Trypanosoma cruzi genotypes associated with domestic Triatoma sordida in Bolivia

Triatoma sordida is the second species of Triatominae considered of epidemiological significance in Bolivia. Associated with Triatoma infestans in various regions, it is as yet the only triatomine species established in human dwellings in localities of Velasco province, Department of Santa Cruz. This domestication is considered as primary. Flagellate parasites were detected in 16.2% of domiciliary T. sordida and the kDNA-PCR confirmed the presence of Trypanosoma cruzi. Frequencies of T. cruzi clonets 20 and 39, common clonets in Bolivian domestic cycle (T. infestans), were established by their direct detection in feces using PCR and hybridization. These clonets present low frequencies in T. sordida and synanthropic mammals. Forty-six stocks were isolated and analysed by multilocus enzyme electrophoresis (MLEE). The MLEE showed a higher clonal diversity than in T. infestans domestic cycle and the genotypes were clustered in the two principal lineages of T. cruzi. Within each lineage, a broad variability was observed. Mixture of genotypes was mostly observed in mammals. The large diversity of T. cruzi in this cycle should be related to its sylvatic origin. Moreover, the current limited sample of stocks suggests a lineage association with specific hosts.     

Diverse Fab specific for acetylcholine receptor epitopes from a myasthenia gravis thymus combinatorial library

The muscle weakness in myasthenia gravis (MG) is caused by heterogeneous high-affinity IgG autoantibodies to the nicotinic acetylcholine receptor (AChR), a complex ion channel glycoprotein. These antibodies are clearly responsible for reducing AChR numbers at the neuromuscular junction in myasthenia; however, the origins, diversity, specificity and pathogenicity of individual antibodies have not yet been established. We have cloned and characterized four different AChR-specific Fab from an MG patient's thymus by screening an IgG1/kappa gene combinatorial lambda phage library with soluble human AChR labeled with [125I] alpha-bungarotoxin. Unlike most previously cloned human antibodies, all four Fab immunoprecipitated soluble human muscle AChR. Two Fab strongly inhibited binding of mAb to the main immunogenic region on the alpha subunits and one Fab bound to an epitope on the fetal-specific gamma subunit. In sensitivity and fine specificity, these Fab resembled the anti-AChR antibodies found in many MG patients, including the donor. The closest germline counterparts for their heavy chains were in VH families 1, 3 and 4; however, there were many differences consistent with an antigen-driven response of diverse B cell clones. The combinatorial approach holds promise for further analysis of human autoantibodies.     

Perspective:Societally connected multimedia across cultures

The advance of the Internet in the past decade has radically changed the way people communicate and col- laborate with each other. Physical distance is no more a barrier in online social networks, but cultural differences (at the individual, community, as well as societal levels) still govern human-human interactions and must be con- sidered and leveraged in the online world. The rapid de-ployment of high-speed Internet allows humans to interact using a rich set of multimedia data such as texts, pictures, and videos. This position paper proposes to define a new research area called ’connected multimedia’, which is the study of a collection of research issues of the super-area social media that receive little attention in the literature. By connected multimedia, we mean the study of the social and technical interactions among users, multimedia data, and devices across cultures and explicitly exploiting the cultural differences. We justify why it is necessary to bring attention to this new research area and what benefits of this new research area may bring to the broader scientific research community and the humanity.     

The effects of withholding feed and water on carcass shrinkage and meat quality in beef cattle

Eighty beef crossbred steers with an average weight of 493 kg (4·66 kg SD) were allocated at random to one of five treatments to assess the effects of withholding feed and water on carcass shrinkage and meat quality. The five treatments were: slaughter from the feedlot (T1); and 12, 24, 36 and 48 h periods without feed and water prior to slaughter (T2-5).Weights were taken of the live animal and the carcass to monitor shrinkage along with relevant meat quality measurements. There were no treatment differences (P > 0·05) in initial farm weight, but plant weight shrinkage increased from 31gkg(-1) for T1 to 106 g kg(-1) for T5. Warm carcass weight decreased (P < 0·05) from 278·8 kg for T1, to 270·7 kg for T3 and 261·9 kg for T5. Liver, alimentary tract components, hide and head decreased as a proportion of farm weight as time without feed and water increased. Muscle pH at 6 days post mortem was increased (P < 0·05) in T3-5 compared to T1, with the result that muscle colour became darker, and steaks had less drip loss. Shear values increased (P < 0·05) from 6·3 kg in T1 to 7·7 kg in T4 and T5 indicating an increase in muscle toughness as time without feed and water increased. It was concluded that steers lose live weight rapidly within the first 24 h without feed and water, and that these relatively short periods of time (24 h) can have detrimental effects on carcass shrinkage and muscle quality.     

What can you verify and enforce at runtime?

The underlying property, its definition, and representation play a major role when monitoring a system. Having a suitable and convenient framework to express properties is thus a concern for runtime analysis. It is desirable to delineate in this framework the sets of properties for which runtime analysis approaches can be applied to. This paper presents a unified view of runtime verification and enforcement of properties in the Safety-Progress classification. First, we extend the Safety-Progress classification of properties in a runtime context. Second, we characterize the set of properties which can be verified (monitorable properties) and enforced (enforceable properties) at runtime. We propose in particular an alternative definition of ??property monitoring?? to the one classically used in this context. Finally, for the delineated sets of properties, we define specialized verification and enforcement monitors.     

