Additive threats from pathogens, climate and land-use change for global amphibian diversity

Amphibian population declines far exceed those of other vertebrate groups, with 30% of all species listed as threatened by the International Union for Conservation of Nature. The causes of these declines are a matter of continued research, but probably include climate change, land-use change and spread of the pathogenic fungal disease chytridiomycosis. Here we assess the spatial distribution and interactions of these primary threats in relation to the global distribution of amphibian species. We show that the greatest proportions of species negatively affected by climate change are projected to be found in Africa, parts of northern South America and the Andes. Regions with the highest projected impact of land-use and climate change coincide, but there is little spatial overlap with regions highly threatened by the fungal disease. Overall, the areas harbouring the richest amphibian faunas are disproportionately more affected by one or multiple threat factors than areas with low richness. Amphibian declines are likely to accelerate in the twenty-first century, because multiple drivers of extinction could jeopardize their populations more than previous, mono-causal, assessments have suggested.     

Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma

Neuroblastoma, a tumour derived from the peripheral sympathetic nervous system, is one of the most frequent solid tumours in childhood. It usually occurs sporadically but familial cases are observed, with a subset of cases occurring in association with congenital malformations of the neural crest being linked to germline mutations of the PHOX2B gene. Here we conducted genome-wide comparative genomic hybridization analysis on a large series of neuroblastomas. Copy number increase at the locus encoding the anaplastic lymphoma kinase (ALK) tyrosine kinase receptor was observed recurrently. One particularly informative case presented a high-level gene amplification that was strictly limited to ALK, indicating that this gene may contribute on its own to neuroblastoma development. Through subsequent direct sequencing of cell lines and primary tumour DNAs we identified somatic mutations of the ALK kinase domain that mainly clustered in two hotspots. Germline mutations were observed in two neuroblastoma families, indicating that ALK is a neuroblastoma predisposition gene. Mutated ALK proteins were overexpressed, hyperphosphorylated and showed constitutive kinase activity. The knockdown of ALK expression in ALK-mutated cells, but also in cell lines overexpressing a wild-type ALK, led to a marked decrease of cell proliferation. Altogether, these data identify ALK as a critical player in neuroblastoma development that may hence represent a very attractive therapeutic target in this disease that is still frequently fatal with current treatments.     

The first hominin of Europe

The earliest hominin occupation of Europe is one of the most debated topics in palaeoanthropology. However, the purportedly oldest of the Early Pleistocene sites in Eurasia lack precise age control and contain stone tools rather than human fossil remains. Here we report the discovery of a human mandible associated with an assemblage of Mode 1 lithic tools and faunal remains bearing traces of hominin processing, in stratigraphic level TE9 at the site of the Sima del Elefante, Atapuerca, Spain. Level TE9 has been dated to the Early Pleistocene (approximately 1.2-1.1 Myr), based on a combination of palaeomagnetism, cosmogenic nuclides and biostratigraphy. The Sima del Elefante site thus emerges as the oldest, most accurately dated record of human occupation in Europe, to our knowledge. The study of the human mandible suggests that the first settlement of Western Europe could be related to an early demographic expansion out of Africa. The new evidence, with previous findings in other Atapuerca sites (level TD6 from Gran Dolina), also suggests that a speciation event occurred in this extreme area of the Eurasian continent during the Early Pleistocene, initiating the hominin lineage represented by the TE9 and TD6 hominins.     

A photosynthetic alveolate closely related to apicomplexan parasites

Many parasitic Apicomplexa, such as Plasmodium falciparum, contain an unpigmented chloroplast remnant termed the apicoplast, which is a target for malaria treatment. However, no close relative of apicomplexans with a functional photosynthetic plastid has yet been described. Here we describe a newly cultured organism that has ultrastructural features typical for alveolates, is phylogenetically related to apicomplexans, and contains a photosynthetic plastid. The plastid is surrounded by four membranes, is pigmented by chlorophyll a, and uses the codon UGA to encode tryptophan in the psbA gene. This genetic feature has been found only in coccidian apicoplasts and various mitochondria. The UGA-Trp codon and phylogenies of plastid and nuclear ribosomal RNA genes indicate that the organism is the closest known photosynthetic relative to apicomplexan parasites and that its plastid shares an origin with the apicoplasts. The discovery of this organism provides a powerful model with which to study the evolution of parasitism in Apicomplexa.     

Ab initio determination of solid-state nanostructure

Advances in materials science and molecular biology followed rapidly from the ability to characterize atomic structure using single crystals. Structure determination is more difficult if single crystals are not available. Many complex inorganic materials that are of interest in nanotechnology have no periodic long-range order and so their structures cannot be solved using crystallographic methods. Here we demonstrate that ab initio structure solution of these nanostructured materials is feasible using diffraction data in combination with distance geometry methods. Precise, sub-?ngstr?m resolution distance data are experimentally available from the atomic pair distribution function (PDF). Current PDF analysis consists of structure refinement from reasonable initial structure guesses and it is not clear, a priori, that sufficient information exists in the PDF to obtain a unique structural solution. Here we present and validate two algorithms for structure reconstruction from precise unassigned interatomic distances for a range of clusters. We then apply the algorithms to find a unique, ab initio, structural solution for C60 from PDF data alone. This opens the door to sub-?ngstr?m resolution structure solution of nanomaterials, even when crystallographic methods fail.     

Abdominal obesity and metabolic syndrome

Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.     

Ion permeation through the Na+,K+-ATPase

P-type ATPase pumps generate concentration gradients of cations across membranes in nearly all cells. They provide a polar transmembrane pathway, to which access is strictly controlled by coupled gates that are constrained to open alternately, thereby enabling thermodynamically uphill ion transport (for example, see ref. 1). Here we examine the ion pathway through the Na+,K+-ATPase, a representative P-type pump, after uncoupling its extra- and intracellular gates with the marine toxin palytoxin. We use small hydrophilic thiol-specific reagents as extracellular probes and we monitor their reactions, and the consequences, with cysteine residues introduced along the anticipated cation pathway through the pump. The distinct effects of differently charged reagents indicate that a wide outer vestibule penetrates deep into the Na+,K+-ATPase, where the pathway narrows and leads to a charge-selectivity filter. Acidic residues in this region, which are conserved to coordinate pumped ions, allow the approach of cations but exclude anions. Reversing the charge at just one of those positions converts the pathway from cation selective to anion selective. Close structural homology among the catalytic subunits of Ca2+-, Na+,K+- and H+,K+-ATPases argues that their extracytosolic cation exchange pathways all share these physical characteristics.     

脑瘤诱发的组织变化和皮层脑电图分析

健康组织和肿瘤组织具有不同的代谢,结构和热力学特性.脑瘤的代谢和结构无序性导致其有较高的熵产生.两种组织不同的熵产生决定了熵由癌流向健康组织.脑瘤和正常细胞在熵和能量方面的差异诱发皮层不同的脑电信号.研究了28个脑瘤患者的脑电图并和健康人进行比较,观察到脑瘤患者脑电图频率的降低.多数情况中慢alpha和theta波出现在肿瘤投影区,此可能与其高熵产生和向外的熵流有关.研究认为,脑瘤的持续高熵产生和热耗散及其它物理效应使得皮层电产生慢化,从而使肿瘤及其邻近的脑组织显示出频率较低的电活性.     

Problem Structuring Methods: A Review of Advances Over the Last Decade

Systemic Practice and Action Research - The Problem Structuring Methods (PSMs) are a set of interactive and participatory modeling approaches for dealing with unstructured complex problems, which...