Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunomodulatory effect of a decellularized skeletal muscle scaffold in a discordant xenotransplantation model

Decellularized (acellular) scaffolds, composed of natural extracellular matrix, form the basis of an emerging generation of tissue-engineered organ and tissue replacements capable of transforming healthcare. Prime requirements for allogeneic, or xenogeneic, decellularized scaffolds are biocompatibility and absence of rejection. The humoral immune response to decellularized scaffolds has been well documented, but there is a lack of data on the cell-mediated immune response toward them in vitro and in vivo. Skeletal muscle scaffolds were decellularized, characterized in vitro, and xenotransplanted. The cellular immune response toward scaffolds was evaluated by immunohistochemistry and quantified stereologically. T-cell proliferation and cytokines, as assessed by flow cytometry using carboxy-fluorescein diacetate succinimidyl ester dye and cytometric bead array, formed an in vitro surrogate marker and correlate of the in vivo host immune response toward the scaffold. Decellularized scaffolds were free of major histocompatibility complex class I and II antigens and were found to exert anti-inflammatory and immunosuppressive effects, as evidenced by delayed biodegradation time in vivo; reduced sensitized T-cell proliferative activity in vitro; reduced IL-2, IFN-γ, and raised IL-10 levels in cell-culture supernatants; polarization of the macrophage response in vivo toward an M2 phenotype; and improved survival of donor-derived xenogeneic cells at 2 and 4 wk in vivo. Decellularized scaffolds polarize host responses away from a classical TH1-proinflammatory profile and appear to down-regulate T-cell xeno responses and TH1 effector function by inducing a state of peripheral T-cell hyporesponsiveness. These results have substantial implications for the future clinical application of tissue-engineered therapies.
The impact of migration on health beliefs and behaviours: The case of Ethiopian refugees in the UK

The Research Centre for Transcultural Studies in Health, Middlesex University and the Ethiopian Community Centre in the UK conducted a study to explore the migration experiences of Ethiopian refugees in the UK and the impact of this on their health beliefs and behaviours. Data was collected via: i) semistructured interviews were conducted with Ethiopians refugees and asylum seekers and Ethiopian professionals providing services for Ethiopian refugees; ii) a semi-structured questionnaire; iii) a documentary analysis of newspaper articles concerning refugees; and iv) an ethnohistory of Ethiopia.The findings revealed that Ethiopian refugees place a stronger emphasis on externalised factors influencing health (such as happiness and good social relations) than they did in Ethiopia.The study found that participants fled Ethiopia due to oppression, violence, fear and poverty; and once in the UK experience poor housing, unemployment, racism and isolation, all of which impact on their health status.Whilst it is difficult to ascertain how these factors affect health beliefs it is probable that these negative experiences and the consequent unhappiness they have caused have highlighted to them the relationship between health and subjective well-being, something that people who have not suffered such life traumas may take for granted. In the UK Ethiopian refugees are more likely to seek Western medicine than they did in Ethiopia, which reflects both acculturation and differences in health resources.This study highlights that Ethiopian refugees, require holistic health care that addresses all their needs - physical, mental, spiritual, environmental and social-cultural. Nurses should understand that many refugees have had traumatic experiences and continue to live in desperate circumstances.Thus nurses should be aware of the experiences, needs and beliefs of refugees and address their own cultural competence.
Selection and Characterization of Escherichia coliVariants Capable of Growth on an Otherwise Toxic Tryptophan Analogue

ABSTRACT Escherichia coli isolates that were tolerant of incorporation of high proportions of 4-fluorotryptophan were evolved by serial growth. The resultant strain still preferred tryptophan for growth but showed improved growth relative to the parental strain on other tryptophan analogues. Evolved clones fully substituted fluorotryptophan for tryptophan in their proteomes within the limits of mass spectral and amino acid analyses. Of the genes sequenced, many genes were found to be unaltered in the evolved strain; however, three genes encoding enzymes involved in tryptophan uptake and utilization were altered: the aromatic amino acid permease (aroP) and tryptophanyl-tRNA synthetase (trpS) contained several amino acid substitutions, and the tyrosine repressor (tyrR) had a nonsense mutation. While kinetic analysis of the tryptophanyl-tRNA synthetase suggests discrimination against 4-fluorotryptophan, an analysis of the incorporation and growth patterns of the evolved bacteria suggest that other mutations also aid in the adaptation to the tryptophan analogue. These results suggest that the incorporation of unnatural amino acids into organismal proteomes may be possible but that extensive evolution may be required to reoptimize proteins and metabolism to accommodate such analogues.
Congenital nephrogenic diabetes insipidus: what can we learn from mouse models?

