427 research outputs found

    Change and Aging Senescence as an adaptation

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    Understanding why we age is a long-lived open problem in evolutionary biology. Aging is prejudicial to the individual and evolutionary forces should prevent it, but many species show signs of senescence as individuals age. Here, I will propose a model for aging based on assumptions that are compatible with evolutionary theory: i) competition is between individuals; ii) there is some degree of locality, so quite often competition will between parents and their progeny; iii) optimal conditions are not stationary, mutation helps each species to keep competitive. When conditions change, a senescent species can drive immortal competitors to extinction. This counter-intuitive result arises from the pruning caused by the death of elder individuals. When there is change and mutation, each generation is slightly better adapted to the new conditions, but some older individuals survive by random chance. Senescence can eliminate those from the genetic pool. Even though individual selection forces always win over group selection ones, it is not exactly the individual that is selected, but its lineage. While senescence damages the individuals and has an evolutionary cost, it has a benefit of its own. It allows each lineage to adapt faster to changing conditions. We age because the world changes.Comment: 19 pages, 4 figure

    National and sub-national under-five mortality profiles in Peru: a basis for informed policy decisions

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    BACKGROUND: Information on profiles for under-five causes of death is important to guide choice of child-survival interventions. Global level data have been published, but information at country level is scarce. We aimed at defining national and departmental trends and profiles of under-five mortality in Peru from 1996 through 2000. METHODS: We used the Ministry of Health registered under-five mortality data. For correction of under-registration, a model life-table that fitted the age distribution of the population and of registered deaths was identified for each year. The mortality rates corresponding to these model life-tables were then assigned to each department in each particular year. Cumulative reduction in under-five mortality rate in the 1996–2000 period was estimated calculating the annual reduction slope for each department. Departmental level mortality profiles were constructed. Differences in mortality profiles and in mortality reduction between coastal, andean and jungle regions were also assessed. RESULTS: At country level, only 4 causes (pneumonia, diarrhoea, neonatal diseases and injuries) accounted for 68% of all deaths in 1996, and for 62% in 2000. There was 32.7% of under-five death reduction from 1996 to 2000. Diarrhoea and pneumonia deaths decreased by 84.5% and 41.8%, respectively, mainly in the andean region, whereas deaths due to neonatal causes and injuries decreased by 37.2% and 21.7%. For 1996–2000 period, the andean, coast and jungle regions accounted for 52.4%, 33.1% and 14.4% of deaths, respectively. These regions represent 41.0%, 46.4% and 12.6% of under-five population. Both diarrhoea and pneumonia constitute 30.6% of under-five deaths in the andean region. As a proportion, neonatal deaths remained stable in the country from 1996 to 2000, accounting for about 30% of under-five deaths, whereas injuries and "other" causes, including congenital anomalies, increased by about 5%. CONCLUSION: Under-five mortality declined substantially in all departments from 1996 to 2000, which is explained mostly by reduction in diarrhoea and pneumonia deaths, particularly in the andean region. There is the need to emphasize interventions to reduce neonatal deaths and emerging causes of death such as injuries and congenital anomalies

    Primary myoepithelial carcinoma of the lung: a rare entity treated with parenchymal sparing resection

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    Primary lung myoepithelial carcinomas are rare neoplasms arising from the salivary glands of the respiratory epithelium. Given the rare occurrences and reports of these tumors, appropriate recommendations for resection are difficult to formulate. Although classified as low-grade neoplasms, these tumors have a significant rate of recurrence and distant metastasis

    Histological response to injected gluteraldehyde cross-linked bovine collagen based implant in a rat model

