Emission Mössbauer studies of some organocobalamins

Subtle changes in Mössbauer parameters are observed while going from methyl- to ethyl- to adenosylcobalamin, and also when the ‘base’ is detached from the cobalt. The observation of these changes demonstrates that the Co-C bond, among others, remains intact after the Auger event, accompanying the electron-capture decay of the cobalt-57.The differences between ethylcobalamin and the other two organocobalamins in the magnitude of the quadrupole splittings have been interpreted on the basis of the σ-donating tendency of the organic moiety and the CoC bond length. The latter is presumably determined by the steric hindrance offered to the group in approaching the cobalt atom.The ethyl- and adenosylcobalamins in their ‘base-off’ form exhibit a larger quadrupole splitting than the corresponding ‘base-on’ form. In the ‘base-off’ form, the cobalt atom is perhaps raised above the mean plane of the four equatorial nitrogen atoms of the corrin ring, which may result in the diminution of the delocalization of the 3d_π electron density. The higher population of d_π orbitals and the enhanced metallic character of the d_z2, resulting from shrink-age of the CoC bond length, enhances the magnitude of the quadrupole splitting.     

The possible mode of action of prostaglandins: VIII — Cortisone, reserpine and the reversal of the antifertility efficacy of prostaglandin E1 in rats

A single injection of prostaglandin E₁ (PGE₁) of 5 mg/kg body weight on Day 13 of pregnancy caused a consistent luteolysis and resorption of fetuses in rats by Day 20. A concomitant regimen of cortisone, a consistent blocker of nonspecific stresses or reserpine, an adrenergic nerve blocking agent as well as a specific inhibitor of GRF and PIF, concurrently with PGE₁ consistently effective in preventing the deleterious efficacy of PGE₁ and maintained the growth of the fetuses, placentae, ovaries and corpora lutea as healthy as recorded in the controls. On the basis of experimental documentation it is believed that the PGE₁-caused fetal demise is possibly due to a break up of an appropriate hormonal synchronization rather than an over stimulation of uterine smooth musculature.     

Association of Endogenous Testosterone with Lipid and Blood Glucose Profiles in Elderly Men with Angiographically Proven Cardiovascular Disease of Nadia and Murshidabad District,West Bengal

Testosterone is commonly known for its role in the regulation of reproductive physiology in men. Epidemiologic studies suggest that endogenous testosterone levels may be implicated in cardiovascular diseases (CVDs). Our study aimed to investigate the relationship between serum total testosterone (TT) levels and lipid profile as well as fasting blood glucose (FBG) levels in male patients ranging from 40 to 70 years old with angiographically proven CVDs from Nadia and Murshidabad district of West Bengal, India. These data were compared with the normal men with no CVD history. We observed a significantly low serum TT levels in CVD patient group compared to the normal group. Among CVD patients, a significant (p < 0.05) negative association was found between serum TT and total cholesterol, triglyceride, low density lipoprotein and very low density lipoprotein, whereas a significant positive correlation (p < 0.05) was found between serum TT and high density lipoprotein. We also observed a highly significant negative correlation between TT and FBG levels in CVD patient group. Thus, in these two densely populated district of West Bengal with poor socio-economic condition, low levels of serum TT in elderly men is associated with CVD that appear together with an atherogenic lipid milieu that may be involved in the pathogenesis of CVD. Results further indicate that low serum TT might have a role in the development of hyperglycemia as evidenced from high FBG level in elderly men.     

Computer‐aided biochemical programming of synthetic microreactors as diagnostic devices

Biological systems have evolved efficient sensing and decision‐making mechanisms to maximize fitness in changing molecular environments. Synthetic biologists have exploited these capabilities to engineer control on information and energy processing in living cells. While engineered organisms pose important technological and ethical challenges, de novo assembly of non‐living biomolecular devices could offer promising avenues toward various real‐world applications. However, assembling biochemical parts into functional information processing systems has remained challenging due to extensive multidimensional parameter spaces that must be sampled comprehensively in order to identify robust, specification compliant molecular implementations. We introduce a systematic methodology based on automated computational design and microfluidics enabling the programming of synthetic cell‐like microreactors embedding biochemical logic circuits, or protosensors, to perform accurate biosensing and biocomputing operations in vitro according to temporal logic specifications. We show that proof‐of‐concept protosensors integrating diagnostic algorithms detect specific patterns of biomarkers in human clinical samples. Protosensors may enable novel approaches to medicine and represent a step toward autonomous micromachines capable of precise interfacing of human physiology or other complex biological environments, ecosystems, or industrial bioprocesses.     

