Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma

The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Most breaks on chromosome 18 are located at the 3'-UTR of the BCL2 gene and are mainly clustered in the major breakpoint region (MBR). Recently, we found that the BCL2 MBR has a non-B DNA character in genomic DNA. Here, we show that single-stranded DNA modeled from the template strand of the BCL2 MBR, forms secondary structures that migrate faster on native PAGE in the presence of potassium, due to the formation of intramolecular G-quadruplexes. Circular dichroism shows evidence for a parallel orientation for G-quadruplex structures in the template strand of the BCL2 MBR. Mutagenesis and the DMS modification assay confirm the presence of three guanine tetrads in the structure. 1H nuclear magnetic resonance studies further confirm the formation of an intramolecular G-quadruplex and a representative model has been built based on all of the experimental evidence. We also provide data consistent with the possible formation of a G-quadruplex structure at the BCL2 MBR within mammalian cells. In summary, these important features could contribute to the single-stranded character at the BCL2 MBR, thereby contributing to chromosomal fragility.

An Approach Toward Homocalystegines and Silyl-homocalystegines. Acid-Mediated Migrations of Acetates in Seven-Membered Ring Systems

A short access to homocalystegine analogues silylated at C7 is described. The synthesis involves the desymmetrization of a (phenyldimethylsilyl)methylcycloheptatriene using osmium-mediated dihydroxylation, followed by the diol protection and a cycloaddition involving the remaining diene moiety and an acylnitroso reagent. Additions of the osmium and acylnitroso reagents were shown, through X-ray diffraction studies of the resulting major isomers, to occur anti and syn, respectively, relative to the SiCH2 substituent. N-O bond cleavage on the resulting cycloadduct then produces the aminopolyol having a silylmethyl substituent. Oxidation of the C-Si bond also afforded an access to unusual amino-heptitols having five contiguous stereogenic centers. In the course of this work, we finally observed a unusual rearrangement taking place on cycloheptanone 18 substituted by two acetyl groups and a neighboring Boc-protected amine. A profound reorganization of the substituents on the seven-membered ring effectively took place under acidic conditions (TFA) leading to the thermodynamically more stable homocalystegine-type compound., DFT calculations of the conformational energy of isomeric silyl homocalystegines indicated that the product observed upon the acid-mediated rearrangement was the most stable of a series of analogues with various distributions of substituents along the seven-membered ring backbone. A tentative mechanism is proposed to rationalize the acetate migrations and inversions of the stereochemistry at various stereocenters.

18-Bit binary inductive voltage divider for self balancing ac bridge applications

The constructional details of an 18-bit binary inductive voltage divider (IVD) for a.c. bridge applications is described. Simplified construction with less number of windings, interconnection of winding through SPDT solid state relays instead of DPDT relays, improves reliability of IVD. High accuracy for most precision measurement achieved without D/A converters. The checks for self consistency in voltage division shows that the error is less than 2 counts in 2(18).

Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma

The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Most breaks on chromosome 18 are located at the 3'-UTR of the BCL2 gene and are mainly clustered in the major breakpoint region (MBR). Recently, we found that the BCL2 MBR has a non-B DNA character in genomic DNA. Here, we show that single-stranded DNA modeled from the template strand of the BCL2 MBR, forms secondary structures that migrate faster on native PAGE in the presence of potassium, due to the formation of intramolecular G-quadruplexes. Circular dichroism shows evidence for a parallel orientation for G-quadruplex structures in the template strand of the BCL2 MBR. Mutagenesis and the DMS modification assay confirm the presence of three guanine tetrads in the structure. 1H nuclear magnetic resonance studies further confirm the formation of an intramolecular G-quadruplex and a representative model has been built based on all of the experimental evidence. We also provide data consistent with the possible formation of a G-quadruplex structure at the BCL2 MBR within mammalian cells. In summary, these important features could contribute to the single-stranded character at the BCL2 MBR, thereby contributing to chromosomal fragility.

