Self healing in System-S

Faults in a cluster are inevitable. The larger the cluster, the more likely the occurrence of some failure in hardware, in software, or by human error. System-S software must detect and self-repair failures while carrying out its prime directive—enabling stream processing program fragments to be distributed and connected to form complex applications. Depending on the type of failure, System-S may be able to continue with little or no disruption to potentially tens of thousands of interdependent and heterogeneous program fragments running across thousands of nodes. We extend the work we previously presented on the self healing nature of the job manager component in System-S by presenting how it can handle failures of other system components, applications and network infrastructure. We also evaluate the recoverability of the job management orchestrator component of System-S, considering crash failures with and without error propagation.

Neuroprotective actions of PIKE-L by inhibition of SET proteolytic degradation by asparagine endopeptidase

Ischemia and seizure cause excessive neuronal excitation that is associated with brain acidosis and neuronal cell death. However, the molecular mechanism of acidification-triggered neuronal injury is incompletely understood. Here, we show that asparagine endopeptidase (AEP) is activated under acidic condition, cuts SET, an inhibitor of DNase, and triggers DNA damage in brain, which is inhibited by PIKE-L. SET, a substrate of caspases, was cleaved by acidic cytosolic extract independent of caspase activation. Fractionation of the acidic cellular extract yielded AEP that is required for SET cleavage. We found that kainate provoked AEP activation and SET cleavage at N175, triggering DNA nicking in wild-type, but not AEP null, mice. PIKE-L strongly bound SET and prevented its degradation by AEP, leading to resistance of neuronal cell death. Moreover, AEP also mediated stroke-provoked SET cleavage and cell death in brain. Thus, AEP might be one of the proteinases activated by acidosis triggering neuronal injury during neuroexcitotoxicity or ischemia.     

Apparent Efficacy of Food-Based Calcium Supplementation in Preventing Rickets in Bangladesh

To determine whether increased Ca intakes can prevent rickets in a susceptible group of children living in a rickets-endemic area of Bangladesh, we conducted a 13-month long, double-blind, clinical trial with 1-to 5-year-old children who did not present with rickets but ranked in the upper decile of plasma alkaline phosphatase (AP) activity of a screening cohort of 1,749 children. A total of 158 children were randomized to a milk-powder-based dietary supplement given daily, 6 days/week, and providing either 50, 250, or 500 mg Ca, or 500 mg Ca plus multivitamins, iron, and zinc. Upon initial screening, 194 healthy children presented with no rachitic leg signs and had serum AP in the upper decile (>260 u/dl) of the cohort. When 183 of those subjects were re-screened after a 7-month pre-trial period, 23 (12.6%) had developed rachitic leg signs, suggesting an annual risk of 21.5% in this cohort. Of those still not presenting with leg signs and completing 13 months of dietary intervention, none showed rachitic leg signs, none showed significant radiological evidence of active rickets, and all showed carpal ossification normal for age after that intervention. These results are consistent with even the lowest amount of supplemental Ca (50 mg/day) being useful in supporting normal bone development in this high-risk population.     

Capsular synovial metaplasia mimicking silicone leak of a breast prosthesis: a case report

Introduction

Synovial metaplasia around a prosthesis and in particular around silicone breast implants has been noted by various investigators, but has unknown clinical significance. We report on a patient where a large amount of synovial fluid mimicked rupture of an implant. We believe this to be an unusual clinical presentation of this phenomenon. Review of the English language literature failed to identify a comparable case.

Case presentation

A 25-year-old woman had undergone bilateral breast augmentation for cosmetic reasons. One implant was subsequently subjected to two attempts at expansion to correct asymmetry. The patient was later found to have a large quantity of viscous fluid around the port of that same prosthesis. Histological assessment of the implant had consequently confirmed capsular synovial metaplasia. This had initially caused the suspicion of a silicone 'bleed' from the implant and had resulted in an unnecessary explantation.

Conclusion

Capsular synovial metaplasia should be ruled out before the removal of breast implants where a leak is suspected. Manipulation and expansion of an implant may be risk factors for the development of synovial metaplasia.

     

Components of SurA required for outer membrane biogenesis in uropathogenic Escherichia coli

Background

SurA is a periplasmic peptidyl-prolyl isomerase (PPIase) and chaperone of Escherichia coli and other Gram-negative bacteria. In contrast to other PPIases, SurA appears to have a distinct role in chaperoning newly synthesized porins destined for insertion into the outer membrane. Previous studies have indicated that the chaperone activity of SurA rests in its “core module” (the N- plus C-terminal domains), based on in vivo envelope phenotypes and in vitro binding and protection of non-native substrates.

