bluuebunny/crossref_metadata_2025 huggingface dataset:
Akt regulates the expression of MafK, synaptotagmin I, and syntenin-1, which play roles in neuronal function
Authors: Ro Young-Tae , Jang Bo-Kwang , Shin Chan Young , Park Eui U , Kim Chul Geun , Yang Sung-Il
Published: March 2010

Background

Akt regulates various cellular processes, including cell growth, survival, and metabolism. Recently, Akt's role in neurite outgrowth has also emerged. We thus aimed to identify neuronal function-related genes that are regulated by Akt.

Methods

We performed suppression subtractive hybridization on two previously established PC12 sublines, one of which overexpresses the wild-type (WT) form and the other, the dominant-negative (DN) form of Akt. These sublines respond differently to NGF's neuronal differentiation effect.

Results

A variety of genes was identified and could be classified into several functional groups, one of which was developmental processes. Two genes involved in neuronal differentiation and function were found in this group. v-Maf musculoaponeurotic fibrosarcoma oncogene homolog K (MafK) induces the neuronal differentiation of PC12 cells and immature telencephalon neurons, and synaptotagmin I (SytI) is essential for neurotransmitter release. Another gene,syntenin-1(Syn-1) was also recognized in the same functional group into whichMafKandSytIwere classified. Syn-1 has been reported to promote the formation of membrane varicosities in neurons. Quantitative reverse transcription polymerase chain reaction analyses show that the transcript levels of these three genes were lower in PC12 (WT-Akt) cells than in parental PC12 and PC12 (DN-Akt) cells. Furthermore, treatment of PC12 (WT-Akt) cells with an Akt inhibitor resulted in the increase of the expression of these genes and the improvement of neurite outgrowth. These results indicate that dominant-negative or pharmacological inhibition of Akt increases the expression ofMafK,SytI, andSyn-1genes. Using lentiviral shRNA to knock down endogenous Syn-1 expression, we demonstrated that Syn-1 promotes an increase in the numbers of neurites and branches.

Conclusions

Taken together, these results indicate that Akt negatively regulates the expression ofMafK,SytI, andSyn-1genes that all participate in regulating neuronal integrity in some way or another.
Analysis of DNA strand-specific differential expression with high density tiling microarrays
Authors: Quintales Luis , Sánchez Mar , Antequera Francisco
Published: March 2010

Background

DNA microarray technology allows the analysis of genome structure and dynamics at genome-wide scale. Expression microarrays (EMA) contain probes for annotated open reading frames (ORF) and are widely used for the analysis of differential gene expression. By contrast, tiling microarrays (TMA) have a much higher probe density and provide unbiased genome-wide coverage. The purpose of this study was to develop a protocol to exploit the high resolution of TMAs for quantitative measurement of DNA strand-specific differential expression of annotated and non-annotated transcripts.

Results

We extensively filtered probes present in Affymetrix Genechip Yeast Genome 2.0 expression and GeneChip S. pombe 1.0FR tiling microarrays to generate custom Chip Description Files (CDF) in order to compare their efficiency. We experimentally tested the potential of our approach by measuring the differential expression of 4904 genes in the yeast Schizosaccharomyces pombe growing under conditions of oxidative stress. The results showed a Pearson correlation coefficient of 0.943 between both platforms, indicating that TMAs are as reliable as EMAs for quantitative expression analysis. A significant advantage of TMAs over EMAs is the possibility of detecting non-annotated transcripts generated only under specific physiological conditions. To take full advantage of this property, we have used a target-labelling protocol that preserves the original polarity of the transcripts and, therefore, allows the strand-specific differential expression of non-annotated transcripts to be determined. By using a segmentation algorithm prior to generating the corresponding custom CDFs, we identified and quantitatively measured the expression of 510 transcripts longer than 180 nucleotides and not overlapping previously annotated ORFs that were differentially expressed at least 2-fold under oxidative stress.

Conclusions

We show that the information derived from TMA hybridization can be processed simultaneously for high-resolution qualitative and quantitative analysis of the differential expression of well-characterized genes and of previously non-annotated and antisense transcripts. The consistency of the performance of TMA, their genome-wide coverage and adaptability to updated genome annotations, and the possibility of measuring strand-specific differential expression makes them a tool of choice for the analysis of gene expression in any organism for which TMA platforms are available.
Different methods for administering 17β-estradiol to ovariectomized rats result in opposite effects on ischemic brain damage
Authors: Strom Jakob O , Theodorsson Elvar , Holm Lovisa , Theodorsson Annette
Published: March 2010

Background

Numerous stroke studies have controversially shown estrogens to be either neuroprotective or neurodamaging. The discordant results observed in rat brain ischemia models may be a consequence of discrepancies in estrogen administration modes resulting in plasma concentration profiles far from those intended. To test this hypothesis we reproduced in detail and extended an earlier study from our lab using a different mode of 17β-estradiol administration; home-made silastic capsules instead of commercial slow-release 17β-estradiol pellets. Four groups of female rats (n = 12) were ovariectomized and administered 17β-estradiol or placebo via silastic capsules. All animals underwent MCAo fourteen days after ovariectomy and were sacrificed three days later.

Results

In contrast to our earlier results using the commercial pellets, the group receiving 17β-estradiol during the entire experiment had significantly smaller lesions than the group receiving placebo (mean ± SEM: 3.85 ± 0.70% versus 7.15 ± 0.27% of total slice area, respectively; p = 0.015). No significant neuroprotection was found when the 17β-estradiol was administered only during the two weeks before or the three days immediately after MCAo.

