Intersex in the gonochoristic crustacean Tanais dulongii (Audouin, 1826) (Peracarida: Tanaidacea: Tanaididae): a comparison of external reproductive characteristics

Tanais dulongii (Audouin, 1826) is a small benthic crustacean with separate sexes and a marked sexual dimorphism characterized by a cephalothorax narrowed anteriorly, larger chelae (claws) and a pair of tiny genital cones in males, and ovisacs that form chambers for carrying embryos in females. Recent studies have described the existence of intersexual individuals with a cephalothorax similar to males, large chelae and ovisacs, but, due to their small size, it has not been possible to confirm the presence of genital cones under normal light microscopy. The present study analyses and compares external reproductive structures under scanning electron microscopy, of male and female T. dulongii, to corroborate the presence of both ovisacs and genital cones in potentially intersex individuals. The possible causes, such as hermaphroditism, environmental sex determination, parasitism, genetic aberration or endocrine-disrupting pollutants, are discussed.     

Variation in genome-wide mutation rates within and between human families

J.B.S. Haldane proposed in 1947 that the male germline may be more mutagenic than the female germline. Diverse studies have supported Haldane's contention of a higher average mutation rate in the male germline in a variety of mammals, including humans. Here we present, to our knowledge, the first direct comparative analysis of male and female germline mutation rates from the complete genome sequences of two parent-offspring trios. Through extensive validation, we identified 49 and 35 germline de novo mutations (DNMs) in two trio offspring, as well as 1,586 non-germline DNMs arising either somatically or in the cell lines from which the DNA was derived. Most strikingly, in one family, we observed that 92% of germline DNMs were from the paternal germline, whereas, in contrast, in the other family, 64% of DNMs were from the maternal germline. These observations suggest considerable variation in mutation rates within and between families.     

Extracting information shocks from the Bank of England inflation density forecasts

This paper shows how to extract the density of information shocks from revisions of the Bank of England's inflation density forecasts. An information shock is defined in this paper as a random variable that contains the set of information made available between two consecutive forecasting exercises and that has been incorporated into a revised forecast for a fixed point event. Studying the moments of these information shocks can be useful in understanding how the Bank has changed its assessment of risks surrounding inflation in the light of new information, and how it has modified its forecasts accordingly. The variance of the information shock is interpreted in this paper as a new measure of ex ante inflation uncertainty that measures the uncertainty that the Bank anticipates information perceived in a particular quarter will pose on inflation. A measure of information absorption that indicates the approximate proportion of the information content in a revised forecast that is attributable to information made available since the last forecast release is also proposed.     

Multiple ADH genes are associated with upper aerodigestive cancers

Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10(-10) and 10(-9), respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.     

The Concept of Sustainable Development Revisited

The concept of sustainable development is here revised in the light of a brief historical analysis, followed by a semantic analysis of the expressions development and sustainability. The authors criticize the common use of this concept in a loose way or in wide generalizations, to conclude, based on the principles of human ecology, that it is only possible to make it operational in limited spans of time and in limited spatial units.     

Structural basis of BMP signalling inhibition by the cystine knot protein Noggin

The interplay between bone morphogenetic proteins (BMPs) and their antagonists governs developmental and cellular processes as diverse as establishment of the embryonic dorsal-ventral axis, induction of neural tissue, formation of joints in the skeletal system and neurogenesis in the adult brain. So far, the three-dimensional structures of BMP antagonists and the structural basis for inactivation have remained unknown. Here we report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors. The BMP-7-binding affinity of site-specific variants of Noggin is correlated with alterations in bone formation and apoptosis in chick limb development, showing that Noggin functions by sequestering its ligand in an inactive complex. The scaffold of Noggin contains a cystine (the oxidized form of cysteine) knot topology similar to that of BMPs; thus, ligand and antagonist seem to have evolved from a common ancestral gene.     

Notch activity acts as a sensor for extracellular calcium during vertebrate left-right determination

During vertebrate embryo development, the breaking of the initial bilateral symmetry is translated into asymmetric gene expression around the node and/or in the lateral plate mesoderm. The earliest conserved feature of this asymmetric gene expression cascade is the left-sided expression of Nodal, which depends on the activity of the Notch signalling pathway. Here we present a mathematical model describing the dynamics of the Notch signalling pathway during chick embryo gastrulation, which reveals a complex and highly robust genetic network that locally activates Notch on the left side of Hensen's node. We identify the source of the asymmetric activation of Notch as a transient accumulation of extracellular calcium, which in turn depends on left-right differences in H+/K+-ATPase activity. Our results uncover a mechanism by which the Notch signalling pathway translates asymmetry in epigenetic factors into asymmetric gene expression around the node.