Suicidality in Body Dysmorphic Disorder

Suicidal ideation, suicide attempts, and completed suicide appear common in individuals with body dysmorphic disorder (BDD). Available evidence indicates that approximately 80% of individuals with BDD experience lifetime suicidal ideation and 24% to 28% have attempted suicide. Although data on completed suicide are limited and preliminary, the suicide rate appears markedly high. These findings underscore the importance of recognizing and effectively treating BDD. However, BDD is underrecognized in clinical settings even though it is relatively common and often presents to psychiatrists and other mental health practitioners, dermatologists, surgeons, and other physicians. This article reviews available evidence on suicidality in BDD and discusses how to recognize and diagnose this often secret disorder. Efficacious treatments for BDD, ie, serotonin reuptake inhibitors (SRIs) and cognitive-behavioral therapy, are also discussed. Although data are limited, it appears that SRIs often diminish suicidality in these patients. Additional research is greatly needed on suicidality rates, characteristics, correlates, risk factors, treatment, and prevention of suicidality in BDD.     

Targeting TOPK sensitises tumour cells to radiation-induced damage by enhancing replication stress

T-LAK-originated protein kinase (TOPK) overexpression is a feature of multiple cancers, yet is absent from most phenotypically normal tissues. As such, TOPK expression profiling and the development of TOPK-targeting pharmaceutical agents have raised hopes for its future potential in the development of targeted therapeutics. Results presented in this paper confirm the value of TOPK as a potential target for the treatment of solid tumours, and demonstrate the efficacy of a TOPK inhibitor (OTS964) when used in combination with radiation treatment. Using H460 and Calu-6 lung cancer xenograft models, we show that pharmaceutical inhibition of TOPK potentiates the efficacy of fractionated irradiation. Furthermore, we provide in vitro evidence that TOPK plays a hitherto unknown role during S phase, showing that TOPK depletion increases fork stalling and collapse under conditions of replication stress and exogenous DNA damage. Transient knockdown of TOPK was shown to impair recovery from fork stalling and to increase the formation of replication-associated single-stranded DNA foci in H460 lung cancer cells. We also show that TOPK interacts directly with CHK1 and Cdc25c, two key players in the checkpoint signalling pathway activated after replication fork collapse. This study thus provides novel insights into the mechanism by which TOPK activity supports the survival of cancer cells, facilitating checkpoint signalling in response to replication stress and DNA damage.Subject terms: Tumour biomarkers, Oncogenes, Preclinical research     

Male dispersal patterns in white-faced capuchins, Cebus capucinus: Part 2: patterns and causes of secondary dispersal

Male dispersal from the birth group is common in the majority of social mammals, and in many species, males also engage in secondary or breeding dispersal following natal emigration. However, the patterns and causes of secondary dispersal are poorly understood due to the difficulty in following emigrants. Here, we detail the patterns and causation of male secondary dispersal in several groups of white-faced capuchins observed between 1985 and 2000 in Santa Rosa National Park, Costa Rica. Subsequent to natal emigration, which occurs between 2 and 8 years of age (median 4.5 years), male white-faced capuchins embark on a life of continual movement. Although males of all age classes engage in voluntary secondary dispersal, the ways by which males enter groups varies according to their age class. Adult males (≥10 years old) are more likely to enter groups aggressively, and they display longer tenure than either subadult males (7-10 years of age) or juvenile males (1-7 years of age). Given our finding that adult males face the highest risks in terms of aggressive interactions with conspecifics, we examined several explanations as to why they continue to disperse throughout their lives. Our data best support the intragroup mating competition hypothesis for secondary dispersal, whereby males move frequently between groups as a means of increasing their reproductive opportunities. Males may also engage in frequent secondary dispersal to avoid mating with their maturing daughters, although this hypothesis was not strongly supported by the current data. Males of all age classes displayed very high levels of parallel dispersal, which probably serves to offset the high costs of dispersal (predation, starvation and/or aggression from conspecifics) and it may also serve as a means of retaining kinship among group males.     

Features of meat digestion by captive chimpanzees (Pan troglodytes)

The pronounced carnivory of many human populations contrasts sharply with feeding habits of other Hominoidea. Of extant great apes, only chimpanzees (Pan spp.) actively seek out vertebrate prey, but meat is only a minor portion of their diet. Some accounts suggest that wild chimpanzees digest prey inefficiently. To investigate the capacity of chimpanzees to digest meat, feeding trials were carried out on three captive chimpanzees (Pan troglodytes) using a fixed amount of nonpurified diet with and without a predetermined amount of boned cooked chicken. The results showed no significant differences in the rate of passage of digesta and digestion of diets with and without chicken. Meat ingestion did not change the nitrogen (N) concentration of feces or the total amount of N defecated. Visual inspection of fecal matter showed no evidence of undigested meat. Taken together, the results indicate that chimpanzees are able to digest meat of the type and quantity consumed during these trials.     

