The mother-to-child transition

Recent genome-scale analyses have uncovered the magnitude of the changes in mRNA populations that occur during the maternal-to-zygotic transition in early Drosophila embryos as well as two of the key regulators of this process, SMAUG and bicoid stability factor (BSF).     

The protein-solvent glass transition

The protein dynamical transition and its connection with the liquid-glass transition (GT) of hydration water and aqueous solvents are reviewed. The protein solvation shell exhibits a regular glass transition, characterized by steps in the specific heat and the thermal expansion coefficient at the calorimetric glass temperature T_G ≈ 170 K. It implies that the time scale of the structural α-relaxation has reached the experimental time window of 1–100 s. The protein dynamical transition, identified from elastic neutron scattering experiments by enhanced amplitudes of molecular motions exceeding the vibrational level [1], probes the α-process on a shorter time scale. The corresponding liquid-glass transition occurs at higher temperatures, typically 240 K. The GT is generally associated with diverging viscosities, the freezing of long-range translational diffusion in the supercooled liquid. Due to mutual hydrogen bonding, both, protein- and solvent relaxational degrees of freedom slow down in paralled near the GT. However, the freezing of protein motions, where surface-coupled rotational and librational degrees of freedom are arrested, is better characterized as a rubber-glass transition. In contrast, internal protein modes such as the rotation of side chains are not affected. Moreover, ligand binding experiments with myoglobin in various glass-forming solvents show, that only ligand entry and exit rates depend on the local viscosity near the protein surface, but protein-internal ligand migration is not coupled to the solvent. The GT leads to structural arrest on a macroscopic scale due to the microscopic cage effect on the scale of the intermolecular distance. Mode coupling theory provides a theoretical framework to understand the microcopic nature of the GT even in complex systems. The role of the α- and β-process in the dynamics of protein hydration water is evaluated. The protein-solvent GT is triggered by hydrogen bond fluctuations, which give rise to fast β-processes. High-frequency neutron scattering spectra indicate increasing hydrogen bond braking above T_G.     

Experimental use of free gastric flaps for the repair of pharyngoesophageal defects.

The repair of large pharyngoesophageal defects was accomplished experimentally in 16 dogs with revascularized free flaps from the greater curvature of the stomach. These flaps were based on the gastroepiploic vessels, and they were anastomosed to the carotid artery and external jugular vein in the neck. The procedure had a low mortality and did not lead to peptic ulceration or hyperchlorhydria in these animals.     

The alkaline transition of swine pepsinogen

At alkaline pH, swine pepsinogen is reversibly inactivated in a transition which involves the cooperative release of two protons from the molecule and is governed by a pK = 9. Stopped flow kinetic studies on the absorbance changes accompanying this reaction show that it can be resolved into two steps, with increasing pH; a slow conformational change, whose amplitude follows the ionisation curve of one group of pK = 9.9, followed by a rapid pH dependent conformational change, linked to a group of pK = 8.2. The pH dependence of the rate of the slow step is interpreted to show the presence of a protonated group which cannot ionise in the neutral form of the zymogen, but is in slow equilibrium with a form where it titrates with a pK = 6.8. At the same time, a histidine in the amino terminal region of the protein becomes reactive to diethyl pyrocarbonate, suggesting this to be the group which triggers the reaction.     

The triplex-hairpin transition in cytosine-rich DNA

We present a theoretical study of the self-complementary single-stranded 30-mer d(TC*TTC*C*TTTTCCTTCTC*CCGAGAAGGTTTT) (PDB ID: 1b4y) that was designed to form an intramolecular triplex by folding back twice on itself. At neutral pH the molecule exists in a duplex hairpin conformation, whereas at acidic pH the cytosines labeled by an asterisk (*) are protonated, forming Hoogsteen hydrogen bonds with guanine of a GC Watson-Crick basepair to generate a triplex. As a first step in an investigation of the energetics of the triplex-hairpin transition, we applied the Bashford-Karplus multiple site model of protonation to calculate the titration curves for the two conformations. Based on these data, a two-state model is used to study the equilibrium properties of transition. Although this model properly describes the thermodynamics of the protonation-deprotonation steps that drive the folding-unfolding of the oligomer, it cannot provide insight into the time-dependent mechanism of the process. A series of molecular dynamics simulations using the ff94 force field of the AMBER 6.0 package was therefore run to explore the dynamics of the folding/unfolding pathway. The molecular dynamics method was combined with Poisson-Boltzmann calculations to determine when a change in protonation state was warranted during a trajectory. This revealed a sequence of elementary protonation steps during the folding/unfolding transition and suggests a strong coupling between ionization and folding in cytosine-rich triple-helical triplexes.     

