A cytokine immunosensor for multiple sclerosis detection based upon label-free electrochemical impedance spectroscopy

A biosensor for the serum cytokine, interleukin-12 (IL-12), based upon a label-free electrochemical impedance spectroscopy monitoring is described. Overexpression of IL-12 has been correlated to the diagnosis of multiple sclerosis (MS). The prototype biosensor was fabricated on a disposable gold-coated silver ribbon electrode by immobilizing anti-IL-12 monoclonal antibodies (mAbs) onto the surface of the electrode. This technique was advantageous as the silver electrodes provided a more rigid and conductive substrate than thin gold foil electrodes and helped in obtaining more reproducible data when used with the electrode holder. Results indicate that IL-12 can be detected at physiological levels, <100 fM with p<0.05 in a label-free and real-time manner. The cost-effective approach described here can be used for diagnosis of diseases (like MS) with known biomarkers in body fluids and for monitoring physiological levels of biomolecules with healthcare, food, and environmental relevance.     

Abnormal Anatomical Connectivity between the Amygdala and Orbitofrontal Cortex in Conduct Disorder

Objective

Previous research suggested that structural and functional abnormalities within the amygdala and orbitofrontal cortex contribute to the pathophysiology of Conduct Disorder (CD). Here, we investigated whether the integrity of the white-matter pathways connecting these regions is abnormal and thus may represent a putative neurobiological marker for CD.

Methods

Diffusion Tensor Imaging (DTI) was used to investigate white-matter microstructural integrity in male adolescents with childhood-onset CD, compared with healthy controls matched in age, sex, intelligence, and socioeconomic status. Two approaches were employed to analyze DTI data: voxel-based morphometry of fractional anisotropy (FA), an index of white-matter integrity, and virtual dissection of white-matter pathways using tractography.

Results

Adolescents with CD displayed higher FA within the right external capsule relative to controls (T = 6.08, P<0.05, Family-Wise Error, whole-brain correction). Tractography analyses showed that FA values within the uncinate fascicle (connecting the amygdala and orbitofrontal cortex) were abnormally increased in individuals with CD relative to controls. This was in contrast with the inferior frontal-occipital fascicle, which showed no significant group differences in FA. The finding of increased FA in the uncinate fascicle remained significant when factoring out the contribution of attention-deficit/hyperactivity disorder symptoms. There were no group differences in the number of streamlines in either of these anatomical tracts.

Conclusions

These results provide evidence that CD is associated with white-matter microstructural abnormalities in the anatomical tract that connects the amygdala and orbitofrontal cortex, the uncinate fascicle. These results implicate abnormal maturation of white-matter pathways which are fundamental in the regulation of emotional behavior in CD.     

Molecular phylogeny of Solms‐laubachia (Brassicaceae) s.l., based on multiple nuclear and plastid DNA sequences,and its biogeographic implications

Abstract The Hengduan Mountains region of south‐west China is a noted biodiversity hotspot, but the geographic origins and historical assembly of its rich endemic flora, including the sky‐island species of Solms‐laubachia Muschl. (Brassicaceae), have been little studied. Previous molecular studies on the phylogeny of Solms‐laubachia showed it to be paraphyletic, leading to considerable expansion not only of its taxonomic limits, but also its geographic range, with the inclusion of taxa from outside the Hengduan region. However, these studies provided little resolution of interspecific relationships, preventing inferences about historical biogeography within the clade. In the present study, new sequence data from two nuclear genes (LEAFY and G3pdh) and two chloroplast intergenic spacers (petN–psbM and psbM–trnD) were combined with existing markers to increase phylogenetic signals. Phaeonychium villosum (Maxim.) Al‐Shehbaz was found to be nested within Solms‐laubachia s.l. In general, phylogenetic relationships appear to be a good predictor of geography, with the Hengduan Mountain endemics embedded in a paraphyletic grade of species from the western Himalayas and central Asia, but they also imply morphological homoplasy. Incongruence was detected between the nuclear and chloroplast gene trees, perhaps resulting from incomplete lineage sorting of ancestral polymorphisms. The crown age of Solms‐laubachia s.l. was estimated to be approximately 1.42–3.68 mya, using Bayesian relaxed molecular clock analysis. Historical biogeographic analysis using a parametric dispersal–extinction–cladogenesis model inferred central Asia and the western Himalayas as most probable ancestral range of Solms‐laubachia s.l., and estimated higher rates of eastward expansion than westward during the diversification of descendant lineages. In summary, our results suggest that Solms‐laubachia s.l. originated during the Pliocene in central Asia, and subsequently migrated eastward into the Hengduan Mountains, colonizing sky‐island, alpine scree‐slope habitats that may have provided novel ecological opportunity and accelerated speciation, ultimately establishing this region as the present center of diversity of the genus.     

