Nse5/6 is a negative regulator of the ATPase activity of the Smc5/6 complex.

The multi-component Smc5/6 complex plays a critical role in the resolution of recombination intermediates formed during mitosis and meiosis, and in the cellular response to replication stress. Using recombinant proteins, we have reconstituted a series of defined Saccharomyces cerevisiae Smc5/6 complexes, visualised them by negative stain electron microscopy, and tested their ability to function as an ATPase. We find that only the six protein 'holo-complex' is capable of turning over ATP and that its activity is significantly increased by the addition of double-stranded DNA to reaction mixes. Furthermore, stimulation is wholly dependent on functional ATP-binding pockets in both Smc5 and Smc6. Importantly, we demonstrate that budding yeast Nse5/6 acts as a negative regulator of Smc5/6 ATPase activity, binding to the head-end of the complex to suppress turnover, irrespective of the DNA-bound status of the complex.

An Innovative, Interdisciplinary Model of Care for Inpatient Child Psychiatry: an Overview.

There are profound effects of childhood psychiatric disorders on families and communities. Given that each year over half a million youth receive mental health services through inpatient psychiatric hospitals, focus on assessment and treatment strategies for this group is paramount The purpose of this paper is to present an overview of an innovative, evidenced-based model of inpatient child psychiatric care that challenges commonly used traditional practices of inpatient child psychiatry. The highlighted model utilizes an interdisciplinary approach to clarify psychiatric diagnoses; create a comprehensive biopsychosocial formulation of the child and family; establish a rational medication regimen; provide individually tailored recommendations; and address the "revolving door" of repeated psychiatric hospitalizations. Descriptive analyses are presented that provide demographic, developmental, and psychiatric characteristics of the children admitted to the unit. The potential benefits of using this innovative model with developmentally and psychiatrically complex children are discussed.

3D Structure of fish muscle myosin filaments.

Myosin filaments isolated from goldfish (Carassius auratus) muscle under relaxing conditions and viewed in negative stain by electron microscopy have been subjected to 3D helical reconstruction to provide details of the myosin head arrangement in relaxed muscle. Previous X-ray diffraction studies of fish muscle (plaice) myosin filaments have suggested that the heads project a long way from the filament surface rather than lying down flat and that heads in a single myosin molecule tend to interact with each other rather than with heads from adjacent molecules. Evidence has also been presented that the head tilt is away from the M-band. Here we seek to confirm these conclusions using a totally independent method. By using 3D helical reconstruction of isolated myosin filaments the known perturbation of the head array in vertebrate muscles was inevitably averaged out. The 3D reconstruction was therefore compared with the X-ray model after it too had been helically averaged. The resulting images showed the same characteristic features: heads projecting out from the filament backbone to high radius and the motor domains at higher radius and further away from the M-band than the light-chain-binding neck domains (lever arms) of the heads.