Average phase difference theory and 1∶1 phase entrainment in interlimb coordination

The dynamics of coupled biological oscillators can be modeled by averaging the effects of coupling over each oscillatory cycle so that the coupling depends on the phase difference between the two oscillators and not on their specific states. Average phase difference theory claims that mode locking phenomena can be predicted by the average effects of the coupling influences. As a starting point for both empirical and theoretical investigations, Rand et al. (1988) have proposed d/dt= — K sin ), with phase-locked solutions =arcsin( /K), where is the difference between the uncoupled frequencies and K is the coupling strength. Phase-locking was evaluated in three experiments using an interlimb coordination paradigm in which a person oscillates hand-held pendulums. was controlled through length differences in the left and right pendulums. The coupled frequency _c was varied by a metronome, and scaled to the eigenfrequency _v of the coupled system K was assumed to vary inversely with _c. The results indicate that: (1) and K contribute multiplicatively to (2) =0 or = regardless of K when =0; (3) 0 or regardless of when K is large (relative to ); (4) results (1) to (3) hold identically for both in phase and antiphase coordination. The results also indicate that the relevant frequency is _c/_v rather than _c. Discussion high-lighted the significance of confirming =arcsin(/K) for more general treatments of phase-locking, such as circle map dynamics, and for the 11 phase-entrainment which characterizes biological movement systems.     

Natural selection: a phase transition?

Information has two aspects: a quantity to be called 'extent' and a quality which may be termed 'content' since it deals with meaning. The latter originates via selective self-organization, which can be described also in quantitative physical terms. A prerequisite is the reproducibility of the informational substrate forming the basis of selection. This paper focuses on selection being the analogue of a physical phase transition. In Section 1 the criteria for phase transitions are formulated. Section 2 introduces the concept of information space and describes information as selected points or regions in this space. In Section 3 selection is analyzed in terms of the criteria for phase transitions, and in Section 4 the concept is confronted with experimental data. The conclusion is reached that information content is generated via selection, which can be described as a phase transition in information space.     

Molecular simulation of solid–solid phase transitions

Applications of dl_poly to solid–solid phase transitions are reviewed, with particular attention to how details of the mechanisms of the transitions may be extracted from molecular dynamics simulations. Two examples in molecular crystals are discussed: the order–disorder transition of p-terphenyl initiated at around 200 K by the unlocking of ring flipping; and the rotator phases of n-alkanes with around 20 carbon atoms per chain, showing distinct molecular mechanisms in the dynamics just below the melting points of odd and even chains. Covalent-ionic materials are represented by an application to an aluminophophate molecular sieve, AlPO₄-5.     

Nucleocytoplasmic transport: diffusion channel or phase transition?

How exactly large molecules translocate through nuclear pores has been mysterious for a long time. Recent kinetic measurements of transport rates through the pore have led to a novel translocation model that elegantly combines selectivity with very high transport rates.     

Biomanipulation: the next phase — making it stable

Review of the literature on biomanipulation shows that fish manipulations have occurred through the following methods: piscivore addition; piscivore catch restriction; habitat enhancement; piscivore removal; planktivore exclusion; planktivore removal by selective catch, lake emptying, fish poisons, fish diseases, winterkill, summerkill; habitat expansion or contraction; planktivore addition; and natural events. The methods can be classified as deliberate, inadvertent, or natural, all of which have successful and unsuccessful examples. However, the problem of perpetuation of successful results remains unsolved. It is proposed that this may be resolved through use of a refuge or refuges from among the following: low light intensity refuge; low temperature refuge; low dissolved oxygen refuge; physical concealment refuge; visual clutter refuge; behavior modification refuge; and predator inefficiency refuge. Perhaps through use of such mechanisms large herbivorous zooplankters can continue to exist in lakes. Examples are given. Contribution no. 383 from the Limnological Research center.     

Cdk1: unsung hero of S phase?

Cdk2 has been viewed as a key cell cycle regulator that is essential for S phase progression. The recent discovery that Cdk2 is not required for cell proliferation in mice now shows that other factors must be able to replace Cdk2 in stimulating DNA replication. Experiments performed in Xenopus egg extracts identify the mitotic protein kinases Cdk1/Cyclin B and Cdk1/Cyclin A as likely candidates. These observations raise the intriguing possibility that Cdk1 normally participates in genome duplication in wild type cells.     

