Validation of the Spanish version of the borderline symptom list, short form (BSL-23)

Background: The Borderline Symptom List-23 (BSL-23) is a reliable and valid self-report instrument for assessing Borderline Personality Disorder (BPD) severity. The psychometric properties of the original version have proven to be adequate. The aim of the present study was to validate the Spanish language version of the BSL-23. Methods: The BSL-23 was administered to 240 subjects with BPD diagnosis. Factor structure, reliability, test-retest stability, convergent validity, and sensitivity to change were analyzed. Results: The Spanish version of the BSL-23 replicates the one-factor structure of the original version. The scale has high reliability (Cronbach's alpha=.949), as well as good test-retest stability, which was checked in a subsample (n=74; r=.734; p<.01). The Spanish BSL-23 shows moderate to high correlations with depressive symptomatology, state and trait anxiety, hostility and impulsivity scores and BPD measures. The Spanish BSL-23 is able to discriminate among different levels of BPD severity and shows satisfactory sensitivity to change after treatment, which was verified by assessing change before and after 12 group sessions of Dialectical Behavioral Therapy in a subgroup of 31 subjects. Conclusions: Similar to the original BSL-23, the Spanish BSL-23 is a reliable and valid instrument for assessing BPD severity and sensitivity to change

Cultural trauma, counter-narratives, and dialogical intellectuals: the works of Murakami Haruki and Mori Tatsuya in the context of the Aum affair

In this article, we offer a new conceptualization of intellectuals as carriers of cultural trauma through a case study of the Aum Affair, a series of crimes and terrorist attacks committed by the Japanese new religious movement Aum Shinrikyō. In understanding the performative roles intellectuals play in trauma construction, we offer a new dichotomy between “authoritative intellectuals,” who draw on their privileged parcours and status to impose a distinct trauma narrative, and “dialogical intellectuals,” who engage with local actors dialogically to produce polyphonic and open-ended trauma narratives. We identify three dimensions of dialogical intellectual action: firstly, the intellectuals may be involved in dialogue with local participants; secondly, the intellectual products themselves may be dialogical in content; and thirdly, there might be a concerted effort on the part of the intellectuals to record and to disseminate dialogue between local participants. In the context of the Aum Affair, we analyze the works of Murakami Haruki and Mori Tatsuya as dialogical intellectuals while they sought, with the help of local actors’ experiences, to challenge and to alter the orthodox trauma narrative of Aum Shinrikyō as exclusively a social evil external to Japanese society and an enemy to be excluded from it. Towards the end of the article, we discuss the broader significance of this case study and suggest that in light of recent societal and technological developments, the role and scope of dialogical intellectuals as carriers of trauma are changing and possibly expanding

Trafficking through COPII Stabilises Cell Polarity and Drives Secretion during Drosophila Epidermal Differentiation

BACKGROUND: The differentiation of an extracellular matrix (ECM) at the apical side of epithelial cells implies massive polarised secretion and membrane trafficking. An epithelial cell is hence engaged in coordinating secretion and cell polarity for a correct and efficient ECM formation. PRINCIPAL FINDINGS: We are studying the molecular mechanisms that Drosophila tracheal and epidermal cells deploy to form their specific apical ECM during differentiation. In this work we demonstrate that the two genetically identified factors haunted and ghost are essential for polarity maintenance, membrane topology as well as for secretion of the tracheal luminal matrix and the cuticle. We show that they code for the Drosophila COPII vesicle-coating components Sec23 and Sec24, respectively, that organise vesicle transport from the ER to the Golgi apparatus. CONCLUSION: Taken together, epithelial differentiation during Drosophila embryogenesis is a concerted action of ECM formation, plasma membrane remodelling and maintenance of cell polarity that all three rely mainly, if not absolutely, on the canonical secretory pathway from the ER over the Golgi apparatus to the plasma membrane. Our results indicate that COPII vesicles constitute a central hub for these processes

A “Coiled-Coil” Motif Is Important for Oligomerization and DNA Binding Properties of Human Cytomegalovirus Protein UL77

