Typical 22q11.2 deletion syndrome appears to confer a reduced risk of schwannoma.

PURPOSE: The LZTR1 gene has been associated with schwannomatosis tumor predisposition and is located in a region that is deleted in the great majority (89%) of patients with 22q11.2 deletion syndrome (22q11.2DS). Since it is known that approximately 1 in 500 people in the general population will develop a sporadic schwannoma and there are no reports of the occurrence of schwannoma in 22q11.2DS, we investigated whether whole-gene deletion of LZTR1 occurs in schwannomatosis and assessed the risk of schwannoma in 22q11.2DS. METHODS: We assessed the genetic testing results for LZTR1-associated schwannomatosis and the clinical phenotypes of patients with 22q11.2DS. RESULTS: There were no reports of schwannoma in over 1,500 patients with 22q11.2DS. In addition, no patients meeting clinical diagnostic criteria for schwannomatosis had a whole-gene deletion in LZTR1. Only 1 patient in 110 with an apparently sporadic vestibular schwannoma had a constitutional whole-gene deletion of LZTR1. CONCLUSION: People with a large 22q11.2 deletion may have a reduced risk of developing a schwannoma compared to the general population.

Innumerable Condyloma Acuminatum Tumors of the Bladder.

Condylomata acuminata caused by human papillomavirus (HPV), a sexually transmitted virus, are rarely seen beyond the external genitalia and anal region. Here, a patient with innumerable condyloma acuminatum of the bladder is presented. Attempted surgical resection was performed and intraoperative photographs are presented.

Defective proviruses rapidly accumulate during acute HIV-1 infection.

Although antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, human immunodeficiency virus type 1 (HIV-1) persists in CD4(+) T cells in a latent form that is not targeted by the immune system or by ART. This latent reservoir is a major barrier to curing individuals of HIV-1 infection. Many individuals initiate ART during chronic infection, and in this setting, most proviruses are defective. However, the dynamics of the accumulation and the persistence of defective proviruses during acute HIV-1 infection are largely unknown. Here we show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. By using an unbiased method to amplify near-full-length proviral genomes from HIV-1-infected adults treated at different stages of infection, we demonstrate that early initiation of ART limits the size of the reservoir but does not profoundly affect the proviral landscape. This analysis allows us to revise our understanding of the composition of proviral populations and estimate the true reservoir size in individuals who were treated early versus late in infection. Additionally, we demonstrate that common assays for measuring the reservoir do not correlate with reservoir size, as determined by the number of genetically intact proviruses. These findings reveal hurdles that must be overcome to successfully analyze future HIV-1 cure strategies.

The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence.

Combination antiretroviral therapy (ART) for HIV-1 infection reduces plasma virus levels to below the limit of detection of clinical assays. However, even with prolonged suppression of viral replication with ART, viremia rebounds rapidly after treatment interruption. Thus, ART is not curative. The principal barrier to cure is a remarkably stable reservoir of latent HIV-1 in resting memory CD4(+) T cells. In this review, we consider explanations for the remarkable stability of the latent reservoir. Stability does not appear to reflect replenishment from new infection events but rather normal physiologic processes that provide for immunologic memory. Of particular importance are proliferative processes that drive clonal expansion of infected cells. Recent evidence suggests that in some infected cells, proliferation is a consequence of proviral integration into host genes associated with cell growth. Efforts to cure HIV-1 infection by targeting the latent reservoir may need to consider the potential of latently infected cells to proliferate.

Rhes, a striatal-selective protein implicated in Huntington disease, binds beclin-1 and activates autophagy.