Conclusions

The results indicate that different estrogen treatment regimens result in diametrically different effects on cerebral ischemia. Thus the effects of estrogens on ischemic damage seem to be concentration-related, with a biphasic, or even more complex, dose-response relation. These findings have implications for the design of animal experiments and also have a bearing on the estrogen doses used for peri-menopausal hormone replacement therapy.
The AP-1 repressor protein, JDP2, potentiates hepatocellular carcinoma in mice
Authors: Bitton-Worms Keren , Pikarsky Eli , Aronheim Ami
Published: March 2010

Background

The AP-1 transcription factor plays a major role in cell proliferation, apoptosis, differentiation and developmental processes. AP-1 proteins are primarily considered to be oncogenic. Gene disruption studies placed c-Jun as an oncogene at the early stage of a mouse model of hepatocellular carcinoma. Mice lacking c-Jun display reduced number and size of hepatic tumors attributed to elevated p53 expression and increased apoptosis. This suggests that c-Jun inhibition may serve as a therapeutic target for liver cancer. The c-Jun dimerization protein 2, JDP2 is an AP-1 repressor protein that potently inhibits AP-1 transcription. On the other hand, the JDP2 locus was found at a recurring viral integration site in T-cell lymphoma. We sought to examine the potential of JDP2 to inhibit c-Jun/AP-1 oncogenic activity in mice. Towards this end, we generated a tetracycline inducible transgenic mouse expressing JDP2 specifically in the liver. We used diethylnitrosamine (DEN) injection to initiate liver cancer in mice and assessed the extent of liver cancer in JDP2-transgenic and wild type control mice by biochemical and molecular biology techniques.

Results

JDP2-transgenic mice display normal liver function. JDP2-transgenic mice displayed potentiation of liver cancer, higher mortality and increased number and size of tumors. The expression of JDP2 at the promotion stage was found to be the most critical for enhancing liver cancer severity.

Conclusions

This study suggests that JDP2 expression may play a critical role in liver cancer development by potentiating the compensatory proliferative response and increased inflammation in the DEN liver cancer model.
Effects of prolonging administration gonadotropin on unexpectedly poor ovarian responders undergoing in vitro fertilization
Authors: Wei Zhaolian , Cheng Xianxia , Li Huirong , Cao Yunxia , Cong Lin , Zhou Ping , Li Jun
Published: March 2010

Background

There are still some patients who show poor response to ovarian stimulation prior to evidence of normal ovarian reserve in vitro fertilization. However, there are few studies about how to treat the unexpectedly ovarian poor responder in vitro fertilization. The main aim of this study evaluate the effect of prolonging administration follicle-stimulating hormone in woman with the unexpectedly ovarian poor responder in vitro fertilization on implantation rate, clinical pregnancy rate and live birth rate.

Methods

922 patients subjected to IVF were divided into two groups according to the predicted criterion of ovarian poor response. 116 patients predicted poor response received the short protocol (group C). The others received the long protocol, among the latter, there were 149 patients undergoing unexpectedly ovarian poor response (group B) and 657 patients exhibited normal ovarian response (group A). The doses of gonadotropin, duration of administration, implantation rate, clinical pregnancy rate and live birth rate were recorded among three groups.

Results

The implantation rate of embryo, clinic pregnancy rate and delivery rate are similar between the group A and group B, while there are significant differences between the doses of gonadotropins (35.1 +/- 8.9 ampules vs.53.0 +/- 15.9 ampules) and the duration of administration (15.3 +/- 3.6D vs. 9.8 +/- 2.6D) of these two groups. There are no significant differences about clinical pregnancy rate and live birth rate between group B and group C.

Conclusion

Prolonging administration gonadotropin on the unexpectedly poor ovarian responders does not lower live birth rate in vitro fertilization.
Radiation therapy of recurrent anal squamous cell carcinoma in-situ: a case report
Authors: Troicki Filip , Pappas Alexandros , Noone Robert , DeNittis Albert
Published: March 2010

Introduction

High-grade anal intraepithelial neoplasia, also referred to as anal squamous carcinoma in-situ, or Bowen's disease of the anus, make up less than 1% of all digestive system cancers in the United States. The treatment of choice is surgical resection with anal mapping. However, this disease often recurs or persists, requiring additional surgery for these patients. This can compromise the anal sphincter leading to leakage. In this case report, we discuss the efficacy of radiation therapy as a modality to treat post-excisional recurrent Bowen's disease, which may prevent sphincter compromise, leading to improved quality of life.

Case presentation

An 84-year-old Caucasian woman presented with post-excisional persistent/recurrent squamous cell carcinoma in-situ. The initial lesion measured 3 cm in diameter on the right lateral side of the anal margin. A standard surgery consisting of wide local excision with anal mapping was performed. The margins were clear and our patient was followed up. Our patient recurred with a 1.2 × 0.8 cm lesion on the left anal verge extending to the anal canal. A biopsy along with mapping was done, and 2 of the 17 mapping specimens were positive for carcinoma in-situ, one in the anal canal. Due to the location of the positive anal mapping, and in order to prevent sphincter compromise on re-excision, our patient was offered definitive radiation therapy. Two years after radiation therapy, our patient showed no signs of recurrent disease and had good sphincter control.

