Challenges for the development of a biotic ligand model predicting copper toxicity in estuaries and seas

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2011 SETAC.An effort is ongoing to develop a biotic ligand model (BLM) that predicts copper (Cu) toxicity in estuarine and marine environments. At present, the BLM accounts for the effects of water chemistry on Cu speciation, but it does not consider the influence of water chemistry on the physiology of the organisms. We discuss how chemistry affects Cu toxicity not only by controlling its speciation, but also by affecting the osmoregulatory physiology of the organism, which varies according to salinity. In an attempt to understand the mechanisms of Cu toxicity and predict its impacts, we explore the hypothesis that the common factor linking the main toxic effects of Cu is the enzyme carbonic anhydrase (CA), because it is a Cu target with multiple functions and salinity-dependent expression and activity. According to this hypothesis, the site of action of Cu in marine fish may be not only the gill, but also the intestine, because in this tissue CA plays an important role in ion transport and water adsorption. Therefore, the BLM of Cu toxicity to marine fish should also consider the intestine as a biotic ligand. Finally, we underline the need to incorporate the osmotic gradient into the BLM calculations to account for the influence of physiology on Cu toxicity.Brunel Universit

Schistosomiasis in Africa: Improving strategies for long-term and sustainable morbidity control

Schistosomiasis affects over 200 million people worldwide [1] and accounts for an estimated 1.9 million disability-adjusted life years (DALYs) annually [2], with 90% of the burden currently concentrated in Africa. The last decade has witnessed an extraordinary surge of advocacy and funding for neglected tropical diseases (NTDs), including schistosomiasis. Large-scale schistosomiasis control is now implemented in 30 countries in Africa [1], funded primarily through support from the United States Agency for International Development (USAID) and the Department for International Development (DFID), private philanthropic funds from the END Fund and through GiveWell recommendations, and leveraging praziquantel donations from Merck KGaA. However, the number of people still requiring treatment remains daunting [1]. The aim of current public health strategies for schistosomiasis is to decrease morbidity through preventive chemotherapy (PC) (Fig 1) [3]. Periodic large-scale administration of the drug praziquantel focusing on the school-aged population and high-risk adults aims to reduce the prevalence and intensity of infection [4]

Evaluation of arterial anatomy in congenital clubfoot with color doppler ultrasound

OBJECTIVE: This investigation intended to evaluate anterior and posterior tibial arteries at the ankle joint level in congenital clubfoot, by using color Doppler ultrasound (CDU). MATERIAL AND METHOD: Twenty patients with idiopathic clubfoot were selected, from which 18 had unilateral involvement and two had bilateral involvement. Of the 18 patients with unilateral clubfoot, 16 went through surgical treatment and the other two were submitted to conservative treatment with serial casting. Of the bilateral cases, one patient was treated surgically and the other was treated with serial casting. All patients were clinically and radiographically assessed. We used the functional rating as described by Lehman. Then, CDU was applied bilaterally at the ankle joint level, trying to identify both posterior and anterior tibial arteries. RESULTS: In our present series of 20 cases with idiopathic clubfoot, in just one patient we could not identify the anterior tibial artery at the ankle joint level. In 12 patients who have had their arterial flow speeds and diameters measured by UDC, a positive correlation was found between functional level and anterior tibial artery diameter. No statistically significant differences were found between both flow speed and diameter of anterior tibial artery of the normal side, when compared to the affected side (in patients with unilateral disease). CONCLUSION: In our sample, we could not find any significant differences in arterial morphology and flow speed between the normal and the affected side. Furthermore, we noticed that the better the clinical result of clubfoot correction, the larger the diameter of anterior tibial artery in affected feet.OBJETIVO: Avaliação ultrassonográfica das artérias tibial anterior e posterior no pé torto congênito (PTC). MATERIAL E MÉTODO: Foram incluídos 20 pacientes portadores de PTC idiopático compreendendo 18 casos unilaterais e dois bilaterais, sendo que 17 pacientes foram submetidos a tratamento cirúrgico e três a tratamento conservador. Todos os pacientes apresentavam pés plantígrados e foram submetidos à avaliação clínica e radiográfica, seguido pelo exame de ultrassom Doppler colorido (UDC), visando a identificação das artérias tibiais anterior e posterior na altura do tornozelo. O nível funcional foi classificado pelos critérios de Lehman. RESULTADOS: Nesta série de 20 pacientes, somente em um não foi identificada a artéria tibial anterior. Nos 12 pacientes submetidos à mensuração de fluxo e calibre pelo UDC, foi encontrada uma correlação positiva entre o grau funcional do PTC e o calibre da artéria tibial anterior. Não houve redução estatisticamente significante entre o fluxo e calibre da artéria tibial anterior do lado normal em comparação com o lado alterado (nos casos de doença unilateral). CONCLUSÕES: Não houve alteração significativa da morfologia e fluxo arterial quando comparamos os lados afetado e normal. Além disso, quanto melhor o resultado clínico da correção do PTC, maior foi o calibre da artéria tibial anterior.UNIFESP Departamento de Ortopedia e TraumatologiaUNIFESP, Depto. de Ortopedia e TraumatologiaSciEL

