Establishment of Plantlets and Evaluation of Differentiated Roots for Alkaloids in Rauwolfia serpentha

Different explants of Rauwolfia serpentina were tested for their capacity and root differentiation. MS sedium containing 2.0 mg I^-1 BAP or 1.5 mg I^-1 BAP with 0.5 mg I-* NAA gave the best shoot proliferation from shoot apices (84.12%). Multiple shoots subcultured on the same media gave higher number of shoots (6–9). Callus formed at the cut ends of explants produced shoots when subcultured on the above media. Rooting was achieved after transfer of shoots either to hormone free or half strength or full strength MS medium with different concentrations of IAA (0.5,1.0 mg I^-1 and IBA (0.5,1.0 mg I^-1).The complete regenerated plantlets have been successfully transferred to earthen pots in green house. Maximum root differentiation from leaves, stem and nodal cuttings derived calli was obtained on MS medium supplemented with NAA (2.0 mg I^-1) and BAP (1.5 mg I^-1). Identification of reserpine and other alkaloids from differentiated roots holds an interesting alternative for controlled production of alkaloids from this endangered, overexploited medicinal plant species.     

Serum Metabolomics of Slow vs. Rapid Motor Progression Parkinson’s Disease: a Pilot Study

Progression of Parkinson’s disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.     

Comparative Assessment of ISSR and RAPD Marker Assays for Genetic Diversity Analysis in Jojoba [Simmondsia chinensis (Link) Schneider]

A collection of male and female plants of ten Jojoba [Simmondsia chinensis (Link) Schneider] genotypes was analyzed with 50 RAPID and 55 ISSR markers to compare the efficiency and utility of these techniques for detecting genetic polymorphism. RAPID and ISSR analysis yielded 442 and 566 scorable amplified products, respectively, of which 60.7 and 69.3% were polymorphic. ISSRs revealed efficiency over RAPDs due to high EMR (effective multiplex ratio), DI (diversity index, mean PIC per primer) and MI (marker index) values. Jaccard similarity matrices among male plants, among female plants and between male and female plants of the ten jojoba genotypes varied between 0.705-0.784. Dendrograms generated by cluster analysis (UPGMA, NTSYS-pc) supported by bootstrap values using RAPID and ISSR datasets led to grouping of most of male and females genotypes in separate clusters. While pattern of clustering remained more or less same, the two dendrograms did differ with respect to the grouping of a few male and female genotypes. The value of the Mantel test shows poor correlation (r = 0.41) between ISSR and RAPID marker datasets.     

High-Resolution Mapping of H1 Linker Histone Variants in Embryonic Stem Cells

H1 linker histones facilitate higher-order chromatin folding and are essential for mammalian development. To achieve high-resolution mapping of H1 variants H1d and H1c in embryonic stem cells (ESCs), we have established a knock-in system and shown that the N-terminally tagged H1 proteins are functionally interchangeable to their endogenous counterparts in vivo. H1d and H1c are depleted from GC- and gene-rich regions and active promoters, inversely correlated with H3K4me3, but positively correlated with H3K9me3 and associated with characteristic sequence features. Surprisingly, both H1d and H1c are significantly enriched at major satellites, which display increased nucleosome spacing compared with bulk chromatin. While also depleted at active promoters and enriched at major satellites, overexpressed H1⁰ displays differential binding patterns in specific repetitive sequences compared with H1d and H1c. Depletion of H1c, H1d, and H1e causes pericentric chromocenter clustering and de-repression of major satellites. These results integrate the localization of an understudied type of chromatin proteins, namely the H1 variants, into the epigenome map of mouse ESCs, and we identify significant changes at pericentric heterochromatin upon depletion of this epigenetic mark.     

Drug formulations that require less than 0.1 mL of stock solution to prepare doses for infants and children

Intravenous doses of medications require formulations that permit accurate preparation and administration. Current equipment does not permit accurate measurement of volumes less than 0.1 mL. In a study of four hypothetical standard pediatric patients, we found that 28 common medications required less than 0.1 mL of available formulation to prepare the dose. In a clinical study of actual use in a pediatric intensive care unit (ICU), 5245 (7.4%) of 71 218 intravenous doses required preparation from less than 0.1 mL of stock solution. For 28.5% of the 1531 ICU admissions, at least one dose was prepared from a volume of less than 0.1 mL. Our findings identify a substantial source of dosing error. Correction will require revision of preparation methods, regulatory requirements and manufacturing practices.Preparation of parenteral doses of medications from small volumes using commercially available syringes is imprecise and may result in serious dosing errors.^1–3 Previously, we showed that 60% of 116 doses prepared from 0.06 mL of stock solution had a dosing error of more than 10%, and 27% had a two-fold dosing error.² We hypothesized that small volumes of commercially available formulations are often required to prepare intravenous doses for infants and children.     