Human cytomegalovirus (HCMV) UL77 gene encodes the essential protein UL77, its function is characterized in the present study. Immunoprecipitation identified monomeric and oligomeric pUL77 in HCMV infected cells. Immunostaining of purified virions and subviral fractions showed that pUL77 is a structural protein associated with capsids. In silico analysis revealed the presence of a coiled-coil motif (CCM) at the N-terminus of pUL77. Chemical cross-linking of either wild-type pUL77 or CCM deletion mutant (pUL77ΔCCM) implicated that CCM is critical for oligomerization of pUL77. Furthermore, co-immunoprecipitations of infected and transfected cells demonstrated that pUL77 interacts with the capsid-associated DNA packaging motor components, pUL56 and pUL104, as well as the major capsid protein. The ability of pUL77 to bind dsDNA was shown by an in vitro assay. Binding to certain DNA was further confirmed by an assay using biotinylated 36-, 250-, 500-, 1000-meric dsDNA and 966-meric HCMV-specific dsDNA designed for this study. The binding efficiency (BE) was determined by image processing program defining values above 1.0 as positive. While the BE of the pUL56 binding to the 36-mer bio-pac1 containing a packaging signal was 10.0±0.63, the one for pUL77 was only 0.2±0.03. In contrast to this observation the BE of pUL77 binding to bio-500 bp or bio-1000 bp was 2.2±0.41 and 4.9±0.71, respectively. By using pUL77ΔCCM it was demonstrated that this protein could not bind to dsDNA. These data indicated that pUL77 (i) could form homodimers, (ii) CCM of pUL77 is crucial for oligomerization and (iii) could bind to dsDNA in a sequence independent manner

Quantitative PCR reveals strong spatial and temporal variation of the wasting disease pathogen, Labyrinthula zosterae in northern European eelgrass (Zostera marina) beds

Seagrass beds are the foundation species of functionally important coastal ecosystems worldwide. The world’s largest losses of the widespread seagrass Zostera marina (eelgrass) have been reported as a consequence of wasting disease, an infection with the endophytic protist Labyrinthula zosterae. During one of the most extended epidemics in the marine realm, ~90% of East and Western Atlantic eelgrass beds died-off between 1932 and 1934. Today, small outbreaks continue to be reported, but the current extent of L. zosterae in European meadows is completely unknown. In this study we quantify the abundance and prevalence of the wasting disease pathogen among 19 Z. marina populations in northern European coastal waters, using quantitative PCR (QPCR) with primers targeting a species specific portion of the internally transcribed spacer (ITS1) of L. zosterae. Spatially, we found marked variation among sites with abundances varying between 0 and 126 cells mg−1 Z. marina dry weight (mean: 5.7 L. zosterae cells mg−1 Z. marina dry weight ±1.9 SE) and prevalences ranged from 0–88.9%. Temporarily, abundances varied between 0 and 271 cells mg−1 Z. marina dry weight (mean: 8.5±2.6 SE), while prevalences ranged from zero in winter and early spring to 96% in summer. Field concentrations accessed via bulk DNA extraction and subsequent QPCR correlated well with prevalence data estimated via isolation and cultivation from live plant tissue. L. zosterae was not only detectable in black lesions, a sign of Labyrinthula-induced necrosis, but also occurred in green, apparently healthy tissue. We conclude that L. zosterae infection is common (84% infected populations) in (northern) European eelgrass populations with highest abundances during the summer months. In the light of global climate change and increasing rate of marine diseases our data provide a baseline for further studies on the causes of pathogenic outbreaks of L. zosterae

Duox, Flotillin-2, and Src42A Are Required to Activate or Delimit the Spread of the Transcriptional Response to Epidermal Wounds in Drosophila

The epidermis is the largest organ of the body for most animals, and the first line of defense against invading pathogens. A breach in the epidermal cell layer triggers a variety of localized responses that in favorable circumstances result in the repair of the wound. Many cellular and genetic responses must be limited to epidermal cells that are close to wounds, but how this is regulated is still poorly understood. The order and hierarchy of epidermal wound signaling factors are also still obscure. The Drosophila embryonic epidermis provides an excellent system to study genes that regulate wound healing processes. We have developed a variety of fluorescent reporters that provide a visible readout of wound-dependent transcriptional activation near epidermal wound sites. A large screen for mutants that alter the activity of these wound reporters has identified seven new genes required to activate or delimit wound-induced transcriptional responses to a narrow zone of cells surrounding wound sites. Among the genes required to delimit the spread of wound responses are Drosophila Flotillin-2 and Src42A, both of which are transcriptionally activated around wound sites. Flotillin-2 and constitutively active Src42A are also sufficient, when overexpressed at high levels, to inhibit wound-induced transcription in epidermal cells. One gene required to activate epidermal wound reporters encodes Dual oxidase, an enzyme that produces hydrogen peroxide. We also find that four biochemical treatments (a serine protease, a Src kinase inhibitor, methyl-ß-cyclodextrin, and hydrogen peroxide) are sufficient to globally activate epidermal wound response genes in Drosophila embryos. We explore the epistatic relationships among the factors that induce or delimit the spread of epidermal wound signals. Our results define new genetic functions that interact to instruct only a limited number of cells around puncture wounds to mount a transcriptional response, mediating local repair and regeneration

Design of a multicentered randomized controlled trial on the clinical and cost effectiveness of schema therapy for personality disorders

<p>Abstract</p> <p>Background</p> <p>Despite international guidelines describing psychotherapy as first choice for people with personality disorders (PDs), well-designed research on the effectiveness and cost-effectiveness of psychotherapy for PD is scarce. Schema therapy (ST) is a specific form of psychological treatment that proved to be effective for borderline PD. Randomized controlled studies on the effectiveness of ST for other PDs are lacking. Another not yet tested new specialized treatment is Clarification Oriented Psychotherapy (COP). The aim of this project is to perform an effectiveness study as well as an economic evaluation study (cost effectiveness as well as cost-utility) comparing ST versus COP versus treatment as usual (TAU). In this study, we focus on avoidant, dependent, obsessive-compulsive, paranoid, histrionic and narcissistic PD.</p> <p>Methods/Design</p> <p>In a multicentered randomized controlled trial, ST, and COP as an extra experimental condition, are compared to TAU. Minimal 300 patients are recruited in 12 mental health institutes throughout the Netherlands, and receive an extensive screening prior to enrolment in the study. When eligible, they are randomly assigned to one of the intervention groups. An economic evaluation and a qualitative research study on patient and therapist perspectives on ST are embedded in this trial. Outcome assessments (both for clinical effectiveness and economic evaluation) take place at 6,12,18,24 and 36 months after start of treatment. Primary outcome is recovery from PD; secondary measures include general psychopathological complaints, social functioning and quality of life. Data for the cost-effectiveness and cost-utility analyses are collected by using a retrospective cost interview. Information on patient and therapist perspectives is gathered using in-depth interviews and focus groups, and focuses on possible helpful and impeding aspects of ST.</p> <p>Discussion</p> <p>This trial is the first to compare ST and COP head-to-head with TAU for people with a cluster C, paranoid, histrionic and/or narcissistic PD. By combining clinical effectiveness data with an economic evaluation and with direct information from primary stakeholders, this trial offers a complete and thorough view on ST as a contribution to the improvement of treatment for this PD patient group.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=566">NTR566</a></p

Evidence for 'critical slowing down' in seagrass:a stress gradient experiment at the southern limit of its range