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    BACKGROUND: The aim of present study is to investigate the short and long term histopathological alterations caused by submucosal injection of gluteraldehyde cross-linked bovine collagen based on an experimental rat model. METHODS: Sixty Sprague-Dawley rats were assigned into two groups as group I and II each containing 30 rats. 0.1 ml of saline solution and 0.1 ml of gluteraldehyde cross-linked bovine collagen were injected into the submucosa of bladder of first (control) and second groups, respectively. Both group I and II were further subdivided into 3 other groups as Group IA, IB, IC and Group IIA, IIB, IIC according to the sacrification period. Group IA and IIA, IB and IIB, IC and IIC rats (10 rats for each group) were sacrificed 3, 6, and 12 months after surgical procedure, respectively. Two slides prepared from injection site of the bladder were evaluated completely for each rat by being unaware of the groups and at random by two independent senior pathologists to determine the fibroblast invasion, collagen formation, capillary ingrowth and inflammatory reaction. Additionally, randomized brain sections from each rat were also examined to detect migration of the injection material. The measurements were made using an ocular micrometer at ×10 magnification. The results were assessed using t-tests for paired and independent samples, with p < 0.05 considered to indicate significant differences; all values were presented as the mean (SD). RESULTS: Migration to the brain was not detected in any group. Significant histopathological changes in the gluteraldehyde cross-linked bovine collagen injected groups were fibroblast invasion in 93.3%, collagen formation in 73.3%, capillary ingrowth in 46.6%, inflamatory reaction in 20%. CONCLUSION: We emphasize that the usage of gluteraldehyde cross-linked bovine collagen in children appears to be safe for endoscopic treatment of vesicoureteral reflux

    Safety assessment of inhaled xylitol in mice and healthy volunteers

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    BACKGROUND: Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers. METHODS: This was a prospective cohort study of C57Bl/6 mice in an animal laboratory and healthy human volunteers at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline or xylitol (5% solution) for 150 minutes and then a follow-up methacholine challenge. The saline and xylitol exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Normal human volunteers underwent exposures to aerosolized saline (10 ml) and xylitol, with spirometry performed at baseline and after inhalation of 1, 5, and 10 ml. Serum osmolarity and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL) was done 20 minutes and 3 hours after aerosolized xylitol exposure for levels of inflammatory markers. RESULTS: In naïve mice, methacholine responsiveness was unchanged after exposures to xylitol compared to inhaled saline (p = 0.49). There was no significant increase in Penh in antigen-challenged mice after xylitol exposure (p = 0.38). There was no change in airway cellular response after xylitol exposure in naïve and antigen-challenged mice. In normal volunteers, there was no change in FEV1 after xylitol exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 ml xylitol exposure, which promptly resolved after exposure completion. BAL cytokine levels were below the detection limits after xylitol exposure in normal volunteers. CONCLUSIONS: Inhalation of aerosolized iso-osmotic xylitol was well-tolerated by naïve and atopic mice, and by healthy human volunteers

    Community referral in home management of malaria in western Uganda: A case series study

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    BACKGROUND: Home Based Management of fever (HBM) was introduced as a national policy in Uganda to increase access to prompt presumptive treatment of malaria. Pre-packed Chloroquine/Fansidar combination is distributed free of charge to febrile children <5 years. Persisting fever or danger signs are referred to the health centre. We assessed overall referral rate, causes of referral, referral completion and reasons for non-completion under the HBM strategy. METHODS: A case-series study was performed during 20 weeks in a West-Ugandan sub-county with an under-five population of 3,600. Community drug distributors (DDs) were visited fortnightly and recording forms collected. Referred children were located and primary caretaker interviewed in the household. Referral health facility records were studied for those stating having completed referral. RESULTS: Overall referral rate was 8% (117/1454). Fever was the main reason for mothers to seek DD care and for DDs to refer. Twenty-six of the 28 (93%) "urgent referrals" accessed referral care but 8 (31%) delayed >24 hours. Waiting for antimalarial drugs to finish caused most delays. Of 32 possible pneumonias only 16 (50%) were urgently referred; most delayed ≥ 2 days before accessing referral care. CONCLUSION: The HBM has high referral compliance and extends primary health care to the communities by maintaining linkages with formal health services. Referral non-completion was not a major issue but failure to recognise pneumonia symptoms and delays in referral care access for respiratory illnesses may pose hazards for children with acute respiratory infections. Extending HBM to also include pneumonia may increase prompt and effective care of the sick child in sub-Saharan Africa

