An alternative plate tectonic model for the Palaeozoic-Early Mesozoic Palaeotethyan evolution of Southeast Asia (northern Thailand-Myanmar)

An alternative model for the geodynamic evolution of Southeast Asia is proposed and inserted in a modern plate tectonic model. The reconstruction methodology is based on dynamic plate boundaries, constrained by data such as spreading rates and subduction velocities; in this way it differs from classical continental drift models proposed so far. The different interpretations about the location of the Palaeotethys suture in Thailand are revised, the Tertiary Mae Yuam fault is seen as the emplacement of the suture. East of the suture we identify an Indochina derived terrane for which we keep the name Shan-Thai, formerly used to identify the Cimmerian block present in Southeast Asia, now called Sibumasu. This nomenclatural choice was made on the basis of the geographic location of the terrane (Eastern Shan States in Burma and Central Thailand) and in order not to introduce new confusing terminology. The closure of the Eastern Palaeotethys is related to a southward subduction of the ocean, that triggered the Eastern Neotethys to open as a back-arc, due to the presence of Late Carboniferous-Early Permian arc magmatism in Mergui (Burma) and in the Lhasa block (South Tibet), and to the absence of arc magmatism of the same age East of the suture. In order to explain the presence of Carboniferous-Early Permian and Permo-Triassic volcanic arcs in Cambodia, Upper Triassic magmatism in Eastern Vietnam and Lower Permian-Middle Permian arc volcanites in Western Sumatra, we introduce the Orang Laut terranes concept. These terranes were detached from Indochina and South China during back-arc opening of the Poko-Song Ma system, due to the westward subduction of the Palaeopacific. This also explains the location of the Cathaysian West Sumatra block to the West of the Cimmerian Sibumasu block.

Variants in MTNR1B influence fasting glucose levels.

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

Normalització del volum d'arxius de so en format MP3

L'estàndard MPEG-1 Layer III va ser creat fa poc més de 10 anys i en aquest curt espai de temps ha revolucionat el fins aleshores estable món de la música. El fet de poder comprimir tota una cançó en uns pocs 'megues' (3 o 4) sense una pèrdua apreciable de qualitat i la proliferació d'ordinadors connectats a Internet va fer que el tràfic de fitxers en aquest format col·lapsés més d'un servidor. Per això, no és estrany que apareguessin autèntiques col·leccions de fitxers musicals en format MP3 procedents de les fonts més variades. Aquest fet (la diversitat de les fonts) i la variabilitat entre els diferents codificadors fa que el volum del so d'aquests fitxers disti molt de ser semblant. I això és precisament el que procura aconseguir aquest projecte: fer que tota col·lecció de fitxers MP3 soni igual de fort.

Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.

Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.

Art contemporani xinès en el segle XXI : introducció a la pugna entre la creació i el mercat a través de cinc artistes destacats i les seves cotitzacions en les subhastes

En el relativament breu lapse de temps que suposen les tres darreres dècades, l'art contemporani xinès ha passat de ser pràcticament invisible i desconegut per al públic general, a ser present en un gran nombre d'escenaris a nivell internacional relacionats amb el món de l'art, sobre tot des de finals de la dècada dels noranta. El present TdR ha intentat apropar-se a qüestions com la imatge i les idees que sobre la RP Xina s'han transmès en l'última dècada a través de les obres o de les accions dels artistes xinesos contemporanis més exposats o cotitzats internacionalment i que viuen a la Xina, i a com s'ha arribat a inserir la producció artística d'aquests autors en el procés de globalització i hibridació de la cultura que estem vivint. Hem delimitat el camp de recerca, bàsicament a l'estudi de l'obra de cinc autors (Song Dong, Ai Weiwei, Zeng Fanzhi, Yue Minjun i Wang Qingsong) i a la seva presència en l'escena internacional de l'art contemporani a través de les subhastes de les dues cases més importants del món, Christie's i Sotheby's.

