Modulating Affect, Cognition, and Behavior – Prospects of Deep Brain Stimulation for Treatment-Resistant Psychiatric Disorders

Most patients suffering from psychiatric disorders respond to combinations of psycho- and psychopharmacotherapy; however there are patients who profit little if anything even after many years of treatment. Since about a decade different modalities of targeted neuromodulation – among them most prominently – deep brain stimulation (DBS) – are being actively researched as putative approaches to very treatment-resistant forms of those disorders. Recently, promising pilot data have been reported both for major depression (MD) and obsessive–compulsive disorder (OCD). Given the fact that patients included in DBS studies had been treated unsuccessfully for many years with conventional treatment methods, renders these findings remarkable. Remarkable is the fact, that in case of the long-term studies underway for MD, patients show a stable response. This gives hope to a substantial percentage of therapy–resistant psychiatric patients requiring new therapy approaches. There are no fundamental ethic objections to its use in psychiatric disorders, but until substantial clinical data is available, mandatory standards are needed. DBS is a unique and very promising method for the treatment of therapy–resistant psychiatric patients. The method allows manipulating pathological neuronal networks in a very precise way

Suicide reporting in the Swiss print media: Frequency, form and content of articles

All the Swiss newspapers were screened for the target words ‘suicide' and ‘attempted suicide' and all relevant articles were analysed for form and content over a period of 8 months. In 151 out of 208 articles suiclde/attempted suicide was the major topic. Large differences between the newspapers regarding the frequency and format of the articles (e.g. placement on front page) were found. In a few newspapers with a large circulation suicide is clearly treated as a major topic of news sensation. The majority of articles reported cases of completed suicide, mainly shooting and hanging by young persons. Attempted suicide was only reported for persons with celebrity status. This survey shows that there is reason for concern in view of the danger of imitation effect

PSYCHIATRY

www,elsevier.com/locate/psychre

HIV-Specific Cellular Immune Response Is Inversely Correlated with Disease Progression as Defined by Decline of CD4+ T Cells in Relation to HIV RNA Load

The average time between infection with human immunodeficiency virus (HIV) and development of acquired immune deficiency syndrome is ∼8 years. However, progression rates vary widely, depending on several determinants, including HIV-specific immunity, host genetic factors, and virulence of the infecting strain. In untreated HIV-infected patients with different progression rates, we examined HIV-specific T cell responses in combination with host genetic markers, such as chemokine/chemokine-receptor (CCR) polymorphisms and human leukocyte antigen (HLA) genotypes. HIV-specific CD4+ T cell responses and, to a lesser extent, HIVspecific CD8+ T cell responses were inversely correlated with progression rate. Slower progression was not related to polymorphisms in CCR genes, HLA genotype, or GB virus C coinfection. These data suggest that HIV-specific T cell responses are involved in protecting the host from disease progressio

A Role for Caveolin and the Urokinase Receptor in Integrin-mediated Adhesion and Signaling

The assembly of signaling molecules surrounding the integrin family of adhesion receptors remains poorly understood. Recently, the membrane protein caveolin was found in complexes with β1 integrins. Caveolin binds cholesterol and several signaling molecules potentially linked to integrin function, e.g., Src family kinases, although caveolin has not been directly implicated in integrin-dependent adhesion. Here we report that depletion of caveolin by antisense methodology in kidney 293 cells disrupts the association of Src kinases with β1 integrins resulting in loss of focal adhesion sites, ligand-induced focal adhesion kinase (FAK) phosphorylation, and adhesion. The nonintegrin urokinase receptor (uPAR) associates with and stabilizes β1 integrin/caveolin complexes. Depletion of caveolin in uPAR-expressing 293 cells also disrupts uPAR/integrin complexes and uPAR-dependent adhesion. Further, β1 integrin/caveolin complexes could be disassociated by uPAR-binding peptides in both uPAR-transfected 293 cells and human vascular smooth muscle cells. Disruption of complexes by peptides in intact smooth muscle cells blocks the association of Src family kinases with β1 integrins and markedly impairs their migration on fibronectin. We conclude that ligand-induced signaling necessary for normal β1 integrin function requires caveolin and is regulated by uPAR. Caveolin and uPAR may operate within adhesion sites to organize kinase-rich lipid domains in proximity to integrins, promoting efficient signal transduction

Myosin II activity regulates vinculin recruitment to focal adhesions through FAK-mediated paxillin phosphorylation

