Temperature Profiles of Accretion Disks around Rapidly Rotating Neutron Stars in General Relativity and Implications for Cygnus X-2

We calculate the temperature profiles of (thin) accretion disks around rapidly rotating neutron stars (with low surface magnetic fields), taking into account the full effects of general relativity. We then consider a model for the spectrum of the X-ray emission from the disk, parameterized by the mass accretion rate, the color temperature and the rotation rate of the neutron star. We derive constraints on these parameters for the X-ray source Cygnus X-2 using the estimates of the maximum temperature in the disk along with the disk and boundary layer luminosities, using the spectrum inferred from the EXOSAT data. Our calculations suggest that the neutron star in Cygnus X-2 rotates close to the centrifugal mass-shed limit. Possible constraints on the neutron star equation of state are also discussed.Comment: 18 pages, 9 figs., 2 tables, uses psbox.tex and emulateapj5.sty. Submitted to Ap

The evolution of a Gondwanan collisional orogen: A structural and geochronological appraisal from the Southern Granulite Terrane, South India

Gondwana amalgamated along a suite of Himalayan-scale collisional orogens, the roots of which lace the continents of Africa, South America, and Antarctica. The Southern Granulite Terrane of India is a generally well-exposed, exhumed, Gondwana-forming orogen that preserves a record of the tectonic evolution of the eastern margin of the East African Orogen during the Ediacaran-Cambrian (circa 600–500 Ma) as central Gondwana formed. The deformation associated with the closure of the Mozambique Ocean and collision of the Indian and East African/Madagascan cratonic domains is believed to have taken place along the southern margin of the Salem Block (the Palghat-Cauvery Shear System, PCSS) in the Southern Granulite Terrane. Investigation of the structural fabrics and the geochronology of the high-grade shear zones within the PCSS system shows that the Moyar-Salem-Attur shear zone to the north of the PCSS system is early Paleoproterozoic in age and associated with dextral strike-slip motion, while the Cauvery shear zone (CSZ) to the south of the PCSS system can be loosely constrained to circa 740–550 Ma and is associated with dip-slip dextral transpression and north side-up motion.To the south of the proposed suture zone (the Cauvery shear zone), the structural fabrics of the Northern Madurai Block suggest four deformational events (D1–D4), some of which are likely to be contemporaneous. The timing of high pressure-ultrahigh temperature metamorphism and deformation (D1–D3) in the Madurai Block (here interpreted as the southern extension of Azania) is constrained to circa 550–500 Ma and interpreted as representing collisional orogeny and subsequent orogenic collapse of the eastern margin of the East African Orogen. The disparity in the nature of the structural fabrics and the timing of the deformation in the Salem and the Madurai Blocks suggest that the two experienced distinct tectonothermal events prior to their amalgamation along the Cauvery shear zone during the Ediacaran/Cambrian

JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny

Background: It has been reported that the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway regulates erythropoietin (EPO)-induced survival, proliferation, and maturation of early erythroid progenitors. Erythroid cell proliferation and survival have also been related to activation of the JAK-STAT pathway. The goal of this study was to observe the function of EPO activation of JAK-STAT and PI3K/AKT pathways in the development of erythroid progenitors from hematopoietic CD34(+) progenitor cells, as well as to distinguish early EPO target genes in human erythroid progenitors during ontogeny. Methods: Hematopoietic CD34(+) progenitor cells, isolated from fetal and adult hematopoietic tissues, were differentiated into erythroid progenitor cells. We have used microarray analysis to examine JAK-STAT and PI3K/AKT related genes, as well as broad gene expression modulation in these human erythroid progenitor cells. Results: In microarray studies, a total of 1755 genes were expressed in fetal liver, 3844 in cord blood, 1770 in adult bone marrow, and 1325 genes in peripheral blood-derived erythroid progenitor cells. The erythroid progenitor cells shared 1011 common genes. Using the Ingenuity Pathways Analysis software, we evaluated the network pathways of genes linked to hematological system development, cellular growth and proliferation. The KITLG, EPO, GATA1, PIM1 and STAT3 genes represent the major connection points in the hematological system development linked genes. Some JAK-STAT signaling pathway-linked genes were steadily upregulated throughout ontogeny (PIM1, SOCS2, MYC, PTPN11), while others were downregulated (PTPN6, PIAS, SPRED2). In addition, some JAK-STAT pathway related genes are differentially expressed only in some stages of ontogeny (STATs, GRB2, CREBB). Beside the continuously upregulated (AKT1, PPP2CA, CHUK, NFKB1) and downregulated (FOXO1, PDPK1, PIK3CG) genes in the PI3K-AKT signaling pathway, we also observed intermittently regulated gene expression (NFKBIA, YWHAH). Conclusions: This broad overview of gene expression in erythropoiesis revealed transcription factors differentially expressed in some stages of ontogenesis. Finally, our results show that EPO-mediated proliferation and survival of erythroid progenitors occurs mainly through modulation of JAK-STAT pathway associated STATs, GRB2 and PIK3 genes, as well as AKT pathway-coupled NFKBIA and YWHAH genes