The theory of critical slowing down, i.e. the increasing recovery times of complex systems close to tipping points, has been proposed as an early warning signal for collapse. Empirical evidence for the reality of such warning signals is still rare in ecology. We studied this on Zostera noltii intertidal seagrass meadows at their southern range limit, the Banc d'Arguin, Mauritania. We analyse the environmental covariates of recovery rates using structural equation modelling (SEM), based on an experiment in which we assessed whether recovery after disturbances (i.e. seagrass & infauna removal) depends on stress intensity (increasing with elevation) and disturbance patch size (1 m(2) vs. 9 m(2)). The SEM analyses revealed that higher biofilm density and sediment accretion best explained seagrass recovery rates. Experimental disturbances were followed by slow rates of recovery, regrowth occurring mainly in the coolest months of the year. Macrofauna recolonisation lagged behind seagrass recovery. Overall, the recovery rate was six times slower in the high intertidal zone than in the low zone. The large disturbances in the low zone recovered faster than the small ones in the high zone. This provides empirical evidence for critical slowing down with increasing desiccation stress in an intertidal seagrass system

Rate-dependent Ca2+ signalling underlying the force-frequency response in rat ventricular myocytes: A coupled electromechanical modeling study

Rate-dependent effects on the Ca2+ sub-system in a rat ventricular myocyte are investigated. Here, we employ a deterministic mathematical model describing various Ca2+ signalling pathways under voltage clamp (VC) conditions, to better understand the important role of calmodulin (CaM) in modulating the key control variables Ca2+/calmodulin-dependent protein kinase-II (CaMKII), calcineurin (CaN), and cyclic adenosine monophosphate (cAMP) as they affect various intracellular targets. In particular, we study the frequency dependence of the peak force generated by the myofilaments, the force-frequency response (FFR). Our cell model incorporates frequency-dependent CaM-mediated spatially heterogenous interaction of CaMKII and CaN with their principal targets (dihydropyridine (DHPR) and ryanodine (RyR) receptors and the SERCA pump). It also accounts for the rate-dependent effects of phospholamban (PLB) on the SERCA pump; the rate-dependent role of cAMP in up-regulation of the L-type Ca2+ channel (ICa;L); and the enhancement in SERCA pump activity via phosphorylation of PLB.Our model reproduces positive peak FFR observed in rat ventricular myocytes during voltage-clamp studies both in the presence/absence of cAMP mediated -adrenergic stimulation. This study provides quantitative insight into the rate-dependence of Ca2+-induced Ca2+-release (CICR) by investigating the frequency-dependence of the trigger current (ICa;L) and RyR-release. It also highlights the relative role of the sodium-calcium exchanger (NCX) and the SERCA pump at higher frequencies, as well as the rate-dependence of sarcoplasmic reticulum (SR) Ca2+ content. A rigorous Ca2+ balance imposed on our investigation of these Ca2+ signalling pathways clarifies their individual roles. Here, we present a coupled electromechanical study emphasizing the rate-dependence of isometric force developed and also investigate the temperature-dependence of FFR. Our model provides mechanistic biophysically based explanations for the rate-dependence of CICR, generating useful and testable hypotheses. Although rat ventricular myocytes exhibit a positive peak FFR in the presence/absence of beta-adrenergic stimulation, they show a characteristic increase in the positive slope in FFR due to the presence of Norepinephrine or Isoproterenol. Our study identifies cAMP-mediated stimulation, and rate-dependent CaMKII-mediated up-regulation of ICa;L as the key mechanisms underlying the aforementioned positive FFR

Low genotypic diversity and long-term ecological decline in a spatially structured seagrass population

In isolated or declining populations, viability may be compromised further by loss of genetic diversity. Therefore, it is important to understand the relationship between long-term ecological trajectories and population genetic structure. However, opportunities to combine these types of data are rare, especially in natural systems. Using an existing panel of 15 microsatellites, we estimated allelic diversity in seagrass, Zostera marina, at five sites around the Isles of Scilly Special Area of Conservation, UK, in 2010 and compared this to 23 years of annual ecological monitoring (1996–2018). We found low diversity and long-term declines in abundance in this relatively pristine but isolated location. Inclusion of the snapshot of genotypic, but less-so genetic, diversity improved prediction of abundance trajectories; however, this was spatial scale-dependent. Selection of the appropriate level of genetic organization and spatial scale for monitoring is, therefore, important to identify drivers of eco-evolutionary dynamics. This has implications for the use of population genetic information in conservation, management, and spatial planning