Simulation of the Elastic Properties of Reinforced Kevlar-Graphene Composites

The compressive strength of unidirectional fiber composites in the form of Kevlar yarn with a thin outer layer of graphene was investigated and modeled. Such fiber structure may be fabricated by using a strong chemical bond between Kevlar yarn and graphene sheets. Chemical functionalization of graphene and Kevlar may achieved by modification of appropriate surface-bound functional (e.g., carboxylic acid) groups on their surfaces. In this report we studied elastic response to unidirectional in-plane applied load with load peaks along the diameter. The 2D linear elasticity model predicts that significant strengthening occurs when graphene outer layer radius is about 4 % of kevlar yarn radius. The polymer chains of Kevlar are linked into locally planar structure by hydrogen bonds across the chains, with transversal strength considerably weaker than longitudinal one. This suggests that introducing outer enveloping layer of graphene, linked to polymer chains by strong chemical bonds may significantly strengthen Kevlar fiber with respect to transversal deformations

Nfix expression critically modulates early B lymphopoiesis and myelopoiesis

The commitment of stem and progenitor cells toward specific hematopoietic lineages is tightly controlled by a number of transcription factors that regulate differentiation programs via the expression of lineage restricting genes. Nuclear factor one (NFI) transcription factors are important in regulating hematopoiesis and here we report an important physiological role of NFIX in B- and myeloid lineage commitment and differentiation. We demonstrate that NFIX acts as a regulator of lineage specification in the haematopoietic system and the expression of Nfix was transcriptionally downregulated as B cells commit and differentiate, whilst maintained in myeloid progenitor cells. Ectopic Nfix expression in vivo blocked early B cell development stage, coincident with the stage of its downregulation. Furthermore, loss of Nfix resulted in the perturbation of myeloid and lymphoid cell differentiation, and a skewing of gene expression involved in lineage fate determination. Nfix was able to promote myeloid differentiation of total bone marrow cells under B cell specific culture conditions but not when expressed in the hematopoietic stem cell (HSPC), consistent with its role in HSPC survival. The lineage choice determined by Nfix correlated with transcriptional changes in a number of genes, such as E2A, C/EBP, and Id genes. These data highlight a novel and critical role for NFIX transcription factor in hematopoiesis and in lineage specification

Efficacy of nisin A and nisin V semi-purified preparations alone and in combination with plant essential oils to control Listeria monocytogenes

peer-reviewedThe foodborne pathogenic bacterium Listeria is known for relatively low morbidity and high mortality rates reaching up to 25-30%. Listeria is a hardy organism and its control in foods represents a significant challenge. Many naturally occurring compounds, including the bacteriocin nisin and a number of plant essential oils, have been widely studied and are reported to be effective as antimicrobial agents against spoilage and pathogenic microorganisms. The aim of this study was to investigate the ability of semi-purified preparations (spp) containing either nisin A or an enhanced bioengineered derivative nisin V, alone and in combination with low concentrations of the essential oils thymol, carvacrol and trans-cinnamaldehyde, to control L. monocytogenes in both laboratory media and model food systems. Combinations of nisin V-containing spp (25 μg/ml) with thymol (0.02%), carvacrol (0.02%) or cinnamaldehyde (0.02%) produced a significantly longer lag phase than any of the essential oil/nisin A combinations. In addition, the log reduction in cell counts achieved by the nisin V + carvacrol or nisin V + cinnamaldehyde combinations was twice that of the equivalent nisin A + essential oil treatment. Significantly, this enhanced activity was validated in model food systems against L. monocytogenes strains of food origin. We conclude that the fermentate form of nisin V in combination with carvacrol and cinnamaldehyde offers significant advantages as a novel, natural and effective means to enhance food safety by inhibiting foodborne pathogens such as L. monocytogenes.This work was supported by the Irish Government under the National Development Plan, through Science Foundation Ireland Investigator awards to C.H. and R.P.R. (10/IN.1/B3027), and C.H., R.P.R. and P.D.C. (06/IN.1/B98)

Bugs, breathing and blood pressure: the microbiota-gut-brain axis in cardiorespiratory control

