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Nir eyal

Yifat Elharar, Shai Schlussel, Nir Hecht, Michael M Meijler, Eyal Gur
Pup, a ubiquitin analog, tags proteins for degradation by the bacterial proteasome. As an intracellular proteolytic system, the Pup-proteasome system (PPS) must be carefully regulated to prevent excessive protein degradation. Currently, those factors underlying PPS regulation remain poorly understood. Here, experimental analysis combined with theoretical modeling of in vivo protein pupylation revealed how the basic PPS design allows stable and controlled protein pupylation. Specifically, the recycling of Pup when targets are degraded allows the PPS to maintain steady state levels of protein pupylation and degradation at a rate limited by proteasome function, and at a pupylome level limited by Pup concentrations...
April 25, 2017: FEBS Journal
Amir Arav, Or Friedman, Yehudit Natan, Eyal Gur, Nir Shani
In 2016 over 5 million reconstructive procedures were performed in the USA. The recent successes of clinical vascularized composite allotransplantations (VCA), hand and face transplantations included, established the tremendous potential of these life-enhancing reconstructions. Nevertheless, Due to limited availability and lifelong immunosuppression, application is limited. Long term banking of composite transplants may increase the availability of esthetically compatible parts with partial or complete HLA matching, reducing the risk of rejection and the immunosuppressive burden...
April 19, 2017: American Journal of Transplantation
Toma E Tomov, Roman Tsukanov, Yair Glick, Yaron Berger, Miran Liber, Dorit Avrahami, Doron Gerber, Eyal Nir
Realization of bioinspired molecular machines that can perform many and diverse operations in response to external chemical commands is a major goal in nanotechnology, but current molecular machines respond to only a few sequential commands. Lack of effective methods for introduction and removal of command compounds and low efficiencies of the reactions involved are major reasons for the limited performance. We introduce here a user interface based on a microfluidics device and single-molecule fluorescence spectroscopy that allows efficient introduction and removal of chemical commands and enables detailed study of the reaction mechanisms involved in the operation of synthetic molecular machines...
April 25, 2017: ACS Nano
Nir Eyal, Marc Lipsitch
During the 2014-2015 Ebola outbreak in Guinea, Liberia and Sierra Leone, many opposed the use of individually randomised controlled trials to test candidate Ebola vaccines. For a raging fatal disease, they explained, it is unethical to relegate some study participants to control arms. In Zika and future emerging infections, similar opposition may hinder urgent vaccine research, so it is best to address these questions now. This article lays out the ethical case for individually randomised control in testing vaccines against many emerging infections, including lethal infections in low-income countries, even when at no point in the trial do the controls receive the countermeasures being tested...
April 10, 2017: Journal of Medical Ethics
Yochai Wolf, Anat Shemer, Michal Polonsky, Mor Gross, Alexander Mildner, Simon Yona, Eyal David, Ki-Wook Kim, Tobias Goldmann, Ido Amit, Mathias Heikenwalder, Sergei Nedospasov, Marco Prinz, Nir Friedman, Steffen Jung
Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart...
April 3, 2017: Journal of Experimental Medicine
Ariel Zilberlicht, Nir Haya, Ido Feferkorn, Eyal Goldschmidt, Anis Kaldawy, Yoram Abramov
AIMS: Patients with overactive bladder (OAB) often describe somatic, psychological, and sexual triggers for their symptoms. The aim of this study was to characterize these triggers and assess their impact on patients' symptoms and quality of life (QoL). METHODS: Patients who visited our urogynecologic clinic between August 2015 and March 2016 and diagnosed with OAB syndrome were asked to fill a questionnaire comprising 34 statements regarding SOmatic, Psychological, and Sexual Triggers for OAB (SOPSETO)...
February 21, 2017: Neurourology and Urodynamics
Shlomo Magdassi, Shoshi Bar-David, Yael Friedman-Levi, Ehud Zigmond, Chen Varol, Guy Lahat, Joseph Klausner, Sara Eyal, Eran Nizri
BACKGROUND: Tumor localization may pose a significant challenge during minimally invasive rectal resection. Near-infrared (NIR) imaging can penetrate biological tissue and afford tumor localization from the external surface of the rectum. Our aim was to develop an NIR-based tool for rectal tumor imaging that can be administered intravenously. METHODS: We prepared indocyanine-green (ICG)-loaded liposomes by sonication. Liposomes were evaluated for their size and morphology...
