Circadian rhythms from flies to human

In this era of jet travel, our body 'remembers' the previous time zone, such that when we travel, our sleep wake pattern, mental alertness, eating habits and many other physiological processes temporarily suffer the consequences of time displacement until we adjust to the new time zone. Although the existence of a circadian clock in humans had been postulated for decades, an understanding of the molecular mechanisms has required the full complement of research tools. To gain the initial insights into circadian mechanisms, researchers turned to genetically tractable model organisms such as Drosophila.     

Replacement fertility, what has it been and what does it mean?

Replacement fertility is a term commonly used by demographers when referring to levels of childbearing and yet is rarely explained. It is normally presented as being around 2.1 children per woman. Continued below replacement fertility in developed countries and fertility falling in developing countries has given the concept of replacement fertility a higher profile. This article explains how replacement level is calculated and explores the concept further. Past replacement fertility levels are calculated for England and Wales. A possible alternative definition of replacement is also presented. Simple projection scenarios are used to show the effect on population of below replacement fertility, and also of postponement of fertility. The importance and implications of below replacement fertility are discussed.     

Colorectal cancer: mutations in a signalling pathway

Protein kinases are enzymes that are important for controlling cellular growth and invasion, and their malfunction is implicated in the development of some tumours. We analysed human colorectal cancers for genetic mutations in 340 serine/threonine kinases and found mutations in eight genes, including in three members of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway. The discovery of this mutational activation of a key cell-signalling pathway may provide new targets for therapeutic intervention.     

Modelling the recent common ancestry of all living humans

If a common ancestor of all living humans is defined as an individual who is a genealogical ancestor of all present-day people, the most recent common ancestor (MRCA) for a randomly mating population would have lived in the very recent past. However, the random mating model ignores essential aspects of population substructure, such as the tendency of individuals to choose mates from the same social group, and the relative isolation of geographically separated groups. Here we show that recent common ancestors also emerge from two models incorporating substantial population substructure. One model, designed for simplicity and theoretical insight, yields explicit mathematical results through a probabilistic analysis. A more elaborate second model, designed to capture historical population dynamics in a more realistic way, is analysed computationally through Monte Carlo simulations. These analyses suggest that the genealogies of all living humans overlap in remarkable ways in the recent past. In particular, the MRCA of all present-day humans lived just a few thousand years ago in these models. Moreover, among all individuals living more than just a few thousand years earlier than the MRCA, each present-day human has exactly the same set of genealogical ancestors.     

Characteristics of sole registered births and the mothers who register them

This article explores the characteristics of live births where no father was present on the birth certificate (sole registrations) using registration data. It then uses data from the ONS Longitudinal Study to examine some characteristics of mothers who have ever experienced a sole registered live birth. It shows that as a proportion of all births, sole registrations have remained fairly constant over the last two decades, although since 1998 there is some evidence of a fall in the proportion. For mothers born between 1955 and 1962 around nine per cent experienced a sole registration. Those who ever experienced a sole registration were around four years younger when they began their childbearing. These women also had larger families and were more likely to come from a lower social class background.     

Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies

Idiopathic generalized epilepsy (IGE) is an inherited neurological disorder affecting about 0.4% of the world's population. Mutations in ten genes causing distinct forms of idiopathic epilepsy have been identified so far, but the genetic basis of many IGE subtypes is still unknown. Here we report a gene associated with the four most common IGE subtypes: childhood and juvenile absence epilepsy (CAE and JAE), juvenile myoclonic epilepsy (JME), and epilepsy with grand mal seizures on awakening (EGMA; ref. 8). We identified three different heterozygous mutations in the chloride-channel gene CLCN2 in three unrelated families with IGE. These mutations result in (i) a premature stop codon (M200fsX231), (ii) an atypical splicing (del74-117) and (iii) a single amino-acid substitution (G715E). All mutations produce functional alterations that provide distinct explanations for their pathogenic phenotypes. M200fsX231 and del74-117 cause a loss of function of ClC-2 channels and are expected to lower the transmembrane chloride gradient essential for GABAergic inhibition. G715E alters voltage-dependent gating, which may cause membrane depolarization and hyperexcitability.