Structural variants of biodegradable polyesterurethane in vivo evoke a cellular and angiogenic response that is dictated by architecture

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2008 Acta Materialia Inc.The aim of this study was to investigate an in vivo tissue response to a biodegradable polyesterurethane, specifically the cellular and angiogenic response evoked by varying implant architectures in a subcutaneous rabbit implant model. A synthetic biodegradable polyesterurethane was synthesized and processed into three different configurations: a non-porous film, a porous mesh and a porous membrane. Glutaraldehyde cross-linked bovine pericardium was used as a control. Sterile polyesterurethane and control samples were implanted subcutaneously in six rabbits (n = 12). The rabbits were killed at 21 and 63 days and the implant sites were sectioned and histologically stained using haemotoxylin and eosin (H&E), Masson’s trichrome, picosirius red and immunostain CD31. The tissue–implant interface thickness was measured from the H&E slides. Stereological techniques were used to quantify the tissue reaction at each time point that included volume fraction of inflammatory cells, fibroblasts, fibrocytes, collagen and the degree of vascularization. Stereological analysis inferred that porous scaffolds with regular topography are better tolerated in vivo compared to non-porous scaffolds, while increasing scaffold porosity promotes angiogenesis and cellular infiltration. The results suggest that this biodegradable polyesterurethane is better tolerated in vivo than the control and that structural variants of biodegradable polyesterurethane in vivo evoke a cellular and angiogenic response that is dictated by architecture.Irish Research Council for Science, Engineering and Technology: funded by the National Development Plan. Enterprise Ireland: Research Innovation Partnership

Comparison of Interactions Between Control and Mutant Macrophages

This paper presents a preliminary study on macrophages migration in Drosophila embryos, comparing two types of cells. The study is carried out by a framework called macrosight which analyses the movement and interaction of migrating macrophages. The framework incorporates a segmentation and tracking algorithm into analysing motion characteristics of cells after contact. In this particular study, the interactions between cells is characterised in the case of control embryos and Shot3 mutants, where the cells have been altered to suppress a specific protein, looking to understand what drives the movement. Statistical significance between control and mutant cells was found when comparing the direction of motion after contact in specific conditions. Such discoveries provide insights for future developments in combining biological experiments to computational analysis

TGFβ1 rapidly activates Src through a non-canonical redox signaling mechanism.

Transforming growth factor-β1 (TGF-β) is involved in multiple cellular processes through Src activation. In the canonical pathway, Src activation is initiated by pTyr530 dephosphorylation followed by a conformational change allowing Tyr419 auto-phosphorylation. A non-canonical pathway in which oxidation of cysteine allows bypassing of pTyr530 dephosphorylation has been reported. Here, we examined how TGF-β activates Src in H358 cells, a small cell lung carcinoma cell line. TGF-β increased Src Tyr419 phosphorylation, but surprisingly, Tyr530 phosphorylation was increased rather than decreased. Vanadate, a protein tyrosine phosphatase inhibitor, stimulated Src activation itself, but rather than inhibiting Src activation by TGF-β, activation by vanadate was additive with TGF-β showing that pTyr530 dephosphorylation was not required. Thus, the involvement of the non-canonical oxidative activation was suspected. TGF-β increased extracellular H2O2 transiently while GSH-ester and catalase abrogated Src activation by TGF-β. Apocynin, a NADPH oxidase inhibitor, inhibited TGF-β-stimulated H2O2 production. Furthermore, mutation of cysteines to alanine, 248C/A, 277C/A, or 501C/A abrogated, while 490C/A significantly reduced, TGF-β-mediated Src activation. Taken together, the results indicate that TGF-β-mediated Src activation operates largely through a redox dependent mechanism, resulting from enhanced H2O2 production through an NADPH oxidase and that cysteines 248, 277, 490, and 501 are critical for this activation

Oxidative stress response and Nrf2 signaling in aging.

Increasing oxidative stress, a major characteristic of aging, has been implicated in a variety of age-related pathologies. In aging, oxidant production from several sources is increased, whereas antioxidant enzymes, the primary lines of defense, are decreased. Repair systems, including the proteasomal degradation of damaged proteins, also decline. Importantly, the adaptive response to oxidative stress declines with aging. Nrf2/EpRE signaling regulates the basal and inducible expression of many antioxidant enzymes and the proteasome. Nrf2/EpRE activity is regulated at several levels, including transcription, posttranslation, and interactions with other proteins. This review summarizes current studies on age-related impairment of Nrf2/EpRE function and discusses the changes in Nrf2 regulatory mechanisms with aging

How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo.

