362 research outputs found

    Homo Datumicus : correcting the market for identity data

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    Effective digital identity systems offer great economic and civic potential. However, unlocking this potential requires dealing with social, behavioural, and structural challenges to efficient market formation. We propose that a marketplace for identity data can be more efficiently formed with an infrastructure that provides a more adequate representation of individuals online. This paper therefore introduces the ontological concept of Homo Datumicus: individuals as data subjects transformed by HAT Microservers, with the axiomatic computational capabilities to transact with their own data at scale. Adoption of this paradigm would lower the social risks of identity orientation, enable privacy preserving transactions by default and mitigate the risks of power imbalances in digital identity systems and markets

    Interaction of HP1 and Brg1/Brm with the Globular Domain of Histone H3 Is Required for HP1-Mediated Repression

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    The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. These proteins contain two related domains known as the chromo- and the chromoshadow-domain. The chromo-domain binds histone H3 tails methylated on lysine 9. However, in vivo and in vitro experiments have shown that the affinity of HP1 proteins to native methylated chromatin is relatively poor and that the opening of chromatin occurring during DNA replication facilitates their binding to nucleosomes. These observations prompted us to investigate whether HP1 proteins have additional histone binding activities, envisioning also affinity for regions potentially occluded by the nucleosome structure. We find that the chromoshadow-domain interacts with histone H3 in a region located partially inside the nucleosomal barrel at the entry/exit point of the nucleosome. Interestingly, this region is also contacted by the catalytic subunits of the human SWI/SNF complex. In vitro, efficient SWI/SNF remodeling requires this contact and is inhibited in the presence of HP1 proteins. The antagonism between SWI/SNF and HP1 proteins is also observed in vivo on a series of interferon-regulated genes. Finally, we show that SWI/SNF activity favors loading of HP1 proteins to chromatin both in vivo and in vitro. Altogether, our data suggest that HP1 chromoshadow-domains can benefit from the opening of nucleosomal structures to bind chromatin and that HP1 proteins use this property to detect and arrest unwanted chromatin remodeling

    Nonvirally Modified Autologous Primary Hepatocytes Correct Diabetes and Prevent Target Organ Injury in a Large Preclinical Model

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    BACKGROUND: Current gene- and cell-based therapies have significant limitations which impede widespread clinical application. Taking diabetes mellitus as a paradigm, we have sought to overcome these limitations by ex vivo electrotransfer of a nonviral insulin expression vector into primary hepatocytes followed by immediate autologous reimplantation in a preclinical model of diabetes. METHODS AND RESULTS: In a single 3-hour procedure, hepatocytes were isolated from a surgically resected liver wedge, electroporated with an insulin expression plasmid ex vivo and reimplanted intraparenchymally under ultrasonic guidance into the liver in each of 10 streptozotocin-induced diabetic Yorkshire pigs. The vector was comprised of a bifunctional, glucose-responsive promoter linked to human insulin cDNA. Ambient glucose concentrations appropriately altered human insulin mRNA expression and C-peptide secretion within minutes in vitro and in vivo. Treated swine showed correction of hyperglycemia, glucose intolerance, dyslipidemia and other metabolic abnormalities for > or = 47 weeks. Metabolic correction correlated significantly with the number of hepatocytes implanted. Importantly, we observed no hypoglycemia even under fasting conditions. Direct intrahepatic implantation of hepatocytes did not alter biochemical indices of liver function or induce abnormal hepatic lobular architecture. About 70% of implanted hepatocytes functionally engrafted, appeared histologically normal, retained vector DNA and expressed human insulin for > or = 47 weeks. Based on structural tissue analyses and transcriptome data, we showed that early correction of diabetes attenuated and even prevented pathological changes in the eye, kidney, liver and aorta. CONCLUSIONS: We demonstrate that autologous hepatocytes can be efficiently, simply and safely modified by electroporation of a nonviral vector to express, process and secrete insulin durably. This strategy, which achieved significant and sustained therapeutic efficacy in a large preclinical model without adverse effects, warrants consideration for clinical development especially as it could have broader future applications for the treatment of other acquired and inherited diseases for which systemic reconstitution of a specific protein deficiency is critical

    Enhancing sampling design in mist-net bat surveys by accounting for sample size optimization

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    The advantages of mist-netting, the main technique used in Neotropical bat community studies to date, include logistical implementation, standardization and sampling representativeness. Nonetheless, study designs still have to deal with issues of detectability related to how different species behave and use the environment. Yet there is considerable sampling heterogeneity across available studies in the literature. Here, we approach the problem of sample size optimization. We evaluated the common sense hypothesis that the first six hours comprise the period of peak night activity for several species, thereby resulting in a representative sample for the whole night. To this end, we combined re-sampling techniques, species accumulation curves, threshold analysis, and community concordance of species compositional data, and applied them to datasets of three different Neotropical biomes (Amazonia, Atlantic Forest and Cerrado). We show that the strategy of restricting sampling to only six hours of the night frequently results in incomplete sampling representation of the entire bat community investigated. From a quantitative standpoint, results corroborated the existence of a major Sample Area effect in all datasets, although for the Amazonia dataset the six-hour strategy was significantly less species-rich after extrapolation, and for the Cerrado dataset it was more efficient. From the qualitative standpoint, however, results demonstrated that, for all three datasets, the identity of species that are effectively sampled will be inherently impacted by choices of sub-sampling schedule. We also propose an alternative six-hour sampling strategy (at the beginning and the end of a sample night) which performed better when resampling Amazonian and Atlantic Forest datasets on bat assemblages. Given the observed magnitude of our results, we propose that sample representativeness has to be carefully weighed against study objectives, and recommend that the trade-off between logistical constraints and additional sampling performance should be carefully evaluated

