Profiling the physiological pitfalls of anti-hepatitis C direct-acting agents in budding yeast

Sofosbuvir and Daclatasvir are among the direct-acting antiviral (DAA) medications prescribed for the treatment of chronic hepatitis C (CHC) virus infection as combination therapy with other antiviral medications. DAA-based therapy achieves high cure rates, reaching up to 97% depending on the genotype of the causative hepatitis C virus (HCV). While DAAs have been approved as an efficient and well-tolerated therapy for CHC, emerging concerns about adverse cardiac side effects, higher risk of recurrence and occurrence of hepatocellular carcinoma (HCC) and doubts of genotoxicity have been reported. In our study, we investigated in detail physiological off-targets of DAAs and dissected the effects of these drugs on cellular organelles using budding yeast, a unicellular eukaryotic organism. DAAs were found to disturb the architecture of the endoplasmic reticulum (ER) and the mitochondria, while showing no apparent genotoxicity or DNA damaging effect. Our study provides evidence that DAAs are not associated with genotoxicity and highlights the necessity for adjunctive antioxidant therapy to mitigate the adverse effects of DAAs on ER and mitochondria.     

In vitro propagation for conservation of the rare date palm (Phoenix dactylifera L.) ‘Amri’ using immature inflorescence

In Vitro Cellular & Developmental Biology - Plant - Immature female inflorescence plays a significant role in date palm micropropagation because inflorescences are available with no practical...     

Abundance and diversity of surface zooplankton in the Gulf of Aqaba, Red Sea, Egypt

Surface zooplankton were studied in Egyptian coastal watersof the Gulf of Aqaba, from bimonthly samples from July 1994to May 1995. Species diversity, numerical abundance and dynamicswere analysed for each taxon, at six sites, inside three Protectorates.A total of 62 taxa and species were identified. At all sites,copepods were predominant in the standing crop with an averageof 1945 ind. M^–3 and formed {small tilde}75.5%, numerically,of the total zooplankton community. The meroplanktonic larvaeoccupied the second rank and they constituted {small tilde}19.7%of the total zooplankton. Seasonally, the main peak of zooplanktonabundance was recorded in winter (January) with an average of3510 ind. M^–3 while September was characterized by thelowest density (1906 ind. m^–3 The relatively higher diversityvalues were recorded at Ras Mohammed Protectorate and a progressivedecline in diversity was observed northward.     

Some properties of chitinase produced by a potent Aspergillus carneus strain

Summary Seven fungal isolates characterized by high chitinolytic activity were isolated from soil and identified. Aspergillus carneus in a 7-day-old shaken culture was the most promising chitinase producer. The use of chitin as a carbon source favoured production of extracellular chitinase enzymes. Maximum chitinase activity was reached at 10 g chitin/1. An initial pH value of the culture medium of 5.0 gave the highest chitinolytic activity. Some properties of the crude enzyme produced by A. carneus were studied. Maximal enzyme activity was reached at pH 4.5 and 40° C after 30 min. Thermal treatments at 70° C and pH 4.5 had the most adverse effect on enzyme activity.Offprint requests to: M. A. Abd El-Naby     

Tumor microenvironment disparity in multiple primary lung cancers: Impact of non-intrinsic factors,histological subtypes,and genetic aberrations

IntroductionMultiple primary lung cancers (MPLCs) occur in common carcinogenetic risks such as lifestyle, biological aging, immune responses, hormones, and metabolism. Although MPLCs harbor various genetic profiles within the same individuals, differences in the tumor microenvironment (TME) are unclear. We investigated the impact of genetic aberrations, non-intrinsic factors, and pathological subtypes on tumor immunity.Materials and MethodsIn total, 73 surgically resected specimens from 32 patients with MPLC were analyzed. PD-L1 expression in tumor cells (TCs) and immune cells (ICs), CD3-positive tumor-infiltrating lymphocytes (TILs), CD8/CD3 ratios, and FOXP3-positive TILs that compose TMEs were evaluated by immunohistochemistry and classified on a score of 0–2. 38 tumors were sequenced for somatic mutations in 409 cancer-associated genes.ResultsFemales and never or light smokers had a higher incidence of PD-L1-negative tumors and a higher concordance rate. PD-L1 positivity in TCs and ICs was significantly less frequent in EGFR-mutated than in wild-type tumors. Differences in the score of TMEs were observed between the KRAS-mutated-only tumor and the KRAS and TP53-co-mutated tumors, and between the KRAS-mutated-only tumor and the KRAS and STK11-co-mutated tumors. Significantly more FOXP3-high TILs were observed in invasive pathological subtypes than in non-invasive ones.ConclusionComparing TMEs among MPLCs revealed that non-smokers or light smokers and females were unlikely to express PD-L1 regardless of tumor site and confirmed that the EGFR mutations and co-occurring KRAS and STK11 or TP53 mutations were associated with TME. Pathological subtypes may impact the efficacy of immune therapy due to their potential correlations with regulatory T cells.     

Growth and water requirements of some range plants under controlled conditions

Summary The growth and water requirements of ten of the native and introduced range species were compared at different levels of moisture stress between the permanent wilting percentage and the moisture equivalent.The most vigorous vegetative growth and highest dry matter production were shown byChloris gayana.The transpiration intensity of all the studied species was low and comparable with that of xerophytes living under extremely dry conditions. At the highest moisture stress which is a xeric condition, the transpiration intensity varied between 90 mg/g.h inOnonis vaginalis and 160 mg/g.h inPanicum antidotale.The osmotic pressure varied widely between 16.5 atm inPennisetum dichotomum and 30.0 atm inOryzopsis miliacea at the highest moisture stress.The present investigation revealed that all the studied species are drought resistant as shown by their transpiration intensity and osmotic pressure which are comparable with those of xerophytes. SinceChloris gayana exhibits the highest dry matter production in addition to its drought resistance therefore it can be considered as the most suitable species for cultivation in desert regions.