'When the skies fight': HIV, violence and pathways of precarity in South Africa

Based on multi-sited ethnographic fieldwork in South Africa, this article explores the skies that fight, the proverbial lightning strikes that bring HIV into women's lives and bodies. Departing from earlier studies on ARV programmes in and beyond South Africa, and broadening out to explore the chronic struggle for life in a context of entrenched socio-economic inequality, this article presents findings on women's embodiment of and strategic resistance to structural and interpersonal violence. These linked forms of violence are discussed in light of the concept of precarity. Across two sections, the findings trace the pathways through which precarity entered women's lives, drawing on verbal, visual and written accounts collected through participant observation, participatory photography and film, and journey mapping. In doing so, the ethnography articulates the intersection of structural and interpersonal violence in women's lives. It also reveals the extent to which women exert a 'constrained agency', on the one hand, to resist structural violence and reconfigure their political relationship with the state through health activism; and, on the other hand, to shift the gender dynamics that fuel interpersonal violence through a careful navigation of intimacy and independence

Biopolitical precarity in the permeable body: the social lives of people, viruses and their medicines

This article is based on multi-sited ethnography that traced a dynamic network of actors (activists, policy-makers, health care systems, pharmaceutical companies) and actants (viruses and medicines) that shaped South African women’s access to, and embodiment of, antiretroviral therapies (ARVs). Using actor network theory and post-humanist performativity as conceptual tools, the article explores how bodies become the meeting place for HIV and ARVs, or non-human actants. The findings centre around two linked sets of narratives that draw the focus out from the body to situate the body in relation to South Africa’s shifting biopolitical landscape. The first set of narratives articulate how people perceive the intra-action of HIV and ARVs in their sustained vitality. The second set of narratives articulate the complex embodiment of these actants as a form biopolitical precarity. These narratives flow into each other and do not represent a totalising view of the effects of HIV and ARVs in the lives of the people with whom I worked. The positive effects of ARVs (as unequivocally essential for sustaining life) were implicit and the precarious vitality of the people in this ethnography was fundamental. However, a related and emergent set of struggles become salient during the study that complicate a view of ARVs as a ‘technofix’. These emergent struggles were biopolitical, and they related first to the intra-action of HIV and ARVs ‘within’ the body; and second, to the ‘outside’ socio-economic context in which people’s bodies were situated

