Selective, Ultra-Sensitive, and Rapid Detection of Serotonin by Optimized ZnO Nanorod FET Biosensor.

BACKGROUND: Fluctuation in serotonin (5-HT) level is an essential manifestation of several neurological disorders. In view of such importance, it is necessary to monitor the levels of 5-HT with good sensitivity, selectivity, affordability and low response time. Zinc oxide (ZnO) based field effect transistors (FET) with attributes like minimized noise levels and large on-off ratio are regarded as emerging high performance biosensor platforms. However, their response is significantly non-linear and there has been no appreciable endeavor for improving the non-linearity. METHOD: In this paper, we have introduced embedded gate electrode encompassing the channel of the FET which improves the uniformity in electric field line distribution through the electrolyte and proportionately enhances the capture of target biomolecule at ultra-low concentrations, thereby increasing the linearity. Further, we have incorporated the optimized parameters of ZnO nanorods reported previously, for rapid and selective detection of 5-HT. RESULTS: It has been observed that the fabricated ZnO FET biosensor lowers the detection limit down to 0.1fM which is at least one order of magnitude lower than the existing reports. The sensor also has wide linear range from 0.1fM to 1nM with a detection time of about 20 minutes. CONCLUSION: The proposed zinc oxide nanorod-based sensor can be used as an excellent tool for future diagnosis of neurological disorders.

Expression profile, transcriptional and post-transcriptional regulation of genes involved in hydrogen sulphide metabolism connecting the balance between development and stress adaptation in plants: a data-mining bioinformatics approach.

Recent research focused on novel aspects of sulphur and sulphur-containing molecules in fundamental plant processes has highlighted the importance of these compounds. Currently, the focus has shifted to the efficacy of hydrogen sulphide (H2 S) as signalling compounds that regulate different development and stress mitigation in plants. Accordingly, we used an in silico approach to study the differential expression patterns of H2 S metabolic genes at different growth/development stages and their tissue-specific expression patterns under a range of abiotic stresses. Moreover, to understand the multilevel regulation of genes involved in H2 S metabolism, we performed computation-based promoter analysis, alternative splice variant analysis, prediction of putative miRNA targets and co-expression network analysis. Gene expression analysis suggests that H2 S biosynthesis is highly influenced by developmental and stress stimuli. The functional annotation of promoter structures reveales a wide range of plant hormone and stress responsive cis-regulatory elements (CREs) that regulate H2 S metabolism. Co-expression analysis suggested that genes involved in H2 S metabolism are also associated with different metabolic processes. In this data-mining study, the primary focus was to understand the genetic architecture governing pathways of H2 S metabolism in different cell compartments under various developmental and stress signalling cascades. The present study will help to understand the genetic architecture of H2 S metabolism via cysteine metabolism and the functional roles of these genes in development and stress tolerance mechanisms.

A focus on long-run sustainability of a harvested prey predator system in the presence of alternative prey.

Within the framework of a general equilibrium model we study the long-run dynamics of a prey-predator model in the presence of an alternative prey. Our results show that sustainability, i.e. a positive value of the population in the long run, essentially depends on individual harvesting efforts and digesting factors relative to alternative prey. A detailed bifurcation analysis evidences the richness of possible long-run dynamics. Our model clearly shows that the role of an alternative prey must be taken into consideration when studying prey-predator dynamics.

Synthesis and anti-inflammatory activity of derivatives of coumarino-lignoid, cleomiscosin A and its methyl ether.

Six novel cleomiscosin A (a coumarino-lignoid), derivatives have been synthesized for the first time by using electrophilic substitution reaction to give nuclear nitrated and halogenated derivatives of cleomiscosin A in good yields. Structures of these compounds were established on the basis of IR, (1)H NMR, (13)C NMR and Mass spectral data. Some of the synthesized derivatives were tested for in-vitro target based anti-inflammatory study using primary macrophages cell culture bioassay system. The results showed that the compounds 1a, 3a and 4a (1 and 10 µg/mL) exhibited potent anti-inflammatory activity.