Dysregulated microbiota-gut-brain axis communication adversely influences neurocontrol systems, consequently affecting brain behaviours. It is plausible that microbiota-gut-brain axis signalling has a role in the control of breathing and cardiovascular function, as networks that govern cardiorespiratory control reside within the brainstem, a region innervated by the vagus nerve, a key signalling pathway of the microbiota-gut-brain axis. Cardiovascular and respiratory diseases are serious, potentially life-threatening conditions with limited treatment options. Thus, improved understanding of the underlying pathophysiology and novel therapeutic approaches are required. We performed an assessment of cardiorespiratory physiology in animal models of modified gut microbiota [antibiotic-treated (ABX) and faecal microbiota transfer (FMT)], and sleep-disordered breathing [chronic intermittent hypoxia (CIH)-exposed guinea-pigs and rats]. We investigated if dietary prebiotic supplementation prevented CIH-induced cardiorespiratory dysfunction in rats. Whole-body plethysmography was used to record ventilation and metabolism in unanaesthetised animals during normoxia and chemostimulation. Under anaesthesia, cardiorespiratory assessments were performed during normoxia, chemosensory stimulation and drug administration. Brainstem neurochemistry was assessed by high-performance liquid chromatography. 16S rRNA and whole-metagenome shotgun sequencing was used to characterise the gut microbiota. ABX and FMT disrupted the gut microbiota, brain neurochemistry and intestinal integrity, blunting chemoreflex control of breathing. Decreased brainstem noradrenaline and altered gut microbiota as well as impaired respiratory and autonomic control were evident in CIH-exposed guinea-pigs. CIH–exposed rats developed cardiorespiratory pathologies and decreased gut Lactobacillus rhamnosus relative abundance. Prebiotic administration increased short-chain fatty acid concentrations, measured by gas chromatography, but Lactobacillus rhamnosus and cardiorespiratory dysfunctions were not restored. Several commensal and pathogenic bacterial species correlated with blood pressure parameters. Our findings add to emerging research exploring microbiota-gut-brain signalling in homeostatic systems, extending investigations to cardiorespiratory control. Our studies draw focus to the potential application of manipulation of the gut microbiota as an adjunctive therapy for cardiorespiratory disease

Bioengineered Nisin A Derivatives with Enhanced Activity against Both Gram Positive and Gram Negative Pathogens

peer-reviewedNisin is a bacteriocin widely utilized in more than 50 countries as a safe and natural antibacterial food preservative. It is the most extensively studied bacteriocin, having undergone decades of bioengineering with a view to improving function and physicochemical properties. The discovery of novel nisin variants with enhanced activity against clinical and foodborne pathogens has recently been described. We screened a randomized bank of nisin A producers and identified a variant with a serine to glycine change at position 29 (S29G), with enhanced efficacy against S. aureus SA113. Using a site-saturation mutagenesis approach we generated three more derivatives (S29A, S29D and S29E) with enhanced activity against a range of Gram positive drug resistant clinical, veterinary and food pathogens. In addition, a number of the nisin S29 derivatives displayed superior antimicrobial activity to nisin A when assessed against a range of Gram negative food-associated pathogens, including E. coli, Salmonella enterica serovar Typhimurium and Cronobacter sakazakii. This is the first report of derivatives of nisin, or indeed any lantibiotic, with enhanced antimicrobial activity against both Gram positive and Gram negative bacteria.This work was supported by the Irish Government under the National Development Plan, through Science Foundation Ireland Investigator awards (10/IN.1/B3027) and (06/IN.1/B98) (http://www.sfi.ie)

Testing mood-activated psychological markers for suicidal ideation

To what extent are death- and life-oriented psychological processes among suicidal individuals activated by mood? According to Teasdale’s (1988) Differential Activation Hypothesis, we would expect that negative mood-activated psychological processes are maladaptive among suicide ideators (vs. non-ideators) and predictive of subsequent suicidal ideation. This, however, has never been prospectively studied. To address this knowledge gap, we conducted a prospective study assessing psychological risk factors via the Death/Life Implicit Association Test (IAT) and the Suicide Stroop task before and after a temporary negative mood induction. Suicidal ideation was assessed one and six months later. Results based on Death/Life IAT performance largely supported hypotheses, such that suicide ideators demonstrated significantly weaker implicit identification with life after (vs. before) the negative mood induction. Non-ideators demonstrated no significant change, maintaining strong identification with life irrespective of mood. Of note, this baseline interaction may have been accounted for by depressive symptoms. Identification with death (vs. life) predicted greater likelihood of suicidal ideation one month later, controlling for depressive symptoms and baseline suicidal ideation. Only negative mood-activated identification with death predicted suicidal ideation six months later. Suicide Stroop scores did not change as a function of mood or predict subsequent suicidal ideation. Death/Life IAT findings support the Differential Activation Hypothesis and suggest that suicide ideators’ identification with life is more variable and easily weakened by negative mood relative to non-ideators. We encourage future work to consider the potential role of transient mood and the importance of measuring psychological processes that pertain to both death and life

