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61.
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62.
  • Acuna, Lillian G., et al. (författare)
  • Architecture and Gene Repertoire of the Flexible Genome of the Extreme Acidophile Acidithiobacillus caldus
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Acidithiobacillus caldus is a sulfur oxidizing extreme acidophile and the only known mesothermophile within the Acidithiobacillales. As such, it is one of the preferred microbes for mineral bioprocessing at moderately high temperatures. In this study, we explore the genomic diversity of A. caldus strains using a combination of bioinformatic and experimental techniques, thus contributing first insights into the elucidation of the species pangenome. Principal Findings: Comparative sequence analysis of A. caldus ATCC 51756 and SM-1 indicate that, despite sharing a conserved and highly syntenic genomic core, both strains have unique gene complements encompassing nearly 20% of their respective genomes. The differential gene complement of each strain is distributed between the chromosomal compartment, one megaplasmid and a variable number of smaller plasmids, and is directly associated to a diverse pool of mobile genetic elements (MGE). These include integrative conjugative and mobilizable elements, genomic islands and insertion sequences. Some of the accessory functions associated to these MGEs have been linked previously to the flexible gene pool in microorganisms inhabiting completely different econiches. Yet, others had not been unambiguously mapped to the flexible gene pool prior to this report and clearly reflect strain-specific adaption to local environmental conditions. Significance: For many years, and because of DNA instability at low pH and recurrent failure to genetically transform acidophilic bacteria, gene transfer in acidic environments was considered negligible. Findings presented herein imply that a more or less conserved pool of actively excising MGEs occurs in the A. caldus population and point to a greater frequency of gene exchange in this econiche than previously recognized. Also, the data suggest that these elements endow the species with capacities to withstand the diverse abiotic and biotic stresses of natural environments, in particular those associated with its extreme econiche.
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63.
  • Acuña Mora, Mariela, 1990, et al. (författare)
  • Patient empowerment in young persons with chronic conditions: Psychometric properties of the Gothenburg Young Persons Empowerment Scale (GYPES).
  • 2018
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 13:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Empowerment in patients can lead to a higher participation in care and self-management skills. However, there are a limited number of high-quality instruments to assess empowerment and its various dimensions in young persons. The aim was to develop and assess the psychometric properties of the Gothenburg Young Persons Empowerment Scale (GYPES).The GYPES is a 15-item questionnaire designed to measure patient empowerment in young persons with chronic conditions. Three studies were conducted to evaluate the psychometric properties of the scale. Studies I and II assessed face, content and factorial validity, as well as responsiveness and reliability in young persons with congenital heart disease and diabetes. After these studies problematic items were identified and reworded and the final version of the GYPES was tested in young persons with diabetes in study III.The content and face validity of the scale was confirmed in study I. Confirmatory factor analyses (CFA) in study II supported the five-factor structure of the GYPES. However, one item had a low factor loading. The scale was revised and evaluated in study III. CFA of this version supported adequate model fit with factor loadings ranging from 0.385-0.941. A second-order model had an adequate fit to the data. Cronbach's alpha for the overall scale was 0.858 and for each subscale, alphas range from 0.609-0.858.GYPES was developed to measure patient empowerment in young persons with chronic conditions. Preliminary evidence supports that the GYPES may be a valid and reliable tool for assessing young persons' empowerment.
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64.
  • Acuña Mora, Mariela, 1990, et al. (författare)
  • The longitudinal association between patient empowerment and patient-reported outcomes: What is the direction of effect?
  • 2022
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Theoretical literature and cross-sectional studies suggest empowerment is associated with other patient-reported outcomes (PROs). However, it is not known if patient empowerment is leading to improvements in other PROs or vice versa.The present study aimed to examine the direction of effects between patient empowerment and PROs in young persons with congenital heart disease (CHD).As part of the STEPSTONES-CHD trial, adolescents with CHD from seven pediatric cardiology centers in Sweden were included in a longitudinal observational study (n = 132). Data were collected when patients were 16 (T0), 17 (T1) and 18 ½ years old (T2). The Gothenburg Young Persons Empowerment Scale (GYPES) was used to measure patient empowerment. Random intercepts cross-lagged panel models between patient empowerment and PROs (communication skills; patient-reported health; quality of life; and transition readiness) were undertaken.We found a significant cross-lagged effect of transition readiness over patient empowerment between T1 and T2, signifying that a higher level of transition readiness predicted a higher level of patient empowerment. No other significant cross-lagged relationships were found.Feeling confident before the transition to adult care is necessary before young persons with CHD can feel in control to manage their health and their lives. Clinicians interested in improving patient empowerment during the transitional period should consider targeting transition readiness.