Aquaporins (AQPs) are central players in mammalian physiology, allowing efficient water transport through cellular membranes. To date, 13 different aquaporins have been identified in mammals (AQP0–AQP12). Knocking out genes in mice and identification of mutations in the human genes provided important information on the role of AQPs in normal physiology. While the physiological role of many AQPs only becomes clear when the putative function is challenged, the lack of AQP2 directly results in a disease phenotype. Aquaporin 2 is highly expressed in the principal cells of the renal collecting duct, where it shuttles between intracellular storage vesicles and the apical membrane. Upon hypernatraemia or hypovolaemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary into blood and binds to its type 2 receptor on renal principal cells. This initiates a cAMP signalling cascade resulting in the translocation of AQP2‐bearing vesicles to the apical membrane. Subsequently, pro‐urinary water reabsorption and urine concentration occurs. This process is reversed by a reduction in circulating AVP levels, which is obtained with the establishment of isotonicity. In humans, mutations in the AQP2 gene cause congenital nephrogenic diabetes insipidus (NDI), a disorder characterized by an inability to concentrate urine in response to vasopressin. Until the recent development of several congenital NDI mouse models, our knowledge on AQP2 regulation was primarily based on in vitro studies. This review focuses on the similarities between the in vitro and in vivo studies and discusses new insights into congenital NDI obtained from the mouse models.
New evidence on the determinants of efficiency at Brazilian ports: a bootstrapped DEA analysis

This paper reports on the use of different approaches for measuring efficiency in 27 major Brazilian ports from 2007 to 2011. Several DEA estimates were generated using the bootstrapping technique presented in Simar and Wilson (1998, 2004), thus allowing bias correction to test for significant differences in efficiency levels and their major determinants. Results not only corroborate previous evidence regarding capacity shortfalls within Brazilian ports, but also suggest a positive impact for: a) connectivity infrastructure on scale efficiency levels; b) private administration on managerial efficiency levels; c) higher technical efficiency levels on handling costs and queuing times.
Model Driven Development of Ontology-Based Grid Services

Grid services play a meaningful role in the development of network infrastructures and software systems. The capability of developing Grid systems by means of semantic services abstractions has important implications in developing Grid-based applications. In fact, Grid-based applications can exploit this semantic representation in order to provide the right abstraction level in modeling cooperating Grid services. We consider a framework enabling to define, model, and deploy Grid services in a standardized and platform-independent way. This framework is supported by our Modeling TOol for Grid and Agent Services (MOTO-GAS). In this paper, we present a real application scenario concerning an e-Government emergency communication system. In this scenario we show how the Grid Services development can be enhanced by ontology references defined by means of WSDL-S. We consider this approach as a concrete infrastructure for the development of model driven ontology based Grid services.
Short‐term intensive atorvastatin therapy improves endothelial function partly via attenuating perivascular adipose tissue inflammation through 5‐lipoxygenase pathway in hyperlipidemic rabbits

