The Avidity Spectrum of T Cell Receptor Interactions Accounts for T Cell Anergy in a Double Transgenic Model

The mechanism of self-tolerance in the CD4+ T cell compartment was examined in a double transgenic (Tg) model in which T cell receptor (TCR)-α/β Tg mice with specificity for the COOH-terminal peptide of moth cytochrome c in association with I-Ek were crossed with antigen Tg mice. Partial deletion of cytochrome-reactive T cells in the thymus allowed some self-specific CD4+ T cells to be selected into the peripheral T cell pool. Upon restimulation with peptide in vitro, these cells upregulated interleukin (IL)-2 receptor but showed substantially lower cytokine production and proliferation than cells from TCR Tg controls. Proliferation and cytokine production were restored to control levels by addition of saturating concentrations of IL-2, consistent with the original in vitro definition of T cell anergy. However, the response of double Tg cells to superantigen stimulation in the absence of exogenous IL-2 was indistinguishable from that of TCR Tg controls, indicating that these self-reactive cells were not intrinsically hyporesponsive. Measurement of surface expression of Tg-encoded TCR α and β chains revealed that cells from double Tg mice expressed the same amount of TCR-β as cells from TCR Tg controls, but only 50% of TCR-α, implying expression of more than one α chain. Naive CD4+ T cells expressing both Tg-encoded and endogenous α chains also manifested an anergic phenotype upon primary stimulation with cytochrome c in vitro, suggesting that low avidity for antigen can produce an anergic phenotype in naive cells. The carboxyfluorescein diacetate succinimidyl ester cell division profiles in response to titered peptide ± IL-2 indicated that expression of IL-2 receptor correlated with peptide concentration but not TCR level, whereas IL-2 production was profoundly affected by the twofold decrease in specific TCR expression. Addition of exogenous IL-2 recruited double Tg cells into division, resulting in a pattern of cell division indistinguishable from that of controls. Thus, in this experimental model, cells expressing more than one α chain escaped negative selection to a soluble self-protein in the thymus and had an anergic phenotype indistinguishable from that of low avidity naive cells. The data are consistent with the notion that avidity-mediated selection for self-reactivity in the thymus may lead to the appearance of anergy within the peripheral, self-reactive T cell repertoire, without invoking the induction of hyporesponsiveness to TCR-mediated signals

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Column Removal of Some Dyestuffs by Activated Carbons Derived from Apricot Stone Shells

Activated carbons (ACs) were prepared from apricot stone shells impregnated with H 3 PO 4 , followed by carbonization at 400–500°C. Fixed-bed removal of two dyestuffs, i.e. Direct Red 99 (DR) and Reactive Orange 11 (RO) was followed at constant bed height and flow rate. Several column characteristics were evaluated from the breakthrough curves obtained including: the volume and loading at breakpoint, the height of the mass transfer zone, the bed service time, the time and loading at exhaustion, and the fractional bed loadings at various stages. The bed performance with RO was better than for DR, which was ascribed to a screening effect towards the larger DR molecules and to enhanced adsorption arising from the polyhalogenated nature of the RO molecule. The removal of colour was favoured as the porosity of the AC developed, being particularly related to its mesoporosity and total pore volume

Adsorption of p-Nitrophenol on Activated Carbon Prepared from Phosphoric Acid-treated Apricot Stone Shells

The effect of temperature on the adsorption of p-nitrophenol (PNP) from aqueous solution has been determined at various initial phenol concentrations. Eight activated carbons were tested, being laboratory-prepared from apricot stone shells impregnated with H 3 PO 4 and carbonized at 300–500°C. The adsorption capacity increased as a function of the percentage of activating acid added as well as the temperature of carbonization. The PNP surface areas evaluated were generally lower than the nitrogen BET surface areas due to restricted adsorption inside certain pores. Enthalpies of adsorption of 20–24 kJ/mol were estimated in all cases, except for one carbon which exhibited 'activated', diffusion-controlled adsorption. Greater than 90% desorption was observed at 100 ppm levels of PNP, but this decreased considerably at higher phenol levels

Porosity Characteristics of Activated Carbons Derived from Olive Oil Wastes Impregnated with HPO