Conclusion

Although the main treatment modality for treating persistent/recurrent Bowen's disease is surgery, an alternative approach using external beam radiation for CIS may be enough to provide a cure for some patients with recurrent disease.
Global and unbiased detection of splice junctions from RNA-seq data
Authors: Ameur Adam , Wetterbom Anna , Feuk Lars , Gyllensten Ulf
Published: March 2010

We have developed a new strategy for de novo prediction of splice junctions in short-read RNA-seq data, suitable for detection of novel splicing events and chimeric transcripts. When tested on mouse RNA-seq data, >31,000 splice events were predicted, of which 88% bridged between two regions separated by ≤100 kb, and 74% connected two exons of the same RefSeq gene. Our method also reports genomic rearrangements such as insertions and deletions.
The Ontogeny of Insulin Signaling in the Preterm Baboon Model
Authors: Blanco Cynthia L. , Liang Hanyu , Joya-Galeana Joaquin , DeFronzo Ralph A. , McCurnin Donald , Musi Nicolas
Published: March 2010

Hyperglycemia, a prevalent condition in premature infants, is thought to be a consequence of incomplete suppression of endogenous glucose production and reduced insulin-stimulated glucose disposal in peripheral tissues. However, the molecular basis for these conditions remains unclear. To test the hypothesis that the insulin transduction pathway is underdeveloped with prematurity, fetal baboons were delivered, anesthetized, and euthanized at 125 d gestational age (GA), 140 d GA, or near term at 175 d GA. Vastus lateralis muscle and liver tissues were obtained, and protein content of insulin signaling molecules [insulin receptor (IR)-β, IR substate-1, p85 subunit of phosphatidylinositol 3-kinase, Akt, and AS160] and glucose transporters (GLUT)-1 and GLUT4 was measured by Western blotting. Muscle from 125 d GA baboons had markedly reduced GLUT1 protein content (16% of 140 d GA and 9% of 175 d GA fetuses). GLUT4 and AS160 also were severely reduced in 125 d GA fetal muscle (43% of 175 d GA and 35% of 175 d GA, respectively). In contrast, the protein content of IR-β, IR substate-1, and Akt was elevated by 1.7-, 5.2-, and 1.9-fold, respectively, in muscle from 125 d GA baboons when compared with 175 d GA fetuses. No differences were found in the content of insulin signaling proteins in liver. In conclusion, significant gestational differences exist in the protein content of several insulin signaling proteins in the muscle of fetal baboons. Reduced muscle content of key glucose transport-regulating proteins (GLUT1, GLUT4, AS160) could play a role in the pathogenesis of neonatal hyperglycemia and reduced insulin-stimulated glucose disposal.
Diabetes Mellitus, Inflammation, Obesity: Proposed Treatment Pathways for Current and Future Therapies
Authors: Sonnett Travis E , Levien Terri L , Gates Brian J , Robinson Jennifer D , Campbell R Keith
Published: March 2010

Objective

To review the pathophysiology, pharmacology, and current or future therapies under study for use in treating diabetes mellitus, inflammation associated with diabetes mellitus, and/or obesity related to diabetes mellitus, through 1 of 4 investigational pathways: adiponectin, ghrelin, resveratrol, or leptin.

Data sources

A literature search using MEDLINE (1966–December 12, 2009), PubMed (1950–December 12, 2009), Science Direct (1994–December 12, 2009), and International Pharmaceutical Abstracts (1970–December 12, 2009) was performed using the terms adiponectin, ghrelin, resveratrol, leptin, inflammation, obesity, and diabetes mellitus. English-language, original research, and review articles were examined, and citations from these articles were assessed as well.

Study selection and data extraction

Clinical studies and in vitro studies were included in addition to any Phase 1, 2, or 3 clinical trials.

Data synthesis

Mechanistic pathways regarding adiponectin, ghrelin, resveratrol, and leptin are of interest as future treatment options for diabetes mellitus. Each of these pathways has produced significant in vitro and in vivo clinical data warranting further research as a possible treatment pathway for diabetes-related inflammation and/or obesity reduction. While research is still underway to determine the exact effects these pathways have on metabolic function, current data suggest that each of these compounds may be of interest for future therapies.

Conclusions

While several pathways under investigation may offer additional benefits in the treatment of diabetes mellitus and associated impairments, further investigation is necessary for both investigational and approved therapies to ensure that the impact in new pathways does not increase risks to patient safety and outcomes.
Optical and electrical properties of π-conjugated polymers built with the 10 π-electron methano[10]annulene ring system
Authors: Peart Patricia A. , Elbaz Giselle A. , Tovar John D.
Published: March 2010

Nontraditional aromatic molecules hold tremendous promise for the design and realization of advanced materials for organic electronics applications. In this report, we describe recent work with the 10 π-electron methano[10]annulene molecule. We used chemistry established by Vogel and by Neidlein to incorporate this molecule into organic semiconducting polymers and found that they provide for highly delocalized charge carriers upon electrochemical oxidation/doping into conductive materials. Extensions to a variety of annulene-heteroaromatic copolymers will be described along with pertinent optical and electrical characterization data.
Ubiquitin fragments: their known biological activities and putative roles
Authors: Pasikowski Paweł , Cydzik Marzena , Kluczyk Alicja , Stefanowicz Piotr , Szewczuk Zbigniew
Published: March 2010

Ubiquitin (Ub) is involved in many key processes of cell biology. Identification of compounds that could interfere in the ubiquitination process is of importance. It could be expected that peptides derived from the Ub-binding regions might be able to interact with Ub receptors themselves and modify an ability of the Ub receptors interactions. This review summarizes current knowledge about known Ub-derived peptides and discusses putative activity of unexplored Ub fragments. Among identified biologically active Ub-derived peptides, its decapeptide fragment of the LEDGRTLSDY sequence was found to exhibit strong immunosuppressive effects on the cellular and humoral immune responses, comparable to that of cyclosporine. Some of the Ub fragments possess strong antibacterial and antifungal potency. In the search for new peptides that could interfere in the interaction of Ub with other proteins, we investigated the pentapeptide Ub sequences present in non-ubiquitin proteins. Based on examination of the Swiss-Prot database, we postulated that sequences of some Ub fragments often exist in other protein molecules. However, some of those motives are represented more frequently than others and could be involved in regulation of cellular processes related to Ub.
Structure and molecular evolution of multicopper blue proteins
Authors: Komori Hirofumi , Higuchi Yoshiki
Published: March 2010