In-Cell Biochemistry Using NMR Spectroscopy

Biochemistry and structural biology are undergoing a dramatic revolution. Until now, mostly in vitro techniques have been used to study subtle and complex biological processes under conditions usually remote from those existing in the cell. We developed a novel in-cell methodology to post-translationally modify interactor proteins and identify the amino acids that comprise the interaction surface of a target protein when bound to the post-translationally modified interactors. Modifying the interactor proteins causes structural changes that manifest themselves on the interacting surface of the target protein and these changes are monitored using in-cell NMR. We show how Ubiquitin interacts with phosphorylated and non-phosphorylated components of the receptor tyrosine kinase (RTK) endocytic sorting machinery: STAM2 (Signal-transducing adaptor molecule), Hrs (Hepatocyte growth factor regulated substrate) and the STAM2-Hrs heterodimer. Ubiquitin binding mediates the processivity of a large network of interactions required for proper functioning of the RTK sorting machinery. The results are consistent with a weakening of the network of interactions when the interactor proteins are phosphorylated. The methodology can be applied to any stable target molecule and may be extended to include other post-translational modifications such as ubiquitination or sumoylation, thus providing a long-awaited leap to high resolution in cell biochemistry

How Humans Differ from Other Animals in Their Levels of Morphological Variation

Animal species come in many shapes and sizes, as do the individuals and populations that make up each species. To us, humans might seem to show particularly high levels of morphological variation, but perhaps this perception is simply based on enhanced recognition of individual conspecifics relative to individual heterospecifics. We here more objectively ask how humans compare to other animals in terms of body size variation. We quantitatively compare levels of variation in body length (height) and mass within and among 99 human populations and 848 animal populations (210 species). We find that humans show low levels of within-population body height variation in comparison to body length variation in other animals. Humans do not, however, show distinctive levels of within-population body mass variation, nor of among-population body height or mass variation. These results are consistent with the idea that natural and sexual selection have reduced human height variation within populations, while maintaining it among populations. We therefore hypothesize that humans have evolved on a rugged adaptive landscape with strong selection for body height optima that differ among locations

Declining resilience of ecosystem functions under biodiversity loss

The composition of species communities is changing rapidly through drivers such as habitat loss and climate change, with potentially serious consequences for the resilience of ecosystem functions on which humans depend. To assess such changes in resilience, we analyse trends in the frequency of species in Great Britain that provide key ecosystem functions-specifically decomposition, carbon sequestration, pollination, pest control and cultural values. For 4,424 species over four decades, there have been significant net declines among animal species that provide pollination, pest control and cultural values. Groups providing decomposition and carbon sequestration remain relatively stable, as fewer species are in decline and these are offset by large numbers of new arrivals into Great Britain. While there is general concern about degradation of a wide range of ecosystem functions, our results suggest actions should focus on particular functions for which there is evidence of substantial erosion of their resilience

Does Day Length Affect Winter Bird Distribution? Testing the Role of an Elusive Variable

