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Felix Almaraz, Author and Teacher, "The Tragic Calvalier."(photograph)
No full textPhotograph of Felix Almaraz, Author and Teacher, "The Tragic Calvalier."
VEGF-expressing mesenchymal stem cells for improved angiogenesis in regenerative medicine : a bone tissue engineering approach
Get PDFRapid vascularization of tissue-engineered grafts is a major bottleneck in the development of regenerative medicine approaches. In order to overcome this limitation, we aimed to develop a bone tissue engineering strategy combining cell therapy with pro-angiogenic gene therapy.
Vascular Endothelial Growth Factor (VEGF) is the master regulator of physiological vascular growth and is commonly used as a therapeutic transgene for the induction of angiogenesis. However, uncontrolled and high levels of VEGF expression can lead to aberrant vascular growth. To achieve controlled expression in vivo, a high-throughput flow cytometry-based method has previously been developed in our group. Linking the VEGF cDNA to a cell-surface marker (a truncated version of CD8a) in a bicistronic construct enabled the rapid purification of genetically modified myoblasts secreting a desired VEGF level, using FACS sorting based on the intensity of CD8 expression in each cell. Controlled VEGF expression in skeletal muscle, achieved by implantation of these FACS-purified myoblast populations, induced only normal, stable and functional vascular networks and avoided any aberrant angiogenesis.
The aims of this thesis were to adapt this method to human adipose tissue- and bone marrow-derived mesenchymal stromal/stem cells (ASC and BMSC), and to apply these in a bone tissue engineering approach to increase the vascularization potential of osteogenic grafts.
As MSC gradually loose their regenerative potential during in vitro expansion, we first optimized our genetic engineering method for MSC, so as to enable high transduction efficiency and FACS-purification with minimal in vitro manipulation. Chapter 2 describes the generation of an optimized protocol allowing routine transduction efficiencies of > 90% of primary human ASC and BMSC already during the first plating, as well as flow cytometry purification of transduced cells at the time of the first passage. In addition we demonstrated that it was possible to FACS-purify specific sub-populations of transduced MSC homogeneously producing desired VEGF doses. Neither retroviral vector transduction, FACS-purification, nor the expression of the transgenes VEGF and CD8 impaired MSC proliferation and in vitro differentiation potential. Transgene expression was not lost during in vitro differentiation.
In Chapter 3, proof-of-principle was obtained by applying this platform to a bone tissue engineering approach. Human BMSC, transduced and rapidly FACS-purified to eliminate non-expressing cells, were seeded onto hydroxyapatite granules to generate non-critically sized constructs, and were implanted subcutaneously in nude rats. In vivo vascularization potential was significantly increased in VEGF-expressing BMSC. Although VEGF expression was heterogeneous, no aberrant angiogenesis was observed. Indeed, orderly vascular beds were induced, with flow-conducting arterioles feeding into extensive capillary networks, where metabolic exchanges can take place efficiently. The improvement in vascularization was not diminished by extensive in vitro expansion of the transduced BMSC up to 35 population doublings, showing that genetic modification conferred a stable angiogenic potential. As expected, these expanded BMSC lost their osteogenic potential. However, their sustained capacity to induce vascularization could be useful in other applications, where effective expansion of the vascular bed is required, but not progenitor differentiation, such as in cell-based approaches for therapeutic angiogenesis in peripheral or coronary artery diseases.
By minimizing cell expansion, both naïve and control transduced MSC generated abundant bone tissue in vivo. However, VEGF over-expression specifically caused a strong reduction in bone formation. This correlated with an increased recruitment of TRAP-positive osteoclasts specifically in VEGF-expressing constructs.
These data suggest that VEGF over-expression might impair bone formation by disrupting the balance between bone formation and resorption towards excessive degradation. To fully understand the underlying mechanism, further experiments will be needed.
The method described in chapter 2 provides a general platform to generate populations of genetically modified MSC, expressing specific levels of a therapeutic transgene, already at the time of the first passage. Therefore, it has the potential to be applied in other fields of regenerative medicine, beyond bone tissue engineering. We briefly describe two recently initiated projects, based on the results described in this thesis, which aim at either promoting or inhibiting angiogenesis in order to improve cardiac function after myocardial infarction, or cartilage tissue formation, respectively
Parents’ assets and child marriage: are mother’s assets more protective than father’s assets?
No full textChild marriage places girls at an increased risk for dropping out of school early, sexually transmitted infections, teenage childbirth, and accompanying childbirth complications, including maternal mortality. The determinants of child marriage are not clearly understood, which hinders efforts to mount effective interventions. This study examined the link between economic resources and child marriage by investigating whether maternal and paternal asset ownership were longitudinally associated with daughters’ child marriage in Ethiopia. Drawing upon household bargaining theory, it was hypothesized that maternal assets would be more protective of daughters’ child marriage than paternal assets. Data for 4,293 girls from the nationally representative Ethiopia Socioeconomic Survey, fielded in 2011 and 2014, were employed. Logistic regression and instrumental variable analyses were used to examine the relationship between transition into child marriage during the study period and maternal and paternal assets, controlling for child-, family-, and community-level characteristics. Results show that a one standard deviation increase in mother’s assets was associated with 37–53% lower odds of daughter’s child marriage whereas a one standard deviation increase in paternal asset holdings was associated with 0–37% higher odds of daughter’s child marriage. Effects were strongest in regions where the dominant mode of marriage payments is bride price. These results suggest that the link between economic resources and child marriage depends on the gender of the parent who owns the resources. This study also highlights the interconnectedness of two targets of the gender equality Sustainable Development Goal—improvement of women’s ownership of assets and the elimination of child marriage—and suggests that the realization of one gender equality target could have implications for other targets.Peer reviewe
Disability among children of immigrants from India and China: is there excess disability among girls?
