Production,Fate and Pathogenicity of Plasma Microparticles in Murine Cerebral Malaria

In patients with cerebral malaria (CM), higher levels of cell-specific microparticles (MP) correlate with the presence of neurological symptoms. MP are submicron plasma membrane-derived vesicles that express antigens of their cell of origin and phosphatidylserine (PS) on their surface, facilitating their role in coagulation, inflammation and cell adhesion. In this study, the in vivo production, fate and pathogenicity of cell-specific MP during Plasmodium berghei infection of mice were evaluated. Using annexin V, a PS ligand, and flow cytometry, analysis of platelet-free plasma from infected mice with cerebral involvement showed a peak of MP levels at the time of the neurological onset. Phenotypic analyses showed that MP from infected mice were predominantly of platelet, endothelial and erythrocytic origins. To determine the in vivo fate of MP, we adoptively transferred fluorescently labelled MP from mice with CM into healthy or infected recipient mice. MP were quickly cleared following intravenous injection, but microscopic examination revealed arrested MP lining the endothelium of brain vessels of infected, but not healthy, recipient mice. To determine the pathogenicity of MP, we transferred MP from activated endothelial cells into healthy recipient mice and this induced CM-like brain and lung pathology. This study supports a pathogenic role for MP in the aggravation of the neurological lesion and suggests a causal relationship between MP and the development of CM.     

A 660-Kb Deletion with Antagonistic Effects on Fertility and Milk Production Segregates at High Frequency in Nordic Red Cattle: Additional Evidence for the Common Occurrence of Balancing Selection in Livestock

In dairy cattle, the widespread use of artificial insemination has resulted in increased selection intensity, which has led to spectacular increase in productivity. However, cow fertility has concomitantly severely declined. It is generally assumed that this reduction is primarily due to the negative energy balance of high-producing cows at the peak of lactation. We herein describe the fine-mapping of a major fertility QTL in Nordic Red cattle, and identify a 660-kb deletion encompassing four genes as the causative variant. We show that the deletion is a recessive embryonically lethal mutation. This probably results from the loss of RNASEH2B, which is known to cause embryonic death in mice. Despite its dramatic effect on fertility, 13%, 23% and 32% of the animals carry the deletion in Danish, Swedish and Finnish Red Cattle, respectively. To explain this, we searched for favorable effects on other traits and found that the deletion has strong positive effects on milk yield. This study demonstrates that embryonic lethal mutations account for a non-negligible fraction of the decline in fertility of domestic cattle, and that associated positive effects on milk yield may account for part of the negative genetic correlation. Our study adds to the evidence that structural variants contribute to animal phenotypic variation, and that balancing selection might be more common in livestock species than previously appreciated.     

Influence of +1245 A/G MT1A polymorphism on advanced glycation end-products (AGEs) in elderly: effect of zinc supplementation

Advanced glycation end-products (AGEs) stimulate reactive oxygen species (ROS) generation and represent a risk factor for atherosclerosis, while their formation seems to be prevented by zinc. Metallothioneins (MT), zinc-binding proteins exert an antioxidant function by regulating intracellular zinc availability and protecting cells from ROS damages. +1245 A/G MT1A polymorphism was implicated in type 2 diabetes and in cardiovascular disease development as well as in the modulation of antioxidant response. The purpose of this study was to investigate the influence of +1245 A/G MT1A polymorphism on AGEs and ROS production and to verify the effect of zinc supplementation on plasma AGEs, zinc status parameters and antioxidant enzyme activity in relation to this SNP. One hundred and ten healthy subjects (72 ± 6 years) from the ZincAge study were supplied with zinc aspartate (10 mg/day for 7 weeks) and screened for +1245 MT1A polymorphism. +1245 MT1A G+ (Arginine) genotype showed higher plasma AGEs and ROS production in peripheral blood mononuclear cells (PBMCs) than G− (Lysine) one at the baseline. No significant changes after zinc supplementation were observed for AGEs, ROS and MT levels as well as for enzyme antioxidant activity in relation to the genotype. Among zinc status parameters, major increases were observed for the intracellular labile zinc (iZnL) and the NO-induced release of zinc in PBMCs, in G+ genotype as compared to G− one. In summary, +1245 G+ carriers showed increased plasma AGEs and ROS production in PBMCs at baseline and a higher improvement in iZnL after zinc intervention with respect to G− individuals.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0426-2) contains supplementary material, which is available to authorized users.     