Background Atherosclerosis is a kind of disease with multiple risk factors, of which hyperlipidemia is a major classical risk factor resulting in its pathogenesis and development. The aim of this study was to determine the effects of short‐term intensive atorvastatin (IA) therapy on vascular endothelial function and explore the possible mechanisms that may help to explain the clinical benefits from short‐term intensive statin therapy. Methods After exposure to high‐fat diet (HFD) for 8 weeks, the animals were, respectively, treated with IA or low‐dose atorvastatin (LA) for 5 days. Blood lipids, C‐reactive protein (CRP), tumor necrosis factor‐&agr; (TNF‐&agr;), interleukin‐6 (IL‐6), nitric oxide (NO), endothelin‐1 (ET‐1), and endothelium‐dependent vasorelaxation function were, respectively, measured. mRNA and protein expression of CRP, TNF‐&agr;, IL‐6, macrophage chemoattractant protein‐1 (MCP‐1), and 5‐lipoxygenase (5‐LO) were also evaluated in pericarotid adipose tissue (PCAT) and cultured adipocytes. Results HFD increased serum inflammatory factor levels; induced significant hyperlipidemia and endothelial dysfunction, including imbalance between NO and ET‐1; enhanced inflammatory factors and 5‐LO expression; and promoted macrophage infiltration into adipose tissue. Five‐day IA therapy could significantly decrease serum inflammatory factor levels and their expression in PCAT; restore the balance between NO and ET‐1; and improve endothelial function and macrophage infiltration without significant changes in blood lipids. However, all of the above were not observed in LA therapy. In vitro experiment found that lipopolysaccharide (LPS) enhanced the expression of inflammatory factors and 5‐LO in cultured adipocytes, which could be attenuated by short‐time (6 hours) treatment of high‐dose (5 &mgr;mol/L) but not low‐dose (0.5 &mgr;mol/L) atorvastatin. In addition, inhibiting 5‐LO by Cinnamyl‐3,4‐dihydroxy‐&agr;‐cyanocinnamate (CDC, a potent and direct 5‐LO inhibitor) could significantly downregulate the above‐mentioned gene expression in LPS‐treated adipocytes. Conclusion Short‐term IA therapy could significantly ameliorate endothelial dysfunction induced by HFD, which may be partly due to attenuating inflammation of PCAT through inhibiting 5‐LO pathway.
The timing of microsurgical reconstruction in lower extremity trauma

The timing of post traumatic microsurgical lower extremity reconstruction was defined by Godina in 1986, with recommendations for flap coverage of Gustillo grade IIIb/c fractures within 72 hours of injury. Godina's study showed the highest risk of infection and flap loss in the delayed period (72 hours–90 days). Subsequent authors have also cited lower rates of flap loss and infection when repair was performed “early”. However, the definition of “early” remains ambiguous. We hypothesized that definitive debridement with optimal dressing care, meticulous microsurgical treatment planning, and vessel anastomoses outside of the zone of injury would allow for delayed reconstruction with high success rates. A retrospective review of 14 lower extremity reconstructions with free flaps was undertaken over a 4‐year period. All patients underwent reconstruction in the delayed (>72 hours) period. There were no flap losses and one case of late osteomyelitis. We conclude that lower extremity reconstruction can be performed safely and effectively in the “delayed” period to allow for wound debridement, stabilization of other injuries, and transfer to a microsurgical facility. © 2008 Wiley‐Liss, Inc. Microsurgery, 2008.
Multifaceted Mechanisms of HIV Inhibition and Resistance to CCR5 Inhibitors PSC-RANTES and Maraviroc

ABSTRACT Small-molecule CCR5 antagonists, such as maraviroc (MVC), likely block HIV-1 through an allosteric, noncompetitive inhibition mechanism, whereas inhibition by agonists such as PSC-RANTES is less defined and may involve receptor removal by cell surface downregulation, competitive inhibition by occluding the HIV-1 envelope binding, and/or allosteric effects by altering CCR5 conformation. We explored the inhibitory mechanisms of maraviroc and PSC-RANTES by employing pairs of virus clones with differential sensitivities to these inhibitors. Intrinsic PSC-RANTES-resistant virus (YA versus RT) or those selected in PSC-RANTES treated macaques (M584 versus P3-4) only displayed resistance in multiple-cycle assays or with a CCR5 mutant that cannot be downregulated. In single-cycle assays, these HIV-1 clones displayed equal sensitivity to PSC-RANTES inhibition, suggesting effective receptor downregulation. Prolonged PSC-RANTES exposure resulted in desensitization of the receptor to internalization such that increasing virus concentration (substrate) could saturate the receptors and overcome PSC-RANTES inhibition. In contrast, resistance to MVC was observed with the MVC-resistant HIV-1 (R3 versus S2) in both multiple- and single-cycle assays and with altered virus concentrations, which is indicative of allosteric inhibition. MVC could also mediate inhibition and possibly resistance through competitive mechanisms.
Excess Carrier Density Variations in Test Structures for Photoconductance-Based Contact Recombination Current Measurements