De la nostalgia a la reflexión : un recorrido por "La canción de la pena eterna", de Wang Anyi

La novela "La canción de la pena eterna" (1995), de la escritora Wang Anyi, es considerada actualmente un clásico moderno de las letras chinas. El objetivo de este trabajo se articula sobre la base de dos orientaciones. Por un lado, se realiza un extenso recorrido interpretativo por la novela, atendiendo a distintos criterios para extraer conclusiones sobre la motivación e intencionalidad de la escritora. Por otro lado, a partir de esas conclusiones, se sitúa la novela en el canon literario chino, en virtud de su propia caracterización, las influencias recibidas y su posible contribución.

Analysis of interaction of cloned human and/or sheep fetal hemoglobin gamma-chain and LPS in augmenting induction of inflammatory cytokine production in vivo and in vitro.

We have reported earlier that purified preparations of sheep fetal hemoglobin, but not adult hemoglobin, in concert with non-stimulatory doses of lipopolysaccharide (LPS) (lipid A), act cooperatively to regulate in vitro production of a number of cytokines, including TNFalpha, TGFbeta and IL-6 from murine and human leukocytes. Following in vivo treatment of mice with the same combination of hemoglobin and LPS, harvested spleen or peritoneal cells showed a similar augmented capacity to release these cytokines into culture supernatants. We report below that genetically cloned gamma-chain of human or sheep fetal hemoglobin, but not cloned alpha- or beta-chains, can produce this cooperative effect, as indeed can HPLC purified, heme-free, gamma-chains derived from cord blood fetal hemoglobin, and that purified haptoglobin completely abolishes the cooperative interaction.

Genetic divergence between two sympatric species of the Lutzomyia longipalpis complex in the paralytic gene, a locus associated with insecticide resistance and lovesong production

The sandfly Lutzomyia longipalpis s.l. is the main vector of American Visceral Leishmaniasis. L. longipalpis s.l. is a species complex but until recently the existence of cryptic sibling species among Brazilian populations was a controversial issue. A fragment of paralytic (para), a voltage dependent sodium channel gene associated with insecticide resistance and courtship song production in Drosophila, was isolated and used as a molecular marker to study the divergence between two sympatric siblings of the L. longipalpis complex from Sobral, Brazil. The results revealed para as the first single locus DNA marker presenting fixed differences between the two species in this locality. In addition, two low frequency amino-acid changes in an otherwise very conserved region of the channel were observed, raising the possibility that it might be associated with incipient resistance in this vector. To the best of our knowledge, the present study represents the first population genetics analysis of insecticide resistance genes in this important leishmaniasis vector.

War and Natural Resource Exploitation

We build a theoretical framework that allows for endogenous conflict behaviour (i.e., fighting efforts) and for endogenous natural resource exploitation (i.e., speed, ownership, and investments). While depletion is spread in a balanced Hotelling fashion during peace, the presence of conflict creates incentives for rapacious extraction, as this lowers the stakes of future contest. This voracious extraction depresses total oil revenue, especially if world oil demand is relatively elastic and the government's weapon advantage is weak. Some of these political distortions can be overcome by bribing rebels or by government investment in weapons. The shadow of conflict can also make less efficient nationalized oil extraction more attractive than private extraction, as insecure property rights create a holdup problem for the private firm and lead to a lower license fee. Furthermore, the government fights less intensely than the rebels under private exploitation, which leads to more government turnover. Without credible commitment to future fighting efforts, private oil depletion is only lucrative if the government's non-oil office rents are large and weaponry powerful, which guarantees the government a stronger grip on office and makes the holdup problem less severe.

A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.

The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P< or =5x10(-8)). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P< or =0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2x10(-19) for lead SNP, rs266717, n = 14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9x10(-8), n = 14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5x10(-6), n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2x10(-3), n = 10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.

The demographic benefits of belligerence and bravery: defeated group repopulation or victorious group size expansion?

