204 research outputs found

    Anhedonia in schizophrenia and major depression: state or trait?

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    <p>Abstract</p> <p>Background</p> <p>In schizophrenia and major depressive disorder, anhedonia (a loss of capacity to feel pleasure) had differently been considered as a premorbid personological trait or as a main symptom of their clinical picture. The aims of this study were to examine the pathological features of anhedonia in schizophrenic and depressed patients, and to investigate its clinical relations with general psychopathology (negative, positive, and depressive dimensions).</p> <p>Methods</p> <p>A total of 145 patients (80 schizophrenics and 65 depressed subjects) were assessed using the Physical Anhedonia Scale and the Social Anhedonia Scale (PAS and SAS, respectively), the Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS, respectively), the Calgary Depression Scale for Schizophrenics (CDSS), and the Hamilton Depression Rating Scale (HDRS). The statistical analysis was performed in two steps. First, the schizophrenic and depressed samples were dichotomised into 'anhedonic' and 'normal hedonic' subgroups (according to the 'double (PAS/SAS) cut-off') and were compared on the general psychopathology scores using the Mann-Whitney Z test. Subsequently, for the total schizophrenic and depressed samples, Spearman correlations were calculated to examine the relation between anhedonia ratings and the other psychopathological parameters.</p> <p>Results</p> <p>In the schizophrenic sample, anhedonia reached high significant levels only in 45% of patients (n = 36). This 'anhedonic' subgroup was distinguished by high scores in the disorganisation and negative dimensions. Positive correlations of anhedonia with disorganised and negative symptoms were also been detected. In the depressed sample, anhedonia reached high significant levels in only 36.9% of subjects (n = 24). This 'anhedonic' subgroup as distinguished by high scores in the depression severity and negative dimensions. Positive correlations of anhedonia with depressive and negative symptoms were also been detected.</p> <p>Conclusion</p> <p>In the schizophrenic sample, anhedonia seems to be a specific subjective psychopathological experience of the negative and disorganised forms of schizophrenia. In the depressed sample, anhedonia seems to be a specific subjective psychopathological experience of those major depressive disorder forms with a marked clinical depression severity.</p

    Assessing the ecological risk posed by a recently established invasive alien predator: Harmonia axyridis as a case study

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    Invasive alien predators are a serious threat to biodiversity worldwide. However, there is no generic method for assessing which local species are most at risk following the invasion of a new predator. The harlequin ladybird, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), is an alien in Europe and many other parts of the world where it affects other species of ladybirds through competition for food and intra-guild predation (IGP). Here, we describe a method developed to assess which European ladybird species are most at risk following the invasion of H. axyridis. The three components of the risk assessment are: the likelihood that the assessed native species encounters H. axyridis in the field, the hazard of competition for food, and the IGP hazard. Thirty native European ladybird species were assessed through data obtained from field observations, laboratory experiments and literature reviews. The species that are considered most at risk are found on deciduous trees, have immature stages which are highly vulnerable to IGP by H. axyridis, and are primarily aphidophagous. These species should be the focus of specific studies and possibly conservation actions. The risk assessment method proposed here could be applied to other alien predators which are considered a threat to native species through competition and predation

    Dio-sensimedia: a novel culture medium for rapid detection of extended spectrum β-lactamases

