Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Competition and parasitism in the native White Clawed Crayfish Austropotamobius pallipes and the invasive Signal Crayfish Pacifastacus leniusculus in the UK

Many crayfish species have been introduced to novel habitats worldwide, often threatening extinction of native species. Here we investigate competitive interactions and parasite infections in the native Austropotamobius pallipes and the invasive Pacifastacus leniusculus from single and mixed species populations in theUK. We found A. pallipes individuals to be significantly smaller in mixed compared to single species populations; conversely P. leniusculus individuals were larger in mixed than in single species populations. Our data provide no support for reproductive interference as a mechanism of competitive displacement and instead suggest competitive exclusion of A. pallipes from refuges by P. leniusculus leading to differential predation. We screened 52 P. leniusculus and 12 A. pallipes for microsporidian infection using PCR. We present the first molecular confirmation of Thelohania contejeani in the native A. pallipes; in addition, we provide the first evidence for T. contejeani in the invasive P. leniusculus. Three novel parasite sequenceswere also isolated fromP. leniusculus with an overall prevalence of microsporidian infection of 38% within this species; we discuss the identity of and the similarity between these three novel sequences. We also screened a subset of fifteen P. leniusculus and three A. pallipes for Aphanomyces astaci, the causative agent of crayfish plague and for the protistan crayfish parasite Psorospermium haeckeli. We found no evidence for infection by either agent in any of the crayfish screened. The high prevalence of microsporidian parasites and occurrence of shared T. contejeani infection lead us to propose that future studies should consider the impact of these parasites on native and invasive host fitness and their potential effects upon the dynamics of native-invader systems

Production of fructooligosaccharides and b-fructofuranosidase by batch and repeated batch fermentation with immobilized cells of Penicillium expansum

The production of fructooligosaccharides (FOS) and b-fructofuranosidase (FFase) by immobilized cells of Penicillium expansum was evaluated. In an initial stage, different low-cost materials including synthetic fiber, polyurethane foam, stainless steel sponge, loofah sponge, and cork oak were tested as carrier for the fungus immobilization. Additionally, the influence of the inoculum age (1 or 3 weeks) on cells immobilization, FOS and FFase production was also verified. Synthetic fiber and polyurethane foam were the best materials for P. expansum immobilization (2.21 and 1.98 g/g carrier, respectively) and FOS production (120.3 and 104.8 g/l), and gave also high results of FFase activity (23.01 and 32.42 U/ml). Then, the production of FOS and FFase by repeated batch fermentation with P. expansum immobilized on synthetic fiber was studied, aiming to improve the batch fermentation results. The results obtained in this stage were very promising with FOS yields of 87, 72, and 44 %, in the 3 initial cycles (60 h), respectively; the FFase activity was constant throughout the process (6 cycles, 96 h). Repeated batch fermentation with immobilized cells of P. expansum was found as being a technology with great potential for FOS and FFase production on industrial scaleThe financial support from FCT, the Portuguese Foundation for Science and Technology (research grant SFRH/BPD/38212/2007) is gratefully acknowledged

Increasing the sensitivity of NMR diffusion measurements by paramagnetic longitudinal relaxation enhancement, with application to ribosome–nascent chain complexes

The translational diffusion of macromolecules can be examined non-invasively by stimulated echo (STE) NMR experiments to accurately determine their molecular sizes. These measurements can be important probes of intermolecular interactions and protein folding and unfolding, and are crucial in monitoring the integrity of large macromolecular assemblies such as ribosome–nascent chain complexes (RNCs). However, NMR studies of these complexes can be severely constrained by their slow tumbling, low solubility (with maximum concentrations of up to 10 μM), and short lifetimes resulting in weak signal, and therefore continuing improvements in experimental sensitivity are essential. Here we explore the use of the paramagnetic longitudinal relaxation enhancement (PLRE) agent NiDO2A on the sensitivity of 15N XSTE and SORDID heteronuclear STE experiments, which can be used to monitor the integrity of these unstable complexes. We exploit the dependence of the PLRE effect on the gyromagnetic ratio and electronic relaxation time to accelerate recovery of 1H magnetization without adversely affecting storage on N z during diffusion delays or introducing significant transverse relaxation line broadening. By applying the longitudinal relaxation-optimized SORDID pulse sequence together with NiDO2A to 70S Escherichia coli ribosomes and RNCs, NMR diffusion sensitivity enhancements of up to 4.5-fold relative to XSTE are achieved, alongside ~1.9-fold improvements in two-dimensional NMR sensitivity, without compromising the sample integrity. We anticipate these results will significantly advance the use of NMR to probe dynamic regions of ribosomes and other large, unstable macromolecular assemblies

