Diacylglycerol Kinase Is Stimulated by Arachidonic Acid in Neural Membranes.

The effect of arachidonic acid (AA) on the activity of diacylglycerol (DG) kinase in neural membranes was investigated. When rat brain cortical membranes were incubated with 0.5 mM dipalmitin and [gamma-P-32]ATP, formation of phosphatidic acid (PA) was observed. It was linear up to 5 min, and the initial rate was similar to 1.0 nmol/min/mg of protein. The DG kinase activity was stimulated twofold by 0.25 mM AA. The stimulation was apparent at the earliest time point measured (1 min) and with the lowest concentration of AA tested (62.5 mu M). The stimulation was proportional to the concentration of AA up to 250 mu M. AA was the most potent stimulator of DG kinase, and linolenic acid showed similar to 40% stimulation. Oleic acid showed no effect, whereas linoleic and the saturated fatty acids tested were inhibitory. AA stimulation of DG kinase was observed only with membranes of cerebrum, cerebellum, and myelin and not with brain cytosol or liver membranes. AA also stimulated the formation of PA in the absence of added dipalmitin (endogenous activity) with membranes prepared from whole brain. DG kinase of neural membranes was extracted with 2 M NaCl, which on dialysis yielded a precipitate. Both the precipitate and the supernatant showed DG kinase activity, but only the enzyme in the precipitate was stimulated by AA at concentrations as low as 25 mu M. It is suggested that AA, through its effect on DG kinase, regulates the level of DG in neural membranes, which in turn regulates protein kinase C activity.

Evolution of Transformation Texture in a Metastable B - Titanium Alloy

Texture evolution in h. c. p. (alpha) phase derived from aging of a differently processed metastable b.c.c. (beta) titanium alloy was investigated. The study was aimed at examining (i) the effect of different b. c. c. cold rolling textures and (ii) the effect of different defect structures on the h. c. p transformation texture. The alloy metastable beta alloy Ti-10V-4.5Fe-1.5Al was rolled at room temperature by unidirectional (UDR) and multi-step cross rolling (MSCR). A piece of the as-rolled materials were subjected to aging in order to derive the h. c. p. (alpha) phase. In the other route, the as-rolled materials were recrystallized and then aged. Textures were measured using X-ray as well as Electron Back Scatter Diffraction. Rolling texture of beta phase, as characterized by the presence of a strong gamma fibre, was found stronger in M S C R compared to UDR, although they were qualitatively similar. The stronger texture of MSCR sample could be attributed to the inhomogeneous deformation taking place in the sample that might contribute to weakening of texture. Upon recrystallization in beta phase field close to beta-transus. the textures qualitatively resembled the corresponding beta deformation textures; however, they got strengthed. The aging of differently beta rolled samples resulted in the product alpha-phase with different textures. The (UDR + Aged) sample had a stronger texture than (MSCR + Aged) sample, which could be due to continuation of defect accumulation in UDR sample, thus providing more potential sites for the nucleation of alpha phase. The trend was reversed in samples recrystallized prior to aging. The (MSCR + Recrystallized + Aged) sample showed stronger texture of alpha phase than the (UDR + Recrystallized + Aged) sample. This could be attributed to extensive defect annihilation in the UDR sample on recrystallization prior to aging. The (MSCR + Aged) sample exhibited more alpha variants when compared to (MSCR + Recrystallized + Aged) sample. This has been attributed to the availability of more potential sites for nucleation of alpha phase in the former. It could be concluded that alpha transformation texture depends mainly on the defect structure of the parent phase.

Calcium/Calmodulin Dependent Protein Kinase II Bound to NMDA Receptor 2B Subunit Exhibits Increased ATP Affinity and Attenuated Dephosphorylation

Calcium/calmodulin dependent protein kinase II (CaMKII) is implicated to play a key role in learning and memory. NR2B subunit of N-methyl-D-aspartate receptor (NMDAR) is a high affinity binding partner of CaMKII at the postsynaptic membrane. NR2B binds to the T-site of CaMKII and modulates its catalysis. By direct measurement using isothermal titration calorimetry (ITC), we show that NR2B binding causes about 11 fold increase in the affinity of CaMKII for ATP gamma S, an analogue of ATP. ITC data is also consistent with an ordered binding mechanism for CaMKII with ATP binding the catalytic site first followed by peptide substrate. We also show that dephosphorylation of phospho-Thr(286)-alpha-CaMKII is attenuated when NR2B is bound to CaMKII. This favors the persistence of Thr(286) autophosphorylated state of CaMKII in a CaMKII/phosphatase conjugate system in vitro. Overall our data indicate that the NR2B- bound state of CaMKII attains unique biochemical properties which could help in the efficient functioning of the proposed molecular switch supporting synaptic memory.