Pseudomonas putida toksiini GraT mõju bakteri füsioloogiale

Väitekirja elektrooniline versioon ei sisalda publikatsiooneLooduses peavad bakterid olema võimelised toime tulema keskkonnatingimuste muutumisega üpris laiades piirides. Selles on bakteritele abiks paljud raku elutegevust ja kasvu kontrollivad süsteemid. Eriti omapärasteks bakteri kasvu regulaatoriteks arvatakse olevat toksiin-antitoksiin (TA) süsteemid. Enamasti koosnevad need kahest väikesest valgust: toksiin on võimeline inhibeerima bakteri elutähtsaid protsesse, kuid tavatingimustel takistab seda temaga seondunud antitoksiin. Selleks, et mõista konkreetse TA süsteemi olulisust ja mõju bakterile, on vaja kirjeldada nii toksiini otsest sihtmärki rakus kui ka bakteri füsioloogilist vastust toksiini toimele. Selle töö eesmärgiks oli tuvastada mullabakteri Pseudomonas putida ühe TA toksiini, GraT, sihtmärk rakus ning kirjeldada toksiini mõju raku elutegevusele. GraT on omapärane toksiin, kuna selle efekt on temperatuuritundlik ning süveneb külmas. Töö tuvastas, et GraT lagundab transleeritavaid mRNA-sid. GraT struktuuri analüüs viitab, et toksiinidele ebatüüpiliselt on valgu esimene viiendik paindlik ja ilma kindla struktuurita. Samuti tuvastati, et GraT toksilisust võimendab teiste valkude voltumist abistav šaperonvalk DnaK, mis võib olla seotud GraT paindliku regiooni voltumisega. GraT füsioloogilisi efekte jälgiti mudelsüsteemis, kus toksiini toodetakse looduslikust genoomsest lookusest, millest puudub antitoksiin. Võrreldes tihti rakendatavate toksiini kunstliku ületootmise süsteemidega, on kasutatud mudel paremaks lähenduseks toksiini loomulikule aktivatsioonile. GraT mõjul täheldati kahetist efekti bakteri stressitaluvusele: mõningate stressiallikate puhul see suureneb, kuid teiste puhul väheneb. Lisaks häirib GraT ribosoomide biogeneesi, mida pole sarnaste toksiinide kohta varem kirjeldatud. GraT mõju all kasvavate rakkude valgulise koostise analüüs näitas, et bakter üritab GraT toksilisust leevendada, suurendades ribosoomide biosünteesi abivalkude hulka ja vähendades süsinikumetabolismi intensiivsust. Kuigi GraT roll P. putida elus ei ole endiselt selge, kirjeldati GraT puhul mitmeid TA toksiinidele ebaharilikke omadusi, mis täiendavad meie arusaamu nende ebatavaliste regulaatorite mitmekesisusest.Free-living bacteria must cope with very different environmental conditions. This is enabled by many systems that control their growth and metabolism. Toxin-antitoxin (TA) systems are thought to be a peculiar example of such regulators. These usually consist of two small proteins: the toxin blocks vital cellular processes but is normally inhibited by antitoxin binding. To understand the importance of a TA system in bacterial life, it is necessary to pinpoint the toxin’s molecular target and to also describe the physiological response to the toxicity. This thesis aimed to identify the target of GraT, a TA toxin in the soil bacterium Pseudomonas putida, and to study the toxin’s effect on bacterial physiology. GraT is an intriguing toxin, as its effect is more pronounced at lower growth temperatures. This work identified that GraT degrades translated mRNAs. Structural analysis of GraT suggests that, atypically for TA toxins, the first one fifth of the protein is disordered. Additionally, it was seen that the chaperone DnaK enhances GraT toxicity, which may be linked to folding the GraT disordered region. The physiological effects of GraT were studied in a model where the toxin is produced from its native locus that lacks the antitoxin gene. Compared to the common systems of artificial toxin overexpression, the applied model is a better estimation of natural toxin activation. GraT was found to have a dual effect on P. putida stress tolerance: the bacterium is more sensitive to some stressors while more resilient against others. Additionally, GraT inhibits ribosome biogenesis, which has not been described before for similar toxins. Analysing the protein composition of cells growing under GraT stress showed that bacteria work to alleviate GraT toxicity by upregulating ribosome assembly factors and downregulating carbon metabolism. Even though the role of GraT in P. putida biology is still uncertain, the thesis described several GraT features unusual for TA toxins and thus enriched our knowledge of TA systems’ diversit

GID1 expression is associated with ovule development of sexual and apomictic plants.

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Managing the Product Quality of Vegetable Crops under Abiotic Stress

Vegetables are an important part of the human diet due to their nutrient density and, at the same time, low calorie content. Producers of vegetable crops mainly aim at achieving high yields with good external quality. However, there is an increasing demand of consumers for vegetables that provide good sensory properties and are rich in secondary compounds that can be valuable for human health. Sub- or supra-optimal abiotic conditions, like high temperatures, drought, excess light, salinity or nutrient deficiency, may alter the composition of vegetable crops and at the same time, result in yield loss. Thus, producers need to adapt their horticultural practices such as through the choice of variety, irrigation regime, light management, fruit thinning, or fertilizer application to improve the yield and quality of the vegetable product. In the future, altered climate conditions such as elevated atmospheric CO2 concentrations, rising temperatures, or altered precipitation patterns may become additional challenges for producers of vegetable crops, especially those that cultivate in the open field. This raises the need for optimized horticultural practices in order to minimize abiotic stresses. As well, specific storage conditions can have large impacts on the quality of vegetables. This Special Issue compiles research that deals with the optimization of vegetable product quality (e.g. sensory aspects, composition) under sub- or supra-optimal abiotic conditions

