Herpesviruses that Infect Fish

Herpesviruses are host specific pathogens that are widespread among vertebrates. Genome sequence data demonstrate that most herpesviruses of fish and amphibians are grouped together (family Alloherpesviridae) and are distantly related to herpesviruses of reptiles, birds and mammals (family Herpesviridae). Yet, many of the biological processes of members of the order Herpesvirales are similar. Among the conserved characteristics are the virion structure, replication process, the ability to establish long term latency and the manipulation of the host immune response. Many of the similar processes may be due to convergent evolution. This overview of identified herpesviruses of fish discusses the diseases that alloherpesviruses cause, the biology of these viruses and the host-pathogen interactions. Much of our knowledge on the biology of Alloherpesvirdae is derived from research with two species: Ictalurid herpesvirus 1 (channel catfish virus) and Cyprinid herpesvirus 3 (koi herpesvirus)

Deep transcranial magnetic stimulation for the treatment of auditory hallucinations: a preliminary open-label study

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a chronic and disabling disease that presents with delusions and hallucinations. Auditory hallucinations are usually expressed as voices speaking to or about the patient. Previous studies have examined the effect of repetitive transcranial magnetic stimulation (TMS) over the temporoparietal cortex on auditory hallucinations in schizophrenic patients. Our aim was to explore the potential effect of deep TMS, using the H coil over the same brain region on auditory hallucinations.</p> <p>Patients and methods</p> <p>Eight schizophrenic patients with refractory auditory hallucinations were recruited, mainly from Beer Ya'akov Mental Health Institution (Tel Aviv university, Israel) ambulatory clinics, as well as from other hospitals outpatient populations. Low-frequency deep TMS was applied for 10 min (600 pulses per session) to the left temporoparietal cortex for either 10 or 20 sessions. Deep TMS was applied using Brainsway's H1 coil apparatus. Patients were evaluated using the Auditory Hallucinations Rating Scale (AHRS) as well as the Scale for the Assessment of Positive Symptoms scores (SAPS), Clinical Global Impressions (CGI) scale, and the Scale for Assessment of Negative Symptoms (SANS).</p> <p>Results</p> <p>This preliminary study demonstrated a significant improvement in AHRS score (an average reduction of 31.7% ± 32.2%) and to a lesser extent improvement in SAPS results (an average reduction of 16.5% ± 20.3%).</p> <p>Conclusions</p> <p>In this study, we have demonstrated the potential of deep TMS treatment over the temporoparietal cortex as an add-on treatment for chronic auditory hallucinations in schizophrenic patients. Larger samples in a double-blind sham-controlled design are now being preformed to evaluate the effectiveness of deep TMS treatment for auditory hallucinations.</p> <p>Trial registration</p> <p>This trial is registered with clinicaltrials.gov (identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00564096">NCT00564096</a>).</p

Deep transcranial magnetic stimulation add-on for the treatment of auditory hallucinations: a double-blind study

<p>Abstract</p> <p>Background</p> <p>About 25% of schizophrenia patients with auditory hallucinations are refractory to pharmacotherapy and electroconvulsive therapy. We conducted a deep transcranial magnetic stimulation (TMS) pilot study in order to evaluate the potential clinical benefit of repeated left temporoparietal cortex stimulation in these patients. The results were encouraging, but a sham-controlled study was needed to rule out a placebo effect.</p> <p>Methods</p> <p>A total of 18 schizophrenic patients with refractory auditory hallucinations were recruited, from Beer Yaakov MHC and other hospitals outpatient populations. Patients received 10 daily treatment sessions with low-frequency (1 Hz for 10 min) deep TMS applied over the left temporoparietal cortex, using the H1 coil at the intensity of 110% of the motor threshold. Procedure was either real or sham according to patient randomization. Patients were evaluated via the Auditory Hallucinations Rating Scale, Scale for the Assessment of Positive Symptoms-Negative Symptoms, Clinical Global Impressions, and Quality of Life Questionnaire.</p> <p>Results</p> <p>In all, 10 patients completed the treatment (10 TMS sessions). Auditory hallucination scores of both groups improved; however, there was no statistical difference in any of the scales between the active and the sham treated groups.</p> <p>Conclusions</p> <p>Low-frequency deep TMS to the left temporoparietal cortex using the protocol mentioned above has no statistically significant effect on auditory hallucinations or the other clinical scales measured in schizophrenic patients.</p> <p>Trial Registration</p> <p><b>Clinicaltrials.gov identifier: </b><a href="http://www.clinicaltrials.gov/ct2/show/NCT00564096">NCT00564096</a>.</p

Global Functional Connectivity Deficits in Schizophrenia Depend on Behavioral State

Schizophrenia is a devastating psychiatric illness characterized by deterioration of cognitive and emotional processing. It has been hypothesized that aberrant cortical connectivity is implicated in the disease (Friston, 1998), yet previous studies of functional connectivity (FC) in schizophrenia have shown mixed results (Garrity et al., 2007; Jafri et al., 2008; Lynall et al., 2010). We measured FC using fMRI in human schizophrenia patients and healthy controls during two different tasks and a rest condition, and constructed a voxel-based global FC index. We found a striking FC decrease in patients compared with controls. In the task conditions, relatively weaker FC was specific to regions of cortex not active during the task. In the rest condition, the FC difference between patients and controls was larger and allowed a case-by-case separation between individuals of the two groups. The results suggest that the relative reduction of FC in schizophrenia is dependent on the state of cortical activity, with voxels not activated by the task showing higher levels of FC deficiency. This novel finding may shed light on previous reports of FC in schizophrenia. Whether this neural characteristic is related to the development of the disorder remains to be established

