Simian Virus 40 Small T Antigen Activates AMPK and Triggers Autophagy To Protect Cancer Cells from Nutrient Deprivation

As tumors grow larger, they often experience an insufficient supply of oxygen and nutrients. Hence, cancer cells must develop mechanisms to overcome these stresses. Using an in vitro transformation model where the presence of the simian virus 40 (SV40) small T (ST) antigen has been shown to be critical for tumorigenic transformation, we investigated whether the ST antigen has a role to play in regulating the energy homeostasis of cancer cells. We find that cells expressing the SV40 ST antigen (+ST cells) are more resistant to glucose deprivation-induced cell death than cells lacking the SV40 ST antigen (-ST cells). Mechanistically, we find that the ST antigen mediates this effect by activating a nutrient-sensing kinase, AMP-activated protein kinase (AMPK). The basal level of active, phosphorylated AMPK was higher in +ST cells than in -ST cells, and these levels increased further in response to glucose deprivation. Additionally, inhibition of AMPK in +ST cells increased the rate of cell death, while activation of AMPK in -ST cells decreased the rate of cell death, under conditions of glucose deprivation. We further show that AMPK mediates its effects, at least in part, by inhibiting mTOR (mammalian target of rapamycin), thereby shutting down protein translation. Finally, we show that +ST cells exhibit a higher percentage of autophagy than -ST cells upon glucose deprivation. Thus, we demonstrate a novel role for the SV40 ST antigen in cancers, where it functions to maintain energy homeostasis during glucose deprivation by activating AMPK, inhibiting mTOR, and inducing autophagy as an alternate energy source.

Late Quaternary vegetational and climatic changes from tropical peats in southern India - An extended record up to 40,000 years BP

Stable carbon isotope ratios of peats dated (by C-14) back to 40 kyr BP from the montane region (> 1800 m asl) of the Nilgiris, southern India, reflect changes in the relative proportions of C3 and C4 plant types, which are influenced by soil moisture (and hence monsoonal precipitation), From prior to 40 kyr BP until 28 kyr BP, a general decline in delta(13)C values from about - 14 per mil to - 19 per mil suggests increased dominance of C3 plants concurrent with increasingly moist conditions, During 28-18 kyr BP there seems relatively little change with delta(13) C of - 19 to - 18 per mil, At about 16 kyr BP a sharp reversal in delta(13)C to a peak of - 14.7 per mil indicates a clear predominance of C4 vegetation associated with arid conditions, possibly during or just after the Last Glacial Maximum, A moist phase at about 9 kyr BP (the Holocene Optimum) with dominance of C3 vegetation type is observed, while arid conditions are re-established during 5-2 kyr BP with an overall dominance of C4 vegetation, New data do not support the occurrence of a moist phase coinciding with the Mediaeval Warm Period (at 0.6 kyr BP) as suggested earlier, Overall, the climate and vegetation in the high altitude regions of the southern Indian tropics seem to have responded to past global climatic changes, and this is consistent with other evidences from India and other tropical regions.

Chiral synthons from carvone, Part 40. A simple, enantiospecific approach to both enantiomers of 1 alpha,25-dihydroxyvitamin D-3 A-ring precursors from R-carvone

A simple and direct approach to both enantiomeric series of A-ring derivatives of 1 alpha,25-dihydroxyvitamin D-3 and the corresponding 1 alpha,3 alpha-derivatives, starting from the abundantly available R-carvone, is described. (C) 2000 Elsevier Science Ltd. All rights reserved.

A study of cubic bismuth oxides of the type bi(26-X)m(X)O(40-delta) (m=ti, mn, fe, co, ni or pb) related to gamma-bi2O3

A structural investigation of cubic oxides (space group I23) of the formula Bi(26-x)M(x)O(40-delta) (M = Ti, Mn, Fe, Co, Ni and Pb) related to the Y-Bi2O3 phase has been carried out by the Rietveld profile analysis of high-resolution X-ray powder diffraction data in order to establish the cation distributions. Compositional dependence of the cation distribution has been examined in the case of Bi26-xCoxO40-delta (1 < x < 16). The study reveals that in Bi(26-X)M(X)O(40-delta) with M = Ti, Mn, Fe, Co or Pb, the M cations tend to occupy tetrahedral (2a) sites when x < 2 while the octahedral (24f) sites are shared by the excess Co or Ni cations with Bi atoms when x > 2. Also experimental magnetic moments of Mn, Co and Ni derivatives have been used to establish the valence state and distribution of these cations.