Morphological complexity affects the diversity of marine microbiomes

Large eukaryotes support diverse communities of microbes on their surface—epibiota—that profoundly influence their biology. Alternate factors known to structure complex patterns of microbial diversity—host evolutionary history and ecology, environmental conditions and stochasticity—do not act independently and it is challenging to disentangle their relative effects. Here, we surveyed the epibiota from 38 sympatric seaweed species that span diverse clades and have convergent morphology, which strongly influences seaweed ecology. Host identity explains most of the variation in epibiont communities and deeper host phylogenetic relationships (e.g., genus level) explain a small but significant portion of epibiont community variation. Strikingly, epibiota community composition is significantly influenced by host morphology and epibiota richness increases with morphological complexity of the seaweed host. This effect is robust after controlling for phylogenetic non-independence and is strongest for crustose seaweeds. We experimentally validated the effect of host morphology by quantifying bacterial community assembly on latex sheets cut to resemble three seaweed morphologies. The patterns match those observed in our field survey. Thus, biodiversity increases with habitat complexity in host-associated microbial communities, mirroring patterns observed in animal communities. We suggest that host morphology and structural complexity are underexplored mechanisms structuring microbial communities.Subject terms: Microbial ecology, Biodiversity     

Radiolabelling of the monate moiety in the study of pseudomonic acid biosynthesis

Abstract Monic acid A was isolated from a Pseudomonas fluorescens fermentation in which pseudomonic acid A (PA) was the principal secondary metabolite. [3-¹⁴C]3-Hydroxy-3-methyl-glutaric acid (HMG) given early in the idiophase radiolabelled PA (1.1% incorporation), confirming experimentally the putative direct involvement of HMG in the biosynthesis of PA, but contributed relatively insignificant radiolabel to the monic acid extracted from the broth at the end of the fermentation. Ethionine inhibited (80%) PA biosynthesis and correspondingly reduced incorporation of [¹⁴C]HMG. In contrast, ethionine increased incorporation of [methyl-¹⁴C]methionine into PA and enhanced specific radioactivity of the antibiotic 8-fold. Ethionine inhibition of secondary metabolite methylations did not divert pseudomonate biosynthesis to give unusual analogues, implying that methylation of a putative pentaketide precursor of the monate moiety forms a vital intermediate of the pseudomonate pathway, but caused a new [¹⁴C]HMG-derived polar metabolite of biosynthetic interest to become evident.     

Protein kinase C inhibits Kv1.1 potassium channel function

The regulation by protein kinase C (PKC) of recombinantvoltage-gated potassium (K) channels in frog oocytes was studied. Phorbol 12-myristate 13-acetate (PMA; 500 nM), an activator of PKC,caused persistent and large (up to 90%) inhibition of mouse, rat, andfly Shaker K currents. K currentinhibition by PMA was blocked by inhibitors of PKC, and inhibition wasnot observed in control experiments with PMA analogs that do notactivate PKC. However, site-directed substitution of potential PKCphosphorylation sites in the Kv1.1 protein did not prevent currentinhibition by PMA. Kv1.1 current inhibition was also not accompanied bychanges in macroscopic activation kinetics or in theconductance-voltage relationship. In Western blots, Kv1.1 membraneprotein was not significantly reduced by PKC activation. The injectionof oocytes with botulinum toxin C3 exoenzyme blocked the PMA inhibitionof Kv1.1 currents. These data are consistent with the hypothesis thatPKC-mediated inhibition of Kv1.1 channel function occurs by a novelmechanism that requires a C3 exoenzyme substrate but does not alterchannel activation gating or promote internalization of the channel protein.

     

Diagnosis of latent tuberculosis infection is associated with reduced HIV viral load and lower risk for opportunistic infections in people living with HIV

Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB. To detect differences in the HIV set point viral load (SPVL), linear regression was used; the frequency of the most common opportunistic infections (OIs) in the SHCS between MTB uninfected patients, patients with LTBI, and patients with active TB were compared using logistic regression and time-to-event analyses. In adjusted models, we corrected for baseline demographic characteristics, i.e., HIV transmission risk group and gender, geographic region, year of HIV diagnosis, and CD4 nadir. A total of 13,943 SHCS patients had at least 1 MTB test documented, of whom 840 (6.0%) had LTBI and 770 (5.5%) developed active TB. Compared to MTB uninfected patients, LTBI was associated with a 0.24 decreased log HIV SPVL in the adjusted model (p < 0.0001). Patients with LTBI had lower odds of having candida stomatitis (adjusted odds ratio (OR) = 0.68, p = 0.0035) and oral hairy leukoplakia (adjusted OR = 0.67, p = 0.033) when compared to MTB uninfected patients. The association of LTBI with a reduced HIV set point virus load and fewer unrelated infections in HIV/TB coinfected patients suggests a more complex interaction between LTBI and HIV than previously assumed.

Surprisingly little is known about how latent tuberculosis infection alters human physiology and immune function. Extensive statistical analyses of the large Swiss HIV Cohort Study suggests that latent tuberculosis infection can be protective in individuals with HIV.     

Knockdown of the plastid-encoded acetyl-CoA carboxylase gene uncovers functions in metabolism and development

De novo fatty acid biosynthesis in plants relies on a prokaryotic-type acetyl-CoA carboxylase (ACCase) that resides in the plastid compartment. The enzyme is composed of four subunits, one of which is encoded in the plastid genome, whereas the other three subunits are encoded by nuclear genes. The plastid gene (accD) encodes the β-carboxyltransferase subunit of ACCase and is essential for cell viability. To facilitate the functional analysis of accD, we pursued a transplastomic knockdown strategy in tobacco (Nicotiana tabacum). By introducing point mutations into the translational start codon of accD, we obtained stable transplastomic lines with altered ACCase activity. Replacement of the standard initiator codon AUG with UUG strongly reduced AccD expression, whereas replacement with GUG had no detectable effects. AccD knockdown mutants displayed reduced ACCase activity, which resulted in changes in the levels of many but not all species of cellular lipids. Limiting fatty acid availability caused a wide range of macroscopic, microscopic, and biochemical phenotypes, including impaired chloroplast division, reduced seed set, and altered storage metabolism. Finally, while the mutants displayed reduced growth under photoautotrophic conditions, they showed exaggerated growth under heterotrophic conditions, thus uncovering an unexpected antagonistic role of AccD activity in autotrophic and heterotrophic growth.

Analysis of the only plastid genome-encoded fatty acid biosynthesis gene reveals functions in plastid division and seed development, and antagonistic roles in autotrophic and heterotrophic growth.