Conformation and orientation of alkyl chains in the layered organic-inorganic hybrids: (CnH2n+1NH3)(2)PbI4 (n=12,16,18)

Layered organic inorganic hybrids based on perovskite-derived alkylammonium lead halides have been demonstrated as important new materials in the construction of molecular electronic devices. Typical of this class of materials are the single-perovskite slab lead iodides of the general formula (CnH2n+1NH3)(2)PbI4. While for small n, these compounds are amenable to single-crystal structure determination, the increasing degree of disorder in the long chain (n = 12,14...) compounds makes such an analysis difficult. In this study, we use powder X-ray diffraction, and vibrational and C-13 NMR spectroscopies to establish the conformation, orientation and organization of hydrocarbon chains in the series of layered alkylammonium lead iodides (CnH2n+1NH3)(2)PbI4 (n = 12,16,18). We find that the alkyl chains adopt a tilted bilayer arrangement, while the structure of the inorganic layer remains invariant with respect to the value of n. Conformation-sensitive methylene stretching modes in the infrared and Raman spectra, as well as the C-13 NMR spectra indicate that bonds in the methylene chain are in trans configuration. The skeletal modes of the alkyl chain in the Raman spectra establish that there is a high degree of all-trans conformational registry for the values of n studied here. From the orientation dependence of the infrared spectra of crystals of (CnH2n+1NH3)(2)PbI4 ( n = 12,16), we find that the molecular axis of the all-trans alkyl chains are tilted away from the interlayer normal by an angle of 55degrees. This value of this tilt angle is consistent with the dependence of the c lattice expansion as a function of n, as determined from powder X-ray diffraction.

Phase transitions in the anchored organic bilayers of long-chain alkylammonium lead iodides (CnH2n+1NH3)(2)PbI4; n=12, 16, 18

The single perovskite slab alkylammonium lead iodides (CnH2n+1NH3)(2)PbI4, n = 12, 16, 18, display two phase transitions, just above room temperature, associated with changes in the alkylammonium chains. We have followed these two phase transitions using scanning calorimetry, X-ray powder diffraction, and IR and Raman spectroscopies. We find the first phase transition to be associated with symmetry changes arising from a dynamic rotational disordering of the ammonium headgroup of the chain whereas the second transition, the melting of the chains in two dimensions, is characterized by an increased conformational disorder of the methylene units of the alkyl chains. We examine these phase transitions in light of the interesting optical properties of these materials, as well as the relevance of these systems as models for phase transitions in lipid bilayers.

The 18 September 2011, North Sikkim earthquake

The 18 September 2011, magnitude Mw 6.9 earthquake close to the Nepal-Sikkim border caused significant damage due to ground shaking and caused several landslides. Observations from the post-earthquake surveys in the affected areas within Sikkim suggest that the poorly engineered, multistoried structures were relatively more impacted. Those located on alluvial terraces were also affected. The morphology of the region is prone to landslides and the possibility for their increased intensity during the forthcoming monsoon need to be considered seriously. From the seismotectonic perspective, the mid-crustal focal depth of the North Sikkim earthquake reflects the ongoing deformation of the subducting Indian plate.

Role of water contamination within the GC column of a GasBench II peripheral on the reproducibility of O-18/O-16 ratios in water samples

The GasBench II peripheral along with MAT 253 combination provides a more sensitive platform for the determination of water isotope ratios. Here, we examined the role of adsorbed moisture within the gas chromatography (GC) column of the GasBench II on measurement uncertainties. The uncertainty in O-18/O-16 ratio measurements is determined by several factors, including the presence of water in the GC. The contamination of GC with water originating from samples as water vapour over a longer timeframe is a critical factor in determining the reproducibility of O-18/O-16 ratios in water samples. The shift in isotope ratios observed in the experiment under dry and wet conditions correlates strongly with the retention time of analyte CO2, indicating the effect of accumulated moisture. Two possible methods to circumvent or minimise the effect of adsorbed water on isotope ratios are presented here. The proposed methodology includes either the regular baking of the GC column at a higher temperature (120 degrees C) after analysis of a batch of 32 sample entries or conducting the experiment at a low GC column temperature (22.5 degrees C). The effects of water contamination on long-term reproducibility of reference water, with and without baking protocol, have been described.

