Mode matches and their locations in the hydrophobic free energy sequences of peptide ligands and their receptor eigenfunctions

Patterns in sequences of amino acid hydrophobic free energies predict secondary structures in proteins. In protein folding, matches in hydrophobic free energy statistical wavelengths appear to contribute to selective aggregation of secondary structures in “hydrophobic zippers.” In a similar setting, the use of Fourier analysis to characterize the dominant statistical wavelengths of peptide ligands’ and receptor proteins’ hydrophobic modes to predict such matches has been limited by the aliasing and end effects of short peptide lengths, as well as the broad-band, mode multiplicity of many of their frequency (power) spectra. In addition, the sequence locations of the matching modes are lost in this transformation. We make new use of three techniques to address these difficulties: (i) eigenfunction construction from the linear decomposition of the lagged covariance matrices of the ligands and receptors as hydrophobic free energy sequences; (ii) maximum entropy, complex poles power spectra, which select the dominant modes of the hydrophobic free energy sequences or their eigenfunctions; and (iii) discrete, best bases, trigonometric wavelet transformations, which confirm the dominant spectral frequencies of the eigenfunctions and locate them as (absolute valued) moduli in the peptide or receptor sequence. The leading eigenfunction of the covariance matrix of a transmembrane receptor sequence locates the same transmembrane segments seen in n-block-averaged hydropathy plots while leaving the remaining hydrophobic modes unsmoothed and available for further analyses as secondary eigenfunctions. In these receptor eigenfunctions, we find a set of statistical wavelength matches between peptide ligands and their G-protein and tyrosine kinase coupled receptors, ranging across examples from 13.10 amino acids in acid fibroblast growth factor to 2.18 residues in corticotropin releasing factor. We find that the wavelet-located receptor modes in the extracellular loops are compatible with studies of receptor chimeric exchanges and point mutations. A nonbinding corticotropin-releasing factor receptor mutant is shown to have lost the signatory mode common to the normal receptor and its ligand. Hydrophobic free energy eigenfunctions and their transformations offer new quantitative physical homologies in database searches for peptide-receptor matches.

Glial cell line-derived neurotrophic factor activates the receptor tyrosine kinase RET and promotes kidney morphogenesis.

The receptor tyrosine kinase RET functions during the development of the kidney and the enteric nervous system, yet no ligand has been identified to date. This report demonstrates that the glial cell line-derived neurotrophic factor (GDNF) activates RET, as measured by tyrosine phosphorylation of the intracellular catalytic domain. GDNF also binds RET with a dissociation constant of 8 nM, and 125I-labeled GDNF can be coimmunoprecipitated with anti-RET antibodies. In addition, exogenous GDNF stimulates both branching and proliferation of embryonic kidneys in organ culture, whereas neutralizing antibodies against GDNF inhibit branching morphogenesis. These data indicate that RET and GDNF are components of a common signaling pathway and point to a role for GDNF in kidney development.

Human Trafficking of Women and Children in the Philippines: Challenges and Solutions

Women and children become victims of human trafficking and exploitation as a result of economic globalization, national history, social structures, and geographical positioning. Human trafficking has increasingly become a global crisis of human rights violations, threatening the lives of women and children in developing countries, like the Philippines. The Philippines can evolve into a model for ending the exploitation of human trafficking if the government commits to implementing internationally recognized strategies, such as strengthening the prosecution of traffickers, providing efficient support for victims, and partnering with international organizations and local non-governmental organizations to further prevent human trafficking from occurring. The results will be felt locally, nationally, and internationally, helping the global community meet the challenges of the Millennium Development Goals.

Tasas de deformación GPS en la cuenca del Bajo Segura (Cordillera Bética oriental)

En este trabajo hemos cuantificado las tasas de deformación actual de la cuenca del Bajo Segura (NE del corredor de cizalla de la Bética oriental), a partir del análisis de una red GPS con 11 vértices geodésicos. Se han analizado los datos de cuatro campañas GPS entre junio de 1999 y enero de 2013, que han sido procesados con la versión 6.2 del software GIPSY-OASIS. Este software utiliza la técnica de posicionamiento puntual de precisión conocido por las siglas PPP. Se observa un acortamiento ~N-S en toda la cuenca de mayor magnitud en el sur, en la zona de falla del Bajo Segura, con valores que varían de oeste a este entre 0,73 y 0,24 mm/año. En el borde septentrional de la cuenca, en la zona de falla de Crevillente, los valores de acortamiento N-S son menores. Sin embargo, en esta falla se ha observado un movimiento lateral sinistrorso que, en la componente E-O, varía entre 0,44 y 0,75 mm/año.