We present arguments for an evolution in our understanding of how antioxidants in fruits and vegetables exert their health-protective effects. There is much epidemiological evidence for disease prevention by dietary antioxidants and chemical evidence that such compounds react in one-electron reactions with free radicals in vitro. Nonetheless, kinetic constraints indicate that in vivo scavenging of radicals is ineffective in antioxidant defense. Instead, enzymatic removal of nonradical electrophiles, such as hydroperoxides, in two-electron redox reactions is the major antioxidant mechanism. Furthermore, we propose that a major mechanism of action for nutritional antioxidants is the paradoxical oxidative activation of the Nrf2 (NF-E2-related factor 2) signaling pathway, which maintains protective oxidoreductases and their nucleophilic substrates. This maintenance of "nucleophilic tone," by a mechanism that can be called "para-hormesis," provides a means for regulating physiological nontoxic concentrations of the nonradical oxidant electrophiles that boost antioxidant enzymes, and damage removal and repair systems (for proteins, lipids, and DNA), at the optimal levels consistent with good health

Mining and analysis of audiology data to find significant factors associated with tinnitus masker

Objectives: The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments. Design: The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques. Setting: This research uses a large audiology data but it also faced the problem of limited data for tinnitus. Participants: It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic. Primary and secondary outcome measures: The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient. Results: The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age<=55 years were more likely to wear a tinnitus masker, as well as those with milder forms of hearing loss. ITE (in the ear) hearing aids were also found associated with tinnitus masker. A feedback on the results of association of mould with tinnitus masker from a professional audiologist of a large NHS (National Health Services, UK) was also taken to better understand them. The results were obtained with different accuracy for different techniques. For example, the chi-squared test results were obtained with 95% accuracy, for Support and Confidence only those results were retained which had more than 1% Support and 80% Confidence. Conclusions: The variables audiograms, age, gender, hearing aid type and mould were found associated with the choice of tinnitus masker in the literature and by using statistical and data mining techniques. The further work in this research would lead to the development of a decision support system for tinnitus masker with an explanation that how that decision was obtained

Two in one: cryptic species discovered in biological control agent populations using molecular data and crossbreeding experiments

There are many examples of cryptic species that have been identified through DNA-barcoding or other genetic techniques. There are, however, very few confirmations of cryptic species being reproductively isolated. This study presents one of the few cases of cryptic species that has been confirmed to be reproductively isolated and therefore true species according to the biological species concept. The cryptic species are of special interest because they were discovered within biological control agent populations. Two geographically isolated populations of Eccritotarsus catarinensis (Carvalho) [Hemiptera: Miridae], a biological control agent for the invasive aquatic macrophyte, water hyacinth, Eichhornia crassipes (Mart.) Solms [Pontederiaceae], in South Africa, were sampled from the native range of the species in South America. Morphological characteristics indicated that both populations were the same species according to the current taxonomy, but subsequent DNA analysis and breeding experiments revealed that the two populations are reproductively isolated. Crossbreeding experiments resulted in very few hybrid offspring when individuals were forced to interbreed with individuals of the other population, and no hybrid offspring were recorded when a choice of mate from either population was offered. The data indicate that the two populations are cryptic species that are reproductively incompatible. Subtle but reliable diagnostic characteristics were then identified to distinguish between the two species which would have been considered intraspecific variation without the data from the genetics and interbreeding experiments. These findings suggest that all consignments of biological control agents from allopatric populations should be screened for cryptic species using genetic techniques and that the importation of multiple consignments of the same species for biological control should be conducted with caution

D-brane anomaly inflow revisited

Axial and gravitational anomaly of field theories, when embedded in string theory, must be accompanied by canceling inflow. We give a self-contained overview for various world-volume theories, and clarify the role of smeared magnetic sources in I-brane/D-brane cases. The proper anomaly descent of the source, as demanded by regularity of RR field strengths H's, turns out to be an essential ingredient. We show how this allows correct inflow to be generated for all such theories, including self-dual cases, and also that the mechanism is now insensitive to the choice between the two related but inequivalent forms of D-brane Chern-Simons couplings. In particular, SO(6)_R axial anomaly of d=4 maximal SYM is canceled by the inflow onto D3-branes via the standard minimal coupling to C_4. We also propose how, for the anomaly cancelation, the four types of Orientifold planes should be coupled to the spacetime curvatures, of which conflicting claims existed previously.Comment: 41 pages, references updated; version to appear in JHE