The multicopper blue protein family, which contains cupredoxin-like domains as a structural unit, is one of the most diverse groups of proteins. This protein family is divided into two functionally different types of enzymes: multicopper oxidase and nitrite reductase. Multicopper oxidase catalyzes the oxidation of the substrate and then reduces dioxygen. The structures of many multicopper oxidases are already known, and until recently they were classified into two main groups: the three- and six-domain types. Both function as monomers and have three spectroscopically different copper sites: Types I (blue), II, and III (tri-nuclear). Nitrite reductase is a closely related protein that contains Types I and II (mono-nuclear) coppers but reduces nitrite instead of dioxygen. Nitrite reductase, which consists of two domains, forms a homotrimer. Multicopper oxidase and nitrite reductase share similar structural architectures and also contain Type I copper. Therefore, it is proposed that they have a common ancestor protein. Recently, some two-domain type multicopper oxidases have been found and their crystal structures have been determined. They have a trimeric quaternary structure and contain an active site at the molecular interface such as nitrite reductase. These results support previous hypotheses and provide an insight into the molecular evolution of multicopper blue proteins.
Leptin Regulates AMPA Receptor Trafficking via PTEN Inhibition
Authors: Moult Peter R. , Cross Alasdair , Santos Sandra D. , Carvalho Ana-Luisa , Lindsay Yvonne , Connolly Christopher N. , Irving Andrew J. , Leslie Nicholas R. , Harvey Jenni
Published: March 2010

The hormone leptin can cross the blood–brain barrier and influences numerous brain functions (Harvey, 2007). Indeed, recent studies have demonstrated that leptin regulates activity-dependent synaptic plasticity in the CA1 region of the hippocampus (Shanley et al., 2001; Li et al., 2002; Durakoglugil et al., 2005; Moult et al., 2009). It is well documented that trafficking of AMPA receptors is pivotal for hippocampal synaptic plasticity (Collingridge et al., 2004), but there is limited knowledge of how hormonal systems like leptin influence this process. In this study we have examined how leptin influences AMPA receptor trafficking and in turn how this impacts on excitatory synaptic function. Here we show that leptin preferentially increases the cell surface expression of GluR1 and the synaptic density of GluR2-lacking AMPA receptors in adult hippocampal slices. The leptin-induced increase in surface GluR1 required NMDA receptor activation and was associated with an increase in cytoplasmic PtdIns(3,4,5)P3levels. In addition, leptin enhanced phosphorylation of the lipid phosphatase PTEN which inhibits PTEN function and elevates PtdIns(3,4,5)P3levels. Moreover, inhibition of PTEN mimicked and occluded the effects of leptin on GluR1 trafficking and excitatory synaptic strength. These data indicate that leptin, via a novel pathway involving PTEN inhibition, promotes GluR1 trafficking to hippocampal synapses. This process has important implications for the role of leptin in hippocampal synaptic function in health and disease.
Dyrk1A Overexpression Inhibits Proliferation and Induces Premature Neuronal Differentiation of Neural Progenitor Cells
Authors: Yabut Odessa , Domogauer Jason , D'Arcangelo Gabriella
Published: March 2010

Dyrk1A is a member of the mammalian Dyrk [dual-specificity tyrosine-(Y)-phosphorylation regulated kinase] family of protein kinases that is expressed at high levels in the brain, but its role in the development and function of this organ is not well understood. The humanDYRK1Agene is located on trisomic chromosome 21 in Down syndrome (DS) patients, leading to its overexpression. Dyrk1A is also overexpressed in animal models of DS and in gene-specific transgenic mice that consistently exhibit cognitive impairment. To elucidate the cellular and molecular mechanisms that are affected by increased levels of Dyrk1A in the developing brain, we overexpressed this kinase in the embryonic mouse neocortex using thein uteroelectroporation technique. We found that Dyrk1A overexpression inhibits neural cell proliferation and promotes premature neuronal differentiation in the developing cerebral cortex without affecting cell fate and layer positioning. These effects are dependent on the Dyrk1A kinase activity and are mediated by the nuclear export and degradation of cyclin D1. This study identifies specific Dyrk1A-induced mechanisms that disrupt the normal process of corticogenesis and possibly contribute to cognitive impairment observed in DS patients and animal models.
White Matter Organization in Cervical Spinal Cord Relates Differently to Age and Control of Grip Force in Healthy Subjects
Authors: Lindberg Påvel G. , Feydy Antoine , Maier Marc A.
Published: March 2010

Diffusion tensor imaging (DTI) can be used to elucidate relations between CNS structure and function. We hypothesized that the degree of spinal white matter organization relates to the accuracy of control of grip force. Healthy subjects of different age were studied using DTI and visuomotor tracking of precision grip force. The latter is a prime component of manual dexterity. A regional analysis of spinal white matter [fractional anisotropy (FA)] across multiple cervical levels (C2–C3, C4–C5, and C6–C7) and in different regions of interest (left and right lateral or medial spinal cord) was performed. FA was highest at the C2–C3 level, higher on the right than the left side, and higher in the lateral than in the medial spinal cord (p< 0.001). FA of whole cervical spinal cord (C2–C7) was lower in subjects with high tracking error (r= −0.56,p= 0.004) and decreased with age (r= −0.63,p= 0.001). A multiple regression analysis revealed an independent contribution of each predictor (semipartial correlations: age,r= −0.55,p< 0.001; tracking error,r= −0.49,p= 0.003). The closest relation between FA and tracking error was found at the C6–C7 level in the lateral spinal cord, in which the corticospinal tract innervates spinal circuitry controlling hand and digit muscles. FA of the medial spinal cord correlated consistently with age across all cervical levels, whereas FA of the lateral spinal cord did not. The results suggest (1) a functionally relevant specialization of lateral spinal cord white matter and (2) an increased sensitivity to age-related decline in medial spinal cord white matter in healthy subjects.
Recovery of Sensorimotor Function after Experimental Stroke Correlates with Restoration of Resting-State Interhemispheric Functional Connectivity
Authors: van Meer Maurits P. A. , van der Marel Kajo , Wang Kun , Otte Willem M. , el Bouazati Soufian , Roeling Tom A. P. , Viergever Max A. , Berkelbach van der Sprenkel Jan Willem , Dijkhuizen Rick M.
Published: March 2010

