159 research outputs found
UPR(mt) regulation and output: a stress response mediated by mitochondrial-nuclear communication
The mitochondrial network is not only required for the production of energy, essential cofactors and amino acids, but also serves as a signaling hub for innate immune and apoptotic pathways. Multiple mechanisms have evolved to identify and combat mitochondrial dysfunction to maintain the health of the organism. One such pathway is the mitochondrial unfolded protein response (UPR(mt)), which is regulated by the mitochondrial import efficiency of the transcription factor ATFS-1 in C. elegans and potentially orthologous transcription factors in mammals (ATF4, ATF5, CHOP). Upon mitochondrial dysfunction, import of ATFS-1 into mitochondria is reduced, allowing it to be trafficked to the nucleus where it promotes the expression of genes that promote survival and recovery of the mitochondrial network. Here, we discuss recent findings underlying UPR(mt) signal transduction and how this adaptive transcriptional response may interact with other mitochondrial stress response pathways
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Novel mutation in CCBE 1 as a cause of recurrent hydrops fetalis from Hennekam lymphangiectasia-lymphedema syndrome-1.
Whole exome sequencing (WES) was used to determine the etiology of recurrent hydrops fetalis in this case of Hennekam lymphangiectasia-lymphedema syndrome-1. WES is a useful approach for diagnosing rare single-gene conditions with nonspecific phenotypes and should be considered early in the diagnostic process of investigating fetal abnormalities
Sibling sex, but not androgens, shapes phenotypes in perinatal common marmosets (\u3ci\u3eCallithrix jacchus\u3c/i\u3e)
When offspring share a womb, interactions among fetuses can impart lasting impressions on phenotypic outcomes. Such intrauterine interactions often are mediated by sex steroids (estrogens and androgens) produced by the developing fetuses. In many mammals, intrauterine interactions between brothers and sisters lead to masculinization of females, which can induce fitness consequences. Many litter-bearing primates, though, seem to escape androgen-mediated litter effects, begging why? Here, we investigated how the sex composition (i.e., same- or mixed-sex) of litters influences perinatal outcomes in the common marmoset monkey (Callithrix jacchus), using a combination of physiological, morphological, and behavioural assays. We hypothesized that androgens from male fetuses would mediate developmental differences across litter types. We found that newborns (24â36âhours old) from same- and mixed-sex litters were indistinguishable by urinary androgen profiles, birth weights, morphometrics, and behaviour. However, monkeys born into same- and mixed-sex litters exhibited subtle morphological and neurobehavioral differences later in the perinatal period, independent of their androgen profiles. Our findings suggest that while androgens from male fetuses likely do not organize their siblingsâ phenotypes, perinatal stimuli may initiate divergent developmental trajectories among siblings, which, in turn, promotes inter-individual variability within families
Sibling sex, but not androgens, shapes phenotypes in perinatal common marmosets (\u3ci\u3eCallithrix jacchus\u3c/i\u3e)
When offspring share a womb, interactions among fetuses can impart lasting impressions on phenotypic outcomes. Such intrauterine interactions often are mediated by sex steroids (estrogens and androgens) produced by the developing fetuses. In many mammals, intrauterine interactions between brothers and sisters lead to masculinization of females, which can induce fitness consequences. Many litter-bearing primates, though, seem to escape androgen-mediated litter effects, begging why? Here, we investigated how the sex composition (i.e., same- or mixed-sex) of litters influences perinatal outcomes in the common marmoset monkey (Callithrix jacchus), using a combination of physiological, morphological, and behavioural assays. We hypothesized that androgens from male fetuses would mediate developmental differences across litter types. We found that newborns (24â36âhours old) from same- and mixed-sex litters were indistinguishable by urinary androgen profiles, birth weights, morphometrics, and behaviour. However, monkeys born into same- and mixed-sex litters exhibited subtle morphological and neurobehavioral differences later in the perinatal period, independent of their androgen profiles. Our findings suggest that while androgens from male fetuses likely do not organize their siblingsâ phenotypes, perinatal stimuli may initiate divergent developmental trajectories among siblings, which, in turn, promotes inter-individual variability within families
