Y. Mosesson and Y. Yarden
Polyubiquitylation of cellular proteins has long been recognized as a prelude to a degradative fate in proteasomes. In recent years, however, ubiquitin conjugation has emerged as a regulatory strategy of considerable versatility. Most notably, monoubiquitylation is attributed an intimate role in trafficking of membrane proteins between various cellular compartments. Diverse classes of transmembrane proteins from across the eukaryotic spectrum (e.g., epidermal growth factor-receptor and other receptor tyrosine kinases) become modified with monoubiquitin molecules. Monoubiquitylation of substrates, in turn, regulates both their endocytosis at the plasma membrane and sorting in endosomes for delivery to lysosomes or vacuoles. A mechanistic rationale lies in the identification of a growing list of ubiquitin-binding domains carried by a variety of endocytic adaptor proteins. Thus, ubiquitin-conjugated membrane proteins may form extensive contacts with the endocytic machinery. Further, ubiquitin-binding adaptors and other endocytic components are, likewise, often monoubiquitylated. In this case, ubiquitin conjugation may serve to enhance intermolecular avidity in cargo-bound endocytic complexes, or alternatively, to mediate timely inactivation of ubiquitin-binding adaptors. Interestingly, the ubiquitin/endocytosis interface is appropriated by pathogenic organisms, for instance, during budding of viruses from host-infected cells. Moreover, compromised ubiquitin-mediated transport of certain signaling receptors is associated with disease states, including oncogenic transformation.
E. Rabinovich, D. Bussi, I. Shapira, G. Alalouf, C. Lipson, Y. Elkabetz, M. Glickman, M. Bajorek and S. Bar-Nun
L. Kaplun, Y. Ivantsiv, A. Bakhrat, R. Tzirkin, K. Baranes, N. Shabek, and D. Raveh
We describe a unique E3, the F-box protein, Ufo1, of yeast. Ufo1 recruits the mating switch endonuclease, Ho, to the SCF complex for ubiquitylation. In addition to the F-box and WD40 protein-protein interaction domains found in all F-box proteins, Ufo1 has a unique domain comprising multiple copies of the ubiquitin-interacting motif. Ufo1 interacts with the UbL-UbA protein, Ddi1, via its UIMs, and this is required for turnover of SCF Ufo1 complexes. This is a novel function for an UbL-UbA protein. Deletion of the genomic UFO1 UIMs is lethal and our data indicate that Ufo1ΔUIM acts as a dominant negative leading to inhibition of the SCF pathway of substrate degradation and to cell cycle arrest. Furthermore, we found that Ddi1 is required for the final stages of degradation of Ho endonuclease. In the absence of Ddi1, Ho does not form a complex with the 19S RP and is stabilized. Stabilization of Ho leads to perturbation of the cell cycle and to the formation of multi-budded cells. Our experiments uncover a novel role for the ubiquitin-proteasome system in maintenance of genome stability.
C. Weissman, L.A. Eidelman, R. Pizov, I. Matot, N. Klein and R. Cohn
Background: Anesthesiology is a vital specialty that permits the safe and humane performance of painful procedures. Most Israeli anesthesiologist are immigrants, while only a minimal number of Israeli medical school graduates enter the specialty. Unfortunately, the supply of immigrant physicians is declining due to falling immigration rates.
Objectives: To examine the current Israeli anesthesiology workforce and project future needs.
Methods: Demographic and professional information about Israeli hospital anesthesiologists was solicited from anesthesiology department heads. Data were also gathered about the past, present and projected future growth, age distribution and birth rate of the Israeli population. Needs and demand-based analyses were used to project future anesthesiology workforce requirements.
Results: Data about 711 anesthesiologists were obtained from 30 hospital anesthesiology department heads. Eighty-seven anesthesiologists (12.2%) graduated from Israeli medical schools and 459 (64.6%) graduated from medical schools in the former Soviet Union. Among the 154 anesthesiology residents were ≤ 40 years old, and only 13 (8.4%) graduated from Israeli medical schools There are approximately 10.8 anesthesiologists per 100,000 population. Projections for 2005–2015 revealed a need for 250–300 new anesthesiologists.
Conclusions: The anesthesiology workforce is predominantly composed of immigrants. This has vast implications for the future viability of the specialty because of the continuing reduction in immigration, the lack of interest in the specialty by Israeli medical school graduates, and the projected need for many new anesthesiologists to replace retirees and to provide care to a growing and aging population
F. Magora, S. Cohen, M. Shochina and E. Dayan
Background: Virtual reality immersion has been advocated as a new effective adjunct to drugs for pain control. The attenuation of pain perception and unpleasantness has been attributed to the patient's attention being diverted from the real, external environment through immersion in a virtual environment transmitted by an interactive 3-D software computer program via a VR helmet.
Objectives: To investigate whether VR immersion can extend the amount of time subjects can tolerate ischemic tourniquet pain.
Methods: The study group comprised 20 healthy adult volunteers. The pain was induced by an inflated blood pressure cuff during two separate, counterbalanced, randomized experimental conditions for each subject: one with VR and the control without VR exposure. The VR equipment consisted of a standard computer, a lightweight helmet and an interactive software game.
Results: Tolerance time to ischemia was significantly longer for VR conditions than for those without (P < 0.001). Visual Analogue Scale (0–10) ratings were recorded for pain intensity, pain unpleasantness, and the time thought about pain. Affective distress ratings of unpleasantness and of time thought about pain were significantly lower during VR as compared with the control condition (P < 0.003 and 0.001 respectively).
Conclusions: The VR method in pain control was shown to be beneficial. The relatively inexpensive equipment will facilitate the use of VR immersion in clinical situations. Future research is necessary to establish the optimal selection of clinical patients appropriate for VR pain therapy and the type of software required according to age, gender, personality, and cultural factors.
O. Bronshtein, V. Katz, T. Freud and R. Peleg
Background: Physicians in the community work on a tight and often pressured schedule; verbal and non-verbal techniques to terminate the patient-physician encounter are therefore necessary.
Objectives: To characterize ways of terminating the encounter.
Methods: Using a structured questionnaire we observed seven family physicians and nine consultants and recorded patient-physician encounters to assess techniques for terminating the encounter.
Results: In all, 320 encounters were recorded, 179 (55.9%) by consultants and 141 (44.1%) by family physicians. The mean duration of the encounters was 9.02 ± 5.34 minutes. The mean duration of encounters with family physicians was longer than consultants (10.39 vs. 7.93 minutes, P < 0.001). In most cases the encounter ended with the patient receiving printed documentation from the physician (no difference between family physicians and consultants). Consultants were more likely to end the encounter with a positive concluding remark such as “feel good” or “be well” (P < 0.01). There was no single occasion where termination of the encounter was initiated by the patient.
Conclusions: Giving a printed document to the patient appears to be perceived by both patients and physicians as an accepted way to end an encounter. Another good way to end the encounter is a positive greeting such as “feel good” or “be well.”
R. Cervera and R.A. Asherson
H. Mazeh, A. Nissan, N. Simanovsky and N. Hiller
L. Kachko, C.M. Platis, R. Efrat and J. Katz
E. Miller, Y. Barnea, A. Karin, D. Leshem, J. Weiss, L. Leider-Trejo and S. Schneebaum
U. Abadi, R. Hadary, L.Shilo, A. Shabun, G. Greenberg and S. Kovatz