bluuebunny/crossref_metadata_2025 huggingface dataset:
Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo
Authors: Parisi Federica , Riccardo Sara , Daniel Margaret , Saqcena Mahesh , Kundu Nandini , Pession Annalisa , Grifoni Daniela , Stocker Hugo , Tabak Esteban , Bellosta Paola
Published: September 2011

Background

Genetic studies in Drosophila melanogaster reveal an important role for Myc in controlling growth. Similar studies have also shown how components of the insulin and target of rapamycin (TOR) pathways are key regulators of growth. Despite a few suggestions that Myc transcriptional activity lies downstream of these pathways, a molecular mechanism linking these signaling pathways to Myc has not been clearly described. Using biochemical and genetic approaches we tried to identify novel mechanisms that control Myc activity upon activation of insulin and TOR signaling pathways.

Results

Our biochemical studies show that insulin induces Myc protein accumulation in Drosophila S2 cells, which correlates with a decrease in the activity of glycogen synthase kinase 3-beta (GSK3β ) a kinase that is responsible for Myc protein degradation. Induction of Myc by insulin is inhibited by the presence of the TOR inhibitor rapamycin, suggesting that insulin-induced Myc protein accumulation depends on the activation of TOR complex 1. Treatment with amino acids that directly activate the TOR pathway results in Myc protein accumulation, which also depends on the ability of S6K kinase to inhibit GSK3β activity. Myc upregulation by insulin and TOR pathways is a mechanism conserved in cells from the wing imaginal disc, where expression of Dp110 and Rheb also induces Myc protein accumulation, while inhibition of insulin and TOR pathways result in the opposite effect. Our functional analysis, aimed at quantifying the relative contribution of Myc to ommatidial growth downstream of insulin and TOR pathways, revealed that Myc activity is necessary to sustain the proliferation of cells from the ommatidia upon Dp110 expression, while its contribution downstream of TOR is significant to control the size of the ommatidia.

Conclusions

Our study presents novel evidence that Myc activity acts downstream of insulin and TOR pathways to control growth in Drosophila. At the biochemical level we found that both these pathways converge at GSK3β to control Myc protein stability, while our genetic analysis shows that insulin and TOR pathways have different requirements for Myc activity during development of the eye, suggesting that Myc might be differentially induced by these pathways during growth or proliferation of cells that make up the ommatidia.
Autoimmune cholangitis mimicking a klatskin tumor: a case report
Authors: Shingina Alexandra , Owen David , Zwirewich Charles , Salh Baljinder
Published: September 2011

Introduction

Autoimmune cholangitis remains an elusive manifestation of immunoglobulin G4-associated systemic disease most commonly encountered in patients with autoimmune pancreatitis. No strict diagnostic criteria have been described to date and diagnosis mainly relies on a combination of clinical and histopathologic findings. It is hence even more challenging to diagnose autoimmune cholangitis in patients with late or atypical presentations, such as without concomitant pancreatic involvement. Early diagnosis of this rare disorder can significantly improve outcomes considering high rates of surgical intervention, as well as high relapse rates in the absence of steroid treatment. To the best of our knowledge the literature is quite sparse on cases with atypical presentations of autoimmune cholangitis.

Case presentation

We report a case of a previously healthy 65-year-old man of Middle-Eastern origin, with a history of pancreatic insufficiency of unknown etiology, evaluated for elevated liver function tests found incidentally on a routine physical examination. Imaging studies revealed an atrophic pancreas and biliary duct dilatation consistent with obstruction. Subsequent endoscopic retrograde cholangiopancreatography showed a bile duct narrowing pattern suggestive of cholangiocarcinoma, but brushings failed to reveal malignant cells. Our patient proceeded to undergo surgical resection. Histological examination of the resected mass revealed lymphoplasmacytic infiltrate with no malignant features. Our patient returned three months later with persistently high liver function tests and no evidence of biliary obstruction on imaging. A presumptive diagnosis of autoimmune cholangitis was made and our patient's symptoms resolved after a short course of an oral steroid regimen. Post factum staining of the resection specimen revealed an immunoglobulin G4 antibody positive immune cell infiltrate, consistent with the proposed diagnosis.

Conclusion

Our case thus highlights the importance of clinician awareness of the autoimmune spectrum of biliary pathologies when confronted with atypical clinical presentations, the paucity of diagnostic measures and the benefit from long-term steroid and/or immunosuppressive treatment.
Stable accumulation of p67phox at the phagosomal membrane and ROS production within the phagosome
Authors: Tlili Asma , Erard Marie , Faure Marie-Cécile , Baudin Xavier , Piolot Tristan , Dupré-Crochet Sophie , Nüße Oliver
Published: September 2011

