浑善达克沙地全新世气候变化与风沙活动—夏日淖湖泊沉积记录

Atmospheric dust as an important factor for climate feedbacks is mainly derived from and drove by the aeolian activities of the semi-arid regions in Asia. Therefore, reconstructing the history of aeolian activities in this region has a great significance in understanding the dynamics of past and future climate changes. This paper made a systematical sedimentology, geochemisty and high-resolution chronology analysis on the sediments from the Xiarinao Lake, which located in Hunshandake Desert, Inner Mongolia, and compared with the meteorological records for identifying the indicator of aeolian activities and climate changes. Based on above work, the evolution history of the aeolian activities and climate changes since 11,000 a BP was reconstructed and the dynamics of the aeolian activities and climate changes in the Hunshandake Desert was discussed. The indicator of aeolian activities was established through the comparison of the clastic and chemical records with the meteorological registers in recent 50 years: 1. The sediments of Xiarinao Lake are mainly derived from eaolian clastic materials and composed of two major components: one is the sand fraction (<4 ) similar to the composition of sand dunes, the other is the silt fraction (>4 ) similar to the atmospheric dust. The sand content and the median grain size, particularly the sand content, show a close association with the intensity of wind, indicating that the particle-size composition of the sediments reflect the variations of the aeolian activities. 2. The proportion of soluble salts relative to the total carbonates in the sediments was correlated to the arid degree registered in meteorological records, suggesting that arid degree might be associated with changes of wind speed and the relative proportion of soluble salts to the total carbonate could be used as the indicator of aridity. 3. The δ18O of authigenic calcite in the Xiarinao Lake show a well correlation with both the atmosphere precipitation and variation of the moisture indicated by the concentrations of soluble salts, suggesting that δ18O of anthigenic calcite is a reliable indicator of humidity. Based on above studies, the evolution history of the aeolian activities and climate changes since 11,000 a BP was reconstructed. At the same time, their association and underlying dynamics was discussed: 1. The evolution history of the eaolian activity was reconstructed by the sand content and median grain size. The result showed that aeolian activities had experienced several different climate periods in the Holocene: the aeolian activities fluctuated with a 500-year cycles during the interval from 10,900 to 8200 a BP; no significant aeolian activities had been developed from 8200 to 6300 a BP; during the interval of 6300 to 2600 a BP, sand content and media grain size had increased gradually, the sand content increased from about 5% to 25%, indicating the intensity of aeolian activity increased in the Hunshandake Desert; since 2600 a BP, intensity of aeolian activity has become stronger and activated the sand dunes. 2. The relative arid degree indicated by the proportion of soluble salts relative to the total carbonate show that both the wind speed and dry degree had being increased since 11,000 a BP. During the interval of 10900 to 6300 a BP, no detectable soluble salt was found in the sediments, indicating the humidity condition; the proportion increased to 20% from 6300 to 4200 a BP, showing the climate became drier; the little change of proportion (20%) suggest that the climate was relative stable during the interval of 4200 to 2600 a BP; after 2600 a BP, the proportion increased, showing the climate became further dry. 3. The δ18O evolution of the lake water was established through analysis of authigenetic calcite δ18O for revealing the variations of relative effective humidity in the Hunshandake Desert. δ18O maintained around -6 ‰ during the interval of 10900 to 8200 a BP, showing the climate was a little dry relative to that of the whole Holocnene; in the period of 8200 to 6300 a BP, δ18O had the most negative values, indicating that it was the most humid interval in Holocene; from 6300 to 4200 a BP, δ18O increased from about -7.5 ‰ to about -3 ‰ gradually, suggesting increased aridity; since 4200 a BP, the climate has become stable and dry. On the whole, the records in this study show that the variation of the relative humidity and aridity is consistent with that of summer monsoon in the Hunshandake Desert. The relationships among the grain size, soluble salts relative content, and the authigenic calcite δ18O indicate aeolian activities is controlled by the aridity in the studied area, and the increased aeolian activities is closely associated with the temperature changes under the relative dry condition. The high wind speed under the low temperature leads to the increased aeolian activity, and the temperature change associated with the aeolian activities might be related with the perturbations of the Siberian High Pressure.

