Immunohistochemical Assessment of TNFAIP3/A20 Expression Correlates With Early Tumorigenesis in Breast Cancer

BACKGROUND/AIM: Limited data exist on the expression pattern of TNFAIP3/A20, as assayed by immunohistochemistry (IHC), in breast cancer tissues. This study aimed to assess A20 expression pattern in breast cancer. Materials and Methods: The expression of A20 was analysed using IHC in 50 breast cancer cases retrieved from the Sharjah Breast Cancer Center at the University Hospital Sharjah, United Arab Emirates. Omics survival data were also used to analyse its association with survival in endocrine-treated subgroups. Results: A20 expression in breast cancer tissues was 'tumor-specific', and as compared to normal tissue areas, its expression was associated with both intensity and extent in early grade 1 (p<0.0001) in all molecular subtypes. In addition, using omics survival data from a cohort of 3,520 breast cancer patients, we showed that A20 overexpression associated with lower overall survival rate in the endocrine treated subgroups [hazard ratio (HR)=2.14, 95%CI=1.61-2.82, p<0.0001]. Conclusion: A20 can serve as a biomarker for early diagnosis of breast cancers

Contribution of proton and electron precipitation to the observed electron concentration in October–November 2003 and September 2005

Understanding the altitude distribution of particle precipitation forcing is vital for the assessment of its atmospheric and climate impacts. However, the proportion of electron and proton forcing around the mesopause region during solar proton events is not always clear due to uncertainties in satellite-based flux observations. Here we use electron concentration observations of the European Incoherent Scatter Scientific Association (EISCAT) incoherent scatter radars located at Tromsø (69.58° N, 19.23° E) to investigate the contribution of proton and electron precipitation to the changes taking place during two solar proton events. The EISCAT measurements are compared to the results from the Sodankylä Ion and Neutral Chemistry Model (SIC). The proton ionization rates are calculated by two different methods – a simple energy deposition calculation and the Atmospheric Ionization Model Osnabrück (AIMOS v1.2), the latter providing also the electron ionization rates. Our results show that in general the combination of AIMOS and SIC is able to reproduce the observed electron concentration within ± 50% when both electron and proton forcing is included. Electron contribution is dominant above 90 km, and can contribute significantly also in the upper mesosphere especially during low or moderate proton forcing. In the case of strong proton forcing, the AIMOS electron ionization rates seem to suffer from proton contamination of satellite-based flux data. This leads to overestimation of modelled electron concentrations by up to 90% between 75–90 km and up to 100–150% at 70–75 km. Above 90 km, the model bias varies significantly between the events. Although we cannot completely rule out EISCAT data issues, the difference is most likely a result of the spatio-temporal fine structure of electron precipitation during individual events that cannot be fully captured by sparse in situ flux (point) measurements, nor by the statistical AIMOS model which is based upon these observations

Effect of Stress Annealing on Domain Wall Dynamics in Nanocrystalline Hitperm-Type Microwires

We have studied the effect of stress induced anisotropy on domain wall dynamics in as-cast and annealed nanocrystalline Hitperm-type microwires. Annealing without stress leads to stress relaxation of the strong stresses frozen-in post the production process. Stress annealing at 300oC under 222.7 and 270.9 MPa, respectively, has triggered most complex domain wall dynamics. Observed results are discussed considering that annealing under higher stresses leads to an enhancement of longitudinal (axial) anisotropy due to positive magnetostriction of both bcc-(Fe, Co) grain as well as the residual amorphous matrix, and subsequently due to the decreasing of axial anisotropy due to back stresses arising from the glass-coating after removing the mechanical load. Magnetic anisotropies (axial and radial ones) after stress annealing can be responsible for the considerable influence of the annealing conditions on domain wall dynamics observed in Hitperm-type microwires. As a result of decreasing both anisotropies by different ways, the domain wall velocity decreased

Evaluation of Galanin Expression in Colorectal Cancer: An Immunohistochemical and Transcriptomic Study

Colorectal cancer (CRC) represents around 10% of all cancers, with an increasing incidence in the younger age group. The gut is considered a unique organ with its distinctive neuronal supply. The neuropeptide, human galanin, is widely distributed in the colon and expressed in many cancers, including the CRC. The current study aimed to explore the role of galanin at different stages of CRC. Eighty-one CRC cases (TNM stages I – IV) were recruited, and formalin-fixed paraffin-embedded samples were analyzed for the expression of galanin and galanin receptor 1 (GALR1) by immunohistochemistry (IHC). Galanin intensity was significantly lower in stage IV (n= 6) in comparison to other stages (p= 0.037 using the Mann-Whitney U test). Whole transcriptomics analysis using NGS was performed for selected samples based on the galanin expression by IHC [early (n=5) with high galanin expression and late (n=6) with low galanin expression]. Five differentially regulated pathways (using Absolute GSEA) were identified as drivers for tumor progression and associated with higher galanin expression, namely, cell cycle, cell division, autophagy, transcriptional regulation of TP53, and immune system process. The top shared genes among the upregulated pathways are AURKA, BIRC5, CCNA1, CCNA2, CDC25C, CDK2, CDK6, EREG, LIG3, PIN1, TGFB1, TPX2. The results were validated using real-time PCR carried out on four cell lines [two primaries (HCT116 and HT29) and two metastatic (LoVo and SK-Co-1)]. The current study shows galanin as a potential negative biomarker. Galanin downregulation is correlated with advanced CRC staging and linked to cell cycle and division, autophagy, transcriptional regulation of TP53 and immune system response