Production of ROS by the leukocyte NADPH oxidase is essential for the destruction of pathogenic bacteria inside phagosomes. The enzyme is a complex of cytosolic and membranous subunits that need to assemble upon activation. Biochemical data suggest that the complex is renewed continuously during activity. Furthermore, it is generally assumed that complex assembly and activity occur in parallel. However, information about the oxidase assembly in individual phagosomes in live cells is scarce. We studied the dynamic behavior of the crucial cytosolic NADPH oxidase component p67phox during phagocytosis by videomicroscopy. p67phox is involved in the regulation of electron flow from NADPH to oxygen, leading to superoxide radical formation inside the phagosome. p67phox-citrine, expressed in myeloid PLB-985 cells, accumulated at the phagosomal membrane during phagocytosis of yeast particles. Using photobleaching techniques (FRAP, FLIP), we demonstrated that p67phox-citrine diffused freely in this phagosomal membrane, but the phagosomal pool of p67phox-citrine did not exchange with the cytosolic pool. This result suggests that once assembled in the NADPH oxidase complex, p67phox is stable in this complex. Furthermore, the time of the presence of p67phox-citrine at the phagosome increased substantially in the presence of complement in the opsonizing serum compared with decomplemented serum. PI(3)P also accumulated around phagosomes for twice as long in the presence of complement. The presence of p67phox-citrine was correlated with the duration of phagosomal ROS production in different opsonization conditions. These data support the critical role of p67phox for ROS production on the level of individual phagosomes.
Identification and Functional Characterization of Zebrafish Solute Carrier Slc16a2 (Mct8) as a Thyroid Hormone Membrane Transporter
Authors: Arjona Francisco J. , de Vrieze Erik , Visser Theo J. , Flik Gert , Klaren Peter H. M.
Published: September 2011

Most components of the thyroid system in bony fish have been described and characterized, with the notable exception of thyroid hormone membrane transporters. We have cloned, sequenced, and expressed the zebrafish solute carrier Slc16a2 (also named monocarboxylate transporter Mct8) cDNA and established its role as a thyroid hormone transport protein. The cloned cDNA shares 56–57% homology with its mammalian orthologs. The 526-amino-acid sequence contains 12 predicted transmembrane domains. An intracellular N-terminal PEST domain, thought to be involved in proteolytic processing of the protein, is present in the zebrafish sequence. Measured at initial rate and at the body/rearing temperature of zebrafish (26 C), T3 uptake by zebrafish Slc16a2 is a saturable process with a calculated Michaelis-Menten constant of 0.8 μM T3. The rate of T3 uptake is temperature dependent and Na+ independent. Interestingly, at 26 C, zebrafish Slc16a2 does not transport T4. This implies that at a normal body temperature in zebrafish, Slc16a2 protein is predominantly involved in T3 uptake. When measured at 37 C, zebrafish Slc16a2 transports T4 in a Na+-independent manner. In adult zebrafish, the Slc16a2 gene is highly expressed in brain, gills, pancreas, liver, pituitary, heart, kidney, and gut. Beginning from the midblastula stage, Slc16a2 is also expressed during zebrafish early development, the highest expression levels occurring 48 h after fertilization. This is the first direct evidence for thyroid hormone membrane transporters in fish. We suggest that Slc16a2 plays a key role in the local availability of T3 in adult tissues as well as during the completion of morphogenesis of primary organ systems.
Deletion of a single allele of thePex11βgene is sufficient to cause oxidative stress, delayed differentiation and neuronal death in mouse brain
Authors: Ahlemeyer Barbara , Gottwald Magdalena , Baumgart-Vogt Eveline
Published: September 2011

Impaired neuronal migration and cell death are commonly observed in patients with peroxisomal biogenesis disorders (PBDs), and in mouse models of this diseases. In Pex11β-deficient mice, we observed that the deletion of a single allele of the Pex11β gene (Pex11β+/− heterozygous mice) caused cell death in primary neuronal cultures prepared from the neocortex and cerebellum, although to a lesser extent as compared with the homozygous-null animals (Pex11β−/− mice). In corresponding brain sections, cell death was rare, but differences between the genotypes were similar to those found in vitro. Because PEX11β has been implicated in peroxisomal proliferation, we searched for alterations in peroxisomal abundance in the brain of heterozygous and homozygous Pex11β-null mice compared with wild-type animals. Deletion of one allele of the Pex11β gene slightly increased the abundance of peroxisomes, whereas the deletion of both alleles caused a 30% reduction in peroxisome number. The size of the peroxisomal compartment did not correlate with neuronal death. Similar to cell death, neuronal development was delayed in Pex11β+/− mice, and to a further extent in Pex11β−/− mice, as measured by a reduced mRNA and protein level of synaptophysin and a reduced protein level of the mature isoform of MAP2. Moreover, a gradual increase in oxidative stress was found in brain sections and primary neuronal cultures from wild-type to heterozygous to homozygous Pex11β-deficient mice. SOD2 was upregulated in neurons from Pex11β+/− mice, but not from Pex11β−/− animals, whereas the level of catalase remained unchanged in neurons from Pex11β+/− mice and was reduced in those from Pex11β−/− mice, suggesting a partial compensation of oxidative stress in the heterozygotes, but a failure thereof in the homozygous Pex11β−/− brain. In conclusion, we report the alterations in the brain caused by the deletion of a single allele of the Pex11β gene. Our data might lead to the reconsideration of the clinical treatment of PBDs and the common way of using knockout mouse models for studying autosomal recessive diseases.
Modeling psychiatric disorders through reprogramming
Authors: Brennand Kristen J. , Gage Fred H.
Published: September 2011