Differential changes in human pharyngoesophageal motor excitability induced by swallowing,pharyngeal stimulation,and anesthesia

We investigated the effects of water swallowing, pharyngeal stimulation, and oropharyngeal anesthesia on corticobulbar and craniobulbar projections to human swallowing musculature. Changes in pathway excitability were measured via electromyography from swallowed intraluminal pharyngeal and esophageal electrodes to motor cerebral and trigeminal nerve magnetic stimulation. After both water swallowing and pharyngeal stimulation, pharyngoesophageal corticobulbar excitability increased (swallowing: pharynx = 59 +/- 12%, P < 0.001; esophagus = 45 +/- 20%, P < 0.05; pharyngeal stimulation: pharynx = 76 +/- 19%, P < 0.001; esophagus = 45 +/- 23%, P = 0.05), being early with swallowing but late with stimulation. By comparison, craniobulbar excitability increased early after swallowing but remained unaffected by pharyngeal stimulation. After anesthesia, both corticobulbar (pharynx =-24 +/- 10%, P < 0.05; esophagus = -28 +/- 7%, P < 0.01) and craniobulbar excitability showed a late decrease. Thus swallowing induces transient early facilitation of corticobulbar and craniobulbar projections, whereas electrical stimulation promotes delayed facilitation mainly in cortex. With removal of input, both corticobulbar and craniobulbar projections show delayed inhibition, implying a reduction in motoneuron and/or cortical activity.     

The transition density for multiple neutral alleles

For a single genetic locus with multiple alleles, Littler and Fackerall (1975, Biometrics 31, 117–123) found the transition density of the allelic proportions in the case of no mutation and no selection. Their method is found to be suitable for a model in which symmetric mutation is allowed between alleles. The sampling probabilities and moments are found. Watterson's (1977, Genetics 85, 789–814) test for selection is found to be non-robust for non-stationary populations.     

The glass transition temperatures of sugar mixtures

We measured the glass transition temperatures of mono-, di-, and trisaccharide mixtures using differential scanning calorimeter (DSC) and analyzed these temperatures using the Gordon-Taylor equation. We found that the glass transition temperatures of monosaccharide-monosaccharide and disaccharide-disaccharide mixtures could be described by the conventional Gordon-Taylor equation. However, the glass transition temperatures of monosaccharide-disaccharide and monosaccharide-trisaccharide mixtures deviated from the conventional Gordon-Taylor equation and the amount of deviation in the monosaccharide-trisaccharide mixtures was larger than those in the monosaccharide-disaccharide mixtures. From these results, we conclude that the size and shape of the sugars play an important role in the glass transition temperature of the mixtures.     

The reproductive endocrinology of the menopausal transition

The menopause transition is a dynamic process that begins with the first appearance of menstrual irregularity and ends with a woman's final menstrual period. As ovarian follicle numbers dwindle, the hypothalamic-pituitary-ovarian axis enters a state of compensated failure. In this state, elevated FSH is capable of maintaining relatively regular folliculogenesis and ovulation, but fertility is reduced. Eventually, this state of compensated failure cannot be sustained, and the ovary becomes unable to produce functioning follicles. Recent multicenter studies from several countries have addressed the pattern of change in hormones and a model form reproductive aging has been developed that helps explain the changes in hormone patterns and fertility that accompany menopause. Perhaps more important, the hormonal changes of the menopausal transition may be predictive of future disease risk. This review will undertake an explanation of the current literature on this topic.