CHILL-COMA TOLERANCE, A MAJOR CLIMATIC ADAPTATION AMONG DROSOPHILA SPECIES

Abstract.— Most drosophilid species can be classified either as temperate or tropical. Adults of species were submitted to a cold treatment (0°C) and then brought back to ambient temperature. They generally exhibited a chill coma and the time needed to recover was measured. We found in a set of 26 temperate species that recovery was rapid (average 1.8 min, range 0.15–4.9). In contrast, a long recovery time (average 56 min, range 24–120) was observed for 48 tropical species. A few species, like Drosophila melanogaster, are cosmopolitan and can proliferate under temperate and tropical climates. In 9 of 10 such species, slight genetic differences were found: a shorter recovery in temperate than in tropical populations. Comparing physiological data to phylogeny suggests that chill‐coma tolerance has been a recurrent adaptation that is selected for in cold climates but tends to disappear under a permanently warm environment. This major climatic adaptation, evidenced in drosophilids, seems to occur in other insect groups also.     

黄果茄植物提取物对不同寄生虫中间宿主

采用常规浸杀灭螺的方法,观察黄果茄植物提取物对不同贝类的生物效应。设8组浓度,观察24 h、48 h和72 h不同贝类的死亡率,并计算LC50。结果表明,当SX浓度为8.640 mg/L,室温在（25±1）℃、水温（23±1）℃时,对湖北钉螺、光滑双脐螺、静水椎实螺浸杀48 h,其死亡率均达100%。48 h的LC50分别为0.332、0.858、0.747 mg/L。研究结果显示,黄果茄植物提取物是一种灭螺效果好且很有苗头的植物灭螺剂。     

Reliable estimation of the key variables and of their rates of change in alcoholic fermentation

The paper establishes a rigorous probabilistic framework for the reconciliation of apparently conflicting data from various physical and chemical measurements related to the key biological variables of alcoholic fermentation: the ethanol and the residual sugar concentrations. The analysis is carried out on a database consisting of 15 beer fermentation experiments, for which off-line determinations of ethanol concentration, fermentable sugar concentration, wort density and refractive index are available, as well as on-line records of evolved CO₂. The basic reconciliation method uses mass balance and monotonicity constraints derived from the biological knowledge of the fermentation process. In order to provide interpolated values and rate estimates, smoothness requirements are added. The reconciliation procedure gives more reliable estimates than any given measurement, detects outliers, helps fixing problems in the experimental setting and is also applicable on line.     

Plasma membrane signaling in HIV-1 infection

Plasma membrane is a multifunctional structure that acts as the initial barrier against infection by intracellular pathogens. The productive HIV-1 infection depends upon the initial interaction of virus and host plasma membrane. Immune cells such as CD4 + T cells and macrophages contain essential cell surface receptors and molecules such as CD4, CXCR4, CCR5 and lipid raft components that facilitate HIV-1 entry. From plasma membrane HIV-1 activates signaling pathways that prepare the grounds for viral replication. Through viral proteins HIV-1 hijacks host plasma membrane receptors such as Fas, TNFRs and DR4/DR5, which results in immune evasion and apoptosis both in infected and uninfected bystander cells. These events are hallmark in HIV-1 pathogenesis that leads towards AIDS. The interplay between HIV-1 and plasma membrane signaling has much to offer in terms of viral fitness and pathogenicity, and a better understanding of this interplay may lead to development of new therapeutic approaches. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking.     

Gigantism among Late Jurassic limulids: New ichnological evidence from the Causses Basin (Lozère,France) and comments on body-size evolution among horseshoe crabs

An abundant ichnological material composed of xiphosuran trackways and isolated traces was discovered in Upper Jurassic limestones from the Causses Basin (Causse Méjean, Lozère, France). The morphology of the imprints supports their identification as Kouphichnium isp. In contrast to the most frequent case, the trackways are composed of omnipresent pusher imprints sometime associated with leg traces, but with no telson mark. We argue that this pattern reflects actual surface traces rather than an incomplete set of undertracks. The size distribution of the sampled ichnites is broadly bimodal. This is best explained by sexual dimorphism, a phenomenon frequently observed in modern xiphosurans. Analysis of the trace fossils further suggests that several growth stages are recorded and that the horseshoe crabs were walking in a protected and flat environment like a lagoon. This area, certainly close to a mating ground, was occasionally affected by a continental influence. The biometric study of the tracks suggests a gigantic size for the trackmakers whose body may have reached 84 cm in length. This discovery complements the few reports on other gigantic horseshoe crabs in the Jurassic of Western Europe, thus casting doubt on the postulated increase in body size from the Palaeozoic to the Recent. Furthermore, a literature review shows that there are still major gaps in the record of limulid body-fossils and tracks. Thus, neither of these archives can be taken at face value for quantifying the body-size evolution of horseshoe crabs.