Male gender construction and representation in Paul : reading 1 Thessalonians through a gender critical, postcolonial optic

Thesis (PhD)--Stellenbosch University, 2018.ENGLISH ABSTRACT: Interpretational approaches to 1 Thessalonians tend either to (excessively) problematise and question the ‘authoritative voice of Paul,’ or to (naively) lionise that same voice, thereby creating a deep tension between what amounts to an academic and a faith based or ecclesial approach. The tension is made all the more palpable when the discursive-rhetorical role of the biblical text is considered in relation to the construction and representation of masculinity. Broadly speaking, then, critical approaches are the province of the academy, while approaches that affirm the normativising role and centrality of Paul, belong to the church. The latter approach, which I characterise as pre-critical and/or ideologically biased, narrowly construes the possibilities for masculine identity construction and representation by seeing masculinity as fixed and stable. Textual engagement conforms to the more traditional approaches of interpretation which, while elucidating likely historical and textual frameworks for meaning-making, tend to either be agnostic about the gendered nature and discursive quality of the text, or downplay the presence of gendered bodies altogether. Critical approaches, by contrast, bring the gendered nature of the text into sharper relief, but often in inaccessible ways. By critical, I mean, approaches specifically aimed at paying meticulous attention to aspects of 1 Thessalonians that are assumed, on ideological/theological grounds, to be precluded from an investigation of the meaning of the text. In other words, while some critical approaches to 1 Thessalonians problematise the text (and its interpretations), not all critical approaches are interested in the question of gender generally, and of masculinity, specifically. At the centre of this dissertation, then, is the question of how 1 Thessalonians reveals a discursively constructed and represented masculinity and draws on the critical optic of gender criticism and postcolonial biblical criticism to “offer more language and recognition to those who found [find] themselves ostracised because they did [do] not confirm (sic.) to restrictive ideas of what it means to be a man or a woman” (quotation from Judith Butler, in Jaschik, 2017). The objective, moreover, for developing and applying this optic to 1 Thessalonians, is to model ethically responsible hermeneutics and in the context of masculinity, break open the narrow ways in which the biblical text is often interpreted and used to shape the “biblical” notion of masculinity (and femininity). In this study, I maintain that the polysemy of the biblical text, especially when read through the lens of gender criticism and postcolonial biblical criticism, together with an understanding of the discursive-rhetorical dimensions of the text, invites wider possibilities for identity construction and representation. This is crystallised in the transgendering which Paul, Silvanus and Timothy seem to adopt in the letter to the Thessalonian assembly.AFRIKAANSE OPSOMMING: Interpretatiewe benaderings tot 1 Tessalonisense is geneig om die “gesaghebbende stem van Paulus” (op oordrewe wyse) te problematiseer of te bevraagteken, of om (op naiewe wyse) dieselfde stem te verheerlik, en sodoende diep spanning te skep tussen wat as 'n akademiese en geloofsgebaseerde of kerklike benadering beskryf kan word. Die spanning word des te meer waarneembaar wanneer die diskursiewe-retoriese rol van die Bybelse teks met betrekking tot die konstruksie en voorstelling van manlikheid in aanmerking geneem word. Oor die algemeen is kritiese benaderings die forte van die akademie, terwyl benaderings wat die normativiserende rol en sentraliteit van Paulus bevestig, aan die kerk behoort. Laasgenoemde benadering, wat ek as voorkritiese en/of ideologiese vooroordeel kenmerk, beperk die interpretasie van die moontlikhede vir manlike identiteitskonstruksie en uitbeelding, deur manlikheid as vas omskrewe en stabiel te beskou. Interaksie met die teks is in ooreenstemming met die meer tradisionele benaderings tot interpretasie, wat alhoewel hulle die waarskynlike historiese en tekstuele raamwerke vir betekenisvorming belig, geneig is om of agnosties te wees oor die gender aard en diskursiewe kwaliteit van die teks of die teenwoordigheid van gendered liggame buite spel plaas. Kritiese benaderings, daarenteen, bring die geslagtelike aard van die teks skerper in beeld, maar dikwels op ontoeganklike maniere. Met krities bedoel ek, benaderings wat spesifiek daarop gemik is om noukeurig aandag te skenk aan aspekte van 1 Tessalonisense wat dikwels en op ideologiese / teologiese gronde uitgesluit word van die soeke na die betekenis van die teks. Met ander woorde, terwyl sommige kritiese benaderings tot 1 Tessalonisense die teks (en interpretasies daarvan) problematiseer, is nie alle kritiese benaderings ingestel op die tema van gender in die algemeen nie, en ook nie van manlikheid in die besonder nie. Sentraal tot hierdie proefskrif is dan die vraag hoe 1 Tessalonisense 'n diskursief gekonstrueerde en uitgebeelde manlikheid aan die lig bring, en steun hiervoor op die kritiese optika van genderkritiek en postkoloniale Bybel kritiek “[to] offer more language and recognition to those who found [find] themselves ostracised because they did [do] not confirm (sic.) to restrictive ideas of what it means to be a man or a woman” (quotation from Judith Butler, in Jaschik, 2017). Die oogmerk om hierdie optika vir 1 Tessalonisense te ontwikkel en toe te pas, is om eties-verantwoordelike hermeneutiek te modelleer en die beperkende maniere waarop die Bybelse teks in die konteks van manlikheid dikwels geinterpreteer word en gebruik word om die "Bybelse" idee van manlikheid (en vroulikheid) te vorm, te bevraagteken en uit te brei. In hierdie studie huldig ek die opinie dat die polisemie van die Bybelse teks, veral wanneer dit deur die lens van genderkritiek en postkoloniale Bybelse kritiek gelees word, tesame met insig in die diskursiewe-retoriese dimensies van die teks, breer moontlikhede bied vir identiteitskonstruksie en verteenwoordiging. Hierdie werkswyse vind uiting in die transgendering wat Paulus, Silvanus en Timoteus in die brief aan die Tessalonisense-samestelling blyk om te aanvaar

Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication

The nucleoside analog N4-hydroxycytidine (NHC) is the active metabolite of the prodrug molnupiravir, which has been approved for the treatment of COVID-19. SARS-CoV-2 incorporates NHC into its RNA, resulting in defective virus genomes. Likewise, inhibitors of dihydroorotate dehydrogenase (DHODH) reduce virus yield upon infection, by suppressing the cellular synthesis of pyrimidines. Here, we show that NHC and DHODH inhibitors strongly synergize in the inhibition of SARS-CoV-2 replication in vitro. We propose that the lack of available pyrimidine nucleotides upon DHODH inhibition increases the incorporation of NHC into nascent viral RNA. This concept is supported by the rescue of virus replication upon addition of pyrimidine nucleosides to the media. DHODH inhibitors increased the antiviral efficiency of molnupiravir not only in organoids of human lung, but also in Syrian Gold hamsters and in K18-hACE2 mice. Combining molnupiravir with DHODH inhibitors may thus improve available therapy options for COVID-19

Comparison of Closure of Gastric Perforation Ulcers With Biodegradable Lactide-Glycolide-Caprolactone or Omental Patches

Results of both methods of gastric closure (omental and biodegradable patch) were similar suggesting that a biodegradable patch glued to the outside of the stomach may be a viable alternative for closure of perforations of the digestive tract

Diversity patterns and community structure of the ground-associated macrofauna along the beach-inland transition zone of small tropical islands

Biodiversity follows distinct and observable patterns. Where two systems meet, biodiversity is often increased, due to overlapping occurrence ranges and the presence of specialized species that can tolerate the dynamic conditions of the transition zone. One of the most pronounced transition zones occurs at shores, where oceans and terrestrial habitat collide, forming the shore–inland transition zone. The relevance of this transition zone in shaping a system’s community structure is particularly pronounced on small islands due to their high shore-to-inland-area ratio. However, the community structure of insular faunas along this transition zone is unknown. Here, we investigated the diversity patterns along the beach–inland transition zone of small islands and tested the hypothesis that species diversity increases toward the transition zone where beach and interior habitat meet. By measuring environmental parameters, resource availability, and ground-associated macrofauna diversity along transects running across the beach–inland transition zone, we show that a gradual change in species composition from beach to the inland exists, but neither taxa richness, diversity, nor overall abundance changed significantly. These findings offer important insights into insular community structure at the transition zone from sea to land that are relevant to better understand the dynamic and unique characteristics of insular ecosystems

Single-incision laparoscopic sterilization of the cheetah (Acinonyx jubatus)

OBJECTIVE : To describe laparoscopic ovariectomy and salpingectomy in the cheetah (Acinonyx jubatus) using single-incision laparoscopic surgery (SILS). STUDY DESIGN : Prospective cohort. ANIMALS : Female cheetahs (Acinonyx jubatus) ( n ¼ 21). METHODS : Cheetahs were randomly divided to receive either ovariectomy (n ¼ 11) or salpingectomy (n ¼ 10). The use and complications of a SILS port was evaluated in all of cheetahs. Surgery duration and insufflation volumes of carbon dioxide (CO2) were recorded and compared across procedures. RESULTS : Laparoscopic ovariectomy and salpingectomy were performed without complications using a SILS port. The poorly-developed mesosalpinx and ovarian bursa facilitated access to the uterine tube for salpingectomy in the cheetah. The median surgery duration for ovariectomy was 24 minutes (interquartile range 3) and for salpingectomy was 19.5 minutes (interquartile range 3) (P ¼.005). The median volume of CO2 used for ovariectomy was 11.25 L (interquartile range 3.08) and for salpingectomy was 4.90 L (interquartile range 2.52), (P ¼.001) CONCLUSIONS : Laparoscopic ovariectomy and salpingectomy can be performed in the cheetah using SILS without perioperative complications. Salpingectomy is faster than ovariectomy and requires less total CO2 for insufflation.NRF grants, AfriCat. Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa and the Arabella Dean fund of the South African Veterinary Foundation.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1532-950X2016-07-30hb2015ab201

Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication

Funding Information: We thank Thorsten Wolff, Daniel Bourquain, Jessica Schulz, and Christian Mache from the Robert-Koch Institute and Martin Beer from the Friedrich Loeffler Institute (FLI) for providing isolates of SARS-CoV-2 variants. We thank Anna Kraft and Gabriele Czerwinski (both FLI) for support in the preparation of samples for pathology, and Catherine Hambly (University of Aberdeen) for help with daily energy expenditure measurements. We would like to thank Cathrin Bierwirth (University Medical Center Göttingen), Isabell Schulz, Anne-Kathrin Donner, and Frank-Thorben Peters for excellent technician assistance and Jasmin Fertey and Alexandra Rockstroh for providing the virus stocks for the mice experiment (Fraunhofer Institute IZI Leipzig). We acknowledge support by the Open Access Publication Funds of the Göttingen University. KMS was a member of the Göttingen Graduate School GGNB during this work. This work was funded by the COVID-19 Forschungsnetzwerk Niedersachsen (COFONI) to MD, by the Federal Ministry of Education and Research Germany ( Bundesministerium für Bildung und Forschung; BMBF ; OrganSARS , 01KI2058 ) to SP and TM, and by a grant of the Max Planck Foundation to DG. Declaration of interests AS, HK, EP, and DV are employees of Immunic AG and own shares and/or stock-options of the parent company of Immunic AG, Immunic Inc. Some of the Immunic AG employees also hold patents for the Immunic compounds described in this manuscript (WO2012/001,148, WO03006425). KMS, AD, and MD are employees of University Medical Center Göttingen, which has signed a License Agreement with Immunic AG covering the combination of DHODH inhibitors and nucleoside analogs to treat viral infections, including COVID-19 (inventors: MD, KMS, and AD). The other authors declare no conflict of interest.Peer reviewedPublisher PD

Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy

Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability

PURA syndrome : clinical delineation and genotype-phenotype study in 32 individuals with review of published literature

Background De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. Objectives T o delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. Methods Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotypephenotype correlations by analysis of both recurrent mutations as well as mutation classes. Results We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. Conclusion We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.Peer reviewe

The Cytosolic Domain of Fis1 Binds and Reversibly Clusters Lipid Vesicles

Every lipid membrane fission event involves the association of two apposing bilayers, mediated by proteins that can promote membrane curvature, fusion and fission. We tested the hypothesis that Fis1, a tail-anchored protein involved in mitochondrial and peroxisomal fission, promotes changes in membrane structure. We found that the cytosolic domain of Fis1 alone binds lipid vesicles, which is enhanced upon protonation and increasing concentrations of anionic phospholipids. Fluorescence and circular dichroism data indicate that the cytosolic domain undergoes a membrane-induced conformational change that buries two tryptophan side chains upon membrane binding. Light scattering and electron microscopy data show that membrane binding promotes lipid vesicle clustering. Remarkably, this vesicle clustering is reversible and vesicles largely retain their original shape and size. This raises the possibility that the Fis1 cytosolic domain might act in membrane fission by promoting a reversible membrane association, a necessary step in membrane fission

CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome.This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R01NS109858, to VAG); the Paul A. Marks Scholar Program at the Columbia University Vagelos College of Physicians and Surgeons (to VAG); a TIGER grant from the TAUB Institute at the Columbia Vagelos College of Physicians and Scientists (to VAG); the Swiss National Science Foundation (SNF 31003A-179371, to TH); the European Joint Program on Rare Diseases (EJP RD+SNF 32ER30-187505, to TH); the Swiss Cancer League (KFS-4999-02-2020, to GD); the EPFL institutional fund (to GD); the Kristian Gerhard Jebsen Foundation (to GD); the Swiss National Science Foundation (SNSF) (310030_184926, to GD); the Swiss Foundation for Research on Muscle Disease (FSRMM, to MAL); the Natural Science and Engineering Research Council of Canada (Discovery Grant 2020-04241, to JEB); the Italian Ministry of Health Young Investigator Grant (GR-2011-02347754, to EL); the Fondazione Istituto di Ricerca Pediatrica – Città della Speranza (18-04, to EL); the Wroclaw Medical University (SUB.E160.21.004, to RS); the National Science Centre, Poland (2017/27/B/NZ5/0222, to RS); Telethon Undiagnosed Diseases Program (TUDP) (GSP15001); the Temple Street Foundation/Children’s Health Foundation Ireland (RPAC 19-02, to IK); the Deutsche Forschungsgemeinschaft (DFG) (PO2366/2–1, to BP); the Instituto de Salud Carlos III, Spain (to ELM, EBS, and BMD); the National Natural Science Foundation of China (81871079 and 81730036, to HG and KX); and the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH (R01 DK115574, to SSC).The DEFIDIAG study is funded by grants from the French Ministry of Health in the framewok of the national French initiative for genomic medicine. The funders were not involved in the study design, data acquisition, analysis, or writing of the manuscript. Funding for the DECIPHER project was provided by Wellcome. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12, granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network.S