Alkaloids of the leaves of Voacanga grandifolia

Besides vobtusine and vobtusine-lactone, deoxyvobtusine was isolated from the leaves of Voacanga grandifolia (Miq. Rolfe. Spectral and chemical evi     

Transient Receptor Potential Channel 6 (TRPC6) Protects Podocytes during Complement-mediated Glomerular Disease

Gain-of-function mutations in the calcium channel TRPC6 lead to autosomal dominant focal segmental glomerulosclerosis and podocyte expression of TRPC6 is increased in some acquired human glomerular diseases, particularly in membranous nephropathy. These observations led to the hypothesis that TRPC6 overactivation is deleterious to podocytes through pathological calcium signaling, both in genetic and acquired diseases. Here, we show that the effects of TRPC6 on podocyte function are context-dependent. Overexpression of TRPC6 alone did not directly affect podocyte morphology and cytoskeletal structure. Unexpectedly, however, overexpression of TRPC6 protected podocytes from complement-mediated injury, whereas genetic or pharmacological TRPC6 inactivation increased podocyte susceptibility to complement. Mechanistically, this effect was mediated by Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) activation. Podocyte-specific TRPC6 transgenic mice showed stronger CaMKII activation, reduced podocyte foot process effacement and reduced levels of proteinuria during nephrotoxic serum nephritis, whereas TRPC6 null mice exhibited reduced CaMKII activation and higher levels of proteinuria compared with wild type littermates. Human membranous nephropathy biopsy samples showed podocyte staining for active CaMKII, which correlated with the degree of TRPC6 expression. Together, these data suggest a dual and context dependent role of TRPC6 in podocytes where acute activation protects from complement-mediated damage, but chronic overactivation leads to focal segmental glomerulosclerosis.     

Interaction among Non-toxic Phytoplankton,Toxic Phytoplankton and Zooplankton: Inferences from Field Observations

We explore the mutual dependencies and interactions among different groups of species of the plankton population, based on an analysis of the long-term field observations carried out by our group in the North–West coast of the Bay of Bengal. The plankton community is structured into three groups of species, namely, non-toxic phytoplankton (NTP), toxic phytoplankton (TPP) and zooplankton. To find the pair-wise dependencies among the three groups of plankton, Pearson and partial correlation coefficients are calculated. To explore the simultaneous interaction among all the three groups, a time series analysis is performed. Following an Expectation Maximization (E-M) algorithm, those data points which are missing due to irregularities in sampling are estimated, and with the completed data set a Vector Auto-Regressive (VAR) model is analyzed. The overall analysis demonstrates that toxin-producing phytoplankton play two distinct roles: the inhibition on consumption of toxic substances reduces the abundance of zooplankton, and the toxic materials released by TPP significantly compensate for the competitive disadvantages among phytoplankton species. Our study suggests that the presence of TPP might be a possible cause for the generation of a complex interaction among the large number of phytoplankton and zooplankton species that might be responsible for the prolonged coexistence of the plankton species in a fluctuating biomass.     

The role of virus infection in a simple phytoplankton zooplankton system

Many planktonic species show spectacular bursts ("blooms") in population density. Though viral infections are known to cause behavioural and other changes in phytoplankton and other aquatic species, yet their role in regulating the phytoplankton population is still far from being understood. To study the role of viral diseases in the planktonic species, we model the phytoplankton-zooplankton system as a prey-predator system. Here the prey (phytoplankton) species is infected with a viral disease that divides the prey population into susceptible and infected classes, with the infected prey being more vulnerable to predation by the predator (zooplankton). The dynamical behaviour of the system is investigated from the point of view of stability and persistence both analytically and numerically. The model shows that infection can be sustained only above a threshold of force of infection, and, there exists a range in the infection rate where this system shows "bloom"-like stable limit cycle oscillations. The time series of natural "blooms" with different types of irregular oscillations can arise in this model simply from a biologically realistic feature, i.e., by the random variation of the epidemiological parameter (rate of infection) in the infected prey population. The difference in mean strength of infection alone can lead to the different types of patterns observed in natural planktonic blooms.     

Differential induction of Leishmania donovani bi-subunit topoisomerase I-DNA cleavage complex by selected flavones and camptothecin: activity of flavones against camptothecin-resistant topoisomerase I