Altered of apoptotic markers of both extrinsic and intrinsic pathways induced by hepatitis C virus infection in peripheral blood mononuclear cells

Background: Chronic hepatitis C (CHC) has emerged as a leading cause of cirrhosis in the U. S. and across the world. To understand the role of apoptotic pathways in hepatitis C virus (HCV) infection, we studied the mRNA and protein expression patterns of apoptosis-related genes in peripheral blood mononuclear cells (PBMC) obtained from patients with HCV infection.Methods: the present study included 50 subjects which plasma samples were positive for HCV, but negative for human immunodeficiency virus (HIV) or hepatitis B virus (HBV). These cases were divided into four groups according to METAVIR, a score-based analysis which helps to interpret a liver biopsy according to the degree of inflammation and fibrosis. mRNA expression of the studied genes were analyzed by reverse transcription of quantitative polymerase chain reaction (RT-qPCR) and protein levels, analyzed by ELISA, was also conducted. HCV genotyping was also determined.Results: HCV infection increased mRNA expression and protein synthesis of caspase 8 in group 1 by 3 fold and 4 fold, respectively (p < 0.05). in group 4 HCV infection increased mRNA expression and protein synthesis of caspase 9 by 2 fold and 1,5 fold, respectively (p < 0.05). Also, caspase 3 mRNA expression and protein synthesis had level augumented by HCV infection in group 1 by 4 fold and 5 fold, respectively, and in group 4 by 6 fold and 7 fold, respectively (p < 0.05).Conclusions: HCV induces alteration at both genomic and protein levels of apoptosis markers involved with extrinsic and intrinsic pathways.

Neuroprotective and immunomodulatory properties of the new PPARγ agonist MDG548: an in vitro and in vivo study in PD models

Neuroinflammation is a key component of Parkinson’s disease (PD) neuropathology. Skewed microglia activation with pro-inflammatory prevailing over anti-inflammatory phenotypes may contribute to neurotoxicity via the production of cytokines and neurotoxic species. Therefore, microglia polarization has been proposed as a target for neuroprotection. The peroxisome proliferator-activated receptor gamma (PPARγ) is expressed in microglia and peripheral immune cells, where it is involved in macrophages polarization and in the control of inflammatory responses, by modulating gene transcription. Several studies have shown that PPARγ agonists are neuroprotective in experimental PD models in rodents and primates. however safety concerns have been raised about PPARγ agonists thiazolidinediones (TZD) currently available, prompting for the development of non-TZD compounds. Aim of this study was to characterize a novel PPARγ agonist non TZD, MDG548, for its potential neuroprotective effect in PD models and its immunomodulatory activity as the underlying mechanism of neuroprotection. The neuroprotective activity of MDG548 was assessed in vivo in the subacute MPTP model and in the chronic MPTP/probenecid (MPTPp) model of PD. MDG548 activity on microglia activation and phenotype was investigated in the substantia nigra pars compacta (SNc) via the evaluation of pro- (TNF-α and iNOS) and anti-inflammatory (CD206) molecules, with fluorescent immunohistochemistry. Moreover, cultured murine microglia MMGT12 were treated with MDG548 in association with the inflammagen LPS, pro- and anti-inflammatory molecules were measured in the medium by ELISA assay and phagocytosis was evaluated by fluorescent immunohistochemistry for CD68. MDG548 arrested dopaminergic cells degeneration in the SNc in both the subacute MPTP and the chronic MPTPp models of PD, and reverted MPTPp-induced motor impairment. Moreover, MDG548 reduced microglia activation, iNOS and TNF-α production, while induced CD206 in microglia. In cultured unstimulated microglia, LPS increased TNF-α production and CD68 expression, while decreased CD206 expression. MDG548 reverted LPS effect on TNF-α and CD206 restoring physiological levels, while strongly increased CD68 expression. Results suggest that the PPARγ agonist MDG548 is neuroprotective in experimental models of PD. MDG548 targets microglia polarization by correcting the imbalance between pro- over antiinflammatory molecules, offering a novel immunomodulatory approach to neuroprotection.