    Prevalence and correlates of physical disability and functional limitation among community dwelling older people in rural Malaysia, a middle income country

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    <p>Abstract</p> <p>Background</p> <p>The prevalence and correlates of physical disability and functional limitation among older people have been studied in many developed countries but not in a middle income country such as Malaysia. The present study investigated the epidemiology of physical disability and functional limitation among older people in Malaysia and compares findings to other countries.</p> <p>Methods</p> <p>A population-based cross sectional study was conducted in Alor Gajah, Malacca. Seven hundred and sixty five older people aged 60 years and above underwent tests of functional limitation (Tinetti Performance Oriented Mobility Assessment Tool). Data were also collected for self reported activities of daily living (ADL) using the Barthel Index (ten items). To compare prevalence with other studies, ADL disability was also defined using six basic ADL's (eating, bathing, dressing, transferring, toileting and walking) and five basic ADL's (eating, bathing, dressing, transferring and toileting).</p> <p>Results</p> <p>Ten, six and five basic ADL disability was reported by 24.7% (95% CI 21.6-27.9), 14.4% (95% CI 11.9-17.2) and 10.6% (95% CI 8.5-13.1), respectively. Functional limitation was found in 19.5% (95% CI 16.8-22.5) of participants. Variables independently associated with 10 item ADL disability physical disability, were advanced age (≥ 75 years: prevalence ratio (PR) 7.9; 95% CI 4.8-12.9), presence of diabetes (PR 1.8; 95% CI 1.4-2.3), stroke (PR 1.5; 95% CI 1.1-2.2), depressive symptomology (PR 1.3; 95% CI 1.1-1.8) and visual impairment (blind: PR 2.0; 95% CI 1.1-3.6). Advancing age (≥ 75 years: PR 3.0; 95% CI 1.7-5.2) being female (PR 2.7; 95% CI 1.2-6.1), presence of arthritis (PR 1.6; 95% CI 1.2-2.1) and depressive symptomology (PR 2.0; 95% CI 1.5-2.7) were significantly associated with functional limitation.</p> <p>Conclusions</p> <p>The prevalence of physical disability and functional limitation among older Malaysians appears to be much higher than in developed countries but is comparable to developing countries. Associations with socio-demographic and other health related variables were consistent with other studies.</p

    †Kenyaichthyidae fam. nov and †Kenyaichthys gen. nov - First Record of a Fossil Aplocheiloid Killifish (Teleostei, Cyprinodontiformes)

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    The extant Cyprinodontiformes (killifishes) with their two suborders Cyprinodontoidei and Aplocheiloidei represent a diverse and well-studied group of fishes. However, their fossil record is comparatively sparse and has so far yielded members of the Cyprinodontoidei only. Here we report on cyprinodontiform fossils from the upper Miocene Lukeino Formation in the Tugen Hills of the Central Rift Valley of Kenya, which represent the first fossil record of an aplocheiloid killifish. A total of 169 specimens - mostly extraordinarily well preserved and a sample of ten extant cyprinodontiform species were studied on the basis of morphometrics, meristics and osteology. A phylogenetic analysis using PAUP was also conducted for the fossils. Both the osteological data and the phylogenetic analysis provide strong evidence for the assignment of the fossils to the Aplocheiloidei, and justify the definition of the new family dagger Kenyaichthyidae, the new genus dagger Kenyaichthys and the new species dagger K. kipkechi sp. nov. The phylogenetic analysis unexpectedly places dagger Kenyaichthys gen. nov. in a sister relationship to the Rivulidae (a purely Neotropical group),a probable explanation might be lack of available synapomorphies for the Rivulidae, Nothobranchiidae and Aplocheilidae. The specimens of dagger K. kipkechi sp. nov. show several polymorphic characters and large overlap in meristic traits, which justifies their interpretation as a species flock in statu nascendi. Patterns of variation in neural and haemal spine dimensions in the caudal vertebrae of dagger Kenyaichthys gen. nov. and the extant species studied indicate that some previously suggested synapomorphies of the Cyprinodontoidei and Aplocheiloidei need to be revised

    Trichomonas vaginalis: Clinical relevance, pathogenicity and diagnosis

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    Trichomonas vaginalis is the etiological agent of trichomoniasis, the most prevalent non-viral sexually transmitted disease worldwide. Trichomoniasis is a widespread, global health concern and occurring at an increasing rate. Infections of the female genital tract can cause a range of symptoms, including vaginitis and cervicitis, while infections in males are generally asymptomatic. The relatively mild symptoms, and lack of evidence for any serious sequelae, have historically led to this disease being under diagnosed, and under researched. However, growing evidence that T. vaginalis infection is associated with other disease states with high morbidity in both men and women has increased the efforts to diagnose and treat patients harboring this parasite. The pathology of trichomoniasis results from damage to the host epithelia, caused by a variety of processes during infection and recent work has highlighted the complex interactions between the parasite and host, commensal microbiome and accompanying symbionts. The commercial release of a number of nucleic acid amplification tests (NAATs) has added to the available diagnostic options. Immunoassay based Point of Care testing is currently available, and a recent initial evaluation of a NAAT Point of Care system has given promising results, which would enable testing and treatment in a single visit

    Is the meiofauna a good indicator for climate change and anthropogenic impacts?

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    Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

    Management of severe paediatric malaria in resource-limited settings

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