On the growth and form of the gut

The developing vertebrate gut tube forms a reproducible looped pattern as it grows into the body cavity. Here we use developmental experiments to eliminate alternative models and show that gut looping morphogenesis is driven by the homogeneous and isotropic forces that arise from the relative growth between the gut tube and the anchoring dorsal mesenteric sheet, tissues that grow at different rates. A simple physical mimic, using a differentially strained composite of a pliable rubber tube and a soft latex sheet is consistent with this mechanism and produces similar patterns. We devise a mathematical theory and a computational model for the number, size and shape of intestinal loops based solely on the measurable geometry, elasticity and relative growth of the tissues. The predictions of our theory are quantitatively consistent with observations of intestinal loops at different stages of development in the chick embryo. Our model also accounts for the qualitative and quantitative variation in the distinct gut looping patterns seen in a variety of species including quail, finch and mouse, illuminating how the simple macroscopic mechanics of differential growth drives the morphology of the developing gut.     

Neuronal basis of age-related working memory decline

Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction. The PFC guides behaviour and thought using working memory, which are essential functions in the information age. Many PFC neurons hold information in working memory through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation. This fragile process is highly dependent on the neurochemical environment. For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels. It is not known if molecular changes associated with normal ageing alter the physiological properties of PFC neurons during working memory, as there have been no in vivo recordings, to our knowledge, from PFC neurons of aged monkeys. Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.     

Regulation of microRNA biogenesis and turnover by animals and their viruses

MicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes.     

Persistent pollen as a tracer for hibernating butterflies: the case of Hesperia juba (Lepidoptera: Hesperiidae)

Pollen grains of plants with well-defined flowering seasons may persist on insects through episodes of dormancy, such as hibernation. When readily recognizable and possibly confounding taxa can be excluded, these pollen grains can serve as direct evidence of life-history phenomena that are notoriously difficult to verify in the field. Pollen of the autumn-flowering composite Chrysothamnus nauseosus was used to demonstrate that the common montane skipper, Hesperia juba , hibernates as an adult in Sierra Nevada. This is the first demonstration of adult overwintering in a temperate-zone hesperiid and may represent the smallest butterfly known to overwinter in a cold climate.     

Distribution and abundance of birds in the White Mountains, California

This paper quantifies the distribution and abundance of birds in the White Mountains, Inyo and Mono counties, California, during spring-summer 1989-91, to establish a baseline for monitoring the area's avifauna. Overall 58 species were encountered in the single-leaf pinyon-Utah juniper ( Pinus monophylla-Juniperus osteosperma ) zone, and 61 species in the bristlecone-limber pine ( P. longaeva-P. flexilis ) zone. The bristlecone-limber pine zone had a significantly greater overall bird abundance relative to the pinyon-juniper. Both zones were characterized by few very abundant species, a few moderately abundant species, and numerous rare species. The Black-throated Gray Warbler (scientific names in tables), Gray Flycatcher, and Pinyon Jay were the most abundant species in the pinyon-juniper whereas the Clark's Nutcracker, Mountain Chickadee, and Cassin's Finch were the most abundant species in the bristlecone-limber pine. There were few ecological or taxonomic replacements of species between zones, with the differences in distribution and abundance related primarily to the interaction between elevation and vegetation. Significant inter-year variation in abundance was found for about 20 species in each zone—more species showed declining rather than increasing trends. The Mountain Chickadee and White-breasted Nuthatch declined, whereas the Gray Flycatcher and Rock Wren increased across years in both zones. Reasons for declines in some species might be the severe drought that continued throughout this study.     

Bird use of riparian vegetation along the Truckee River, Califonia and Nevada

The Truckee River in California and Nevada is subject to diverse water regimes and a corresponding variety of flow rates. Original riparian vegetation has been altered by these variable flow rates and by a variety of human uses resulting in loss of native riparian vegetation from its historic extent. We conducted bird surveys along the Truckee River during spring 193 to (1) determine relationships between birds and the present vegetation; (2) determine the importance of different vegetation types to sensitive bird species that have declined recently in the western United States due to competition from exotic plant species, cowbird ( Molothrus ater ) parasitism, reduction in nesting habitat, or other unidentified reasons; and (3) establish a monitoring program and collect baseline data for future comparisons. The most frequently detected bird species throughout the study was the Brown-headed Cowbird. The greatest number of bird species (98 of 116) was found in the native mixed willow ( Salix spp.) riparian scrub vegetation type. We recommend protecting the remaining native riparian vegetation types for bird habitat along the Truckee River.     

Comparative genomics of the neglected human malaria parasite Plasmodium vivax

The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.     

Onset of submarine debris flow deposition far from original giant landslide

Submarine landslides can generate sediment-laden flows whose scale is impressive. Individual flow deposits have been mapped that extend for 1,500 km offshore from northwest Africa. These are the longest run-out sediment density flow deposits yet documented on Earth. This contribution analyses one of these deposits, which contains ten times the mass of sediment transported annually by all of the world's rivers. Understanding how this type of submarine flow evolves is a significant problem, because they are extremely difficult to monitor directly. Previous work has shown how progressive disintegration of landslide blocks can generate debris flow, the deposit of which extends downslope from the original landslide. We provide evidence that submarine flows can produce giant debris flow deposits that start several hundred kilometres from the original landslide, encased within deposits of a more dilute flow type called turbidity current. Very little sediment was deposited across the intervening large expanse of sea floor, where the flow was locally very erosive. Sediment deposition was finally triggered by a remarkably small but abrupt decrease in sea-floor gradient from 0.05 degrees to 0.01 degrees. This debris flow was probably generated by flow transformation from the decelerating turbidity current. The alternative is that non-channelized debris flow left almost no trace of its passage across one hundred kilometres of flat (0.2 degrees to 0.05 degrees) sea floor. Our work shows that initially well-mixed and highly erosive submarine flows can produce extensive debris flow deposits beyond subtle slope breaks located far out in the deep ocean.     

Calcineurin sets the bandwidth for discrimination of signals during thymocyte development

At critical times in development, cells are able to convert graded signals into discrete developmental outcomes; however, the mechanisms involved are poorly understood. During thymocyte development, cell fate is determined by signals originating from the alphabeta T-cell receptor. Low-affinity/avidity interactions between the T-cell receptor and peptide-MHC complexes direct differentiation to the single-positive stage (positive selection), whereas high-affinity/avidity interactions induce death by apoptosis (negative selection). Here we show that mice deficient in both calcineurin and nuclear factor of activated T cells (NFAT)c2/c3 lack a population of preselection thymocytes with enhanced ability to activate the mitogen-activated protein kinase (Raf-MEK-ERK) pathway, and fail to undergo positive selection. This defect can be partially rescued with constitutively active Raf, indicating that calcineurin controls MAPK signalling. Analysis of mice deficient in both Bim (which is required for negative selection) and calcineurin revealed that calcineurin-induced ERK (extracellular signal-regulated kinase) sensitization is required for differentiation in response to 'weak' positive selecting signals but not in response to 'strong' negative selecting signals (which normally induce apoptosis). These results indicate that early calcineurin/NFAT signalling produces a developmental period of ERK hypersensitivity, allowing very weak signals to induce positive selection. This mechanism might be generally useful in the discrimination of graded signals that induce different cell fates.     

Insights into hominid evolution from the gorilla genome sequence

Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution.