7 research outputs found
Antibacterial activity of a newly developed peptide-modified lysin against Acinetobacter baumannii and Pseudomonas aeruginosa
No full textThe global emergence of multidrug-resistant (MDR) bacteria is a growing threat to public health worldwide. Natural bacteriophage lysins are promising alternatives in the treatment of infections caused by Gram-positive pathogens, but not Gram-negative ones, like Acinetobacter baumannii and Pseudomonas aeruginosa, due to the barriers posed by their outer membranes. Recently, modifying a natural lysin with an antimicrobial peptide was found able to break the barriers, and to kill Gram-negative pathogens. Herein, a new peptide-modified lysin (PlyA) was constructed by fusing the cecropin A peptide residues 1–8 (KWKLFKKI) with the OBPgp279 lysin and its antibacterial activity was studied. PlyA showed good and broad antibacterial activities against logarithmic phase A. baumannii and P. aeruginosa, but much reduced activities against the cells in stationary phase. Addition of outer membrane permeabilizers (EDTA and citric acid) could enhance the antibacterial activity of PlyA against stationary phase cells. Finally, no antibacterial activity of PlyA could be observed in some bio-matrices, such as culture media, milk, and sera. In conclusion, we reported here a novel peptide-modified lysin with significant antibacterial activity against both logarithmic (without OMPs) and stationary phase (with OMPs) A. baumannii and P. aeruginosa cells in buffer, but further optimization is needed to achieve broad activity in diverse bio-matrices
Engineered bacteriophage lysins as novel anti-infectives
No full textBacteriophage lysins, the highly evolved special peptidoglycan hydrolases, have long been demonstrated to be an effective enzybiotics in various infectious models. The modular structure of lysins makes it possible to design bioengineered lysins that have desired properties, such as higher activity, broader killing spectrum. Moreover, lysins can even be engineered to kill gram-negative bacterial pathogens from without, a property that is unavailable for natural lysins. In this era of ever increased multidrug resistant pathogens, engineered lysins represent a new class of enzybiotics that are powerful and readily available to fight the antimicrobial resistance
Stigmatic bodies: The corporeal Qiu Miaojin
No full textB1 - Research Book ChaptersDeposited with permission of University of Hawaii PressQiu Miaojin (1969–1995) is Taiwan’s best-known lesbian author. In local lesbian (nütongzhi) subcultures, Qiu’s books are frequently cited as classics, particularly her 1994 novel The Crocodile’s Journal (Eyu shouji), the first novel in Taiwan’s modern literary history to be written by an author commonly known to be a lesbian that takes erotic relationships between women as its central theme. Qiu’s fiction is much celebrated, too, in the mainstream literary establishment; The Crocodile’s Journal won the prestigious China Times Honorary Prize for Literature for Qiu posthumously, following her suicide in mid-1995. Qiu’s unique literary style—mingling cerebral, experimental language use, psychological realism, biting social critique through allegory, and a surrealist effect deriving from the use of arrestingly unusual metaphors—is strongly influenced by both European and Japanese literary and cinematic modernisms. Although her fiction has been compared, in its principal subject-matter, to Radclyffe Hall’s 1920s classic of lesbian alienation, The Well of Loneliness, most frequently cited in Qiu’s writings are male modernist and postmodernist ‘masters’ (many of whose work shows a strongly homoerotic aesthetic) including Andre Gide, Jean Genet, Kobo Abe, Yukio Mishima, Haruki Murakami, Andrei Tarkovsky, and Derek Jarman—locally, Qiu’s work has been critiqued for this apparent masculinist bias. Qiu’s early short stories ‘Zero Degree’ (‘Linjiedian,’ 1988) and ‘Platonic Hair’ (‘Bolatu zhi fa,’ 1990), to be discussed in this chapter, appeared in her first collection, The Revelry of Ghosts (Guide kuanghuan) in 1991, following their earlier serialization in local daily newspapers. They are Qiu’s first works to treat thematically homoerotic desire between women
A novel pro-inflammatory protein of Streptococcus suis 2 induces the Toll-like receptor 2-dependent expression of pro-inflammatory cytokines in RAW 264.7 macrophages via activation of ERK1/2 pathway
No full textStreptococcus suis 2 is an important swine pathogen and an emergent zoonotic pathogen. Excessive inflammation caused by S. suis is responsible for the high levels of early mortality observed in septic shock-like syndrome cases. However, the mechanisms through which S. suis 2 (SS2) causes excessive inflammation remain unclear. Thus, this study aimed to identify novel pro-inflammatory mediators that play important roles in the development of therapies against SS2 infection. In this study, the novel pro-inflammatory protein HP0459, which was encoded by the SSUSC84_0459 gene, was discovered. The stimulation of RAW 264.7 macrophages with recombinant HP0459 protein induced the expression of pro-inflammatory cytokines (IL-1β, MCP-1 and TNF-α). Compared with the wild-type strain, the isogenic knockout of HP0459 in SS2 led to reduced production of pro-inflammatory cytokines in RAW264.7 macrophages and in vivo. The pro-inflammatory activity of HP0459 was significantly reduced by an antibody against Toll-like receptor 2 (TLR2) in RAW264.7 macrophages and was lower in TLR2-deficient (TLR2-/-) macrophages than in wild-type (WT) macrophages. Furthermore, specific inhibitors of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathways significantly decreased the HP0459-induced pro-inflammatory cytokine production, and a western blot assay showed that HP0459 stimulation induced the activation of the ERK1/2 pathway. Taken together, our data indicate that HP0459 is a novel pro-inflammatory mediator of SS2 and induces TLR2-dependent pro-inflammatory activity in RAW264.7 macrophages through the ERK1/2 pathway
