Human growth factor-mediated signalling through lipid rafts regulates stem cell proliferation, development and survival of Schistosoma mansoni

Although the mechanisms by which schistosomes grow and develop in humans are poorly defined, their unique outer tegument layer, which interfaces with host blood, is considered vital to homeostasis of the parasite. Here, we investigated the importance of tegument lipid rafts to the biology of Schistosoma mansoni in the context of host–parasite interactions. We demonstrate the temporal clustering of lipid rafts in response to human epidermal growth factor (EGF) during early somule development, concomitant with the localization of anteriorly orientated EGF receptors (EGFRs) and insulin receptors, mapped using fluorescent EGF/insulin ligand. Methyl-β-cyclodextrin (MβCD)-mediated depletion of cholesterol from lipid rafts abrogated the EGFR/IR binding at the parasite surface and led to modulation of protein kinase C, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and Akt signalling pathways within the parasite. Furthermore, MβCD-mediated lipid raft disruption, and blockade of EGFRs using canertinib, profoundly reduced somule motility and survival, and attenuated stem cell proliferation and somule growth and development particularly to the fast-growing liver stage. These findings provide a novel paradigm for schistosome development and vitality in the host, driven through host–parasite interactions at the tegument, that might be exploitable for developing innovative therapeutic approaches to combat human schistosomiasis

Mental health issues in pregnant women in Nepal

Mental health of pregnant women and new mothers is a growing area of concern in both low- and high-income countries. This editorial highlights some of the key mental issues faced by women in rural Nepal and outlines an intervention based on training community health care workers by experienced UK volunteers

The uncertain consequences of transferring bacterial strains between laboratories - rpoS instability as an example

Abstract\ud \ud \ud \ud Background\ud \ud Microbiological studies frequently involve exchanges of strains between laboratories and/or stock centers. The integrity of exchanged strains is vital for archival reasons and to ensure reproducible experimental results. For at least 50 years, one of the most common means of shipping bacteria was by inoculating bacterial samples in agar stabs. Long-term cultures in stabs exhibit genetic instabilities and one common instability is in rpoS. The sigma factor RpoS accumulates in response to several stresses and in the stationary phase. One consequence of RpoS accumulation is the competition with the vegetative sigma factor σ70. Under nutrient limiting conditions mutations in rpoS or in genes that regulate its expression tend to accumulate. Here, we investigate whether short-term storage and mailing of cultures in stabs results in genetic heterogeneity.\ud \ud \ud \ud Results\ud \ud We found that samples of the E. coli K-12 strain MC4100TF exchanged on three separate occasions by mail between our laboratories became heterogeneous. Reconstruction studies indicated that LB-stabs exhibited mutations previously found in GASP studies in stationary phase LB broth. At least 40% of reconstructed stocks and an equivalent proportion of actually mailed stock contained these mutations. Mutants with low RpoS levels emerged within 7 days of incubation in the stabs. Sequence analysis of ten of these segregants revealed that they harboured each of three different rpoS mutations. These mutants displayed the classical phenotypes of bacteria lacking rpoS. The genetic stability of MC4100TF was also tested in filter disks embedded in glycerol. Under these conditions, GASP mutants emerge only after a 3-week period. We also confirm that the intrinsic high RpoS level in MC4100TF is mainly due to the presence of an IS1 insertion in rssB.\ud \ud \ud \ud Conclusions\ud \ud Given that many E. coli strains contain high RpoS levels similar to MC4100TF, the integrity of such strains during transfers and storage is questionable. Variations in important collections may be due to storage-transfer related issues. These results raise important questions on the integrity of bacterial archives and transferred strains, explain variation like in the ECOR collection between laboratories and indicate a need for the development of better methods of strain transfer.We are grateful to Fundação de Amparo á Pesquisa do Estado de São Paulo (FAPESP-Brazil), who supported this study and provided a travel allowance for TF. TF was also supported by the the Australian Research Council and the US Army Research Office. We also thank K. C. Murphy and S. Kushner for respectively providing strain KM32 and plasmid pWKS130

Translation and cross-cultural adaptation of Nepali versions of the patient-reported outcomes measurement information system (PROMIS®) pain intensity, pain interference, pain behavior, depression, and sleep disturbance short forms in chronic musculoskeletal pain

Purpose: The Patient-Reported Outcomes Meaurement Information System (PROMIS®) measures have been translated into many languages and have been shown to have strong measurement properties across a wide range of clinical conditions. However, Nepali translations of the PROMIS short forms are not yet available. The aim of this study was to translate and cross-culturally adapt the PROMIS Pain Intensity, Pain Interference, Pain Behavior, Depression, and Sleep Disturbance short forms into Nepali. Methods: We used the Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology, which incorporated two forward translations, synthesis of the translations, a back-translation, and three independent reviews, harmonization, cognitive debriefing, revisions, and proof reading. The translation and review teams were fluent in Nepali and English and represented five different countries and four continents. We evaluated the short forms for comprehensibility and relevance (two key aspects of the content validity of an instrument), conducting cognitive debriefing with six adults with chronic musculoskeletal pain, in compliance with recommendations by the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The final version was proofread by two native Nepali speakers before and three new proofreaders after cognitive debriefing. Results: All five short forms were successfully translated and cross-culturally adapted into Nepali while maintaining equivalence to the source. Conclusions: The translation and review team, along with a sample from the target population with chronic musculoskeletal pain and the proofreaders considered all five PROMIS short forms relevant and comprehensible. An important next step is to evaluate the measurement properties of these instruments

