372 research outputs found

    Survival and Synapse Formation of Transplanted Rat Rods

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    Isolated rods enzymatically removed from normal adult rat retina have been transplanted to the subretinal space of adult rats with a retinal dystrophy winich has destroyed almost all the photoreceptors. These transplanted rods survive for months after transplantation during which time they form synapses with other retinal cells. Rod spherules with large amounts of synaptic vesicles and synaptic ribbons are found forming discreet contacts with pre- and postsynaptic densities in arrangements closely resembling those seen in the normal retina

    Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

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    Background: The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180).Methods: A genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain's evolution.Results: GPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage phi OXC141. Prior to the introduction of PCV13, this Glade's composition shifted towards a phi OXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also phi OXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the similar to 100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage phi OXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in -30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation.Conclusion: This interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics

    Modeling the interrelating effects of plastic deformation and stress on magnetic properties of materials

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    A model has been developed that describes the interrelating effects of plastic deformation and applied stress on hysteresis loops based on the theory of ferromagnetichysteresis. In the current model the strength of pinning sites for domain walls is characterized by the pinning coefficient keff given by keff=k0+kā€²Ļƒ. The term k0 depicts pinning of domain walls by dislocations and is proportional to Ļn, where Ļ is the number density of dislocation which is related to the amount of plastic strain, and the exponent n depends on the strength of pinning sites. The second term kā€²Ļƒāˆāˆ’3/2Ī»s/2mĻƒ, where m is magnetization and Ī»s is magnetostriction constant, describes the changes in pinning strength on a domain wall induced by an applied stress Ļƒ. The model was capable of reproducing the stress dependence of hysteresis loop properties such as coercivity and remanence of a series of nickel samples which were pre-strained to various plastic strain levels. An empirical relation was found between the parameter k0 and the plastic strain, which can be interpreted in terms of the effects on the strength of domain wall pinning of changes in dislocation density and substructure under plastic deformation

    Expression profiling identifies genes involved in emphysema severity

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    Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients

    The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II).

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    Vancomycin is a front-line antibiotic used for the treatment of nosocomial infections, particularly those caused by methicillin-resistant Staphylococcus aureus. Despite its clinical importance the global effects of vancomycin exposure on bacterial physiology are poorly understood. In a previous transcriptomic analysis we identified a number of Zur regulon genes which were highly but transiently up-regulated by vancomycin in Streptomyces coelicolor. Here, we show that vancomycin also induces similar zinc homeostasis systems in a range of other bacteria and demonstrate that vancomycin binds to Zn(II) in vitro. This implies that vancomycin treatment sequesters zinc from bacterial cells thereby triggering a Zur-dependent zinc starvation response. The Kd value of the binding between vancomycin and Zn(II) was calculated using a novel fluorometric assay, and NMR was used to identify the binding site. These findings highlight a new biologically relevant aspect of the chemical property of vancomycin as a zinc chelator.This work was supported by funding from the Royal Society, UK (516002.K5877/ROG), the Medical Research Council, UK (G0700141). A.Z. was supported from the Said foundation and Cambridge Trust.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep1960

    A model for hysteretic magnetic properties under the application of noncoaxial stress and field

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    Although descriptions of the effect of stress on spontaneous magnetization within a single domain already exist, there remains no adequate mathematical model for the effects of noncoaxial magnetic field and stress on bulk magnetization in a multidomained specimen. This article addresses the problem and provides a phenomenological theory that applies to the case of bulk isotropic materials. The magnetomechanical hysteresis model of Sablik and Jiles is thus extended to treat magnetic properties in the case of noncoaxial stress and magnetic field in an isotropic, polycrystalline medium. In the modeling, noncollinearity between magnetization and magnetic field is taken into account. The effect of rollā€axis anisotropy is also considered. Both magnetic and magnetostrictive hysteresis are describable by the extended model. Emphasis in this article is on describing properties like coercivity, remanence,hysteresis loss, maximum flux density, and maximum differential permeability as a function of stress for various angular orientations between field and stress axis. The model predictions are compared with experimental results

    Defining minimal invasive surgical therapy for benign prostatic obstruction surgery: Perspectives from a global knowledge, attitude, and practice survey

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    Objective: To scrutinize the definitions of minimal invasive surgical therapy (MIST) and to investigate urologistsā€™ knowledge, attitudes, and practices for benign prostatic obstruction surgeries. Methods: A 36-item survey was developed with a Delphi method. Questions on definitions of MIST and attitudes and practices of benign prostatic obstruction surgeries were included. Urologists were invited globally to complete the online survey. Consensus was achieved when more than or equal to 70% responses were ā€œagree or strongly agreeā€ and less than or equal to 15% responses were ā€œdisagree or strongly disagreeā€ (consensus agree), or when more than or equal to 70% responses were ā€œdisagree or strongly disagreeā€ and less than or equal to 15% responses were ā€œagree or strongly agreeā€ (consensus disagree). Results: The top three qualities for defining MIST were minimal blood loss (n=466, 80.3%), fast post-operative recovery (n=431, 74.3%), and short hospital stay (n=425, 73.3%). The top three surgeries that were regarded as MIST were UroliftĀ® (n=361, 62.2%), RezumĀ® (n=351, 60.5%), and endoscopic enucleation of the prostate (EEP) (n=332, 57.2%). Consensus in the knowledge section was achieved for the superiority of UroliftĀ®, RezumĀ®, and iTINDĀ® over transurethral resection of the prostate with regard to blood loss, recovery, day surgery feasibility, and post-operative continence. Consensus in the attitudes section was achieved for the superiority of UroliftĀ®, RezumĀ®, and iTINDĀ® over transurethral resection of the prostate with regard to blood loss, recovery, and day surgery feasibility. Consensus on both sections was achieved for EEP as the option with the better symptoms and flow improvement, lower retreatment rate, and better suitable for prostate more than 80 mL. Conclusion: Minimal blood loss, fast post-operative recovery, and short hospital stay were the most important qualities for defining MIST. UroliftĀ®, RezumĀ®, and EEP were regarded as MIST by most urologists
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