KCNQ channels regulate age-related memory impairment:KCNQ regulates age-related memory

In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ) when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment

Direct and simple approach for assigning absolute configuration in wedge dash projection

The procedure of assignment of absolute configuration to optical stereoisomers in various projections has been already described in  literature. Most common methods utilize the Fischer Projection as the standard and hence demands a three dimensional structure (wedge dash projection, newmann projection, sawhorse projection) to be inter converted to two dimensional planar Fischer Projection. This adds on an extra exercise which may sometimes cause error while specifying Absolute Configuration to a molecule originally represented in  three dimensional projections. Hence this assignment of configuration to optical isomers should be directly taught to undergraduates through three dimensional representation of the molecule as stereochemistry deals with three dimensional aspects of an organic  compound. This method assigns absolute configuration to the chiral molecules directly in wedge dash projection without interconverting to Fischer Projection

Mimicking reproductive endocrinology to achieve successful pregnancy in frozen embryo replacement cycle in luteinized unruptured follicle (LUF)

Frozen embryo replacement cycles are commonly performed in all ART centres for various indications. In FER cycles, aim is to achieve the synchronization between the endometrium and the embryo. It can be undertaken in a natural or in an artificially prepared endometrium. Artificial preparation utilizes either the ovulation induction agents or hormones. Luteinized unruptured follicle is commonly encountered nowadays due to better resonance USG machines and frequent monitoring. It is still unclear among the practitioners whether to perform an embryo transfer in LUF.  In this case report, authors are highlighting that in case of FER cycles using ovulation induction agent, despite inability to ovulate (LUF), if authors are able to achieve optimum synchronization between endometrium and the embryo using USG and serum hormonal levels, successful outcome could be expected.

Impact of different grades of anaemia severity during pregnancy on maternal and neonatal outcomes: a prospective study

Background: Anaemia in pregnancy is a universal health problem that may cause a number of obstetrical and neonatal complications. This prospective observational study aims to evaluate and compare maternal and neonatal outcomes in different grades of anaemia severity.Methods: A total of 400 pregnant women with anaemia in third trimester were classified into three groups according to haemoglobin (Hb) levels-group I with Hb:10-10.9 g/dl, group II with Hb:7-9.9g/dl and group III with Hb<7 g/dl. Maternal and neonatal outcomes of women with different severity of anaemia were analyzed and compared. Two groups means were compared by Student’s t-independent test and more than two groups means by one way analysis of variance test followed by post-hoc pairwise comparison using Bonferroni test.Results: The prevalence of anaemia in the study population was 35.2%. Mild, moderate and severe anaemia were found in 58% (n=232), 29.0% (n=116) and 13% (n=52) women respectively. A statistically significant difference in maternal outcomes such as Preterm labor (p=0.001), Prelabor premature rupture of membranes (p=0.044), Intrauterine growth restriction (p=0.002) and postpartum hemorrhage (p=0.001) was observed amongst the three groups. Cardiac failure occurred in 26.9% (n=14) and mortality in 13.4% (n=7) women with severe anaemia. Amongst the neonatal morbidities, the rate of low birth weight, preterm birth, respiratory distress syndrome, septicaemia, pneumonitis and jaundice revealed an increasing trend with rising severity of anaemia which was statistically significant.Conclusions: Targeted interventions addressing early detection and appropriate treatment in early pregnancy can prevent and avoid dismal maternal and neonatal consequences

Expression of 3-hydroxy-3-methylglutaryl-CoA reductase, p-hydroxybenzoate-m-geranyltransferase and genes of phenylpropanoid pathway exhibits positive correlation with shikonins content in arnebia [Arnebia euchroma (Royle) Johnston]

<p>Abstract</p> <p>Background</p> <p>Geranyl pyrophosphate (GPP) and <it>p</it>-hydroxybenzoate (PHB) are the basic precursors involved in shikonins biosynthesis. GPP is derived from mevalonate (MVA) and/or 2-<it>C</it>-methyl-D-erythritol 4-phosphate (MEP) pathway(s), depending upon the metabolite and the plant system under consideration. PHB, however, is synthesized by only phenylpropanoid (PP) pathway. GPP and PHB are central moieties to yield shikonins through the synthesis of <it>m</it>-geranyl-<it>p</it>-hydroxybenzoate (GHB). Enzyme <it>p</it>-hydroxybenzoate-<it>m</it>-geranyltransferase (PGT) catalyses the coupling of GPP and PHB to yield GHB.</p> <p>The present research was carried out in shikonins yielding plant arnebia [<it>Arnebia euchroma </it>(Royle) Johnston], wherein no molecular work has been reported so far. The objective of the work was to identify the preferred GPP synthesizing pathway for shikonins biosynthesis, and to determine the regulatory genes involved in the biosynthesis of GPP, PHB and GHB.</p> <p>Results</p> <p>A cell suspension culture-based, low and high shikonins production systems were developed to facilitate pathway identification and finding the regulatory gene. Studies with mevinolin and fosmidomycin, inhibitors of MVA and MEP pathway, respectively suggested MVA as a preferred route of GPP supply for shikonins biosynthesis in arnebia. Accordingly, genes of MVA pathway (eight genes), PP pathway (three genes), and GHB biosynthesis were cloned. Expression studies showed down-regulation of all the genes in response to mevinolin treatment, whereas gene expression was not influenced by fosmidomycin. Expression of all the twelve genes vis-à-vis shikonins content in low and high shikonins production system, over a period of twelve days at frequent intervals, identified critical genes of shikonins biosynthesis in arnebia.</p> <p>Conclusion</p> <p>A positive correlation between shikonins content and expression of <it>3-hydroxy-3-methylglutaryl-CoA reductase </it>(<it>AeHMGR</it>) and <it>AePGT </it>suggested critical role played by these genes in shikonins biosynthesis. Higher expression of genes of PP pathway was a general feature for higher shikonins biosynthesis.</p

