A new role for PGRP-S (Tag7) in immune defense: lymphocyte migration is induced by a chemoattractant complex of Tag7 with Mts1

PGRP-S (Tag7) is an innate immunity protein involved in the antimicrobial defense systems, both in insects and in mammals. We have previously shown that Tag7 specifically interacts with several proteins, including Hsp70 and the calcium binding protein S100A4 (Mts1), providing a number of novel cellular functions. Here we show that Tag7–Mts1 complex causes chemotactic migration of lymphocytes, with NK cells being a preferred target. Cells of either innate immunity (neutrophils and monocytes) or acquired immunity (CD4⁺ and CD8⁺ lymphocytes) can produce this complex, which confirms the close connection between components of the 2 branches of immune response.     

Synthesis and antiviral evaluation of benzimidazoles, quinoxalines and indoles from dehydroabietic acid

Several heterocycles, such as benzimidazoles, quinoxalines and indoles incorporated into a hydrophenanthrene and naphthalene skeleton, were synthesised from two useful ortho-bromonitro precursors derived from dehydroabietic acid: methyl 12-bromo-13-nitro-deisopropyldehydroabietate and methyl 12-bromo-13,14-dinitro-deisopropyldehydroabietate. The new heterocycles were evaluated for their activity in vitro against several RNA and DNA viruses.     

Non-random chromosomal distribution of SSLPs: systematic assessment using a novel genetic linkage map between two closely related rat strains

Simple sequence length polymorphisms (SSLPs) are a widely used tool for genetic studies in humans and model animals. Experimental crosses among closely related strains that differ primarily in the trait that is to be mapped carry the advantage of avoiding co-segregation of potentially confounding traits. However, their realization is encumbered by the limited availability of newly arisen informative SSLPs among such strains. Here we report the establishment of a genome-wide SSLP panel for the spontaneously hypertensive rat (SHR) and its close relative, the stroke-prone SHR (SHRSP), consisting of a total of 273 polymorphic markers that were found among 2,734 rat SSLPs screened. In addition to limitations in numbers, we also found the distribution of informative markers to be heterogeneous, with clustering and paucity of informative markers, respectively, in particular regions. Notably, the majority of regions thus identified was also seen when we examined an unrelated set of strains from the literature, indicating, on a more generic level, the presence of mutagenically more and less stable genomic regions.     

Carotid Intima-Media Thickness at Age 30, Birth Weight,Accelerated Growth during Infancy and Breastfeeding: A Birth Cohort Study in Southern Brazil

Objective

To examine the relationship between carotid intima-media thickness (IMT) at age 30 and birth characteristics, growth during infancy, and breastfeeding duration, among subjects who have been prospectively followed since birth.

Methods and Results

In 1982, all births in the city of Pelotas, southern Brazil, were identified and those children (n = 5,914) whose families lived in the urban area of the city have been followed and evaluated at several time points. The cohort participants were evaluated in 2012–13, and IMT was measured at the posterior wall of the right and left common carotid arteries in longitudinal planes using ultrasound imaging. We obtained valid IMT measurements for 3,188 individuals. Weight-for-age z-score (WAZ) at age 2 years, weight-for-height z-score (WHZ) at age 4, height-for-age z-score (HAZ) at 4 years, WAZ at age 4 and relative conditional weight at 4 years were positively associated with IMT, even after controlling for confounding variables. The beta-coefficient associated with ≥1 s.d. WAZ at age 2 (compared to those with a <–1 s.d.) was 3.62 μm (95% CI 0.86 to 6.38). The beta-coefficient associated with ≥1 s.d. WHZ at 4 (in relation to <–1 s.d) was 3.83 μm (95% CI 0.24 to 7.42). For HAZ at 4, the beta-coefficient for ≥1 s.d. in relation to <–1 s.d. was 4.19 μm (95% CI 1.14 to 7.25). For WAZ at 4, the beta-coefficient associated with ≥1 s.d. in relation to <–1 s.d. was 4.28 μm (95% CI 1.59 to 6.97). The beta-coefficient associated with conditional weight gain at age 2–4 was 1.26 μm (95% CI 0.49 to 2.02).

Conclusion

IMT at age 30 was positively associated with WAZ at age 2 years, WHZ at age 4, HAZ at age 4, WAZ at age 4 and conditional weight gain at age 4 years.     

Cross-Sectional and Prospective Associations between Physical Activity and C-Reactive Protein in Males

BackgroundThere is conflicting evidence about the association between physical activity and inflammatory markers. Few prospective studies are available, particularly from low and middle-income countries. This study was aimed at assessing the cross-sectional and prospective associations between physical activity and C-reactive protein (CRP) levels in males belonging to the 1982 Pelotas (Brazil) Birth Cohort Study.MethodsThe sample comprised 2,213 males followed up at the ages of 18 and 23 years. We performed high sensitivity CRP assays; we used a cut-off of 3 mg/L in categorical analyses. We measured physical activity by self-report at ages 18 and 23 years. Body mass index and waist circumference were studies as possible mediators.ResultsCRP levels above the 3mg/L cut-off were found in 13.3% (95%CI: 11.7; 14.8) of the individuals. We found no evidence for an association between physical activity (leisure-time or all-domains) and either continuous (geometrical mean) or categorical CRP. We confirmed these null findings in (a) prospective and cross-sectional analyses; (b) trajectories analyses.ConclusionsThere was no association between CRP levels and physical activity levels in early adulthood in a large birth cohort. Little variability in CRP at this early age is the likely explanation for these null findings.     