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65.
  • Adamo, Hanibal Hani, et al. (författare)
  • Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness
  • 2015
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues.
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66.
  • Adamo, Hanibal Hani, et al. (författare)
  • Characterization of a Gene Expression Signature in Normal Rat Prostate Tissue Induced by the Presence of a Tumor Elsewhere in the Organ
  • 2015
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating changes in the tumor-bearing organ, for example growth of the vasculature, an altered extracellular matrix, and influx of inflammatory cells. To investigate this response further, we compared prostate morphology and the gene expression profile of tumor-bearing normal rat prostate tissue (termed tumor-instructed/indicating normal tissue (TINT)) with that of prostate tissue from controls. Dunning rat AT-1 prostate cancer cells were injected into rat prostate and tumors were established after 10 days. As controls we used intact animals, animals injected with heat-killed AT-1 cells or cell culture medium. None of the controls showed morphological TINT-changes. A rat Illumina whole-genome expression array was used to analyze gene expression in AT-1 tumors, TINT, and in medium injected prostate tissue. We identified 423 upregulated genes and 38 downregulated genes (p<0.05, >= 2-fold change) in TINT relative to controls. Quantitative RT-PCR analysis verified key TINT-changes, and they were not detected in controls. Expression of some genes was changed in a manner similar to that in the tumor, whereas other changes were exclusive to TINT. Ontological analysis using GeneGo software showed that the TINT gene expression profile was coupled to processes such as inflammation, immune response, and wounding. Many of the genes whose expression is altered in TINT have well-established roles in tumor biology, and the present findings indicate that they may also function by adapting the surrounding tumor-bearing organ to the needs of the tumor. Even though a minor tumor cell contamination in TINT samples cannot be ruled out, our data suggest that there are tumor-induced changes in gene expression in the normal tumor-bearing organ which can probably not be explained by tumor cell contamination. It is important to validate these changes further, as they could hypothetically serve as novel diagnostic and prognostic markers of prostate cancer.
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67.
  • Adams, A. M., et al. (författare)
  • Growth dynamics among adolescent girls in Bangladesh : Evidence from nationally representative data spanning 2011-2014
  • 2021
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:7
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAdolescence is the last opportunity to reverse any growth faltering accumulated from fetal life through childhood and it is considered a crucial period to optimize human development. In Bangladesh, a growing double burden of underweight and obesity in adolescents is recognized, yet limited data exists on how, when, and where to intervene. This study assesses the dynamics of growth among adolescent girls in Bangladesh, providing insight about critical junctures where faltering occurs and where immediate interventions are warranted.MethodsWe pooled data from Bangladesh’s Food Security and Nutrition Surveillance Project collected between 2011 and 2014 to document the age dynamics of weight and linear growth. 20,572 adolescent girls were measured for height and 19,345 for weight. We constructed growth curves for height, weight, stunting, and underweight. We also stratified growth dynamics by wealth quintile to assess socioeconomic inequities in adolescent trajectories.ResultsHeight-for-age z-score (HAZ) in Bangladeshi girls deteriorates throughout adolescence and especially during the early years. Mean HAZ decreases by 0.20 standard deviations (sd) per year in early adolescence (10–14 years) vs 0.06 sd/year during late adolescence (15–19 years), while stunting increases by 16 percentage points (pp) vs 6.7 pp, respectively. Conversely, BMI-for-age z-score (BAZ) increases by 0.13 sd/year in early adolescence vs 0.02 sd/year in late adolescence, and underweight decreases by 12.8 pp vs 3.2 pp. Adolescent girls in all socioeconomic groups show a similar pattern of HAZ and BAZ dynamics, but the curve for the richest quintile stays above that of the poorest across all ages.ConclusionsTrends and levels of stunting and underweight among adolescent girls in Bangladesh are worrisome, suggesting substantial linear growth faltering in early adolescence, with improving weight-for-age occurring only as linear growth slows and stops. Given the rising burden of non-communicable diseases (NCDs) in Bangladesh and emerging evidence of the link between stunting and later chronic diseases, greater attention to adolescent growth and development is needed. Our findings suggest that, to address stunting, interventions in early adolescence would have the greatest benefits. School-based interventions could be a way to target this population.
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68.