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    BACKGROUND: Resistance to contemporary broad-spectrum β-lactams, mediated by extended-spectrum β-lactamases (ESBL), is an increasing problem worldwide. Many of the emerging antimicrobial resistance problems of this decade have been characterized by difficulty in the recognition of resistance in the laboratory, particularly by rapid susceptibility test methods. The plasmid-encoded ESBL represent such a resistance phenomenon that is difficult to recognize. We compared Dio-Sensimedia-ES (DSM-ES; Diomed, Istanbul, Turkey) and Mueller-Hinton (MH) agar in the double-disk synergy test (DDST) as a novel rapid system for detecting ESBL directly from bacterial culture. METHODS: Sixty ESBL-producing Klebsiella pneumoniae isolates cultured from blood (30), endotracheal aspirates (20), urine (5) and pus (5), as well as 40 Escherichia coli isolates cultured from endotracheal aspirates (15), urine (10), blood (8) and pus (7) were studied. Isolates positive for ESBL by the combined disk tests were tested with the DDST using MH and DSM-ES agar to detect ESBL-mediated resistance in K. pneumoniae and E. coli. DSM-ES agar was also used to determine the susceptibility of Enterobacteriaceae and staphylococci. RESULTS: Among 60 ESBL-producing K. pneumoniae isolates, 59 (98.3%) were identified as ESBL-positive by the DDST using MH, and 58 (96.6%), using DSM-ES agar. Of 40 ESBL-producing E. coli isolates, 38 (95%) were ESBL-positive by the DDST on MH agar, and 37 (92.5%), on DSM-ES agar. The average incubation period required for ESBL detection by the DDST on DSM-ES agar was 4 hours. CONCLUSIONS: Since the DDST results were available within 4 hours when DSM-ES agar was used, the use of this media may significantly lower the length of hospital stay, the total cost for patient care and even the mortality rate by fascilitating early treatment against ESBL-producing organisms

    Comprehensive in silico functional specification of mouse retina transcripts

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    BACKGROUND: The retina is a well-defined portion of the central nervous system (CNS) that has been used as a model for CNS development and function studies. The full specification of transcripts in an individual tissue or cell type, like retina, can greatly aid the understanding of the control of cell differentiation and cell function. In this study, we have integrated computational bioinformatics and microarray experimental approaches to classify the tissue specificity and developmental distribution of mouse retina transcripts. RESULTS: We have classified a set of retina-specific genes using sequence-based screening integrated with computational and retina tissue-specific microarray approaches. 33,737 non-redundant sequences were identified as retina transcript clusters (RTCs) from more than 81,000 mouse retina ESTs. We estimate that about 19,000 to 20,000 genes might express in mouse retina from embryonic to adult stages. 39.1% of the RTCs are not covered by 60,770 RIKEN full-length cDNAs. Through comparison with 2 million mouse ESTs, spectra of neural, retinal, late-generated retinal, and photoreceptor -enriched RTCs have been generated. More than 70% of these RTCs have data from biological experiments confirming their tissue-specific expression pattern. The highest-grade retina-enriched pool covered almost all the known genes encoding proteins involved in photo-transduction. CONCLUSION: This study provides a comprehensive mouse retina transcript profile for further gene discovery in retina and suggests that tissue-specific transcripts contribute substantially to the whole transcriptome

    Hemoglobin E syndromes in Pakistani population

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    <p>Abstract</p> <p>Background</p> <p>Hemoglobin E is an important hemoglobin variant with a worldwide distribution. A number of hemoglobinopathies have been reported from Pakistan. However a comprehensive description of hemoglobin E syndromes for the country was never made. This study aimed to describe various hemoglobin E disorders based on hematological parameters and chromatography. The sub-aim was to characterize hemoglobin E at molecular level.</p> <p>Methods</p> <p>This was a hospital based study conducted prospectively for a period of one year extending from January 1 to December 31, 2008. EDTA blood samples were analyzed for completed blood counts and hemoglobin variants through automated hematology analyzer and Bio-Rad beta thalassaemia short program respectively. Six samples were randomly selected to characterize HbE at molecular level through RFLP-PCR utilizing <it>Mnl</it>I restriction enzyme.</p> <p>Results</p> <p>During the study period, 11403 chromatograms were analyzed and Hb E was detected in 41 (or 0.36%) samples. Different hemoglobin E syndromes identified were HbEA (n = 20 or 49%), HbE/β-thalassemia (n = 14 or 34%), HbEE (n = 6 or 15%) and HbE/HbS (n = 1 or 2%). Compound heterozygosity for HbE and beta thalassaemia was found to be the most severely affected phenotype. RFLP-PCR utilizing <it>Mnl</it>I successfully characterized HbE at molecular level in six randomly selected samples.</p> <p>Conclusions</p> <p>Various HbE phenotypes are prevalent in Pakistan with HbEA and HbE/β thalassaemia representing the most common syndromes. Chromatography cannot only successfully identify hemoglobin E but also assist in further characterization into its phenotype including compound heterozygosity. Definitive diagnosis of HbE can easily be achieved through RFLP-PCR.</p

    What Was the Set of Ubiquitin and Ubiquitin-Like Conjugating Enzymes in the Eukaryote Common Ancestor?