    Natural Selection Fails to Optimize Mutation Rates for Long-Term Adaptation on Rugged Fitness Landscapes

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    The rate of mutation is central to evolution. Mutations are required for adaptation, yet most mutations with phenotypic effects are deleterious. As a consequence, the mutation rate that maximizes adaptation will be some intermediate value. Here, we used digital organisms to investigate the ability of natural selection to adjust and optimize mutation rates. We assessed the optimal mutation rate by empirically determining what mutation rate produced the highest rate of adaptation. Then, we allowed mutation rates to evolve, and we evaluated the proximity to the optimum. Although we chose conditions favorable for mutation rate optimization, the evolved rates were invariably far below the optimum across a wide range of experimental parameter settings. We hypothesized that the reason that mutation rates evolved to be suboptimal was the ruggedness of fitness landscapes. To test this hypothesis, we created a simplified landscape without any fitness valleys and found that, in such conditions, populations evolved near-optimal mutation rates. In contrast, when fitness valleys were added to this simple landscape, the ability of evolving populations to find the optimal mutation rate was lost. We conclude that rugged fitness landscapes can prevent the evolution of mutation rates that are optimal for long-term adaptation. This finding has important implications for applied evolutionary research in both biological and computational realms

    Family history of breast cancer and young age at diagnosis of breast cancer increase risk of second primary malignancies in women: a population-based cohort study

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    Among 152 600 breast cancer patients diagnosed during 1958–2000, there was a 22% increased risk of developing a second primary non-breast malignancy (standardised incidence ratio (SIR)=1.22; 95% confidence interval (CI): 1.19–1.24). The highest risk was seen for connective tissue cancer (SIR=1.78; 95% CI: 1.49–2.10). Increased risks were noted among women diagnosed with breast cancer before age 50. Oesophagus cancer and non-Hodgkin's lymphoma showed six- and four-fold higher risks, respectively, in women with a family history of breast cancer compared to those without in the ⩾10-year follow-up period

    Three SRA-Domain Methylcytosine-Binding Proteins Cooperate to Maintain Global CpG Methylation and Epigenetic Silencing in Arabidopsis

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    Methylcytosine-binding proteins decipher the epigenetic information encoded by DNA methylation and provide a link between DNA methylation, modification of chromatin structure, and gene silencing. VARIANT IN METHYLATION 1 (VIM1) encodes an SRA (SET- and RING-associated) domain methylcytosine-binding protein in Arabidopsis thaliana, and loss of VIM1 function causes centromere DNA hypomethylation and centromeric heterochromatin decondensation in interphase. In the Arabidopsis genome, there are five VIM genes that share very high sequence similarity and encode proteins containing a PHD domain, two RING domains, and an SRA domain. To gain further insight into the function and potential redundancy among the VIM proteins, we investigated strains combining different vim mutations and transgenic vim knock-down lines that down-regulate multiple VIM family genes. The vim1 vim3 double mutant and the transgenic vim knock-down lines showed decreased DNA methylation primarily at CpG sites in genic regions, as well as repeated sequences in heterochromatic regions. In addition, transcriptional silencing was released in these plants at most heterochromatin regions examined. Interestingly, the vim1 vim3 mutant and vim knock-down lines gained ectopic CpHpH methylation in the 5S rRNA genes against a background of CpG hypomethylation. The vim1 vim2 vim3 triple mutant displayed abnormal morphological phenotypes including late flowering, which is associated with DNA hypomethylation of the 5′ region of FWA and release of FWA gene silencing. Our findings demonstrate that VIM1, VIM2, and VIM3 have overlapping functions in maintenance of global CpG methylation and epigenetic transcriptional silencing
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