No full textWe investigate whether there is excess morbidity among daughters of Indian or Chinese immigrants in the US by studying the prevalence of disability among children. We use data from the 2012–14 American Community Surveys on approximately 20,000 US-born children of Indian and Chinese immigrants. Children of US natives are used as a comparison group to account for innate differences in disability between the sexes. Results indicate that there is excess disability among daughters compared with sons among children of Chinese immigrants and children of immigrants from northern or western Indian states; this excess disability declines with younger age at arrival or longer exposure to the host country. Analysis using children of Filipino immigrants as an alternative comparison group yields similar excess disability rates for females.Peer reviewe
Effect of Food Subsidies on Micronutrient Consumption
No full textIn this article, we study the effect of an exogenous increase in wheat and rice price subsidy to poor families resulting from a targeted food price subsidy program in India called the Targeted Public Distribution System (TPDS) on micronutrient intake in low-income families. Descriptive results show that wheat and rice have one of the lowest micronutrient density scores, suggesting that these are poor suppliers of micronutrients. Empirical analysis suggests that the increase in subsidy amount of Rs. 15-18 resulting from the TPDS expansion lowered calcium intake by 12-14 percent and had negligible to small (often negative) effects on the consumption of most micronutrients.Peer reviewe
Sex composition of children and spousal sexual violence in sub-Saharan Africa
No full textObjective
In societies with a cultural preference for sons over daughters, women who do not bear sons may be at increased risk for spousal violence. This study examined whether women with daughters only are at an elevated risk for spousal sexual violence compared to women with sons only in sub-Saharan Africa. The study tested the hypothesis that the association between sex composition of children and spousal sexual violence would be observed only in large families.
Methods
Data were from the most recent (as at February, 2016) Demographic and Health Surveys conducted in 22 sub-Saharan African countries for 37,915 women. Odds ratios comparing experience of spousal sexual violence of women with sons only to those with daughters only were estimated, separately for women with three or fewer children and those with four or more children, controlling for age, age at first cohabitation, age at first birth, educational attainment, urban residence, and household wealth.
Results
Having daughters only was associated with a greater likelihood of spousal sexual violence among women with many children (adjusted odds ratio [AOR] = 1.53; 95% CI = 1.02–2.30) but not among those with few children (AOR = 0.92; 95% CI = 0.82–1.04).
Conclusions for practice
A higher risk of sexual violence for women without sons suggests that son preference may have implications on women’s health and wellbeing. Efforts to further understand and address increased risk of sexual violence for women without sons should consider son preference and intra-couple conflict concerning fertility intentions.Peer reviewe
Culture, labor supply, and fertility across immigrant generations in the United States
No full textRecent immigration to the United States and other developed nations has increasingly been from countries that have relatively traditional gender norms. This study uses data from the Current Population Survey for 2000–14 to investigate how source-country gender norms influence the labor supply and fertility of married women across immigrant generations in the US. It finds that immigrants’ and descendants’ labor supply and fertility are associated with the female-to-male labor force participation ratio and total fertility rate in the source country; importantly, the association declines across successive generations. Husbands’ source-country characteristics are also associated with the labor supply and fertility of immigrant women. These findings indicate evolution and assimilation of traditional gender norms in the long run.Peer reviewe
The genome and proteome of a virulent Escherichia coli O157:H7 bacteriophage closely resembling Salmonella phage Felix O1
No full textBased upon whole genome and proteome analysis, Escherichia coli O157:H7-specific bacteriophage (phage) wV8 belongs to the new myoviral genus, "the Felix O1-like viruses" along with Salmonella phage Felix O1 and Erwinia amylovora phage φEa21-4. The genome characteristics of phage wV8 (size 88.49 kb, mol%G+C 38.9, 138 ORFs, 23 tRNAs) are very similar to those of phage Felix O1 (86.16 kb, 39.0 mol%G+C, 131 ORFs and 22 tRNAs) and, indeed most of the proteins have their closest homologs within Felix O1. Approximately one-half of the Escherichia coli O157:H7 mutants resistant to phage wV8 still serotype as O157:H7 indicating that this phage may recognize, like coliphage T4, two different surface receptors: lipopolysaccharide and, perhaps, an outer membrane protein
Felix Grant and Peter Ustinov
No full textFelix Grant and internationally renowned actor, author and playwright Peter Ustinov converse.Made available in DSpace on 2012-10-09T17:40:17Z (GMT). No. of bitstreams: 4
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Previous issue date: 2002-11-04Handwritten on back: "Felix Grant and / Peter Ustinof [sic]
Track seed classification with Deep Neural Networks
No full textauthor Felix DietrichMasterarbeit Universität Innsbruck 202
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