JUSTEIS: JISC Usage Surveys: Trends in Electronic Information Services Final report 2003/2004 Cycle Five

Urquhart, C., Spink, S., Thomas, R., Yeoman, A., Durbin, J., Turner, J., Fenton, R. & Armstrong, C. (2004). JUSTEIS: JISC Usage Surveys: Trends in Electronic Information Services Final report 2003/2004 Cycle Five. Aberystwyth: Department of Information Studies, University of Wales Aberystwyth. Sponsorship: JISC

Antioxidant supplementation and immunoendocrine responses to prolonged exercise

Davison, Glen, et al., 'Antioxidant supplementation and immunoendocrine responses to prolonged exercise', Medicine and Science in Sports and Exercise, (2007) 39(4) pp.645-652 RAE2008

Plasmid biology of natural Lactococcus lactis strains and molecular mechanisms of bacteriophage-host interaction

Lacticin 3147, enterocin AS-48, lacticin 481, variacin, and sakacin P are bacteriocins offering promising perspectives in terms of preservation and shelf-life extension of food products and should find commercial application in the near future. The studies detailing their characterization and bio-preservative applications are reviewed. Transcriptomic analyses showed a cell wall-targeted response of Lactococcus lactis IL1403 during the early stages of infection with the lytic bacteriophage c2, which is probably orchestrated by a number of membrane stress proteins and involves D-alanylation of membrane lipoteichoic acids, restoration of the physiological proton motive force disrupted following bacteriophage infection, and energy conservation. Sequencing of the eight plasmids of L. lactis subsp. cremoris DPC3758 from raw milk cheese revealed three anti-phage restriction/modification (R/M) systems, immunity/resistance to nisin, lacticin 481, cadmium and copper, and six conjugative/mobilization regions. A food-grade derivative strain with enhanced bacteriophage resistance was generated via stacking of R/M plasmids. Sequencing and functional analysis of the four plasmids of L. lactis subsp. lactis biovar. diacetylactis DPC3901 from raw milk cheese revealed genes novel to Lactococcus and typical of bacteria associated with plants, in addition to genes associated with plant-derived lactococcal strains. The functionality of a novel high-affinity regulated system for cobalt uptake was demonstrated. The bacteriophage resistant and bacteriocin-producing plasmid pMRC01 places a metabolic burden on lactococcal hosts resulting in lowered growth rates and increased cell permeability and autolysis. The magnitude of these effects is strain dependent but not related to bacteriocin production. Starters’ acidification capacity is not significantly affected. Transcriptomic analyses showed that pMRC01 abortive infection (Abi) system is probably subjected to a complex regulatory control by Rgg-like ORF51 and CopG-like ORF58 proteins. These regulators are suggested to modulate the activity of the putative Abi effectors ORF50 and ORF49 exhibiting topology and functional similarities to the Rex system aborting bacteriophage λ lytic growth.

Becoming a CEO: an exploration of the theory and practice of effective organisational leadership

This Thesis is an exploration of potential enhancement in effectiveness, personally, professionally and organisationally through the use of Theory as an Apparatus of Thought. Enhanced effectiveness was sought by the practitioner (Subject), while in transition to becoming Chief Executive of his organization. The introduction outlines the content and the structure of the University College Cork DBA. Essay One outlines what Theory is, what Adult Mental Development is and an exploration of Theories held in the Authors past professional practice. Immunity to change is also reflected on. Essay Two looks at the construct of the key Theories used in the Thesis. Prof. Robert Kegan’s Theory of Adult Mental Development was used to aid the generation of insight. The other key Theories used were The Theory of The Business, Theory of the Co‐operative and a Theory of Organisational Leadership. Essay Three explores the application of the key Theories in a professional setting. The findings of the Thesis were that the subject was capable of dealing with increased environmental complexity and uncertainty by using Theory as an Apparatus of Thought, which in turn enhanced personal, professional and organisational effectiveness. This was achieved by becoming more aware of the Theories held by the practitioner, the experiences from the application of those Theories, which then led to greater insight. The author also found that a detailed understanding of the Theory of the Business and a Theory of Leadership would support any new CEO in the challenging early part of their tenure.

