Expression of serotonergic receptors in psoriatic skin

Psoriasis appears to be influenced by stress, which causes release of adrenal hormones. Serotonin, or hormonal actions on serotonin and serotonin receptors, may have a role in psoriasis. Distribution of serotonin receptors was studied in involved and noninvolved skin in patients with psoriasis and compared to normal skin, by using immunohistochemistry and antibodies to 5-HT1A, 5-HT2A and 5-HT3 receptors (R). There was a decreased (P<0.001) number of 5-HT1AR positive cells, the majority being tryptase positive, in involved and noninvolved psoriatic papillary dermis, compared to normal skin. 5-HTlAR expression was also found in the upper part of the epidermis, on vessel walls and on melanocytes. 5-HT2AR expressing papillary mononuclear cells, CD3 positive, were increased (P<0.001 and P<0.01, respectively) in involved and noninvolved psoriatic skin, compared to normal skin, an increase (P<0.01) also being found in the involved compared to noninvolved skin. Expression of 5-HT3R could be found in the basal epidermal layer of noninvolved but not in the involved skin of psoriasis, where it was only found in the acrosyringium. The present findings are compatible with the 5-HT1A and 5-HT2A receptors having antagonistic functions, and raise the possibility of using receptor specific drugs in the treatment of psoriasis.     

Factors influencing scores on the social responsiveness scale

Background: The Social Responsiveness Scale (SRS) is a parent‐completed screening questionnaire often used to measure autism spectrum disorders (ASD) severity. Although child characteristics are known to influence scores from other ASD‐symptom measures, as well as parent‐questionnaires more broadly, there has been limited consideration of how non‐ASD‐specific factors may affect interpretation of SRS scores. Previous studies have explored effects of behavior problems on SRS specificity, but have not addressed influences on the use of the SRS as a quantitative measure of ASD‐symptoms. Method: Raw scores (SRS‐Raw) from parent‐completed SRS were analyzed for 2,368 probands with ASD and 1,913 unaffected siblings. Regression analyses were used to assess associations between SRS scores and demographic, language, cognitive, and behavior measures. Results: For probands, higher SRS‐Raw were associated with greater non‐ASD behavior problems, higher age, and more impaired language and cognitive skills, as well as scores from other parent report measures of social development and ASD‐symptoms. For unaffected siblings, having more behavior problems predicted higher SRS‐Raw; male gender, younger age, and poorer adaptive social and expressive communication skills also showed small, but significant effects. Conclusions: When using the SRS as a quantitative phenotype measure, the influence of behavior problems, age, and expressive language or cognitive level on scores must be considered. If effects of non‐ASD‐specific factors are not addressed, SRS scores are more appropriately interpreted as indicating general levels of impairment, than as severity of ASD‐specific symptoms or social impairment. Additional research is needed to consider how these factors influence the SRS’ sensitivity and specificity in large, clinical samples including individuals with disorders other than ASD.     

Cadmium neurotoxicity

The Cd has been recognized as one of the most toxic environmental and industrial pollutants due to its ability to induce disturbances in several organs and tissues following either acute or chronic exposure. This review accounts for the recent evidence on its mechanisms to induce neurotoxicity, the role of the blood–brain barrier, oxidative stress, interference with calcium, and zinc-dependent processes and apoptosis induction as well as the modulatory effect of metallothionein. Discussion about cadmium neurotoxicity is centered on mechanisms of induction of cellular disfunctions. Future investigations must address those neuronal mechanisms in detail in order to understand cadmium-induced neurotoxicity.     

Depolymerization dynamics of individual filaments of bacterial cytoskeletal protein FtsZ

We report observation and analysis of the depolymerization filaments of the bacterial cytoskeletal protein FtsZ (filament temperature-sensitive Z) formed on a mica surface. At low concentration, proteins adsorbed on the surface polymerize forming curved filaments that close into rings that remain stable for some time before opening irreversibly and fully depolymerizing. The distribution of ring lifetimes (T) as a function of length (N), shows that the rate of ring aperture correlates with filament length. If this ring lifetime is expressed as a bond survival time, (T_b ≡ NT), this correlation is abolished, indicating that these rupture events occur randomly and independently at each monomer interface. After rings open irreversibly, depolymerization of the remaining filaments is fast, but can be slowed down and followed using a nonhydrolyzing GTP analogue. The histogram of depolymerization velocities of individual filaments has an asymmetric distribution that can be fit with a computer model that assumes two rupture rates, a slow one similar to the one observed for ring aperture, affecting monomers in the central part of the filaments, and a faster one affecting monomers closer to the open ends. From the quantitative analysis, we conclude that the depolymerization rate is affected both by nucleotide hydrolysis rate and by its exchange along the filament, that all monomer interfaces are equally competent for hydrolysis, although depolymerization is faster at the open ends than in central filament regions, and that all monomer–monomer interactions, regardless of the nucleotide present, can adopt a curved configuration.     

Vector competence of Simulium oyapockense s.l. and S. incrustatum for Onchocerca volvulus: Implications for ivermectin-based control in the Amazonian focus of human onchocerciasis, a multi-vector-host system

Although it is now well established that in the Amazonian onchocerciasis focus, straddling between Venezuela and Brazil, the main vectors in the highland (hyperendemic) and lowland (hypoendemic) areas, are respectively Simulium guianense sensu lato Wise and S. oyapockense s.l. Floch and Abonnenc, investigation of the vectorial role of a third anthropophagic species, Simulium incrustatum Lutz has remained inconclusive. Here we compare the vector competence of S. incrustatum with that of S. oyapockense s.l. by conducting, in the Venezuelan part of the focus, a series of feeding experiments designed to analyze their relative: (a) microfilarial intakes when fed upon the same skin load; (b) proportions of microfilariae (mf) surviving damage inflicted by the cibarial armature (present in both species); and (c) infective (L3) larval outputs. Although the ability of S. oyapockense s.l. to ingest mf, for a given microfilaridermia, was markedly higher than that of S. incrustatum, the (density-dependent) proportions of those ingested mf that were damaged by the armature were also consistently higher, with the resulting output of L3 larvae being significantly lower in S. oyapockense s.l. than in S. incrustatum. These results indicate that S. incrustatum plays a more important role in onchocerciasis transmission in the Amazonian focus than previously realized. We discuss the implications of our findings for the control and elimination of onchocerciasis with mass administration of ivermectin in this focus, where the three main anthropophagic species often co-occur.     

Growth hormone enhances thymic function in HIV-1-infected adults

Growth hormone (GH) is an underappreciated but important regulator of T cell development that can reverse age-related declines in thymopoiesis in rodents. Here, we report findings of a prospective randomized study examining the effects of GH on the immune system of HIV-1-infected adults. GH treatment was associated with increased thymic mass. In addition, GH treatment enhanced thymic output, as measured by both the frequency of T cell receptor rearrangement excision circles in circulating T cells and the numbers of circulating naive and total CD4(+) T cells. These findings provide compelling evidence that GH induces de novo T cell production and may, accordingly, facilitate CD4(+) T cell recovery in HIV-1-infected adults. Further, these randomized, prospective data have shown that thymic involution can be pharmacologically reversed in humans, suggesting that immune-based therapies could be used to enhance thymopoiesis in immunodeficient individuals.