Identification and characterisation of a novel SOX2+ stem cell population in the adrenal medulla

The adrenal glands are two major endocrine organs responsible for multiple physiological processes, including the stress response, modulating the immune system and metabolism. The adrenal is composed of an outer cortex and an inner medulla with distinct developmental origin and function. While tissue-specific stem/progenitor populations of the adrenal cortex have been widely identified and characterised, the presence of a functional stem/progenitor population in the medulla is unclear. Establishing cell hierarchy of the adrenal medulla essential to understand normal homeostasis, disease pathogenesis and establishing regenerative medicine strategies, therefore the identification of a stem/progenitor population would provide an important starting point for further basic and translational studies. Cell composition of the adrenal medulla includes three main cell types: chromaffin cells, which secrete catecholamines, neurons, which stimulate catecholamine production, and a third cell type with an unspecified “support” function called sustentacular cells. Using transcriptomics and genetic approaches in mouse, I established that a population of sustentacular cells express the stem/progenitor marker SOX2. These cells are present throughout life and have a developmental origin congruent with the rest of the gland. Through genetic lineage-tracing using the Sox2CreERT2 strain, I demonstrate that SOX2+ cells are an expanding population, capable of giving rise to the catecholamine-producing chromaffin cells, consistent with a stem cell role in vivo. I further demonstrate the self-renewal potential of SOX2+ cells through in vitro isolation and expansion, using a Sox2eGFP mouse line. Analysis of SOX2+ cells in physiological organ challenge suggests potential involvement of these cells in the response to perturbation of normal homeostasis. Through analysis of FFPE sections of human adrenals, I confirm the presence of SOX2+ cells in the normal adult organ, as well as in pheochromocytomas. Taken together, these data support the identification of a previously undescribed stem cell population in the mammalian adrenal medulla and confirm its functional relevance