Investigating the function of PINK1 in cancer development and pathogenesis

PTEN‐induced kinase 1 (PINK1) was identified initially in cancer cells as a gene up‐regulated by overexpression of the central tumour suppressor, PTEN. Loss‐of‐function mutations in PINK1 were discovered subsequently to cause autosomal recessive Parkinsonʹs disease (ARPD). Despite much research focusing on the proposed mechanism(s) through which loss of PINKI function causes neurodegeneration, few studies have focused on a direct role for this serine/threonine kinase in cancer biology. The focus of this thesis was to examine a direct role for PINK1 function in tumourigenesis. Initial studies showed that loss of PINK1 reduces tumour‐associated phenotypes including cell growth, colony formation and invasiveness, in several cell types in vitro, indicating a pro‐tumourigenic role for PINK1 in cancer. Furthermore, results revealed for the first time that PINK1 deletion, examined in mouse embryonic fibroblasts (MEFS) from PINK1 knock‐out animals, causes cell cycle defects, whereby cells arrest at in cytokinesis, giving rise to a highly significant increase in the number of multinucleated cells. This results in several key changes in the expression profile of cell cycle associated protein. In addition, PINK1‐deficient MEFs were found to resist cell cycle exit, with a proportion of cells remaining in proliferative phases upon removal of serum. The ability of cells to progress through mitosis conferred by PINK1 expression was independent of its kinase activity, while the cell cycle exit following serum withdrawal was kinase dependent. Investigations into the mechanism through which loss of PINK1 function gives rise to cell cycle defects revealed that dynamin related protein 1 (Drp1)‐mediated mitochondrial fission is enhanced in PINK1‐ deficient MEFs, and that increased expression of Drp1 on mitochondria and activation of Drp1 is highly significant in PINK1‐deficient multinucleated cells. Deregulated and increased levels and activation of mitochondrial fission via Drp1 was shown to be a major feature of cell cycle defects caused by PINK1 deletion, both during progression through G2/M and cell cycle exit following serum removal. Altered PINK1 localisation was also observed during progression of mitosis, and upon serum deprivation. Thus, PINK1 dissociated from the mitochondria during the mitotic phases and localised to mitochondria upon serum withdrawal. During serum withdrawal deletion of PINK1 disabled the ability of MEFs to increase mitochondrial membrane potential (ΔΨm), and increase autophagy. This was co‐incident with increased mitochondrial fission, and increased localisation of Drp1 to mitochondria following serum deprivation. Together, this indicates an inability of PINK1‐negative cells to respond protectively to this stress‐induced state, primarily via impaired mitochondrial function. In contrast, PINK1 overexpression was found to protect cells from DNA damage following treatment with oxidants. In addition, deletion of PINK1 blocked the ability of cells to re‐enter the cell cycle in response to insulin‐like growth factor‐1 (IGF‐1), a major cancer promoting agonistwhich acts primarily via PI3‐kinase/Akt activation. Furthermore, PINK1 mRNA expression was significantly increased following serum deprivation of MCF‐7 cells, and this was rendered more significant upon additional inhibition of PI3‐kinase. Conversely, IGF‐1 activation of PI3‐kinase/Akt causes a time‐dependent and significant reduction of PINK1 mRNA expression that was PI3‐kinase dependent. Together these results indicate that PINK1 expression is necessary for IGF‐1 signalling and is regulated reciprocally in the absence and presence of IGF‐1, via PI3‐kinase/Akt, a signalling system which has major tumour‐promoting capacity in cancer cell biology. The results of this thesis indicate PINK1 is a candidate tumour-promoting gene which has a significant function in the regulation of the cell cycle, and growth factor responses, at key cell cycle checkpoints, namely, during progression through G2/M and during exit of the cell cycle following removal of serum. Furthermore, the results reveal that the regulation of mitochondrial fission and Drp1 function is mechanistically important in the regulation of cell cycle control by PINK1. As deregulation of the cell cycle is linked to both tumourigenesis and neurodegeneration, the findings of this thesis are of importance not just for understanding cancer biology, but also in the context of PINK1‐associated neurodegeneration.

