Isentropic and isothermal compressibilities of the backbone glycyl group of proteins in aqueous solution

The partial molar isentropic compressibilities at infinite dilution, K(S,2)(o), have been determined for the peptides serylglycine, serylglycylglycine and serylglycylglycylglycine in aqueous solution at 25 degrees C. The partial molar volumes at infinite dilution, V(2)(o), have also been determined for these peptides in aqueous solution at the temperatures 15, 30 and 40 degrees C. These results, along with those obtained previously at 25 degrees C, were used to derive the partial molar exansibilities, E(2)(o), of the peptides at 25 degrees C, which in turn were used to convert the isentropic compressibilities into the partial molar isothermal compressibilities at infinite dilution, K(T,2)(o). These K(S,2)(o) and K(T,2)(o) results were used to obtain the partial molar compressibilities of the glycyl group CH(2)CONH at 25 degrees C. The results are compared with those obtained using data for other series of peptides of sequence ala(gly)(n), n=1-4, and (gly)(n), n=2-5.     

Group additivity calculations of the thermodynamic properties of unfolded proteins in aqueous solution: a critical comparison of peptide-based and HKF models

A recent paper in this journal [Amend and Helgeson, Biophys. Chem. 84 (2000) 105] presented a new group additivity model to calculate various thermodynamic properties of unfolded proteins in aqueous solution. The parameters given for the revised Helgeson-Kirkham-Flowers (HKF) equations of state for all the constituent groups of unfolded proteins can be used, in principle, to calculate the partial molar heat capacity, C(o)p.2, and volume, V2(0), at infinite dilution of any polypeptide. Calculations of the values of C(o)p.2 and V2(0) for several polypeptides have been carried out to test the predictive utility of the HKF group additivity model. The results obtained are in very poor agreement with experimental data, and also with results calculated using a peptide-based group additivity model. A critical assessment of these two additivity models is presented.     

Obesity reduction within a generation: the dual roles of prevention and treatment

In 2010, the White House Task Force on Childhood Obesity provided benchmark goals for reducing childhood obesity. We evaluated the balance of prevention and treatment required for achieving Task Force goals in benchmark years 2015, 2020, and 2030. We created a simulation of US birth cohorts (2-19 years) born 2008-2030. For each year, we assumed "old" birth cohorts (part of previous benchmark obesity estimates) would benefit from obesity treatment strategies, and "new" birth cohorts would benefit from obesity prevention strategies. We assessed obesity prevalence that must be achieved through prevention strategies, under varying assumptions of treatment effectiveness. When we assumed a 1% absolute reduction in prevalence through treatment, we found that prevention strategies would need to achieve an obesity prevalence of 12% by 2015, 8% by 2020, and 0.3% by 2030. Because of higher obesity prevalence among minority children, prevention strategies would need to achieve a negative prevalence by 2030, which is implausible. Under more generous assumptions of treatment effectiveness, estimates became positive but remained low. Task Force goals are more difficult to achieve with each benchmark year. Policies must focus on obesity treatment interventions, particularly targeted to racial/ethnic minority children, to make progress in stemming the epidemic.     

Changes in rodent thyroid hormones and cyclic-AMP following treatment with pineal indolic compounds.

Treatment of rats with pineal indolic compounds 5-methoxytryptophol, 5-hydroxytryptophol and serotonin brought about a significant increase in serum thyroxine levels, while serotonin and melatonin caused an increase in thyroid cAMP content with corresponding decrease in the gland's hormones. The total quantity of cAMP in the thyroid was also increased by melatonin in the organ culture system. All these findings would indicate that some of the pineal indoleamines elicit a direct action on the thyroid by stimulating the adenyl cyclase activity and intrathyroidal cAMP, bringing about increased release of thyroxine into the blood stream, and that this is usually not accompanied by adequate synthesis in the gland. Our observation that continuous darkness, which stimulates pineal activity, also brought about an increase in cAMP, concours with our finding of a stimulatory effect of the indolic compounds on thyroid hormone release.     

On the control of stridulation in the acridid grasshopper Omocestus viridulus L.