New galactic star clusters discovered in the VVV survey. Candidates projected on the inner disk and bulge

Context. VISTA Variables in the Vía Láctea (VVV) is one of six ESO Public Surveys using the 4 meter Visible and Infrared Survey Telescope for Astronomy (VISTA). The VVV survey covers the Milky Way bulge and an adjacent section of the disk, and one of the principal objectives is to search for new star clusters within previously unreachable obscured parts of the Galaxy. Aims. The primary motivation behind this work is to discover and analyze obscured star clusters in the direction of the inner Galactic disk and bulge. Methods. Regions of the inner disk and bulge covered by the VVV survey were visually inspected using composite JHKS color images to select new cluster candidates on the basis of apparent overdensities. DR1, DR2, CASU, and point spread function photometry of 10 × 10 arcmin fields centered on each candidate cluster were used to construct color–magnitude and color–color diagrams. Follow-up spectroscopy of the brightest members of several cluster candidates was obtained in order to clarify their nature. Results. We report the discovery of 58 new infrared cluster candidates. Fundamental parameters such as age, distance, and metallicity were determined for 20 of the most populous clusters.

Identification of YAP as sperm-PAWP’s predominant binding partner in MII-arrested oocytes and the relevance of this WWI domain modular interaction to oocyte activation

PAWP, a candidate sperm-borne oocyte activating factor, induces oocyte activation and acts upstream of the calcium signalling pathway, however, PAWP’s downstream signalling pathway in oocyte cytoplasm remains to be uncovered. Data from our lab suggested that the interacting partner of PAWP, at least in the frog (Xenopus laevis) model may be YAP, a highly expressed protein in amphibian and mammalian oocytes. Therefore, the objectives of this study were to confirm that PAWP’s predominant binding partner in Xenopus laevis oocyte is YAP; to determine if mammalian oocyte activation is also dependent on PAWP-YAP interaction; and to verify that the PAWP-YAP interaction during oocyte activation is dependent on the WWI domain module. By immunohistochemistry, YAP was localized predominantly in the cytosol of metaphase II-arrested Xenopus laevis oocytes, where presumably the PAWP-YAP interaction occurs. Utilizing Far Western blotting, YAP was identified as the predominant binding partner of PAWP, in metaphase II-arrested frog (Xenopus laevis), swine (Sus scrofa) and mouse (mus musculus) oocytes. The specificity of this interaction was then tested on Far Western blotting of mouse ovarian and oocyte cytosolic extracts, by competition with both wild-type and point-mutated recombinant WWI domains derived from YAP. The removal of GST from the wild-type WWI-GST fusion protein was a requirement for effective blockage of WWI module interaction between PAWP and YAP. As expected, the mutated WWI domain was ineffective in inhibiting the PAWP-YAP interaction. To conclude, this study identified YAP as the predominant binding partner of PAWP in both amphibian and mammalian oocytes, and showed this interaction is dependent on the WWI modular interaction. The results allow us to test the functional relevance of this WWI modular interaction during oocyte activation in vivo, in the future.

Nonsense-mediated mRNA decay: novel mechanistic insights and biological impact

Nonsense-mediated mRNA decay (NMD) was originally coined to define a quality control mechanism that targets mRNAs with truncated open reading frames due to the presence of a premature termination codon. Meanwhile, it became clear that NMD has a much broader impact on gene expression and additional biological functions beyond quality control are continuously being discovered. We review here the current views regarding the molecular mechanisms of NMD, according to which NMD ensues on mRNAs that fail to terminate translation properly, and point out the gaps in our understanding. We further summarize the recent literature on an ever-rising spectrum of biological processes in which NMD appears to be involved, including homeostatic control of gene expression, development and differentiation, as well as viral defense.