Physical properties of detergent-based aqueous two–phase systems

The physical behavior of the binary phase systems of the non-ionic polyoxyethylene detergent Agrimul NRE 1205 and water was investigated. This technical detergent can be used for the large-scale recovery of biomolecules in detergent based aqueous two-phase systems. The phase diagram was determined. It shows significant and unexpected differences to highly purified detergents. Very similar to neat detergents the phase diagram can be influenced by auxiliary chemicals thus shifting the entire phase diagram in general to lower temperatures. This was demonstrated by lowering the cloud-point by various additions. The concentration factor, as an important parameter of a first capture step in purification was investigated and modeled. Auxiliary chemicals, temperature change and change in detergent concentration also influence the viscosity and density of the phases. These experimental data are shown. They can help to explain the separation behavior of proteins. In large-scale separations aqueous two-phase systems are separated using disc-stack centrifuges. It is demonstrated that this is not a feasible method for detergent-based aqueous two-phase extraction and the physical reason is presented. This revised version was published online in July 2006 with corrections to the Cover Date.     

A phase I/II trial of oxidized autologous tumor vaccines during the “watch and wait” phase of chronic lymphocytic leukemia

Based on their activity in patients with advanced stage chronic lymphocytic leukemia (CLL), a phase I/II study was designed to evaluate the feasibility, safety, and efficacy of autologous vaccines made from oxidized tumor cells in patients with earlier stage CLL, and to determine an optimal schedule of injections. Eighteen patients (at risk for disease progression and with white blood cell counts between 15 and 100×10⁶ cells/ml) were injected intramuscularly with 10 ml of oxidized autologous blood (composed mainly of CLL cells) either 12 times over 6 weeks (group 1), 12 times over 16 days (group 2), or 4 times over 6 weeks (group 3). Fourteen out of eighteen patients had Rai stage 0–II disease, while 4/18 had stage III–IV disease but did not require conventional treatment. Partial clinical responses, associated with enhanced anti-tumor T cell activity in vitro, were observed in 5/18 patients of whom three were in group 2. Stable disease was observed in six patients while disease progression appeared not to be affected in the remaining patients. Toxicity was minimal. Vaccination with oxidized autologous tumor cells appears worthy of further investigation and may be a potential alternative to a watch and wait strategy for selected CLL patients.     

Bright light therapy for winter depression--is phase advancing beneficial?

Bright light is the recommended treatment for winter seasonal affective disorder (SAD). Previously we showed that the antidepressant effect of morning (but not evening) light was greater than placebo after 3 weeks of treatment. Here, we determined if the magnitude and direction of circadian rhythm phase shifts produced by the bright light in the previous study were related to the antidepressant effects. Twenty-six SAD patients from the original sample of 96 had their rectal temperature continuously monitored while they participated in a placebo-controlled parallel design conducted over six winters. After a baseline week, there were three treatments for 4 weeks-morning light, evening light, or morning placebo. Bright light was produced by light boxes (approximately 6000 lux). Placebos were sham negative ion generators. All treatments were 1.5 h in duration. Depression ratings were made weekly by blind raters. Circadian phase shifts were determined from changes in the timing of the core body temperature minimum (Tmin). Morning light advanced and evening light delayed the Tmin by about 1 h. The placebo treatment did not alter circadian phase. As the sleep schedule was held constant, morning light increased and evening light decreased the Tmin to wake interval, or phase angle between circadian rhythms and sleep. Phase advance shifts and increases in the phase angle were only weakly associated with antidepressant response. However, there was an inverted U-shaped function showing that regardless of treatment assignment the greatest antidepressant effects occurred when the phase angle was about 3h, and that patients who moved closer to this phase angle benefited more than those who moved farther from it. However 46% of our sample had a phase angle within 30 min of this 3 h interval at baseline. So it does not appear that an abnormal phase angle can entirely account for the etiology of SAD. A majority (75%) of the responders by strict joint criteria had a phase angle within this range after treatment, so it appears that obtaining the ideal phase relationship may account for some, but not all of the antidepressant response. In any case, regardless of the mechanism for the antidepressant effect of morning light, it can be enhanced when patients sleep at the ideal circadian phase and reduced when they sleep at a more abnormal circadian phase.     

Is the “soluble” phase of cells structured?