Network Events on Multiple Space and Time Scales in Cultured Neural Networks and in a Stochastic Rate Model

Cortical networks, in-vitro as well as in-vivo, can spontaneously generate a variety of collective dynamical events such as network spikes, UP and DOWN states, global oscillations, and avalanches. Though each of them has been variously recognized in previous works as expression of the excitability of the cortical tissue and the associated nonlinear dynamics, a unified picture of the determinant factors (dynamical and architectural) is desirable and not yet available. Progress has also been partially hindered by the use of a variety of statistical measures to define the network events of interest. We propose here a common probabilistic definition of network events that, applied to the firing activity of cultured neural networks, highlights the co-occurrence of network spikes, power-law distributed avalanches, and exponentially distributed ‘quasi-orbits’, which offer a third type of collective behavior. A rate model, including synaptic excitation and inhibition with no imposed topology, synaptic short-term depression, and finite-size noise, accounts for all these different, coexisting phenomena. We find that their emergence is largely regulated by the proximity to an oscillatory instability of the dynamics, where the non-linear excitable behavior leads to a self-amplification of activity fluctuations over a wide range of scales in space and time. In this sense, the cultured network dynamics is compatible with an excitation-inhibition balance corresponding to a slightly sub-critical regime. Finally, we propose and test a method to infer the characteristic time of the fatigue process, from the observed time course of the network’s firing rate. Unlike the model, possessing a single fatigue mechanism, the cultured network appears to show multiple time scales, signalling the possible coexistence of different fatigue mechanisms.     

Analysis of the Role of Interleukin 6 Receptor Haplotypes in the Regulation of Circulating Levels of Inflammatory Biomarkers and Risk of Coronary Heart Disease

Variants at the interleukin 6 receptor (IL6R) gene regulate inflammation and are associated with risk of coronary heart disease (CHD). The aim of the present study was to investigate the effects of IL6R haplotypes on circulating levels of inflammatory biomarkers and risk of CHD. We performed a discovery analysis in SHEEP, a myocardial infarction (MI) case control study (n = 2,774) and replicated our results in two large, independent European populations, PROCARDIS, a CHD case control study (n = 7,998), and IMPROVE (n = 3,711) a prospective cardiovascular cohort study. Two major haplotype blocks (rs12083537A/G and rs4075015A/T—block 1; and rs8192282G/A, rs4553185T/C, rs8192284A/C, rs4240872T/C and rs7514452T/C—block 2) were identified in the IL6R gene. IL6R haplotype associations with C-reactive protein (CRP), fibrinogen, IL6, soluble IL6R (sIL6R), IL6, IL8 and TNF-α in SHEEP, CRP and fibrinogen in PROCARDIS and CRP in IMPROVE as well as association with risk of MI and CHD, were analyzed by THESIAS. Haplotypes in block 1 were associated neither with circulating inflammatory biomarkers nor with the MI/CHD risk. Haplotypes in block 2 were associated with circulating levels of CRP, in all three study populations, with fibrinogen in SHEEP and PROCARDIS, with IL8 and sIL6Rin SHEEP and with a modest, non significant, increase (7%) in MI/CHD risk in the three populations studied. Our results indicate that IL6R haplotypes regulate the circulating levels of inflammatory biomarkers. Lack of association with the risk of CHD may be explained by the combined effect of SNPs with opposite effect on the CHD risk, the sample size as well as by structural changes affecting sIL6R stability in the circulation.     

<Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> inhibits <Emphasis Type="Italic">in-vitro Candida</Emphasis> biofilm development

Background  

Elucidation of the communal behavior of microbes in mixed species biofilms may have a major impact on understanding infectious diseases and for the therapeutics. Although, the structure and the properties of monospecies biofilms and their role in disease have been extensively studied during the last decade, the interactions within mixed biofilms consisting of bacteria and fungi such as Candida spp. have not been illustrated in depth. Hence, the aim of this study was to evaluate the interspecies interactions of Pseudomonas aeruginosa and six different species of Candida comprising C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and C. dubliniensis in dual species biofilm development.     

Molecular determinants of caste differentiation in the highly eusocial honeybee <Emphasis Type="Italic">Apis mellifera</Emphasis>

Background  

In honeybees, differential feeding of female larvae promotes the occurrence of two different phenotypes, a queen and a worker, from identical genotypes, through incremental alterations, which affect general growth, and character state alterations that result in the presence or absence of specific structures. Although previous studies revealed a link between incremental alterations and differential expression of physiometabolic genes, the molecular changes accompanying character state alterations remain unknown.     

Natural and within-farmland biodiversity enhances crop productivity

Ongoing expansion of large-scale agriculture critically threatens natural habitats and the pollination services they offer. Creating patches with high plant diversity within farmland is commonly suggested as a measure to benefit pollinators. However, farmers rarely adopt such practice, instead removing naturally occurring plants (weeds). By combining pollinator exclusion experiments with analysis of honeybee behaviour and flower-visitation webs, we found that the presence of weeds allowed pollinators to persist within sunflower fields, maximizing the benefits of the remaining patches of natural habitat to productivity of this large-scale crop. Weed diversity increased flower visitor diversity, hence ameliorating the measured negative effects of isolation from natural habitat. Although honeybees were the most abundant visitors, diversity of flower visitors enhanced honeybee movement, being the main factor influencing productivity. Conservation of natural patches combined with promoting flowering plants within crops can maximize productivity and, therefore, reduce the need for cropland expansion, contributing towards sustainable agriculture.