Field evaluation of Musa germplasm for resistance against banana stem weevil, Odoiporus longicollis (Oliver) (Curculionidae: Coleoptera) in Kadapa district of Andhra Pradesh

Banana germplasm with 17 different accessions for resistance were screened against banana stem weevil, Odoiporous longicollis in Koduru region of Kadapa district (Andhra Pradesh). All the accessions had infestation of stem weevil but with varying percent infestation. The 17 accessions of germplasm had weevil infestation ranging from 10.0–100 percent in 2012 with maximum infestation of 100 percent in red banana (AAA genome) followed by Bontha selection-88.88 % (ABB), Karpuravalli-84.60% (AAB) and Ellakibale-64.7% (AB) and the lowest was inSugandhalu-10.00% (AAB). In the year 2013, the infestation was in the range of 13.00-90.40% and with respect to infestation levels in different accessions, and the trend remained same as the earlier year wherein the highest infestation was recorded in red banana-90.40% followed by Bontha selection with the damage of 83.50 %, Karpuravalli (79.80%), Ellakibale (70.00%) and least in Sugandhalu-13.0% (AAB). There was no correlation between number of adults observed and percent damage and similarly no relation can be drawn between percent infestation and height of oviposition, This implies that the infestation caused by the weevils varied in different genotypes and also this information will be further helpful in selecting the resistant germplasms for future

Nanoparticle-assisted optical tethering of endosomes reveals the cooperative function of dyneins in retrograde axonal transport

Dynein-dependent transport of organelles from the axon terminals to the cell bodies is essential to the survival and function of neurons. However, quantitative knowledge of dyneins on axonal organelles and their collective function during this long-distance transport is lacking because current technologies to do such measurements are not applicable to neurons. Here, we report a new method termed nanoparticle-assisted optical tethering of endosomes (NOTE) that made it possible to study the cooperative mechanics of dyneins on retrograde axonal endosomes in live neurons. In this method, the opposing force from an elastic tether causes the endosomes to gradually stall under load and detach with a recoil velocity proportional to the dynein forces. These recoil velocities reveal that the axonal endosomes, despite their small size, can recruit up to 7 dyneins that function as independent mechanical units stochastically sharing load, which is vital for robust retrograde axonal transport. This study shows that NOTE, which relies on controlled generation of reactive oxygen species, is a viable method to manipulate small cellular cargos that are beyond the reach of current technology.National Institutes of Health (U.S.) (DP2-NS082125)National Science Foundation (U.S.) (Award 1055112)National Science Foundation (U.S.) (Award 1344302

Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms

The transforming JAK2V617F kinase is frequently associated with myeloproliferative neoplasms (MPNs) and thought to be instrumental for the overproduction of myeloid lineage cells. Several small molecule drugs targeting JAK2 are currently in clinical development for treatment in these diseases. We performed a high-throughput in vitro screen to identify point mutations in JAK2V617F that would be predicted to have potential clinical relevance and associated with drug resistance to the JAK2 inhibitor ruxolitinib (INCB018424). Seven libraries of mutagenized JAK2V617F cDNA were screened to specifically identify mutations in the predicted drug-binding region that would confer resistance to ruxolitinib, using a BaF3 cell-based assay. We identified 5 different non-synonymous point mutations that conferred drug resistance. Cells containing mutations had a 9 to 33-fold higher EC50 for ruxolitinib compared to native JAK2V617F. Our results further indicated that these mutations also conferred cross-resistance to all JAK2 kinase inhibitors tested, including AZD1480, TG101348, lestaurtinib (CEP-701) and CYT-387. Surprisingly, introduction of the ‘gatekeeper’ mutation (M929I) in JAK2V617F affected only ruxolitinib sensitivity (4-fold increase in EC50). These results suggest that JAK2 inhibitors currently in clinical trials may be prone to resistance as a result of point mutations and caution should be exercised when administering these drugs

Impact of sequence variation in the ul128 locus on production of human cytomegalovirus in fibroblast and epithelial cells

The human cytomegalovirus (HCMV) virion envelope contains a complex consisting of glycoproteins gH and gL plus proteins encoded by the UL128 locus (UL128L): pUL128, pUL130, and pUL131A. UL128L is necessary for efficient infection of myeloid, epithelial, and endothelial cells but limits replication in fibroblasts. Consequently, disrupting mutations in UL128L are rapidly selected when clinical isolates are cultured in fibroblasts. In contrast, bacterial artificial chromosome (BAC)-cloned strains TB40-BAC4, FIX, and TR do not contain overt disruptions in UL128L, yet no virus reconstituted from them has been reported to acquire mutations in UL128L in vitro. We performed BAC mutagenesis and reconstitution experiments to test the hypothesis that these strains contain subtle mutations in UL128L that were acquired during passage prior to BAC cloning. Compared to strain Merlin containing wild-type UL128L, all three strains produced higher yields of cell-free virus. Moreover, TB40-BAC4 and FIX spread cell to cell more rapidly than wild-type Merlin in fibroblasts but more slowly in epithelial cells. The differential growth properties of TB40-BAC4 and FIX (but not TR) were mapped to single-nucleotide substitutions in UL128L. The substitution in TB40-BAC4 reduced the splicing efficiency of UL128, and that in FIX resulted in an amino acid substitution in UL130. Introduction of these substitutions into Merlin dramatically increased yields of cell-free virus and increased cell-to-cell spread in fibroblasts but reduced the abundance of pUL128 in the virion and the efficiency of epithelial cell infection. These substitutions appear to represent mutations in UL128L that permit virus to be propagated in fibroblasts while retaining epithelial cell tropism

Co-evolution, opportunity seeking and institutional change: Entrepreneurship and the Indian telecommunications industry 1923-2009

"This is an Author's Original Manuscript of an article submitted for consideration in Business History [copyright Taylor & Francis]; Business History is available online at http://www.tandfonline.com/." 10.1080/00076791.2012.687538In this paper, we demonstrate the importance for entrepreneurship of historical contexts and processes, and the co-evolution of institutions, practices, discourses and cultural norms. Drawing on discourse and institutional theories, we develop a model of the entrepreneurial field, and apply this in analysing the rise to global prominence of the Indian telecommunications industry. We draw on entrepreneurial life histories to show how various discourses and discursive processes ultimately worked to generate change and the creation of new business opportunities. We propose that entrepreneurship involves more than individual acts of business creation, but also implies collective endeavours to shape the future direction of the entrepreneurial field

The experiences and beliefs of people with severe haemophilia and healthcare professionals on pain management, and their views of using exercise as an aspect of intervention: a qualitative study

Purpose: To explore the experiences, views and beliefs of people with severe haemophilia and healthcare professionals (HCPs) on approaches for pain management, as well as their views on exercise being used as an aspect of management. Methods: Taking a qualitative inquiry approach using focus groups and semi-structured interviews, participants included people with severe haemophilia living with chronic pain and haemophilia HCPs. Data were analysed using reflexive thematic analysis. Results: Fourteen men with haemophilia with a median age of 47 (range 23–73) and six haemophilia HCPs agreed to participate. Of the people with haemophilia, 11 attended two focus groups and three were interviewed over telephone. Healthcare professionals were interviewed face-to-face. Two themes were conceptualised from the data: (i) haemophilia management and pain management is discordant (imbalance between good haemophilia care but poor pain management, historical medico-social influences on pain management, the need for trust); (ii) uncertain about exercise but clear on what matters (conflicting views on exercise, the need for proof of safety, personalised care). Conclusions: Options for effective pain management remain limited and what is used is heavily influenced by beliefs and experience. Exercise as a treatment option in pain management is conceptually acceptable for people with haemophilia. Effective pain management requires understanding of individual beliefs and fears, and a personalised approach supported by knowledgeable, trusted clinicians

How does a lifetime of painful experiences influence sensations and beliefs about pain in adults with severe haemophilia? A qualitative study

Purpose: To explore the life experiences of pain in people with severe haemophilia and understand how such experiences influence beliefs and sensation of pain in adulthood. Methods: A qualitative inquiry approach using focus groups and semi-structured individual interviews was used. Participants included people with severe haemophilia living with chronic pain. Data were analysed using reflexive thematic analysis. Results: Fourteen men with a median age of 47 (range 23–73) agreed to take part. Eleven participated in two focus groups and three were interviewed over telephone. Two themes were conceptualised from the data: (i) haemophilia and pain – an evolving life biography (the personal narrative, historical, social, and medical context, continuous adaptation of activity choices, surveillance of pain and its meaning); (ii) “My normal isn’t normal” – identity and self-agency (pain as a feature of life and identify with severe haemophilia, loss of enjoyable activities balanced against staying active, barriers to participation). Conclusions: Pain is a constantly evolving, lifetime feature for many adults with haemophilia and it is viewed as part of their identity with their condition. Healthcare professionals working in haemophilia should try to better understand the influence of an individuals lived experience with their haemophilia on beliefs and behaviours of pai

Physiotherapy interventions for pain management in haemophilia: A systematic review

Purpose: Approximately 35%-50% of people with haemophilia (PWH) report living with chronic musculoskeletal pain. Although exercise based rehabilitation is effective for pain in other arthritises, there are no published guidelines for management of chronic pain in PWH. This review aims to evaluate and appraise the current evidence of effectiveness of physiotherapy interventions on (a) pain intensity, (b) quality of life (QoL) and (c) function in PWH. Methods: A systematic review of five databases AMED and CINAHL, EMBASE and MEDLINE and PEDro, as well as trial registries, grey literature and hand searching key journals was completed. Included studies were critically appraised and evaluated for risk of bias. The GRADE approach was used to rate the quality of the evidence. Results: Nine trials consisting of 235 participants met the inclusion criteria. All studies had an overall risk of bias with low methodological quality. Meta-analysis was not possible due to heterogeneity across trials. Studies comparing a range of physiotherapy interventions against no intervention showed no clear beneficial effect on pain intensity or QoL. Only one study, investigating hydrotherapy or land-based exercise against control, showed positive effect for pain intensity, but rated very low on GRADE assessment. Studies comparing one physiotherapy intervention against another showed no clear benefit on pain intensity, QoL or function. LASER with exercise and hydrotherapy were shown to have some positive effects on pain intensity, but no clear benefit on function. Conclusions: At present, there is limited evidence for the use of physiotherapy interventions in addressing the issue of pain in PWH. Better designed trials with higher quality and explicit methodology along with user involvement are needed to assess the efficacy of any proposed intervention