We recently proposed a novel test structure for the extraction of recombination characteristics of metal-contacted areas on silicon wafers using quasi-steady state photoconductance measurements. In this test structure, photoconductance measurements are performed on several wafer areas with different contact fractions. Each area consists of a lattice of point contacts on an otherwise passivated wafer. The requirement of constant excess carrier densities throughout the quasi-neutral wafer bulk is absolutely essential for the simple extraction of figures of merit for contact recombination. In this study, we first discuss the requirements for constant injection levels during photoconductance measurements, without reference to a particular geometry. Then, we use a simple 1-D model to elucidate how injection levels vary in the test structure plane. We use the model to investigate limiting cases for which the requirement of constant injection levels is satisfied. In addition, we investigate the breakdown of the assumption of constant injection levels. We discuss the influence of nonconstant excess carrier concentrations on photoconductance measurements in the context of our test structure. Finally, we validate our model by comparison with experiments. Our analysis is particularly useful in the context of understanding the design rules for contact size and pitch in our test structure.
Tris(1,10-phenanthroline-κ2 N,N′)iron(II) bis(1,1,3,3-tetracyano-2-ethoxypropenide) hemihydrate

In the title hydrated molecular salt, [Fe(C12H8N2)3](C9H5N4O)2·0.5H2O, the water molecule site is half-occupied. The Fe—N bond lengths within the octahedral tris-chelate [Fe(phen)3]2+ ion (phen is 1,10-phenantroline) are indicative of a low-spin d 6 electronic configuration for the metal ion. The C—N, C—C and C—O bond lengths in the polynitrile anions indicate extensive electronic delocalization. In the crystal, the components are linked through O—H⋯N hydrogen bonds, forming [100] chains, as well as through Coulombic interactions.
Differential regulation of c‐Jun N‐terminal kinase and NF‐κB pathway by caffeic acid phenethyl ester in astroglial and monocytic cells

Caffeic acid phenethyl ester (CAPE), an active component of propolis extracts, has been known for its specific inhibition of nuclear factor κB (NF‐κB) and subsequent anti‐inflammatory activity. In this study, we report that (i) CAPE exerts its anti‐inflammatory action (inhibition of tumor necrosis factor‐induced expression of intercellular adhesion molecule‐1 and CC chemokine ligand‐2) via NF‐κB inhibition by two distinct molecular mechanisms in a cell‐specific manner: CAPE inhibited downstream pathways of inhibitor κB (IκB) degradation in monocytic cells, while activation of upstream IκB kinase was suppressed by CAPE pre‐treatment in astroglial cells; and (ii) CAPE paradoxically activates the c‐Jun N‐terminal kinase (JNK) pathway, which might be responsible for its pro‐apoptotic action and divergent regulation of proinflammatory mediators such as CXC chemokine ligand‐8.
Formaldehyde Fixation Contributes to Detoxification for Growth of a Nonmethylotroph, Burkholderia cepacia TM1, on Vanillic Acid

ABSTRACT During bacterial degradation of methoxylated lignin monomers, such as vanillin and vanillic acid, formaldehyde is released through the reaction catalyzed by vanillic acid demethylase. When Burkholderia cepacia TM1 was grown on vanillin or vanillic acid as the sole carbon source, the enzymes 3-hexulose-6-phosphate synthase (HPS) and 6-phospho-3-hexuloisomerase (PHI) were induced. These enzymes were also expressed during growth on Luria-Bertani medium containing formaldehyde. To understand the roles of these enzymes, the hps and phi genes from a methylotrophic bacterium, Methylomonas aminofaciens 77a, were introduced into B. cepacia TM1. The transformant strain constitutively expressed the genes for HPS and PHI, and these activities were two- or threefold higher than the activities in the wild strain. Incorporation of [14C]formaldehyde into the cell constituents was increased by overexpression of the genes. Furthermore, the degradation of vanillic acid and the growth yield were significantly improved at a high concentration of vanillic acid (60 mM) in the transformant strain. These results suggest that HPS and PHI play significant roles in the detoxification and assimilation of formaldehyde. This is the first report that enhancement of the HPS/PHI pathway could improve the degradation of vanillic acid in nonmethylotrophic bacteria.
Effects of prenatal multimicronutrient supplementation on pregnancy outcomes: a meta-analysis

