Amino acid substitutions in specific proteins correlate with farnesol unresponsiveness in Candida albicans.

BACKGROUND: The quorum-sensing molecule farnesol, in opportunistic yeast Candida albicans, modulates its dimorphic switch between yeast and hyphal forms, and biofilm formation. Although there is an increasing interest in farnesol as a potential antifungal drug, the molecular mechanism by which C. albicans responds to this molecule is still not fully understood. RESULTS: A comparative genomic analysis between C. albicans strains that are naturally unresponsive to 30 µM of farnesol on TYE plates at 37 °C versus responsive strains uncovered new molecular determinants involved in the response to farnesol. While no signature gene was identified, amino acid changes in specific proteins were shown to correlate with the unresponsiveness to farnesol, particularly with substitutions in proteins known to be involved in the farnesol response. Although amino acid changes occur primarily in disordered regions of proteins, some amino acid changes were also found in known domains. Finally, the genomic investigation of intermediate-response strains showed that the non-response to farnesol occurs gradually following the successive accumulation of amino acid changes at specific positions. CONCLUSION: It is known that large genomic changes, such as recombinations and gene flow (losses and gains), can cause major phenotypic changes in pathogens. However, it is still not well known or documented how more subtle changes, such as amino acid substitutions, play a role in the adaptation of pathogens. The present study shows that amino acid changes can modulate C. albicans yeast's response to farnesol. This study also improves our understanding of the network of proteins involved in the response to farnesol, and of the involvement of amino acid substitutions in cellular behavior.

Prevention and control of non-communicable diseases in iran: the case for Investment.

BACKGROUND: Non-communicable diseases are imposing a considerable burden on Iran. This study aims to assess the Return on Investment (ROI) for implementation of Non-communicable diseases (NCDs) prevention program in Iran. METHODS: Four disease groups including cardiovascular diseases, diabetes, cancer, and respiratory diseases were included in our ROI analysis. The study followed four steps: 1) Estimating the total economic burden of NCDs using the Cost-of-Illness approach. 2) Estimating the total costs of implementing clinical and preventive interventions using an ingredient based costing at delivering level and a program costing method at central level.3) Calculating health impacts and economic benefits of interventions using the impact measures of avoided incidence, avoided mortality, healthy life years (HLYs) gained, and avoided direct treatment costs. 4) Calculating the ROI for each intervention in 5- and 15- year time horizons. RESULTS: The total economic burden of NCDs to the Iranian economy was IRR 838.49 trillion per year (2018), which was equivalent to 5% of the country's annual Gross Domestic Product (GDP). The package of NCD will lead to 549 000 deaths averted and 2 370 000 healthy life years gained over 15 years, and, financially, Iranian economy will gain IRR 542.22 trillion over 15 years. The highest ROI was observed for the package of physical activity interventions, followed by the interventions addressing salt, tobacco package and clinical interventions. Conclusions NCDs in Iran are causing a surge in health care costs and are contributing to reduced productivity. Those actions to prevent NCDs in Iran, as well as yielding to a notable health impact, are giving a good economic return to the society. This study underscores an essential need for establishment of a national multi-sectorial NCD coordination mechanism to bring together and strengthen existing cross-agency initiatives on NCDs.

Novel endophytic fungal species Pithoascus kurdistanensis producing morphine compounds.

Papaver genus, commonly known as popies, is a valuable source of alkaloids used in medicine, including papaverine, morphine, codeine, and thebaine. We isolated six endophytic fungal isolates producing morphinan alkaloids from four Papaver species growing in Kurdistan Province, Iran. To do this, a 1:1 mixture of methanol and chloroform was used to extract fungal cultures. The contents of morphinan alkaloids in the extracts were subsequently determined using phase high-performance liquid chromatography. Among the morphinan alkaloid-producing fungal isolates, IRAN 4653C had the highest yield giving 23.06 (mg/g) morphine and 2.03 (mg/g) codeine when grown in potato dextrose liquid medium. The identity of this isolate was examined and recognized as a new fungal species named as Pithoascus kurdistanesis sp. nov. based on multi-gene phylogenetic analyses of ITS, TEF-1α, and TUB2 sequences data and morphological features. The morphinan-producing endophytic fungus and the isolated Pithoascus species from Papaver are being reported for the first time. Accordingly, this fungus shows promise as a new source of valuable compounds which is illustrated and introduced here as a new Microascaceae member belonging to Pithoascus from Kurdistan Province, Iran. Moreover, the morphinan productivity of P. kurdistanesis was further validated by gas chromatography-mass spectrometry (GC-MS).