Development of QSAR model for immunomodulatory activity of natural coumarinolignoids.

Immunomodulation is the process of alteration in immune response due to foreign intrusion of molecules inside the body. Along with the available drugs, a large number of herbal drugs are promoted in traditional Indian treatments, for their immunomodulating activity. Natural coumarinolignoids isolated from the seeds of Cleome viscose have been recognized as having hepatoprotective action and have recently been tested preclinically for their immunomodulatory activity affecting both cell-mediated and humoral immune response. To explore the immunomodulatory compound from derivatives of coumarinolignoids, a quantitative structure activity relationship (QSAR) and molecular docking studies were performed. Theoretical results are in accord with the in vivo experimental data studied on Swiss albino mice. Immunostimulatory activity was predicted through QSAR model, developed by forward feed multiple linear regression method with leave-one-out approach. Relationship correlating measure of QSAR model was 99% (R(2) = 0.99) and predictive accuracy was 96% (RCV(2) = 0.96). QSAR studies indicate that dipole moment, steric energy, amide group count, lambda max (UV-visible), and molar refractivity correlates well with biological activity, while decrease in dipole moment, steric energy, and molar refractivity has negative correlation. Docking studies also showed strong binding affinity to immunomodulatory receptors.

The histopathologic and molecular basis for the diagnosis of histiocytic sarcoma and histiocyte-associated lymphoma of mice.

Histiocytic sarcoma (HS) and histiocyte-associated lymphoma (HAL) of mice are difficult to distinguish histologically. Studies of multiple cases initially diagnosed as HS or HAL allowed us to define HS as round, fusiform, or mixed cell types that were F4/80+, Mac-2+, and PAX5-; that lacked markers for other sarcomas; and that had immune receptor genes in germline configuration. Two other subsets had clonal populations of lymphocytes. The first, HAL, featured malignant lymphocytes admixed with large populations of normal-appearing histiocytes. The second appeared to be composites of lymphoma and HS. Several cases suggestive of B myeloid-lineage plasticity were also observed.

Hepatoprotective Effects and Safety Evaluation of Coumarinolignoids Isolated from Cleome viscosa Seeds.

The aim of the present work was to investigate the in vivo hepatoprotective potential of coumarinolignoids (cleomiscosins A, B, and C) isolated from the seeds of C. viscosa. The study was performed against CCl(4)-induced hepatotoxicity in albino rats. Rats were divided into four groups. The animals of group I served as normal and was given only vehicle. Group II served as toxin control and administered with CCl(4) (50% solution liquid paraffin, 2 ml/kg intraperitoneally). The animals of group III received coumarinolignoids (50 mg/kg) for six days orally as well as CCl(4) (2 ml/kg) on 4(th) day i.p. Similarly animals of group IV received silymarin (50 mg/kg) for six days orally as well as CCl(4) on 4(th) day i.p. On 7(th) day various parameters viz. serum glutamyl oxaloacetic transaminase, serum glutamyl pyruvate transaminase, serum alkaline phosphatase, serum bilirubin, liver glycogen were estimated and histopathology was performed. Additionally, acute oral toxicity of the said coumarinolignoids was carried out in swiss albino mice. The coumarinolignoids were found to be effective as hepatoprotective against CCl(4)-induced hepatotoxicity as evidenced by in vivo and histopathological studies in small animals. Safety evaluation studies also exhibit that coumarinolignoids are well tolerated by small animals in acute oral toxicity study except minor changes in red blood cell count and hepatic protein content at 5000 mg/kg body weight as a single oral dose. Coumarinolignoids which is the mixture of three compounds (cleomiscosin A, B and C) is showing the significant protective effects against CCl(4)-induced hepatotoxicity in small animals and also coumarinolignoids are well tolerated by small animals in acute oral study.

Modulation of inflammatory mediators by coumarinolignoids from Cleome viscosa in female swiss albino mice.