Withanolides and related steroids

Since the isolation of the first withanolides in the mid-1960s, over 600 new members of this group of compounds have been described, with most from genera of the plant family Solanaceae. The basic structure of withaferin A, a C28 ergostane with a modified side chain forming a δ-lactone between carbons 22 and 26, was considered for many years the basic template for the withanolides. Nowadays, a considerable number of related structures are also considered part of the withanolide class; among them are those containing γ-lactones in the side chain that have come to be at least as common as the δ-lactones. The reduced versions (γ and δ-lactols) are also known. Further structural variations include modified skeletons (including C27 compounds), aromatic rings and additional rings, which may coexist in a single plant species. Seasonal and geographical variations have also been described in the concentration levels and types of withanolides that may occur, especially in the Jaborosa and Salpichroa genera, and biogenetic relationships among those withanolides may be inferred from the structural variations detected. Withania is the parent genus of the withanolides and a special section is devoted to the new structures isolated from species in this genus. Following this, all other new structures are grouped by structural types. Many withanolides have shown a variety of interesting biological activities ranging from antitumor, cytotoxic and potential cancer chemopreventive effects, to feeding deterrence for several insects as well as selective phytotoxicity towards monocotyledoneous and dicotyledoneous species. Trypanocidal, leishmanicidal, antibacterial, and antifungal activities have also been reported. A comprehensive description of the different activities and their significance has been included in this chapter. The final section is devoted to chemotaxonomic implications of withanolide distribution within the Solanaceae. Overall, this chapter covers the advances in the chemistry and biology of withanolides over the last 16 years.Fil: Misico, Rosana Isabel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); ArgentinaFil: Nicotra, V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Oberti, Juan Carlos María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Barboza, Gloria Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Gil, Roberto Ricardo. University Of Carnegie Mellon; Estados UnidosFil: Burton, Gerardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos Aplicados a la Química Orgánica (i); Argentin

SEASONAL DISTRIBUTION OF MALARIA VECTORS (DIPTERA: CULICIDAE) IN RURAL LOCALITIES OF PORTO VELHO, RONDÔNIA, BRAZILIAN AMAZON

We conducted a survey of the malaria vectors in an area where a power line had been constructed, between the municipalities of Porto Velho and Rio Branco, in the states of Rondônia and Acre, respectively. The present paper relates to the results of the survey of Anopheles fauna conducted in the state of Rondônia. Mosquito field collections were performed in six villages along the federal highway BR 364 in the municipality of Porto Velho, namely Porto Velho, Jaci Paraná, Mutum Paraná, Vila Abunã, Vista Alegre do Abunã, and Extrema. Mosquito captures were performed at three distinct sites in each locality during the months of February, July, and October 2011 using a protected human-landing catch method; outdoor and indoor captures were conducted simultaneously at each site for six hours. In the six sampled areas, we captured 2,185 mosquitoes belonging to seven Anopheles species. Of these specimens, 95.1% consisted of Anopheles darlingi, 1.8% An. triannulatus l.s., 1.7% An. deaneorum, 0.8% An. konderi l.s., 0.4 An. braziliensis, 0.1% An. albitarsis l.s., and 0.1% An. benarrochi. An. darlingi was the only species found in all localities; the remaining species occurred in sites with specific characteristics

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Annual variations in the number of malaria cases related to two different patterns of Anopheles darlingi transmission potential in the Maroni area of French Guiana

<p>Abstract</p> <p>Background</p> <p>With an Annual Parasite Incidence (API) of 132.1, in the high and moderate risks zones, the Maroni area of French Guiana has the second highest malaria incidence of South-America after Guyana (API = 183.54) and far above Brazil (API = 28.25). Malaria transmission is occurring despite strong medical assistance and active vector control, based on general WHO recommendations. This situation is generated by two main factors that are the social and cultural characteristics of this border area, where several ethnic groups are living, and the lack of understanding of transmission dynamics of the main mosquito vector, <it>Anopheles darlingi.</it> In this context, entomological data collected in two villages belonging to two different ethnic groups of the French border of the Maroni River, were retrospectively analysed to find out how the mosquito bionomics are related to the malaria transmission patterns.</p> <p>Methods</p> <p>Data were provided by human landing catches of mosquitoes carried out each month for two years in two villages belonging to two ethnic groups, the Amerindians Wayanas and the Aloukous of African origin. The mosquitoes were sorted by species, sex, date, hour and place of collection and processed for <it>Plasmodium sp</it>. parasite detection. The data were compiled to provide the following variables: human biting rates (HBR), parity rates (PR), numbers of infective bites (IB), entomological inoculation rates (EIR) and numbers of infected mosquitoes surviving enough to transmit (IMT). Spatial and temporal differences of variables between locations and during the night were tested by the Kruskall-Wallis analysis of variance to find out significant variations.</p> <p>Results</p> <p>The populations of the main mosquito vector <it>An. darlingi </it>showed significant variations in the spatial and temporal HBR/person/night and HBR/person/hour, IB/person/month and IB/person/hour, and IMT/village/night and IMT/village/hour. In the village of Loca (Aloukous), the IMT peaked from June to August with a very low transmission during the other months. The risks were higher during the first part of the night and an EIR of 10 infective bites per person and per year was estimated. In the village of Twenke (Wayanas), high level of transmission was reported all year with small peaks in March and October. The risk was higher during the second part of the night and an EIR of 5 infective bites per person and per year was estimated.</p> <p>Conclusion</p> <p>For the first time in the past 40 years, the mosquito bionomics was related to the malaria transmission patterns in French Guiana. The peak of malaria cases reported from August to October in the Maroni region is concomitant with the significant peak of <it>An. darlingi </it>IMT, reported from the village of Loca where transmission is higher. However, the persistent number of cases reported all year long may also be related to the transmission in the Amerindian villages. The <it>An. darlingi </it>bionomics for these two close populations were found significantly different and may explain why a uniform vector control method is inadequate. Following these findings, malaria prevention measures adapted to the local conditions are needed. Finally, the question of the presence of <it>An. darlingi </it>sub-species is raised.</p

Results of a Zika Virus (ZIKV) Immunoglobulin M-Specific Diagnostic Assay Are Highly Correlated With Detection of Neutralizing Anti-ZIKV Antibodies in Neonates With Congenital Disease.

:  Usually, immunoglobulin M (IgM) serologic analysis is not sufficiently specific to confirm Zika virus (ZIKV) infection. However, since IgM does not cross the placenta, it may be a good marker of infection in neonates. :  We tested blood from 42 mothers and neonates with microcephaly and collected cerebrospinal fluid (CSF) specimens from 30 neonates. Molecular assays were performed for detection of ZIKV, dengue virus, and chikungunya virus; IgM enzyme-linked immunosorbent assays and plaque-reduction neutralization tests (PRNTs) were performed to detect ZIKV and dengue virus. No control neonates without microcephaly were evaluated. :  Among neonates, all 42 tested positive for ZIKV IgM: 38 of 42 serum specimens (90.5%) were positive, whereas 30 of 30 CSF specimens (100%) were positive. ZIKV IgM-specific ELISA ratios, calculated as the mean optical density (OD) of the test sample when reacted on viral antigen divided by the mean OD of the negative control when reacted with viral antigen, were higher in CSF specimens (median, 14.9 [range, 9.3-16.4]) than in serum (median, 8.9 [range, 2.1-20.6]; P = .0003). All ZIKV IgM-positive results among the neonates were confirmed by the detection of neutralizing antibodies. Mother/neonate pairs with primary ZIKV infection had neutralizing antibodies to ZIKV only, and mother/neonate pairs with ZIKV virus infection secondary to infection with another flavivirus had high titers of neutralizing antibodies to ZIKV. Among secondary infections, median titers in serum were 2072 (range, 232-12 980) for mothers and 2730 (range, 398-12 980) for neonates (P &lt; .0001), and the median titer in CSF was 93 (range, 40-578) among neonates (P &lt; .0001). :  Among neonates, detection of ZIKV IgM in serum is confirmatory of congenital ZIKV infection, and detection of ZIKV IgM in CSF is confirmatory of neurologic infection. Therefore, we recommend testing for ZIKV IgM in neonates suspected of having congenital ZIKV infection and performance of PRNTs in equivocal cases.<br/

Intimate partner violence against women in rural Vietnam - different socio-demographic factors are associated with different forms of violence: Need for new intervention guidelines?

Background: This population-based study investigated the different forms, magnitude and risk factors of men's violence against women in intimate relationships in a rural part of northern Vietnam and whether a difference in risk factors were at hand for the different forms of violence. Vietnam has undergone a rapid transition in the last 20 years, moving towards a more equal situation for men and women however, Confucian doctrine is still strong and little is known about men's violence against women within the Vietnamese family. Methods: This is a cross-sectional population-based study that used a questionnaire developed by the World Health Organisation for investigating women's health and violence against women in different settings. Face-to face structured interviewing was performed and 883 married women, aged 17 to 60 participated. Bi- and multivariate analyses was used for risk factor assessment. Results: The lifetime prevalence of physical violence was 30.9 percent and past year prevalence was 8.3 per cent, while the corresponding figures for physical and sexual violence combined was 32.7 and 9.2 percent. The lifetime prevalence was highest for psychological abuse ( 27.9 percent) as a single entity. In most cases the violence was of a severe nature and exercised as repeated acts over time. Woman's low educational level, husband's low education, low household income and the husband having more than one wife/partner were risk factors for lifetime and past year physical/sexual violence. The pattern of factors associated with psychological abuse alone was however different. Husband's low professional status and women's intermediate level of education appeared as risk factors. Conclusion: Men's violence against women in intimate relationships is commonly occurring in rural Vietnam. There is an obvious need of preventive and treatment activities. Our findings point at that pure psychological abuse is different from physical/sexual violence in terms of differing characteristics of the perpetrators and it might be that also different strategies are needed to reduce and prevent this violence