Despite the success of functional imaging to map changes in brain activation patterns after stroke, spatiotemporal dynamics of cerebral reorganization in correlation with behavioral recovery remain incompletely characterized. Here, we applied resting-state functional magnetic resonance imaging (rs-fMRI) together with behavioral testing to longitudinally assess functional connectivity within neuronal networks, in relation to changes in associated function after unilateral stroke in rats. Our specific goals were (1) to identify temporal alterations in functional connectivity within the bilateral cortical sensorimotor system and (2) to elucidate the relationship between those alterations and changes in sensorimotor function. Our study revealed considerable loss of functional connectivity between ipsilesional and contralesional primary sensorimotor cortex regions, alongside significant sensorimotor function deficits in the first days after stroke. The interhemispheric functional connectivity restored in the following weeks, but remained significantly reduced up to 10 weeks after stroke in animals with lesions that comprised subcortical and cortical tissue, whereas transcallosal neuroanatomical connections were preserved. Intrahemispheric functional connectivity between primary somatosensory and motor cortex areas was preserved in the lesion border zone and moderately enhanced contralesionally. The temporal pattern of changes in functional connectivity between bilateral primary motor and somatosensory cortices correlated significantly with the evolution of sensorimotor function scores. Our study (1) demonstrates that poststroke loss and recovery of sensorimotor function is associated with acute deterioration and subsequent retrieval of interhemispheric functional connectivity within the sensorimotor system and (2) underscores the potential of rs-fMRI to assess spatiotemporal characteristics of functional brain reorganization that may underlie behavioral recovery after brain injury.
RET Signaling Is Required for Survival and Normal Function of Nonpeptidergic Nociceptors
Authors: Golden Judith P. , Hoshi Masato , Nassar Mohammed A. , Enomoto Hideki , Wood John N. , Milbrandt Jeffrey , Gereau Robert W. , Johnson Eugene M. , Jain Sanjay
Published: March 2010

Small unmyelinated sensory neurons classified as nociceptors are divided into two subpopulations based on phenotypic differences, including expression of neurotrophic factor receptors. Approximately half of unmyelinated nociceptors express the NGF receptor TrkA, and half express the GDNF family ligand (GFL) receptor Ret. The function of NGF/TrkA signaling in the TrkA population of nociceptors has been extensively studied, and NGF/TrkA signaling is a well established mediator of pain. The GFLs are analgesic in models of neuropathic pain emphasizing the importance of understanding the physiological function of GFL/Ret signaling in nociceptors. However, perinatal lethality ofRet-null mice has precluded the study of the physiological role of GFL/Ret signaling in the survival, maintenance, and function of nociceptors in viable mice. We deletedRetexclusively in nociceptors by crossing nociceptor-specificNav1.8Cre andRetconditional mice to produceRet-Nav1.8conditional knock-out (CKO) mice. Loss of Ret exclusively in nociceptors results in a reduction in nociceptor number and size, indicating that Ret signaling is important for the survival and trophic support of these cells.Ret-Nav1.8CKO mice exhibit reduced epidermal innervation but normal central projections. In addition,Ret-Nav1.8CKO mice have increased sensitivity to cold and increased formalin-induced pain, demonstrating that Ret signaling modulates the function of nociceptorsin vivo. Enhanced inflammation-induced pain may be mediated by decreased prostatic acid phosphatase (PAP), as PAP levels are markedly reduced inRet-Nav1.8CKO mice. The results of this study identify the physiological role of endogenous Ret signaling in the survival and function of nociceptors.
Human ovarian cancer stem cells
Authors: Bapat Sharmila A
Published: March 2010

The isolation and identification of stem-like cells in solid tumors or cancer stem cells (CSCs) have been exciting developments of the last decade, although these rare populations had been earlier identified in leukemia. CSC biology necessitates a detailed delineation of normal stem cell functioning and maintenance of homeostasis within the organ. Ovarian CSC biology has unfortunately not benefited from a pre-established knowledge of stem cell lineage demarcation and functioning in the normal organ. In the absence of such information, some of the classical parameters such as long-term culture-initiating assays to isolate stem cell clones from tumors, screening and evaluation of other epithelial stem cell surface markers, dye efflux, and label retention have been applied toward the putative isolation of CSCs from ovarian tumors. The present review presents an outline of the various approaches developed so far and the various perspectives revealed that are now required to be dealt with toward better disease management.
Aberrant Synthesis of Indole-3-Acetic Acid inSaccharomyces cerevisiaeTriggers Morphogenic Transition, a Virulence Trait of Pathogenic Fungi
Authors: Rao Reeta Prusty , Hunter Ally , Kashpur Olga , Normanly Jennifer
Published: March 2010

