Effect of starvation and subsequent feeding on glycogen concentration, behavior and mortality in the golden mussel Limnoperna Fortunei (Dunker, 1857) (Bivalvia: Mytilidae)

The success of Limnoperna fortunei as an invasive species is related to its physiological plasticity that allows them to endure adverse environmental conditions. Starvation tolerance is considered to be an important trait associated with bivalve invasiveness. In natural ecosystems, food resources can vary during the year, exposing mussels to variable periods of starvation or limited food availability. Thus, mussels have developed physiological strategies to tolerate fluctuations in food availability. Glycogen concentration has been used in different monitoring studies as an indicator of the nutritional condition of bivalves. The aim of this study was to investigate the physiological responses of L. fortunei based on the glycogen concentrations of specimens under four treatments, comprising differentcombinations of feeding and starvation, during 125 days. The experiment was carried out in two phases. In the phase I, mussels were divided in two treatments: starvation (S) and feeding (F). After 100 days, tissue samples were collected to quantify glycogen concentrations and, each phase I group was divided in two subgroups: starvation (S) and feeding (F), resulting in four treatments. In the phase II, that lasted 25 days, starvation specimens (S) from phase I were allowed to feed (starvation-feeding treatment, or S-F), or continued to undergo starvation (starvation-starvation treatment, or S-S) and the feeding specimens (F) continued feeding (feeding-feeding group, or F-F), or were subjected to starvation (feeding-starvation treatment, or F-S). Behavior (valve-closing) and mortality were recorded in 24 h intervals. After the 25 days (phase II) all specimens were killed, and thei r soft tissue was removed to quantify glycogen concentrations. The glycogen concentration of the S-F treatment was lower than that of the F-S treatment, which was initially allowed to feed (phase I) and then subjected to starvation (phase II). Stability in the glycogen concentrations was observed when the phase II feeding conditions were maintained during the experiments, as observed in the S-S (continued starvation) and F-F (continued feeding) treatments. Based on our glycogen concentrations results, the golden mussel shows a higher tolerance to starvation (125 days) than has previously been published, which suggests that its tolerance strongly influences its invasive behavior.Facultad de Ciencias Naturales y Muse

Effect of starvation and subsequent feeding on glycogen concentration, behavior and mortality in the golden mussel Limnoperna Fortunei (Dunker, 1857) (Bivalvia: Mytilidae)

The success of Limnoperna fortunei as an invasive species is related to its physiological plasticity that allows them to endure adverse environmental conditions. Starvation tolerance is considered to be an important trait associated with bivalve invasiveness. In natural ecosystems, food resources can vary during the year, exposing mussels to variable periods of starvation or limited food availability. Thus, mussels have developed physiological strategies to tolerate fluctuations in food availability. Glycogen concentration has been used in different monitoring studies as an indicator of the nutritional condition of bivalves. The aim of this study was to investigate the physiological responses of L. fortunei based on the glycogen concentrations of specimens under four treatments, comprising differentcombinations of feeding and starvation, during 125 days. The experiment was carried out in two phases. In the phase I, mussels were divided in two treatments: starvation (S) and feeding (F). After 100 days, tissue samples were collected to quantify glycogen concentrations and, each phase I group was divided in two subgroups: starvation (S) and feeding (F), resulting in four treatments. In the phase II, that lasted 25 days, starvation specimens (S) from phase I were allowed to feed (starvation-feeding treatment, or S-F), or continued to undergo starvation (starvation-starvation treatment, or S-S) and the feeding specimens (F) continued feeding (feeding-feeding group, or F-F), or were subjected to starvation (feeding-starvation treatment, or F-S). Behavior (valve-closing) and mortality were recorded in 24 h intervals. After the 25 days (phase II) all specimens were killed, and thei r soft tissue was removed to quantify glycogen concentrations. The glycogen concentration of the S-F treatment was lower than that of the F-S treatment, which was initially allowed to feed (phase I) and then subjected to starvation (phase II). Stability in the glycogen concentrations was observed when the phase II feeding conditions were maintained during the experiments, as observed in the S-S (continued starvation) and F-F (continued feeding) treatments. Based on our glycogen concentrations results, the golden mussel shows a higher tolerance to starvation (125 days) than has previously been published, which suggests that its tolerance strongly influences its invasive behavior.Facultad de Ciencias Naturales y Muse

Effect of starvation and subsequent feeding on glycogen concentration, behavior and mortality in the golden mussel Limnoperna Fortunei (Dunker, 1857) (Bivalvia: Mytilidae)