The ways in which new public management ideas impact upon the administrative culture of 'street-level' bureaucrats and professionals working within Irish social policy

The conventional meaning of culture is ‘widely shared and strongly held values’ of a particular group or society (Bradley and Parker, 2006: 89). Culture is not a rigid concept; it can be influenced or altered by new ideas or forces. This research examines the ways in which one set of ideas in particular, that is, those associated with New Public Management, have impacted upon the administrative culture of 'street-level' bureaucrats and professionals within Irish social policy. Lipsky (1980: 3) defined 'street-level' bureaucrats as ‘public service workers who interact directly with citizens in the course of their jobs, and who have substantial discretion in the execution of their work’. Utilising the Competing Values Framework (CVF) in the analysis of eighty three semi-structured interviews with 'street-level' bureaucrats and professionals, an evaluation is made as to the impact of NPM ideas on both visible and invisible aspects of administrative culture. Overall, the influence of NPM is confined to superficial aspects of administrative culture such as; increased flexibility in working hours and to some degree job contracts; increased time commitment; and a customer service focus. However, the extent of these changes varies depending on policy sector and occupational group. Aspects of consensual and hierarchical cultures remain firmly in place. These coincide with features of developmental and market cultures. Contrary to the view that members of hierarchical and consensual culture would pose resistance to change, this research clearly illustrates that a very large appetite for change exists in the attitudes of 'street-level' bureaucrats and professionals within Irish social policy, with many of them suggesting changes that correspond to NPM ideas. This study demonstrates the relevance of employing the CVF model as it is clear that administrative culture is very much a dynamic system of competing and co-existing cultures.

Characterization of the degradation of wild-type and mutant HFE proteins during stress signalling in the endoplasmic reticulum

HFE is a transmembrane protein that becomes N-glycosylated during transport to the cell membrane. It acts to regulate cellular iron uptake by interacting with the Type 1 transferrin receptor and interfering with its ability to bind iron-loaded transferrin. There is also evidence that HFE regulates systemic iron levels by binding to the Type II transferrin receptor although the mechanism by which this occurs is still not well understood. Mutations to HFE that disrupt this function, or physiological conditions that decrease HFE protein levels, are associated with increased iron uptake, and its accumulation in tissues and organs. This is exemplified by the point mutation that results in conversion of cysteine residue 282 to tyrosine (C282Y), and gives rise to the majority of HFE-related hemochromatoses. The C282Y mutation prevents the formation of a disulfide bridge and disrupts the interaction with its co-chaperone β2-microglobulin. The resulting misfolded protein is retained within the endoplasmic reticulum (ER) where it activates the Unfolded Protein Response (UPR) and is subjected to proteasomal degradation. The absence of functional HFE at the cell surface leads to unregulated iron uptake and iron loading. While the E3 ubiquitin ligase involved in the degradation of HFE-C282Y has been identified, the mechanism by which it is targeted for degradation remains relatively obscure. The primary objective of this project was to further our understanding of how the iron regulatory HFE protein is targeted for degradation. Our studies suggest that the glycosylation status, and the active process of deglycosylation, are central to this process. We identified a number of additional factors that can contribute towards degradation and explored their regulation during ER stress conditions.

Estimation of in-canopy ammonia sources and sinks in a fertilized Zea mays field.

