May 1963

Massachusetts Turf and Lawn Grass Council Better Turf Through Research and Educatio

Evolution of NMDA receptor cytoplasmic interaction domains: implications for organisation of synaptic signalling complexes

<p>Abstract</p> <p>Background</p> <p>Glutamate gated postsynaptic receptors in the central nervous system (CNS) are essential for environmentally stimulated behaviours including learning and memory in both invertebrates and vertebrates. Though their genetics, biochemistry, physiology, and role in behaviour have been intensely studied <it>in vitro </it>and <it>in vivo</it>, their molecular evolution and structural aspects remain poorly understood. To understand how these receptors have evolved different physiological requirements we have investigated the molecular evolution of glutamate gated receptors and ion channels, in particular the <it>N</it>-methyl-<it>D</it>-aspartate (NMDA) receptor, which is essential for higher cognitive function. Studies of rodent NMDA receptors show that the C-terminal intracellular domain forms a signalling complex with enzymes and scaffold proteins, which is important for neuronal and behavioural plasticity</p> <p>Results</p> <p>The vertebrate NMDA receptor was found to have subunits with C-terminal domains up to 500 amino acids longer than invertebrates. This extension was specific to the NR2 subunit and occurred before the duplication and subsequent divergence of NR2 in the vertebrate lineage. The shorter invertebrate C-terminus lacked vertebrate protein interaction motifs involved with forming a signaling complex although the terminal PDZ interaction domain was conserved. The vertebrate NR2 C-terminal domain was predicted to be intrinsically disordered but with a conserved secondary structure.</p> <p>Conclusion</p> <p>We highlight an evolutionary adaptation specific to vertebrate NMDA receptor NR2 subunits. Using <it>in silico </it>methods we find that evolution has shaped the NMDA receptor C-terminus into an unstructured but modular intracellular domain that parallels the expansion in complexity of an NMDA receptor signalling complex in the vertebrate lineage. We propose the NR2 C-terminus has evolved to be a natively unstructured yet flexible hub organising postsynaptic signalling. The evolution of the NR2 C-terminus and its associated signalling complex may contribute to species differences in behaviour and in particular cognitive function.</p

Measurement of renin in both renal veins: its use in diagnosis of renovascular hypertension

THE RECENT development of a simple reliable method for measuring plasma renin activity, together with the availability of a safe procedure for obtaining samples of blood from both renal veins, has prompted us to assess the utility of such measurements in the diagnosis of surgically correctable renovascular hypertension. Previous studies of this type have been reported by McPhaul,1 Fitz,2 Kirkendall,3 and Ueda,4 and their associates. A series of 22 patients, diagnosed by conventional measures as having renovascular hypertension, were subjected to operative treatment. Proof of the diagnosis was considered to be established if there was unquestionable improvement in blood pressure after corrective surgery. This is a report of the measurements of renin activity in blood plasma specimens obtained from both renal veins preoperatively and, whenever possible, postoperatively. In addition, plasma renin activity in effluent blood from both kidneys was measured in 13 patients with "essential" hypertension, who were not subjecte

Happiness, Health, or Relationships? Managerial Practices and Employee Well-Being Tradeoffs.

Although managerial practices are often structured with the explicit goal of improving performance by increasing employee well-being, these practices frequently create tradeoffs between different dimensions of employee well-being, whereby one aspect of employee well-being improves but another aspect of employee well-being decreases. We call attention to the multi-dimensional nature of well-being and highlight the importance and prevalence of these well-being tradeoffs. Our review sheds new light on the effects of managerial practices on employee well-being, and offers guidelines for managing and mitigating well-being tradeoffs. Employee well-being is a hot topic in organiza-tional life. The popular press is full of booksthat offer guidelines for protecting and promot-ing employee satisfaction, fulfillment, and health (Bakke, 2005; Dalai Lama &amp; Cutler, 2003). Or-ganizations that foster employee well-being are honored by awards, such as Fortune magazine’s annual list of the “100 Best Companies to Work For, ” and are recognized by current and prospec-tive employees as desirable places to work. Th

Spacings of Quarkonium Levels with the Same Principal Quantum Number

The spacings between bound-state levels of the Schr\"odinger equation with the same principal quantum number $N$ but orbital angular momenta $\ell$ differing by unity are found to be nearly equal for a wide range of power potentials $V = \lambda r^\nu$, with $E_{N \ell} \approx F(\nu, N) - G(\nu,N) \ell$. Semiclassical approximations are in accord with this behavior. The result is applied to estimates of masses for quarkonium levels which have not yet been observed, including the 2P $c \bar c$ states and the 1D $b \bar b$ states.Comment: 20 pages, latex, 3 uuencoded figures submitted separately (process using psfig.sty

Genetic diversity of selected genes that are potentially economically important in feral sheep of New Zealand

Background: Feral sheep are considered to be a source of genetic variation that has been lost from their domestic counterparts through selection. Methods: This study investigates variation in the genes KRTAP1-1, KRT33, ADRB3 and DQA2 in Merino-like feral sheep populations from New Zealand and its offshore islands. These genes have previously been shown to influence wool, lamb survival and animal health. Results: All the genes were polymorphic, but no new allele was identified in the feral populations. In some of these populations, allele frequencies differed from those observed in commercial Merino sheep and other breeds found in New Zealand. Heterozygosity levels were comparable to those observed in other studies on feral sheep. Our results suggest that some of the feral populations may have been either inbred or outbred over the duration of their apparent isolation. Conclusion: The variation described here allows us to draw some conclusions about the likely genetic origin of the populations and selective pressures that may have acted upon them, but they do not appear to be a source of new genetic material, at least for these four genes.This research was supported by the Brian Mason Scientific and Technical Trust

Efficacy of secondary isoniazid preventive therapy among HIVinfected Southern Africans: time to change policy?

Objective. To determine the efficacy of secondary preventive therapy against tuberculosis (TB) among goldminers working in South Africa. Design. An observational study. Methods. The incidence of recurrent TB was compared between two cohorts of HIV-infected miners: one cohort had received secondary preventive therapy with isoniazid and the other had not. Setting. Health service providing comprehensive care for goldminers. Participants. 338 men received secondary preventive therapy and 221 did not. Main outcome measure. Incidence of recurrent TB. Results. The overall incidence of recurrent TB was reduced by 55% among men who received isoniazid preventive therapy (IPT) compared to those who did not (incidence rates 8.6 and 19.1 per 100 person-years respectively, incidence rate ratio 0.45; 95% CI 0.26 – 0.78). The efficacy of isoniazid preventive therapy was unchanged after controlling for CD4 count and age. The number of person-years of isoniazid preventive therapy required to prevent one case of recurrent TB among individuals with a CD4 count < 200/µl and &#8805;&#61472;200/µl was 5 and 19, respectively. Conclusion. Secondary preventive therapy reduces TB recurrence: the absolute impact appears to be greatest among individuals with low CD4 counts. International TB preventive therapy guidelines for HIV-infected individuals need to be expanded to include recommendations for secondary preventive therapy in settings where TB prevalence is high. Southern African Journal of HIV Medicine Vol. 5(3) 2004: 8-1