The success of Limnoperna fortunei as an invasive species is related to its physiological plasticity that allows them to endure adverse environmental conditions. Starvation tolerance is considered to be an important trait associated with bivalve invasiveness. In natural ecosystems, food resources can vary during the year, exposing mussels to variable periods of starvation or limited food availability. Thus, mussels have developed physiological strategies to tolerate fluctuations in food availability. Glycogen concentration has been used in different monitoring studies as an indicator of the nutritional condition of bivalves. The aim of this study was to investigate the physiological responses of L. fortunei based on the glycogen concentrations of specimens under four treatments, comprising differentcombinations of feeding and starvation, during 125 days. The experiment was carried out in two phases. In the phase I, mussels were divided in two treatments: starvation (S) and feeding (F). After 100 days, tissue samples were collected to quantify glycogen concentrations and, each phase I group was divided in two subgroups: starvation (S) and feeding (F), resulting in four treatments. In the phase II, that lasted 25 days, starvation specimens (S) from phase I were allowed to feed (starvation-feeding treatment, or S-F), or continued to undergo starvation (starvation-starvation treatment, or S-S) and the feeding specimens (F) continued feeding (feeding-feeding group, or F-F), or were subjected to starvation (feeding-starvation treatment, or F-S). Behavior (valve-closing) and mortality were recorded in 24 h intervals. After the 25 days (phase II) all specimens were killed, and thei r soft tissue was removed to quantify glycogen concentrations. The glycogen concentration of the S-F treatment was lower than that of the F-S treatment, which was initially allowed to feed (phase I) and then subjected to starvation (phase II). Stability in the glycogen concentrations was observed when the phase II feeding conditions were maintained during the experiments, as observed in the S-S (continued starvation) and F-F (continued feeding) treatments. Based on our glycogen concentrations results, the golden mussel shows a higher tolerance to starvation (125 days) than has previously been published, which suggests that its tolerance strongly influences its invasive behavior.Fil: Cordeiro, Nelmara I. S.. Universidade Federal de Minas Gerais; BrasilFil: Andrade, Jennifer T. M.. Universidade Federal de Minas Gerais; BrasilFil: Montresor, Lângia C.. Fundación Oswaldo Cruz; BrasilFil: Luz, Dalva M. R.. Universidade Federal de Minas Gerais; BrasilFil: Martinez, Carlos B.. Universidade Federal de Minas Gerais; BrasilFil: Darrigran, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Naturales y Museo. División Zoología Invertebrados; ArgentinaFil: Pinheiro, Jairo. Universidade Federal Rural Do Rio de Janeiro;Fil: Vidigal, Teofânia H. D. A.. Universidade Federal de Minas Gerais; Brasi

Development of lifetime comorbidity in the world health organization world mental health surveys

CONTEXT: Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. OBJECTIVE: To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the World Health Organization World Mental Health Surveys. DESIGN: Nationally or regionally representative community surveys. SETTING: Fourteen countries. PARTICIPANTS: A total of 21 229 survey respondents. MAIN OUTCOME MEASURES: First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the World Health Organization Composite International Diagnostic Interview. RESULTS: Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (ie, internalizing or externalizing) associations were generally stronger than between-domain associations. Most time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity and oppositional defiant disorders (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. CONCLUSIONS: The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered herein. These common pathways should be the focus of future research on the development of comorbidity, although several important pairwise associations that cannot be accounted for by latent variables also exist that warrant further focused study

Myocardial citrullination in rheumatoid arthritis: a correlative histopathologic study

The aim of this study was to explore the presence and localization of myocardial citrullination in samples from rheumatoid arthritis (RA) patients compared to rheumatic and non-rheumatic disease control groups. Archived myocardial samples obtained during autopsy from 1995 to 2009 were assembled into four groups: RA; scleroderma; fatal myocarditis; and non-rheumatic disease controls. Samples were examined by immunohistochemistry (IHC) for the presence and localization of citrullination and peptidyl arginine deiminase enzymes (PADs) by a single cardiovascular pathologist blinded to disease group and clinical characteristics. Myocardial samples from seventeen RA patients were compared with those from fourteen controls, five fatal myocarditis patients, and ten scleroderma patients. Strong citrullination staining was detected exclusively in the myocardial interstitium in each of the groups. However, average and peak anti-citrulline staining was 59% and 44% higher, respectively, for the RA group compared to the combined non-RA groups (P < 0.05 for both comparisons). Myocardial fibrosis did not differ between the groups. In contrast to citrullination, PADs 1 to 3 and 6 were detected in cardiomyocytes (primarily PADs 1 and 3), resident inflammatory cells (primarily PADs 2 and 4), and, to a smaller extent, in endothelial cells and vascular smooth muscle cells. PAD staining did not co-localize with anti-citrulline staining in the interstitium and did not vary by disease state. Staining for citrullination was higher in the myocardial interstitium of RA compared to other disease states, a finding that could link autoimmunity to the known increase in myocardial dysfunction and heart failure in RA