Intraspecific coalitional aggression between groups of individuals is a widespread trait in the animal world. It occurs in invertebrates and vertebrates, and is prevalent in humans. What are the conditions under which coalitional aggression evolves in natural populations? In this article, I develop a mathematical model delineating conditions where natural selection can favor the coevolution of belligerence and bravery between small-scale societies. Belligerence increases an actor's group probability of trying to conquer another group and bravery increase the actors's group probability of defeating an attacked group. The model takes into account two different types of demographic scenarios that may lead to the coevolution of belligerence and bravery. Under the first, the fitness benefits driving the coevolution of belligerence and bravery come through the repopulation of defeated groups by fission of victorious ones. Under the second demographic scenario, the fitness benefits come through a temporary increase in the local carrying capacity of victorious groups, after transfer of resources from defeated groups to victorious ones. The analysis of the model suggests that the selective pressures on belligerence and bravery are stronger when defeated groups can be repopulated by victorious ones. The analysis also suggests that, depending on the shape of the contest success function, costly bravery can evolve in groups of any size.

New insights into dendritic cell biology and histiocytosis through a transgenic tumor model

SUMMARY The effective development of an immune response depends on the careful interplay and the regulation between innate and adaptive immunity. As the dendritic cells (DCs) are equipped with many receptors, such as Toll-like receptors, which can detect the presence of infection by recognizing different component of bacteria, fungi and even viruses, they are the among the first cells to respond to the infection. Upon pathogen challenge, the DCs interpret the innate system activation as a maturation signal, resulting in the migration of the DCS to a draining lymph node site. There, activated DCs present efficiently antigens to naïve T cells, which are in turn activated and initiate adaptive immunity. Therefore, DCs are the main connectors between innate and adaptive immune systems. In addition to be the most efficient antigen- presenting cells, DCs play a central role in the regulation of immune responses and immune tolerance. Despite extensive research, many aspects related to DC biology are still unsolved and/or controversial. The low frequency of DCs in vivo often hamper study of DC biology and in vitro-derived DCs are not suited to address certain questions, such as the development of DC. We sought of transforming in vivo the DCs through the specific expression of an oncogene, in order to obtain unlimited numbers of these cells. To achieve this goal, transgenic mouse lines expressing the SV40 Large T oncogene under the control of the CD1 1 c promoter were generated. These transgenic mice are healthy until the age of three to four months without alterations in the DC biology. Thereafter transgenic mice develop a fatal disease that shows features of a human pathology, named histiocytosis, involving DCs. We demonstrate that the disease development in the transgenic mice correlates with a massive accumulation of transformed DCs in the affected organs. Importantly, transformed DCs are immature and fully conserve their capacity to mature in antigen presenting cells. We observe hyperproliferation of transformed DCs only in the sick transgenic mice. Surprisingly, transformed DCs do not proliferate in vitro, but transfer of the transformed DCs into immunodeficient or tolerant host leads to tumor formation. Altoghether, the transgenic mouse lines we have generated represent a valuable tumor model for human histiocytosis, and provide excellent tools to study DC biology. RESUME Le développement d'une réponse immunitaire efficace dépend d'une minutieuse interaction et régulation entre l'immunité innée et adaptative. Comme les cellules dendritiques (DCs) sont équipées de nombreux récepteurs, tels que les récepteurs Toll-like, qui peuvent détecter la présence d'une infection en reconnaissant différents composants bactériens, issus de champignons ou même viraux, elles sont parmi les premières cellules à répondre à l'infection. Suite à la stimulation induite par le pathogène, les DCs interprètent l'activation du système immunitaire inné comme un signal de maturation, résultant dans la migration des DCs vers le ganglion drainant le site d'infection. Là, les DCs actives présentent efficacement des antigènes aux cellules T, qui sont à leur tour activées et initient les systèmes d'immunité adaptative. Ainsi, les DCs forment le lien principal entre les réponses immunitaires innées et adaptatives. En plus d'être les cellules présentatrices d'antigènes les plus efficaces, les DCs jouent un rôle central dans la régulation du système immunitaire et dans le phénomène de tolérance. Malgré des recherches intensives, de nombreux aspects liés à la biologie des DCs sont encore irrésolus et/ou controversés. La faible fréquence des DCs in vivo gêne souvent l'étude de la biologie de ces cellules et les DCs dérivées in vitro ne sont pas adéquates pour adresser certaines questions, telles que le développement des DCs. Afin d'obtenir des quantités illimitées de DCs, nous avons songé à transformer in vivo les DC grâce à l'expression spécifique d'un oncogène. Afin d'atteindre ce but, nous avons généré des lignées de souris transgéniques qui expriment l'oncogène SV40 Large T sous le contrôle du promoter CD1 le. Ces souris transgéniques sont saines jusqu'à l'âge de trois à quatre mois et ne présentent pas d'altération dans la biologie des DCs. Ensuite, les souris transgéniques développent une maladie présentant les traits caractéristiques d'une pathologie humaine nommée histiocytose, qui implique les DCs. Nous montrons que le développement de cette maladie corrèle avec une accumulation massive des DCs transformées dans les organes touchés. De plus, les DCs transformées sont immatures et conservent leur capacité à différencier en cellules présentatrices d'antigène. Nous observons une hyper-prolifération des DCs transformées seulement dans les souris transgéniques malades. Etonnament, les DC transformées ne prolifèrent pas in vitro, par contre, le transfert des DCs transformées dans des hôtes immuno-déficients ou tolérant conduit à la formation de tumeurs. Globalement, les lignées de souris transgéniques que nous avons générées représentent un modèle valide pour l'histiocytose humaine, et de plus, offrent d'excellents outils pour étudier la biologie des DCs.

