B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Long-lived magnetism from solidification-driven convection on the pallasite parent body.

Palaeomagnetic measurements of meteorites suggest that, shortly after the birth of the Solar System, the molten metallic cores of many small planetary bodies convected vigorously and were capable of generating magnetic fields. Convection on these bodies is currently thought to have been thermally driven, implying that magnetic activity would have been short-lived. Here we report a time-series palaeomagnetic record derived from nanomagnetic imaging of the Imilac and Esquel pallasite meteorites, a group of meteorites consisting of centimetre-sized metallic and silicate phases. We find a history of long-lived magnetic activity on the pallasite parent body, capturing the decay and eventual shutdown of the magnetic field as core solidification completed. We demonstrate that magnetic activity driven by progressive solidification of an inner core is consistent with our measured magnetic field characteristics and cooling rates. Solidification-driven convection was probably common among small body cores, and, in contrast to thermally driven convection, will have led to a relatively late (hundreds of millions of years after accretion), long-lasting, intense and widespread epoch of magnetic activity among these bodies in the early Solar System.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement No. 320750, the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 312284, the Natural Environment Research Council, Fundación ARAID and the Spanish MINECO MAT2011-23791.This is the accepted manuscript. The final version is available from Nature at http://www.nature.com/nature/journal/v517/n7535/full/nature14114.html

Health and Pleasure in Consumers' Dietary Food Choices: Individual Differences in the Brain's Value System

Taking into account how people value the healthiness and tastiness of food at both the behavioral and brain levels may help to better understand and address overweight and obesity-related issues. Here, we investigate whether brain activity in those areas involved in self-control may increase significantly when individuals with a high body-mass index (BMI) focus their attention on the taste rather than on the health benefits related to healthy food choices. Under such conditions, BMI is positively correlated with both the neural responses to healthy food choices in those brain areas associated with gustation (insula), reward value (orbitofrontal cortex), and self-control (inferior frontal gyrus), and with the percent of healthy food choices. By contrast, when attention is directed towards health benefits, BMI is negatively correlated with neural activity in gustatory and reward-related brain areas (insula, inferior frontal operculum). Taken together, these findings suggest that those individuals with a high BMI do not necessarily have reduced capacities for self-control but that they may be facilitated by external cues that direct their attention toward the tastiness of healthy food. Thus, promoting the taste of healthy food in communication campaigns and/or food packaging may lead to more successful self-control and healthy food behaviors for consumers with a higher BMI, an issue which needs to be further researched

Tracing Functional Antigen-Specific CCR6+ Th17 Cells after Vaccination

BACKGROUND: The function of T helper cell subsets in vivo depends on their location, and one hallmark of T cell differentiation is the sequential regulation of migration-inducing chemokine receptor expression. CC-chemokine receptor 6 (CCR6) is a trait of tissue-homing effector T cells and has recently been described as a receptor on T helper type 17 (Th17) cells. Th17 cells are associated with autoimmunity and the defence against certain infections. Although, the polarization of Th cells into Th17 cells has been studied extensively in vitro, the development of those cells during the physiological immune response is still elusive. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the development and functionality of Th17 cells in immune-competent mice during an ongoing immune response. In naïve and vaccinated animals CCR6(+) Th cells produce IL-17. The robust homeostatic proliferation and the presence of activation markers on CCR6(+) Th cells indicate their activated status. Vaccination induces antigen-specific CCR6(+) Th17 cells that respond to in vitro re-stimulation with cytokine production and proliferation. Furthermore, depletion of CCR6(+) Th cells from donor leukocytes prevents recipients from severe disease in experimental autoimmune encephalomyelitis, a model for multiple sclerosis in mice. CONCLUSIONS/SIGNIFICANCE: In conclusion, we defined CCR6 as a specific marker for functional antigen-specific Th17 cells during the immune response. Since IL-17 production reaches the highest levels during the immediate early phase of the immune response and the activation of Th17 cells precedes the Th1 cell differentiation we tent to speculate that this particular Th cell subset may represent a first line effector Th cell subpopulation. Interference with the activation of this Th cell subtype provides an interesting strategy to prevent autoimmunity as well as to establish protective immunity against infections

LMS vs XMSS: Comparison of Stateful Hash-Based Signature Schemes on ARM Cortex-M4

Stateful hash-based signature schemes are among the most efficient approaches for post-quantum signature schemes. Although not suitable for general use, they may be suitable for some use cases on constrained devices. LMS and XMSS are hash-based signature schemes that are conjectured to be quantum secure. In this work, we compared multiple instantiations of both schemes on an ARM Cortex-M4. More precisely, we compared performance, stack consumption, and other figures for key generation, signing and verifying. To achieve this, we evaluated LMS and XMSS using optimised implementations of SHA-256, SHAKE256, Gimli-Hash, and different variants of Keccak. Furthermore, we present slightly optimised implementations of XMSS achieving speedups of up to 3.11x for key generation, 3.11x for signing, and 4.32x for verifying

Serious, Minor, and Non-Delinquents in Early Adolescence: The Impact of Cumulative Risk and Promotive Factors. The TRAILS Study