HIV-1 Inhibits Autophagy in Bystander Macrophage/Monocytic Cells through Src-Akt and STAT3

Autophagy is a homeostatic mechanism of lysosomal degradation. Defective autophagy has been linked to various disorders such as impaired control of pathogens and neurodegeneration. Autophagy is regulated by a complex array of signaling pathways that act upstream of autophagy proteins. Little is known about the role of altered regulatory signaling in disorders associated with defective autophagy. In particular, it is not known if pathogens inhibit autophagy by modulation of upstream regulatory pathways. Cells infected with HIV-1 blocked rapamycin-induced autophagy and CD40-induced autophagic killing of Toxoplasma gondii in bystander (non-HIV-1 infected) macrophage/monocytic cells. Blockade of autophagy was dependent on Src-Akt and STAT3 triggered by HIV-1 Tat and IL-10. Neutralization of the upstream receptors VEGFR, β-integrin or CXCR4, as well as of HIV-1 Tat or IL-10 restored autophagy in macrophage/monocytic cells exposed to HIV-1-infected cells. Defective autophagic killing of T. gondii was detected in monocyte-derived macrophages from a subset of HIV-1+ patients. This defect was also reverted by neutralization of Tat or IL-10. These studies revealed that a pathogen can impair autophagy in non-infected cells by activating counter-regulatory pathways. The fact that pharmacologic manipulation of cell signaling restored autophagy in cells exposed to HIV-1-infected cells raises the possibility of therapeutic manipulation of cell signaling to restore autophagy in HIV-1 infection

A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury

Background & Aims We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility. Methods We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings. Results We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28–1.62; P = 1.2 × 10–9 and replicated the finding in the validation set (OR 1.48; 95% CI 1.09–1.99; P = .01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32–1.98; P = 4.0 × 10–6; allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21–1.56; P = 1.5 × 10–6; allele frequency = 11.5%). Among amoxicillin- and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A*02:01 and DRB1*15:01. Conclusions In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI

Deregulation of Rab and Rab Effector Genes in Bladder Cancer

Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer

Toxoplasma gondii-Induced Activation of EGFR Prevents Autophagy Protein-Mediated Killing of the Parasite

Toxoplasma gondii resides in an intracellular compartment (parasitophorous vacuole) that excludes transmembrane molecules required for endosome-lysosome recruitment. Thus, the parasite survives by avoiding lysosomal degradation. However, autophagy can re-route the parasitophorous vacuole to the lysosomes and cause parasite killing. This raises the possibility that T. gondii may deploy a strategy to prevent autophagic targeting to maintain the non-fusogenic nature of the vacuole. We report that T. gondii activated EGFR in endothelial cells, retinal pigment epithelial cells and microglia. Blockade of EGFR or its downstream molecule, Akt, caused targeting of the parasite by LC3(+) structures, vacuole-lysosomal fusion, lysosomal degradation and killing of the parasite that were dependent on the autophagy proteins Atg7 and Beclin 1. Disassembly of GPCR or inhibition of metalloproteinases did not prevent EGFR-Akt activation. T. gondii micronemal proteins (MICs) containing EGF domains (EGF-MICs; MIC3 and MIC6) appeared to promote EGFR activation. Parasites defective in EGF-MICs (MIC1 ko, deficient in MIC1 and secretion of MIC6; MIC3 ko, deficient in MIC3; and MIC1-3 ko, deficient in MIC1, MIC3 and secretion of MIC6) caused impaired EGFR-Akt activation and recombinant EGF-MICs (MIC3 and MIC6) caused EGFR-Akt activation. In cells treated with autophagy stimulators (CD154, rapamycin) EGFR signaling inhibited LC3 accumulation around the parasite. Moreover, increased LC3 accumulation and parasite killing were noted in CD154-activated cells infected with MIC1-3 ko parasites. Finally, recombinant MIC3 and MIC6 inhibited parasite killing triggered by CD154 particularly against MIC1-3 ko parasites. Thus, our findings identified EGFR activation as a strategy used by T. gondii to maintain the non-fusogenic nature of the parasitophorous vacuole and suggest that EGF-MICs have a novel role in affecting signaling in host cells to promote parasite survival