The Bcl‐2 proteins Bax and Bak can permeabilize the outer mitochondrial membrane and commit cells to apoptosis. Pro‐survival Bcl‐2 proteins control Bax by constant retrotranslocation into the cytosol ...of healthy cells. The stabilization of cytosolic Bax raises the question whether the functionally redundant but largely mitochondrial Bak shares this level of regulation. Here we report that Bak is retrotranslocated from the mitochondria by pro‐survival Bcl‐2 proteins. Bak is present in the cytosol of human cells and tissues, but low shuttling rates cause predominant mitochondrial Bak localization. Interchanging the membrane anchors of Bax and Bak reverses their subcellular localization compared to the wild‐type proteins. Strikingly, the reduction of Bax shuttling to the level of Bak retrotranslocation results in full Bax toxicity even in absence of apoptosis induction. Thus, fast Bax retrotranslocation is required to protect cells from commitment to programmed death.
Synopsis
Pro‐apoptotic proteins Bax and Bak kill cells by permeabilizing the outer mitochondrial membrane. Mitochondrial localization and thus apoptosis induction by both proteins is controlled by their retrotranslocation dynamics governed by the hydrophobicity of the C‐terminal membrane anchor.
The pro‐apoptotic Bcl‐2 protein Bak is retrotranslocated from the mitochondria into the cytosol dependent on pro‐survival Bcl‐2 proteins.
Bax and Bak retrotranslocate at different rates by the same retrotranslocation process.
Rapid Bax shuttling protects cells from apoptosis in the presence or absence of apoptotic stimuli.
The hydrophobicity of the membrane anchor determines shuttling and localization of Bax and Bak.
Pro‐apoptotic proteins Bax and Bak kill cells by permeabilizing the outer mitochondrial membrane. Mitochondrial localization and thus apoptosis induction by both proteins is controlled by their retrotranslocation dynamics governed by the hydrophobicity of the C‐terminal membrane anchor.
Achieving universal health coverage (UHC) is a priority of most low- and middle-income countries, reflecting governments' commitments to improved population health. However, high levels of informal ...employment in many countries create challenges to progress toward UHC, with governments struggling to extend access and financial protection to informal workers. One region characterized by a high prevalence of informal employment is Southeast Asia. Focusing on this region, we systematically reviewed and synthesized published evidence of health financing schemes implemented to extend UHC to informal workers. Following PRISMA guidelines, we systematically searched for both peer-reviewed articles and reports in the grey literature. We appraised study quality using the Joanna Briggs Institute checklists for systematic reviews. We synthesized extracted data using thematic analysis based on a common conceptual framework for analyzing health financing schemes, and we categorized the effect of these schemes on progress towards UHC along the dimensions of financial protection, population coverage, and service access. Findings suggest that countries have taken a variety of approaches to extend UHC to informal workers and implemented schemes with different revenue raising, pooling, and purchasing provisions. Population coverage rates differed across health financing schemes; those with explicit political commitments toward UHC that adopted universalist approaches reached the highest coverage of informal workers. Results for financial protection indicators were mixed, though indicated overall downward trends in out-of-pocket expenditures, catastrophic health expenditure, and impoverishment. Publications generally reported increased utilization rates through the introduced health financing schemes. Overall, this review supports the existing evidence base that predominant reliance on general revenues with full subsidies for and mandatory coverage of informal workers are promising directions for reform. Importantly, the paper extends existing research by offering countries committed to progressively realizing UHC around the world a relevant updated resource, mapping evidence-informed approaches toward accelerated progress on the UHC goals.
► Several phenolic acid derivatives were newly detected in coriander leaves and fruits. ► Upon blanching rutin was identified for the first time in coriander fruits. ► Steam- and water-blanching did ...not cause losses of phenolic antioxidants. ► Short-time blanching retains polyphenols and antioxidant capacity of coriander.
Fresh coriander leaves were steam- and water-blanched at 100°C and at 90 and 100°C, respectively, for 1–10min, and subsequently comminuted to form a paste. Pasty products obtained from coriander fruits were processed after water-blanching applying the same time-temperature regimes. Among the 11 phenolics characterised in leaves by high-performance liquid chromatography coupled to mass spectrometric detection, several caffeic acid derivatives, 5-feruloylquinic and 5-p-coumaroylquinic acids were tentatively identified for the first time. In fruits, 10 phenolics were detected, whereas rutin, a dicaffeic acid derivative and two feruloylquinic and caffeoylquinic acid isomers were newly detected. Upon steam-blanching for 1min, phenolic contents and antioxidant capacities remained virtually unchanged. In contrast, water-blanching and extended steam-blanching even yielded increased levels compared to the unheated control, whereas short-time water-blanching resulted in higher values than prolonged heat treatment. Thus, short-time water-blanching is recommended as the initial unit in the processing of coriander leaves and fruits into novel pasty products.