COMPARATIVE EVALUATION OF NOVEL ACARICIDES AGAINST TWO SPOTTED SPIDER MITE. TETRANYCHUS URTICAE KOCH. INFESTING CUCUMBER (CUCUMIS SATIVUS) UNDER LABORATORY AND GREEN HOUSE CONDITIONS

Five commercially available new acaricides viz., Abamectin, Fenazaquin, Spiromesifen, Fenpyroximate and Hexythiazox were compared to a standard acaricide, Dicofol and Propargite for efficacy against the two spotted spider mite, Tetranychus urticae (koch) under laboratory and green house field conditions. In laboratory trials, all the acaricides resulted in 31.13 to 100 percent mortality with highest in Fenazaquin and Abamectin treatments during I season and 46.32 to 100 percent in II season with lowest percent mortality in Hexythiazox @ 0.75 mL/ L. No mite were found to be alive after 48h of treatment in Fenazaquin and Abamectin treatment compared to other acaricides and control, however in the treatments of Propargite, Hexythiazox, and Dicofol, lower mortality (<70 percent) was observed even 48 hrs after treatment during both the seasons. During first crop season, Fenazaquin 10EC @ 1.7mL/L and Abamectin 1.9EC @1.0 ml/L caused mortality in the range of 92.39–100 percent compared to Spiromesifen (88.87%), Fenpyroximate (70.03%), Hexythiazox (37.40-60.80%), Propargite (45.06%) and Dicofol (26.30%) where the efficacy declined on 14th day observation. During II season observation, lower mortality of mites was recorded in standard acaricides viz., Dicofol (74.00%; 22.30%) and Propargite (81.30%; 39.24%) on 1 and 14th day, respectively indicating that at initial period though the mortality was higher but these acaricides lost their efficacy over a period of time and may be failure in control of spider mites. Abamectin @ 0.5ml/L (89.29%; 94.55%) and 1.0ml/L (93.85%; 98.71%), Fenazaquin (97.68%; 94.33%), Spiromesifen (93.90%; 87.30%), Fenproximate (79.20%; 59.74%), Hexythiazox @ 1.25 ml/L (83.87%; 55.73%) showed higher mortality on 1st and 14th day, respectively and efficacy in terms of mortality was prolonged till last day observation. All the acaricides tested in both laboratory and green house conditions were proved superior over control and Abamactin and Fenazaquin were superior over other acarcides tested

Exercise-based telerehabilitation for the management of chronic pain in people with severe haemophilia: a mixed-methods feasibility study.

Background: Chronic pain is reported by between 30 and 71% of people with haemophilia (PWH). Exercise is shown to be effective for pain management in other arthritis’s, but it remains unclear if such an approach is effective or acceptable to PWH. The aim of this study was to evaluate the feasibility and acceptability of a telerehabilitation exercise intervention for PWH living with chronic pain. Methods: This was a multisite, non-randomised, pre-post feasibility design, with a nested qualitative study. People with severe haemophilia>18 years, living with chronic pain, were recruited. The intervention comprised 12 low-impact/moderate intensity, individualised exercise sessions and 3 knowledge-sharing and discussion sessions. Primary objectives assessed according to predefined progression criteria were as follows: (a) recruitment rate (5 participants enrolled per site over 8 weeks), (b) adherence (≥75% participants would adhere to≥75% of sessions), (c) follow-up rate (≥75% completion of self-reported measures), (d) fidelity (intervention delivered as described in protocol) and (e) safety (≤30% participants would report adverse events). Acceptability was evaluated from thematic analysis of post-intervention participant interviews. Preliminary evaluation of self-reported pain, function and quality of life (QoL) was a secondary objective. Results were reported using descriptive statistics integrated with qualitative findings. Results: Ten PWH were recruited and completed the intervention. Nine agreed to be interviewed post intervention. Attendance at individual sessions was 84.5% compared to 52.1% for the group sessions. Outcome measures were successfully completed for 100% at baseline, 70% at intervention end and 60% at 3-month follow-up. No serious adverse events were recorded. Group median values in outcome measures (pain, function, QoL) showed minimal change post intervention. Participant interviews highlighted high levels of enjoyment, confidence in continuing exercises independently and positive views of virtual delivery and condition-specific exercise. Conclusions: Recruitment rate and safety met the predefined progression criteria. Fidelity partially met the progression criteria, but the follow-up rate for self-reported measures did not. The study was acceptable to both participants and physiotherapists. Further intervention development is needed to review approaches to outcome measure collection and refine the usefulness of the knowledge-sharing sessions