The effect of coumarinolignoid cleomiscosins A, B and C isolated from the plant Cleome viscosa on inflammatory mediators were studied in female swiss albino mice. A mixture of coumarinolignoid A, B, and C at 10, 30 and 100 mg/kg body weight once a day for 14 consecutive days were administered orally to the mice. Pro-inflammatory mediators such as IL-6, TNF-alpha and nitric oxide were estimated from culture supernatant obtained from peritoneal macrophages stimulated by LPS and anti-inflammatory mediator IL-4 was estimated from culture supernatant obtained from spleenocytes stimulated by Con-A. For further confirmation, expressions of inflammatory mediators from serum and mortality rate were studied in LPS-induced toxicity model in mice. The expression of Pro-inflammatory mediators was significantly (P <0.05) decreased in coumarinolignoids treatment group in dose dependent manner, whereas the anti-inflammatory mediator expression was significantly increased in coumarinolignoids at 10 mg/kg treatment. Mortality rate was also significantly reduced in treatment group in LPS-induced toxicity model. The result of this study concluded that the oral administration of coumarinolignoids inhibited the pro-inflammatory mediators and enhances the production of anti-inflammatory mediator in dose dependent manner.

HELLP syndrome--a pregnancy disorder with poor prognosis.

HELLP syndrome is a pregnancy-specific disorder defined by hemolysis, elevated liver enzymes and low platelet count that is found in parturients, more frequent in older multiparas. It is frequently associated with severe preeclampsia or eclampsia, but can also be diagnosed in the absence of these disorders. The etiology of HELLP syndrome is unknown, and the pathogenesis of this disorder (including the hepatological manifestations) is not fully understood. The most widely accepted hypotheses are: a change in the immune feto-maternal balance, platelet aggregation, endothelial dysfunction, arterial hypertension and an inborn error of the fatty acid oxidative metabolism. Hepatic involvement occurs by intravascular fibrin deposition and hypovolemia. Serum LDH and platelet count are the two most important clinical tools for disease assessment. LDH reflects both the extent of hemolysis and hepatic dysfunction. Maternofetal complications cause a 7.0-70.0% perinatal mortality rate and a 1.0-24.0% maternal mortality rate. The recognition of HELLP syndrome and an aggressive multidisciplinary approach and prompt transfer of these women to obstetric centers with expertise in this field are required for the improvement of materno-fetal prognosis.

Synthesis of diverse analogues of Oenostacin and their antibacterial activities.

Several diverse analogues of Oenostacin, a naturally occurring potent antibacterial phenolic acid derivative, have been synthesized. A small library with more than forty analogues having different aromatic rings and varied side chains has been achieved through solution phase synthesis. Some of these analogues, that is, 22, 23 and 42, possessed potent antibacterial activities against Staphylococcus epidermidis and Staphylococcus aureus having EC(50) ranging from 0.49 to 0.67 microM as compared to Oenostacin (EC(50)=0.12 microM).

LC-ESI-MS analysis of taxoids from the bark of Taxus wallichiana.

LC-ESI-MS analysis was carried out for taxoid profiling of partially purified methanol extracts of the stem bark of Taxus wallichiana growing in different regions of the Himalayas (Kashmir, Himachal Pradesh, UP hills, Sikkim and Arunachal Pradesh). Cone voltage fragmentation of the protonated, ammonium or sodium cationized molecular species resulted in diagnostic fragment ions. Thus, information about the number and nature of substituents and the taxane skeleton (whether it is normal or rearranged) was readily available from the LC-ESI-MS spectra. The rearranged 11(15-->1)-abeo-taxanes showed a characteristic elimination of the hydroxyisopropyl along with an acetoxy group. The identification of the taxoids was achieved by comparison of the ESI mass spectra with those of the authentic taxoids available to us or by interpreting the ESI mass spectra. The results were also corroborated by MS/MS analysis of the partially purified extract injected directly into the ESI source. Paclitaxel, its analogues and their xylosides are present in samples from all the regions. An interesting observation is the detection of a large number of basic taxoids having nitrogen-containing side chains.