Three dimensional lithospheric structure of the western continental margin of India constrained from gravity modelling: implication for tectonic evolution

This paper describes a 3-D lithospheric density model of the Western Continental Margin of India (WCMI) based on forward modelling of gravity data derived from satellite altimetry over the ocean and surface measurements on the Indian peninsula. The model covers the north-eastern Arabian Sea and the western part of the Indian Peninsula and incorporates constraints from a wide variety of geophysical and geological information. Salient features of the density model include: (1) the Moho depth varying from 13 km below the oceanic crust to 46 km below the continental interior; (2) the lithosphere–asthenosphere boundary (LAB) located at depths between 70 km in the southwestern corner (under oceanic crust) and about 165 km below the continental region; (3) thickening of the crust under the Chagos–Laccadive and Laxmi Ridges and (4) a revised definition of the continent–ocean boundary. The 3-D density structure of the region enables us to propose an evolutionary model of the WCMI that revisits earlier views of passive rifting. The first stage of continental-scale rifting of Madagascar from India at about 90 Ma is marked by relatively small amounts of magmatism. A second episode of rifting and large-scale magmatism was possibly initiated around 70 Ma with the opening of the Gop Rift. Subsequently at around 68 Ma, the drifting away of the Seychelles and formation of the Laxmi Ridge was a consequence of the down-faulting of the northern margin. During this second episode of rifting, the northern part of the WCMI witnessed massive volcanism attributed to interaction with the Reunion hotspot at around 65 Ma. Subsequent stretching of the transitional crust between about 65 and 62 Ma formed the Laxmi Basin, the southward extension of the failed Gop Rift. As the interaction between plume and lithosphere continued, the Chagos–Laccadive Ridge was emplaced on the edge of the nascent oceanic crust/rifted continental margin in the south as the Indian Plate was moving northwards

Whole Exome Sequencing Reveals the Major Genetic Contributors to Nonsyndromic Tetralogy of Fallot

Rationale: Familial recurrence studies provide strong evidence for a genetic component to the predisposition to sporadic, nonsyndromic Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease phenotype. Rare genetic variants have been identified as important contributors to the risk of congenital heart disease, but relatively small numbers of TOF cases have been studied to date. Objective: We used whole exome sequencing to assess the prevalence of unique, deleterious variants in the largest cohort of nonsyndromic TOF patients reported to date. Methods and Results: Eight hundred twenty-nine TOF patients underwent whole exome sequencing. The presence of unique, deleterious variants was determined; defined by their absence in the Genome Aggregation Database and a scaled combined annotation-dependent depletion score of ≥20. The clustering of variants in 2 genes, NOTCH1 and FLT4, surpassed thresholds for genome-wide significance (assigned as P<5×10−8) after correction for multiple comparisons. NOTCH1 was most frequently found to harbor unique, deleterious variants. Thirty-one changes were observed in 37 probands (4.5%; 95% CI, 3.2%–6.1%) and included 7 loss-of-function variants 22 missense variants and 2 in-frame indels. Sanger sequencing of the unaffected parents of 7 cases identified 5 de novo variants. Three NOTCH1 variants (p.G200R, p.C607Y, and p.N1875S) were subjected to functional evaluation, and 2 showed a reduction in Jagged1-induced NOTCH signaling. FLT4 variants were found in 2.4% (95% CI, 1.6%–3.8%) of TOF patients, with 21 patients harboring 22 unique, deleterious variants. The variants identified were distinct to those that cause the congenital lymphoedema syndrome Milroy disease. In addition to NOTCH1, FLT4 and the well-established TOF gene, TBX1, we identified potential association with variants in several other candidates, including RYR1, ZFPM1, CAMTA2, DLX6, and PCM1. Conclusions: The NOTCH1 locus is the most frequent site of genetic variants predisposing to nonsyndromic TOF, followed by FLT4. Together, variants in these genes are found in almost 7% of TOF patients

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field