Beyond Suez---the Anglo-Israeli relationship 1956--1958.

This thesis examines the Anglo-Israeli relationship from early 1956 to the summer of 1958 against the wider background of the Cold War, super power rivalries and upheavals in the Middle East. In the period under study Anglo-Israeli relations went through two major phases. The first phase, from early 1956 to early 1957 was marked by growing tension in the Middle East when relations between Israel and Britain were at best cool and at times hostile. The second phase, from March 1957 to summer/autumn 1958, was characterised by the growing instability of pro- Western states in the region and by an eventual breakthrough in Anglo-Israeli relations. Anglo-Israeli relations were overshadowed by Britain's interests in the Middle East, which were essentially to keep oil supply routes and communication with the Indian ocean open. It was only the Iraqi coup d'etat in 1958 and the collapse of the Baghdad Pact which paved the way for the change in Anglo-Israeli relations. This dramatic set of events, coupled with Israel's willingness to cooperate with the British military rescue operation in Jordan, led to a less antagonistic and distrustful relationship resulting in a definite change in Whitehall's attitudes. This development poses the question of whether the origins of this change lay in the semi-cooperation that had taken place between Britain and Israel during the Suez war or whether the latter was merely a temporary act of collusion that was followed by a retreat into old patterns of political behaviour. This study aims to demonstrate that as far as Anglo-Israeli relations were concerned it was the upheavals after the Suez war and primarily the crisis during the summer of 1958 that led to an enhanced understanding between Israel and Britain. In other words it was not the Suez war that brought an end to the traditional British interests and view of the region, but rather that the fundamental change came in 1958 due to the specific crises that developed during that year. This thesis, based predominately on Israeli and British diplomatic sources, political diaries, and memoirs seeks to provide a broad study on theses events highlight issues as they were seen from Jerusalem and London, and to deliver a comparative study which has hitherto been absent. This research takes into consideration the various components that influenced Israel's foreign and defence policy before and after the Suez war such as coalition considerations, public morale and support as well as financial, Jewish immigration and financial limitations, as far as these issues were reflected in the diplomatic sources. Furthermore most of the books and research written on Suez as well as on Israeli foreign policy, do not go beyond early 1957, and no serious study of Anglo-Israeli relations in the period following the Suez war period has yet been published

The Calbindin-D28k binding site on inositol monophosphatase may allow inhibition independent of the lithium site of action

Among numerous reported biochemical effects the lithium-inhibitable enzyme inositol-monophosphatase (IMPase) remains a viable target for lithium's therapeutic mechanism of action. Calbindin-D28k (calbindin) interacts with IMPase enhancing its activity. In the present study in silico modeling of IMPase-calbindin binding using the program MolFit indicated that the 55-66 amino acid segment of IMPase anchors calbindin via Lys59 and Lys61 with a glutamate in between (Lys-Glu-Lys motif). The model further suggested that the Lys-Glu-Lys motif interacts with residues Asp24 and Asp26 of calbindin. Indeed, we found that differently from wildtype calbindin, IMPase was not activated by mutated calbindin in which Asp24 and Asp26 were replaced by alanine. Calbindin's effect was significantly reduced by a peptide with the sequence of amino acids 58-63 of IMPase (peptide 1) and by six amino-acid peptides including at least part of the Lys-Glu-Lys motif. The three amino-acid peptide Lys-Glu-Lys or five amino-acid peptides containing this motif were ineffective. Intracerebroventricular administration of peptide 1 resulted in a significant antidepressant-like reduced immobility in the Porsolt forced swim test (FST) compared with mice treated with a scrambled peptide or artificial cerebrospinal fluid. Based on the sequence of peptide 1, and to potentially increase the peptide's stability, cyclic and linear pre-cyclic analog peptides were synthesized. One cyclic and one linear pre-cyclic analog peptides exhibited an inhibitory effect on calbindin-activated brain IMPase activity in vitro. These findings may lead to the development of molecules capable of inhibiting IMPase activity at an alternative site than that of lithium

Conformational changes and loose packing promote E. coli Tryptophanase cold lability

<p>Abstract</p> <p>Background</p> <p>Oligomeric enzymes can undergo a reversible loss of activity at low temperatures. One such enzyme is tryptophanase (Trpase) from <it>Escherichia coli</it>. Trpase is a pyridoxal phosphate (PLP)-dependent tetrameric enzyme with a Mw of 210 kD. PLP is covalently bound through an enamine bond to Lys270 at the active site. The incubation of holo <it>E. coli </it>Trpases at 2°C for 20 h results in breaking this enamine bond and PLP release, as well as a reversible loss of activity and dissociation into dimers. This sequence of events is termed cold lability and its understanding bears relevance to protein stability and shelf life.</p> <p>Results</p> <p>We studied the reversible cold lability of <it>E. coli </it>Trpase and its Y74F, C298S and W330F mutants. In contrast to the holo <it>E. coli </it>Trpase all apo forms of Trpase dissociated into dimers already at 25°C and even further upon cooling to 2°C. The crystal structures of the two mutants, Y74F and C298S in their apo form were determined at 1.9Å resolution. These apo mutants were found in an open conformation compared to the closed conformation found for <it>P. vulgaris </it>in its holo form. This conformational change is further supported by a high pressure study.</p> <p>Conclusion</p> <p>We suggest that cold lability of <it>E. coli </it>Trpases is primarily affected by PLP release. The enhanced loss of activity of the three mutants is presumably due to the reduced size of the side chain of the amino acids. This prevents the tight assembly of the active tetramer, making it more susceptible to the cold driven changes in hydrophobic interactions which facilitate PLP release. The hydrophobic interactions along the non catalytic interface overshadow the effect of point mutations and may account for the differences in the dissociation of <it>E. coli </it>Trpase to dimers and <it>P. vulgaris </it>Trpase to monomers.</p

Infectious disease burden and antibiotic prescribing in primary care in Israel

Abstract Background Antibiotics are frequently prescribed at many of the visits to primary care clinics, often for conditions for which they provide no benefit, including viral respiratory tract infections. Objectives The aim was to evaluate primary care visits due to infectious diseases, and to estimate antibiotic prescribing and antibiotic dispensing by pharmacies. Methods Diagnosis of infectious disease, antibiotic prescribing and dispensing data at the individual patient level were extracted for 2015 from Clalit Health Services’ electronic medical records and linked to determine the condition for which the antimicrobial was prescribed. Results There were 6.6 million visits due to infections, representing 22% of all primary care visits. The most common events were upper respiratory tract infections (38%) and pharyngitis (10%). Highest prescription rates were for urinary tract infections (80%), otitis media (64%), pharyngitis (71%), sinusitis (63%), and lower respiratory tract infections (76%). The highest rates of undispensed prescriptions were for acute gastroenteritis, urinary tract infections, and pharyngitis (24, 23, and 16%, respectively). Conclusions Infectious diseases constitute a heavy burden on primary care, with overprescribing of antibiotics. Intervention to reduce unwarranted antibiotic use is needed. In pediatric care, interventions should focus on better controlling antibiotic consumption and encouraging adherence to guidelines for upper respiratory tract infections, pharyngitis, and otitis media. In adults interventions should aim to monitor antibiotic prescribing for upper respiratory tract infections and improve adherence to guidelines for urinary tract infections

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Additional file 1: Appendix. Diagnostic conditions ICD9 classification and antibiotic recommendation reference