Summary In tethered, minimally dissected grasshoppers stridulation was elicited by DC brain stimulation. Intracellular recording, stimulation and staining of interneurons in the metathoracic ganglion complex were performed simultaneously with measurements of hindleg movements. The functional significance of interneurons for generation of the stridulation rhythm and bilateral coordination of the hindlegs was tested and quantitatively analysed. Interneurons involved in stridulation were found in the metathoracic and abdominal neuromeres. Typically they included arborizations in a dorsal neuropil parallel to the long axis of the ganglion. Interneuron T3-LI-3 started and drove the ipsilateral rhythm generator. The stridulation rhythm was reset by interneuron A1-AC-1. It was stopped if interneuron T3-AC-1 was stimulated. Bilateral coordination of stridulation movements was based on excitatory and inhibitory pathways between the hemiganglionic networks. Switching in the coordination of hindleg movement patterns was induced by changes in the discharge rate of the bilateral arborizing interneuron T3-LC-4. The hemiganglionic interneurons T3-LI-3 and T3-LI-1 influenced coordination via the activity level within the networks.     

Population sex ratio shift from fledging to recruitment: consequences for demography in a philopatric seabird

In many dimorphic bird species, offspring sex ratio is skewed towards the production of the smaller sex. Offspring sex ratio can be biased in monomorphic birds however, and the demographic consequences of such bias are unknown. Sex-specific mortality and dispersal are fundamental mechanisms of sex ratio adjustment at the population level, but evidence for adjustments is weak and feedback into population dynamics poorly understood. Here, we link sex ratio at fledging with sex-specific subadult return and recruitment at the Banter See common tern Sterna hirundo colony. Using molecular sexing methods and a remote detection system, we permanently tracked individuals from four complete cohorts (n=1171 fledglings) across these life-history stages at their natal colony site, which permitted a structured analysis of sex ratio across multiple seasons. Sex ratio shifted significantly from significant daughter dominance at fledging to higher proportions of natal males among recruits; return and recruitment rates of sons were significantly higher than daughters (p≤0.002). No significant between-year differences were detected. 47.4% of natal male recruits were paired with a non-natal female, but only 37.0% of natal female recruits had a non-natal partner. Elasticity analysis suggested that natal males have a greater influence on natal population growth rate than natal females. Sex biased dispersal is the most probable reason for these results indicating higher emigration to and immigration from other colonies in females, the less territorial and less philopatric sex. This pattern may be related to different gender roles in parental duties and with respect to competition for local resources.     

Partial molar volumes of proteins: amino acid side-chain contributions derived from the partial molar volumes of some tripeptides over the temperature range 10-90 degrees C

The partial molar volumes of tripeptides of sequence glycyl-X-glycine, where X is one of the amino acids alanine, leucine, threonine, glutamine, phenylalanine, histidine, cysteine, proline, glutamic acid, and arginine, have been determined in aqueous solution over the temperature range 10-90 degrees C using differential scanning densitometry . These data, together with those reported previously, have been used to derive the partial molar volumes of the side-chains of all 20 amino acids. The side-chain volumes are critically compared with literature values derived using partial molar volumes for alternative model compounds. The new amino acid side-chain volumes, along with that for the backbone glycyl group, were used to calculate the partial specific volumes of several proteins in aqueous solution. The results obtained are compared with those observed experimentally. The new side-chain volumes have also been used to re-determine residue volume changes upon protein folding.     

Acute myeloid leukemia: treatment over 60

Undertreatment of older patients with acute myeloid leukemia (AML) can explain, in part, their inferior outcome when compared to that of younger patients. In agreement with the benefit seen by patients under age 60 from high-dose cytosine arabinoside (Ara-C), there are dose effects in the over 60s, in particular for daunorubicin, in induction treatment and for the duration of postremission treatment. The use of these effects can partly overcome the mostly unfavorable disease biology in older age AML, as expressed by the absence of favorable and the over-representation of adverse chromosomal abnormalities as well as the expression of drug resistance. We recommend an adequate dosage of 60 mg/m2 daunorubicin on 3 days in combination with standard dose Ara-C and 6-thioguanine given for induction and consolidation, and followed by a prolonged monthly maintenance chemotherapy for at least 1 year's duration. Further improvements in supportive care may help to deliver additional antileukemic cytotoxicity. As a novel approach, nonmyeloablative preparative regimens may open up the possibility of allogeneic transplantation for older patients with AML. Other new options like multidrug resistance modulators, antibody targeted therapies and molecular targeting are under clinical investigation. A questionnaire study in patients with AML showed that, according to patients' self-assessment, intensive and prolonged treatment did not result in a diminished quality of life. This finding did not vary by age, under or over 60 years. As the median age in this disease is more than 60 years, the adequate management of AML in older patients remains the major challenge.