Many plant-associated microbes synthesize the auxin indole-3-acetic acid (IAA), and several IAA biosynthetic pathways have been identified in microbes and plants. Saccharomyces cerevisiae has previously been shown to respond to IAA by inducing pseudohyphal growth. We observed that IAA also induced hyphal growth in the human pathogen Candida albicans and thus may function as a secondary metabolite signal that regulates virulence traits such as hyphal transition in pathogenic fungi. Aldehyde dehydrogenase (Ald) is required for IAA synthesis from a tryptophan (Trp) precursor in Ustilago maydis. Mutant S. cerevisiae with deletions in two ALD genes are unable to convert radiolabeled Trp to IAA, yet produce IAA in the absence of exogenous Trp and at levels higher than wild type. These data suggest that yeast may have multiple pathways for IAA synthesis, one of which is not dependent on Trp.
Identification of Genes Affecting Wing Patterning Through a Loss-of-Function Mutagenesis Screen and Characterization of med15 Function During Wing Development
Authors: Terriente-Félix Ana , López-Varea Ana , de Celis Jose F
Published: March 2010

The development of the Drosophila melanogaster wing depends on the correct regulation of cell survival, growth, proliferation, differentiation, and pattern formation. These processes, and the genes controlling then, are common to the development of epithelia in many different organisms. To identify additional genes contributing to wing development we have carried out a genetic screen in mosaic wings carrying clones of homozygous mutant cells. We obtained 12 complementation groups corresponding to genes with a proven role in wing formation such as smoothened, thick veins, mothers against dpp, expanded, and fat and 71 new complementation groups affecting the pattern of veins and the size of wing. We mapped one of these groups to the mediator15 gene (med15), a component of the Mediator complex. We show that Med15 and other members of the Mediator complex are required, among other processes, for the transcription of decapentaplegic target genes.
Hepatitis C virus genotypes in hemodialysis patients in the Federal District, Brazil
Authors: Amorim Regina M.S. , Raiol Tainá , Trevizoli José E. , Neves Francisco A. R. , Martins Cláudia R.F. , Martins Regina M.B.
Published: March 2010

Hepatitis C virus (HCV) genotypes and subtypes were determined in hemodialysis patients in the Federal District, Brazil, by sequencing of the 5' noncoding (NC) and nonstructural 5B (NS5B) regions. From 761 patients, 66 anti-HCV-positive samples were tested for HCV RNA. All 51 HCV RNA-positive samples by PCR of the 5' NC region were genotyped as genotypes 1 (90.2%) and 3 (9.8%). Subtype 1a (82.3%) was the most prevalent, followed by subtypes 3a (9.8%), 1b (5.9%) and 1a/1b (2.0%). Forty-two samples could be amplified and genotyped in the NS5B region: 38 (90.5%) as genotype 1, subtypes 1a, and 8 (9.5%) as genotype 3, subtype 3a. For the 42 samples sequenced in both regions, the genotypes and subtypes determined were concordant in 100% and 95.2% of cases, respectively. Two samples presented discrepant results, with the 5' NC region not distinguishing correctly the subtypes 1a and 1b. These findings indicate that the HCV genotype 1, subtype 1a, is the most prevalent among hemodialysis patients in the Federal District, Brazil.
Occurrence of positivity for Trypanosoma cruzi in triatomine from municipalities in Southeastern Brazil, from 2002 to 2004
Authors: Paula Márcia Beatriz Cardoso de , Costa Idessânia Nazareth da , Freitas Paula de Albuquerque , Limongi Jean Ezequiel , Pajuaba Neto Adalberto de Albuquerque , Pinto Rogério de Melo Costa , Gonçalves Ana Lúcia Ribeiro , Costa-Cruz Julia Maria
Published: March 2010

INTRODUCTION: from an epidemiological point of view, more than 120 species of triatomine (Hemiptera, Reduviidae) are known. The occurrence and positivity for Trypanosoma cruzi in triatomines in 16 municipalities of the Triângulo Mineiro and Alto Paranaíba were evaluated from January 2002 to December 2004. METHODS: the triatomines were captured basically according to the classic norms of the National Health Foundation. The parasitological exams of the triatomines were conducted according to the technique described by the Ministry of Health. During the study period, 990 specimens of triatomines were captured and of these, 771 could be examined. RESULTS: five species were identified: Triatoma sordida, Panstrongylus diasi, Panstrongylus megistus, Panstrongylus geniculatus and Rhodnius neglectus. Triatoma sordida represented 71.5% of all the triatomines captured, followed by Panstrongylus megistus (18%), Rhodnius neglectus (9.3%), Panstrongylus diasi (0.8%) and Panstrongylus geniculatus (0.4%). Of the total number of triatomines examined, 2.7% were positive for Trypanosoma cruzi. Panstrongylus megistus was the species that presented the highest rates of infection by Trypanosoma cruzi (8.3%), followed by Rhodnius neglectus (2.9%) and Triatoma sordida (1.4%). CONCLUSIONS: there is a need to adapt to new circumstances in epidemiology, with greater emphasis on entomological surveillance, since the potential for adaptation of secondary species of triatomines exists, especially where Chagas' disease is already under control.
Risk factors for physical disability at diagnosis of 19,283 new cases of leprosy
Authors: Moschioni Cristiane , Antunes Carlos Maurício de Figueiredo , Grossi Maria Aparecida Faria , Lambertucci José Roberto
Published: March 2010

INTRODUCTION: The purpose of this study was to evaluate risk factors for physical disability at the moment of leprosy diagnosis. METHODS: This is a retrospective, descriptive and exploratory investigation of 19,283 patients with leprosy, registered in the State of Minas Gerais, Brazil, between 2000 and 2005. RESULTS: The risk of Grade 2 disability was 16.5-fold higher in patients with lepromatous leprosy, and 12.8-fold higher in patients presenting the borderline form, compared to patients presenting indeterminate leprosy. The occurrence of more than one thickened nerve increased the odds of a patient developing Grade 2 disability, 8.4-fold. Age <15 years, multibacillary leprosy and no formal education presented 7.0, 5.7 and 5.6 odds of developing physical disability, respectively. CONCLUSIONS: These factors should be considered as strong prognostic indicators in the development of physical disability at diagnosis.
Malária autóctone notificada no Estado de São Paulo: aspectos clínicos e epidemiológicos de 1980 a 2007
Authors: Couto Renata D'Avila , Latorre Maria do Rosário Dias de Oliveira , Di Santi Silvia Maria , Natal Delsio
Published: March 2010