Evidence suggesting that small molecular-weight precursors as well as polymers such as proteins and RNA, are not homogeneously distributed in the "soluble" phase of the cell, and that there may be, on one hand, hitherto unidentified barriers to normal diffusion within the cell and, on the other, channels through which certain molecular species may move in the cell sap much faster than their diffusion coefficients will permit, is discussed. Some implications of such barriers and channels, if they exist, are stated.     

Protein SUMOylation and phase separation: partners in stress?

Protein SUMOylation is one of the most prevalent post-translational modifications (PTMs) and important for maintaining cellular homeostasis in response to various cellular stresses. Emerging evidence reveals the role of liquid–liquid phase separation (LLPS)/biomolecular condensates in cellular SUMOylation, potentially solving a puzzle regarding the cellular mechanism of SUMOylation regulation.     

Are aberrant phase transitions a driver of cellular aging?

Why do cells age? Recent advances show that the cytoplasm is organized into many membrane‐less compartments via a process known as phase separation, which ensures spatiotemporal control over diffusion‐limited biochemical reactions. Although phase separation is a powerful mechanism to organize biochemical reactions, it comes with the trade‐off that it is extremely sensitive to changes in physical‐chemical parameters, such as protein concentration, pH, or cellular energy levels. Here, we highlight recent findings showing that age‐related neurodegenerative diseases are linked to aberrant phase transitions in neurons. We discuss how these aberrant phase transitions could be tied to a failure to maintain physiological physical‐chemical conditions. We generalize this idea to suggest that the process of cellular aging involves a progressive loss of the organization of phase‐separated compartments in the cytoplasm.

     

Mild cognitive impairment: a prodromal phase of dementia?

Cognitive decline without dementia is common among older persons. A variety of clinical concepts have been introduced in the past 30 years, in order to describe these cognitive deficits arising in older persons. The most frequently used concept is Mild Cognitive Impairment (MCI). MCI is generally seen as a prodromal phase of Alzheimer disease (AD). Several concepts are described, with the neuropsychiatric features and predictors of conversion to dementia c.q. AD. Finally, consequences of preclinically diagnoses for health care are clarified.     

Can hydration forces induce lateral phase separations in lamellar phases?

Large repulsive forces measured between membranes of lamellar lipid phases at low hydration are attributed to hydration interactions which vary widely among lipid species. We include this interaction in a model of lamellar phases of two membrane components (two lipids or lipid and protein). The surface polarization of a mixture is taken as a linear combination of those of the components. The model predicts phase separation at low hydration. This may have important consequences for living cells which are dehydrated either by the osmotic effects of tissue freezing, or by desiccation in unsaturated atmospheres.Abbreviations used ACC cold acclimated protoplasts - NA non cold acclimated protoplasts - DLPC dilauralphosphatidylcholine - DPPC dipalmitoylphosphatidylcholine - DPPE dipalmitoylphosphatidylethanolamine - PC phosphatidylcholine - PE phosphatidylethanolamine - L fluid lamellar phase - H_ii inverse hexagonal phase     

Lipid and phase specificity of α-toxin from S. aureus

The pore forming toxin Hla (α-toxin) from Staphylococcus aureus is an important pathogenic factor of the bacterium S. aureus and also a model system for the process of membrane-induced protein oligomerisation and pore formation. It has been shown that binding to lipid membranes at neutral or basic pH requires the presence of a phosphocholine-headgroup. Thus, sphingomyelin and phosphatidylcholine may serve as interaction partners in cellular membranes. Based on earlier studies it has been suggested that rafts of sphingomyelin are particularly efficient in toxin binding. In this study we compared the oligomerisation of Hla on liposomes of various lipid compositions in order to identify the preferred interaction partners and conditions. Hla seems to have an intrinsic preference for sphingomyelin compared to phosphatidylcholine due to a higher probability of oligomerisation of membrane bound monomer. We also can show that increasing the surface density of Hla-binding sites enhances the oligomerisation efficiency. Thus, preferential binding to lipid rafts can be expected in the cellular context. On the other hand, sphingomyelin in the liquid disordered phase is a more favourable binding partner for Hla than sphingomyelin in the liquid ordered phase, which makes the membrane outside of lipid rafts the more preferred region of interaction. Thus, the partitioning of Hla is expected to strongly depend on the exact composition of raft and non-raft domains in the membrane.