HAM-5 functions as a MAP kinase scaffold during cell fusion in Neurospora crassa.

Cell fusion in genetically identical Neurospora crassa germlings and in hyphae is a highly regulated process involving the activation of a conserved MAP kinase cascade that includes NRC-1, MEK-2 and MAK-2. During chemotrophic growth in germlings, the MAP kinase cascade members localize to conidial anastomosis tube (CAT) tips every ∼8 minutes, perfectly out of phase with another protein that is recruited to the tip: SOFT, a recently identified scaffold for the MAK-1 MAP kinase pathway in Sordaria macrospora. How the MAK-2 oscillation process is initiated, maintained and what proteins regulate the MAP kinase cascade is currently unclear. A global phosphoproteomics approach using an allele of mak-2 (mak-2Q100G) that can be specifically inhibited by the ATP analog 1NM-PP1 was utilized to identify MAK-2 kinase targets in germlings that were potentially involved in this process. One such putative target was HAM-5, a protein of unknown biochemical function. Previously, Δham-5 mutants were shown to be deficient for hyphal fusion. Here we show that HAM-5-GFP co-localized with NRC-1, MEK-2 and MAK-2 and oscillated with identical dynamics from the cytoplasm to CAT tips during chemotropic interactions. In the Δmak-2 strain, HAM-5-GFP localized to punctate complexes that did not oscillate, but still localized to the germling tip, suggesting that MAK-2 activity influences HAM-5 function/localization. However, MAK-2-GFP showed cytoplasmic and nuclear localization in a Δham-5 strain and did not localize to puncta. Via co-immunoprecipitation experiments, HAM-5 was shown to physically interact with NRC-1, MEK-2 and MAK-2, suggesting that it functions as a scaffold/transport hub for the MAP kinase cascade members for oscillation and chemotropic interactions during germling and hyphal fusion in N. crassa. The identification of HAM-5 as a scaffold-like protein will help to link the activation of MAK-2 cascade to upstream factors and proteins involved in this intriguing process of fungal communication

A Viral Ubiquitin Ligase Has Substrate Preferential SUMO Targeted Ubiquitin Ligase Activity that Counteracts Intrinsic Antiviral Defence

Intrinsic antiviral resistance represents the first line of intracellular defence against virus infection. During herpes simplex virus type-1 (HSV-1) infection this response can lead to the repression of viral gene expression but is counteracted by the viral ubiquitin ligase ICP0. Here we address the mechanisms by which ICP0 overcomes this antiviral response. We report that ICP0 induces the widespread proteasome-dependent degradation of SUMO-conjugated proteins during infection and has properties related to those of cellular SUMO-targeted ubiquitin ligases (STUbLs). Mutation of putative SUMO interaction motifs within ICP0 not only affects its ability to degrade SUMO conjugates, but also its capacity to stimulate HSV-1 lytic infection and reactivation from quiescence. We demonstrate that in the absence of this viral countermeasure the SUMO conjugation pathway plays an important role in mediating intrinsic antiviral resistance and the repression of HSV-1 infection. Using PML as a model substrate, we found that whilst ICP0 preferentially targets SUMO-modified isoforms of PML for degradation, it also induces the degradation of PML isoform I in a SUMO modification-independent manner. PML was degraded by ICP0 more rapidly than the bulk of SUMO-modified proteins in general, implying that the identity of a SUMO-modified protein, as well as the presence of SUMO modification, is involved in ICP0 targeting. We conclude that ICP0 has dual targeting mechanisms involving both SUMO- and substrate-dependent targeting specificities in order to counteract intrinsic antiviral resistance to HSV-1 infection

Trophic Garnishes: Cat–Rat Interactions in an Urban Environment

BACKGROUND:Community interactions can produce complex dynamics with counterintuitive responses. Synanthropic community members are of increasing practical interest for their effects on biodiversity and public health. Most studies incorporating introduced species have been performed on islands where they may pose a risk to the native fauna. Few have examined their interactions in urban environments where they represent the majority of species. We characterized house cat (Felis catus) predation on wild Norway rats (Rattus norvegicus), and its population effects in an urban area as a model system. Three aspects of predation likely to influence population dynamics were examined; the stratum of the prey population killed by predators, the intensity of the predation, and the size of the predator population. METHODOLOGY/PRINCIPAL FINDINGS:Predation pressure was estimated from the sizes of the rat and cat populations, and the characteristics of rats killed in 20 alleys. Short and long term responses of rat population to perturbations were examined by removal trapping. Perturbations removed an average of 56% of the rats/alley but had no negative long-term impact on the size of the rat population (49.6+/-12.5 rats/alley and 123.8+/-42.2 rats/alley over two years). The sizes of the cat population during two years (3.5 animals/alley and 2.7 animals/alley) also were unaffected by rat population perturbations. Predation by cats occurred in 9/20 alleys. Predated rats were predominantly juveniles and significantly smaller (144.6 g+/-17.8 g) than the trapped rats (385.0 g+/-135.6 g). Cats rarely preyed on the larger, older portion of the rat population. CONCLUSIONS/SIGNIFICANCE:The rat population appears resilient to perturbation from even substantial population reduction using targeted removal. In this area there is a relatively low population density of cats and they only occasionally prey on the rat population. This occasional predation primarily removes the juvenile proportion of the rat population. The top predator in this urban ecosystem appears to have little impact on the size of the prey population, and similarly, reduction in rat populations doesn't impact the size of the cat population. However, the selected targeting of small rats may locally influence the size structure of the population which may have consequences for patterns of pathogen transmission