The pragmatics of computer-mediated communication between South African and Mexican drug traffickers

South Africa and Mexico are ripe with drug trafficking. The gangs and syndicates running the drug businesses in these two countries collaborate occasionally. Communication between these international drug business partners takes place on social media. Their main language of communication is English, mixed with some limited use of Spanish and Afrikaans. The key purpose of the interactions between the South African and Mexican parties is the organisation of their business activities. This study aims at examining how the drug traffickers position each other and themselves regarding their common business interest and how their relationship evolves throughout their interactions. Moreover, it is of interest to look at how these people make use of different social media and their affordances. For this a qualitative analysis of the interaction between two drug traffickers (one South African and one Mexican) on Facebook, Threema and PlayStation 4 was performed. Computer-mediated communication between these two main informants was studied at various stages of their relationship. Results show that at first the interaction between the South African and Mexican drug traffickers consists of interpersonal negotiations of power. The high risk of the drug business and gang/syndicate membership paired with intercultural frictions causes the two interlocutors to be extremely cautious and at the same time to mark their position. As their relationship develops and they gain trust in each other a shift to interpersonal negotiations of solidarity takes place. In these discursive practices diverse linguistic strategies are employed for creating relational effects and for positioning the other and the self. The discursive activities of the interactants are also identity practices. Thus, the two drug traffickers construct identities through these social practices, positioning and their interpersonal relationship.

(Table1) Sedimentation rates and age-control points form ODP Hole 152-919A

Planktic d18O and d13C records and point count records of biogenic, volcanic, and nonvolcanic terrigenous [ice-rafted debris (IRD)] sediment components from Hole 919A in the Irminger basin, northern North Atlantic provide a comprehensive dataset from which a paleoceanographic reconstruction for the last 630 kyr has been developed. The paleoceanographic evolution of the Irminger basin during this time contains both long-term patterns and significant developmental steps. One long-term pattern observed is the persistent deposition of hematite-stained ice-rafted debris. This record suggests that the modern and late Pleistocene discharges of icebergs from northern redbed regions to the Irminger Sea lie in the low end of the range observed over the last 630 kyr. In addition, Arctic front fluctuations appear to have been the main controlling factor on the long-term accumulation patterns of IRD and planktic biogenic groups. The Hole 919A sediment record also contains a long-term association between felsic volcanic ash abundances and light d18O excursions in both interglacial and glacial stages, which suggests a causal link between deglaciations and explosive Icelandic eruptions. A significant developmental step in the paleoceanographic reconstruction based on benthic evidence was for diminished supply of Denmark Strait Overflow Water (DSOW) beginning at ~380 ka, possibly initiated by the influx of meltwater from broad-scale iceberg discharges along the east Greenland coast. There is also planktic evidence of a two-step cooling of sea surface conditions in the Irminger basin, first at ~338-309 ka and later at ~211-190 ka, after which both glacials and interglacials were colder as the Arctic front migrated southeast of Site 919. In addition to offering these findings, this reconstruction provides a longer-term geologic context for the interpretation of more recent paleoceanographic events and patterns of deposition from this region.

Ichthyolith (fish tooth and denticle) counts from DSDP Site 91-596 and ODP Site 145-886

While the history of taxonomic diversification in open ocean lineages of ray-finned fish and elasmobranchs is increasingly known, the evolution of their roles within the open ocean ecosystem remains poorly understood. To assess the relative importance of these groups through time, we measured the accumulation rate of microfossil fish teeth and elasmobranch dermal denticles (ichthyoliths) in deep sea sediment cores from the North and South Pacific gyres over the past 85 million years. We find three distinct and stable open ocean ecosystem structures, each defined by the relative and absolute abundance of elasmobranch and ray-finned fish remains. The Cretaceous Ocean (pre-66 Ma), was characterized by abundant elasmobranch denticles, but low abundances of fish teeth. The Paleogene Ocean (66-20 Ma), initiated by the Cretaceous/Paleogene Mass Extinction, had nearly 4 times the abundance of fish teeth compared to elasmobranch denticles. This Paleogene Ocean structure remained stable during the Eocene greenhouse (50 Ma) and the Eocene-Oligocene glaciation (34 Ma), despite large changes in overall accumulation of both groups during those intervals, suggesting that climate change is not a primary driver of ecosystem structure. Dermal denticles virtually disappeared from open ocean ichthyolith assemblages about 20 Ma, while fish tooth accumulation increased dramatically in variability, marking the beginning of the Modern Ocean. Together, these results suggest that open ocean fish community structure is stable on long timescales, independent of total production and climate change. The timing of the abrupt transitions between these states suggests that the transitions may be due to interactions with other, non-preserved pelagic consumer groups.