Anthracnose Disease (Colletotrichum sp.) Affecting Olive Fruit Quality and Its Control in Egypt

Abstract Olive anthracnose is the most important fungal disease of olive fruits worldwide. It occurs in humid olive-growing areas of many countries and causes heavy yield losses and lowering of oil quality. Colletotrichum acutatum was isolated and identified from rotten olive fruits. Pathogenicity test of C. acutatum was confirmed. It was found to be decreased all physical characteristics measured i.e. weight (gm), length (mm), diameter (mm) and volume (ml3). Also, C. acutatum was found to decrease the oil content of the fruits, while increasing their total titratable acidity and moisture content. Physiological studies resulted that, the highest growth rate and sporulation was recorded with PDA medium, PH 6.5 and Light/dark cycle treatments. Hot water treatments at 45, 50 and 55°C were able to decreased spore viability of C. acutatum compared with untreated (control). The best treatment of hot water was recorded with 55°C. in vivo. Also, hot water treatment at 55°C was successful in reducing the percentage of anthracnose disease incidence on olive fruits in vitro. All tested alternative substrates i. e. Ascorbic acid, Benzoic acid, potassium sorbate and citric acid used were able to reduce the linear growth rate of C. acutatum in vitro. Benzoic acid was found to be the best alternative substrate used which gave completely fruit protection (hundred of reduction percent) followed by Ascorbic acid, Potassium sorbate and Citric acid. This is thought to be the first report of anthracnose disease of olive fruits in Egypt

Identifying Immunological and Clinical Predictors of COVID-19 Severity and Sequelae by Mathematical Modeling

Since its emergence as a pandemic in March 2020, coronavirus disease (COVID-19) outcome has been explored via several predictive models, using specific clinical or biochemical parameters. In the current study, we developed an integrative non-linear predictive model of COVID-19 outcome, using clinical, biochemical, immunological, and radiological data of patients with different disease severities. Initially, the immunological signature of the disease was investigated through transcriptomics analysis of nasopharyngeal swab samples of patients with different COVID-19 severity versus control subjects (exploratory cohort, n=61), identifying significant differential expression of several cytokines. Accordingly, 24 cytokines were validated using a multiplex assay in the serum of COVID-19 patients and control subjects (validation cohort, n=77). Predictors of severity were Interleukin (IL)-10, Programmed Death-Ligand-1 (PDL-1), Tumor necrosis factors-α, absolute neutrophil count, C-reactive protein, lactate dehydrogenase, blood urea nitrogen, and ferritin; with high predictive efficacy (AUC=0.93 and 0.98 using ROC analysis of the predictive capacity of cytokines and biochemical markers, respectively). Increased IL-6 and granzyme B were found to predict liver injury in COVID-19 patients, whereas interferon-gamma (IFN-γ), IL-1 receptor-a (IL-1Ra) and PD-L1 were predictors of remarkable radiological findings. The model revealed consistent elevation of IL-15 and IL-10 in severe cases. Combining basic biochemical and radiological investigations with a limited number of curated cytokines will likely attain accurate predictive value in COVID-19. The model-derived cytokines highlight critical pathways in the pathophysiology of the COVID-19 with insight towards potential therapeutic targets. Our modeling methodology can be implemented using new datasets to identify key players and predict outcomes in new variants of COVID-19

A rational framework for evaluating the next generation of vaccines against Mycobacterium avium subspecies paratuberculosis

Since the early 1980s, several investigations have focused on developing a vaccine against Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne\u27s disease in cattle and sheep. These studies used whole-cell inactived vaccines that have proven useful in limiting disease progression, but have not prevented infection. In contrast, modified live vaccines that invoke a Th1 type immune response, may improve protection against infection. Spurred by recent advances in the ability to create defined knockouts in MAP, several independent laboratories have developed modified live vaccine candidates by transcriptional mutation of virulence and metablolic genes in MAP. In order to accelerate the process of identification and comparative elvaluation of he most promising modified live MAP vaccine candidates, members of a multi-institutional USDA- funded research consortium, the Johne\u27s disease integrated program (JDIP), met to established a standardized testing platform using agreed upon protocols. A total of 22 candidates vaccine strains developed in five independent laboratories in the United States and New Zealand voluntarily entered into a double blind gated trial pipeline. In Phase I, the survival characteristics of each candidate were determined in bovine macrophages. Attenuated strains moved to Phase II, where tissue colonization of C57/BL6 mice were evaluated in a challenge model. In Phase III, five promising candidates from Phase I and II were evaluated for their ability to reduce fecal shedding, tissue colonization and pathology in a baby goat challenge model. Formation of a multi-institutional consortium for vaccine strain evaluation has revealed insights for the implementation of vaccine trials for Johne\u27s disease and other animals pathogens. We conclude by suggesting the best way forward based on this 3-phase trial experience and challenge the rationale for use of a macrophage-to-mouse-to native host pipeline for MAP vaccine development