Psychiatric disorders, including autism spectrum disorders and schizophrenia, are extremely heritable complex genetic neurodevelopmental disorders. It is now possible to directly reprogram fibroblasts from psychiatric patients into human induced pluripotent stem cells (hiPSCs) and subsequently differentiate these disorder-specific hiPSCs into neurons. This means that researchers can generate nearly limitless quantities of live human neurons with genetic backgrounds that are known to result in psychiatric disorders, without knowing which genes are interacting to produce the disease state in each patient. With these new human-cell-based models, scientists can investigate the precise cell types that are affected in these disorders and elucidate the cellular and molecular defects that contribute to disease initiation and progression. Here, we present a short review of experiments using hiPSCs and other sophisticated in vitro approaches to study the pathways underlying psychiatric disorders.
Differential segmental strain during active lengthening in a large biarticular thigh muscle during running
Authors: Carr Jennifer A. , Ellerby David J. , Marsh Richard L.
Published: September 2011

The iliotibialis lateralis pars postacetabularis (ILPO) is the largest muscle in the hindlimb of the guinea fowl and is thought to play an important role during the stance phase of running, both absorbing and producing work. Using sonomicrometry and electromyography, we examined whether the ILPO experiences differential strain between proximal, central and distal portions of the posterior fascicles. When the ILPO is being lengthened while active, the distal portion was found to lengthen significantly more than either the proximal or central portions of the muscle. Our data support the hypothesis that the distal segment lengthened farther and faster because it began activity at shorter sarcomere lengths on the ascending limb of the length–tension curve. Probably because of the self-stabilizing effects of operating on the ascending limb of the length–tension curve, all segments reached the end of lengthening and started shortening at the same sarcomere length. During shortening, this similarity in sarcomere length among the segments was maintained, as predicted from force–velocity effects, and shortening strain was similar in all segments. The differential active strain during active lengthening is thus ultimately determined by differences in strain during the passive portion of the cycle. The sarcomere lengths of all segments of the fascicles were similar at the end of active shortening, but after the passive portion of the cycle the distal segment was shorter. Differential strain in the segments during the passive portion of the cycle may be caused by differential joint excursions at the knee and hip acting on the ends of the muscle and being transmitted differentially by the passive visco-elastic properties of the muscle. Alternatively, the differential passive strain could be due to the action of active or passive muscles in the thigh that transmit force to the IPLO in shear. Based on basic sarcomere dynamics we predict that differential strain is more likely to occur in muscles undergoing active lengthening at the beginning of contraction than those undergoing only shortening.
Role of the lateral line mechanosensory system in directionality of goldfish auditory evoked escape response
Authors: Mirjany Mana , Preuss Thomas , Faber Donald S.
Published: September 2011

Goldfish (Carassius auratus) escape responses to sudden auditory stimuli are mediated by a pair of reticulospinal neurons, the Mauthner (M-) cells, which integrate mechanosensory inputs from the inner ear and the lateral line (LL) to initiate a fast directional response away from the aversive stimulus. This behavior is context dependent; when near an obstruction the fish may rather turn towards the sound to avoid hitting the object. Mechanisms underlying this directionality remain unknown. Here we investigate the contribution of the LL system to auditory evoked escapes and provide behavioral evidence that it transmits stimulus – and environmental-dependent information that determines the initial response direction of the escape. We quantified escape latency, probability and directionality following abrupt sound stimuli before and after removal of the entire LL with 0.03 mmol l–1 cobalt chloride (CoCl2), 0.002% gentamicin or selective posterior LL nerve (pLLn) transection. CoCl2 significantly increased escape onset latency without affecting probability and reduced open field directionality from 77% to chance, 52%. This effect on directionality was also observed with gentamicin. Transection of the pLLn had no effect on directionality, indicating the anterior LL nerve (aLLn) afferents are more likely to transmit directional information to the M-cell. When the fish were near a wall, the error rate was quadrupled by both CoCl2 and pLLn transection. Visual elimination had no influence on directionality unless combined with LL elimination.
Carotenoid intake does not affect immune-stimulated oxidative burst in greenfinches
Authors: Sild Elin , Sepp Tuul , Männiste Marju , Hõrak Peeter
Published: September 2011

Carotenoid-based integument colouration is extremely widespread in the animal kingdom. It has been hypothesized that carotenoid colouration is used for communicating the health status of the bearers because carotenoids are efficient immunomodulators or antioxidants. However, the latter argument has been recently debated and the mechanisms by which carotenoids modulate immunity or oxidative balance are poorly known. We performed an experiment on wild-caught captive greenfinches, passerine birds with carotenoid-based plumage colouration, in order to test whether dietary carotenoid supplementation affects immune-stimulated oxidative burst of phagocytes in the whole blood and humoral immune response to a novel antigen, Brucella abortus (BA). Additionally, we tested whether immune stimulation with bacterial lipopolysaccharide (LPS) affects blood carotenoid levels. We thus tested the effects of carotenoids on the oxidative burst of phagocytes under neutral conditions and during in vivo immune challenge. LPS injection depleted plasma carotenoids, indicating involvement of these phytochemicals in the immune response. However, we did not find any evidence that manipulation of carotenoid intake had modulated anti-BA antibody production, LPS-stimulated oxidative burst of phagocytes, or basal levels of circulating reactive oxygen species. This indicates that carotenoid intake does not affect endogenous production of reactive oxygen species by immune cells. This finding is consistent with the view that carotenoids are unlikely to provide a direct link between oxidative stress and colouration. However, it remains to be tested whether the oxidative burst of phagocytes induced in our experiment actually inflicts oxidative damage and whether carotenoids play a role in the attenuation of such potential damages.
Synthesis and Characterization of Ni-doped Silica Membranes Prepared Using a Hybrid Sol–Gel/CVD Method
Authors: Araki Sadao , Yano Hiroyuki , Tanaka Shunsuke , Miyake Yoshikazu
Published: September 2011