Regulatory module involving FGF13, miR-504, and p53 regulates ribosomal biogenesis and supports cancer cell survival

The microRNA miR-504 targets TP53 mRNA encoding the p53 tumor suppressor. miR-504 resides within the fibroblast growth factor 13 (FGF13) gene, which is overexpressed in various cancers. We report that the FGF13 locus, comprising FGF13 and miR-504, is transcriptionally repressed by p53, defining an additional negative feedback loop in the p53 network. Furthermore, we show that FGF13 1A is a nucleolar protein that represses ribosomal RNA transcription and attenuates protein synthesis. Importantly, in cancer cells expressing high levels of FGF13, the depletion of FGF13 elicits increased proteostasis stress, associated with the accumulation of reactive oxygen species and apoptosis. Notably, stepwise neoplastic transformation is accompanied by a gradual increase in FGF13 expression and increased dependence on FGF13 for survival ("nononcogene addiction"). Moreover, FGF13 overexpression enables cells to cope more effectively with the stress elicited by oncogenic Ras protein. We propose that, in cells in which activated oncogenes drive excessive protein synthesis, FGF13 may favor survival by maintaining translation rates at a level compatible with the protein quality- control capacity of the cell. Thus, FGF13 may serve as an enabler, allowing cancer cells to evade proteostasis stress triggered by oncogene activation

Three year naturalistic outcome study of panic disorder patients treated with paroxetine

BACKGROUND: This naturalistic open label follow-up study had three objectives: 1) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment 2) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia. 3) To observe paroxetine's tolerability over a 24 month period. METHODS: 143 patients with panic disorder (PD), with or without agoraphobia, successfully finished a short-term (ie 12 week) trial of paroxetine treatment. All patients then continued to receive paroxetine maintenance therapy for a total of 12 months. At the end of this period, 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase. The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored, as in the first group, for another year while medication-free. The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a randomized manner. RESULTS: Only 21 of 143 patients (14%) relapsed during the one year medication discontinuation follow-up phase. There were no significant differences in relapse rates between the patients who received intermediate-term (up to 12 months) paroxetine and those who chose the long-term course (24 month paroxetine treatment). 43 patients (30.1%) reported sexual dysfunction. The patients exhibited an average weight gain of 5.06 kg. All patients who eventually relapsed demonstrated significantly greater weight increase (7.3 kg) during the treatment phase. CONCLUSIONS: The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation. Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment

Half a century of amyloids: past, present and future

Amyloid diseases are global epidemics with profound health, social and economic implications and yet remain without a cure. This dire situation calls for research into the origin and pathological manifestations of amyloidosis to stimulate continued development of new therapeutics. In basic science and engineering, the cross-ß architecture has been a constant thread underlying the structural characteristics of pathological and functional amyloids, and realizing that amyloid structures can be both pathological and functional in nature has fuelled innovations in artificial amyloids, whose use today ranges from water purification to 3D printing. At the conclusion of a half century since Eanes and Glenner's seminal study of amyloids in humans, this review commemorates the occasion by documenting the major milestones in amyloid research to date, from the perspectives of structural biology, biophysics, medicine, microbiology, engineering and nanotechnology. We also discuss new challenges and opportunities to drive this interdisciplinary field moving forward. This journal i

Functional characterization of the p53 “mutome”

Phenotypic characterization of mutations in the tumor protein p53 (TP53) gene has so far focused on a handful of relatively frequent “hotspot” mutations, accounting for only ~ 30% of cases. We expanded the scope and quantitatively measured the impact of thousands of distinct TP53 mutations in vitro and in vivo, providing insights into the connections between structure, function, evolutionary conservation and clinical impact

Characterization of a Novel Virus Causing a Lethal Disease in Carp and Koi

Since 1998 a lethal disease of carp and ornamental koi (Cyprinus carpio) has afflicted fisheries in North America, Europe, and Asia, causing severe economic losses to the fish farming industry. This review summarizes the isolation and identification of the disease-causing agent and describes the currently known molecular characteristics of this newly isolated virus, distinguishing it from other known large DNA viruses. In addition, we summarize the clinical and histopathological manifestations of the disease. Providing information on the immune response to this virus and evaluating the available means of diagnosis and protection should help to reduce the damage induced by this disease. This review does not discuss the economic aspects of the disease or the debate on whether the disease should be registered; both of these issues were recently reviewed in detail (O. L. M. Haenen, K. Way, S. M. Bergmann, and E. Ariel, Bull. Eur. Assoc. Fish Pathol. 24:293-307, 2004; D. Pokorova, T. Vesely, V. Piackova, S. Reschova, and J. Hulova, Vet. Med. Czech. 50:139-147, 2005)