Defining genes: a computational framework

The precise elucidation of the gene concept has become the subject of intense discussion in light of results from several, large high-throughput surveys of transcriptomes and proteomes. In previous work, we proposed an approach for constructing gene concepts that combines genomic heritability with elements of function. Here, we introduce a definition of the gene within a computational framework of cellular interactions. The definition seeks to satisfy the practical requirements imposed by annotation, capture logical aspects of regulation, and encompass the evolutionary property of homology

Impact of the COVID-19 Pandemic on Loneliness and Social Isolation: A Multi-Country Study

Copyright: © 2021 by the authors. The COVID-19 global pandemic and subsequent public health social measures have challenged our social and economic life, with increasing concerns around potentially rising levels of social isolation and loneliness. This paper is based on cross-sectional online survey data (available in 10 languages, from 2 June to 16 November 2020) with 20,398 respondents from 101 different countries. It aims to help increase our understanding of the global risk factors that are associated with social isolation and loneliness, irrespective of culture or country, to support evidence-based policy, services and public health interventions. We found the prevalence of severe loneliness was 21% during COVID-19 with 6% retrospectively reporting severe loneliness prior to the pandemic. A fifth were defined as isolated based on their usual connections, with 13% reporting a substantial increase in isolation during COVID-19. Personal finances and mental health were overarching and consistently cross-cutting predictors of loneliness and social isolation, both before and during the pandemic. With the likelihood of future waves of COVID-19 and related restrictions, it must be a public health priority to address the root causes of loneliness and social isolation and, in particular, address the needs of specific groups such as carers or those living alone

Cross-sectional validation of the Aging Perceptions Questionnaire: a multidimensional instrument for assessing self-perceptions of aging

<p>Abstract</p> <p>Background</p> <p>Self-perceptions of aging have been implicated as independent predictors of functional disability and mortality in older adults. In spite of this, research on self-perceptions of aging is limited. One reason for this is the absence of adequate measures. Specifically, there is a need to develop a measure that is theoretically-derived, has good psychometric properties, and is multidimensional in nature. The present research seeks to address this need by adopting the Self-Regulation Model as a framework and using it to develop a comprehensive, multi-dimensional instrument for assessing self-perceptions of aging. This study describes the validation of this newly-developed instrument, the Aging Perceptions Questionnaire (APQ).</p> <p>Methods</p> <p>Participants were 2,033 randomly selected community-dwelling older (+65 yrs) Irish adults who completed the APQ alongside measures of physical and psychological health. The APQ assesses self-perceptions of aging along eight distinct domains or subscales; seven of these examine views about own aging, these are: timeline chronic, timeline cyclical, consequences positive, consequences negative, control positive, control negative, and emotional representations; the eighth domain is the identity domain and this examines the experience of health-related changes.</p> <p>Results</p> <p>Mokken scale analysis showed that the majority of items within the views about aging subscales were strongly scalable. Confirmatory factor analysis also indicated that the model provided a good fit for the data. Overall, subscales had good internal reliabilities. Hierarchical linear regression was conducted to investigate the independent contribution of APQ subscales to physical and psychological health and in doing so determine the construct validity of the APQ. Results showed that self-perceptions of aging were independently related to physical and psychological health. Mediation testing also supported a role for self-perceptions of aging as partial mediators in the relationship between indices of physical functioning and physical and psychological health outcomes.</p> <p>Conclusion</p> <p>Findings support the complex and multifaceted nature of the aging experience. The good internal reliability and construct validity of the subscales suggests that the APQ is a promising instrument that can enable a theoretically informed, multidimensional assessment of self-perceptions of aging. The potential role of self-perceptions of aging in facilitating physical and psychological health in later life is also highlighted.</p

Bioavailable Trace Metals in Neurological Diseases

Medical treatment in Wilson’s disease includes chelators (d-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators’ doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron

Influences on pre-hospital delay in the diagnosis of colorectal cancer: a systematic review

Colorectal cancer is a major global health problem, with survival varying according to stage at diagnosis. Delayed diagnosis can result from patient, practitioner or hospital delay. This paper reports the results of a review of the factors influencing pre-hospital delay – the time between a patient first noticing a cancer symptom and presenting to primary care or between first presentation and referral to secondary care. A systematic methodology was applied, including extensive searches of the literature published from 1970 to 2003, systematic data extraction, quality assessment and narrative data synthesis. Fifty-four studies were included. Patients' non-recognition of symptom seriousness increased delay, as did symptom denial. Patient delay was greater for rectal than colon cancers and the presence of more serious symptoms, such as pain, reduced delay. There appears to be no relationship between delay and patients' age, sex or socioeconomic status. Initial misdiagnosis, inadequate examination and inaccurate investigations increased practitioner delay. Use of referral guidelines may reduce delay, although evidence is currently limited. No intervention studies were identified. If delayed diagnosis is to be reduced, there must be increased recognition of the significance of symptoms among patients, and development and evaluation of interventions that are designed to ensure appropriate diagnosis and examination by practitioners

Comparative analyses of vertebrate posterior HoxD clusters reveal atypical cluster architecture in the caecilian Typhlonectes natans

<p>Abstract</p> <p>Background</p> <p>The posterior genes of the <it>HoxD </it>cluster play a crucial role in the patterning of the tetrapod limb. This region is under the control of a global, long-range enhancer that is present in all vertebrates. Variation in limb types, as is the case in amphibians, can probably not only be attributed to variation in <it>Hox </it>genes, but is likely to be the product of differences in gene regulation. With a collection of vertebrate genome sequences available today, we used a comparative genomics approach to study the posterior <it>HoxD </it>cluster of amphibians. A frog and a caecilian were included in the study to compare coding sequences as well as to determine the gain and loss of putative regulatory sequences.</p> <p>Results</p> <p>We sequenced the posterior end of the <it>HoxD </it>cluster of a caecilian and performed comparative analyses of this region using <it>HoxD </it>clusters of other vertebrates. We determined the presence of conserved non-coding sequences and traced gains and losses of these footprints during vertebrate evolution, with particular focus on amphibians. We found that the caecilian <it>HoxD </it>cluster is almost three times larger than its mammalian counterpart. This enlargement is accompanied with the loss of one gene and the accumulation of repeats in that area. A similar phenomenon was observed in the coelacanth, where a different gene was lost and expansion of the area where the gene was lost has occurred. At least one phylogenetic footprint present in all vertebrates was lost in amphibians. This conserved region is a known regulatory element and functions as a boundary element in neural tissue to prevent expression of <it>Hoxd </it>genes.</p> <p>Conclusion</p> <p>The posterior part of the <it>HoxD </it>cluster of <it>Typhlonectes natans </it>is among the largest known today. The loss of <it>Hoxd-12 </it>and the expansion of the intergenic region may exert an influence on the limb enhancer, by having to bypass a distance seven times that of regular <it>HoxD </it>clusters. Whether or not there is a correlation with the loss of limbs remains to be investigated. These results, together with data on other vertebrates show that the tetrapod <it>Hox </it>clusters are more variable than previously thought.</p