A Unifying Theory of Biological Function

A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism’s fitness, and modulates the organism’s variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories

Fundamental differences in patterns of retinal ageing between primates and mice

Photoreceptors have high metabolic demands and age rapidly, undermining visual function. We base our understanding mainly on ageing mice where elevated inflammation, extracellular deposition, including that of amyloid beta, and rod and cone photoreceptor loss occur, but cones are not lost in ageing primate although their function declines, revealing that primate and mouse age differently. We examine ageing primate retinae and show elevated stress but low inflammation. However, aged primates have a >70% reduction in adenosine triphosphate (ATP) and a decrease in cytochrome c oxidase. There is a shift in cone mitochondrial positioning and glycolytic activity increases. Bruch’s membrane thickens but unlike in mice, amyloid beta is absent. Hence, reduced ATP may explain cone functional decline in ageing but their retained presence offers the possibility of functional restoration if they can be fuelled appropriately to restore cellular function. This is important because as humans we largely depend on cone function to see and are rarely fully dark adapted. Presence of limited aged inflammation and amyloid beta deposition question some of the therapeutic approaches taken to resolve problems of retinal ageing in humans and the possible lack of success in clinical trials in macular degeneration that have targeted inflammatory agents

Social network size, loneliness, physical functioning and depressive symptoms among older adults: Examining reciprocal associations in four waves of the Longitudinal Aging Study Amsterdam (LASA)

Previous research indicates that social isolation, loneliness, physical dysfunction and depressive symptoms are interrelated factors, little is known about the potential pathways among them. The aim of the study is to analyse simultaneously reciprocal relationships that could exist between the four factors to clarify potential mediation effects. METHODS Within a large representative sample of older people in the Longitudinal Aging Study Amsterdam (LASA), participants aged 75 and over were followed up over a period of 11 years (four waves). We tested cross-lagged and autoregressive longitudinal associations of social network size, loneliness, physical functioning and depressive symptoms using structural equation modelling (SEM). RESULTS Several statistically significant cross-lagged associations were found: decreasing physical functioning (Coef.=-0.03; p<0.05), as well as social network size (Coef.=-0.02; p<0.05), predicted higher levels of loneliness, which predicted an increase in depressive symptoms (Coef.=0.17; p<0.05) and further reduction of social network (Coef.=-0.20; p<0.05). Decreasing physical functioning also predicted an increase in depressive symptoms (Coef.=-0.08; p<0.05). All autoregressive associations were statistically significant. CONCLUSION Interventions focused on promoting social activities among older adults after negative life events, such as loss of social contacts or declining physical function, may alleviate feelings of loneliness and act as mental health protector

Older adult loneliness: myths and realities

The focus in this paper is on the social domain of quality of life, and more particularly loneliness. The empirical literature on older adult loneliness is reviewed, thereby challenging three often-held assumptions that figure prominently in public debates on loneliness. The first assumption that loneliness is a problem specifically for older people finds only partial support. Loneliness is common only among the very old. The second assumption is that people in individualistic societies are most lonely. Contrary to this belief, findings show that older adults in northern European countries tend to be less lonely than those in the more familialistic southern European countries. The scarce data on Central and Eastern Europe suggest a high prevalence of older adult loneliness in those countries. The third assumption that loneliness has increased over the past decades finds no support. Loneliness levels have decreased, albeit slightly. The review notes the persistence of ageist attitudes, and underscores the importance of considering people’s frame of reference and normative orientation in analyses of loneliness

Neuroendocrine carcinoma arising in soft tissue: three case reports and literature review

<p>Abstract</p> <p>Background</p> <p>Neuroendocrine tumours (NET) are tumours arising from neuroendocrine cells of neural crest origin. They are characterised by the presence of neurosecretory granules which react positively to silver stains and to specific markers including neuron specific enolase, synaptophysin and chromogranin. Metastasis to the skin occurs infrequently but primary soft tissue NET is excessively rare.</p> <p>Case presentation</p> <p>We report our experience with 3 such cases. In the first case, the NET originated in muscle and was treated with wide surgical excision and adjuvant radiotherapy. The second case presented as a subcutaneous mass in the foot and the tumour was positive on ¹²³I mIBG scan. She has had prolonged recurrence-free survival following primary hypo-fractionated radiotherapy. In the third case, a cutaneous nodule proved to be a NET and at surgery, lymph node disease was present. He has remained disease-free after surgical excision without the need for external beam radiotherapy.</p> <p>Conclusion</p> <p>These tumours appear to have a good prognosis. Complete excision offers potentially curative treatment. Adjuvant radiotherapy may be helpful when the tumour margin is narrow. For patients with unresectable disease or where surgery would not be appropriate, radiotherapy appears to be an effective therapeutic option.</p

The De Jong Gierveld short scales for emotional and social loneliness: tested on data from 7 countries in the UN generations and gender surveys

Loneliness concerns the subjective evaluation of the situation individuals are involved in, characterized either by a number of relationships with friends and colleagues which is smaller than is considered desirable (social loneliness), as well as situations where the intimacy in confidant relationships one wishes for has not been realized (emotional loneliness). To identify people who are lonely direct questions are not sufficient; loneliness scales are preferred. In this article, the quality of the three-item scale for emotional loneliness and the three-item scale for social loneliness has been investigated for use in the following countries participating in the United Nations “Generations and Gender Surveys”: France, Germany, the Netherlands, Russia, Bulgaria, Georgia, and Japan. Sample sizes for the 7 countries varied between 8,158 and 12,828. Translations of the De Jong Gierveld loneliness scale have been tested using reliability and validity tests including a confirmatory factor analysis to test the two-dimensional structure of loneliness. Test outcomes indicated for each of the countries under investigation reliable and valid scales for emotional and social loneliness, respectively

Insulin Degrading Enzyme Induces a Conformational Change in Varicella-Zoster Virus gE, and Enhances Virus Infectivity and Stability

Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for virus infectivity and binds to a cellular receptor, insulin-degrading enzyme (IDE), through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE) enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines