A gene regulatory network controlling the embryonic specification of endoderm

Specification of endoderm is the prerequisite for gut formation in the embryogenesis of bilaterian organisms. Modern lineage labelling studies have shown that in the sea urchin embryo model system, descendants of the veg1 and veg2 cell lineages produce the endoderm, and that the veg2 lineage also gives rise to mesodermal cell types. It is known that Wnt/β-catenin signalling is required for endoderm specification and Delta/Notch signalling is required for mesoderm specification. Some direct cis-regulatory targets of these signals have been found and various phenomenological patterns of gene expression have been observed in the pre-gastrular endomesoderm. However, no comprehensive, causal explanation of endoderm specification has been conceived for sea urchins, nor for any other deuterostome. Here we propose a model, on the basis of the underlying genomic control system, that provides such an explanation, built at several levels of biological organization. The hardwired core of the control system consists of the cis-regulatory apparatus of endodermal regulatory genes, which determine the relationship between the inputs to which these genes are exposed and their outputs. The architecture of the network circuitry controlling the dynamic process of endoderm specification then explains, at the system level, a sequence of developmental logic operations, which generate the biological process. The control system initiates non-interacting endodermal and mesodermal gene regulatory networks in veg2-derived cells and extinguishes the endodermal gene regulatory network in mesodermal precursors. It also generates a cross-regulatory network that specifies future anterior endoderm in veg2 descendants and institutes a distinct network specifying posterior endoderm in veg1-derived cells. The network model provides an explanatory framework that relates endoderm specification to the genomic regulatory code.     

Multigate transistors as the future of classical metal-oxide-semiconductor field-effect transistors

For more than four decades, transistors have been shrinking exponentially in size, and therefore the number of transistors in a single microelectronic chip has been increasing exponentially. Such an increase in packing density was made possible by continually shrinking the metal-oxide-semiconductor field-effect transistor (MOSFET). In the current generation of transistors, the transistor dimensions have shrunk to such an extent that the electrical characteristics of the device can be markedly degraded, making it unlikely that the exponential decrease in transistor size can continue. Recently, however, a new generation of MOSFETs, called multigate transistors, has emerged, and this multigate geometry will allow the continuing enhancement of computer performance into the next decade.     

Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes

Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-selective and Na(+)-selective currents in chicken ASIC1a at pH?7.25 and 5.5, respectively. Crystal structures of ASIC1a-psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. At pH?7.25 the pore is approximately 10?? in diameter, whereas at pH?5.5 the pore is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7??, consistent with a barrier mechanism for ion selectivity. These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents.     

The virophage as a unique parasite of the giant mimivirus

Viruses are obligate parasites of Eukarya, Archaea and Bacteria. Acanthamoeba polyphaga mimivirus (APMV) is the largest known virus; it grows only in amoeba and is visible under the optical microscope. Mimivirus possesses a 1,185-kilobase double-stranded linear chromosome whose coding capacity is greater than that of numerous bacteria and archaea1, 2, 3. Here we describe an icosahedral small virus, Sputnik, 50 nm in size, found associated with a new strain of APMV. Sputnik cannot multiply in Acanthamoeba castellanii but grows rapidly, after an eclipse phase, in the giant virus factory found in amoebae co-infected with APMV4. Sputnik growth is deleterious to APMV and results in the production of abortive forms and abnormal capsid assembly of the host virus. The Sputnik genome is an 18.343-kilobase circular double-stranded DNA and contains genes that are linked to viruses infecting each of the three domains of life Eukarya, Archaea and Bacteria. Of the 21 predicted protein-coding genes, eight encode proteins with detectable homologues, including three proteins apparently derived from APMV, a homologue of an archaeal virus integrase, a predicted primase-helicase, a packaging ATPase with homologues in bacteriophages and eukaryotic viruses, a distant homologue of bacterial insertion sequence transposase DNA-binding subunit, and a Zn-ribbon protein. The closest homologues of the last four of these proteins were detected in the Global Ocean Survey environmental data set5, suggesting that Sputnik represents a currently unknown family of viruses. Considering its functional analogy with bacteriophages, we classify this virus as a virophage. The virophage could be a vehicle mediating lateral gene transfer between giant viruses.     

First births by age and education in Britain, France and Norway

Progressively later starting of childbearing has been a feature of cohort change in fertility across Europe and elsewhere over recent decades. Growing differences in the age patterns of childbearing between the Anglo-American and continental European countries, however, have also been found. The present study uses large linked-record databases in Britain, France and Norway to analyse these differences in more detail, focussing on age at entry to motherhood (first childbearing) by level of educational attainment among women born in the 1950s and in the 1960s. The shift between these two cohorts towards a later pattern of first childbearing in Britain was confined to women with secondary school qualifications and above. For women born in the 1960s, the peak age for risk of first childbearing among those with secondary school qualifications grew to be between seven and eleven years later than among women without secondary school qualifications. In France and Norway, the peak ages for risk of first childbearing shifted more uniformly across education levels between the two cohorts. For these 1950s and 1960s cohorts, improvements in women's educational levels also occurred more uniformly in France and Norway, moving more women into education categories characterised by later patterns of first childbearing.     

Animal mimicry: choosing when to be a cleaner-fish mimic

Mimicry in vertebrates is usually a permanent state--mimics resemble and normally accompany their model throughout the life stages during which they act as mimics. Here we show that the bluestriped fangblenny fish (Plagiotremus rhinorhynchos), which aggressively attacks other coral-reef fish, can turn off the mimetic colours that disguise it as the benign bluestreak cleaner wrasse, Labroides dimidiatus, and assume a radically different appearance. This opportunistic facultative mimicry extends the fangblenny's scope by allowing it to blend into shoals of small reef fish as well as to remain inconspicuous at cleaning stations.     

Combining theoretical and experimental data to decipher CFTR 3D structures and functions

Cryo-electron microscopy (cryo-EM) has recently provided invaluable experimental data about the full-length cystic fibrosis transmembrane conductance regulator (CFTR) 3D structure. However, this experimental information deals with inactive states of the channel, either in an apo, quiescent conformation, in which nucleotide-binding domains (NBDs) are widely separated or in an ATP-bound, yet closed conformation. Here, we show that 3D structure models of the open and closed forms of the channel, now further supported by metadynamics simulations and by comparison with the cryo-EM data, could be used to gain some insights into critical features of the conformational transition toward active CFTR forms. These critical elements lie within membrane-spanning domains but also within NBD1 and the N-terminal extension, in which conformational plasticity is predicted to occur to help the interaction with filamin, one of the CFTR cellular partners.