Finite Element Modeling of the Dynamic Response of Critical Zones in a Ballasted Railway Track

The critical zones are the discontinuities along a railway line that are highly susceptible to differential settlement, due to an abrupt variation in the support conditions over a short span. Consequently, these zones require frequent maintenance to ensure adequate levels of passenger safety and comfort. A proper understanding of the behavior of railway tracks at critical zones is imperative to enhance their performance and reduce the frequency of costly maintenance operations. This paper investigates the dynamic behavior of the critical zone along a bridge-open track transition under moving train loads using two-dimensional finite element approach. The influence of different subgrade types on the track behavior is studied. The effectiveness of using geogrids, wedge-shaped engineered backfill and zone with reduced sleeper spacing in improving the performance of the critical zone is evaluated. The numerical model is successfully validated against the field data reported in the literature. The results indicate that the subgrade soil significantly influences the track response on the softer side of the critical zone. The difference in vertical displacement between the stiffer and the softer side of a track transition decreases significantly with an increase in the strength and stiffness of the subgrade soil. The subgrade layer also influences the contribution of the granular layers (ballast and subballast) to the overall track response. As the subgrade becomes stiffer and stronger, the contribution of the granular layers to the overall track displacement increases. The mitigation techniques that improve the stiffness or strength of granular layers may prove more effective for critical zones with stiff subgrade than critical zones with soft subgrade. Among all the mitigation techniques investigated, the wedge-shaped engineered backfill significantly improved the performance of the critical zone by gradually increasing the track stiffness.</jats:p

Production, purification, and characterization of thermostable alkaline xylanase from Anoxybacillus kamchatkensis NASTPD13

Anoxybacillus kamchatkensis NASTPD13 used herein as a source for thermostable alkaline xylanase were isolated from Paudwar Hot Springs, Nepal. NASTPD13 cultured at 60°C, pH 7 and in presence of inorganic (ammonium sulfate) or organic (yeast extract) nitrogen sources, produced maximum xylanase enzyme. Xylanase production in the cultures was monitored by following the ability of culture media to hydrolyze beech wood xylan producing xylooligosaccharide and xylose by thin layer chromatography (TLC). The extracellular xylanase was isolated from optimized A. kamchatkensis NASTPD13 cultures by ammonium sulfate (80%) precipitation; the enriched xylanase preparation was dialyzed and purified using Sephadex G100 column chromatography. The purified xylanaseshowed 11-fold enrichment with a specific activity of 33 U/mg and molecular weight were37 kDa based on SDS-PAGE and PAGE-Zymography. The optimum pH and temperature of purified xylanase was 9.0 and 65°C respectively retainingmore than 50% of its maximal activity over a broad range of pH (6–9) and temperature (30–65°C). With beech wood xylan, the enzyme showed Km 0.7 mg/ml and Vmax 66.64 μM/min/mg The xylanase described herein is a secretory enzyme produced in large quantities by NASTPD13 and is a novel thermostable, alkaline xylanase with potential biotechnological applications.Scopu

Virtual Inertia: Current Trends and Future Directions

The modern power system is progressing from a synchronous machine-based system towards an inverter-dominated system, with large-scale penetration of renewable energy sources (RESs) like wind and photovoltaics. RES units today represent a major share of the generation, and the traditional approach of integrating them as grid following units can lead to frequency instability. Many researchers have pointed towards using inverters with virtual inertia control algorithms so that they appear as synchronous generators to the grid, maintaining and enhancing system stability. This paper presents a literature review of the current state-of-the-art of virtual inertia implementation techniques, and explores potential research directions and challenges. The major virtual inertia topologies are compared and classified. Through literature review and simulations of some selected topologies it has been shown that similar inertial response can be achieved by relating the parameters of these topologies through time constants and inertia constants, although the exact frequency dynamics may vary slightly. The suitability of a topology depends on system control architecture and desired level of detail in replication of the dynamics of synchronous generators. A discussion on the challenges and research directions points out several research needs, especially for systems level integration of virtual inertia systems

Opioid Tapering and Its Associations with Risk of Opioid Use Disorder and Mortality Among Older Adults

Corresponding with CDC’s Guideline for Prescribing Opioids for Chronic Pain in 2016 and policies and procedures enacted by payers, quality organizations, and state agencies, prescriptions for opioid medications have witnessed a sharp decreasing trend with increases in opioid dose tapering and discontinuation. But opioid-related mortality has not shown a parallel decline. Several observational studies have explored the potential adverse effects of opioid dose tapering and discontinuation, with a growing focus on the rate of dose tapering. We hypothesized that many of the negative consequences of opioid tapering may be associated with the rate of opioid tapering or discontinuation.https://egrove.olemiss.edu/pharm_annual_posters_2024/1005/thumbnail.jp