Deformation of NiO single crystals below room temperature: dislocation configurations

NiO single crystals prepared by two crystal growth techniques (zone melting in an arc-image furnace and Verneuil crystallization have been deformed by compression along 001 at temperatures as low as 4.2 K, and the dislocation substructure observed by transmission electron microscopy. The Peierls mechanism has been suggested as the mechanism controlling the mechanical behaviour at the lower temperatures. The dislocations generated at cavities found in the zone-melted crystals may be responsible for the increase of the flow stress of these crystals compared with the Verneuil ones.     

Nuclear Receptor Nur77 Controls Cardiac Fibrosis through Distinct Actions on Fibroblasts and Cardiomyocytes

Fibrosis is a hallmark of adverse cardiac remodeling, which promotes heart failure, but it is also an essential repair mechanism to prevent cardiac rupture, signifying the importance of appropriate regulation of this process. In the remodeling heart, cardiac fibroblasts (CFs) differentiate into myofibroblasts (MyoFB), which are the key mediators of the fibrotic response. Additionally, cardiomyocytes are involved by providing pro-fibrotic cues. Nuclear receptor Nur77 is known to reduce cardiac hypertrophy and associated fibrosis; however, the exact function of Nur77 in the fibrotic response is yet unknown. Here, we show that Nur77-deficient mice exhibit severe myocardial wall thinning, rupture and reduced collagen fiber density after myocardial infarction and chronic isoproterenol (ISO) infusion. Upon Nur77 knockdown in cultured rat CFs, expression of MyoFB markers and extracellular matrix proteins is reduced after stimulation with ISO or transforming growth factor–β (TGF-β). Accordingly, Nur77-depleted CFs produce less collagen and exhibit diminished proliferation and wound closure capacity. Interestingly, Nur77 knockdown in neonatal rat cardiomyocytes results in increased paracrine induction of MyoFB differentiation, which was blocked by TGF-β receptor antagonism. Taken together, Nur77-mediated regulation involves CF-intrinsic promotion of CF-to-MyoFB transition and inhibition of cardiomyocyte-driven paracrine TGF-β-mediated MyoFB differentiation. As such, Nur77 provides distinct, cell-specific regulation of cardiac fibrosis.     

Is LRP2 Involved in Leptin Transport over the Blood-Brain Barrier and Development of Obesity?

The mechanisms underlying the transport of leptin into the brain are still largely unclear. While the leptin receptor has been implicated in the transport process, recent evidence has suggested an additional role of LRP2 (megalin). To evaluate the function of LRP2 for leptin transport across the blood-brain barrier (BBB), we developed a novel leptin-luciferase fusion protein (pLG), which stimulated leptin signaling and was transported in an in vitro BBB model based on porcine endothelial cells. The LRP inhibitor RAP did not affect leptin transport, arguing against a role of LRP2. In line with this, the selective deletion of LRP2 in brain endothelial cells and epithelial cells of the choroid plexus did not influence bodyweight, body composition, food intake, or energy expenditure of mice. These findings suggest that LRP2 at the BBB is not involved in the transport of leptin into the brain, nor in the development of obesity as has previously been described.     

PGRP-LB: An Inside View into the Mechanism of the Amidase Reaction

Peptidoglycan recognition proteins (PGRPs) are ubiquitous among animals and play pivotal functions in insect immunity. Non-catalytic PGRPs are involved in the activation of immune pathways by binding to the peptidoglycan (PGN), whereas amidase PGRPs are capable of cleaving the PGN into non-immunogenic compounds. Drosophila PGRP-LB belongs to the amidase PGRPs and downregulates the immune deficiency (IMD) pathway by cleaving meso-2,6-diaminopimelic (meso-DAP or DAP)-type PGN. While the recognition process is well analyzed for the non-catalytic PGRPs, little is known about the enzymatic mechanism for the amidase PGRPs, despite their essential function in immune homeostasis. Here, we analyzed the specific activity of different isoforms of Drosophila PGRP-LB towards various PGN substrates to understand their specificity and role in Drosophila immunity. We show that these isoforms have similar activity towards the different compounds. To analyze the mechanism of the amidase activity, we performed site directed mutagenesis and solved the X-ray structures of wild-type Drosophila PGRP-LB and its mutants, with one of these structures presenting a protein complexed with the tracheal cytotoxin (TCT), a muropeptide derived from the PGN. Only the Y78F mutation abolished the PGN cleavage while other mutations reduced the activity solely. Together, our findings suggest the dynamic role of the residue Y78 in the amidase mechanism by nucleophilic attack through a water molecule to the carbonyl group of the amide function destabilized by Zn²⁺.     

“Modification V” of poly 4-methylpentene-1 from cyclopentane solutions and gels

A new crystalline structure of poly 4-methylpentene-1 (P4MP1), modiification named modification V, is obtained from cyclopentane solutions and gels, for polymer volume fractions between 0.01 and 0.10. The effect of the thermal history imparted to the solution is analyzed. The relation between gelation, polymorphism and existence of helical conformations of P4MP1 in solution is discussed. Modification V is tentatively indexed on the basis of an hexagonal unit cell with dimensions a = 22.17 ± 0.14 Å and c = 6.69 ±0.02 Å. The crystal transforms into modification I at 130 ± 5°C, the heat of transition being + 15 ±2 J.g^?1.