Modularity of stress response evolution

Responses to extracellular stress directly confer survival fitness by means of complex regulatory networks. Despite their complexity, the networks must be evolvable because of changing ecological and environmental pressures. Although the regulatory networks underlying stress responses are characterized extensively, their mechanism of evolution remains poorly understood. Here, we examine the evolution of three candidate stress response networks (chemotaxis, competence for DNA uptake, and endospore formation) by analyzing their phylogenetic distribution across several hundred diverse bacterial and archaeal lineages. We report that genes in the chemotaxis and sporulation networks group into well defined evolutionary modules with distinct functions, phenotypes, and substitution rates as compared with control sets of randomly chosen genes. The evolutionary modules vary in both number and cohesiveness among the three pathways. Chemotaxis has five coherent modules whose distribution among species shows a clear pattern of interdependence and rewiring. Sporulation, by contrast, is nearly monolithic and seems to be inherited vertically, with three weak modules constituting early and late stages of the pathway. Competence does not seem to exhibit well defined modules either at or below the pathway level. Many of the detected modules are better understood in engineering terms than in protein functional terms, as we demonstrate using a control-based ontology that classifies gene function according to roles such as "sensor," "regulator," and "actuator." Moreover, we show that combinations of the modules predict phenotype, yet surprisingly do not necessarily correlate with phylogenetic inheritance. The architectures of these three pathways are therefore emblematic of different modes and constraints on evolution.     

Corrosive acid ingestion in man - a clinical and endoscopic study

Sixteen patients with corrosive acid ingestion were studied. The majority of patients (n = 10) had ingested sulphuric acid, and three other patients had ingested hydrochloric acid. The extent and severity of upper gastrointestinal tract injury was determined by fibreoptic endoscopy and necropsy. All the patients had oesophageal and gastric involvement but the duodenum was spared in the majority. The injury was not considered as mild (grade I) in any of these patients; five patients having moderate (grade II) and 10 patients having severe (grade III) injury. Complications and mortality occurred only in patients with grade III injury. Feeding jejunostomy for nutritional support was used in five patients (all grade III) with good results.     

Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole,Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species

We compared EUCAST and CLSI antifungal susceptibility testing (AFST) methods for triazoles and amphotericin B against 124 clinical Mucorales isolates. The EUCAST method yielded MIC values 1- to 3-fold dilutions higher than those of the CLSI method for amphotericin B. The essential agreements between the two methods for triazoles were high, i.e., 99.1% (voriconazole), 98.3% (isavuconazole), and 87% (posaconazole), whereas it was significantly lower for amphotericin B (66.1%). Strategies for harmonization of the two methods for Mucorales AFST are warranted.     

Cross-Protection of Influenza A Virus Infection by a DNA Aptamer Targeting the PA Endonuclease Domain

Amino acid residues in the N-terminal of the PA subunit (PA_N) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PA_N is highly conserved among different subtypes of influenza virus, which suggests PA_N to be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PA_N domain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation of in vitro endonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PA_N were selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PA_N-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC₅₀) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs.     

Marker Based In-vitro Antioxidant Potential,Microscopy and Validated High Performance Thin Layer Chromatographic Method for Saffron

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - In vitro antioxidant potential of methanolic extract of saffron and crocetin was assessed along with...     

Prosthetic Rehabilitation Following Socket Reconstruction with Blair‐Brown Graft and Conformer Therapy for Management of Severe Post‐Enucleation Socket Syndrome – A Clinical Report

One of the most common tumors of the eye diagnosed in childhood is retinoblastoma, which mandates enucleation with adjunctive chemotherapy and radiotherapy to save the patient's life. The most common late enucleation complication is post‐enucleation socket syndrome (PESS), which poses a management dilemma for the prosthodontist and surgeon, along with being a major esthetic concern for the patient. The reconstruction of such sockets is complex. The purpose of this clinical report is to describe the rehabilitation of such a pediatric patient with severe PESS. The patient was successfully rehabilitated by presurgical conformer therapy, socket reconstruction surgery with non‐meshed intermediate split thickness skin graft (STSG)/Blair‐Brown graft, and postsurgical conformer stent. This was followed by fabrication of a custom ocular prosthesis, to achieve favorable functional, physical, and psychological effects.     

PEG hydrogel degradation and the role of the surrounding tissue environment

Poly(ethylene glycol) (PEG)‐based hydrogels are extensively used in a variety of biomedical applications, due to ease of synthesis and tissue‐like properties. Recently there have been varied reports regarding PEG hydrogel's degradation kinetics and in vivo host response. In particular, these studies suggest that the surrounding tissue environment could play a critical role in defining the inflammatory response and degradation kinetics of PEG implants. In the present study we demonstrated a potential mechanism of PEG hydrogel degradation, and in addition we show potential evidence of the role of the surrounding tissue environment on producing variable inflammatory responses. Copyright © 2013 John Wiley & Sons, Ltd.