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Doctor Badri Teymourtash (1908‒1995) was among the first Iranian lady dentists. She was one of the founders of Mashhad Dental School and one of the pioneers of modern dentistry in Iran. This paper takes a glance at the story of the life of this academic woman with its ebbs and flows.

Doctor Joseph Désiré Tholozan was a French physician who became the special physician of Nassereddin Shah, King of Persia (Iran) in the 19th century. He studied lots of topics in the field of epidemiology of infectious diseases. His efforts led to the discovery of the main vector of Iranian tick-born relapsing fever, Ornithodoros tholozani. He was also one of the pioneers of the Iranian Sanitary Council, whose efforts led to the foundation of the Ministry of Health of Iran a few decades later. This paper is a brief review of his biography and his roles in promoting health in Iran in the 19th century.

The multidrug resistant (MDR) opportunistic pathogen Klebsiella pneumoniae has previously been shown to adapt to chlorhexidine by increasing expression of the MFS efflux pump smvA . Here we show that loss of the regulator SmvR, through adaptation to chlorhexidine, results in increased resistance to a number of cationic biocides in K. pneumoniae and other members of the Enterobacteriaceae. Clinical Enterobacteriaceae isolates which lack smvA and smvR also have an increased susceptibility to chlorhexidine. When smvA from Salmonella and K. pneumoniae are expressed in Escherichia coli , which lacks a homologue to SmvAR, resistance to chlorhexidine increased (4-fold) but plasmid carriage of smvA alone was detrimental to the cell. Challenge of K. pneumoniae with chlorhexidine and another cationic biocide, octenidine, resulted in increased expression of smvA (approx. 70 fold). Adaptation to octenidine was achieved through mutating key residues in SmvA (A363V; Y391N) rather than abolishing the function of SmvR, as with chlorhexidine adaptation. Molecular modelling was able to predict that octenidine interacted more strongly with these mutated SmvA forms. These results show that SmvA is a major efflux pump for cationic biocides in several bacterial species and that increased efflux through SmvA can lead to increased chlorhexidine and octenidine tolerance.

Mass cytometry is a cutting-edge high-dimensional technology for profiling marker expression at the single-cell level, advancing clinical research in immune monitoring. Nevertheless, the vast data generated by cytometry by time-of-flight (CyTOF) poses a significant analytical challenge. To address this, we describe ImmCellTyper ( https://github.com/JingAnyaSun/ImmCellTyper ), a novel toolkit for CyTOF data analysis. This framework incorporates BinaryClust, an in-house developed semi-supervised clustering tool that automatically identifies main cell types. BinaryClust outperforms existing clustering tools in accuracy and speed, as shown in benchmarks with two datasets of approximately 4 million cells, matching the precision of manual gating by human experts. Furthermore, ImmCellTyper offers various visualisation and analytical tools, spanning from quality control to differential analysis, tailored to users’ specific needs for a comprehensive CyTOF data analysis solution. The workflow includes five key steps: (1) batch effect evaluation and correction, (2) data quality control and pre-processing, (3) main cell lineage characterisation and quantification, (4) in-depth investigation of specific cell types; and (5) differential analysis of cell abundance and functional marker expression across study groups. Overall, ImmCellTyper combines expert biological knowledge in a semi-supervised approach to accurately deconvolute well-defined main cell lineages, while maintaining the potential of unsupervised methods to discover novel cell subsets, thus facilitating high-dimensional immune profiling.

The Aurora B abscission checkpoint delays cytokinesis until resolution of DNA trapped in the cleavage furrow. This process involves PKCε phosphorylation of Aurora B S227. Assessing if this PKCε-Aurora B module provides a more widely exploited genome-protective control for the cell cycle, we show Aurora B phosphorylation at S227 by PKCε also occurs during mitosis. Expression of Aurora B S227A phenocopies inhibition of PKCε in by-passing the delay and resolution at anaphase entry that is associated with non-disjunction and catenation of sister chromatids. Implementation of this anaphase delay is reflected in PKCε activation following cell cycle dependent cleavage by caspase 7; knock-down of caspase 7 phenocopies PKCε loss, in a manner rescued by ectopically expressing/generating a free PKCε catalytic domain. Molecular dynamics indicates that Aurora B S227 phosphorylation induces conformational changes and this manifests in a profound switch in specificity towards S29 TopoIIα phosphorylation, a response necessary for catenation resolution during mitosis. In mitosis, Aurora B switches substrate specificity in response to phosphorylation of S227 in the activation loop by a cell cycle-processed active fragment of PKCε. Here, the authors show that this switch protects from chromosome non-disjunction by delaying anaphase entry and promoting TopoIIα-dependent resolution.