Interaction of A beta peptide (1-40) with amino acid aluminium complexes: relevance to Alzheimer's disease

A beta (39-43 aminoacid residues) is the principal peptide component of amyloid deposits in Alzheimer's disease (AD). A beta peptide is derived from the amyloid precursor protein (APP) in which mutations give rise to many forms of familial AD. Aluminium is reported to play a key role in inducing conformational change in the synthetic beta-amyloid peptide (1-40)from alpha-helix to beta-pleated sheet, leading to aggregation and fibrillar formation. We have studied the interaction of amino acid-Al complexes such as D-Asp-Al and L-Glu-Al with A beta(1-40) in TFE/buffer (70% TFE and 30% H2O v/v pH 6.7) mixture using CD spectroscopy. The interaction of either of these amino acid complexes with A beta(1-40) results in loss of alpha-helical content and the peptide is more unstructured compared to free Al3+ in the solution. Our data strongly support the idea, that the Al3+ in the form of aminoacid-Al complexes is more effective in inducing random coil conformation in the A beta peptide than the free Al3+ present in the solution.

Magnetocaloric effect in La1-xSrxCoO3 (0.05 <= x <= 0.40)

We report studies of magnetocaloric effect in lanthanum cobaltate doped with different Sr-concentrations, La1-xSrxCoO3 (0.05 less than or equal to x less than or equal to 0.4). The study has revealed that La0.6Sr0.4CoO3, which exhibits a moderately large value of maximum entropy change of about 1.45 J/kg/K in 1.5 T DC-fieid around its Curie temperature (of 235 K), can be used as an active magnetic refrigerant (AMR) material at similar to 2.35 K. (C) 1999 Elsevier Science B.V. Al rights reserved.

Electrical switching studies on AS(40)Te(60-x)Se(x) and As35Te65-xSex glasses

The I-V characteristics of bulk As40Te60-xSex and As35Te65-xSex glasses have been studied with a current sweep of 0-18 mA-0, over a wide range of compositions (4 less than or equal to x less than or equal to 22). All the glasses studied showed a threshold electrical switching behaviour. The number of switching cycles withstood by the samples has been found to depend on the ON-state current. It is seen that the switching voltages increase with increase in selenium content. Further, the switching voltages are found to be almost independent of the thickness of the sample (d), in the range 0.18-0.3 mm. Also, the switching voltages and the number of switching cycles withstood by the samples are found to decrease with temperature.

An Exported Heat Shock Protein 40 Associates with Pathogenesis-Related Knobs in Plasmodium falciparum Infected Erythrocytes

Cell surface structures termed knobs are one of the most important pathogenesis related protein complexes deployed by the malaria parasite Plasmodium falciparum at the surface of the infected erythrocyte. Despite their relevance to the disease, their structure, mechanisms of traffic and their process of assembly remain poorly understood. In this study, we have explored the possible role of a parasite-encoded Hsp40 class of chaperone, namely PFB0090c/PF3D7_0201800 (KAHsp40) in protein trafficking in the infected erythrocyte. We found the gene coding for PF3D7_0201800 to be located in a chromosomal cluster together with knob components KAHRP and PfEMP3. Like the knob components, KAHsp40 too showed the presence of PEXEL motif required for transport to the erythrocyte compartment. Indeed, sub-cellular fractionation and immunofluorescence analysis (IFA) showed KAHsp40 to be exported in the erythrocyte cytoplasm in a stage dependent manner localizing as punctuate spots in the erythrocyte periphery, distinctly from Maurer's cleft, in structures which could be the reminiscent of knobs. Double IFA analysis revealed co-localization of PF3D7_0201800 with the markers of knobs (KAHRP, PfEMP1 and PfEMP3) and components of the PEXEL translocon (Hsp101, PTEX150). KAHsp40 was also found to be in a complex with KAHRP, PfEMP3 and Hsp101 as confirmed by co-immunoprecipitation assay. Our results suggest potential involvement of a parasite encoded Hsp40 in chaperoning knob assembly in the erythrocyte compartment.

Texture transition in cold-rolled nickel-40 wt.% cobalt alloy

The micromechanical aspects of rolling texture development in Ni-40 wt.% Co alloy during very large reductions (up to epsilon(t) = 3.9) have been studied. The alloy showed a typical Cu-type texture up to a true strain of epsilon(t) = 3; however, the texture undergoes an abrupt transition to Bs-type on further rolling to epsilon(t) approximate to 4. (The Bs-type texture, here, comprises almost equal fractions of Goss and Bs components.) Microstructural observations, at early stages, show that deformation is accommodated entirely by slip, and very little presence of deformation twinning is observed to explain the texture transition. However, at much higher reduction levels, micrographs show a high fraction of Cu-type shear bands. These bands are predominantly found in Cu-oriented grains and the crystallites inside the shear bands are preferentially oriented towards Goss, which could explain the final texture evolution. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.