Background: Reduced intake of micronutrients during pregnancy exposes women to nutritional deficiencies and may affect fetal growth. We conducted a systematic review to examine the efficacy of prenatal supplementation with multimicronutrients on pregnancy outcomes. Methods: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library for relevant articles published in English up to December 2008. We also searched the bibliographies of selected articles as well as clinical trial registries. The primary outcome was low birth weight; secondary outcomes were preterm birth, small-for-gestational-age infants, birth weight and gestational age. Results: We observed a significant reduction in the risk of low birth weight among infants born to women who received multimicronutrients during pregnancy compared with placebo (relative risk [RR] 0.81, 95% confidence interval [CI] 0.73–0.91) or iron–folic acid supplementation (RR 0.83, 95% CI 0.74–0.93). Birth weight was significantly higher among infants whose mothers were in the multimicronutrient group than among those whose mothers received iron–folic acid supplementation (weighted mean difference 54 g, 95% CI 36 g–72 g). There was no significant differences in the risk of preterm birth or small-for-gestational-age infants between the 3 study groups. Interpretation: Prenatal multimicronutrient supplementation was associated with a significantly reduced risk of low birth weight and with improved birth weight when compared with iron–folic acid supplementation. There was no significant effect of multimicronutrient supplementation on the risk of preterm birth or small-for-gestational-age infants.
Vitamin D Receptor ApaI (rs7975232) Polymorphism Confers Decreased Risk of Pulmonary Tuberculosis in Overall and African Population, but not in Asians: Evidence from a Meta‐analysis

Goals. The involvement of the VDR ApaI gene polymorphism in the development of pulmonary tuberculosis (PTB) has been reported by numerous published studies and yielded inconsistent results. The present meta‐analysis evaluated the association of VDR ApaI polymorphism and risk of PTB occurrence. Procedures. PubMed (Medline), EMBASE and Google Scholar web‐databases were searched and a metaanalysis was performed by calculating the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). Results. This meta‐analysis included a total of 14 eligible studies comprising of 1958 confirmed PTB cases and 2938 controls. We observed decreased risk of PTB in allelic (a vs. A: p=0.003; OR=0.873, 95% CI=0.798 to 0.955), homozygous (aa vs. AA: p=0.006; OR=0.761, 95% CI=0.626 to 0.924), dominant (aa+Aa vs. AA: p=0.039; OR=0.874, 95% CI=0.769 to 0.993) and recessive (aa vs. AA+Aa: p=0.025; OR=0.819, 95% CI=0.688 to 0.975) genetic models. During subgroup analysis, allele (a vs. A: p=0.005; OR=0.846, 95% CI=0.753 to 0.951), homozygous (aa vs. AA: p=0.002; OR=0.662, 95% CI=0.513 to 0.854) and recessive genetic models (aa vs. AA+Aa: p=0.003; OR=0.709, 95% CI=0.566 to 0.889) demonstrated decreased PTB risk in African population. However, no significant association was observed in Asian population. Conclusion. In conclusion, VDR ApaI polymorphism is significantly associated with decreased risk of PTB for in overall and African population, but not in Asians.
The critical role of mast cell‐derived hypoxia‐inducible factor‐1α in human and mice melanoma growth

Mast cells play an important role in tumorigenesis. Histamine released from mast cells stimulates new vessel formation by acting through the histamine1 (H1) receptor. Despite the evidence of the role of mast cells in tumor growth and angiogenesis, the potential mechanism remains to be elucidated. Therefore, we investigated the role of mast cell‐derived HIF‐1α in melanoma growth. Here, we identify that the most positive cells for HIF‐1α staining are seen in mast cells of human and animal melanoma tissue. The number of the stromal cell types (fibroblasts, macrophages and endothelial cells) was also increased in melanoma tissues. In activated bone marrow‐derived mast cells (BMMCs), expressions of HIF‐1α and VEGF were increased. Histamine also induced the expressions of HIF‐1α and VEGF in BMMCs. H1 receptor antagonists significantly improved overall survival rates and substantially suppressed tumor growth as well as the infiltration of mast cells and levels of VEGF through the inhibition of HIF‐1α expression in B16F10 melanoma‐bearing mice. Furthermore, the injection of HIF‐1α depleted BMMCs markedly inhibited the growth of tumors and migration of mast cells and increased the survival rate of the mice. These findings emphasize that the growth of melanoma can actually be exacerbated by mast cell‐derived HIF‐1α. In aggregate, our results reveal a novel role for mast cell‐derived HIF‐1α in the melanoma microenvironment and have important implications for the design of therapeutic strategies.