Controls on intense silicate weathering in a tropical river, southwestern India

The Silicate Weathering Rate (SWR) and associated Carbon dioxide Consumption Rate (CCR) in tropical silicate terrain is assessed through a study of the major ion chemistry in a small west flowing river of Peninsular India, the Nethravati River. The specific features of the river basin are high mean annual rainfall and temperature, high runoff and a Precambrian basement composed of granitic-gneiss, charnockite and minor metasediments. The water samples (n = 56) were collected from three locations along the Nethravati River and from two of its tributaries over a period of twelve months. Chemical Weathering Rate (CWR) for the entire watershed is calculated by applying rainwater correction using river chloride as a tracer. Chemical Weathering Rate in the Nethravati watershed is estimated to 44 t.km(-2).y(-1) encompassing a SWR of 42 t.km(-2).y(-1) and a maximum carbonate contribution of 2 t.km(-2).y(-1). This SWR is among the highest reported for granito-gneissic terrains. The assessed CCR is 2.9 . 10(5) mol.km(-2).y(-1). The weathering index (Re). calculated from molecular ratios of dissolved cations and silica in the river, suggests an intense silicate weathering leading to kaolinite-gibbsite precipitation in the weathering covers. The intense SWR and CCR could be due to the combination of high runoff and temperature along with the thickness and nature of the weathering cover. The comparison of silicate weathering fluxes with other watersheds reveals that under similar morpho-climatic settings basalt weathering would be 2.5 times higher than the granite-gneissic rocks. (C) 2012 Elsevier B.V. All rights reserved.

Mechanism of Fragility at BCL2 Gene Minor Breakpoint Cluster Region during t(14;18) Chromosomal Translocation

The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Breaks in chromosome 18 are localized at the 3'-UTR of BCL2 gene or downstream and are mainly clustered in either the major breakpoint region or the minor breakpoint cluster region (mcr). The recombination activating gene (RAG) complex induces breaks at IgH locus of chromosome 14, whereas the mechanism of fragility at BCL2 mcr remains unclear. Here, for the first time, we show that RAGs can nick mcr; however, the mechanism is unique. Three independent nicks of equal efficiency are generated, when both Mg2+ and Mn2+ are present, unlike a single nick during V(D)J recombination. Further, we demonstrate that RAG binding and nicking at the mcr are independent of nonamer, whereas a CCACCTCT motif plays a critical role in its fragility, as shown by sequential mutagenesis. More importantly, we recapitulate the BCL2 mcr translocation and find that mcr can undergo synapsis with a standard recombination signal sequence within the cells, in a RAG-dependent manner. Further, mutation to the CCACCTCT motif abolishes recombination within the cells, indicating its vital role. Hence, our data suggest a novel, physiologically relevant, nonamer-independent mechanism of RAG nicking at mcr, which may be important for generation of chromosomal translocations in humans.

Synthesis and spectral characterization of cyclotriphosphazene based 18-membered macrocycles

New 18-membered cyclotriphosphazene-containing macrocycles 7-10 were obtained by 1 + 1 condensation reaction of dispiro-N3P3(C12H8O2)(2)((N(Me)N=CH)(2) N4C20H26)] (2) with N,N'-dimethyl-ethylenediamine-1,4-diyldimethylenebis(4-methyl-2-formylph enol) (3), N,N'-dimethyl-ethylenediamine-1,4-diyldimethylenebis(4,5-dimethyl-2-form ylphenol) (4), N,N'-dimethyl-ethylenediamine-1,4-diyldimethylenebis(5-chloro-2-formylph enol) (5) and N,N'-dimethyl-ethylenediamine-1,4-diyldimethylenebis(5-bromo-2-formylphe nol) (6), respectively. (C) 2012 Elsevier B.V. All rights reserved.

Characterization of groundwater chemistry under the influence of lithologic and anthropogenic factors along a climatic gradient in Upper Cauvery basin, South India

