; Taguchis L-16 Orthogonal Array; Surface Roughness; S/N Ratio.
Selection of alternative material for common rail direct injection system
Authors: Senguttuvan N. , Raja S , Sasidharan R.
Published: May 2014

Common rail direct fuel injection is a modern variant of direct fuel injection system for petrol and diesel engines. The common rail system prototype was developed in the late 1960s by Robert Huber of Switzerland and the technology further developed by Dr. Marco. In petrol engine MPFI technology was developed and implemented in earlier days. Basically common rail tube was fabricated by steel for petrol engines. In the current study Steel, Brass, Aluminum alloy a356 and ABS materials were analyzed separately and aluminum is found the best material among the steel, brass and ABS material for common rail injection tube. Keywords: Common Rail Injection System, Alternate Material.