INTRODUÇÃO: A malária autóctone no Estado de São Paulo caracteriza-se por surtos esporádicos na região oeste e transmissão persistente na região leste onde ocorrem casos oligossintomáticos com baixa parasitemia pelo Plasmodium vivax. Os objetivos deste estudo foram: analisar a completitude das fichas de notificação de malária autóctone; estimar a tendência da incidência de casos autóctones no ESP de 1980 a 2007; analisar o comportamento clínico e epidemiológico dos casos em duas regiões de autoctonia neste período. MÉTODOS: Foi realizado um estudo descritivo com 18 variáveis das FIN de malária do ESP, analisadas em duas regiões e em dois períodos (1980-1993 e 1994-2007). Fontes de dados: SUCEN/SES/SP, SINAN/CVE/SES/SP e DATASUS. RESULTADOS: A completitude foi superior a 85% em 11 variáveis. A tendência da incidência foi decrescente. Foram notificados 821 casos autóctones, 91,6% na região leste, predominando Plasmodium vivax. A infecção assintomática teve maior porcentagem no segundo período (p<0,001). CONCLUSÕES: A completitude das informações foi considerada satisfatória. As diferenças clínicas encontradas merecem atenção da vigilância epidemiológica que deve lidar com o desafio da infecção assintomática por Plasmodium.
Estudo transversal de toxoplasmose em alunas de um curso superior da região de Presidente Prudente, Estado de São Paulo
Authors: Souza Cristiane de Oliveira , Tashima Nair Toshiko , Silva Maria Aparecida da , Tumitan Ana Rita Paladino
Published: March 2010

INTRODUÇÃO: toxoplasmose é uma doença parasitária causada pelo protozoário Toxoplasma gondii, que acomete o homem e outros animais. A forma mais grave é a toxoplasmose congênita, sendo então importante estabelecer o perfil sorológico da mulher antes da gestação. Este trabalho objetivou analisar a sorologia para toxoplasmose de alunas do curso de Enfermagem da UNOESTE (Universidade do Oeste Paulista) Presidente Prudente/SP. MÉTODOS: foram coletadas amostras de sangue de 80 alunas, com idade de 18 a 35 anos após assinatura do Termo de Consentimento. A ocorrência de anticorpos IgM e IgG anti-Toxoplasma gondii foi determinada pelo método ELISA. Este trabalho foi aprovado pelo Comitê de Ética da Instituição e realizado no Laboratório de Imunologia da UNOESTE. RESULTADOS: das 80 amostras de sangue analisadas, 27 alunas apresentaram IgG positiva e nenhuma apresentou anticorpo IgM. CONCLUSÕES: das 80 alunas, 53 (66,2%), são suscetíveis à toxoplasmose numa possível gestação. Sendo 27 (33,8) as alunas consideradas soropositivas.
Perfil epidemiológico da hanseníase em um município brasileiro, no período de 2000 a 2006
Authors: Miranzi Sybelle de Souza Castro , Pereira Lívia Helena de Morais , Nunes Altacílio Aparecido
Published: March 2010

INTRODUÇÃO: A hanseníase é considerada um grande problema de saúde pública nos países em desenvolvimento. Estima-se que somente 1/3 dos doentes sejam notificados e que, dentre esses, muitos fazem tratamento irregular ou o abandonam, aumentando o impacto da doença. Assim o objetivo desse artigo foi descrever o perfil epidemiológico da população com diagnóstico de hanseníase, no município de Uberaba, Estado de Minas Gerais, Brasil, no período de 2000 a 2006. MÉTODOS: Trata-se de um estudo retrospectivo, que utilizou os dados secundários de notificação de casos hanseníase do Sistema de Informação de Agravos de Notificação do Ministério da Saúde do Brasil. RESULTADOS: Foram registrados 455 casos da doença, sendo 55,4% do sexo masculino, a faixa etária dos 34 a 49 anos (31,4 %) foi a mais afetada, houve registro de nove (2%) casos de hanseníase em menores de 15 anos. A forma clínica prevalente foi a dimorfa (69,1%) e a classe operacional foi a multibacilar (87%). Tais achados são preocupantes, considerando-se que são de faixa etária economicamente ativa e potencialmente, os principais disseminadores da doença. CONCLUSÕES: O relato de que a maioria dos casos eram multibacilares, indica diagnósticos tardios, assim, torna-se necessário descentralizar o serviço de hanseníase e capacitar mais profissionais para possibilitar diagnóstico e tratamentos mais precoces.
Distribuição espacial e características dos criadouros de Aedes albopictus e Aedes aegypti em Fortaleza, Estado do Ceará
Authors: Martins Victor Emanuel Pessoa , Alencar Carlos Henrique Morais de , Facó Patrícia Emília Gomes , Dutra Rosa Fireman , Alves Carlucio Roberto , Pontes Ricardo José Soares , Guedes Maria Izabel Florindo
Published: March 2010