Improving the hydrogen permeation flux, while maintaining high hydrogen selectivity, is important for reducing membrane areas and enhancing membrane reactor (MR) performance. We have attempted to enhance the hydrogen permeation through the addition of nickel, which will improve both hydrogen adsorption and pore size control. The silica layer was deposited with high selectivity, using an extended counter-diffusion CVD method.
Rapid Dopamine Signaling Differentially Modulates Distinct Microcircuits within the Nucleus Accumbens during Sucrose-Directed Behavior
Authors: Cacciapaglia Fabio , Wightman R. Mark , Carelli Regina M.
Published: September 2011

The mesolimbic dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) is critical in mediating reward-related behaviors, but the precise role of dopamine in this process remains unknown. We completed a series of studies to examine whether coincident changes occur in NAc cell firing and rapid dopamine release during goal-directed behaviors for sucrose and if so, to determine whether the two are causally linked. We show that distinct populations of NAc neurons differentially encode sucrose-directed behaviors, and using a combined electrophysiology/electrochemistry technique, further show that it is at those locations that rapid dopamine signaling is observed. To determine causality, NAc cell firing was recorded during selective pharmacological inactivation of dopamine burst firing using the NMDA receptor antagonist, AP-5. We show that phasic dopamine selectively modulates excitatory but not inhibitory responses of NAc neurons during sucrose-seeking behavior. Thus, rapid dopamine signaling does not exert global actions in the NAc but selectively modulates discrete NAc microcircuits that ultimately influence goal-directed actions.
Homeostatic Interactions at the Front of Migration Control the Integrity and the Efficiency of a Migratory Glial Chain
Authors: Berzsenyi Sara , Kumar Arun , Giangrande Angela
Published: September 2011

In metazoans, cell migration often occurs in a collective manner: the cells move while physically and functionally connected to their neighbors. The coordinated and timely movement of the cells eventually ensures the proper organization of tissues, and deregulation in such a process contributes to the development of severe diseases. Thus, understanding the cellular mechanisms underlying coordinated cell movement is of great interest in basic and medical science.

The developingDrosophilawing provides an excellent model to follow the chain migration of glial cellsin vivo. Cells at the tip of the glial collective have been shown to control the timely movement of the chain. In the present study, we show that while pioneers trigger chain migration, they cannot move as single cells. We also show that isolating cell clusters at the chain tip restores the formation of smaller migratory communities. Interestingly, the migratory efficiency of thesede novoformed communities depends on the number of cells and progressively improves as the size of the cluster increases. Thus, homeostatic events at the migratory front control community integrity, efficiency, and coordination, emphasizing the importance of interactions and cell counting in fine-tuning collective processes.
Vagal Afferent Stimulation Activates Astrocytes in the Nucleus of the Solitary Tract Via AMPA Receptors: Evidence of an Atypical Neural–Glial Interaction in the Brainstem
Authors: McDougal David H. , Hermann Gerlinda E. , Rogers Richard C.
Published: September 2011

The nucleus of the solitary tract (NST), located in the dorsomedial medulla, is the site of visceral sensory modulation of a variety of homeostatic reflexes. Given recent advancements in the understanding of active regulation of synaptic information flow by astrocytes, we sought to determine whether afferent sensory inputs to NST neurons also activates NST astrocytes. Using confocal, live-cell calcium imaging of brainstem slices, we investigated the possibility that stimulation of vagal sensory afferents, the major sensory input into the NST, activated NST astrocytes, as indicated by increases in astrocytic intracellular calcium concentrations ([Ca2+]i). Astrocytes and neurons were preloaded with the calcium reporter dye Calcium Green, and astrocytes were selectively stained by sulforhodamine 101. Electrical stimulation of vagal afferent axons produced rapid increases in [Ca2+]iin NST astrocytes as well as neurons. Surprisingly, this effect on astrocytes was blocked by the AMPA receptor antagonist NBQX and was unaffected by antagonism of NMDA and metabotropic glutamate receptors. Bath application of AMPA also activated astrocytes. This activation was dependent on extracellular Ca2+influx through both typical AMPA receptors and calcium-permeable AMPA receptors. This AMPA-mediated Ca2+influx was further amplified by actions of the ryanodine receptor by way of calcium-induced calcium release. Our immunohistochemical staining of NST cells further verified the presence of the AMPAR subunit GluR1 on astrocytes. These observations suggest that NST astrocytes may be active participants in the regulation of autonomic reflexes even in the normal, healthy state.
Neonatal presentation of familial glucocorticoid deficiency resulting from a novel splice mutation in the melanocortin 2 receptor accessory protein
Authors: Jain V , Metherell L A , David A , Sharma R , Sharma P K , Clark A J L , Chan L F
Published: September 2011

Background

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by isolated glucocorticoid deficiency. Mutations in the ACTH receptor/melanocortin 2 receptor (MC2R), the MC2R accessory protein (MRAP) or the STAR protein (STAR) cause FGD types 1, 2 and 3, respectively, accounting for ∼50% of all cases.