Inhibition of Oncogenic and Activated Wild-Type ras-p21 Protein-Induced Oocyte Maturation by Peptides from the ras-Binding Domain of the raf-p74 Protein, Identified from Molecular Dynamics Calculations

In the preceding paper we found from molecular dynamics calculations that the structure of the ras-binding domain (RBD) of raf changes predominantly in three regions depending upon whether it binds to ras-p21 protein or to its inhibitor protein, rap-1A. These three regions of the RBD involve residues from the protein–protein interaction interface, e.g., between residues 60 and 72, residues 97–110, and 111–121. Since the rap-1A–RBD complex is inactive, these three regions are implicated in ras-p21-induced activation of raf. We have therefore co-microinjected peptides corresponding to these three regions, 62–76, 97–110, and 111–121, into oocytes with oncogenic p21 and microinjected them into oocytes incubated in in insulin, which activates normal p2l. All three peptides, but not a control peptide, strongly inhibit both oncogenic p21- and insulin-induced oocyte maturation. These findings corroborate our conclusions from the theoretical results that these three regions constitute raf effector domains. Since the 97–110 peptide is the strongest inhibitor of oncogenic p21, while the 111–121 peptide is the strongest inhibitor of insulin-induced oocyte maturation, the possibility exists that oncogenic and activated normal p21 proteins interact differently with the RBD of raf.     

An optimal algorithm for perfect phylogeny haplotyping.

Inferring haplotype data from genotype data is a crucial step in linking SNPs to human diseases. Given n genotypes over m SNP sites, the haplotype inference (HI) problem deals with finding a set of haplotypes so that each given genotype can be formed by a combining a pair of haplotypes from the set. The perfect phylogeny haplotyping (PPH) problem is one of the many computational approaches to the HI problem. Though it was conjectured that the complexity of the PPH problem was O(nm), the complexity of all the solutions presented until recently was O(nm (2)). In this paper, we make complete use of the column-ordering that was presented earlier and show that there must be some interdependencies among the pairwise relationships between SNP sites in order for the given genotypes to allow a perfect phylogeny. Based on these interdependencies, we introduce the FlexTree (flexible tree) data structure that represents all the pairwise relationships in O(m) space. The FlexTree data structure provides a compact representation of all the perfect phylogenies for the given set of genotypes. We also introduce an ordering of the genotypes that allows the genotypes to be added to the FlexTree sequentially. The column ordering, the FlexTree data structure, and the row ordering we introduce make the O(nm) OPPH algorithm possible. We present some results on simulated data which demonstrate that the OPPH algorithm performs quiet impressively when compared to the previous algorithms. The OPPH algorithm is one of the first O(nm) algorithms presented for the PPH problem.     

Evaluation of persistence and distribution of intra-dermally administered PKH26 labelled goat bone marrow derived mesenchymal stem cells in cutaneous wound healing model

The current study was designed to study the persistence and distribution of caprine bone marrow derived mesenchymal stem cells (cBM-MSCs) when administered intra-dermally in experimentally induced cutaneous wounds in rabbits. MSC’s from goat bone marrow were isolated and their differentiation potential towards adipogenic and osteogenic lineages were assayed in vitro. The isolated cells were phenotypically analysed using flow cytometry for the expression of MSC specific matrix receptors (CD73, CD105 and Stro-1) and absence of hematopoietic lineage markers. Further, these in vitro expanded MSCs were stained with PKH26 lipophilic cell membrane red fluorescent dye and prepared for transplantation into cutaneous wounds created on rabbits. Five, 2 cm linear full thickness skin incisions were created on either side of dorsal midline of New Zealand white rabbits (n = 4). Four wounds in each animal were implanted intra-dermally with PKH26 labelled cBM-MSCs suspended in 500 µl of Phosphate Buffer Saline (PBS). Fifth wound was injected with PBS alone and treated as negative control. The skin samples were collected from respective wounds on 3, 7, 10 and 14 days after the wound creation, and cryosections of 6 µM were made from it. Fluorescent microscopy of these cryosections showed that the PKH26 labelled transplanted cells and their daughter cells demonstrated a diffuse pattern of distribution initially and were later concentrated towards the wound edges and finally appeared to be engrafted with the newly developed skin tissues. The labelled cells were found retained in the wound bed throughout the period of 14 days of experimental study with a gradual decline in their intensity of red fluorescence probably due to the dye dilution as a result of multiple cell division. The retention of transplanted MSCs within the wound bed even after the complete wound healing suggests that in addition to their paracrine actions as already been reported, they may have direct involvement in various stages of intricate wound healing process which needs to be explored further.