Locally discarded olive oil waste was tested as a potential raw material for the preparation of activated carbons. Chemical activation by impregnation with H 3 PO 4 was employed using acid solutions of varying concentration in the range 30–70% followed by thermal treatment at 500–700°C. The development of porosity was followed from an analysis of the nitrogen adsorption isotherms obtained at 77 K by applying standard BET and t-plot methods. Carbons with low to moderate surface areas (273–827 m 2 /g) and total pore volumes (0.27–0.69 ml/g), containing essentially micropores with diameters of 8.2 Å up to 12.4 Å were obtained. Increasing the concentration of impregnant led to the development of porosity with the optimum being attained at 60% H 3 PO 4 . Phosphoric acid is visualized as acting both as an acid catalyst promoting bond-cleavage reactions and the formation of new crosslinks and also as a reactant which combines with organic species to form phosphate and polyphosphate bridges which connect and crosslink biopolymer fragments. The present study suggests many applications for environmental pollution control, firstly by utilizing accumulating low-cost agricultural by-products and secondly by producing a multi-purpose high-capacity adsorbent useful in the remediation of micropollutants in various water courses

OPTICAL GAUSSONS IN BIREFRINGENT FIBERS AND DWDM SYSTEMS WITH INTER-MODAL DISPERSION

WOS: 000308975300001This paper studies the optical solitons in birefringent fibers and DWDM systems in presence of log-law nonlinearity with inter-modal dispersion. The Gaussian ansatz is used to carry out the integration of the governing equation. The exact solutions are obtained and the constraint conditions, for the existence of these Gaussons, fall out during the course of derivation of the solution. A brief discussion on Thirring solitons is also included.Serbian Ministry of Education and Science [11144006]The work of the second author (DM) presented in this paper was supported by the Serbian Ministry of Education and Science (Project 11144006) and this support is sincerely appreciated

Implementation of ketogenic diet in children with drug-resistant epilepsy in a medium resources setting: Egyptian experience

Background: Even with the extensive use of ketogenic dietary therapies (KD), there still exist many areas of the world that do not provide these treatments. Implementing the ketogenic diet in different countries forms a real challenge in order to match the cultural and economic differences. Aim: To assess the feasibility of implementing a ketogenic diet plan in a limited resource setting with identification of the compliance, tolerability and side effects in the target population and to assess the efficacy of the ketogenic diet in children with intractable epilepsy. Method of the study: The medical records of 28 patients with intractable epilepsy, treated at The Children's Hospital — Cairo University from December 2012 to March 2014 with ketogenic dietary therapy were reviewed. The non-fasting protocol was followed without hospital admission. All children were started on a standardized classic ketogenic diet with a ratio ranging from 2.5–4:1 (grams of fat to combined carbohydrate and protein). Patients were followed at 1, 3 and 6 months after diet initiation. Results: The median age was 60 months (range, 30–110). After 1 month from diet initiation, 16 patients (57%) remained on the diet. One of them (6.3%) had more than 90% reduction in seizure frequency, an additional 6 patients (37.5%) had a 50–90% reduction in seizure frequency. In total, seven out of the 16 patients continuing the diet for 1 month (43.8%) had more than 50% improvement in seizure control from the base line. Despite having 50–90% seizure control, three children discontinued the diet after one month.Three months after diet initiation, 6 patients (22%) remained on diet, 4 of them (66.7%) had more than 50% reduction in seizure frequency.At 6 months, only 3 patients remained on diet, 2 of them (66.6%) had 50–90% reduction in seizure frequency, while one patient (33.3%) showed better than 90% decrease in seizure. Conclusion: The current study shows that the ketogenic diet could be implemented in medium resources countries and should be included in the management of children with intractable epilepsy. Keywords: Intractable epilepsy, Ketogenic diet, Pediatric epilepsy, Seizure

Selective screening for inborn errors of metabolism by tandem mass spectrometry in Egyptian children: a 5 year report

In order to enhance awareness and promote registry for inborn errors of metabolism (IEMs) in Egypt, we aimed to evaluate the prevalence and main clinical findings of IEMs detectable by tandem mass spectrometry (MS/MS) among high risk pediatric patients presenting to our tertiary care facility at Cairo University Children's Hospital over a period of 5 years and to compare the disease burden in Egypt in the absence of a national screening program for inherited metabolic disorders with other populations.status: publishe

Lysosomal Storage Disorders in Egyptian Children

To describe the spectrum, relative prevalence and molecular background of lysosomal storage disorders in Egypt.status: publishe