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61.
62.
Michal Maes Aviad Levin Zvi Hayouka Deborah E. Shalev Abraham Loyter Assaf Friedler 《Bioorganic & medicinal chemistry》2009,17(22):7635-7642
The HIV-1 integrase enzyme (IN) catalyzes integration of viral DNA into the host genome. We previously developed peptides that inhibit IN in vitro and HIV-1 replication in cells. Here we present the design, synthesis and evaluation of several derivatives of one of these inhibitory peptides, the 20-mer IN1. The peptide corresponding to the N-terminal half of IN1 (IN1 1–10) was easier to synthesize and much more soluble than the 20-mer IN1. IN1 1–10 bound IN with improved affinity and inhibited IN activity as well as HIV replication and integration in infected cells. While IN1 bound the IN tetramer, its shorter derivatives bound dimeric IN. Mapping the peptide binding sites in IN provided a model that explains this difference. We conclude that IN1 1–10 is an improved lead compound for further development of IN inhibitors. 相似文献
63.
Assaf Shwartz Diederik Strubbe Chris John Butler Erik Matthysen Salit Kark 《Diversity & distributions》2009,15(2):310-318
Aim Some invasive species succeed particularly well and manage to establish populations across a wide variety of regions and climatic conditions. Understanding how biotic and environmental factors facilitate their invasion success remains a challenge. Here, we assess the role of two major hypotheses explaining invasion success: (1) enemy‐release, which argues that invasive species are freed from their native predators and parasites in the new areas; and (2) climate‐matching, which argues that the climatic similarity between the exotic and native range determines the success of invasive populations. Location India, Israel and the UK. Methods We studied the reproductive success of one of the most successful avian invaders, the rose‐ringed parakeet (Psittacula krameri), in its native range (India) and in two introduced regions, varying in their climate conditions (Israel and the UK). We combined literature and field data to evaluate the role of predation pressure and climatic conditions in explaining the differences in reproductive success between the three regions. Results We found significant differences in reproductive success between regions. In accordance with the enemy‐release hypothesis, we discovered that while predation was the main factor responsible for the reduction of fecundity in India, it did not significantly affect the fecundities of parakeet populations in the two introduced regions. In accordance with the climate‐matching hypothesis, we found that in the colder temperate UK, egg infertility was high, resulting in lower fecundities. Populations in both the warmer Mediterranean climate of Israel and in the native Indian range had significantly lower egg infertility and higher fecundities than the UK populations. Main conclusions Our findings support both the enemy‐release and the climate‐matching hypotheses. While release from predators facilitates the reproductive success and therefore the invasiveness of parakeets in both the UK and in Israel, colder climate impedes reproduction and therefore the spread of parakeets in the UK. 相似文献
64.
65.
Ziv Dadon Assaf Cohen Yael M. Szterenlicht Marc V. Assous Yair Barzilay David Raveh-Brawer Amos M. Yinnon Gabriel Munter 《Annals of clinical microbiology and antimicrobials》2017,16(1):68
Background
Streptococcus gordonii is an infrequent cause of infective endocarditis (IE); associated spondylodiskitis has not yet been described in the literature.Purpose
We describe 2 patients who presented with new-onset, severe back pain; blood cultures revealed S. gordonii bacteremia, which led to the diagnosis of spondylodiskitis and IE. We review our 2-decade experience with S. gordonii bacteremia to describe the clinical and epidemiological characteristics of these patients.Results
In our hospital over the last 20 years (1998–2017), a total of 15 patients with S. gordonii bacteremia were diagnosed, including 11 men and 4 women, and the mean age was 65 ± 22 (range 23–95). The most common diagnosis was IE (9 patients), spondylodiskitis (the presented 2 patients, who in addition were diagnosed with endocarditis), necrotizing fasciitis (1), sternitis (1), septic arthritis (1) and pneumonia (1). The 11 patients with IE were treated with penicillin ± gentamicin, or ceftriaxone for 6 weeks, 5 required valve surgery and 10/11 (91%) attained complete cure. The 2 patients with diskitis required 2–3 months of intravenous antibiotics to achieve complete cure.Conclusion
Spondylodiskitis was the presenting symptom of 2/11 (18%) patients with S. gordonii endocarditis. Spondylodiskitis should probably be looked for in patients diagnosed with S. gordonii endocarditis and back pain as duration of antibiotic treatment to achieve complete cure may be considerably longer.66.
67.
de Armas-Ricard M Levicán G Katz A Moser J Jahn D Orellana O 《Biochemical and biophysical research communications》2011,(1):134-139
Prestin, a multipass transmembrane protein whose N- and C-termini are localized to the cytoplasm, must be trafficked to the plasma membrane to fulfill its cellular function as a molecular motor. One challenge in studying prestin sequence-function relationships within living cells is separating the effects of amino acid substitutions on prestin trafficking, plasma membrane localization and function. To develop an approach for directly assessing prestin levels at the plasma membrane, we have investigated whether fusion of prestin to a single pass transmembrane protein results in a functional fusion protein with a surface-exposed N-terminal tag that can be detected in living cells. We find that fusion of the biotin-acceptor peptide (BAP) and transmembrane domain of the platelet-derived growth factor receptor (PDGFR) to the N-terminus of prestin-GFP yields a membrane protein that can be metabolically-labeled with biotin, trafficked to the plasma membrane, and selectively detected at the plasma membrane using fluorescently-tagged streptavidin. Furthermore, we show that the addition of a surface detectable tag and a single-pass transmembrane domain to prestin does not disrupt its voltage-sensitive activity. 相似文献
68.
69.
Noutsou M Duarte AM Anvarian Z Didenko T Minde DP Kuper I de Ridder I Oikonomou C Friedler A Boelens R Rüdiger SG Maurice MM 《Journal of molecular biology》2011,405(3):773-786
The Wnt pathway tumor-suppressor protein Axin coordinates the formation of a critical multiprotein destruction complex that serves to downregulate β-catenin protein levels, thereby preventing target gene activation. Given the lack of structural information on some of the major functional parts of Axin, it remains unresolved how the recruitment and positioning of Wnt pathway kinases, such as glycogen synthase kinase 3β, are coordinated to bring about β-catenin phosphorylation. Using various biochemical and biophysical methods, we demonstrate here that the central region of Axin that is implicated in binding glycogen synthase kinase 3β and β-catenin is natively unfolded. Our results support a model in which the unfolded nature of these critical scaffolding regions in Axin facilitates dynamic interactions with a kinase and its substrate, which in turn act upon each other. 相似文献
70.
Mohler WA Shemer G del Campo JJ Valansi C Opoku-Serebuoh E Scranton V Assaf N White JG Podbilewicz B 《Developmental cell》2002,2(3):355-362
Multinucleate cells are widespread in nature, yet the mechanism by which cells fuse their plasma membranes is poorly understood. To identify animal fusogens, we performed new screens for mutations that abolish cell fusion within tissues of C. elegans throughout development. We identified the gene eff-1, which is expressed as cells acquire fusion competence and encodes a novel integral membrane protein. EFF-1 sequence motifs suggest physicochemical actions that could cause adjacent bilayers to fuse. Mutations in the extracellular domain of EFF-1 completely block epithelial cell membrane fusion without affecting other perfusion events such as cell generation, patterning, differentiation, and adhesion. Thus, EFF-1 is a key component in the mechanism of cell fusion, a process essential to normal animal development. 相似文献