Enhanced ethanol production from sugarcane juice by galactose adaptation of a newly isolated thermotolerant strain of Pichia kudriavzevii

The thermotolerant yeast strain isolated from sugarcane juice through enrichment technique was identified as a strain of Pichiakudriavzevii (Issatchenkiaorientalis) through molecular characterization. The P. kudriavzevii cells adapted to galactose medium produced about 30% more ethanol from sugarcane juice than the non-adapted cells. The recycled cells could be used for four successive cycles without a significant drop in ethanol production. Fermentation in a laboratory fermenter with galactose adapted P. kudriavzevii cells at 40 °C resulted in an ethanol concentration and productivity of 71.9 g L⁻¹ and 4.0 g L⁻¹ h⁻¹, respectively from sugarcane juice composed of about 14% (w/v) sucrose, 2% (w/v) glucose and 1% (w/v) fructose. In addition to ethanol, 3.30 g L⁻¹ arabitol and 4.19 g L⁻¹ glycerol were also produced, whereas sorbitol and xylitol were not formed during fermentation. Use of galactose adapted P. kudriavzevii cells for ethanol production from sugarcane juice holds potential for scale-up studies.     

Dental implications of bisphophonate-related osteonecrosis

doi: 10.1111/j.1741‐2358.2012.00622.x
Dental implications of bisphophonate‐related osteonecrosis Objectives: The aim is to explore the current theories about clinical , pathological and dental management of bisphosphonate related osteonecrosis of the jaws. Also discussed are the actions of bisphosphonates, pathogenesis related to the susceptibility of jaws, the predisposing risk factors for the development of bisphosphonate‐related osteonecrosis of the jaws (BRONJ) and diagnostic criteria based on the literature review. Discussion: Osteoporosis is a disease that generally affects the mineral status of both cortical and trabecular bone in post menopausal women. Bisphosphonates are a group of drugs that preserve and increase bone mass. Bisphosphonate drugs are classified according to use and method of delivery. The bisphosphonates used for the treatment of osteoporosis are taken orally. Little is known about the side effects and dangers of the long‐term use of therapeutic doses of Bisphosphonates. A recent complication reported is osteonecrosis of jaws. The use of IV bisphosphonates for multiple myeloma and metastatic bone diseases suggests that dosage, length of treatment, and route of administration, as well as cofactors such as use of glucocorticoids and immunosuppressive agents, and dental surgery, could all be related to the incidence of BRONJ. This review provides an update on current knowledge about clinical, pathological and management aspects of BRONJ. Conclusions: Little evidence exists to direct the prosthodontic management of patients with a history of bisphosphonate use. Patients with active osteonecrosis related to bisphosphonate use have reduced tissue tolerance to function with removable prostheses and decreased potential for osseointegration of dental implants. Decisions should be based on clinical judgment tempered by the presenting conditions, medical profile, and patient needs. A better understanding would help in a dental setting to prevent any complication and help to improve the prognosis for those being treated for osteoradionecrosis.Until further evidence emerges regarding management of patients with active bisphosphonate‐ related osteonecrosis, conservative prosthodontic treatment is reasonable and prudent.     

Investigation of the spinal cord as a natural receptor antenna for incident electromagnetic waves and possible impact on the central nervous system

The effects of electromagnetic field (EMF) exposure on biological systems have been studied for many years, both as a source of medical therapy and also for potential health risks. In particular, the mechanisms of EMF absorption in the human or animal body is of medical/engineering interest, and modern modelling techniques, such as the Finite Difference Time Domain (FDTD), can be utilized to simulate the voltages and currents induced in different parts of the body. The simulation of one particular component, the spinal cord, is the focus of this article, and this study is motivated by the fact that the spinal cord can be modelled as a linear conducting structure, capable of generating a significant amount of voltage from incident EMF. In this article, we show, through a FDTD simulation analysis of an incoming electromagnetic field (EMF), that the spinal cord acts as a natural antenna, with frequency dependent induced electric voltage and current distribution. The multi-frequency (100-2400?MHz) simulation results show that peak voltage and current response is observed in the FM radio range around 100?MHz, with significant strength to potentially cause changes in the CNS. This work can contribute to the understanding of the mechanism behind EMF energy leakage into the CNS, and the possible contribution of the latter energy leakage towards the weakening of the blood brain barrier (BBB), whose degradation is associated with the progress of many diseases, including Acquired Immuno-Deficiency Syndrome (AIDS).     

Metabolic Consequences of Chronic Alcohol Abuse in Non-Smokers: A Pilot Study

An alcohol use disorder (AUD) is associated with an increased susceptibility to respiratory infection and injury and, upon hospitalization, higher mortality rates. Studies in model systems show effects of alcohol on mitochondrial function, lipid metabolism and antioxidant systems. The present study applied high-resolution metabolomics to test for these changes in bronchoalveolar lavage fluid (BALF) of subjects with an AUD. Smokers were excluded to avoid confounding effects and compliance was verified by cotinine measurements. Statistically significant metabolic features, differentially expressed by control and AUD subjects, were identified by statistical and bioinformatic methods. The results show that fatty acid and acylcarnitine concentrations were increased in AUD subjects, consistent with perturbed mitochondrial and lipid metabolism. Decreased concentrations of methyl-donor compounds suggest altered one-carbon metabolism and oxidative stress. An accumulation of peptides suggests proteolytic activity, which could reflect altered epithelial barrier function. Two metabolites of possible microbial origin suggest subclinical bacterial infection. Furthermore, increased diacetylspermine suggests additional metabolic perturbations, which could contribute to dysregulated alveolar macrophage function and vulnerability to infection. Together, the results show an extended metabolic consequence of AUD in the bronchoalveolar space.