Neurofibromas in NF1: Schwann cell origin and role of tumor environment     

Zhu Y  Ghosh P  Charnay P  Burns DK  Parada LF 《Science (New York, N.Y.)》2002,296(5569):920-922

Neurofibromatosis type 1 (NF1) is one of the most prevalent dominantly inherited genetic diseases of the nervous system. NF1 encodes a tumor suppressor whose functional loss results in the development of benign neurofibromas that can progress to malignancy. Neurofibromas are complex tumors composed of axonal processes, Schwann cells, fibroblasts, perineurial cells, and mast cells. Through use of a conditional (cre/lox) allele, we show that loss of NF1 in the Schwann cell lineage is sufficient to generate tumors. In addition, complete NF1-mediated tumorigenicity requires both a loss of NF1 in cells destined to become neoplastic as well as heterozygosity in non-neoplastic cells. The requirement for a permissive haploinsufficient environment to allow tumorigenesis may have therapeutic implications for NF1 and other familial cancers.  相似文献   

PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation     

Lee KY  D'Acquisto F  Hayden MS  Shim JH  Ghosh S 《Science (New York, N.Y.)》2005,308(5718):114-118

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Coiled-coil irregularities and instabilities in group A Streptococcus M1 are required for virulence     

McNamara C  Zinkernagel AS  Macheboeuf P  Cunningham MW  Nizet V  Ghosh P 《Science (New York, N.Y.)》2008,319(5868):1405-1408

Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus (GAS). Here, we report the approximately 3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.  相似文献   

Modification of the active site of alkaline phosphatase by site-directed mutagenesis   总被引：4，自引：0，他引：4  

S S Ghosh  S C Bock  S E Rokita  E T Kaiser 《Science (New York, N.Y.)》1986,231(4734):145-148

The catalytically essential amino acid in the active site of bacterial alkaline phosphatase (Ser-102) has been replaced with a cysteine by site-directed mutagenesis. The resulting thiol enzyme catalyzes the hydrolysis of a variety of phosphate monoesters. The rate-determining step of hydrolysis, however, is no longer the same for catalysis when the active protein nucleophile is changed from the hydroxyl of serine to the thiol of cysteine. Unlike the steady-state kinetics of native alkaline phosphatase, those of the mutant show sensitivity to the leaving group of the phosphate ester.  相似文献   

Development of an agricultural crops spectral library and classification of crops at cultivar level using hyperspectral data   总被引：1，自引：0，他引：1  

N. Rama Rao  P. K. Garg  S. K. Ghosh 《Precision Agriculture》2007,8(4-5):173-185

In the context of a growing interest in remote sensing for precision agriculture applications, the utility of space-borne hyperspectral imaging for the development of a crop-specific spectral library and automatic identification and classification of three cultivars for each of rice (Oryza sativa L.), chilli (Capsicum annuum L.), sugarcane (Saccharum officinarum L.) and cotton (Gossipium hirsutum L.) crops have been investigated in this study. The classification of crops at cultivar level using two spectral libraries developed using hyperspectral reflectance data at canopy scale (in-situ hyperspectral measurements) and at pixel scale (Hyperion data) has shown promising results with 86.5 and 88.8% overall classification accuracy, respectively. This observation highlights the possible integration of in-situ hyperspectral measurements with space-borne hyperspectral remote sensing data for automatic identification and discrimination of various crop cultivars. However, considerable spectral similarity is observed between cultivars of rice and sugarcane crops which may pose problems in the accurate identification of various crop cultivars.  相似文献   

Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor     

Hong L  Koelsch G  Lin X  Wu S  Terzyan S  Ghosh AK  Zhang XC  Tang J 《Science (New York, N.Y.)》2000,290(5489):150-153

Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease involved in the production of beta-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S4 to S2' are well defined. A kink of the inhibitor chain at P2' and the change of chain direction of P3' and P4' may be mimicked to provide inhibitor selectivity.  相似文献   

Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo     

Meyron-Holtz EG  Ghosh MC  Rouault TA 《Science (New York, N.Y.)》2004,306(5704):2087-2090

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Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi network     

Doray B  Ghosh P  Griffith J  Geuze HJ  Kornfeld S 《Science (New York, N.Y.)》2002,297(5587):1700-1703

The Golgi-localized, gamma-ear-containing, adenosine diphosphate ribosylation factor-binding proteins (GGAs) are multidomain proteins that bind mannose 6-phosphate receptors (MPRs) in the Golgi and have an essential role in lysosomal enzyme sorting. Here the GGAs and the coat protein adaptor protein-1 (AP-1) were shown to colocalize in clathrin-coated buds of the trans-Golgi networks of mouse L cells and human HeLa cells. Binding studies revealed a direct interaction between the hinge domains of the GGAs and the gamma-ear domain of AP-1. Further, AP-1 contained bound casein kinase-2 that phosphorylated GGA1 and GGA3, thereby causing autoinhibition. This could induce the directed transfer of the MPRs from GGAs to AP-1. MPRs that are defective in binding to GGAs are poorly incorporated into AP-1-containing clathrin-coated vesicles. Thus, the GGAs and AP-1 interact to package MPRs into AP-1-containing coated vesicles.  相似文献   

Hydrous Ferric Oxide (HFO)—a Scavenger for Fluoride from Contaminated Water     

Dey  Soumen  Goswami  Saswati  Ghosh  Uday Chand 《Water, air, and soil pollution》2004,158(1):311-323

Groundwaters contaminated with excess fluoride (above 1.5 mg/L) posed some risks to the public health in India. Methods available for fluoride contaminated water treatment are cogaulation–filtration using alum + lime + bleaching powder (Nalgonda technique) and adsorption using activated alumina. Use of aluminium compounds for water treatment purpose needs replacement on neurological health problem. Objective to this, the synthesis and fluoride adsorption behavior of hydrous ferric oxide (HFO) are reported here. It is seen that fluoride adsorption density varies as a function of pH, contact time, aging time, drying temperature and particle size of HFO. Highest adsorption density for fluoride is found to be at pH 4.0. Effects of competing anions in removing fluoride from solution were tested. Arsenite, arsenate, phosphate and sulfate show strong interfering effect at high anions to fluoride molar ratio in solution. Adsorption of fluoride on HFO follows the Freundlich isotherm and the Lagergren first-order kinetic model. It was also determined that HFO is a better adsorbent in removing fluoride from high fluoride groundwater than some other adsorbents. Regeneration of fluoride-rich HFO results showed that 1.0 M NaOH solution could be used up to a maximum of 75% regeneration.  相似文献   

Studies on Management of Chromium(VI) – Contaminated Industrial Waste Effluent using Hydrous Titanium Oxide (HTO)     

Ghosh  Uday Chand  Dasgupta  Manotosh  Debnath  Sushanta  Bhat  Subhas Chandra 《Water, air, and soil pollution》2003,143(1-4):245-256

The anion exchange behaviour of hydrous titanium oxide(HTO) has been exploited for the management of industrialwaste effluents contaminated with chromium(VI). Theadsorption of chromium(VI) by HTO (74.0–140.0 micron) in thepH range 0.5–8.0 has been studied. It is found that theadsorption of chromium(VI) by HTO is at a maximum in the pHrange 1.5–2.0. The interference of diverse foreign ionssuch as nitrate, chloride, sulfate, phosphate, calcium,magnesium, nickel, iron(III), barium etc. on the adsorptionof chromium(VI) by HTO at optimum pH has been investigatedby a batch-operation technique. Break-through capacity,adsorption and elution of chromium(VI) using HTO have beenstudied. It is found that HTO could be reused as anadsorbent for chromium(VI). Finally, chromium(VI) wasrecovered as insoluble chromate compound from waste effluentof Hindustan Motor Limited (HML) of Hooghly, West Bengal, India.  相似文献