Solvophobic and solvophilic contributions in the water-to-aqueous guanidinium chloride transfer free energy of model peptides

We study the solvation free energy of two different conformations (helix and extended) of two different peptides (deca-alanine and deca-glycine) in two different solvents (water and aqueous guanidinium chloride, GdmCl). The free energies are obtained using the quasichemical organization of the potential distribution theorem, an approach that naturally provides the repulsive (solvophobic or cavity) and attractive (solvophilic) contributions to solvation. The solvophilic contribution is further parsed into a chemistry contribution arising from solute interaction with the solvent in the first solvation shell and a long-range contribution arising from non-specific interactions between the solute and the solvent beyond the first solvation shell. The cavity contribution is obtained for two different envelopes, $\Sigma_{SE}$ which theory identifies as the solvent excluded volume and a larger envelope ($\Sigma_G$) beyond which solute-solvent interactions are Gaussian. For both envelopes, the cavity contribution in water is proportional to the surface area of the envelope. The same does not hold for GdmCl(aq), revealing limitations of using molecular area to assess solvation energetics, especially in mixed solvents. The $\Sigma_G$-cavity contribution predicts that GdmCl(aq) should favor the more compact state, contrary to the role of GdmCl in unfolding proteins. The chemistry contribution attenuates this effect, but still the net local (chemistry plus $\Sigma_G$-packing) contribution is inadequate in capturing the role of GdmCl. With the inclusion of the long-range contribution, which is dominated by van~der~Waals interaction, aqueous GdmCl favors the extended conformation over the compact conformation. Our finding emphasizes the importance of weak, but attractive, long-range dispersion interactions in protein solution thermodynamics

A bright future for colloidal quantum dot lasers

A

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Formulation and characterization of chewable tablets of paracetamol and metoclopramide hydrochloride

The present study was aimed to formulate and characterized chewable tablets of Paracetamol and Metoclopramide hydrochloride. Paracetamol and Metoclopramide hydrochloride is an oral fixed dose combination for the preparation of chewable tablets used to treat the symptoms of migraine as it comply with physicochemical properties require to improve the effectiveness of therapeutic agent, better bioavailability, improved patient acceptance (especially pediatrics) through pleasant taste, patient convenience; need no water for swallowing, fasten the absorption of drug and for rapid onset of action. The investigation was carried out to study the effect of different proportion of Avicel 101, Avicel 102 and moringa gum, which are superdisintegrating agents. The chewable tablets of Paracetamol and Metoclopramide hydrochloride were prepared by wet granulation method. Several physicochemical parameters like thickness, diameter, hardness, %weight variation, %loss in weight, drug content, disintegration time, in vitro dissolution studies, kinetics of drug release and stability studies for all the formulations were studied and were found within the acceptance limits. Formulation F7 (containing moringa gum 1%) showed the best cumulative drug release and disintegration time of 56 secs

Cell-cycle-dependent transcriptional and translational DNA-damage response of 2 ribonucleotide reductase genes in S. cerevisiae

The ribonucleotide reductase (RNR) enzyme catalyzes an essential step in the production of deoxyribonucleotide triphosphates (dNTPs) in cells. Bulk biochemical measurements in synchronized Saccharomyces cerevisiae cells suggest that RNR mRNA production is maximal in late G1 and S phases; however, damaged DNA induces RNR transcription throughout the cell cycle. But such en masse measurements reveal neither cell-to-cell heterogeneity in responses nor direct correlations between transcript and protein expression or localization in single cells which may be central to function. We overcame these limitations by simultaneous detection of single RNR transcripts and also Rnr proteins in the same individual asynchronous S. cerevisiae cells, with and without DNA damage by methyl methanesulfonate (MMS). Surprisingly, RNR subunit mRNA levels were comparably low in both damaged and undamaged G1 cells and highly induced in damaged S/G2 cells. Transcript numbers became correlated with both protein levels and localization only upon DNA damage in a cell cycle-dependent manner. Further, we showed that the differential RNR response to DNA damage correlated with variable Mec1 kinase activity in the cell cycle in single cells. The transcription of RNR genes was found to be noisy and non-Poissonian in nature. Our results provide vital insight into cell cycle-dependent RNR regulation under conditions of genotoxic stress.Massachusetts Institute of Technology. Center for Environmental Health Sciences (deriving from NIH P30-ES002109)National Institutes of Health (U.S.) (grant R01-CA055042)National Institutes of Health (U.S.) (grant DP1-OD006422)Massachusetts Institute of Technology (CSBi Merck-MIT Fellowship