Bioconjugated lanthanide luminescent helicates as multilabels for lab-on-a-chip detection of cancer biomarkers.

The lanthanide binuclear helicate [Eu(2)(L(C2(CO(2)H)))(3)] is coupled to avidin to yield a luminescent bioconjugate EuB1 (Q = 9.3%, tau((5)D(0)) = 2.17 ms). MALDI/TOF mass spectrometry confirms the covalent binding of the Eu chelate and UV-visible spectroscopy allows one to determine a luminophore/protein ratio equal to 3.2. Bio-affinity assays involving the recognition of a mucin-like protein expressed on human breast cancer MCF-7 cells by a biotinylated monoclonal antibody 5D10 to which EuB1 is attached via avidin-biotin coupling demonstrate that (i) avidin activity is little affected by the coupling reaction and (ii) detection limits obtained by time-resolved (TR) luminescence with EuB1 and a commercial Eu-avidin conjugate are one order of magnitude lower than those of an organic conjugate (FITC-streptavidin). In the second part of the paper, conditions for growing MCF-7 cells in 100-200 microm wide microchannels engraved in PDMS are established; we demonstrate that EuB1 can be applied as effectively on this lab-on-a-chip device for the detection of tumour-associated antigens as on MCF-7 cells grown in normal culture vials. In order to exploit the versatility of the ligand used for self-assembling [Ln(2)(L(C2(CO(2)H)))(3)] helicates, which sensitizes the luminescence of both Eu(III) and Tb(III) ions, a dual on-chip assay is proposed in which estrogen receptors (ERs) and human epidermal growth factor receptors (Her2/neu) can be simultaneously detected on human breast cancer tissue sections. The Ln helicates are coupled to two secondary antibodies: ERs are visualized by red-emitting EuB4 using goat anti-mouse IgG and Her2/neu receptors by green-emitting TbB5 using goat anti-rabbit IgG. The fact that the assay is more than 6 times faster and requires 5 times less reactants than conventional immunohistochemical assays provides essential advantages over conventional immunohistochemistry for future clinical biomarker detection.

Molecular analysis of an odorant-binding protein gene in two sympatric species of Lutzomyia longipalpis s.l.

Lutzomyia longipalpis s.l. is the main vector of American visceral leishmaniasis (AVL) and occurs as a species complex. DNA samples from two Brazilian sympatric species that differ in pheromone and courtship song production were used to analyse molecular polymorphisms in an odorant-binding protein ( obp29 ) gene. OBPs are proteins related to olfaction and are involved in activities fundamental to survival, such as foraging, mating and choice of oviposition site. In this study, the marker obp29 was found to be highly polymorphic in Lu. longipalpis s.l. , with no fixed differences observed between the two species. A pairwise fixation index test indicated a moderate level of genetic differentiation between the samples analysed.

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.