  • Adem, Abdu, et al. (författare)
  • ANP and BNP Responses to Dehydration in the One-Humped Camel and Effects of Blocking the Renin-Angiotensin System
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3, s. e57806-
  • Tidskriftsartikel (refereegranskat)abstract
    • The objectives of this study were to investigate and compare the responses of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in the circulation of hydrated, dehydrated, and dehydrated losartan - treated camels; and to document the cardiac storage form of B-type natriuretic peptide in the camel heart. Eighteen male camels were used in the study: control or hydrated camels (n = 6), dehydrated camels (n = 6) and dehydrated losartan-treated camels (n = 6) which were dehydrated and received the angiotensin II (Ang II) AT-1 receptor blocker, losartan, at a dose of 5 mg/kg body weight intravenously for 20 days. Control animals were supplied with feed and water ad-libitum while both dehydrated and dehydrated-losartan treated groups were supplied with feed ad-libitum but no water for 20 days. Compared with time-matched controls, dehydrated camels exhibited a significant decrease in plasma levels of both ANP and BNP. Losartan-treated camels also exhibited a significant decline in ANP and BNP levels across 20 days of dehydration but the changes were not different from those seen with dehydration alone. Size exclusion high performance liquid chromatography of extracts of camel heart indicated that proB-type natriuretic peptide is the storage form of the peptide. We conclude first, that dehydration in the camel induces vigorous decrements in circulating levels of ANP and BNP; second, blockade of the renin-angiotensin system has little or no modulatory effect on the ANP and BNP responses to dehydration; third, proB-type natriuretic peptide is the storage form of this hormone in the heart of the one-humped camel.
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69.
  • Adhikari, Deepak, et al. (författare)
  • Pharmacological Inhibition of mTORC1 Prevents Over-Activation of the Primordial Follicle Pool in Response to Elevated PI3K Signaling
  • 2013
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The majority of ovarian primordial follicles must be preserved in a quiescent state to allow for the regular production of gametes over the female reproductive lifespan. However, the molecular mechanism that maintains the long quiescence of primordial follicles is poorly understood. Under certain pathological conditions, the entire pool of primordial follicles matures simultaneously leading to an accelerated loss of primordial follicles and to premature ovarian failure (POF). We have previously shown that loss of Pten (phosphatase and tensin homolog deleted on chromosome ten) in mouse oocytes leads to premature activation of the entire pool of primordial follicles, subsequent follicular depletion in early adulthood, and the onset of POF. Lack of PTEN leads to increased phosphatidylinositol 3-kinase (PI3K)-Akt and mammalian target of rapamycin complex 1 (mTORC1) signaling in the oocytes. To study the functional and pathological roles of elevated mTORC1 signaling in the oocytes, we treated the Pten-mutant mice with the specific mTORC1 inhibitor rapamycin. When administered to Pten-deficient mice prior to the activation of the primordial follicles, rapamycin effectively prevented global follicular activation and preserved the ovarian reserve. These results provide a rationale for exploring the possible use of rapamycin as a drug for the preservation of the primordial follicle pool, and the possible prevention of POF.
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70.
  • Adhikari, Deepak, et al. (författare)
  • The Safe Use of a PTEN Inhibitor for the Activation of Dormant Mouse Primordial Follicles and Generation of Fertilizable Eggs
  • 2012
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Primordial ovarian follicles, which are often present in the ovaries of premature ovarian failure (POF) patients or are cryopreserved from the ovaries of young cancer patients who are undergoing gonadotoxic anticancer therapies, cannot be used to generate mature oocytes for in vitro fertilization (IVF). There has been very little success in triggering growth of primordial follicles to obtain fertilizable oocytes due to the poor understanding of the biology of primordial follicle activation. Methodology/Principal Findings: We have recently reported that PTEN (phosphatase and tensin homolog deleted on chromosome ten) prevents primordial follicle activation in mice, and deletion of Pten from the oocytes of primordial follicles leads to follicular activation. Consequently, the PTEN inhibitor has been successfully used in vitro to activate primordial follicles in both mouse and human ovaries. These results suggest that PTEN inhibitors could be used in ovarian culture medium to trigger the activation of primordial follicle. To study the safety and efficacy of the use of such inhibitors, we activated primordial follicles from neonatal mouse ovaries by transient treatment with a PTEN inhibitor bpV(HOpic). These ovaries were then transplanted under the kidney capsules of recipient mice to generate mature oocytes. The mature oocytes were fertilized in vitro and progeny mice were obtained after embryo transfer. Results and Conclusions: Long-term monitoring up to the second generation of progeny mice showed that the mice were reproductively active and were free from any overt signs or symptoms of chronic illnesses. Our results indicate that the use of PTEN inhibitors could be a safe and effective way of generating mature human oocytes for use in novel IVF techniques.
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