The protein mutated in Huntington disease (HD), mutant huntingtin (mHtt), is expressed throughout the brain and body. However, the pathology of HD is characterized by early and dramatic destruction selectively of the striatum. We previously reported that the striatal-specific protein Rhes binds mHtt and enhances its cytotoxicity. Moreover, Rhes-deleted mice are dramatically protected from neurodegeneration and motor dysfunction in mouse models of HD. We now report a function of Rhes in autophagy, a lysosomal degradation pathway implicated in aging and HD neurodegeneration. In PC12 cells, deletion of endogenous Rhes decreases autophagy, whereas Rhes overexpression activates autophagy. These effects are independent of mTOR and opposite in the direction predicted by the known activation of mTOR by Rhes. Rhes robustly binds the autophagy regulator Beclin-1, decreasing its inhibitory interaction with Bcl-2 independent of JNK-1 signaling. Finally, co-expression of mHtt blocks Rhes-induced autophagy activation. Thus, the isolated pathology and delayed onset of HD may reflect the striatal-selective expression and changes in autophagic activity of Rhes.

The role of potential agents in making spatial perspective taking social.

A striking relationship between visual spatial perspective taking (VSPT) and social skills has been demonstrated for perspective-taking tasks in which the target of the imagined or inferred perspective is a potential agent, suggesting that the presence of a potential agent may create a social context for the seemingly spatial task of imagining a novel visual perspective. In a series of studies, we set out to investigate how and when a target might be viewed as sufficiently agent-like to incur a social influence on VSPT performance. By varying the perceptual and conceptual features that defined the targets as potential agents, we find that even something as simple as suggesting animacy for a simple wooden block may be sufficient. More critically, we found that experience with one potential agent influenced the performance with subsequent targets, either by inducing or eliminating the influence of social skills on VSPT performance. These carryover effects suggest that the relationship between social skills and VSPT performance is mediated by a complex relationship that includes the task, the target, and the context in which that target is perceived. These findings highlight potential problems that arise when identifying a task as belonging exclusively to a single cognitive domain and stress instead the highly interactive nature of cognitive domains and their susceptibility to cross-domain individual differences.

Should social savvy equal good spatial skills? The interaction of social skills with spatial perspective taking.

Real-world perspective-taking problems frequently involve interactions among individuals, suggesting a potential social element to this seemingly spatial problem. Previous studies have suggested that the agency of the target in a perspective-taking task might influence reasoning. This hypothesis is tested directly by manipulating whether one takes the perspective of a potential agent or an object. The results were striking: Even though no overall differences in performance were observed with and without agents, performance was differentially associated with social skills. In particular, participants with better social skills were more accurate than less social peers when the target was a potential agent, whereas no such relationship was observed when the target was an object. These results suggest that bringing domain-specific investigations to bear on real-world problems requires understanding how that domain exists in the broader context of interacting skills and biases.

The stigmatising implications of presenting schizophrenia as a genetic disease.

This study aimed to investigate the hypothesis that belief in a genetic aetiology of schizophrenia will increase the stigma associated with the disorder. Levels of five potentially stigmatising attitudes were compared in two groups of participants who had read a vignette describing an individual who has schizophrenia. In one group the disorder was explained as being caused by 'genetic' factors, and in the other by 'environmental' factors. This study found that three of the five potentially stigmatising attitudes measured were increased when participants read a vignette with a genetic causation rather than an environmental causation. Firstly, genetic attributions increased levels of associative stigma towards close relatives (p < 0.001). Secondly, participants viewed recovery as less likely when genetic factors were implicated as causative (p < 0.001). Finally, there was also an increased perception of the character's "dangerousness" when the condition was explained by genetic factors (p < 0.05). Contrary to previous research was the finding that perceived aetiology had no effect on participant's desire for social distance from an affected individual. Neither did perceived aetiology influence beliefs about moral accountability. The implications of these findings suggest that genetic counsellors and other health professionals, who are providing genetic information to those affected by schizophrenia should be aware of the possibility that a genetic explanation of schizophrenia could increase potentially stigmatising attitudes towards their clients and their clients' families. It is also possible that individuals with a diagnosis of schizophrenia may themselves form deterministic interpretations of the genetic information they receive and subsequently be less likely to adopt behavioural advice or adhere to treatment. Counsellors and health professionals should strive to present information in a balanced manner, ensuring recipients understand the multi-factorial causes of the disease.