Complete genome sequences of agricultural azole-resistant Penicillium rubens encoding CYP51A and ERG11 paralogues.

Azoles are major antifungals in agriculture and medicine. However, the surge of intrinsic azole resistance is critical for public health. Here, we present the complete long-read sequencing of three azole-resistant Penicillium rubens from food crops. The presence of CYP51A and ERG11 paralogues was confirmed, as in other azole-resistant P. rubens.

A new species of Acanthodactylus Fitzinger, 1834 (Sauria: Lacertidae) from the Zagros Mountains, Iran.

Acanthodactylus boskianus is a widespread species in Northern Africa and Western Asia. In this study, we used morphological and genetic approaches to study populations of A. boskianus from the Zagros Mountains in western Iran, the easternmost limit of the species distribution. Our morphological and genetic data indicate that populations of A. boskianus in Iran are distinct from other populations of A. boskianus. Therefore, we describe the Iranian populations as Acanthodactylus zagrosicus sp. nov. The new species is the third endemic species of Acanthodactylus in Iran and the ninth Acanthodactylus species distributed in Iran overall. According to our surveys, this species is distributed widely in the Zagros Mountains including Kermanshah, Lorestan, Ilam, and Khuzestan Provinces.

Mechanism and adverse effects of COVID-19 drugs: a basic review.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus disease 2019 (COVID-19) is chronic, inflammatory. Although the exact mechanisms of COVID-19 have not been yet discovered some drugs are found helpful for its treatment. These drugs which are divided into some lines therapies, have demonstrated to be helpful for COVID-19 patients based on immune basic and its antiviral properties of the disease. Previous studies have been indicated that deterioration of COVID-19 condition is associated with a weaker immune system. Most of these therapies impact on the immune system and immune cells. Beside many beneficial effects of these drugs, some adverse effects (AE) have been reported in many experiments and clinical trials among patients suffering from COVID-19. In this review, we conclude some AEs of vitamin-D, zinc, remdesivir, hydroxychloroquine or chloroquine, azithromycin, dexamethasone, amantadine, aspirin reported in different papers and we continue the rest of the drugs in second part of our review article.

Hairy root induction and Farnesiferol B production of endemic medicinal plant Ferula pseudalliacea.

The effects of medium, gibberellic acid (GA3) and stratification treatments on the seed germination of Ferula pseudalliacea were evaluated. Filter paper medium, 500 micro molar GA3 and 8 week chilling treatment were resulted in significantly more seed germination than others. F. pseudalliacea was also transformed by Agrobacterium rhizogenes. Explants from young leaves, stems, cotyledon, and embryo were inoculated with A. rhizogenes strains ATCC 15834, 1724, A4, LB9402 and Ar318. Hairy roots were induced only from 10 to 12-days embryo explants using strains ATCC 15824 and 1724. Although, the transformation efficiency of ATCC 15834 (4%) strain was higher than 1724 (2%). Maximum hairy root transformation frequency (25%) was obtained in infection time of 10 min compared to that of 20 (20%) and 30 (5%) min. In addition, the transformation rate was significantly higher at the inoculation time of 72 h (29%) compared to that of 48 h (22%) and 24 h (6%). Transgenic hairy root lines were confirmed by PCR amplification of rolB gene. Hairy root lines were produced higher biomass in half B5 medium compared to that of half MS medium. Hairy roots lines from the strain ATCC 15834 produced more hairy root numbers and fresh and dried biomass compared to that of the strain 1724. Analyses of transgenic hairy root and natural roots extracts using HPLC showed that all the hairy root lines produced farnesiferol B.