IgM-producing tumors in the BALB/c mouse: a model for B-cell maturation

Five adjuvant induced BALB/c tumors producing IgM—McPc 1748, W 3469, TEPC 183, McPc 774, and Y 5781—were characterized morphologically by electron microscopy, analysis of the distribution of surface-bound and intracytoplasmic IgM using immunofluorescence, and by biochemical study of IgM synthesis, turnover, and secretion. The cells of different tumors appear to represent different stages in B-cell maturation when compared to normal, lipopolysaccharide-stimulated B cells. Thus, McPc 1748 tumor cells resemble 10–25-h stimulated normal B cells, 3469 cells resemble 20–35-h stimulated B cells, TEPC 183 cells resemble 45–65-h stimulated B cells, Y 5781 cells resemble 80–110-h stimulated B cells, and McPc 774 cells resemble 100–130-h stimulated B cells

The dynamical transition in proteins and non-Gaussian behavior of low frequency modes in Self Consistent Normal Mode Analysis

Self Consistent Normal Mode Analysis (SCNMA) is applied to heme c type cytochrome f to study temperature dependent protein motion. Classical Normal Mode Analysis (NMA) assumes harmonic behavior and the protein Mean Square Displacement (MSD) has a linear dependence on temperature. This is only consistent with low temperature experimental results. To connect the protein vibrational motions between low temperature and physiological temperature, we have incorporated a fitted set of anharmonic potentials into SCNMA. In addition, Quantum Harmonic Oscillator (QHO) theory has been used to calculate the displacement distribution for individual vibrational modes. We find that the modes involving soft bonds exhibit significant non-Gaussian dynamics at physiological temperature, which suggests it may be the cause of the non-Gaussian behavior of the protein motions probed by Elastic Incoherent Neutron Scattering (EINS). The combined theory displays a dynamical transition caused by the softening of few "torsional" modes in the low frequency regime (< 50cm-1or 0.6ps). These modes change from Gaussian to a classical distribution upon heating. Our theory provides an alternative way to understand the microscopic origin of the protein dynamical transition.Comment: 17 pages, 6 figures, 1 tabl

RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis

Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC

Isothermal Recombinase Polymerase amplification (RPA) of Schistosoma haematobium DNA and oligochromatographic lateral flow detection

© 2015 Rosser et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

El Mañana: Año II Número 9 - (09/01/29)

There is no consensus on the treatment of multifocal primary cutaneous anaplastic large cell lymphoma (C-ALCL). Radiotherapy (RT) and methotrexate (MTX) are the current treatment options, but their efficacy is unknown. Recently, targeted therapies showed promising results in C-ALCL, and may therefore be an attractive first choice of treatment. To assess the efficacy of conventional treatment strategies for patients with multifocal C-ALCL, and to define which patients may require novel targeted therapies. In this multicenter study, treatment was evaluated in patients initially presenting (n=24) or relapsing with multifocal C-ALCL (n=17; 23 relapses). Distinction was made between cases with ≤ 5 (n=36) and >5 lesions (n=11). Treatments most commonly used were radiotherapy (n=21), systemic chemotherapy (n=9) and low-dose methotrexate (MTX; n=7) with complete response rates of 100%, 78% and 43%, respectively, and an overall response rate of 100%, 100%, and 57%, respectively. Four patients showed a complete spontaneous regression. Sixteen of 24 patients (67%) first presenting with multifocal C-ALCL relapsed, including all five patients initially treated with CHOP. Compared with patients presenting with 2-5 skin lesions, patients presenting with >5 lesions had a higher chance of developing extracutaneous relapse (56 vs 20%) and more often died of lymphoma (44% vs 7%). Patients with ≤5 lesions should be treated with low-dose RT (2x4 Gy). Maintenance low-dose MTX (20 mg/week) is a suitable option in patients with >5 lesions. Targeted therapies may be considered in rare patients refractory to MTX or patients developing extracutaneous disease. This article is protected by copyright. All rights reserve

Impact assessment of onchocerciasis through lymphatic filariasis transmission assessment surveys using Ov-16 rapid diagnostic tests in Sierra Leone

Background: Onchocerciasis is endemic in 14 of Sierra Leone's 16 districts with high prevalence (47–88.5%) according to skin snips at baseline. After 11 rounds of mass treatment with ivermectin with good coverage, an impact assessment was conducted in 2017 to assess the progress towards eliminating onchocerciasis in the country. Methods: A cluster survey was conducted, either integrated with lymphatic filariasis (LF) transmission assessment survey (TAS) or standalone with the LF TAS sampling strategy in 12 (now 14) endemic districts. Finger prick blood samples of randomly selected children in Grades 1–4 were tested in the field using SD Bioline Onchocerciasis IgG4 rapid tests. Results: In total, 17,402 children aged 4–19 years in 177 schools were tested, and data from 17,364 children aged 4–14 years (14,230 children aged 5–9 years) were analyzed. Three hundred forty-six children were confirmed positive for Ov-16 IgG4 antibodies, a prevalence of 2.0% (95% CI 1.8–2.2%) in children aged 4–14 years with prevalence increasing with age. Prevalence in boys (2.4%; 95% CI 2.1–2.7%) was higher than in girls (1.6%; 95% CI 1.4–1.9%). There was a trend of continued reduction from baseline to 2010. Using data from children aged 5–9 years, overall prevalence was 1.7% (95% CI 1.5–1.9%). The site prevalence ranged from 0 to 33.3% (median prevalence = 0.0%): &lt; 2% in 127 schools, 2 to &lt; 5% in 34 schools and ≥ 5% in 16 schools. There was a significant difference in average prevalence between districts. Using spatial analysis, the Ov-16 IgG4 antibody prevalence was predicted to be &lt; 2% in coastal areas and in large parts of Koinadugu, Bombali and Tonkolili Districts, while high prevalence (&gt; 5%) was predicted in some focal areas, centered in Karene, Kailahun and Moyamba/Tonkolili. Conclusions:Low Ov-16 IgG4 antibody prevalence was shown in most areas across Sierra Leone. In particular, low seroprevalence in children aged 5–9 years suggests that the infection was reduced to a low level after 11 rounds of treatment intervention. Sierra Leone has made major progress towards elimination of onchocerciasis. However, attention must be paid to those high prevalence focal areas. Graphical Abstract: (Figure presented.)</p