INTRODUÇÃO: desde seu registro, em 2005, no município de Fortaleza, o Aedes albopictus tem exibido uma rápida dispersão. Um estudo visando à identificação das áreas de sua ocorrência, os seus criadouros e a associação com Aedes aegypti e outros culicídeos foi realizado durante o ano de 2008. MÉTODOS: foram coletadas, de janeiro a julho de 2008, amostras de formas imaturas de culicídeos provenientes de imóveis situados nos bairros de Fortaleza, ressaltando-se algumas características dos criadouros, tais como localização (intradomicílio ou peridomicílio), presença de cobertura (proteção contra a incidência de raios solares e chuva), turbidez da água (água límpida e não límpida), material constituinte, volume, altura em relação ao nível do solo e presença simultânea de diferentes espécies de culicídeos no mesmo criadouro. RESULTADOS: a localização no intradomicílio foi um fator importante para os criadouros do Aedes albopictus [RP=0,52 IC95% (0,33-0,81)], por outro lado, a turbidez da água e a cobertura do depósito não se mostraram como diferenciadores para a infestação [p>0,05]. Para o Aedes aegypti a ausência de turbidez da água foi significativa para a infestação nos criadouros [RP=1,14 IC95% (1,06-1,22)]. CONCLUSÕES: a ausência de uma das espécies nos criadouros favorecia sua infestação por outra; criadouros não infestados por Aedes albopictus tinham uma prevalência de infestação de 2,05 [IC95%1,72-2,44] vezes maior pelo Aedes aegypti. Não houve associação significativa entre volume e altura do criadouro e infestação por ambas as espécies. As duas espécies encontram-se dispersas por todo o município, ocupando os mais diversos tipos de criadouros. No entanto, pode-se identificar uma ligeira separação física, com uma infestação maior do Aedes albopictus no peridomicílio.
Fauna de flebotomíneos (Diptera: Psychodidae) de uma reserva de campina no Estado do Amazonas, e sua importância epidemiológica
Authors: Silva Plínio Eudson Santos da , Freitas Rui Alves de , Silva Dílvia Ferreira da , Alencar Ronildo Baiatone
Published: March 2010

INTRODUÇÃO: No Brasil, a maior diversidade de flebotomíneos é encontrada na Região Amazônica, principalmente em floresta primária de terra-firme. No entanto, sua fauna ainda é pouco conhecida em outros ecossistemas desta região. MÉTODOS: a fim de conhecer a fauna de flebotomíneos de outro ecossistema amazônico, coletas com armadilhas de luz CDC foram realizadas em uma área de campina/campinarana na zona periurbana da Cidade de Manaus. RESULTADOS: foram capturados 814 flebotomíneos de 26 espécies, sendo as mais abundantes: Lutzomyia flaviscutellata (64,5%); Lutzomyia georgii (14%); Lutzomyia olmeca nociva (8,1%); Lutzomyia furcata (3,2%); Lutzomyia monstruosa (1,3%); Lutzomyia umbratilis (1,1%) outros (7,8%). CONCLUSÕES: Campina/campinarana revelou-se de grande importância epidemiológica devido a elevada abundância de Lutzomyia flaviscutellata e Lutzomyia olmeca nociva, ambas vetoras de Leishmania (Leishmania) amazonensis. Com base nestas informações, será possível traçar metas para estudos parasitológicos e conscientizar pesquisadores e estudantes, que mantém constante exposição nesta área realizando trabalhos de pesquisa, sobre o possível risco de contaminação por Leishmania.
Arraias em rios da região Sudeste do Brasil: locais de ocorrência e impactos sobre a população
Authors: Garrone Neto Domingos , Haddad Junior Vidal
Published: March 2010

INTRODUÇÃO: No presente trabalho objetivamos descrever o processo de colonização da Bacia do Alto Paraná, Sudeste do Brasil, por arraias, demonstrando sua atual situação e provável tendência, os impactos gerados e discutindo algumas ações de manejo e medidas mitigadoras. MÉTODOS: Foram realizadas entrevistas com ribeirinhos e profissionais de saúde para o levantamento de informações sobre a ocorrência de arraias e acidentes associados a estes animais, além de coletas e observações subaquáticas de potamotrigonídeos, entre 2004 e 2009, em localidades situadas nos Estados de São Paulo, Paraná e Mato Grosso do Sul, no Sudeste, Sul e parte do Centro-Oeste do Brasil. RESULTADOS: Três espécies de arraias foram identificadas na área de estudo, demonstrando utilizar os caminhos abertos pela Hidrovia Tietê-Paraná para se dispersarem. Dezesseis vítimas de acidentes envolvendo esses animais foram encontradas, notadamente banhistas e pescadores, chamando a atenção pelo fato dos casos não serem notificados e apresentarem elevada morbidade, com marcante incapacidade temporária para o trabalho. CONCLUSÕES: Este é o primeiro relato de invasão biológica envolvendo espécies de elasmobrânquios conhecido na literatura e, pelas arraias estarem colonizando áreas densamente povoadas e ampliando sua área de distribuição a cada ano, é de se esperar que sua interação negativa com humanos se intensifique, provocando alterações importantes no perfil epidemiológico dos acidentes por animais peçonhentos ocorridos no sudeste brasileiro.
Polineuropatia desmielinizante inflamatória crônica pós-tratamento com interferon peguilado alfa 2b em um paciente co-infectado HIV/HCV: relato de caso
Authors: Bassetti Bil Randerson , Trés Eduardo Sturzeneker , Ciríaco Jovana Gobbi Marchesi , Pinto Neto Lauro Ferreira Silva
Published: March 2010

A polineuropatia desmielinizante inflamatória cônica possui forte associação com a infecção pelo HIV e HCV. Uma rara associação entre PDIC e o tratamento da hepatite C com interferon peguilado alfa foi descrita recentemente. Nós descrevemos o primeiro caso de polineuropatia desmielinizante inflamatória crônica em um paciente branco, sexo masculino infectado por HIV e HCV associado a interferon peguilado alfa 2b. O paciente recuperou-se completamente após o uso de imunoglobulina hiperimune endovenosa. Infectologistas e hapatologistas devem estar atentos à esta rara e grave associação, que exige imediata descontinuação da droga e tratamento precoce.