Towards a better understanding of Artemisia vulgaris: botany, phytochemistry, pharmacological and biotechnological potential

Artemisia vulgaris is one of the important medicinal plant species of the genus Artemisia, which is usually known for its volatile oils. The genus Artemisia has become the subject of great interest due to its chemical and biological diversity as well as the discovery and isolation of promising anti-malarial drug artemisinin. A. vulgaris has a long history in treatment of human ailments by medicinal plants in various parts of the world. This medicinal plant possesses a broad spectrum of therapeutic properties including: anti-malarial, anti-inflammatory, anti-hypertensive, anti-oxidant, anti-tumoral, immunomodulatory, hepatoprotective, anti-spasmodic and anti-septic. These activities are mainly attributed to the presence of various classes of secondary metabolites, including flavonoids, sesquiterpene lactones, coumarins, acetylenes, phenolic acids, organic acids, mono- and sesquiterpenes. Studies related to A. vulgaris morphology, anatomy and phytochemistry has gained a significant interest for better understanding of production and accumulation of therapeutic compounds in this species. Recently, phytochemical and pharmacological investigations have corroborated the therapeutic potential of bioactive compounds of A. vulgaris. These findings provided further evidence for gaining deeper insight into the identification and isolation of novel compounds, which act as alternative sources of anti-malarial drugs in a cost-effective manner. Considering the rising demand and various medical applications of A. vulgaris, this review highlights the recent reports on the chemistry, biological activities and biotechnological interventions for controlled and continuous production of bioactive compounds from this plant species

What Matters to You? Engaging With Children in the James Lind Alliance Children’s Cancer Priority Setting Partnership

BACKGROUND: Previous priority setting exercises have sought to involve children, but in the final reporting, it is evident that few children had been engaged through the process. A primary aim in the Children\u27s Cancer Priority Setting Partnership was to find out from children what they want research to focus on. We report on our experience to inform methods of engagement with children in future James Lind Alliance Priority Setting Partnerships and similar exercises. METHODS: We followed the James Lind Alliance process, collecting and shortlisting questions via online surveys with adult survivors of childhood cancer, carers, and professionals, and holding a final workshop. Alongside this, a parallel process to collect and prioritise questions from children was undertaken. We created animations for parents/carers to explain the project and surveys to children, gathered questions via online surveys and held a workshop with children to identify their priorities. RESULTS: Sixty-one children and young people with cancer and 10 siblings, aged 3-21 years, submitted 252 potential questions/topics via the surveys. Submissions were refined into 24 summary questions. These questions were discussed at a workshop with eight children; they also added more questions on topics of importance to them. Workshop participants prioritised the Top 5 questions; top priority was, \u27How can we make being in hospital a better experience for children and young people? (like having better food, internet, toys, and open visiting so other family members can be more involved in the child\u27s care)\u27. The Top 5 also included cancer prevention, treatments closer to home, early diagnosis, and emotional support. These questions were taken to the final workshop at which the Top 10 priorities were decided, all five children\u27s priorities were reflected in the final Top 10. CONCLUSIONS: We have demonstrated that it is possible to successfully involve children directly in setting priorities for future research. Future priority setting exercises on topics relevant to children, should seek to include their views. The Children\u27s Cancer Top 10 priorities reflect the voices of children and should inform the funding of future research

Development of a practicum tool to analyze the angular speed and direction of the heel's movement

This research aims to develop a practicum tool to analyze the angular velocity and direction of rotation produced by the wheel's movement. The study method used is research and development which is the most reliable in scientific knowledge and is concerned with changes that lead to improvements. The research and development stage begins with a discussion stage for collecting ideas, submitting designs, and making tools. The working principle of the tool was to connect the tool to the electric current. So that the wheels can rotate and observe the direction of rotation. The rotation of the wheels that touch each other is connected by a rope. The data that will be obtained from this experiment is the number of turns on the wheel, the length of time the wheel rotates, and the diameter of each wheel. Data analysis was carried out by determining the frequency, angular velocity, and direction of rotation of each wheel. The result showed the intersecting wheels had different rotational directions and angular velocities. The wheel connected to the rope has a rotating direction in the same direction at different angular velocities. Thus, the practicum tool developed can analyze the angular velocity and direction of the wheel's movement rotation

First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal

BACKGROUND: Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. METHODS AND FINDINGS: We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42-4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43-5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. CONCLUSIONS: We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian reg