United in Separation? Lozi Secessionism in Zambia and Namibia
Secessionism perseveres as a complex political phenomenon in Africa, yet often a more in-depth analysis is overshadowed by the aspirational simplicity of pursuing a new state. Using historical and contemporary approaches, this edited volume offers the most exhaustive collection of empirical studies of African secessionism to date. The respected expert contributors put salient and lesser known cases into comparative perspective, covering Biafra, Katanga, Eritrea and South Sudan alongside Barotseland, Cabinda, and the Comoros, among others. Suggesting that African secessionism can be understood through the categories of aspiration, grievance, performance, and disenchantment, the book's analytical framework promises to be a building block for future studies of the topic
UPRmt scales mitochondrial network expansion with protein synthesis via mitochondrial import [preprint]
As organisms develop, individual cells generate mitochondria to fulfill physiologic requirements. However, it remains unknown how mitochondrial network expansion is scaled to cell growth and impacted by environmental cues. The mitochondrial unfolded protein response (UPRmt) is a signaling pathway mediated by the transcription factor ATFS-1 which harbors a mitochondrial targeting sequence (MTS)1. Here, we demonstrate that ATFS-1 mediates an adaptable mitochondrial expansion program that is active throughout normal development. Developmental mitochondrial network expansion required the relatively inefficient MTS2 in ATFS-1, which allowed the transcription factor to be responsive to parameters that impact protein import capacity of the entire mitochondrial network. Increasing the strength of the ATFS-1 MTS impaired UPRmt activity throughout development due to increased accumulation within mitochondria. The insulin-like signaling-TORC13 and AMPK pathways affected UPRmt activation4,5 in a manner that correlated with protein synthesis. Manipulation to increase protein synthesis caused UPRmt activation. Alternatively, S6 kinase inhibition had the opposite effect due to increased mitochondrial accumulation of ATFS-1. However, ATFS-1 with a dysfunctional MTS6 constitutively increased UPRmt activity independent of TORC1 function. Lastly, expression of a single protein with a strong MTS, was sufficient to expand the muscle cell mitochondrial network in an ATFS-1-dependent manner. We propose that mitochondrial network expansion during development is an emergent property of the synthesis of highly expressed mitochondrial proteins that exclude ATFS-1 from mitochondrial import, causing UPRmt activation. Mitochondrial network expansion is attenuated once ATFS-1 can be imported
UPR(mt) scales mitochondrial network expansion with protein synthesis via mitochondrial import in Caenorhabditis elegans
As organisms develop, individual cells generate mitochondria to fulfill physiological requirements. However, it remains unknown how mitochondrial network expansion is scaled to cell growth. The mitochondrial unfolded protein response (UPR(mt)) is a signaling pathway mediated by the transcription factor ATFS-1 which harbors a mitochondrial targeting sequence (MTS). Here, using the model organism Caenorhabditis elegans we demonstrate that ATFS-1 mediates an adaptable mitochondrial network expansion program that is active throughout normal development. Mitochondrial network expansion requires the relatively inefficient MTS in ATFS-1, which allows the transcription factor to be responsive to parameters that impact protein import capacity of the mitochondrial network. Increasing the strength of the ATFS-1 MTS impairs UPR(mt) activity by increasing accumulation within mitochondria. Manipulations of TORC1 activity increase or decrease ATFS-1 activity in a manner that correlates with protein synthesis. Lastly, expression of mitochondrial-targeted GFP is sufficient to expand the muscle cell mitochondrial network in an ATFS-1-dependent manner. We propose that mitochondrial network expansion during development is an emergent property of the synthesis of highly expressed mitochondrial proteins that exclude ATFS-1 from mitochondrial import, causing UPR(mt) activation
Reâweighing the 5% tagging recommendation: assessing the potential impacts of tags on the behaviour and body condition of bats