Transhumanism and One Health Zinsstag, Jakob; Grolimund, Andrea Kaiser; Tulay, Engin ...
CABI One Health,
06/2024, Letnik:
3, Številka:
1
Journal Article
Recenzirano
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Abstract In this article, we draw on an interdisciplinary seminar at the University of Basel in the spring semester 2023. The seminar firstly discussed technical transhumanism between improving human ...lives through technological innovation and breathtaking advances in artificial intelligence (AI). Secondly, integrative approaches to health such as One Health have a transhumanist dimension, meaning that the interaction of human and animal health contributes to human health and development. As technological and biological dimensions of transhumanism raise philosophical, anthropological and ethical questions, we ask what is specifically human and what kind of future human-technology interactions is societally acceptable. With the rapid recent development of AI, questions arise about algorithms taking over human intellectual functions. Transhumanism can be described as a current of a posthumanist turn that generally asks where the limits of the human body and also of human existence lie. From an anthropological point of view a controversial discussion is held ‘beyond the human’ about blurring of the boundaries between humans, animals and nature. The One Health approach demands that animals should not suffer in place of humans and that the health of humans, animals, plants and the environment must be promoted simultaneously. This places the One Health approach in a tension and dilemma between conflicting ethical and purely human demands for the protection and welfare of animals, as well as the legitimate demands for animal food and sheer survival in many areas of the world. A biological transhumanism certainly has less of a claim to surpass specifically human performance and thus stands less or not at all in the more gnostic technological current of technical transhumanism, which replaces human labour and suddenly achieves the ability to turn against humans. One Health impact statement Integrative approaches to health such as One Health have a transhumanist dimension, meaning that the interaction of human and animal health contributes to human health and development. The One Health approach demands that animals should not suffer in place of humans and that the health of humans, animals, plants and the environment must be promoted simultaneously. This places the One Health approach in a tension and dilemma between conflicting ethical and purely human demands for the protection and welfare of animals, as well as the legitimate demands for animal food and sheer survival in many areas of the world. Because of the high variability of the culturally-religiously shaped human-animal-environment relationship, such a transdisciplinary, participatory consensus would need to be contextually adapted, that is, to geographically, culturally-religiously distinct situations.Keywords: Transhumanism, Technical, Biological, One Health, Anthropology, Ontology, Ethics
The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity ...influences behavior are poorly understood. To address this question in the model organism Drosophila melanogaster, we developed new loss of function mutations in Drosophila SERT (dSERT). Previous studies in both flies and mammals have implicated serotonin as an important neuromodulator of sleep, and our newly generated dSERT mutants show an increase in total sleep and altered sleep architecture that is mimicked by feeding the SSRI citalopram. Differences in daytime versus nighttime sleep architecture as well as genetic rescue experiments unexpectedly suggest that distinct serotonergic circuits may modulate daytime versus nighttime sleep. dSERT mutants also show defects in copulation and food intake, akin to the clinical side effects of SSRIs and consistent with the pleomorphic influence of serotonin on the behavior of D. melanogaster. Starvation did not overcome the sleep drive in the mutants and in male dSERT mutants, the drive to mate also failed to overcome sleep drive. dSERT may be used to further explore the mechanisms by which serotonin regulates sleep and its interplay with other complex behaviors.
Attraction to ethanol is common in both flies and humans, but the neuromodulatory mechanisms underlying this innate attraction are not well understood. Here, we dissect the function of the key ...regulator of serotonin signaling-the serotonin transporter-in innate olfactory attraction to ethanol in Drosophila melanogaster. We generated a mutated version of the serotonin transporter that prolongs serotonin signaling in the synaptic cleft and is targeted via the Gal4 system to different sets of serotonergic neurons. We identified four serotonergic neurons that inhibit the olfactory attraction to ethanol and two additional neurons that counteract this inhibition by strengthening olfactory information. Our results reveal that compensation can occur on the circuit level and that serotonin has a bidirectional function in modulating the innate attraction to ethanol. Given the evolutionarily conserved nature of the serotonin transporter and serotonin, the bidirectional serotonergic mechanisms delineate a basic principle for how random behavior is switched into targeted approach behavior.
To explore availability, prices and affordability of essential medicines for diabetes and hypertension treatment in private pharmacies in three provinces of Zambia.