February 1, 2017: Surgical Innovation
Menahem Pirchi, Roman Tsukanov, Rashid Khamis, Toma E Tomov, Yaron Berger, Dinesh C Khara, Hadas Volkov, Gilad Haran, Eyal Nir
The function of biological macromolecules involves large-scale conformational dynamics spanning multiple time scales, from microseconds to seconds. Such conformational motions, which may involve whole domains or subunits of a protein, play a key role in allosteric regulation. There is an urgent need for experimental methods to probe the fastest of these motions. Single-molecule fluorescence experiments can in principle be used for observing such dynamics, but there is a lack of analysis methods that can extract the maximum amount of information from the data, down to the microsecond time scale...
December 29, 2016: Journal of Physical Chemistry. B
Inessa Semenenko, Emma Portnoy, Mohammed Aboukaoud, Serge Guzy, Miriam Shmuel, Gal Itzhak, Sara Eyal
Aim: The multidrug resistance protein 1 (MDR1; P-glycoprotein) has been associated with efflux of chemotherapeutic agents from tumor cells and with poor patient prognosis. This study evaluated the feasibility of non-invasive, non-radioactive near infrared (NIR) imaging methodology for detection of MDR1 functional activity in tumors. Methods: Initial accumulation assays were conducted in MDR1-overexpressing MDCK cells (MDCK-MDR1) and control MDCK cells (MDCK-CT) using the NIR dyes indocyanine green (ICG), IR-783, IR-775, rhodamine 800, XenoLight DiR, and Genhance 750, at 0...
2016: Frontiers in Pharmacology
Justin Healy, Rebecca Hope, Jacqueline Bhabha, Nir Eyal
With the expansion of antiretroviral treatment programmes, many children and adolescents with HIV in sub-Saharan Africa could expect to live healthy lives. Yet adolescents have the highest levels of poor antiretroviral adherence and of loss to follow-up compared with other age groups. This can lead to increased morbidity and mortality, to the development of drug-resistant strains, and to high societal costs. While financial incentives have been extensively used to promote medication adherence among adults, their use among adolescents remains rare...
September 19, 2016: Journal of Medical Ethics
Inna Solomonov, Eldar Zehorai, Dalit Talmi-Frank, Sharon G Wolf, Alla Shainskaya, Alina Zhuravlev, Elena Kartvelishvily, Robert Visse, Yishai Levin, Nir Kampf, Diego Adhemar Jaitin, Eyal David, Ido Amit, Hideaki Nagase, Irit Sagi
It is well established that the expression profiles of multiple and possibly redundant matrix-remodeling proteases (e.g., collagenases) differ strongly in health, disease, and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in vivo activity can lead to extremely diverse tissue-remodeling outcomes. We observed that proteolysis of collagen-rich natural extracellular matrix (ECM), performed uniquely by individual homologous proteases, leads to distinct events that eventually affect overall ECM morphology, viscoelastic properties, and molecular composition...
September 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
Eyal Lotan, Omer Weissman, Larisa Guranda, Nir Kleinmann, Rachel Schor, Harry Winkler, Orith Portnoy
OBJECTIVE: The purpose of this study was to determine the value of clinical parameters and radiologic findings on unenhanced CT to the choice between interventional and conservative management for patients with acute renal colic. MATERIALS AND METHODS: Unenhanced CT records of 183 consecutive patients with acute renal colic were retrospectively reviewed. Urolithiasis was confirmed at both unenhanced CT and clinical follow-up findings of 80 patients (study group)...
November 2016: AJR. American Journal of Roentgenology
Ofir Regev, Maayan Korman, Nir Hecht, Ziv Roth, Nadav Forer, Raz Zarivach, Eyal Gur
Pupylation, the bacterial equivalent of ubiquitylation, involves the conjugation of a prokaryotic ubiquitin-like protein (Pup) to protein targets. In contrast to the ubiquitin system, where many ubiquitin ligases exist, a single bacterial ligase, PafA, catalyzes the conjugation of Pup to a wide array of protein targets. As mediators of target recognition by PafA have not been identified, it would appear that PafA alone determines pupylation target selection. Previous studies indicated that broad specificity and promiscuity are indeed inherent PafA characteristics that probably dictate which proteins are selected for degradation by the Pup-proteasome system...
