It's all in the timing: coital frequency and fertility awareness-based methods of family planning

Fertility awareness-based methods of family planning help women to identify the days of the cycle they should avoid unprotected intercourse to prevent pregnancy. Therefore using fertility awareness-based methods influences the timing of sexual activity, which may affect the nature of the sexual relationship. Data are used from the clinical trials of two fertility awareness-based methods--the Standard Days Method and the TwoDay Method--to determine the frequency and timing of intercourse during the cycle, and the determinants of coital frequency. The mean coital frequency of study participants was similar to that reported by users of other methods. Results suggest that coital frequency increases with consecutive cycles of method use. At the same time the frequency of intercourse during the identified fertile days and during menses decreases. This evidence implies a behavioural change as couples get more experience using their method and communicating about the fertile days. Coital frequency was also influenced by the method used and by the study sites. Potential differences between the methods and sites that may contribute to this effect are discussed.     

Cortical plasticity: It's all the range!

When rats learn a motor skill, synaptic potentials in the motor cortex are enhanced. A new study has revealed that this learning-induced enhancement limits further synaptic potentiation, but not synaptic depression. These findings support the view that activity-dependent synaptic plasticity is the brain's memory mechanism.     

It's all in the timing: Modeling isovolumic contraction through development and disease with a dynamic dual electromechanical bioreactor system

This commentary discusses the rationale behind our recently reported work entitled “Mimicking isovolumic contraction with combined electromechanical stimulation improves the development of engineered cardiac constructs,” introduces new data supporting our hypothesis, and discusses future applications of our bioreactor system. The ability to stimulate engineered cardiac tissue in a bioreactor system that combines both electrical and mechanical stimulation offers a unique opportunity to simulate the appropriate dynamics between stretch and contraction and model isovolumic contraction in vitro. Our previous study demonstrated that combined electromechanical stimulation that simulated the timing of isovolumic contraction in healthy tissue improved force generation via increased contractile and calcium handling protein expression and improved hypertrophic pathway activation. In new data presented here, we further demonstrate that modification of the timing between electrical and mechanical stimulation to mimic a non-physiological process negatively impacts the functionality of the engineered constructs. We close by exploring the various disease states that have altered timing between the electrical and mechanical stimulation signals as potential future directions for the use of this system.     

Metarhizium: jack of all trades,master of many

The genus Metarhizium and Pochonia chlamydosporia comprise a monophyletic clade of highly abundant globally distributed fungi that can transition between long-term beneficial associations with plants to transitory pathogenic associations with frequently encountered protozoans, nematodes or insects. Some very common ‘specialist generalist’ species are adapted to particular soil and plant ecologies, but can overpower a wide spectrum of insects with numerous enzymes and toxins that result from extensive gene duplications made possible by loss of meiosis and associated genome defence mechanisms. These species use parasexuality instead of sex to combine beneficial mutations from separate clonal individuals into one genome (Vicar of Bray dynamics). More weakly endophytic species which kill a narrow range of insects retain sexuality to facilitate host–pathogen coevolution (Red Queen dynamics). Metarhizium species can fit into numerous environments because they are very flexible at the genetic, physiological and ecological levels, providing tractable models to address how new mechanisms for econutritional heterogeneity, host switching and virulence are acquired and relate to diverse sexual life histories and speciation. Many new molecules and functions have been discovered that underpin Metarhizium associations, and have furthered our understanding of the crucial ecology of these fungi in multiple habitats.     

When clocks go bad: neurobehavioural consequences of disrupted circadian timing

Progress in unravelling the cellular and molecular basis of mammalian circadian regulation over the past decade has provided us with new avenues through which we can explore central nervous system disease. Deteriorations in measurable circadian output parameters, such as sleep/wake deficits and dysregulation of circulating hormone levels, are common features of most central nervous system disorders. At the core of the mammalian circadian system is a complex of molecular oscillations within the hypothalamic suprachiasmatic nucleus. These oscillations are modifiable by afferent signals from the environment, and integrated signals are subsequently conveyed to remote central neural circuits where specific output rhythms are regulated. Mutations in circadian genes in mice can disturb both molecular oscillations and measurable output rhythms. Moreover, systematic analysis of these mutants indicates that they can express an array of abnormal behavioural phenotypes that are intermediate signatures of central nervous system disorders. Furthermore, the response of these mutants to psychoactive drugs suggests that clock genes can modify a number of the brain’s critical neurotransmitter systems. This evidence has led to promising investigations into clock gene polymorphisms in psychiatric disease. Preliminary indications favour the systematic investigation of the contribution of circadian genes to central nervous system disease.     