An analytical model was developed to describe in-canopy vertical distribution of ammonia (NH(3)) sources and sinks and vertical fluxes in a fertilized agricultural setting using measured in-canopy mean NH(3) concentration and wind speed profiles. This model was applied to quantify in-canopy air-surface exchange rates and above-canopy NH(3) fluxes in a fertilized corn (Zea mays) field. Modeled air-canopy NH(3) fluxes agreed well with independent above-canopy flux estimates. Based on the model results, the urea fertilized soil surface was a consistent source of NH(3) one month following the fertilizer application, whereas the vegetation canopy was typically a net NH(3) sink with the lower portion of the canopy being a constant sink. The model results suggested that the canopy was a sink for some 70% of the estimated soil NH(3) emissions. A logical conclusion is that parametrization of within-canopy processes in air quality models are necessary to explore the impact of agricultural field level management practices on regional air quality. Moreover, there are agronomic and environmental benefits to timing liquid fertilizer applications as close to canopy closure as possible. Finally, given the large within-canopy mean NH(3) concentration gradients in such agricultural settings, a discussion about the suitability of the proposed model is also presented.

Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule.

Cryptococcus neoformans is a prevalent human fungal pathogen that must survive within various tissues in order to establish a human infection. We have identified the C. neoformans Rim101 transcription factor, a highly conserved pH-response regulator in many fungal species. The rim101 multiply sign in circle mutant strain displays growth defects similar to other fungal species in the presence of alkaline pH, increased salt concentrations, and iron limitation. However, the rim101 multiply sign in circle strain is also characterized by a striking defect in capsule, an important virulence-associated phenotype. This capsular defect is likely due to alterations in polysaccharide attachment to the cell surface, not in polysaccharide biosynthesis. In contrast to many other C. neoformans capsule-defective strains, the rim101 multiply sign in circle mutant is hypervirulent in animal models of cryptococcosis. Whereas Rim101 activation in other fungal species occurs through the conserved Rim pathway, we demonstrate that C. neoformans Rim101 is also activated by the cAMP/PKA pathway. We report here that C. neoformans uses PKA and the Rim pathway to regulate the localization, activation, and processing of the Rim101 transcription factor. We also demonstrate specific host-relevant activating conditions for Rim101 cleavage, showing that C. neoformans has co-opted conserved signaling pathways to respond to the specific niche within the infected host. These results establish a novel mechanism for Rim101 activation and the integration of two conserved signaling cascades in response to host environmental conditions.

Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance.

Release of endogenous dynorphin opioids within the spinal cord after partial sciatic nerve ligation (pSNL) is known to contribute to the neuropathic pain processes. Using a phosphoselective antibody [kappa opioid receptor (KOR-P)] able to detect the serine 369 phosphorylated form of the KOR, we determined possible sites of dynorphin action within the spinal cord after pSNL. KOR-P immunoreactivity (IR) was markedly increased in the L4-L5 spinal dorsal horn of wild-type C57BL/6 mice (7-21 d) after lesion, but not in mice pretreated with the KOR antagonist nor-binaltorphimine (norBNI). In addition, knock-out mice lacking prodynorphin, KOR, or G-protein receptor kinase 3 (GRK3) did not show significant increases in KOR-P IR after pSNL. KOR-P IR was colocalized in both GABAergic neurons and GFAP-positive astrocytes in both ipsilateral and contralateral spinal dorsal horn. Consistent with sustained opioid release, KOR knock-out mice developed significantly increased tactile allodynia and thermal hyperalgesia in both the early (first week) and late (third week) interval after lesion. Similarly, mice pretreated with norBNI showed enhanced hyperalgesia and allodynia during the 3 weeks after pSNL. Because sustained activation of opioid receptors might induce tolerance, we measured the antinociceptive effect of the kappa agonist U50,488 using radiant heat applied to the ipsilateral hindpaw, and we found that agonist potency was significantly decreased 7 d after pSNL. In contrast, neither prodynorphin nor GRK3 knock-out mice showed U50,488 tolerance after pSNL. These findings suggest that pSNL induced a sustained release of endogenous prodynorphin-derived opioid peptides that activated an anti-nociceptive KOR system in mouse spinal cord. Thus, endogenous dynorphin had both pronociceptive and antinociceptive actions after nerve injury and induced GRK3-mediated opioid tolerance.