Talin Autoinhibition Is Required for Morphogenesis

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Global Disease Monitoring and Forecasting with Wikipedia

Infectious disease is a leading threat to public health, economic stability, and other key social structures. Efforts to mitigate these impacts depend on accurate and timely monitoring to measure the risk and progress of disease. Traditional, biologically-focused monitoring techniques are accurate but costly and slow; in response, new techniques based on social internet data, such as social media and search queries, are emerging. These efforts are promising, but important challenges in the areas of scientific peer review, breadth of diseases and countries, and forecasting hamper their operational usefulness. We examine a freely available, open data source for this use: access logs from the online encyclopedia Wikipedia. Using linear models, language as a proxy for location, and a systematic yet simple article selection procedure, we tested 14 location-disease combinations and demonstrate that these data feasibly support an approach that overcomes these challenges. Specifically, our proof-of-concept yields models with up to 0.92, forecasting value up to the 28 days tested, and several pairs of models similar enough to suggest that transferring models from one location to another without re-training is feasible. Based on these preliminary results, we close with a research agenda designed to overcome these challenges and produce a disease monitoring and forecasting system that is significantly more effective, robust, and globally comprehensive than the current state of the art.     

Blebs produced by actin–myosin contraction during apoptosis release damage-associated molecular pattern proteins before secondary necrosis occurs

Apoptosis is a fundamental homeostatic mechanism essential for the normal growth, development and maintenance of every tissue and organ. Dying cells have been defined as apoptotic by distinguishing features, including cell contraction, nuclear fragmentation, blebbing, apoptotic body formation and maintenance of intact cellular membranes to prevent massive protein release and consequent inflammation. We now show that during early apoptosis limited membrane permeabilization occurs in blebs and apoptotic bodies, which allows release of proteins that may affect the proximal microenvironment before the catastrophic loss of membrane integrity during secondary necrosis. Blebbing, apoptotic body formation and protein release during early apoptosis are dependent on ROCK and myosin ATPase activity to drive actomyosin contraction. We identified 231 proteins released from actomyosin contraction-dependent blebs and apoptotic bodies by adapted SILAC (stable isotope labeling with amino acids in cell culture) combined with mass spectrometry analysis. The most enriched proteins released were the nucleosomal histones, which have previously been identified as damage-associated molecular pattern proteins (DAMPs) that can initiate sterile inflammatory responses. These results indicate that limited membrane permeabilization occurs in blebs and apoptotic bodies before secondary necrosis, leading to acute and localized release of immunomodulatory proteins during the early phase of active apoptotic membrane blebbing. Therefore, the shift from apoptosis to secondary necrosis is more graded than a simple binary switch, with the membrane permeabilization of apoptotic bodies and consequent limited release of DAMPs contributing to the transition between these states.     

Studies on sodium bypass flow in lateral rootless mutants lrt1 and lrt2, and crown rootless mutant crl1 of rice (Oryza sativa L.)

An apoplastic pathway, the so‐called bypass flow, is important for Na⁺ uptake in rice (Oryza sativa L.) under saline conditions; however, the precise site of entry is not yet known. We report the results of our test of the hypothesis that bypass flow of Na⁺ in rice occurs at the site where lateral roots emerge from the main roots. We investigated Na⁺ uptake and bypass flow in lateral rootless mutants (lrt1, lrt2), a crown rootless mutant (crl1), their wild types (Oochikara, Nipponbare and Taichung 65, respectively) and in seedlings of rice cv. IR36. The results showed that shoot Na⁺ concentration in lrt1, lrt2 and crl1 was lower (by 20–23%) than that of their wild types. In contrast, the bypass flow quantified using trisodium‐8‐hydroxy‐1,3,6‐pyrenetrisulphonic acid (PTS) was significantly increased in the mutants, from an average of 1.1% in the wild types to 3.2% in the mutants. Similarly, bypass flow in shoots of IR36 where the number of lateral and crown roots had been reduced through physical and hormonal manipulations was dramatically increased (from 5.6 to 12.5%) as compared to the controls. The results suggest that the path of bypass flow in rice is not at the sites of lateral root emergence.     

Directional and balancing selection in human beta-defensins

Background  

In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations.