Search bioRxiv⌕ Search

Biology subjects

Cherif, A.

Publications and source records attributed to Cherif, A..

3 recordsLinked to original sources

Metataxonomic analysis of halophilic archaea community in two geothermal springs sources in southern Tunisian Sahara

In this study, we assess the phylogenetic diversity of the halophilic archaeal community of biotechnological interest that inhabit in geothermal water in southern Tunisia. These waters are usually used for farming purposes, particularly for irrigation of the oases and greenhouses, due to the limited availability of surface freshwater resources and the arid climate. The samples processed from two separated geothermal sources in southern Tunisia based on the Illumina Miseq sequencing approach. Three samples including water, sediment, and halite-soil crust, were collected from downstream of two geothermal springs of Ksar Ghilane (KGH) and Zaouet Al Aness (ZAN) oases. Results showed that several haloarchaea-related members were identified in geothermal springs. The average taxonomic composition showed that 20 genera out of 33 were shared between the two geothermal sources with uneven distribution, where the Halogranum genus is the most represented genus with an abundance of 18.9% and 11.58% for ZAW and KGH, respectively. Several unique site-specific genera were also observed; the case of Halonotius, Halopelagius, Natronorubrum, and Haloarcula in ZAN, and Haloprofundus, Halomarina, Halovivax, Haloplanus, Natrinema, Halobium, Natronoarchaeum, Haloterrigena detected in KGH pool. We noticed that the majority of genus members are usually found in low-salinity ecosystems. The finding of this study suggests that haloarchaea-related members could survive in downstream geothermal sources, which may have resulted from the leaching of salts and minerals through drilling waters creating chemically complex saline systems.

microbiology↗

Modeling osteoporosis to design and optimize pharmacologic therapies comprising multiple drug types

For the treatment of postmenopausal osteoporosis, several drug classes with different mechanisms of action are available. Since only a limited set of dosing regimens and drug combinations can be tested in clinical trials, it is currently unclear whether common medication strategies achieve optimal bone mineral density gains or are outperformed by alternative dosing schemes and combination therapies that have not been explored so far. Here we develop a mathematical framework of drug interventions for postmenopausal osteoporosis that unifies fundamental mechanisms of bone remodeling and the mechanisms of action of four drug classes: bisphosphonates, parathyroid hormone (PTH) analogs, sclerostin inhibitors and receptor activator of NF-{kappa}B ligand (RANKL) inhibitors. Using data from several clinical trials, we calibrate and validate the model, demonstrating its predictive capacity for complex medication scenarios including sequential and parallel drug combinations. Via simulations, we reveal that there is a large potential to improve gains in bone mineral density by exploiting synergistic interactions between different drug classes, without increasing the total amount of drug administered.

pharmacology and toxicology↗

In silico screening of TMPRSS2 SNPs that affect its binding with SARS-CoV2 spike protein and directly involved in the interaction affinity changes

In this paper, we used in silico analysis to shed light on the possible interaction between TMPRSS2 and SARS-CoV2 spike (S) protein by examining the role of TMPRSS2 single nucleotide polymorphisms (SNPs) in relation with susceptibility and inter-individual variability of SARS-CoV2 infection. First, we used molecular docking of human TMPRSS2 protein to predict the binding site of TMPRSS2, especially the TMPRSS2 link loops, in order to assess the effect TMPRSS2 SNPs. The latter lead to missense variants on the interaction between TMPRSS2 and SARS-CoV2 S protein. In a second step, we further refine our analysis by performing a structure-function analysis of the complexes using PyMol software, and finally by MD simulations to validate the as-obtained results. Our findings show that 17 SNPs among the 692 natural TMPRSS2 coding variants are in positions to influence the binding of TMPRSS2 with the viral S protein. All of them give more important interaction energy as assessed by docking. Among the 17 SNPs, four missense variants E389A, K392Q, T393S and Q438E lead to "directly increasing" the interaction affinity and 2 missense variants R470I and Y416C cause it "directly decreasing". The R470I and Y416C present in African and American population, respectively. While the other 4 SNP variants (E389A; K392Q; T393S and Q438E) are present only in the European population, which could link the viral infection susceptibility to demographic, geographic and genetic factors.

bioinformatics↗