MS/MS profiling of taxoids from the needles of Taxus wallichiana.

Ammonium cationisation has been used for taxoid profiling of partially purified methanolic extracts of needles of Taxus wallichiana growing in different regions of the Himalayas (Kashmir, Himachal Pradesh, UP Hills, Darjeeling, Sikkim and Arunachal Pradesh) by electrospray ionisation tandem mass spectrometry (MS/MS). The MS/MS spectra of the [M + NH4]+ or [M + H]+ ions gave structurally diagnostic fragment ions which revealed information about the taxane skeleton as well as the number and nature of the substituents. The rearranged 11(15-->1)-abeo-taxanes showed a characteristic elimination of the hydroxyisopropyl group with an acetoxy/benzoyloxy group from C-9. The identification of the taxoids was achieved by comparison of the MS/MS spectra with those of authentic taxoids or was based on biogenetic grounds. The results were corroborated by liquid chromatography-MS analysis. Out of the 50 taxoids identified, 21 belonged to the rearranged class. The presence of paclitaxel in the samples from four regions was confirmed: the study also revealed the occurrence of several basic taxoids in these samples. MS/MS profiling by electrospray ionisation was shown to be a fast and reliable technique for the analysis of taxoid samples.

Elimination of 118 Da: a characteristic fragmentation in the tandem mass spectra of 11(15 --> 1)-abeo-taxanes.

The mechanism of the elimination of 118 Da from 11(15-->1)-abeo-taxanes was elucidated with the help of the tandem mass spectra of [M + NH(4)](+) and [M + Li](+) ions and the corresponding D-exchanged species. The fragmentation is triggered by the initial loss of the C-10 substituent. Evidence was also obtained for the stepwise elimination of acetone and acetic acid. Acetone is eliminated from the C-1 hydroxyisopropyl group and acetic acid from either the C-9 or C-7 acetoxy groups. The presence of an additional acetoxy group at C-13 leads to the direct elimination of 118 Da from [M + NH(4)](+) and [M + Li](+) ions involving the C-13 acetoxy group.

Combined histologic and molecular features reveal previously unappreciated subsets of lymphoma in AKXD recombinant inbred mice.

Hematopoietic neoplasms developing in AKXD recombinant inbred, NFS.V(+) and ICSBP knockout mice were assessed using morphologic, cytologic and molecular criteria that relate these disorders to human lymphoma and leukemia. Lymphoma types included precursor T-cell and B-cell lymphoblastic, small lymphocytic, splenic marginal zone, follicular, and diffuse large cell (DLCL). In addition to previously defined subtypes of DLCL composed of centroblasts or immunoblasts, two additional subtypes are defined here: lymphoblastic lymphoma like (LL) and lymphoma characterized by a histiocytic reaction (HS). DLCL(HS) were distinguished from true histiocytic lymphomas by the presence of clonal Ig gene rearrangements.

Non-Hodgkin lymphomas of mice.

Studies of lymphoid neoplasms occurring in normal or genetically engineered mice have revealed parallels and differences to non-Hodgkin lymphomas (NHL) of humans. Some mouse lymphomas have strong histologic similarities to the human NHL subsets including precursor B- and T-cell lymphoblastic, small lymphocytic, splenic marginal zone, and diffuse large-cell B-cell lymphomas (DLCL); whether molecular parallels also exist is under study. Others mouse types such as sIg+ lymphoblastic B-cell lymphoma have no histologic equivalent in human NHL even though they share molecular deregulation of BCL6 with human DLCL. Finally, Burkitt lymphoma does not appear to occur naturally in mice, but it can be induced with appropriately engineered transgenes.

Absorption spectroscopic study of EDA complexes of.