October 9, 2016: Journal of Molecular Biology
Steven G Deeks, Sharon R Lewin, Anna Laura Ross, Jintanat Ananworanich, Monsef Benkirane, Paula Cannon, Nicolas Chomont, Daniel Douek, Jeffrey D Lifson, Ying-Ru Lo, Daniel Kuritzkes, David Margolis, John Mellors, Deborah Persaud, Joseph D Tucker, Françoise Barre-Sinoussi, Galit Alter, Judith Auerbach, Brigitte Autran, Dan H Barouch, Georg Behrens, Marina Cavazzana, Zhiwei Chen, Éric A Cohen, Giulio Maria Corbelli, Serge Eholié, Nir Eyal, Sarah Fidler, Laurindo Garcia, Cynthia Grossman, Gail Henderson, Timothy J Henrich, Richard Jefferys, Hans-Peter Kiem, Joseph McCune, Keymanthri Moodley, Peter A Newman, Monique Nijhuis, Moses Supercharger Nsubuga, Melanie Ott, Sarah Palmer, Douglas Richman, Asier Saez-Cirion, Matthew Sharp, Janet Siliciano, Guido Silvestri, Jerome Singh, Bruno Spire, Jeffrey Taylor, Martin Tolstrup, Susana Valente, Jan van Lunzen, Rochelle Walensky, Ira Wilson, Jerome Zack
Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.
August 2016: Nature Medicine
Nir Eyal
This is an afterword to the JME symposium on the benefit/risk ratio challenge in clinical research, and the case of HIV cure. It notes implications of the symposium for research ethics in general.
February 2017: Journal of Medical Ethics
Nir Eyal
This piece introduces the JME symposium 'The benefit/risk ratio challenge in clinical research, and the case of HIV cure.'
February 2017: Journal of Medical Ethics
Nir Horesh, Eyal Klang, Aviad Gravetz, Yehonatan Nevo, Imri Amiel, Michal Marianne Amitai, Danny Rosin, Mordechai Gutman, Oded Zmora
BACKGROUND: Jejunal diverticulitis is a rare clinical entity often overlooked by physicians as a cause for abdominal pain. Although diagnostic capabilities improved in recent years, there is little data about diverticular disease in the proximal small bowel. The aim of this study is to present the clinical course and management in a series of eight cases of jejunal diverticulitis and possible therapeutic interventions. METHODS: A cohort retrospective analysis of all patients admitted for acute jejunal diverticulitis between January 2010 and June 2015 was conducted...
August 2016: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
Nir Sorkin, Amir Rosenblatt, Eyal Cohen, Oded Ohana, Chaim Stolovitch, Gad Dotan
PURPOSE: To compare the standard Ishihara booklet with color-vision-testing smartphone applications. METHODS: A prospective observational diagnostic study on 42 normal trichromats and 38 color-deficient subjects. Patients were presented with three color vision tests in random order: an Ishihara test booklet and two color-vision-testing smartphone applications: Eye2Phone and the Color Vision Test application (CVT app). Sensitivity and specificity of the electronic tests was compared with Ishihara results, and in each one of these applications every plate was individually analyzed for success/failure rate...
July 2016: Optometry and Vision Science: Official Publication of the American Academy of Optometry
Yifat Elharar, Ziv Roth, Nir Hecht, Ron Rotkopf, Isam Khalaila, Eyal Gur
The proper functioning of any biological system depends on the coordinated activity of its components. Regulation at the genetic level is, in many cases, effective in determining the cellular levels of system components. However, in cases where regulation at the genetic level is insufficient for attaining harmonic system function, posttranslational regulatory mechanisms are often used. Here, we uncover posttranslational regulatory mechanisms in the prokaryotic ubiquitin-like protein (Pup)-proteasome system (PPS), the bacterial equivalent of the eukaryotic ubiquitin-proteasome system...
March 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
Mark Zimmerman, Sharada Shah, Rabina Shakya, Bal Sundar Chansi, Kashim Shah, Daniel Munday, Nir Eyal, Bruce Hayes
PROBLEM: District hospitals in Nepal struggle to provide essential services such as caesarean sections. APPROACH: Retention of health workers is critical to the delivery of long-term, quality health-care services. To promote retention and enhance performance in rural public hospitals, the Government of Nepal and the Nick Simons Institute progressively implemented a rural staff support programme in remote hospitals. After competitive selection for a compulsory-service scholarship and training, family practice doctors who could do basic surgery, orthopaedics and obstetrics were hired under a binding three-year contract in each participating hospital...
January 1, 2016: Bulletin of the World Health Organization
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