Patient and methods

We report a neonate of Indian origin, who was diagnosed with FGD in the first few days of life. He presented with hypoglycaemic seizures and was noted to have generalised intense hyperpigmentation and normal male genitalia. Biochemical investigations revealed hypocortisolaemia (cortisol 0.223 μg/dl; NR 1–23 μg/dl) and elevated plasma ACTH (170 pg/ml). Serum electrolytes, aldosterone and plasma renin activity were normal. Peak cortisol following a standard synacthen test was 0.018 μg/dl. He responded to hydrocortisone treatment and continues on replacement. Patient DNA was analysed by direct sequencing. The effect of the novel mutation was assessed by an in vitro splicing assay using wild type and mutant heterologous minigenes.

Results

A novel homozygous mutation c.106+2_3dupTA was found in the MRAP gene. Both parents were heterozygous for the mutation. In an in vitro splicing assay, the mutation resulted in the skipping of exon 3.

Conclusion

We have identified a novel MRAP mutation where disruption of the intron 3 splice-site results in a prematurely terminated translation product. This protein (if produced) would lack the transmembrane domain that is essential for MC2R interaction. We predict that this would cause complete lack of ACTH response thus explaining the early presentation in this case.
The Conserved Foot Domain of RNA Pol II Associates with Proteins Involved in Transcriptional Initiation and/or Early Elongation
Authors: García-López M Carmen , Pelechano Vicent , Mirón-García M Carmen , Garrido-Godino Ana I , García Alicia , Calvo Olga , Werner Michel , Pérez-Ortín José E , Navarro Francisco
Published: September 2011

RNA polymerase (pol) II establishes many protein–protein interactions with transcriptional regulators to coordinate different steps of transcription. Although some of these interactions have been well described, little is known about the existence of RNA pol II regions involved in contact with transcriptional regulators. We hypothesize that conserved regions on the surface of RNA pol II contact transcriptional regulators. We identified such an RNA pol II conserved region that includes the majority of the “foot” domain and identified interactions of this region with Mvp1, a protein required for sorting proteins to the vacuole, and Spo14, a phospholipase D. Deletion of MVP1 and SPO14 affects the transcription of their target genes and increases phosphorylation of Ser5 in the carboxy-terminal domain (CTD). Genetic, phenotypic, and functional analyses point to a role for these proteins in transcriptional initiation and/or early elongation, consistent with their genetic interactions with CEG1, a guanylyltransferase subunit of the Saccharomyces cerevisiae capping enzyme.
Adjunct Mirtazapine for Negative Symptoms of Schizophrenia
Authors: Phan Stephanie V. , Kreys Tiffany‐Jade M.
Published: September 2011

Negative symptoms of schizophrenia are characterized by affective flattening, alogia, avolition, and anhedonia and are often nonresponsive to antipsychotic therapy. Because negative symptoms are predictive of poor occupational and social functioning, as well as poor global outcomes, numerous studies evaluating adjunct therapy to antipsychotics have been conducted. This review focuses on the use of the antidepressant mirtazapine as adjunct therapy to antipsychotics for the treatment of negative symptoms of schizophrenia. A literature search of the MEDLINE database (from inception‐March 2011) identified eight relevant articles: six were randomized, double‐blind, placebo‐controlled trials, and two were open‐label trials. Of the six randomized trials reviewed, four studies assessed add‐on mirtazapine to second‐generation antipsychotics, whereas two studies examined add‐on mirtazapine to firstgeneration antipsychotics. Five of the six randomized trials supported the use of mirtazapine for negative symptoms of schizophrenia. Of the two open‐label trials, one naturalistic study demonstrated that mirtazapine add‐on therapy to clozapine was not associated with improvements in negative symptoms; however, this study focused primarily on improvements in cognition, not negative symptoms. An open‐label extension phase to a randomized controlled trial showed that mirtazapine continued to produce significant improvement in negative symptoms over a longer duration of time, when added to first‐generation antipsychotic therapy. Overall, mirtazapine appears to be well tolerated and associated with few drug interactions. Although adjunct mirtazapine to antipsychotics has been shown to be effective at doses of 30 mg/day in most of the trials, limitations of these studies include short study duration and small sample sizes. To improve generalizability, larger multicenter studies with broader inclusion criteria should be conducted. In addition, studies of longer duration that use different mirtazapine dosages are needed to further assess the benefits of mirtazapine for negative symptoms of schizophrenia.
Efficacy, Safety, and Cost of Thrombolytic Agents for the Management of Dysfunctional Hemodialysis Catheters: A Systematic Review
Authors: Hilleman Daniel , Campbell Jennifer
Published: September 2011