Hydrogeological and climatic effect on chemical behavior of groundwater along a climatic gradient is studied along a river basin. `Semi-arid' (500-800 mm of mean annual rainfall), `sub-humid' (800-1,200 mm/year) and `humid' (1,200-1,500 mm/year) are the climatic zones chosen along the granito-gneissic plains of Kabini basin in South India for the present analysis. Data on groundwater chemistry is initially checked for its quality using NICB ratio (<+/- 5 %), EC versus TZ+ (similar to 0.85 correlation), EC versus TDS and EC versus TH analysis. Groundwater in the three climatic zones is `hard' to `very hard' in terms of Ca-Mg hardness. Polluted wells are identified (> 40 % of pollution) and eliminated for the characterization. Piper's diagram with mean concentrations indicates the evolution of CaNaHCO3 (semi-arid) from CaHCO3 (humid zone) along the climatic gradient. Carbonates dominate other anions and strong acids exceeded weak acids in the region. Mule Hole SEW, an experimental watershed in sub-humid zone, is characterized initially using hydrogeochemistry and is observed to be a replica of entire sub-humid zone (with 25 wells). Extension of the studies for the entire basin (120 wells) showed a chemical gradient along the climatic gradient with sub-humid zone bridging semi-arid and humid zones. Ca/Na molar ratio varies by more than 100 times from semi-arid to humid zones. Semi-arid zone is more silicaceous than sub-humid while humid zone is more carbonaceous (Ca/Cl similar to 14). Along the climatic gradient, groundwater is undersaturated (humid), saturated (sub-humid) and slightly supersaturated (semi-arid) with calcite and dolomite. Concentration-depth profiles are in support of the geological stratification i.e., not approximate to 18 m of saprolite and similar to 25 m of fracture rock with parent gneiss beneath. All the wells are classified into four groups based on groundwater fluctuations and further into `deep' and `shallow' based on the depth to groundwater. Higher the fluctuations, larger is its impact on groundwater chemistry. Actual seasonal patterns are identified using `recharge-discharge' concept based on rainfall intensity instead of traditional monsoon-non-monsoon concept. Non-pumped wells have low Na/Cl and Ca/Cl ratios in recharge period than in discharge period (Dilution). Few other wells, which are subjected to pumping, still exhibit dilution chemistry though water level fluctuations are high due to annual recharge. Other wells which do not receive sufficient rainfall and are constantly pumped showed high concentrations in recharge period rather than in discharge period (Anti-dilution). In summary, recharge-discharge concept demarcates the pumped wells from natural deep wells thus, characterizing the basin.

Sources of major ions and processes affecting the geochemical and isotopic signatures of subsurface waters along a tropical river, Southwestern India

Systematic monitoring of subsurface hydrogeochemistry has been carried out for a period of one year in a humid tropical region along the Nethravati-Gurupur River. The major ion and stable isotope (delta O-18 and delta H-2) compositions are used to understand the hydrogeochemistry of groundwater and its interaction with surface water. In the study, it is observed that intense weathering of source rocks is the major source of chemical elements to the surface and subsurface waters. In addition, agricultural activities and atmospheric contributions also control the major ion chemistry of water in the study area. There is a clear seasonality in the groundwater chemistry, which is related to the recharge and discharge of the hydrological system. On a temporal scale, there is a decrease in major cation concentrations during the monsoon which is a result of dilution of sources from the weathering of rock minerals, and an increase in anion concentrations which is contributed by the atmosphere, accompanied by an increase in water level during the monsoon. The stable isotope composition indicates that groundwater in the basin is of meteoric origin and recharged directly from the local precipitation during the monsoonal season. Soon after the monsoon, groundwater and surface water mix in the subsurface region. The groundwater feeds the surface water during the lean river flow season.

Influence of the upwelling events on the delta C-13 and delta O-18 of the benthic bivalve shells of the South Western Continental Margin of India

In this study, the influence of the spatial and temporal variability of upwelling intensity and the associated biological productivity observed during different phases of summer monsoon along the southwestern continental margin of India (SWCMI) on the delta C-13 and delta O-18 of the inorganic biogenic carbonate shells was investigated. Multispecies benthic bivalve shells (1-5 mm) separated from ten surface sediment samples of SWCMI (off 12 degrees N, 10 degrees N and 9 degrees N) collected during the onset (OSM) and peak (PSM) phase of the summer monsoon of 2009 were analysed for delta C-13 and delta O-18. Sea surface temperature along the study region indicates prominent upwelling in PSM than in OSM. A comparison of analytical and predicted values for delta O-18 in the bivalve shells confirmed their in situ origin during both the sampling periods. During PSM, the delta C-13 values in the benthic bivalve shells were more depleted in C-13 than during OSM which recorded lower values of delta C-13 in dissolved inorganic carbon of bottom waters expected in the study region in PSM due to the upwelled waters, high surface productivity and the associated high degradation of the organic matter in the subsurface and bottom waters. However, this depletion of delta C-13 was not observed in benthic bivalve shells obtained from 10 degrees N, since it is influenced by high export fluxes of carbon from the Cochin estuary since early monsoon months.