Emergence of the bi-subunit topoisomerase I in the kinetoplastid family (Trypanosoma and Leishmania) has brought a new twist in topoisomerase research related to evolution, functional conservation and preferential sensitivities to the specific inhibitors of type IB topoisomerase family. In the present study, we describe that naturally occurring flavones baicalein, luteolin and quercetin are potent inhibitors of the recombinant Leishmania donovani topoisomerase I. These compounds bind to the free enzyme and also intercalate into the DNA at a very high concentration (300 µM) without binding to the minor grove. Here, we show that inhibition of topoisomerase I by these flavones is due to stabilization of topoisomerase I–DNA cleavage complexes, which subsequently inhibit the religation step. Their ability to stabilize the covalent topoisomerase I–DNA complex in vitro and in living cells is similar to that of the known topoisomerase I inhibitor camptothecin (CPT). However, in contrast to CPT, baicalein and luteolin failed to inhibit the religation step when the drugs were added to pre-formed enzyme substrate binary complex. This differential mechanism to induce the stabilization of cleavable complex with topoisomerase I and DNA by these selected flavones and CPT led us to investigate the effect of baicalein and luteolin on CPT-resistant mutant enzyme LdTOP1Δ39LS lacking 1–39 amino acids of the large subunit [B. B. Das, N. Sen, S. B. Dasgupta, A. Ganguly and H. K. Majumder (2005) J. Biol. Chem. 280, 16335–16344]. Baicalein and luteolin stabilize duplex oligonucleotide cleavage with LdTOP1Δ39LS. This observation was further supported by the stabilization of in vivo cleavable complex by baicalein and luteolin with highly CPT-resistant L.donovani strain. Taken together, our data suggest that the interacting amino acid residues of topoisomerase I may be partially overlapping or different for flavones and CPT. This study illuminates new properties of the flavones and provide additional insights into the ligand binding properties of L.donovani topoisomerase I.     

Echitoserpidine: A new alkaloid of the fruits of Alstonia venenata

The structure of echitoserpidine, a new alkaloid of the fruits of Alstonia venenata has been established as (1) on the basis of spectral and chemical evidence.     

Overexpression and purification of folded domain of prostate cancer related proteins MSMB and PSA

Overexpression of domains of a human protein using recombinant DNA technology has been challenging because individual domains intend to accumulate as non-soluble aggregate when expressed separately. Studies on identifying right sequences for a domain to be able to fold independently may help understand the folding pattern and underlying protein-engineering events to isolate the functional domains of a protein. In this report, individual domains of prostate cancer related biomarkers; MSMB and PSA were overexpressed in bacterial system and purified in their folded forms using affinity chromatography. The western blotting experiment using domain specific antibodies further confirmed these proteins. The designed nucleotide sequences domains were truncated using fold index software and folding were predicted by phyre2 and I-TASSER software. Other parameters were optimized for their overexpression and purification using Co-NTA affinity chromatography. Purified domains of each protein showed secondary structures such as α + β type for PSA, α/β and β type for the each domains of PSA and MSMB respectively. This is the first report on producing PSA and MSMB individual domains in functional folded forms. This study may help produce the folded domain of many such proteins to be used for better diagnostic purpose.     

Reductive thiocyanolysis of tetraoxorhenate (VII): Synthesis, crystal structure, catalytic oxidation and kinetic studies of (PPh4)2[Re(NCS)6] and (PPh4)2[ReO(NCS)5]

Thiocyanate ions reduce perrhenate in aqueous acidic solution, and on addition of a suitable countercation (PPh₄Cl) afford (PPh₄)₂[Re(NCS)₆] (1) and (PPh₄)₂[ReO(NCS)₅] (2), which have been confirmed by X-ray crystallography. The kinetics of the above reaction has been studied. Both the complexes exhibit efficient and highly selective catalytic epoxidation ability in the presence of NaHCO₃ as a co-catalyst and competent catalytic properties in the selective oxidation of alcohols to the corresponding aldehydes or ketones in the presence of pyrazole as an additive and sulfides to sulfoxides and sulfones. H₂O₂ was used as the terminal oxidant in all the above-mentioned oxidation reactions.     

Host load prediction using linear models

This paper evaluates linear models for predicting the Digital Unix fivesecond host load average from 1 to 30 seconds into the future. A detailed statistical study of a large number of long, fine grain load traces from a variety of real machines leads to consideration of the Box–Jenkins models (AR, MA, ARMA, ARIMA), and the ARFIMA models (due to selfsimilarity.) We also consider a simple windowedmean model. The computational requirements of these models span a wide range, making some more practical than others for incorporation into an online prediction system. We rigorously evaluate the predictive power of the models by running a large number of randomized testcases on the load traces and then datamining their results. The main conclusions are that load is consistently predictable to a very useful degree, and that the simple, practical models such as AR are sufficient for host load prediction. We recommend AR(16) models or better for host load prediction. We implement an online host load prediction system around the AR(16) model and evaluate its overhead, finding that it uses miniscule amounts of CPU time and network bandwidth.     

Height, weight and earnings among coalminers in India

This paper analyses earning/wage differentials by height among coalmine workers in India. Our findings suggest that workers of above average height earn 9-17% more than their shorter counterparts and 6-13% more than average reference height. The results suggest that long-term investments in health human capital might ensure increase of labour productivity and thereby earnings, particularly in underdeveloped economies.