© The Authors, 2010. This article is distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License. The definitive version was published in Journal of Cell Biology 188 (2010): 877-890, doi:10.1083/jcb.200906012.Focal adhesions (FAs) are mechanosensitive adhesion and signaling complexes that grow and change composition in response to myosin II–mediated cytoskeletal tension in a process known as FA maturation. To understand tension-mediated FA maturation, we sought to identify proteins that are recruited to FAs in a myosin II–dependent manner and to examine the mechanism for their myosin II–sensitive FA association. We find that FA recruitment of both the cytoskeletal adapter protein vinculin and the tyrosine kinase FA kinase (FAK) are myosin II and extracellular matrix (ECM) stiffness dependent. Myosin II activity promotes FAK/Src-mediated phosphorylation of paxillin on tyrosines 31 and 118 and vinculin association with paxillin. We show that phosphomimic mutations of paxillin can specifically induce the recruitment of vinculin to adhesions independent of myosin II activity. These results reveal an important role for paxillin in adhesion mechanosensing via myosin II–mediated FAK phosphorylation of paxillin that promotes vinculin FA recruitment to reinforce the cytoskeletal ECM linkage and drive FA maturation.This work was supported by NHLBI (C.M. Waterman and A.M. Pasapera; and grant HL093156 to D.D. Schlaepfer) and the Burroughs Wellcome Fund (E. Rericha)

Lethal trap created by adaptive evolutionary response to an exotic resource

International audienceGlobal transport of organisms by humans provides novel resources to wild species, which often respond maladaptively. Native herbivorous insects have been killed feeding on toxic exotic plants, which acted as ‘ecological traps’1,2,3,4. We document a novel ‘eco-evolutionary trap’ stemming from the opposite effect; that is, high fitness on an exotic resource despite lack of adaptation to it. Plantago lanceolata was introduced to western North America by cattle-ranching. Feeding on this exotic plant released a large, isolated population of the native butterfly Euphydryas editha from a longstanding trade-off between maternal fecundity and offspring mortality. Because of this release—and despite a reduced insect developmental rate when feeding on this exotic—Plantago immediately supported higher larval survival than did the insects’ traditional host, Collinsia parviflora5. Previous work from the 1980s documented an evolving preference for Plantago by ovipositing adults6. We predicted that if this trend continued the insects could endanger themselves, because the availability of Plantago to butterflies is controlled by humans, who change land management practices faster than butterflies evolve6. Here we report the fulfilment of this prediction. The butterflies abandoned Collinsia and evolved total dependence on Plantago. The trap was set. In 2005, humans withdrew their cattle, springing the trap. Grasses grew around the Plantago, cooling the thermophilic insects, which then went extinct. This local extinction could have been prevented if the population had retained partial use of Collinsia, which occupied drier microhabitats unaffected by cattle removal. The flush of grasses abated quickly, rendering the meadow once again suitable for Euphydryas feeding on either host, but no butterflies were observed from 2008 to 2012. In 2013–2014, the site was naturally recolonized by Euphydryas feeding exclusively on Collinsia, returning the system to its starting point and setting the stage for a repeat of the anthropogenic evolutionary cycle

Optimal timing for managed relocation of species faced with climate change

Managed relocation is a controversial climate-adaptation strategy to combat negative climate change impacts on biodiversity. While the scientific community debates the merits of managed relocation(1-12), species are already being moved to new areas predicted to be more suitable under climate change(13,14). To inform these moves, we construct a quantitative decision framework to evaluate the timing of relocation in the face of climate change. We find that the optimal timing depends on many factors, including the size of the population, the demographic costs of translocation and the expected carrying capacities over time in the source and destination habitats. In some settings, such as when a small population would benefit from time to grow before risking translocation losses, haste is ill advised. We also find that active adaptive management(15,16) is valuable when the effect of climate change on source habitat is uncertain, and leads to delayed movement

Seeking international agreement on what it means to be 'native'

The management of harmful nonnative species is a priority for governments worldwide. However, confusion concerning what constitutes a “native” species has led to ambiguous or even contradictory wording in adopted legislation. A key issue concerns the treatment of species dispersing beyond their normal ranges in response to global change. Range-expanding species can have negative impacts on the ecosystems they colonize, prompting some authorities to class them as “nonnatives.” However, range-shifts are becoming increasingly necessary for species persistence in response to climate and habitat change. Distinguishing these “desirable” range-shifts from other human-driven introductions is therefore a core requirement of legislation. Here, we propose a simplified framework that can be applied unambiguously across the policy arena. We suggest that the “nonnative” moniker should apply exclusively to species transported outside their native range by direct transport (defined herein), leaving species moving via unassisted dispersal as “natives,” even if they are responding indirectly to anthropogenic change. We believe that widespread adoption of this simplified approach will facilitate more consistent multinational policies to target problematic invasive species