This study uses a social-ecological approach to the development of delinquency. The authors emphasize that a balance between eliminating risk and enhancing protection across domains is essential in reducing problems and promoting competence. The cumulative risk and promotive effects of temperament, family and school factors in preadolescence were examined on different groups of delinquents (based on self-report) in early adolescence. Data from the first two waves of the TRAILS study (N = 2,230) were used. The results provide evidence for a compensatory model that assumes main effects of risk and promotive factors on problem behavior. Accumulation of risks in preadolescence promoted being a serious delinquent in early adolescence, with the strongest effects for temperament. Accumulation of promotive effects decreased being a delinquent and supported being a non-delinquent. Furthermore, evidence is found for a counter-balancing effect of cumulative promotive and risk factors. Exposure to more promotive domains in the relative absence of risk domains decreased the percentage of serious delinquents. Our results did not support a protective model. Implications for prevention and intervention are discussed

HYPEST study: profile of hypertensive patients in Estonia

<p>Abstract</p> <p>Background</p> <p>More than one third of adult population in Estonia has problems with elevated blood pressure (BP). The <it>Hypertension in Estonia </it>(HYPEST) study represents the country's first hypertension-targeted sample collection aiming to examine the epidemiological and genetic determinants for hypertension (HTN) and related cardiovascular diseases (CVD) in Estonian population. The HYPEST subjects (n = 1,966) were recruited across Estonia between 2004-2007 including clinically diagnosed HTN cases and population-based controls. The present report is focused on the clinical and epidemiological profile of HYPEST cases, and gender-specific effects on the pathophysiology of hypertension.</p> <p>Methods</p> <p>Current analysis was performed on 1,007 clinically diagnosed HTN patients (617 women and 390 men) aged 18-85 years. The hypertensives were recruited to the study by BP specialists at the North Estonia Medical Center, Centre of Cardiology, Tallinn or at the Cardiology Clinic, Tartu University Hospital, Estonia. Longitudinal BP data was extracted retrospectively from clinical records. Current and retrospective data of patient's medical history, medication intake and lifestyle habits were derived from self-administrated questionnaire and each variable was examined separately for men and women. Eleven biochemical parameters were measured from fasting serum samples of 756 patients.</p> <p>Results</p> <p>The distribution of recruited men and women was 39% and 61% respectively. Majority of Estonian HTN patients (85%) were overweight (BMI ≥ 25 kg/m²) and a total of 79% of patients had additional complications with cardiovascular system. In men, the hypertension started almost 5 years earlier than in women (40.5 ± 14.5 vs 46.1 ± 12.7 years), which led to earlier age of first myocardial infarction (MI) and overall higher incidence rate of MI among male patients (men 21.2%, women 8.9%, <it>P </it>< 0.0001). Heart arrhythmia, thyroid diseases, renal tubulo-intestinal diseases and hyperlipidemia were more prevalent in hypertensive women compared to men (<it>P </it>< 0.0001). An earlier age of HTN onset was significantly associated with smoking (<it>P </it>= 0.00007), obesity (BMI ≥ 30 kg/m²; <it>P </it>= 0.0003), increased stress (<it>P </it>= 0.0003) and alcohol consumption (<it>P </it>= 0.004).</p> <p>Conclusion</p> <p>Understanding the clinical profile of HTN patients contributes to CVD management. Estonian hypertension patients exhibited different disease and risk profiles of male and female patients. This well-characterized sample set provides a good resource for studying hypertension and other cardiovascular phenotypes.</p

Creation and annihilation of topological meron pairs in in-plane magnetized films

Merons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in chiral magnet Co8Zn9Mn3 raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii-Moriya interaction

Differential Actions of Chlorhexidine on the Cell Wall of Bacillus subtilis and Escherichia coli

Chlorhexidine is a chlorinated phenolic disinfectant used commonly in mouthwash for its action against bacteria. However, a comparative study of the action of chlorhexidine on the cell morphology of Gram-positive and Gram-negative bacteria is lacking. In this study, the actions of chlorhexidine on the cell morphology were identified with the aids of electron microscopy. After exposure to chlorhexidine, numerous spots of indentation on the cell wall were found in both Bacillus subtilis and Escherichia coli. The number of indentation spots increased with time of incubation and increasing chlorhexidine concentration. Interestingly, the dented spots found in B. subtilis appeared mainly at the hemispherical caps of the cells, while in E. coli the dented spots were found all over the cells. After being exposed to chlorhexidine for a prolonged period, leakage of cellular contents and subsequent ghost cells were observed, especially from B subtilis. By using 2-D gel/MS-MS analysis, five proteins related to purine nucleoside interconversion and metabolism were preferentially induced in the cell wall of E. coli, while three proteins related to stress response and four others in amino acid biosynthesis were up-regulated in the cell wall materials of B. subtilis. The localized morphological damages together with the biochemical and protein analysis of the chlorhexidine-treated cells suggest that chlorhexidine may act on the differentially distributed lipids in the cell membranes/wall of B. subtilis and E. coli