Differences in day length may act as a critical factor in bird biology by introducing time constraints in energy acquisition during winter. Thus, differences in day length might operate as a main determinant of bird abundance along latitudinal gradients. This work examines the influence of day length on the abundance of wintering crested tits (Lophophanes cristatus) in 26 localities of Spanish juniper (Juniperus thurifera) dwarf woodlands (average height of 5 m) located along a latitudinal gradient in the Spanish highlands, while controlling for the influence of food availability, minimum night temperature, habitat structure and landscape characteristics. Top regression models in the AIC framework explained 56% of variance in bird numbers. All models incorporated day length as the variable with the highest magnitude effect. Food availability also played an important role, although only the crop of ripe juniper fruits, but not arthropods, positively affected crested tit abundance. Differences in vegetation structure across localities had also a strong positive effect (average tree height and juniper tree density). Geographical variation in night temperature had no influence on crested tit distribution, despite the low winter temperatures reached in these dwarf forests. This paper demonstrates for the first time that winter bird abundance increases with day length after controlling for the effect of other environmental variables. Winter average difference in day length was only 10.5 minutes per day along the 1°47′ latitudinal interval (190 km) included in this study. This amount of time, which reaches 13.5 h accumulated throughout the winter season, appears to be large enough to affect the long-term energy budget of small passerines during winter and to shape the distribution of winter bird abundance under restrictive environmental conditions

Inflammation and blood-brain barrier breach remote from the primary injury following neurotrauma

Background: Following injury to the central nervous system, increased microglia, secretion of pro- and anti-inflammatory cytokines, and altered blood-brain barrier permeability, a hallmark of degeneration, are observed at and immediately adjacent to the injury site. However, few studies investigate how regions remote from the primary injury could also suffer from inflammation and secondary degeneration. Methods: Adult female Piebald-Viral-Glaxo (PVG) rats underwent partial transection of the right optic nerve, with normal, age-matched, unoperated animals as controls. Perfusion-fixed brains and right optic nerves were harvested for immunohistochemical assessment of inflammatory markers and blood-brain barrier integrity; fresh-frozen brains were used for multiplex cytokine analysis. Results: Immediately ventral to the optic nerve injury, immunointensity of both the pro-inflammatory biomarker inducible nitric oxide synthase (iNOS) and the anti-inflammatory biomarker arginase-1 (Arg1) increased at 7 days post-injury, with colocalization of iNOS and Arg1 immunoreactivity within individual cells. CD11b+ and CD45+ cells were increased 7 days post-injury, with altered BBB permeability still evident at this time. In the lower and middle optic tract and superior colliculus, IBA1+ resident microglia were first increased at 3 days; ED1+ and CD11b+ cells were first increased in the middle and upper tract and superior colliculus 7 days post-injury. Increased fibrinogen immunoreactivity indicative of altered BBB permeability was first observed in the contralateral upper tract at 3 days and middle tract at 7 days post-injury. Multiplex cytokine analysis of brain homogenates indicated significant increases in the pro-inflammatory cytokines, IL-2 and TNFa, and anti-inflammatory cytokine IL-10 1 day post-injury, decreasing to control levels at 3 days for TNFa and 7 days for IL-2. IL-10 was significantly elevated at 1 and 7 days post-injury with a dip at 3 days post-injury. Conclusions: Partial injury to the optic nerve induces a complex remote inflammatory response, characterized by rapidly increased pro- and anti-inflammatory cytokines in brain homogenates, increased numbers of IBA1+ cells throughout the visual pathways, and increased CD11b+ and ED1+ inflammatory cells, particularly towards the synaptic terminals. BBB permeability can increase prior to inflammatory cell infiltration, dependent on the brain region

BB0172, a Borrelia burgdorferi Outer Membrane Protein That Binds Integrin Α3Β1

Lyme disease is a multisystemic disorder caused by Borrelia burgdorferi infection. Upon infection, some B. burgdorferi genes are upregulated, including members of the microbial surface components recognizing adhesive matrix molecule (MSCRAMM) protein family, which facilitate B. burgdorferi adherence to extracellular matrix components of the host. Comparative genome analysis has revealed a new family of B. burgdorferi proteins containing the von Willebrand factor A (vWFA) domain. In the present study, we characterized the expression and membrane association of the vWFA domain-containing protein BB0172 by using in vitro transcription/translation systems in the presence of microsomal membranes and with detergent phase separation assays. Our results showed evidence of BB0172 localization in the outer membrane, the orientation of the vWFA domain to the extracellular environment, and its function as a metal ion-dependent integrin-binding protein. This is the first report of a borrelial adhesin with a metal ion-dependent adhesion site (MIDAS) motif that is similar to those observed in eukaryotic integrins and has a similar function