Regulation of diacylglycerol kinase in rat brain membranes by docosahexaenoic acid

The effect of docosahexaenoic acid (DHA) on the diacylglycerol kinase (DG kinase) activity in rat brain membranes was investigated. DHA at 500 mu M concentration, stimulated the enzyme activity by about 2 fold. This effect was concentration-and time-dependent and was observed after very short periods of incubation (one min). DHA stimulation of DG kinase was observed only with rat brain membranes, and not with rat brain cytosol or rat liver membranes. Treating the rat brain membranes with phospholipase A(2) which released free fatty acids including DHA, significantly stimulated the DG kinase activity. It is concluded that DHA through its stimulatory effect on DG kinase may regulate the signalling events in growth-related situations in the brain such as synaptogenesis.

Asymmetric synthesis of steroidal Tröger's base analogues. X-Ray molecular structure of methyl 3?,12?-{6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2,8-bisacetoxy}-5?-cholan-24-oate

Cyclization of compound 5c in trifluoroacetic acid/hexamethylenetetramine produces Tröger's base analogue 6c in 75% yield with 70% diastereoselectivity.

Design and realization of high-performance wave-pipelined 8×8 b multiplier in CMOS technology

Wave pipelining is a design technique for increasing the throughput of a digital circuit or system without introducing pipelining registers between adjacent combinational logic blocks in the circuit/system. However, this requires balancing of the delays along all the paths from the input to the output which comes the way of its implementation. Static CMOS is inherently susceptible to delay variation with input data, and hence, receives a low priority for wave pipelined digital design. On the other hand, ECL and CML, which are amenable to wave pipelining, lack the compactness and low power attributes of CMOS. In this paper we attempt to exploit wave pipelining in CMOS technology. We use a single generic building block in Normal Process Complementary Pass Transistor Logic (NPCPL), modeled after CPL, to achieve equal delay along all the propagation paths in the logic structure. An 8×8 b multiplier is designed using this logic in a 0.8 ?m technology. The carry-save multiplier architecture is modified suitably to support wave pipelining, viz., the logic depth of all the paths are made identical. The 1 mm×0.6 mm multiplier core supports a throughput of 400 MHz and dissipates a total power of 0.6 W. We develop simple enhancements to the NPCPL building blocks that allow the multiplier to sustain throughputs in excess of 600 MHz. The methodology can be extended to introduce wave pipelining in other circuits as well

Synthetic approaches to homogynolides A and B

A four step, efficient and general methodology for the conversion of a cyclic ketone into the corresponding alpha-spiro-beta-methylene-gamma-butyrolactone, the key structural feature present in tricyclic sesquiterpenes bakkanes, has been developed employing a regiospecific 5-exo dig radical cyclisation reaction as the key step. The methodology has been extended to the total synthesis of bakkanes including homogynolide-B and chiral homogynolide-A.

Role of Water in the Enzymatic Catalysis: Study of ATP plus AMP -> 2ADP Conversion by Adenylate Kinase

The catalytic conversion ATP + AMP -> 2ADP by the enzyme adenylate kinase (ADK) involves the binding of one ATP. molecule to the LID domain and one AMP molecule to the NMP domain. The latter is followed by a. phosphate transfer and then the release of two ADP molecules. We have computed a novel two-dimensional configurational free energy surface (2DCFES), with one reaction coordinate each for the LID and the NMP domain motions, while considering explicit water interactions. Our computed 2DCFES clearly reveals the existence of a stable half-open half-closed (HOHC) intermediate stale of the enzyme. Cycling of the enzyme through the HOHC state reduces the conformational free energy barrier for. the reaction by about 20 kJ/mol. We find that the stability of the HOHC state (missed in all earlier studies with implicit solvent model) is largely because of the increase of specific interactions of the polar amino acid side chains with water, particularly with the arginine and the histidine residues. Free energy surface of the LID domain is rather rugged, which can conveniently slow down LID's conformational motion, thus facilitating a new substrate capture after the product release in the catalytic cycle.