Massic magnetic susceptibility and CaCO3 content at the P. ohmi and T. hugii zones from the Rio Argos X.Ag-1 section, southeastern Spain

An orbital floating time scale of the Hauterivian-Barremian transition (Early Cretaceous) is proposed using high-resolution magnetic susceptibility measurements. Orbital tuning was performed on the Río Argos section (southeast Spain), the candidate for a Global boundary Stratotype Section and Point (GSSP) for the Hauterivian-Barremian transition. Spectral analyses of MS variations, coupled with the frequency ratio method, allow the recognition of precession, obliquity and eccentricity frequency bands. Orbitally-tuned magnetic susceptibility provides minimum durations for ammonite biozones. The durations of well-constrained ammonite zones are assessed at 0.78 myr for Pseudothurmannia ohmi (Late Hauterivian) and 0.57 myr for Taveraidiscus hugii (Early Barremian). These results are consistent with previous estimates from the other reference section (Angles, southeast France) and tend to show that the Río Argos section displays a complete succession for this time interval. They differ significantly from those proposed in the Geologic Time Scale 2008 and may help to improve the next compilation. The Faraoni Oceanic Anoxic Event, a key Early Cretaceous oceanographic perturbation occurring at the P. ohmi/P. catulloi subzone boundary has a duration estimated at 0.10-0.15 myr, which is similar to previous assessments.

Carbon isotope record of 3 profiles from Campanian-Maastrichtian

Carbon-isotope stratigraphy has proven to be a powerful tool in the global correlation of Cretaceous successions. Here we present new, high-resolution carbon-isotope records for the Global Boundary Stratotype Section and Point (GSSP) of the Maastrichtian stage at Tercis les Bains (France), the Bottaccione and Contessa sections at Gubbio (Italy), and the coastal sections at Norfolk (UK) to provide a global d13C correlation between shelf-sea and oceanic sites. The new d13C records are correlated with d13C-stratigraphies of the boreal chalk sea (Trunch borehole, Norfolk, UK, Lägerdorf-Kronsmoor-Hemmoor section, northern Germany, Stevns-1 core, Denmark), the tropical Pacific (ODP-Hole 1210B, Shatsky Rise) and the South Atlantic and Southern Ocean (DSDP Hole 525A, ODP Hole 690C) by using an assembled Gubbio d13C record as a reference curve. The global correlation allows the identification of significant high-frequency d13C variations that occur superimposed on prominent Campanian-Maastrichtian events, namely the Late Campanian Event (LCE), the Campanian-Maastrichtian Boundary Event (CMBE), the mid-Maastrichtian Event (MME), and the Cretaceous-Paleogene transition (KPgE). The carbon-isotope events are correlated with the geomagnetic polarity scale recalculated using the astronomical 40Ar/39Ar calibration of the Fish Canyon sanidine. This technique allows the evaluation of the relative timing of base occurrences of stratigraphic index fossils such as ammonites, planktonic foraminifera and calcareous nannofossils. Furthermore, the Campanian-Maastrichtian boundary, as defined in the stratotype at Tercis, can be precisely positioned relative to carbon-isotope stratigraphy and the geomagnetic polarity timescale. The average value for the age of the Campanian-Maastrichtian boundary is 72.1 ± 0.1 Ma, estimated by three independent approaches that utilize the Fish Canyon sanidine calibration and Option 2 of the Maastrichtian astronomical timescale. The CMBE covers a time span of 2.5 Myr and reflects changes in the global carbon cycle probably related to tectonic processes than to glacioeustasy. The duration of the high-frequency d13C variations instead coincides with the frequency band of long eccentricity, indicative of orbital forcing of changes in climate and the global carbon cycle.