Approximately 100,000 patients begin hemodialysis each year in the United States. Although an arteriovenous fistula or graft is the preferred method for long‐term vascular access during hemodialysis, as these types of vascular access are the most reliable, approximately 30% of patients require the use of catheters to continue hemodialysis. Tunneled, cuffed hemodialysis catheters are discouraged for permanent vascular access because of their high rates of infection, morbidity and mortality, and thrombotic and technical complications. These catheters have a short functional life span and require medical intervention, often thrombolytic therapy, to treat the catheter malfunction. No thrombolytic agent is specifically indicated for the management of occluded hemodialysis catheters. Thus, we performed a systematic review to critically evaluate all available studies that examined the efficacy, safety, and cost of thrombolytic therapy for the management of dysfunctional hemodialysis catheters. Studies were included if they reported efficacy in a specific proportion of affected dysfunctional hemodialysis catheters; reported the proportion of patients experiencing an adverse outcome (especially bleeding); and described the type of catheter used, dose of thrombolytic agent, administration protocol, dwell time, definition of treatment success, time to follow‐up for study end points, and sample size. Eighteen studies met the inclusion criteria. The mean ± SD success rate in clearing dysfunctional hemodialysis catheters was greatest with reteplase at 88 ± 4%, followed by alteplase at 81 ± 37% and tenecteplase at 41 ± 5%. Adverse effects associated with the use of these thrombolytic agents administered at low doses were extremely rare. No serious adverse bleeding events attributed to thrombolytic therapy were reported in any of the trials. Aliquotted reteplase from vials for intravenous use was the least costly thrombolytic agent. Thus, at centers that use high volumes of thrombolytics for dysfunctional hemodialysis catheters, reteplase is the thrombolytic agent of choice.
Key Articles Related to Complementary and Alternative Medicine in Cardiovascular Disease: Part 2
Authors: Chow Sheryl L. , Singh Harleen , DiDomenico Robert J. , Dunn Steven P. , Johnson Samuel G. , Marrs Joel C. , Vardeny Orly , Bleske Barry E.
Published: September 2011

The utilization of complementary and alternative medicine (CAM) has increased over the past several years, largely based on unsubstantiated benefits and aggressive marketing. However, the safety of nontraditional products is often overlooked and undocumented. Clinicians should become familiar with the potential risks of CAM and inform patients about associated adverse effects and/or serious drug interactions. This bibliography paper compiled key articles specific to CAM therapy and cardiovascular disease, which include primary literature and review articles. Based on the numerous published reports available on this topic, this bibliography, as part 2 of 2, focuses on the safety of CAM therapy in cardiovascular disease.
Minority Cosmopolitanism
Authors: Koshy Susan
Published: September 2011

The topography of literary production and consumption has been transformed as writers and texts travel, ethnic literature is taught and translated in multiple national venues, and writers’ locations, audiences, and subject matter resist ready alignment. he growing internationalization of ethnic literary production has produced a heterogeneous range of texts, which challenge the established boundaries of ethnic and world literature. Because they focus on minorities, these texts have been slow to win recognition as world literature even though they depict transnational movements and identifications that diverge from those in canonical ethnic narratives. I develop the analytic of minority cosmopolitanism to examine the ways in which these literary narratives of worlding contest contemporary economic and political processes of globalization and Eurocentric accounts of globality. This essay considers how the gendered figure of the diasporic citizen serves as a vehicle for minority cosmopolitanism in Jhumpa Lahiri's Interpreter of Maladies (1999).
The Concept of the Sinophone
Authors: Shih Shu-Mei
Published: September 2011

The spectacular rise of China as a superpower perhaps only now compels us to recalibrate existing discourses of empire and postcoloniality, but China has been an empire in the modern sense since the mid–eighteenth century, when it conquered vast lands north and west of “China proper.” This history has been largely hidden from view because of two unacknowledged obsessions: the fetishization of Western empires over other empires and the prevailing discourse of Chinese victimhood at the hands of Western empires. The rise of China would not have caught so many by surprise if our vision had not been persistently clouded by our privileging of the oceanic (i.e., Western) mode of colonial expansion, which paradoxically centered the West as the most deserving object of critical attention and intellectual labor. It also would not have been a surprise if we had looked back at the Manchu conquests of inner Asia, which present-day China largely inherited and consolidated in a continuous colonial project. Postcolonial theory as we know it, particularly its critiques of orientalism, may prove irrelevant or even complicit when we consider how the positions of Chinese intellectuals critical of Western imperialism and orientalism easily slip into an unreflective nationalism, whose flip side may be a new imperialism.
The width of riparian habitats for understory birds in an Amazonian forest
Authors: Bueno Anderson Saldanha , Bruno Renato Saragoça , Pimentel Tania Pena , Sanaiotti Tânia Margarete , Magnusson William Ernest
Published: September 2011

Riparian habitats are important for the maintenance of regional biodiversity. Many studies have compared bird distributions between riparian and non‐riparian habitats but have not established how wide riparian habitats used by birds are, as measured by distance from the nearest stream. We investigated the distribution of understory birds along gradients of distance from streams, soil clay content, and slope in a central Amazonian forest, by mist‐netting birds three times in 45 plots. We used nonmetric multidimensional scaling (NMDS) to reduce the dimensionality of species quantitative (abundance) and qualitative (presence–absence) composition to one multivariate axis. Estimates of the width of riparian habitats as indicated by understory birds depended on the community attribute considered, measuring 90 m for species quantitative composition and 140 m for species qualitative composition. Species distributions were correlated with clay content but were independent of slope, while distance from streams was positively correlated with clay content but independent of slope. Clay content affects plant species composition, which in turn, may influence bird species composition. However, distribution patterns of birds in relation to distance from streams are consistent among studies carried out in many different temperate and tropical regions, indicating an effect of distance from streams itself. Protection of riparian habitats is one of the most widely used conservation strategies, and Brazilian environmental legislation mandates the protection of a 30 m wide strip of riparian vegetation on either side of small streams. We show that the protected strip should be much wider and recommend strategies to place other forms of land protection contiguous with riparian areas so that Brazilian environmental legislation better fulfills its role of protecting biodiversity associated with riparian habitats.
Building Passion Develops Meaningful Mentoring Relationships among Canadian Physiotherapists
Authors: Ezzat Allison M. , Maly Monica R.
Published: September 2011

Purpose: To describe the meaning of mentorship among Canadian orthopaedic physiotherapists. Methods: As part of a phenomenological qualitative study, 14 registered physiotherapists (13 women, 1 man) each participated in a single 60-minute, semi-structured face-to-face interview. Participants reflected on their experiences in receiving and providing mentorship and described the impact of mentorship on their careers. Interviews were transcribed verbatim and analyzed using a phenomenological approach. Results: Participants described mentorship as any nurturing process in which they used their skills and experience to guide, teach, and encourage a less skilled or less experienced colleague for the purpose of promoting professional and personal development. Participants experienced mentorship as a positive, reflective phenomenon. According to participants, the true essence of mentorship in physiotherapy consists of building passion, keeping fresh, making us stronger, and promoting deeper learning. Conclusions: Building a shared passion for learning, as well as a mentor's commitment to the mentee's success, forms the foundation of meaningful mentorship in physiotherapy. These mentoring relationships enable physiotherapists to adapt to the changing health care system, advance patient care, and develop the profession.
3D-QSAR Studies on Thiazolidin-4-one S1P1 Receptor Agonists by CoMFA and CoMSIA
Authors: Qian Chuiwen , Zheng Junxia , Xiao Gaokeng , Guo Jialiang , Yang Zhaoqi , Huang Li , Chao Wei , Rao Longyi , Sun Pinghua
Published: September 2011

Selective S1P1 receptor agonists have therapeutic potential to treat a variety of immune-mediated diseases. A series of 2-imino-thiazolidin-4-one derivatives displaying potent S1P1 receptor agonistic activity were selected to establish 3D-QSAR models using CoMFA and CoMSIA methods. Internal and external cross-validation techniques were investigated as well as some measures including region focusing, progressive scrambling, bootstraping and leave-group-out. The satisfactory CoMFA model predicted a q2 value of 0.751 and an r2 value of 0.973, indicating that electrostatic and steric properties play a significant role in potency. The best CoMSIA model, based on a combination of steric, electrostatic, hydrophobic and H-bond donor descriptors, predicted a q2 value of 0.739 and an r2 value of 0.923. The models were graphically interpreted using contour plots which gave more insight into the structural requirements for increasing the activity of a compound, providing a solid basis for future rational design of more active S1P1 receptor agonists.
Comparative QSTR Study Using Semi-Empirical and First Principle Methods Based Descriptors for Acute Toxicity of Diverse Organic Compounds to the Fathead Minnow
Authors: Eroglu Erol , Palaz Selami , Oltulu Oral , Turkmen Hasan , Ozaydın Cihat
Published: September 2011

Several quantum-mechanics-based descriptors were derived for a diverse set of48 organic compounds using AM1, PM3, HF/6-31 G, and DFT-B3LYP/6-31 G (d) level ofthe theory. LC50 values of acute toxicity of the compounds were correlated to the fatheadminnow and predicted using calculated descriptors by employing ComprehensiveDescriptors for Structural and Statistical Analysis (CODESSA) program. The heuristicmethod, implemented in the CODESSA program for selecting the ‘best’ regression model,was applied to a pre-selection of the most-representative descriptors by sequentiallyeliminating descriptors that did not satisfy a certain level of statistical criterion. First model,statistically, the most significant one has been drawn up with the help of DFT calculationsin which the squared correlation coefficient R2 is 0.85, and the squared cross-validationcorrelation coefficient 2CV R is 0.79. Second model, which has been drawn up with the helpof HF calculations, has its statistical quality very close to the DFT-based one and in thismodel value of R2 is 0.84 and that of R2CV is 0.78. Third and fourth models have been drawnup with the help of AM1 and PM3 calculations, respectively. The values of R2 and R2CV in thethird case are correspondingly 0.79 and 0.66, whereas in the fourth case they are 0.78 and0.65 respectively. Results of this study clearly demonstrate that for the calculations of descriptors in modeling of acute toxicity of organic compounds to the fathead minnow, firstprincipal methods are much more useful than semi-empirical methods.Keywords: Comparative QSTR; fathead minnow; acute toxicity; DFT; HF;
Reactive Oxygen Species-Induced Impairment of Endothelium-Dependent Relaxations in Rat Aortic Rings: Protection by Methanolic Extracts of Phoebe grandis
Authors: Yeh-Siang Lau , Subramaniam Gopal , Hadi A. Hamid A. , Murugan Dharmani , Mustafa Mohd Rais
Published: September 2011