A unique research was developed to achieve an effective and efficient method for tracing and identifying Beluga sturgeon species, Huso huso using eDNA in concrete fish ponds. Sampling was performed from the water of the Beluga pond and fixed with precipitation premix solution. DNA was extracted from fixed water, and fin tissue of Beluga. Three short fragments were selected from a nuclear and two mitochondrial genes region of Beluga DNA. The specificity of primers was checked by conventional PCR for Beluga with fin tissue DNA samples. In this study, two conventional methods of molecular identification were performed on residual DNA samples of fish pond water and fin tissue, exhibiting that they were not suitable for measuring the residual DNA of Beluga in fish ponds due to the low rate of DNA. PCR amplification of sturgeon's DNA of mitochondrial CO? gene in third PCR primers was successful in low level of DNA extracted from water column and sediment by conventional and Quantitative PCR. The linear relationship between the threshold cycle (ct) value and Beluga DNA concentration was measured by the Mini-Barcoding quantitative Real-Time PCR. DNA samples of fish ponds generated a uniform curve in water column and sediment. In identifying residual DNA in the Picogram level of Beluga pond, SYBER Green Real-Time PCR method can be an acceptable method for barcoding with high efficiency compared to other methods such as conventional PCR method and non-invasive which is advantageous for the conservation of critically endangered sturgeons such as Beluga. This research results can also be used as a model for tracing fish species in rivers and seas.

Severe immune aplastic anemia is a fatal disease due to the destruction of marrow hematopoietic cells by cytotoxic lymphocytes, serving as a paradigm for marrow failure syndromes and autoimmune diseases. To better understand its pathophysiology, we apply advanced single cell methodologies, including mass cytometry, single-cell RNA, and TCR/BCR sequencing, to patient samples from a clinical trial of immunosuppression and growth factor stimulation. We observe opposing changes in the abundance of myeloid cells and T cells, with T cell clonal expansion dominated by effector memory cells. Therapy reduces and suppresses cytotoxic T cells, but new T cell clones emerge hindering robust hematopoietic recovery. Enhanced cell-cell interactions including between hematopoietic cells and immune cells, in particular evolving IFNG and IFNGR, are noted in patients and are suppressed post-therapy. Hematologic recovery occurs with increases in the progenitor rather than stem cells. Genetic predispositions linked to immune activation genes enhances cytotoxic T cell activity and crosstalk with target cells. The transcriptional phenotype of immune cells associated with severe aplastic anaemia (SAA) may change post immunotherapy. Here the authors analyse single cell transcriptomics of hematopoietic and immune cells from SAA patients and assess how these phenotypes change after treatment showing alterations in myeloid cells and TCR clonal abundance correlate with robustness of hematopoietic response.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Antibiotic resistance poses an increasing threat to global health. To tackle this problem, the identification of principal reservoirs of antibiotic resistance genes (ARGs) plus an understanding of drivers for their evolutionary selection are important. During a PCR-based screen of ARGs associated with integrons in saliva-derived metagenomic DNA of healthy human volunteers, two novel variants of genes encoding a d -alanine- d -alanine ligase ( ddl6 and ddl7 ) located within gene cassettes in the first position of a reverse integron were identified. Treponema denticola was identified as the likely host of the ddl cassettes. Both ddl6 and ddl7 conferred high level resistance to d -cycloserine when expressed in Escherichia coli with ddl7 conferring four-fold higher resistance to D-cycloserine compared to ddl6 . A SNP was found to be responsible for this difference in resistance phenotype between the two ddl variants. Molecular dynamics simulations were used to explain the mechanism of this phenotypic change at the atomic scale. A hypothesis for the evolutionary selection of ddl containing integron gene cassettes is proposed, based on molecular docking of plant metabolites within the ATP and d -cycloserine binding pockets of Ddl.