11 research outputs found
Optimality Theory and Sound Change
No full textSince Kiparsky (1968) it has been standard practice in generative phonology to account for sound change by means of rule addition, rule simplification, rule reordering and rule loss. Given that the phonological rule as such no longer exists in recently proposed constraint-based theories of phonology, such as Optimality Theory (cf. Prince and Smolensky (1993), McCarthy and Prince (1993a and b), the question arises how sound change must be accounted for in these theories.
In this paper we will address this issue. It will be claimed that in Optimality Theory, sound change can straightforwardly be accounted for by constraint reranking. This will be illustrated by two examples of sound change in the historical phonology of French. The first example involves a change in the syllable structure conditions that occurred between Gallo-Romance (5th-9th century) and Old French (11th/12th century), the second example involves the loss of the possibility to phonologically encliticize an unstressed object pronoun to a preceding stressed element (phonological enclisis). The formal account of both cases relies on a reordering of Alignment constraints.
This paper purports to show not only that sound change can be analyzed as constraint-reranking (an expected result), but also that the analyses proposed are not thwarted by the same drawbacks of previous derivational nonlinear accounts. Finally, we will raise the issue of how to account for markedness and unmarkedness in sound change.The definitive version of this paper was published in NELS 25: Proceedings of the North East Linguistics Society and is available at http://glsa.hypermart.netJacobs, H. (1995). Optimality theory and sound change. In J.N. Beckman (Ed.), NELS 25: Proceedings of the North East Linguistics Society (pp. 219-232). Amherst, MA: GLSA (Graduate Linguistic Student Association), Dept. of Linguistics, University of Massachusetts
Структура широкомасштабного управления в районе станции Академик Вернадский
No full textThe article is devoted to actual issues on methodological provisions for Antarctic activity. Geographical distribution and further diversification of human activities in this region became an environmental threat that needs more comprehensive approach for management in Antarctic in whole and specifically in the region of Ukrainian scientific interests.Стаття присвячена актуальним питанням науково-методичного забезпечення антарктичної діяльності, географічне поширення та подальша диверсифікація якої набувають нових загрозливих масштабів як в Антарктиці в цілому, так і в зоні відповідальності станції Академік Вернадський зокрема.Статья посвящена актуальным вопросам научно-методического обеспечения антарктической деятельности, географическое распространение и дальнейшая диверсификация которой приобретают новые угрожающие масштабы как в Антарктике в целом, так и в районе станции Академик Вернадский в частности. Проанализирована функциональная структура основных типов подохранных территорий Антарктики, показаны причины их высокой концентрации вдоль северо-западной оконечностиThe article prepared by preliminary results of the research grant À/08/97389, supported by the German Academic Exchange Service (July, 2009). The author wishes to thank Administration of the National Antarctic Scientific Center of Ukraine, for access to archival material and reports; supervisors of author's DAAD scholarship, Dr Haike Herata, Head of Antarctic Protected Section, Federal Environmental Agency, and Dr Hans-Ulrich Peter, Head of Polar birds and ecology group, University Jena – for useful comments and suggestions; and Dmyrto Lyashenko, PhD, research officer, Department of Cartography, Institute of Geography, National Academy of Sciences of Ukraine – for help in preparation of maps for this article
Структура широкомасштабного управления в районе станции Академик Вернадский
No full textThe article is devoted to actual issues on methodological provisions for Antarctic activity. Geographical distribution and further diversification of human activities in this region became an environmental threat that needs more comprehensive approach for management in Antarctic in whole and specifically in the region of Ukrainian scientific interests.Стаття присвячена актуальним питанням науково-методичного забезпечення антарктичної діяльності, географічне поширення та подальша диверсифікація якої набувають нових загрозливих масштабів як в Антарктиці в цілому, так і в зоні відповідальності станції Академік Вернадський зокрема.Статья посвящена актуальным вопросам научно-методического обеспечения антарктической деятельности, географическое распространение и дальнейшая диверсификация которой приобретают новые угрожающие масштабы как в Антарктике в целом, так и в районе станции Академик Вернадский в частности. Проанализирована функциональная структура основных типов подохранных территорий Антарктики, показаны причины их высокой концентрации вдоль северо-западной оконечностиThe article prepared by preliminary results of the research grant À/08/97389, supported by the German Academic Exchange Service (July, 2009). The author wishes to thank Administration of the National Antarctic Scientific Center of Ukraine, for access to archival material and reports; supervisors of author's DAAD scholarship, Dr Haike Herata, Head of Antarctic Protected Section, Federal Environmental Agency, and Dr Hans-Ulrich Peter, Head of Polar birds and ecology group, University Jena – for useful comments and suggestions; and Dmyrto Lyashenko, PhD, research officer, Department of Cartography, Institute of Geography, National Academy of Sciences of Ukraine – for help in preparation of maps for this article
Структура широкомасштабного управления в районе станции Академик Вернадский
No full textThe article is devoted to actual issues on methodological provisions for Antarctic activity. Geographical distribution and further diversification of human activities in this region became an environmental threat that needs more comprehensive approach for management in Antarctic in whole and specifically in the region of Ukrainian scientific interests.Стаття присвячена актуальним питанням науково-методичного забезпечення антарктичної діяльності, географічне поширення та подальша диверсифікація якої набувають нових загрозливих масштабів як в Антарктиці в цілому, так і в зоні відповідальності станції Академік Вернадський зокрема.Статья посвящена актуальным вопросам научно-методического обеспечения антарктической деятельности, географическое распространение и дальнейшая диверсификация которой приобретают новые угрожающие масштабы как в Антарктике в целом, так и в районе станции Академик Вернадский в частности. Проанализирована функциональная структура основных типов подохранных территорий Антарктики, показаны причины их высокой концентрации вдоль северо-западной оконечностиThe article prepared by preliminary results of the research grant À/08/97389, supported by the German Academic Exchange Service (July, 2009). The author wishes to thank Administration of the National Antarctic Scientific Center of Ukraine, for access to archival material and reports; supervisors of author's DAAD scholarship, Dr Haike Herata, Head of Antarctic Protected Section, Federal Environmental Agency, and Dr Hans-Ulrich Peter, Head of Polar birds and ecology group, University Jena – for useful comments and suggestions; and Dmyrto Lyashenko, PhD, research officer, Department of Cartography, Institute of Geography, National Academy of Sciences of Ukraine – for help in preparation of maps for this article
The plant-derived naphthoquinone lapachol causes an oxidative stress response in Staphylococcus aureus.
No full textLinzner N, Fritsch VN, Busche T, et al. The plant-derived naphthoquinone lapachol causes an oxidative stress response in Staphylococcus aureus. Free radical biology & medicine. 2020;158:126-136.Staphylococcus aureus is a major human pathogen, which causes life-threatening systemic and chronic infections and rapidly acquires resistance to multiple antibiotics. Thus, new antimicrobial compounds are required to combat infections with drug resistant S. aureus isolates. The 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone lapachol was previously shown to exert antimicrobial effects. In this study, we investigated the antimicrobial mode of action of lapachol in S. aureus using RNAseq transcriptomics, redox biosensor measurements, S-bacillithiolation assays and phenotype analyses of mutants. In the RNA-seq transcriptome, lapachol caused an oxidative and quinone stress response as well as protein damage as revealed by induction of the PerR, HypR, QsrR, MhqR, CtsR and HrcA regulons. Lapachol treatment further resulted in up-regulation of the SigB and GraRS regulons, which is indicative for cell wall and general stress responses. The redox-cycling mode of action of lapachol was supported by an elevated bacillithiol (BSH) redox potential (EBSH), higher endogenous ROS levels, a faster H2O2 detoxification capacity and increased thiol-oxidation of GapDH and the HypR repressor in vivo. The ROS scavenger N-acetyl cysteine and microaerophilic growth conditions improved the survival of lapachol-treated S. aureus cells. Phenotype analyses revealed an involvement of the catalase KatA and the Brx/BSH/YpdA pathway in protection against lapachol-induced ROS-formation in S. aureus. However, no evidence for irreversible protein alkylation and aggregation was found in lapachol-treated S. aureus cells. Thus, the antimicrobial mode of action of lapachol in S. aureus is mainly caused by ROS formation resulting in an oxidative stress response, an oxidative shift of the EBSH and increased protein thiol-oxidation. As ROS-generating compound, lapachol is an attractive alternative antimicrobial to combat multi-resistant S. aureus isolates. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved
Rehabilitation for individuals with post-tuberculosis lung disease
No full textTuberculosis (TB) continues to be a global clinical and public health threat, particularly in low- and middle-income countries. TB care has primarily been centred around timely diagnosis and expanding access to treatment. Post-TB lung disease (PTLD), characterised by persistent respiratory symptoms, functional impairment and structural lung changes, is highly prevalent among TB survivors, with a prevalence ranging from 40% to 90%. This requires an effort to evaluate TB survivors in need of further care at the end of anti-TB treatment, for consideration of pulmonary rehabilitation.This review provides an overview of the current evidence and best practices in pulmonary rehabilitation for PTLD. This article aims to bridge the gap between evidence and practice, supporting tailored, multidisciplinary approaches to pulmonary rehabilitation, building on the existing experiences and challenges from diverse settings. Furthermore, this review supports the ongoing educational efforts of healthcare professionals to reframe TB care, placing long-term health and patient wellbeing at the centre of post-TB management
The alarmone (p)ppGpp confers tolerance to oxidative stress during the stationary phase by maintenance of redox and iron homeostasis in Staphylococcus aureus
No full textFritsch VN, Loi VV, Busche T, et al. The alarmone (p)ppGpp confers tolerance to oxidative stress during the stationary phase by maintenance of redox and iron homeostasis in Staphylococcus aureus. Free radical biology & medicine. 2020.Slow growing stationary phase bacteria are often tolerant to multiple stressors and antimicrobials. Here, we show that the pathogen Staphylococcus aureus develops a non-specific tolerance towards oxidative stress during the stationary phase, which is mediated by the nucleotide second messenger (p)ppGpp. The (p)ppGpp0 mutant was highly susceptible to HOCl stress during the stationary phase. Transcriptome analysis of the (p)ppGpp0 mutant revealed an increased expression of the PerR, SigB, QsrR, CtsR and HrcA regulons during the stationary phase, indicating an oxidative stress response. The (p)ppGpp0 mutant showed a slight oxidative shift in the bacillithiol (BSH) redox potential (EBSH) and an impaired H2O2 detoxification due to higher endogenous ROS levels. The increased ROS levels in the (p)ppGpp0 mutant were shown to be caused by higher respiratory chain activity and elevated total and free iron levels. Consistent with these results, N-acetyl cysteine and the iron-chelator dipyridyl improved the growth and survival of the (p)ppGpp0 mutant under oxidative stress. Elevated free iron levels caused 8 to 31-fold increased transcription of Fe-storage proteins ferritin (ftnA) and miniferritin (dps) in the (p)ppGpp0 mutant, while Fur-regulated uptake systems for iron, heme or siderophores (efeOBU, isdABCDEFG, sirABC and sstADBCD) were repressed. Finally, the susceptibility of the (p)ppGpp0 mutant towards the bactericidal action of the antibiotics ciprofloxacin and tetracycline was abrogated with N-acetyl cysteine and dipyridyl. Taken together, (p)ppGpp confers tolerance to ROS and antibiotics by down-regulation of respiratory chain activity and free iron levels, lowering ROS formation to ensure redox homeostasis in S. aureus. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved
Proteomic Assessment of Tanshinone II A Sodium Sulfonate on Doxorubicin Induced Nephropathy
No full textAlthough doxorubicin (DXR) is an important antineoplastic agent, the serious toxicity mediated by the production of reactive oxygen species has remained a considerable clinical problem. Our hypothesis is that tanshinone II A sodium sulfonate (TSNIIA-SS), which holds significant effects against oxidative stress, protects against DXR-induced nephropathy. Firstly, the antioxidative effects of TSNIIA-SS were confirmed using oxygen radicals absorbance capacities (ORAC) assay in vitro. Then, DXR nephropathy was induced by repeated DXR treatment and verified by kidney index (20.76 +/- 3.04 mg/mm versus 14.76 +/- 3.04 mg/mm, p < 0.001) and histochemical stain. The mice were randomized into three groups.Control group, DXR group and DXR-TSNIIA-SS group. TSNIIA-SS treatment not only improved DXR lesion identified by histochemical stain, but also regulated the expression of several proteins related with the cytoskeleton, oxidative stress and protein synthesis or degradation detected by two-dimensional electrophoresis (2-DE). These data have provided the evidence that TSNIIA-SS is a protective agent against DXR-induced nephropathy.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000289154800015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Integrative & Complementary MedicineMedicine, General & InternalSCI(E)9ARTICLE2395-4093
Identification and biochemical characterization of DC07090 as a novel potent small molecule inhibitor against human enterovirus 71 3C protease by structure-based virtual screening
No full textHand, foot and mouth disease (HFMD) is a serious, highly contagious disease. HFMD caused by Enterovirus 71 (EV71), results in severe complications and even death. The pivotal role of EV71 3C(Pro) in the viral life cycle makes it an attractive target for drug discovery and development to treat HFMD. In this study, we identified novel EV71 3C(Pro) inhibitors by docking-based virtual screening. Totally 50 compounds were selected to test their inhibitory activity against EV71 3C(Pro). The best inhibitor DC07090 exhibited the inhibition potency with an IC50 Value of 21.72 +/- 0.95 mu M without apparent toxicity (CC50 > 200 mu M). To explore structure-activity relationship of DC07090, 15 new derivatives were designed, synthesized and evaluated in vitro enzyme assay accordingly. Interestingly, four compounds showed inhibitory activities against EV71 3C(Pro) and only DC07090 inhibited EV71 replication with an EC50 value of 22.09 +/- 1.07 mu M. Enzyme inhibition kinetic experiments showed that the compound was a reversible and competitive inhibitor. The Ki value was determined to be 23.29 +/- 12.08 mu M. Further molecular docking, MD simulation and mutagenesis studies confirmed the binding mode of DC07090 and EV71 3C(Pro). Besides, DC07090 could also inhibit coxsackievirus A16 (CVA16) replication with an EC50 value of 27.76 +/- 0.88 mu M. Therefore, DC07090 represents a new non-peptidyl small molecule inhibitor for further development of antiviral therapy against EV71 or other picornaviruses. (C) 2016 Elsevier Masson SAS. All rights reserved.National Natural Science Foundation of China [81220108025, 81573351]; State Key Laboratory of Natural and Biomimetic DrugsSCI(E)[email protected]; [email protected]; [email protected]
Syntactic variation in sixteenth-century Portuguese: the position of clitic pronouns
No full textEste trabalho desenvolve, à luz de novos dados, uma proposta apresentada em Martins (2011) relativamente à história da colocação dos pronomes clíticos no português. Aparentemente trata-se de uma mudança sintática com um percurso evolutivo surpreendente por apresentar, depois do século XVI, uma súbita inversão da direção da mudança. O problema de análises anteriores (incluindo as da autora) é, argumenta-se aqui, o de não reconhecerem a existência no português quinhentista (e para além dele) de dois dialetos no que diz respeito à colocação dos pronomes clíticos. Uma observação simplista das fontes textuais mascara a complexidade da situação linguística da época relevante e cria a ilusão de uma linha de continuidade entre objetos distintos. A presente investigação usa o Livro de Cozinha de um Frade Português do Século XVI, editado por Anabela Leal de Barros (2013), como fonte textual especialmente valiosa para a compreensão da história da colocação dos pronomes clíticos.This work reexamines in the light of new data a proposal put forward in Martins (2011) concerning the historical development of clitic placement in Portuguese. Prima facie, this syntactic change follows a surprising path apparently involving a sudden reversal in the direction of change after the sixteenth century. It is argued in this paper that previous analyses, including that of the present author, fail to recognise the existence in sixteenth century and later Portuguese of two (social) dialects as regards the position of clitic pronouns. A simplistic observation of textual sources masks the complexity of the linguistic situation in the historical period in question, creating an illusion of continuity between different objects. The present study uses the sixteenth century cookbook Livro de Cozinha de um Frade Português do Século XVI, edited by Anabela Leal de Barros (2013), as an especially valuable textual source to help us understand the history of clitic placement in Portuguese