Generation of reactive oxygen species plays a pivotal role in the development of cardiovascular diseases. The present study describes the effects of the methanolic extract of Phoebe grandis (MPG) stem bark on reactive oxygen species-induced endothelial dysfunction in vitro. Endothelium-dependent (acetylcholine, ACh) and -independent relaxation (sodium nitroprusside, SNP) was investigated from isolated rat aorta of Sprague-Dawley (SD) in the presence of the β-NADH (enzymatic superoxide inducer) and MPG extract. Superoxide anion production in aortic vessels was measured by lucigen chemiluminesence. Thirty minutes incubation of the rat aorta in vitro with β-NADH increased superoxide radical production and significantly inhibited ACh-induced relaxations. Pretreatment with MPG (0.5, 5 and 50 μg/mL) restored the ACh-induced relaxations (Rmax: 92.29% ± 2.93, 91.02% ± 4.54 and 88.31 ± 2.36, respectively) in the presence of β-NADH. MPG was ineffective in reversing the impaired ACh-induced relaxations caused by pyrogallol, a non-enzymatic superoxide generator. Superoxide dismutase (a superoxide scavenger), however, reversed the impaired ACh relaxations induced by both β-NADH and pyrogallol. MPG also markedly inhibited the β-NADH-induced generation of the superoxide radicals. Furthermore, MPG scavenging peroxyl radicals generated by tBuOOH (10−4 M).These results indicate that MPG may improve the endothelium dependent relaxations to ACh through its scavenging activity as well as by inhibiting the NADH/NADPH oxidase induced generation of superoxide anions.
Intelligent Method for Diagnosing Structural Faults of Rotating Machinery Using Ant Colony Optimization
Authors: Li Ke , Chen Peng
Published: September 2011

Structural faults, such as unbalance, misalignment and looseness, etc., often occur in the shafts of rotating machinery. These faults may cause serious machine accidents and lead to great production losses. This paper proposes an intelligent method for diagnosing structural faults of rotating machinery using ant colony optimization (ACO) and relative ratio symptom parameters (RRSPs) in order to detect faults and distinguish fault types at an early stage. New symptom parameters called “relative ratio symptom parameters” are defined for reflecting the features of vibration signals measured in each state. Synthetic detection index (SDI) using statistical theory has also been defined to evaluate the applicability of the RRSPs. The SDI can be used to indicate the fitness of a RRSP for ACO. Lastly, this paper also compares the proposed method with the conventional neural networks (NN) method. Practical examples of fault diagnosis for a centrifugal fan are provided to verify the effectiveness of the proposed method. The verification results show that the structural faults often occurring in the centrifugal fan, such as unbalance, misalignment and looseness states are effectively identified by the proposed method, while these faults are difficult to detect using conventional neural networks.
The Potential for Harvesting Energy from the Movement of Trees
Authors: McGarry Scott , Knight Chris
Published: September 2011

Over the last decade, wireless devices have decreased in size and power requirements. These devices generally use batteries as a power source but can employ additional means of power, such as solar, thermal or wind energy. However, sensor networks are often deployed in conditions of minimal lighting and thermal gradient such as densely wooded environments, where even normal wind energy harvesting is limited. In these cases a possible source of energy is from the motion of the trees themselves. We investigated the amount of energy and power available from the motion of a tree in a sheltered position, during Beaufort 4 winds. We measured the work performed by the tree to lift a mass, we measured horizontal acceleration of free movement, and we determined the angular deflection of the movement of the tree trunk, to determine the energy and power available to various types of harvesting devices. We found that the amount of power available from the tree, as demonstrated by lifting a mass, compares favourably with the power required to run a wireless sensor node.
Use of Positron Emission Tomography to Detect Infection Around Antibiotic-loaded Cement Spacers in Patients With High C-Reactive Protein Levels
Authors: Huang Ming-Jhe , Hsieh Pang-Hsin , Ueng Steve W.N. , Ho Kung-Chu , Yen Tzu-Chen , Lee Mel S.
Published: September 2011

In patients who have antibiotic-loaded cement hip spacers in the interim period, the correct diagnosis of infection eradication is the major determinant before reimplantation arthroplasty. Diagnosis is usually based on clinical findings and serum C-reactive protein (CRP) levels. However, diagnosis can be challenging when the clinical findings are normal but the CRP level is high. From March 2007 to January 2008, fluorodeoxy-glucose positron emission tomography (FDG-PET) was used to detect infection around antibiotic-loaded cement spacers in 13 patients (mean age, 60 years). Although patients’ clinical conditions were deemed suitable for reimplantation, their serum CRP levels were persistently elevated (mean, 54 mg/L) an average of 120 days (range, 28–413 days) after the first-stage operation. Reimplantation total hip arthroplasty (THA) was subsequently performed in 7 patients based on the negative findings of FDG-PET. In 6 patients, FDG-PET was positive for infection. The persistence of infection was confirmed in 3 of these patients by another debridement surgery. Staged reimplantation THA was delayed in 1 patient who underwent repeat debridement and in 3 patients who were treated with extended periods of oral antibiotics. Of the 11 staged reimplantation THAs, only 1 reinfection was noted at an average follow-up of 48 months. The success rate of 91% suggests FDG-PET could help in the differential diagnosis of infection around cement spacers, especially in patients with normal clinical findings but elevated CRP levels.