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    Ubiquitin (Ub)-conjugating enzymes (E2) are key enzymes in ubiquitination or Ub-like modifications of proteins. We searched for all proteins belonging to the E2 enzyme super-family in seven species (Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Schizosaccharomyces pombe, Saccharomyces cerevisiae, and Arabidopsis thaliana) to identify families and to reconstruct each family’s phylogeny. Our phylogenetic analysis of 207 genes led us to define 17 E2 families, with 37 E2 genes, in the human genome. The subdivision of E2 into four classes did not correspond to the phylogenetic tree. The sequence signature HPN (histidine–proline–asparagine), followed by a tryptophan residue at 16 (up to 29) amino acids, was highly conserved. When present, the active cysteine was found 7 to 8 amino acids from the C-terminal end of HPN. The secondary structures were characterized by a canonical alpha/beta fold. Only family 10 deviated from the common organization because the proteins were devoid of enzymatic activity. Family 7 had an insertion between beta strands 1 and 2; families 3, 5 and 14 had an insertion between the active cysteine and the conserved tryptophan. The three-dimensional data of these proteins highlight a strong structural conservation of the core domain. Our analysis shows that the primitive eukaryote ancestor possessed a diversified set of E2 enzymes, thus emphasizing the importance of the Ub pathway. This comprehensive overview of E2 enzymes emphasizes the diversity and evolution of this superfamily and helps clarify the nomenclature and true orthologies. A better understanding of the functions of these enzymes is necessary to decipher several human diseases

    Mutations in a Guanylate Cyclase GCY-35/GCY-36 Modify Bardet-Biedl Syndrome–Associated Phenotypes in Caenorhabditis elegans

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    Ciliopathies are pleiotropic and genetically heterogeneous disorders caused by defective development and function of the primary cilium. Bardet-Biedl syndrome (BBS) proteins localize to the base of cilia and undergo intraflagellar transport, and the loss of their functions leads to a multisystemic ciliopathy. Here we report the identification of mutations in guanylate cyclases (GCYs) as modifiers of Caenorhabditis elegans bbs endophenotypes. The loss of GCY-35 or GCY-36 results in suppression of the small body size, developmental delay, and exploration defects exhibited by multiple bbs mutants. Moreover, an effector of cGMP signalling, a cGMP-dependent protein kinase, EGL-4, also modifies bbs mutant defects. We propose that a misregulation of cGMP signalling, which underlies developmental and some behavioural defects of C. elegans bbs mutants, may also contribute to some BBS features in other organisms

    An Essential Role for DYF-11/MIP-T3 in Assembling Functional Intraflagellar Transport Complexes

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    MIP-T3 is a human protein found previously to associate with microtubules and the kinesin-interacting neuronal protein DISC1 (Disrupted-in-Schizophrenia 1), but whose cellular function(s) remains unknown. Here we demonstrate that the C. elegans MIP-T3 ortholog DYF-11 is an intraflagellar transport (IFT) protein that plays a critical role in assembling functional kinesin motor-IFT particle complexes. We have cloned a loss of function dyf-11 mutant in which several key components of the IFT machinery, including Kinesin-II, as well as IFT subcomplex A and B proteins, fail to enter ciliary axonemes and/or mislocalize, resulting in compromised ciliary structures and sensory functions, and abnormal lipid accumulation. Analyses in different mutant backgrounds further suggest that DYF-11 functions as a novel component of IFT subcomplex B. Consistent with an evolutionarily conserved cilia-associated role, mammalian MIP-T3 localizes to basal bodies and cilia, and zebrafish mipt3 functions synergistically with the Bardet-Biedl syndrome protein Bbs4 to ensure proper gastrulation, a key cilium- and basal body-dependent developmental process. Our findings therefore implicate MIP-T3 in a previously unknown but critical role in cilium biogenesis and further highlight the emerging role of this organelle in vertebrate development

    Outcomes of pediatric patients with therapy-related myeloid neoplasms

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    Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs
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