Epigenetic silencing by early life hypoxic stress programmes respiratory motor control

Preterm birth is a risk factor for the development of cardiorespiratory complications. Infants that are born prematurely face myriad challenges due to physiological immaturity. Respiratory control impairments in early life including apnoea of prematurity with resultant disruption to systemic oxygen status can provoke long-term disability, including increased propensity to develop morbidities in later life such as sleep-disordered breathing. In rodents, exposure to intermittent hypoxia mimicking recurrent episodes of oxygen desaturation that are characteristic of apnoeas, provokes plasticity at multiple sites of the respiratory control network culminating in breathing instabilities, altered chemoreflex control of breathing and impaired respiratory motor nerve and muscle function. Persistent effects of stressors presenting during critical periods of early development may be sustained by epigenetic mechanisms. Such changes may be especially relevant to perinatal exposure to intermittent hypoxia since it is established that hypermethylation of genes encoding antioxidant enzymes underlies carotid body chemoreceptor sensitization and respiratory instability following exposure to intermittent hypoxia during postnatal development

Implications for Chk1 Regulation: The 1.7 Å Crystal Structure of Human Cell Cycle Checkpoint Kinase Chk1

AbstractThe checkpoint kinase Chk1 is an important mediator of cell cycle arrest following DNA damage. The 1.7 Å resolution crystal structures of the human Chk1 kinase domain and its binary complex with an ATP analog has revealed an identical open kinase conformation. The secondary structure and side chain interactions stabilize the activation loop of Chk1 and enable kinase activity without phosphorylation of the catalytic domain. Molecular modeling of the interaction of a Cdc25C peptide with Chk1 has uncovered several conserved residues that are important for substrate selectivity. In addition, we found that the less conserved C-terminal region negatively impacts Chk1 kinase activity

Assessing the Quality of Decision Support Technologies Using the International Patient Decision Aid Standards instrument (IPDASi)

Objectives To describe the development, validation and inter-rater reliability of an instrument to measure the quality of patient decision support technologies (decision aids). Design Scale development study, involving construct, item and scale development, validation and reliability testing. Setting There has been increasing use of decision support technologies – adjuncts to the discussions clinicians have with patients about difficult decisions. A global interest in developing these interventions exists among both for-profit and not-for-profit organisations. It is therefore essential to have internationally accepted standards to assess the quality of their development, process, content, potential bias and method of field testing and evaluation. Methods Scale development study, involving construct, item and scale development, validation and reliability testing. Participants Twenty-five researcher-members of the International Patient Decision Aid Standards Collaboration worked together to develop the instrument (IPDASi). In the fourth Stage (reliability study), eight raters assessed thirty randomly selected decision support technologies. Results IPDASi measures quality in 10 dimensions, using 47 items, and provides an overall quality score (scaled from 0 to 100) for each intervention. Overall IPDASi scores ranged from 33 to 82 across the decision support technologies sampled (n = 30), enabling discrimination. The inter-rater intraclass correlation for the overall quality score was 0.80. Correlations of dimension scores with the overall score were all positive (0.31 to 0.68). Cronbach's alpha values for the 8 raters ranged from 0.72 to 0.93. Cronbach's alphas based on the dimension means ranged from 0.50 to 0.81, indicating that the dimensions, although well correlated, measure different aspects of decision support technology quality. A short version (19 items) was also developed that had very similar mean scores to IPDASi and high correlation between short score and overall score 0.87 (CI 0.79 to 0.92). Conclusions This work demonstrates that IPDASi has the ability to assess the quality of decision support technologies. The existing IPDASi provides an assessment of the quality of a DST's components and will be used as a tool to provide formative advice to DSTs developers and summative assessments for those who want to compare their tools against an existing benchmark