[70]Fullerene has been shown to form 1:1 molecular complexes with toluene, p-xylene, m-xylene, 1,2,4,5-tetramethyl benzene (durene) and pentamethyl benzene (PMB) in CCl4 medium by absorption spectroscopic method. Isosbestic points have been detected in case of complexes with PMB and durene. Charge transfer absorption band could not be detected but the intensity of the broad absorption band of C70 in CCl4 decreases systematically with increase in the concentration of the added methylbenzenes. From this trend the formation constants (Kc) of the complexes have been determined at three different wavelengths. The constancy of Kc with respect to change in the wavelength of measurement supports the view that complex of a single stoichiometry (1:1) is formed in each case.

Genomic organisation and expression of BCL6 in murine B-cell lymphomas.

BCL6 encodes a transcription factor deregulated by chromosomal translocations in human diffuse large cell B lymphomas (DLCL). This study was designed to determine whether Bcl6 might also be involved in lymphomas of mice. BCL6 protein was expressed at high levels in 90% or more of DLCL but not in low grade B lymphomas. Southern hybridisation studies demonstrated altered organisation of Bcl6 in three primary DLCL and the WEHI 231 B-cell lymphoma cell line but not in low grade tumours. Chromosomal painting and fluorescence in situ hybridisation (FISH) analyses of the WEHI 231 metaphase spreads revealed a T(5;16) translocation with Bcl6 on Chromosome 16 at the translocation breakpoint. Deregulated expression of BCL6 is thus likely to contribute to the genesis of DLCL of mice as well as of humans.

Lymphomas and high-level expression of murine leukemia viruses in CFW mice.

Historically, Swiss Webster mice of the CFW subline, both inbred and random-bred stocks, have been considered to have a low spontaneous occurrence of hematopoietic system tumors, and previous reports of infectious expression of murine leukemia viruses (MuLVs) have been rare and unremarkable. In marked contrast, in the present study of CFW mice from one source observed by two laboratories over a 2-year period, nearly 60% developed tumors, 85% of which were lymphomas, the majority of B-cell origin. All tumors tested expressed ecotropic MuLVs, and most expressed mink cell focus-inducing (MCF) MuLVs. Among normal mice of weanling to advanced age, over one-half were positive for ecotropic virus in tail or lymphoid tissues, and MCF virus was frequently present in lymphoid tissue, less often in tail. Patterns of ecotropic proviral integration indicated that natural infection occurred by both genetic and exogenous routes. Lymphomas were induced in NIH Swiss mice infected as neonates with tissue culture-propagated MuLVs isolated from normal and tumor tissue of CFW mice.

Accelerated appearance of multiple B cell lymphoma types in NFS/N mice congenic for ecotropic murine leukemia viruses.

Spontaneous lymphomas occur at high frequency in NFS x V+ mice, strains congenic for ecotropic murine leukemia virus (MuLV) proviral genes and expressing virus at high titer. In the present study, a total of 703 NFS x V+ lymphomas were studied by histopathology, immunophenotypic analysis, immunoglobulin heavy chain or T cell receptor beta chain rearrangements, and somatic ecotropic MuLV integrations; 90% of the lymphomas tested were of B cell lineage. Low-grade tumors included small lymphocytic, follicular, and splenic marginal zone lymphomas, while high-grade tumors comprised diffuse large-cell (centroblastic and immunoblastic types), splenic marginal zone, and lymphoblastic lymphomas. Comparison of mice of similar genetic background except for presence (NFS x V+) or absence (NFS x V-) of functional ecotropic MuLV genomes showed that NFS x V-clonal lymphomas developed at about one-half the rate of those occurring in NFS x V+ mice, and most were low-grade B cell lymphomas with extended latent periods. In NFS x V+ mice, clonal outgrowth, defined by Ig gene rearrangements, was associated with acquisition of somatic ecotropic proviral integrations, suggesting that, although generation of B cell clones can be virus independent, ecotropic virus may act to increase the rate of generation of clones and speed their evolution to lymphoma. The mechanism remains undefined, because only rare rearrangements were detected in several cellular loci previously associated with MuLV insertional mutagenesis.