Methodology/Principal Findings

In this study, we determined the components of SurA required for chaperone activity using in vivo phenotypes relevant to disease causation by uropathogenic E. coli (UPEC), namely membrane resistance to permeation by antimicrobials and maturation of the type 1 pilus usher FimD. FimD is a SurA-dependent, integral outer membrane protein through which heteropolymeric type 1 pili, which confer bladder epithelial binding and invasion capacity upon uropathogenic E. coli, are assembled and extruded. Consistent with prior results, the in vivo chaperone activity of SurA in UPEC rested primarily in the core module. However, the PPIase domains I and II were not expendable for wild-type resistance to novobiocin in broth culture. Steady-state levels of FimD were substantially restored in the UPEC surA mutant complemented with the SurA N- plus C-terminal domains. The addition of PPIase domain I augmented FimD maturation into the outer membrane, consistent with a model in which domain I enhances stability of and/or substrate binding by the core module.

Conclusions/Significance

Our results confirm the core module of E. coli SurA as a potential target for novel anti-infective development.     

Transplantation of Human Skin-Derived Mesenchymal Stromal Cells Improves Locomotor Recovery After Spinal Cord Injury in Rats

Spinal cord injury (SCI) is a devastating neurologic disorder with significant impacts on quality of life, life expectancy, and economic burden. Although there are no fully restorative treatments yet available, several animal and small-scale clinical studies have highlighted the therapeutic potential of cellular interventions for SCI. Mesenchymal stem cells (MSCs)—which are conventionally isolated from the bone marrow—recently emerged as promising candidates for treating SCI and have been shown to provide trophic support, ameliorate inflammatory responses, and reduce cell death following the mechanical trauma. Here we evaluated the human skin as an alternative source of adult MSCs suitable for autologous cell transplantation strategies for SCI. We showed that human skin-derived MSCs (hSD-MSCs) express a range of neural markers under standard culture conditions and are able to survive and respond to neurogenic stimulation in vitro. In addition, using histological analysis and behavioral assessment, we demonstrated as a proof-of-principle that hSD-MSC transplantation reduces the severity of tissue loss and facilitates locomotor recovery in a rat model of SCI. Altogether, the study provides further characterization of skin-derived MSC cultures and indicates that the human skin may represent an attractive source for cell-based therapies for SCI and other neurological disorders. Further investigation is needed to elucidate the mechanisms by which hSD-MSCs elicit tissue repair and/or locomotor recovery.     

The ‘chicken or the egg’: which comes first,forest tree decline or loss of mycorrhizae?

Forest trees are experiencing massive declines globally caused by a multitude of stressors, both abiotic (pollution, fragmentation and climate change) and biotic (fungi, bacteria, viruses and insects). Mycorrhizal fungi aid plants in the requisition of nutrients through their mutualistic relationship with plant roots and are integral to tree health. Stresses affecting tree health will also influence mycorrhizal fungi directly or indirectly, and thus alter the pathways responsible for nutrient absorption. Such an intimate association is a true chicken or egg quandary; do external stressors cause a loss of mycorrhizae which leads to tree decline, does tree decline result in a loss of mycorrhizae, or is it a combination of both? A review of literature has identified six stressors known to contribute to tree decline and to impact directly on mycorrhizae; global climate change, pesticides, heavy metals, excess fertilizer, pathogens and habitat fragmentation. A few review papers have highlighted the link; however, what is missing is irrefutable empirical research. This review documents the known direct impacts of the six stressors on mycorrhizal communities and places this in the context of decline syndromes in long-lived forest trees. We also discuss methodologies available to identify fungi and future research needed to unravel the complex relationships between forest tree declines and their associated mycorrhizal fungi.     

Structural properties of amyloid β(1‐40) dimer explored by replica exchange molecular dynamics simulations

Replica exchange molecular dynamics simulations (300 ns) were used to study the dimerization of amyloid β(1‐40) (Aβ(1‐40)) polypeptide. Configurational entropy calculations revealed that at physiological temperature (310 K, 37°C) dynamic dimers are formed by randomly docked monomers. Free energy of binding of the two chains to each other was ?93.56 ± 6.341 kJ mol^?1. Prevalence of random coil conformations was found for both chains with the exceptions of increased β‐sheet content from residues 16‐21 and 29‐32 of chain A and residues 15‐21 and 30‐33 of chain B with β‐turn/β‐bend conformations in both chains from residues 1‐16, 21‐29 of chain A, 1‐16, and 21‐29 of chain B. There is a mixed β‐turn/β‐sheet region from residues 33‐38 of both chains. Analysis of intra‐ and interchain residue distances shows that, although the individual chains are highly flexible, the dimer system stays in a loosely packed antiparallel β‐sheet configuration with contacts between residues 17‐21 of chain A with residues 17‐21 and 31‐36 of chain B as well as residues 31‐36 of chain A with residues 17‐21 and 31‐36 of chain B. Based on dihedral principal component analysis, the antiparallel β‐sheet‐loop‐β‐sheet conformational motif is favored for many low energy sampled conformations. Our results show that Aβ(1‐40) can form dynamic dimers in aqueous solution that have significant conformational flexibility and are stabilized by collapse of the central and C‐terminal hydrophobic cores with the expected β‐sheet‐loop‐β‐sheet conformational motif. Proteins 2017; 85:1024–1045. © 2017 Wiley Periodicals, Inc.