A cross-sectional survey was ...conducted in 99 pharmacies across three Zambian provinces. Methods were based on a standardized methodology by the World Health Organization and Health Action International. Availability was analysed as mean availability per pharmacy and individual medicine. Median prices were compared to international reference prices and differences in price between medicine forms (original brand or generic product) were computed. Affordability was assessed as number of days' salaries required to purchase a standard treatment course using the absolute poverty line and mean per capita provincial household income as standard. An analysis identifying medicines considered both available and affordable was conducted.
Two antidiabetics and nine antihypertensives had high-level availability (≥80%) in all provinces; availability levels for the remaining surveyed antidiabetics and antihypertensives were largely found below 50%. Availability further varied markedly across medicines and medicine forms. Prices for most medicines were higher than international reference prices and great price variations were found between pharmacies, medicines and medicine forms. Compared to original brand products, purchase of generics was associated with price savings for patients between 21.54% and 96.47%. No medicine was affordable against the absolute poverty line and only between four and eleven using mean per capita provincial incomes. Seven generics in Copperbelt/Lusaka and two in Central province were highly available and affordable.
The study showed that the majority of surveyed antidiabetic and antihypertensive medicines was inadequately available (<80%). In addition, most prices were higher than their international reference prices and that treatment with these medicines was largely unaffordable against the set affordability thresholds. Underlying reasons for the findings should be explored as a basis for targeted policy initiatives.
Transfigurations of aging Kaiser-Grolimund, Andrea
Medicine Anthropology Theory,
04/2020, Letnik:
7, Številka:
1
Journal Article
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To date, most social anthropological studies on aging in African contexts focus on care for poor older people provided by related others. The focus of this article is different as it focuses on older ...people with better financial means than the average: civil servants belonging to Dar es Salaam’s middle class. Furthermore, this contribution shifts the focus from care provided through related others to practices of everyday self-care, the care that these older people provide for themselves with the help of relatives in Tanzania and the USA. In order to stay healthy and cope with diagnosed chronic conditions, older participants in this study engage in physical exercises, eat ‘good food’, and go for regular medical check-ups. This article argues that these health-promoting self-care practices of older urban dwellers reflect changing experiences of aging, health, and care, and point to transfigurations of the social imaginary of aging in Dar es Salaam’s middle class.
Low- and middle-income countries have committed to achieving universal health coverage (UHC) as a means to enhance access to services and improve financial protection. One of the key health financing ...reforms to achieve UHC is the introduction or expansion of health insurance to enhance access to basic health services, including maternal and reproductive health care. However, there is a paucity of evidence of the extent to which these reforms have had impact on the main policy objectives of enhancing service utilization and financial protection. The aim of this systematic review is to assess the existing evidence on the causal impact of health insurance on maternal and reproductive health service utilization and financial protection in low- and lower middle-income countries.
The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search included six databases: Medline, Embase, Web of Science, Cochrane, CINAHL, and Scopus as of 23rd May 2023. The keywords included health insurance, impact, utilisation, financial protection, and maternal and reproductive health. The search was followed by independent title and abstract screening and full text review by two reviewers using the Covidence software. Studies published in English since 2010, which reported on the impact of health insurance on maternal and reproductive health utilisation and or financial protection were included in the review. The ROBINS-I tool was used to assess the quality of the included studies.
A total of 17 studies fulfilled the inclusion criteria. The majority of the studies (82.4%, n = 14) were nationally representative. Most studies found that health insurance had a significant positive impact on having at least four antenatal care (ANC) visits, delivery at a health facility and having a delivery assisted by a skilled attendant with average treatment effects ranging from 0.02 to 0.11, 0.03 to 0.34 and 0.03 to 0.23 respectively. There was no evidence that health insurance had increased postnatal care, access to contraception and financial protection for maternal and reproductive health services. Various maternal and reproductive health indicators were reported in studies. ANC had the greatest number of reported indicators (n = 10), followed by financial protection (n = 6), postnatal care (n = 5), and delivery care (n = 4). The overall quality of the evidence was moderate based on the risk of bias assessment.
The introduction or expansion of various types of health insurance can be a useful intervention to improve ANC (receiving at least four ANC visits) and delivery care (delivery at health facility and delivery assisted by skilled birth attendant) service utilization in low- and lower-middle-income countries. Implementation of health insurance could enable countries' progress towards UHC and reduce maternal mortality. However, more research using rigorous impact evaluation methods is needed to investigate the causal impact of health insurance coverage on postnatal care utilization, contraceptive use and financial protection both in the general population and by socioeconomic status.
This study was registered with Prospero (CRD42021285776).
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