Who tests, who doesn't, and why? Uptake of mobile HIV counseling and testing in the Kilimanjaro Region of Tanzania.

BACKGROUND: Optimally, expanded HIV testing programs should reduce barriers to testing while attracting new and high-risk testers. We assessed barriers to testing and HIV risk among clients participating in mobile voluntary counseling and testing (MVCT) campaigns in four rural villages in the Kilimanjaro Region of Tanzania. METHODS: Between December 2007 and April 2008, 878 MVCT participants and 506 randomly selected community residents who did not access MVCT were surveyed. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing between MVCT participants and community residents who did not access MVCT. Gender-specific logistic regression models were used to describe differences in socioeconomic characteristics, HIV exposure risk, testing histories, HIV related stigma, and attitudes toward testing, between the two groups. RESULTS: MVCT clients reported greater HIV exposure risk (OR 1.20 [1.04 to 1.38] for males; OR 1.11 [1.03 to 1.19] for females). Female MVCT clients were more likely to report low household expenditures (OR 1.47 [1.04 to 2.05]), male clients reported higher rates of unstable income sources (OR 1.99 [1.22 to 3.24]). First-time testers were more likely than non-testers to cite distance to testing sites as a reason for not having previously tested (OR 2.17 [1.05 to 4.48] for males; OR 5.95 [2.85 to 12.45] for females). HIV-related stigma, fears of testing or test disclosure, and not being able to leave work were strongly associated with non-participation in MVCT (ORs from 0.11 to 0.84). CONCLUSIONS: MVCT attracted clients with increased exposure risk and fewer economic resources; HIV related stigma and testing-related fears remained barriers to testing. MVCT did not disproportionately attract either first-time or frequent repeat testers. Educational campaigns to reduce stigma and fears of testing could improve the effectiveness of MVCT in attracting new and high-risk populations.

Induced pluripotent stem cell-derived cardiac progenitors differentiate to cardiomyocytes and form biosynthetic tissues.

The mammalian heart has little capacity to regenerate, and following injury the myocardium is replaced by non-contractile scar tissue. Consequently, increased wall stress and workload on the remaining myocardium leads to chamber dilation, dysfunction, and heart failure. Cell-based therapy with an autologous, epigenetically reprogrammed, and cardiac-committed progenitor cell source could potentially reverse this process by replacing the damaged myocardium with functional tissue. However, it is unclear whether cardiac progenitor cell-derived cardiomyocytes are capable of attaining levels of structural and functional maturity comparable to that of terminally-fated cardiomyocytes. Here, we first describe the derivation of mouse induced pluripotent stem (iPS) cells, which once differentiated allow for the enrichment of Nkx2-5(+) cardiac progenitors, and the cardiomyocyte-specific expression of the red fluorescent protein. We show that the cardiac progenitors are multipotent and capable of differentiating into endothelial cells, smooth muscle cells and cardiomyocytes. Moreover, cardiac progenitor selection corresponds to cKit(+) cell enrichment, while cardiomyocyte cell-lineage commitment is concomitant with dual expression of either cKit/Flk1 or cKit/Sca-1. We proceed to show that the cardiac progenitor-derived cardiomyocytes are capable of forming electrically and mechanically coupled large-scale 2D cell cultures with mature electrophysiological properties. Finally, we examine the cell progenitors' ability to form electromechanically coherent macroscopic tissues, using a physiologically relevant 3D culture model and demonstrate that following long-term culture the cardiomyocytes align, and form robust electromechanical connections throughout the volume of the biosynthetic tissue construct. We conclude that the iPS cell-derived cardiac progenitors are a robust cell source for tissue engineering applications and a 3D culture platform for pharmacological screening and drug development studies.