Sedimentology, geochemistry and paleomagnetic of ODP Hole 151-913B

The Eocene and Oligocene epochs (55 to 23 million years ago) comprise a critical phase in Earth history. An array of geological records (Zachos et al., 2001, doi:10.1126/science.1059412; Lear et al., 2000, doi:10.1126/science.287.5451.269; Coxall et al., 2005, doi:10.1038/nature03135; Pekar et al., 2005; doi:10.1130/B25486.1; Strand et al., 2003, doi:10.1016/S0031-0182(03)00396-1) supported by climate modelling (DeConto and Pollard, 2003, doi:10.1038/nature01290) indicates a profound shift in global climate during this interval, from a state that was largely free of polar ice caps to one in which ice sheets on Antarctica approached their modern size. However, the early glaciation history of the Northern Hemisphere is a subject of controversy (Coxall et al., 2005, doi:10.1038/nature03135; Tripati et al., 2005, doi:10.1038/nature03874; Wolf-Welling et al., 1996, doi:10.2973/odp.proc.sr.151.139.1996; Moran et al., 2006, doi:10.1038/nature04800). Here we report stratigraphically extensive ice-rafted debris, including macroscopic dropstones, in late Eocene to early Oligocene sediments from the Norwegian-Greenland Sea that were deposited between about 38 and 30 million years ago. Our data indicate sediment rafting by glacial ice, rather than sea ice, and point to East Greenland as the likely source. Records of this type from one site alone cannot be used to determine the extent of ice involved. However, our data suggest the existence of (at least) isolated glaciers on Greenland about 20 million years earlier than previously documented (Winkler et al., 2002, doi:10.1007/s005310100199), at a time when temperatures and atmospheric carbon dioxide concentrations were substantially higher.

Traité élémentaire de géométrie descriptive

livre I. Définitions, lecture, notations.--livre II. Problèmes de position relative du point, de la droite et du plan.-livre III. Intersections des lignes et des surfaces.

Geological and trace element evidence for a marine sedimentary environment of deposition and biogenicity of 3.45 Ga stromatolitic carbonates in the Pilbara Craton, and support for a reducing Archaean ocean

Bedded carbonate rocks from the 3.45 Ga Warrawoona Group, Pilbara Craton, contain structures that have been regarded either as the oldest known stromatolites or as abiotic hydrothermal deposits. We present new field and petrological observations and high-precision REE + Y data from the carbonates in order to test the origin of the deposits. Trace element geochemistry from a number of laminated stromatolitic dolomite samples of the c. 3.40 Ga Strelley Pool Chert conclusively shows that they precipitated from anoxic seawater, probably in a very shallow environment consistent with previous sedimentological observations. Edge-wise conglomerates in troughs between stromatolites and widespread cross-stratification provide additional evidence of stromatolite construction, at least partly, from layers of particulate sediment, rather than solely from rigid crusts. Accumulation of particulate sediment on steep stromatolite sides in a high-energy environment suggests organic binding of the surface. Relative and absolute REE + Y contents are exactly comparable with Late Archaean microbial carbonates of widely agreed biological origin. Ankerite from a unit of bedded ankerite–chert couplets from near the top of the stratigraphically older (3.49 Ga) Dresser Formation, which immediately underlies wrinkly stromatolites with small, broad, low-amplitude domes, also precipitated from anoxic seawater. The REE + Y data of carbonates from the Strelley Pool Chert and Dresser Formation contrast strongly with those from siderite layers in a jasper–siderite–Fe-chlorite banded iron-formation from the base of the Panorama Formation (3.45 Ga), which is clearly hydrothermal in origin. The geochemical results, together with sedimentological data, strongly support: (1) deposition of Dresser Formation and Strelley Pool Chert carbonates from Archaean seawater, in part as particulate carbonate sediment; (2) biogenicity of the stromatolitic carbonates; (3) a reducing Archaean atmosphere; (4) ongoing extensive terrestrial erosion prior to ∼3.45 Ga.