What makes a cell tick? The A, B and C of the matter

Nuclear lamina in an eukaryotic cell is primarily composed of the lamins A, B and C. The A type lamins are found only in differentiated cell types while the B type lamins are present both in differentiated and undifferentiated cells. Lamin B interacts with the inner nuclear membrane, In recent years there have been extensive studies on the relationship between the dynamic state of lamin B and the nuclear envelope integrity with respect to the fate of a particular cell, In this article, we have analysed the recent developments and have considered the sequence of events that might be contributing to the fate of a cell either to undergo normal cell division or uncontrolled cellular proliferation or apoptosis.

Enantioselective total synthesis of iso-cladospolide B, cladospolide C and cladospolide B from tartaric acid

The enantioselective synthesis of the natural products cladospolide B, cladospolide C, and iso-cladospolide B has been accomplished from tartaric acid. Key reactions in the synthetic sequence include the elaboration of a gamma-hydroxy amide derived from tartaric acid via alkene cross metathesis, Yamaguchi lactonization, and ring closing metathesis. (C) 2011 Elsevier Ltd. All rights reserved.

B Physics: WHEPP-XI working group report

We present the report of the B physics working group of the Workshop on High Energy Physics Phenomenology (WHEPP-XI), held at the Physical Research Laboratory, Ahmedabad, in January 2010.

Synthesis and biological evaluation of novel 2-aralkyl-5-substituted-6-(4 `-fluorophenyl)-imidazo2,1-b]1,3,4]thiadiazole derivatives as potent anticancer agents

Levamisole, the imidazo2,1-b]thiazole derivative has been reported as a potential antitumor agent. In the present study, we synthesized, characterized and evaluated biological activity of its novel analogues with substitution in the aralkyl group and on imidazothiadiazole molecules with same chemical backbone but different side chains namely 2-aralkyl-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]thiadiazoles (SCR1), 2-aralkyl-5-bromo-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]-thiadiaz oles (SCR2), 2-aralkyl-5-formyl-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]-thiadia zoles (SCR3) and 2-aralkyl-5-thiocyanato-6-(4'-fluorophenyl)-imidazo2,1-b]1,3,4]-th iadiazoles (SCR4) on leukemia cells. The cytotoxic studies showed that 3a, 4a, and 4c exhibited strong cytotoxicity while others had moderate cytotoxicity. Among these we chose 4a (IC50, 8 mu M) for understanding its mechanism of cytotoxicity. FACS analysis in conjunction with mitochondrial membrane potential and DNA fragmentation studies indicated that 4a induced apoptosis without cell cycle arrest suggesting that it could be used as a potential chemotherapeutic agent. (C) 2011 Elsevier Masson SAS. All rights reserved.

LiSr1.65 square 0.35B1.3B ' O-1.7(9) (B = Ti, Zr; B ' = Nb, Ta): New lithium ion conductors based on the perovskite structure

We describe the design and synthesis of new lithium ion conductors with the formula, LiSr(1.65)rectangle(0.35)B(1.3)B'O-1.7(9) (rectangle = vacancy; B = Ti, Zr; B' = Nb, Ta), on the basis of a systematic consideration of the composition-structure-property correlations in the well-known lithium-ion conductor, La-(2/3-x)Li(3x)rectangle((1/3)-2x)TiO3 (I), as well as the perovskite oxides in Li-A-B,B'-O (A = Ca, Sr, Ba; B = Ti, Zr; B' = Nb, Ta) systems. A high lithium-ion conductivity of ca. 0.12 S/cm at 360 degrees C is exhibited by LiSr(1.65)rectangle(0.35)Ti(1.3)Ta(1.7)O(9) (III) and LiSr(1.65)rectangle(0.35)Zr(1.3)Ta(1.7)O(9) (IV), of which the latter containing stable Zr(IV) and Ta(V) oxidation states is likely to be a candidate electrolyte material for all-solid-state lithium battery application. More importantly, we believe the approach described here could be extended to synthesize newer, possibly better, lithium ion conductors.