Ribosoomide heterogeensus bakterites Escherichia coli bL31 paraloogide näitel

Väitekirja elektrooniline versioon ei sisalda publikatsiooneSelleks, et ellu jääda, kasvada ja paljuneda, vajavad organismid sadu erinevaid valke, mis toimivad struktuursete komponentide, ensüümide, signaalivahendajate, transpordi- ja säilitusmolekulidena. Lisaks sellele on elutähtis, et valgud oleksid funktsionaalsed sobivas koguses, õigel ajal ja vajalikus kohas – seetõttu on valgusüntees ja selle regulatsioon kesksemaid eluprotsesse. Kõiki valke sünteesivad ribosoomid, RNA-st ja valkudest koosnevad kompleksid. Bakteri ribosoom, selle doktoritöö uurimisobjekt, koosneb kolmest ribosoomi RNAst ja rohkem kui 50 ribosoomi valgust, mis jagunevad kahe subühiku vahel. Eksperimentaalselt on kindlaks tehtud, et nii päris- kui eeltuumsed organismid sisaldavad mõnevõrra erineva ülesehitusega ribosoome. Samas ei ole selle nähtuse – ribosoomide heterogeensuse – bioloogiline tähtsus teada. Käesoleva doktoritöö fookuses on soolekepikese (E. coli) teatud tüüpi ribosoomi valgud (paraloogid), millel on ühine eellane, kuid mis kodeerivad erinevaid valke. Küsimus on, kas E. coli ribosoomid on paraloogide poolest heterogeensed. Mis võiks olla sellise molekulaarse mitmekesisuse roll valgusünteesil ja bakterite kasvu jaoks? E. coli ribosoomide valgulise koostise analüüs tuvastas, et nii kiire kasvu korral kui statsionaarses kasvufaasis esinevad samaaegselt ribosoomi valkude paraloogide poolest heterogeensed ribosoomid. Kasvukatsed näitasid, et ribosoomi valk bL31 paraloogid (bL31A ja bL31B) on olulised, ent mitte samaväärsed bakterite kasvuks madalamatel temperatuuridel. Nimelt annab bL31A olemasolu bakterirakkudele kiire kasvu faasis kasvueelise võrreldes bL31B-ga. bL31A ja bL31B osalevad üksteisega samaväärselt optimaalse translatsiooni initsiatsiooni etapi kiiruse ja ribosoomi subühikute ühendamise tagamisel. Samas näitavad meie tulemused, et võrreldes bL31B-d sisaldavate ribosoomidega on bL31A-d sisaldavad ribosoomid protsessiivsemad ja teevad vähem vigu valgusünteesi käigus. Doktoritöö tulemused avardavad oluliselt teadmisi ribosoomide heterogeensusest bakterites ning ribosoomi valgu bL31 tähtsusest valgusünteesil.To survive, grow and reproduce all organisms need hundreds of proteins acting as enzymes, messengers, structural components, transport and storage molecules. In addition, proteins are required to be functional at the right place, time and in sufficient amount. Therefore, protein synthesis and its regulation belong to the most central life processes. Proteins are synthesized by RNA-protein complexes called ribosomes. Experimental evidence indicates that eukaryotic and procaryotic organisms produce ribosomes with slightly different structure. The biological meaning of the phenomenon – ribosome heterogeneity – is not known. This thesis focuses on bacterial ribosome heterogeneity originating from a certain type of ribosomal proteins (paralogs) in E. coli. Paralogs have a common ancestor gene, but they encode proteins with different amino acid sequence. How does ribosome heterogeneity in ribosomal protein bL31 paralog content affect bacterial growth and translation? Analysis of ribosomal protein content showed that E. coli ribosomes are heterogeneous with respect to paralogs during fast and stationary growth phase. Subsequent work on bL31 paralogs (bL31A and bL31B) demonstrated that they are important but not equivalent for bacterial growth at lower temperatures because bL31A gives growth advantage over bL31B during fast growth. Both bL31 paralogs contribute to similar extent to translation initiation, especially to subunit joining. Interestingly, bL31A containing ribosomes are more processive and they make less errors during translation as compared to ribosomes with bL31B. This indicates that ribosome heterogeneity in bL31 paralog content may regulate translation. This thesis shed light onto functional importance of bacterial ribosome heterogeneity and thus helps us to better understand its biological meaning.https://www.ester.ee/record=b550899

Epigenetic regulation of somatostatin receptors in neuroendocrine tumors:A Novel Therapeutic Approach?

The overexpression of somatostatin type-2 receptors (SSTR2) on neuroendocrine tumor (NET) cells forms a pivotal biomarker for theranostic approaches. Radiolabeled somatostatin analogues (SSAs), most frequently [68Ga]Ga-DOTATATE and [177Lu]Lu-DOTATATE for nuclear imaging and therapy, respectively, have shown to be of great importance for NET disease management. [177Lu]Lu-DOTATATE treatment, known as peptide receptor radionuclide therapy (PRRT), is EMA and FDA approved for unresectable or metastatic, progressive, well-differentiated SSTR2-positive gastroenteropancreatic NET patients. However, complete responses after therapy are rare and progressive disease is often observed. Approaches to further improve PRRT efficacy are thus of great need. The aim of the studies described in this thesis is to upregulate SSTR2 on NET cells by modulating the epigenetic machinery, in order to increase radiolabeled SSA uptake and ultimately improve treatment response. Furthermore, we aimed to gain more insights into the interaction between epigenetic marks and the regulation of SSTR2 expression. Our studies were performed preclinically using different NET cell lines. In addition to in vitro studies with these cell lines, mice with tumors derived from these cell lines and NET patient tissue samples were used. Furthermore, the effect of epigenetic drugs on the uptake of [68Ga]Ga-DOTATATE was investigated in NET patients