Phenotypic lag in macroconidia of N. crassa his-3\u3csup\u3e+\u3c/sup\u3e transsformants and its implication in estimation of nuclear ratios

A majority of prototrophic macroconidia of two of the three histidine transformants of Neurospora crassa tested required histidine for germination. This condition led to an underestimation of the proportion of his-3+ macroconidia in the samples and wronged the estimation of ratio of his-3+/ his-3 nuclei by direct plating method. To correctly estimate nuclear ratio, a sample of colonies from histidine-supplemented plating medium was transferred to histidine drop-out slants and the proportion of auxotrophic and prototrophic colonies was determined from their growth response. The amino acid requirement by prototrophic macroconidia was not specific, was limited to colony formation and was not due to low endogenous content of amino acids

Engineered Nanomedicine with Alendronic Acid Corona Improves Targeting to Osteosarcoma

Citation: Nguyen, T. D. T., Pitchaimani, A., & Aryal, S. (2016). Engineered Nanomedicine with Alendronic Acid Corona Improves Targeting to Osteosarcoma. Scientific Reports, 6, 36707.We engineered nanomedicine with the stealth corona made up of densely packed bone seeking ligand, alendronic acid. In a typical nanoconstruct, alendronic acid is conjugated with hydrophilic head moiety of phospholipid that has an ability to self-assemble with hydrophobic polymeric core through its hydrophobic long carbon-chain. Proposed nanomedicine has three distinct compartments namely; poly(l-lactic-co-glycolic acid) polymeric core acting as a drug reservoir and skeleton of the nanoconstruct, phospholipid monolayer covers the core acting as a diffusion barrier, and a densely packed alendronic acid corona acting as a stabilizer and targeting moiety. Thus engineered nanomedicine attain spherical entity with ~90 ± 6 nm having negative zeta potential, −37.7 ± 2 mV, and has an ability to load 7 ± 0.3 wt% of doxorubicin. In-vitro bone targeting efficiency of nanomedicine was studied using hydroxyapatite crystals as a bone model, and found significant accumulation of nanoparticle in the crystals. Moreover, cellular internalization studies with mouse osteosarcoma confirm the selectivity of nanomedicine when compared to its internalization in non-targeted mouse melanoma. This nanomedicine shows prolong stability in serum and deliver the drug into the cell exhibiting an IC50 of 3.7 μM. Given the strong interacting property of alendronic acid with bone, the proposed nanomedicine hold promises in delivering drug to bone microenvironment

Increase in germination and plating efficiency of Neurospora crassa microconidia by amino acid supplementation

A major difficulty that has limited the use of uninucleate microconidia in genetic research is their low and erratic germination. We found that the supplementation of sorbose plating medium by amino acids, notably aspartic acid and methionine, markedly improved germination and plating efficiency of microconidia of mcm and pe fl genotypes of N. crassa. The plating efficiency of mcm microconidia in amino acid supplemented medium was comparable to macroconidia

Design and Performance Analysis of a Switched Reluctance Motor Using Finite Element Analysis and Magnetic Equivalent Circuit Model

By being magnet-free, and mechanically robust with a longer constant power range, switched reluctance motor (SRM) is gathering much attention as a potential choice to propel electric vehicles (EVs) and hybrid electric vehicles (HEVs). This paper comprehensively investigates the performance sensitivity to geometric design variables such as rotor diameter, pole arc angles, and yoke thicknesses for an SRM using static two-dimensional (2D) electromagnetic Finite-Element Analysis (FEA). The reason for the change in static characteristics due to variation in reluctance between SRM designs has not been detailed previously. This is addressed by the magnetic equivalent circuit (MEC) model that simplifies the design analysis. Results indicate that stator pole reluctance needs to be given due importance while studying the influence of rotor diameter. Also, it is imperative to set an adequate thickness of the stator and rotor yokes to minimize the effect of saturation on the performance. Rotor diameter and stator pole arc angle have a pronounced influence on the performance while the influence of rotor pole arc angle and yoke thicknesses was relatively less

AZALEP a randomized controlled trial of azathioprine to treat leprosy nerve damage and Type 1 reactions in India: Main findings.

BACKGROUND: Leprosy Type 1 reactions are difficult to treat and only 70% of patients respond to steroid treatment. Azathioprine has been used as an immune-suppressant and we tested its efficacy in treating leprosy T1R. METHODOLOGY: Randomised controlled trial adding azathioprine to steroid treatment for leprosy reactions. This trial was conducted in four leprosy hospitals in India. Patients with a new leprosy Type 1 reaction affecting either skin or nerve were recruited. They were given a 20 week course of oral prednisolone either with placebo or azathioprine 50mg for 24, 36 or 48 weeks. Outcomes were measured using a verified combined clinical reaction severity score (CCS) and the score difference between baseline and end of study calculated. An intention to treat analysis was done on the 279 patients who had an outcome. PRINCIPAL FINDINGS: 345 patients were recruited, 145 were lost due to adverse events, loss to follow up or death. 36% needed extra steroids due to a recurrence of their skin and/or nerve reaction. 76% of patients had improvements in their CCS the end of the study, 22% had no change and 1.1% deteriorated. Adding azathioprine to steroid treatment did not improve CCS. So the improvements were attributable to treatment with steroids. We analysed the skin, sensory and motor scores separately and found that skin improvement contributed most with 78.9% of patients having skin improvement, azathioprine treatment for 48 weeks improved sensory scores it also improved motor scores but so did treatment with prednisolone alone. We identified significant adverse effects attributable to steroid treatment. When azathioprine and Dapsone were given together significant numbers of patients developed significant anaemia. CONCLUSIONS: Azathioprine is not recommended for the treatment of leprosy reactions and does not improve steroid treatment. Recurrent reactions are a major challenge. We have also identified that 65% of patients with sensory and 50% with motor nerve damage do not improve. Future studies should test giving azathioprine in the treatment of nerve damage and giving a higher dose for 48 weeks to patients. These findings highlight the difficulty in switching off leprosy inflammation and the need for better treatments for reactions and nerve damage. There is also a research need to identify patients who have recurrences and optimize treatments for them. Patients with recurrences may benefit from combined treatment with steroids and azathioprine. We have also shown that significant numbers of patients treated with steroids develop adverse effects and this needs to be highlighted in leprosy programmes. Research is needed to identify patients who do not respond to steroid treatment and develop alternative treatments for them. TRIAL REGISTRATION: ClinicalTrials.gov This trial was registered with the Indian Council of Medical research clinical Trial register as a clinical trial Number-REFCTRI/2016/12/007558

Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth

AbstractTaxane efficacy in triple negative breast cancer (TNBC) is limited by insufficient tumor accumulation and severe off-target effects. Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug. Here, 1,000 nm × 400 nm discoidal polymeric nanoconstructs (DPN) encapsulating docetaxel (DTXL) and the near infrared compound lipid-Cy5 were engineered. DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol) template with a polymer mixture comprising poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) diacrylate (PEG-DA) chains together with therapeutic and imaging agents. The resulting "multi-passage" DPN exhibited higher DTXL loading, lipid-Cy5 stability, and stiffness as compared to the conventional "single-passage" approach. Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof. Empty DPN had no toxicity on TNBC cells, whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL (IC50 = 2.6 nM ± 1.0 nM vs. 7.0 nM ± 1.09 nM at 72 h). In orthotopic murine models, DPN accumulated in TNBC more efficiently than free-DTXL. With only 2 mg/kg DTXL, intravenously administered every 2 days for a total of 13 treatments, DTXL-DPN induced tumor regression and were associated to an overall 80% survival rate as opposed to a 30% survival rate for free-DTXL, at 120 days. All untreated mice succumbed before 90 days. Collectively, this data demonstrates that vascular confined multi-passage DPN, biomimicking the behavior of circulating platelets, can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses

Biomass-derived Mesoporous Carbons and Their Applications in Electrochemical Biosensors and Energy Storage

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