Molecular evolution of the period gene in Drosophila athabasca

We measured nucleotide variability within and between the three semispecies of the Drosophila athabasca complex, at the period (per) gene by using a polymerase chain reaction-based four-cutter restriction- enzyme analysis. The levels of polymorphism varied considerably between the three semispecies. Our results for per, combined with previous data for X-linked allozymes, suggest that the X chromosome in the western- northern semispecies is less variable than expected under an equilibrium-neutral model. Both the pattern of divergence between the semispecies and a cladistic clustering of per haplotypes support the previously hypothesized grouping of eastern A and eastern B as the two most recently diverged semispecies. A 21-bp in-frame segment in the region of per which shares sequence similarity with the neuronal development gene single minded is deleted in all eastern A and eastern B flies examined but is present in all of the western-northern flies and all other published per sequences. Despite these hints that there may be significant differences at the per gene between the semispecies, especially the western-northern group versus the two eastern groups, there is no compelling evidence that per is involved in the mating song differences between the semispecies.      

Human müllerian inhibiting substance: enhanced purification imparts biochemical stability and restores antiproliferative effects.

Separation of copurifying protease activity from recombinant human Müllerian inhibiting substance (rhMIS) bound to a monoclonal antibody immunoaffinity column by a high-salt wash results in cleaner preparations of rhMIS resistant to cleavage upon storage. In addition, an inhibitor of rhMIS antiproliferative activity is removed. Proteolytic cleavages produced by either a copurifying protease or exogenous plasmin occur at residues 229 and 427 but do not abolish rhMIS biological activity. This report details the modified immunoaffinity column isolation protocol suitable for proteins such as rhMIS and describes the biochemical and antiproliferative properties of this protein.     

Proposed follow up programme after curative resection for lower third oesophageal cancer

Cyclins are indispensable elements of the cell cycle and derangement of their function can lead to cancer formation. Recent studies have also revealed more mechanisms through which cyclins can express their oncogenic potential. This review focuses on the aberrant expression of G1/S cyclins and especially cyclin D and cyclin E; the pathways through which they lead to tumour formation and their involvement in different types of cancer. These elements indicate the mechanisms that could act as targets for cancer therapy.     

Strategies to Improve Survival from Surgery for Heart Valve Implantation in Sheep

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by difficulties in restarting the heart, causing significant on-table mortality. Therefore, optimal cardioprotective management during heart valve implantation in sheep is essential. However, little is known about successful cardioprotective management techniques in sheep. This article reports our experience in the cardioprotective management of 20 female sheep that underwent surgical aortic valve replacement with a stented tissue-engineered heart valve prosthesis. During this series of experiments, we modified our cardioprotection protocol to improve survival. We emphasize the importance of total body hypothermia and external cooling of the heart. Furthermore, we recommend repeated cardioplegia administration at 20 min intervals during surgery, with the final dosage of cardioplegia given immediately before the de-clamping of the aorta. To reduce the number of defibrillator shocks during a state of ventricular fibrillation (VF), we have learned to restart the heart by reclamping the aorta, administering cardioplegia until cardiac arrest, and de-clamping the aorta thereafter. Despite these encouraging results, more research is needed to finalize a protocol for this procedure.

Sheep are a commonly used and well-validated model for cardiovascular research, particularly for heart valve research, as blood pressure, heart rate, cardiac output, and intracardiac pressures are similar between sheep and humans. Sheep are particularly useful for heart valve research because observable changes in implanted heart valve bioprostheses that would take several years to develop in humans are apparent after only a few months in sheep.^3,11 This feature allows the ovine model to provide relevant and important information about heart valve prostheses in a relatively short time span. The first preclinical step in developing novel heart valves is to test the valve in the pulmonary position in sheep. This surgical technique is relatively easy, as the procedure can be performed on a beating heart in a low-pressure circulation. However, aortic valve surgery is the most frequently performed valvular surgical intervention in human patients.¹² Thus, an important next step is to prove the clinical applicability of a new valve by testing the valve in-vivo in the aortic position in an animal model. In contrast to pulmonary valve replacement, aortic valve replacement must be performed on an arrested heart, which makes the surgical procedure significantly more complex. The sheep is a difficult model for aortic valve replacements due to its narrow annulus, short distance between the annulus and coronary ostia, a short ascending aorta, and difficulty in de-airing of the heart prior to suturing the aortotomy.¹⁹ Consequently, high on-table mortality rates, ranging from 9% to 33%, have been reported.^1,18,21,24 Furthermore, the incidence of mortality during the first 30 d after surgery, directly related to the surgical procedure, is often high, ranging from 17% to 50%.^1,2,16,18,21 Therefore, optimizing cardioprotective strategies during surgery would improve postoperative survival. However, little is known about protective strategies in sheep. In the current series of experiments, we implanted stented, tissue engineered, aortic heart valve prostheses in 20 adult domestic sheep and developed cardioprotective techniques to increase survival rates. In this observational study, we share our experience and insights regarding cardioprotective management to potentially improve the outcome of future surgeries that require an arrested heart in sheep.