Considerable advances and breakthroughs in wildlife tracking technology have occurred in recent years, allowing researchers to gain insights into the movements and behaviours of a broad range of animals. Considering the accessibility and increase in use of tracking devices in wildlife studies, it is important to better understand the effects on these on animals. Our endeavour revisits a guideline established in 1988, which proposes that bats may encounter body condition or health problems and alter their behaviour when carrying tags weighing more than 5% of their body mass. Through a systematic literature review, we conducted a metaâanalysis to identify the impacts of tags on bats, including 367 papers from 1976 to 2023 that discussed, mentioned, employed, or quantified tagging of bats. We noted that the proportion of studies exceeding the 5% rule has not changed in recent years. However, the impact of tags was quantified in few studies for behaviour (n = 7) and body condition (n = 10) of bats. We were unable to assess whether tags weighing less or more than 5% of the bat's body mass impacted bats, but our metaâanalysis did identify that tags, irrespective of mass, affect the behaviour and body condition of bats. Although the overall magnitude of measured effects of tags on bats was small, progress has been made to advance our understanding of tag mass on bats. Naturally, there is a bias in reporting of significant results, illustrating the need of reporting results when there is no apparent effect of tags on bats. Our findings highlight the need for rigorous reporting of behaviour and body condition data associated with tagging of animals and illustrate the importance for studies comparing how tracking devices of different dimensions and masses may impact bat species to ensure research meets rigorous ethical standards
The anthropology of extraction: critical perspectives on the resource curse
Attempts to address the resource curse remain focussed on revenue management, seeking technical solutions to political problems over examinations of relations of power. In this paper, we provide a review of the contribution anthropological research has made over the past decade to understanding the dynamic interplay of social relations, economic interests and struggles over power at stake in the political economy of extraction. In doing so, we show how the constellation of subaltern and elite agency at work within processes of resource extraction is vital in order to confront the complexities, incompatibilities, and inequities in the exploitation of mineral resources
Engineered nanomaterials: toward effective safety management in research laboratories
It is still unknown which types of nanomaterials and associated doses represent an actual danger to humans and environment. Meanwhile, there is consensus on applying the precautionary principle to these novel materials until more information is available. To deal with the rapid evolution of research, including the fast turnover of collaborators, a user-friendly and easy-to-apply risk assessment tool offering adequate preventive and protective measures has to be provided.Results: Based on new information concerning the hazards of engineered nanomaterials, we improved a previously developed risk assessment tool by following a simple scheme to gain in efficiency. In the first step, using a logical decision tree, one of the three hazard levels, from H1 to H3, is assigned to the nanomaterial. Using a combination of decision trees and matrices, the second step links the hazard with the emission and exposure potential to assign one of the three nanorisk levels (Nano 3 highest risk; Nano 1 lowest risk) to the activity. These operations are repeated at each process step, leading to the laboratory classification. The third step provides detailed preventive and protective measures for the determined level of nanorisk.Conclusions: We developed an adapted simple and intuitive method for nanomaterial risk management in research laboratories. It allows classifying the nanoactivities into three levels, additionally proposing concrete preventive and protective measures and associated actions. This method is a valuable tool for all the participants in nanomaterial safety. The users experience an essential learning opportunity and increase their safety awareness. Laboratory managers have a reliable tool to obtain an overview of the operations involving nanomaterials in their laboratories; this is essential, as they are responsible for the employee safety, but are sometimes unaware of the works performed. Bringing this risk to a three-band scale (like other types of risks such as biological, radiation, chemical, etc.) facilitates the management for occupational health and safety specialists. Institutes and school managers can obtain the necessary information to implement an adequate safety management system. Having an easy-to-use tool enables a dialog between all these partners, whose semantic and priorities in terms of safety are often different
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