Characterization of Burkholderia rhizoxinica and B. endofungorum Isolated from Clinical Specimens

Eight isolates submitted to CDC from 1989 to 2006 from clinical specimens were initially identified as members of the genus Burkholderia based on preliminary cellular fatty acid analysis and/or 16S rRNA gene sequencing. With the recent descriptions of the new species B. rhizoxinica and B. endofungorum, which are considered endosymbiotic bacteria in Rhizopus microsporus fungi, we now identify seven of these clinical isolates as B. rhizoxinica and one as B. endofungorum based on biochemical testing, 16s rRNA, and DNA-DNA hybridization results. We also further characterize these isolates by assessing toxin production and/or by multiple locus sequence typing

Exploring the Relationship Between Online Social Network Site Usage and the Impact on Quality of Life for Older and Younger Users: An Interaction Analysis

This is an Open Access journal. ©Darren Quinn, Liming Chen, Maurice D Mulvenna, Raymond Bond. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 29.09.2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited

A waitlist-controlled trial of group cognitive behavioural therapy for depression and anxiety in Parkinson’s disease

Background: The aim of this study was to evaluate the efficacy of a group Cognitive Behavioural Therapy (CBT) treatment for depression and anxiety in Parkinson’s disease (PD). Methods: A waitlist-controlled trial design was used. Eighteen adults with PD and a comorbid DSM-IV-TR diagnosis of depression and/or anxiety were randomised to either Intervention (8-week group CBT treatment) or Waitlist (8-week clinical monitoring preceding treatment). The Depression, Anxiety, Stress Scale-21 (DASS-21) was the primary outcome. Assessments were completed at Time 1 (pretreatment), Time 2 (posttreatment/post-waitlist) and 1-month and 6-month follow-ups. Results: At Time 2, participants who received CBT reported greater reductions in depression (Mchange = -2.45) than Waitlist participants (Mchange = .29) and this effect was large, d = 1.12, p = .011. Large secondary effects on anxiety were also observed for CBT participants, d = .89, p = .025. All treatment gains were maintained and continued to improve during the follow-up period. At 6-month follow-up, significant and large effects were observed for both depression (d = 2.07) and anxiety (d = 2.26). Conclusions: Group CBT appears to be an efficacious treatment approach for depression and anxiety in PD however further controlled trials with larger numbers of participants are required

Apparent temperature and acute myocardial infarction hospital admissions in Copenhagen, Denmark: a case-crossover study

<p>Abstract</p> <p>Background</p> <p>The influence of temperature on acute myocardial infarction (AMI) has not been investigated as extensively as the effects of broader outcomes of morbidity and mortality. Sixteen studies reported inconsistent results and two considered confounding by air pollution. We addressed some of the methodological limitations of the previous studies in this study.</p> <p>Methods</p> <p>This is the first study of the association between the daily 3-hour maximum apparent temperature (Tapp_max) and AMI hospital admissions in Copenhagen. The study period covered 1 January 1999-31 December 2006, stratified in warm (April - September) and cold (October - March) periods. A case-crossover epidemiology study design was applied. Models were adjusted for public holidays and influenza, confounding by PM₁₀, NO₂and CO was investigated, the lag and non-linear effects of Tapp_maxwas examined, effect modification by age, sex and SES was explored, and the results of the case-crossover models were compared to those of the generalised additive Poisson time-series and generalised estimating equation models.</p> <p>Results</p> <p>14 456 AMI hospital admissions (12 995 people) occurred during the study period. For an inter-quartile range (6 or 7°C) increase in the 5-day cumulative average of Tapp_max, a 4% (95% CI:-2%; 10%) and 9% (95% CI: 3%; 14%) decrease in the AMI admission rate was observed in the warm and cold periods, respectively. The 19-65 year old group, men and highest SES group seemed to be more susceptible in the cold period.</p> <p>Conclusion</p> <p>An increase in Tapp_maxis associated with a decrease in AMI admissions during the colder months.</p

Dwelling in Strangeness: accounts of the Kingsley Hall Community, London (1965-1970)

This article explores archival accounts of the experimental community, Kingsley Hall (1965-70), established by R. D. Laing, the radical Scottish psychiatrist. The paper contributes to renewed interest in Kingsley Hall, R. D. Laing's radical psychiatry and UK counterculture. Archival sources enable not only the further exploration of already known figures but also let us hear previously unheard voices. Following a discussion of archival materials, the Hall is analyzed thematically and historically as (i) an inner spaceship; (ii) an embattled middle-class countercultural plantation; (iii) a site of spiritual renewal and development; (iv) a single-building arts colony; and (v) a countercultural experiment. Finally, it is argued that with re-evaluation of 1960s and 1970s counterculture now underway on the Left, the Hall’s experiment in Laingian countercultural psychiatry—as we may fittingly call it—may yet inform future radical projects (in mental health and beyond)

Smoking Comorbidity in Alcoholism: Neurobiological and Neurocognitive Consequences

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65249/1/j.1530-0277.2006.00034.x.pd