Facies characterisation of a shallow-water deltaic succession: the Upper Jurassic Wagad Sandstone Formation of Kachchh, western India

Ancient deltaic facies are difficult to differentiate from tidally influenced shallow-marine facies. The Wagad Sandstone Formation of the Wagad Highland (eastern Kachchh Basin) is typified by offshore and deltaic facies with sedimentary characteristics that represent different conditions of hydrodynamics and related depositional processes. The study area, the Adhoi Anticline, constitutes a ~154-m-thick, shale-dominated sequence with progressive upward intercalations of bioturbated micritic sandstone and quartz arenite. Two thick Astarte beds (sandy allochemic limestone), with an erosional base and gravel blanketing, illustrate tidal amplification and high-energy stochastic events such as storms. Sedimentological characteristics document three depositional facies: an offshore, shale-dominated sequence prograding to proximal prodeltaic micritic sandstone and quartz arenite with sandy allochemic limestones, further prograding to mouth bars and abandoned channel deposits. The Wagad Sandstone Formation displays depositional environmental conditions that are dissimilar from those of coeval deposits in Kachchh sub-basins as well as on regional and global scales. This is attributed to a reactivation of the Kachchh Mainland and South Wagad faults which resulted in detachment and uplift of the Wagad block which then experienced prograding deltaic conditions

Tests for finding complex patterns of differential expression in cancers: towards individualized medicine

BACKGROUND: Microarray studies in cancer compare expression levels between two or more sample groups on thousands of genes. Data analysis follows a population-level approach (e.g., comparison of sample means) to identify differentially expressed genes. This leads to the discovery of 'population-level' markers, i.e., genes with the expression patterns A > B and B > A. We introduce the PPST test that identifies genes where a significantly large subset of cases exhibit expression values beyond upper and lower thresholds observed in the control samples. RESULTS: Interestingly, the test identifies A > B and B < A pattern genes that are missed by population-level approaches, such as the t-test, and many genes that exhibit both significant overexpression and significant underexpression in statistically significantly large subsets of cancer patients (ABA pattern genes). These patterns tend to show distributions that are unique to individual genes, and are aptly visualized in a 'gene expression pattern grid'. The low degree of among-gene correlations in these genes suggests unique underlying genomic pathologies and high degree of unique tumor-specific differential expression. We compare the PPST and the ABA test to the parametric and non-parametric t-test by analyzing two independently published data sets from studies of progression in astrocytoma. CONCLUSIONS: The PPST test resulted findings similar to the nonparametric t-test with higher self-consistency. These tests and the gene expression pattern grid may be useful for the identification of therapeutic targets and diagnostic or prognostic markers that are present only in subsets of cancer patients, and provide a more complete portrait of differential expression in cancer

Genetic sequence stratigraphy on the basis of ichnology for the Middle Jurassic basin margin succession of Chorar Island (eastern Kachchh Basin, western India)

Synrift basin margin successions are greatly influenced by eustatic sea level changes, tectonics and accommodation space filled in by sediments. The Middle Jurassic (Bajocian–Callovian) of Chorar Island (western India) comprises a ~109-m-thick synrift basin margin succession of clastic, non-clastic and mixed siliciclastic-carbonate rocks which are here analysed and categorised into nine lithofacies. The succession is bioturbated to varying intensities; 16 identified ichnogenera can be assigned to environmentally related groups of five trace fossil assemblages, which include Gyro- chorte, Hillichnus, Rhizocorallium, Skolithos and Thalassinoides. These ichnoassemblages document the Skolithos and Cruz- iana Ichnofacies which marks a change in energy conditions, sedimentation dispersal patterns and bathymetry in a shal- low-marine environment. The Bajocian–Callovian succession is further analysed on the basis of sedimentological and ichnological data that show two genetic sequences consisting of Transgressive Systems Tract and Highstand Systems Tract bounded by Maximum Flooding Surface. The synrift basin margin succession of the Middle Jurassic of Chorar Island shows cyclicity in deposition; the Bajocian–Bathonian succession represents progradational to retrogradational coastlines, while the Callovian succession documents an aggrading progradational coastline

New mono- and polynuclear copper(II) complexes: Structural characterization, quantum chemical calculations and antioxidant superoxide dismutase studies