FMRI evidence for the interaction between orthography and phonology in reading Chinese compound words
No full textCompound words make up a major part of modern Chinese vocabulary. Behavioral studies have demonstrated that access to lexical semantics of compound words is driven by the interaction between orthographic and phonological information. However, little is known about the neural underpins of compound word processing. In this fMRI study, we asked participants to perform lexical decision to pseudohomophones, which were constructed by replacing one or both constituents of two-character compound words with orthographically dissimilar homophonic characters. Mixed pseudohomophones, which shared the first constituent with the base words, were more difficult to reject than non-pseudohomophone nonwords. This effect was accompanied by the increased activation of bilateral inferior frontal gyrus (IFG), left inferior parietal lobule (IPL), and left angular gyrus. The pure pseudohomophones, which shared no constituent with their base words, were rejected as quickly as nonword controls and did not elicit any significant neural activation. The effective connectivity of a phonological pathway from left IPL to left IFG was enhanced for the mixed pseudohomophones but not for pure pseudohomophones. These findings demonstrated that phonological activation alone, as in the case of the pure pseudohomophones, is not sufficient to drive access to lexical representations of compound words, and that orthographic information interacts with phonology, playing a gating role in the recognition of Chinese compound words
Stochastic Learning in Oxide Binary Synaptic Device for Neuromorphic Computing
No full textHardware implementation of neuromorphic computing is attractive as a computing paradigm beyond the conventional digital computing. In this work, we show that the SET (off-to-on) transition of metal oxide resistance switching memory becomes probabilistic under a weak programming condition. The switching variability of the binary synaptic device implements a stochastic learning rule. Such stochastic SET transition was statistically measured and modeled for a simulation of a winner-take-all network for competitive learning. The simulation illustrates that with such stochastic learning, the orientation classification function of input patterns can be effectively realized. The system performance metrics were compared between the conventional approach using the analog synapse and the approach in this work that employs the binary synapse utilizing the stochastic learning. The feasibility of using binary synapse in the neurormorphic computing may relax the constraints to engineer continuous multilevel intermediate states and widens the material choice for the synaptic device design
ДВИЖЕНИЕ ИЛИ ПОКОЙ: ЧТО ПРЕДПОЧТИТЕЛЬНЕЕ ДЛЯ ПАЦИЕНТОВ С ЮВЕНИЛЬНЫМ ИДИОПАТИЧЕСКИМ АРТРИТОМ?
No full textThe paper reviews the literature dealing with juvenile idiopathic arthritis (JIA) prognosis, patient physical activity, its role in the development of functional problems that cause limited vital activity and reduced quality of life, as well as the efficiency of physical exercises (exercise therapy (ET)) in the treatment of this disease. It stresses the relationship between physical developmental delay in patients with JIA and the occurrence of psychological and social problems. There are data of publications about the need for physical loads for patients with various rheumatic diseases, as well as for adults. Special attention is paid to the good endurance of ET that is identified by a number of authors as an additional treatment for JIA patients, which improves their functional status, but fails to affect the course and outcome of the disease. The author analyzes survey papers on the multidisciplinary rehabilitation of children, adolescents in particular, and the importance of science-based propaganda of active lifestyle. By having analyzed the literature, the author concludes that it is expedient to include ET into standard treatment for patients with JIA. Представлен обзор литературы, посвященной прогнозу при ювенильном идиопатическом артрите (ЮИА), физической активности пациентов, ее роли в развитии функциональных проблем, вызывающих ограничение жизнедеятельности и снижение качества жизни, а также эффективности физических упражнений (exercise therapy, лечебной физкультуры – ЛФК) в лечении данной патологии. Подчеркивается связь между отставанием в физическом развитии больных ЮИА и возникновением у них психологических и социальных проблем. Приведены данные публикаций о необходимости физических нагрузок для пациентов с различной ревматологической патологией, в том числе и взрослых. Особое внимание уделено хорошей переносимости ЛФК, которую ряд авторов называет дополнительным лечением больных ЮИА, улучшающим функциональное состояние, но не влияющим на течение и исход заболевания. Проанализированы обзорные работы, посвященные мультидисциплинарной проблеме реабилитации детей и, особенно, подростков и важности научно обоснованной пропаганды активного образа жизни. На основании проведенного анализа литературы сделан вывод о целесообразности включения лечебной гимнастики в стандарты лечения больных ЮИА.