Adiponectin—It's all about the modifications

Adiponectin is an adipokine (adipocyte-derived hormone) with multiple salutary effects. It is secreted into the circulation as low molecular weight (LMW) and high molecular weight (HMW) multimers with the latter being more metabolically active. Extensive post-translational modifications (PTMs) are required for efficient adiponectin multimerisation and secretion. Recent studies have identified novel PTMs that contribute to the efficacy of adiponectin production and clearance. Thiol-mediated retention of adiponectin occurs during transit through the ER, via direct interactions with chaperones including ERp44 and DsbA-L, and facilitates multimerisation and secretion. Interestingly, this appears to be in direct competition with adiponectin succination. Adiponectin is also subject to O-glycosylation/sialylation which affects clearance from the circulation. In contrast to most adipokines, reduced adiponectin levels, particularly HMW, contribute to the aetiology of obesity-related diseases such as type 2 diabetes and cardiovascular disease. Strategies that modulate processes governing PTM of adiponectin represent attractive therapeutic approaches.     

Peripheral clocks and their role in circadian timing: insights from insects.

Impressive advances have been made recently in our understanding of the molecular basis of the cell-autonomous circadian feedback loop; however, much less is known about the overall organization of the circadian systems. How many clocks tick in a multicellular animal, such as an insect, and what are their roles and the relationships between them? Most attempts to locate clock-containing tissues were based on the analysis of behavioural rhythms and identified brain-located timing centres in a variety of animals. Characterization of several essential clock genes and analysis of their expression patterns revealed that molecular components of the clock are active not only in the brain, but also in many peripheral organs of Drosophila and other insects as well as in vertebrates. Subsequent experiments have shown that isolated peripheral organs can maintain self-sustained and light sensitive cycling of clock genes in vitro. This, together with earlier demonstrations that physiological output rhythms persist in isolated organs and tissues, provide strong evidence for the existence of functionally autonomous local circadian clocks in insects and other animals. Circadian systems in complex animals may include many peripheral clocks with tissue-specific functions and a varying degree of autonomy, which seems to be correlated with their sensitivity to external entraining signals.     

Bayesian random local clocks,or one rate to rule them all

Background  

Relaxed molecular clock models allow divergence time dating and "relaxed phylogenetic" inference, in which a time tree is estimated in the face of unequal rates across lineages. We present a new method for relaxing the assumption of a strict molecular clock using Markov chain Monte Carlo to implement Bayesian modeling averaging over random local molecular clocks. The new method approaches the problem of rate variation among lineages by proposing a series of local molecular clocks, each extending over a subregion of the full phylogeny. Each branch in a phylogeny (subtending a clade) is a possible location for a change of rate from one local clock to a new one. Thus, including both the global molecular clock and the unconstrained model results, there are a total of 2^2n-2 possible rate models available for averaging with 1, 2, ..., 2n - 2 different rate categories.     

Circadian clocks for all meal-times: anticipation of 2 daily meals in rats

Anticipation of a daily meal in rats has been conceptualized as a rest-activity rhythm driven by a food-entrained circadian oscillator separate from the pacemaker generating light-dark (LD) entrained rhythms. Rats can also anticipate two daily mealtimes, but whether this involves independently entrained oscillators, one 'continuously consulted' clock, cue-dependent non-circadian interval timing or a combination of processes, is unclear. Rats received two daily meals, beginning 3-h (meal 1) and 13-h (meal 2) after lights-on (LD 14:10). Anticipatory wheel running began 68±8 min prior to meal 1 and 101±9 min prior to meal 2 but neither the duration nor the variability of anticipation bout lengths exhibited the scalar property, a hallmark of interval timing. Meal omission tests in LD and constant dark (DD) did not alter the timing of either bout of anticipation, and anticipation of meal 2 was not altered by a 3-h advance of meal 1. Food anticipatory running in this 2-meal protocol thus does not exhibit properties of interval timing despite the availability of external time cues in LD. Across all days, the two bouts of anticipation were uncorrelated, a result more consistent with two independently entrained oscillators than a single consulted clock. Similar results were obtained for meals scheduled 3-h and 10-h after lights-on, and for a food-bin measure of anticipation. Most rats that showed weak or no anticipation to one or both meals exhibited elevated activity at mealtime during 1 or 2 day food deprivation tests in DD, suggesting covert operation of circadian timing in the absence of anticipatory behavior. A control experiment confirmed that daytime feeding did not shift LD-entrained rhythms, ruling out displaced nocturnal activity as an explanation for daytime activity. The results favor a multiple oscillator basis for 2-meal anticipatory rhythms and provide no evidence for involvement of cue-dependent interval timing.