506-518Two copper(II) complexes have been synthesized and characterized using elemental and spectral analysis. The molecular structures of both complexes have been confirmed by single crystal X-ray analysis. The stability of the metal centre was examined using cyclic and differential pulse voltammetry in DMSO solution. X-band electron paramagnetic spectra were recorded both in solid and frozen solution to confirm the d9 configuration. Frozen solution spectra of complexes have the trend in the spin Hamiltonian parameters gǁ > g > 2.0023 and Aǁ 156 x 10-4 cm-1 revealing a dx2-y2 ground state with tetragonal symmetry for copper(II) ion. Density functional calculations have been performed and results are found to agree with the experimental results. Antibacterial activities of complexes were screened by taking gram-positive and gram-negative bacteria. Further, in vitro antioxidant (superoxide dismutase) properties of 1 and 2 showed considerable activity compared to other SOD mimics

New mono- and polynuclear copper(II) complexes: Structural characterization, quantum chemical calculations and antioxidant superoxide dismutase studies

Two copper(II) complexes have been synthesized and characterized using elemental and spectral analysis. The molecular structures of both complexes have been confirmed by single crystal X-ray analysis. The stability of the metal centre was examined using cyclic and differential pulse voltammetry in DMSO solution. X-band electron paramagnetic spectra were recorded both in solid and frozen solution to confirm the d9 configuration. Frozen solution spectra of complexes have the trend in the spin Hamiltonian parameters  and  cm-1 revealing a  ground state with tetragonal symmetry for copper(II) ion. Density functional calculations have been performed and results are found to agree with the experimental results. Antibacterial activities of complexes were screened by taking gram-positive and gram-negative bacteria. Further, in vitro antioxidant (superoxide dismutase) properties of 1 and 2 showed considerable activity compared to other SOD mimics

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA\u27s research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC

PCYT1A Regulates Phosphatidylcholine Homeostasis from the Inner Nuclear Membrane in Response to Membrane Stored Curvature Elastic Stress.

Cell and organelle membranes consist of a complex mixture of phospholipids (PLs) that determine their size, shape, and function. Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic membranes, yet how cells sense and regulate its levels in vivo remains unclear. Here we show that PCYT1A, the rate-limiting enzyme of PC synthesis, is intranuclear and re-locates to the nuclear membrane in response to the need for membrane PL synthesis in yeast, fly, and mammalian cells. By aligning imaging with lipidomic analysis and data-driven modeling, we demonstrate that yeast PCYT1A membrane association correlates with membrane stored curvature elastic stress estimates. Furthermore, this process occurs inside the nucleus, although nuclear localization signal mutants can compensate for the loss of endogenous PCYT1A in yeast and in fly photoreceptors. These data suggest an ancient mechanism by which nucleoplasmic PCYT1A senses surface PL packing defects on the inner nuclear membrane to control PC homeostasis

Effects of scleroderma antibodies and pooled human immunoglobulin on anal sphincter and colonic smooth muscle function.

BACKGROUND & AIMS: Patients with systemic sclerosis (SSc) have impairments in gastrointestinal smooth muscle function. The disorder has been associated with circulating antibodies to cholinergic muscarinic the type-3 receptor (M(3)-R). We investigated whether it is possible to neutralize these antibodies with pooled human IgGs (pooledhIgG). METHODS: We studied the effects of IgGs purified from patients with SSc (SScIgGs) on cholinergic nerve stimulation in rat colon tissues. We also examined the effects of SScIgGs on M(3)-R activation by bethanechol (BeCh), M(3)-R occupancy, and receptor binding using immunofluorescence, immunoblot, and enzyme-linked immunosorbent analyses of human internal anal sphincter (IAS) smooth muscle cells, before and after administration of pooledhIgG. Functional displacement of M(3)-R occupancy by the SScIgGs was compared with that of other IgGs during the sustained phase of BeCh-induced contraction of intact smooth muscles from rats. RESULTS: SScIgG significantly attenuated neurally mediated contraction and acetylcholine release in rat colon as well as BeCh-induced sustained contraction of the IAS smooth muscle. In immunofluorescence analysis, SScIgG co-localized with M(3)-R. In immunoblot and enzyme-linked immunosorbent analyses, M(3)-R loop-2 peptide and human IAS SMC membrane lysates bound significant amounts of SScIgG, compared with IgGs from healthy individuals and pooledhIgG. Binding was attenuated significantly by application of pooledhIgG, which by itself had no significant effect. Incubation of samples with pooledhIgG, or mixing pooledhIgG with SScIgG before administration to tissues, significantly reduced binding of SScIgG, indicating that pooledhIgG prevents SScIgG blockade of M(3)-R. CONCLUSIONS: In studies of rat and human tissues, pooled human IgG prevent and reverses the cholinergic dysfunction associated with the progressive gastrointestinal manifestations of SSc by neutralizing functional M(3)-R antibodies present in the circulation of patients with SSc