Background
Trichophyton mentagrophytes (formerly Arthroderma vanbreuseghemii) and its clonal offshoot Trichophyton interdigitale, which are leading causes of dermatophytoses, have recently been ...recognized as two separate species. Over the last 20 years, several internal transcribed spacer (ITS) genotypes of Trichophyton mentagrophytes and Trichophyton interdigitale have been identified, some of which have specific characteristics and lead to typical clinical manifestations.
Objectives
The aim of this study was to determine the current epidemiology of Trichophyton mentagrophytes and Trichophyton interdigitale genotypes in Switzerland, particularly in the Zurich area.
Methods
Consecutive cases diagnosed by ITS sequencing between 2009 and 2019 were retrospectively analysed.
Results
A total of 81 Trichophyton mentagrophytes and 81 Trichophyton interdigitale cases were investigated. T. mentagrophytes infections clearly differed from T. interdigitale infections by affecting younger and more frequently female patients, targeting almost exclusively head and body rather than feet and toenails, leading to inflammatory dermatophytosis and often requiring a combination of systemic and topical treatment. Seven different T. mentagrophytes genotypes (II*, III, III*, IV, VII, VIII and XXVI) were observed, with genotype XXVI being discovered in this study. Genotype III occurred most frequently (56% of all T. mentagrophytes cases) and affected predominantly children. Genotypes III* and VII led to inflammatory tinea in most cases. Four strains that proved to be terbinafine resistant belonged to the ‘Indian genotype’ VIII, which mostly caused tinea glutealis and inguinalis.
Conclusion
Being able to distinguish between Trichophyton mentagrophytes and Trichophyton interdigitale is of paramount importance as the two species cause different clinical presentations. In addition, ITS genotyping allows recognizing sources of infection and potential terbinafine resistance. The latter needs to be confirmed by resistance testing or by sequencing part of the squalene epoxidase (SQLE) gene.
Apicomplexan parasites invade host cells in an active process involving their ability to move by gliding motility. While the acto-myosin system of the parasite plays a crucial role in the formation ...and release of attachment sites during this process, there are still open questions regarding the involvement of other mechanisms in parasite motility. In many eukaryotes, a secretory-endocytic cycle leads to the recycling of receptors (integrins), necessary to form attachment sites, regulation of surface area during motility, and generation of retrograde membrane flow. Here, we demonstrate that endocytosis operates during gliding motility in Toxoplasma gondii and appears to be crucial for the establishment of retrograde membrane flow, because inhibition of endocytosis blocks retrograde flow and motility. We demonstrate that extracellular parasites can efficiently incorporate exogenous material, such as labelled phospholipids, nanogold particles (NGPs), antibodies, and Concanavalin A (ConA). Using labelled phospholipids, we observed that the endocytic and secretory pathways of the parasite converge, and endocytosed lipids are subsequently secreted, demonstrating the operation of an endocytic-secretory cycle. Together our data consolidate previous findings, and we propose an additional model, working in parallel to the acto-myosin motor, that reconciles parasite motility with observations in other eukaryotes: an apicomplexan fountain-flow-model for parasite motility.
The membrane-trafficking system is a defining facet of eukaryotic cells. The best-known organelles and major protein families of this system are largely conserved across the vast diversity of ...eukaryotes, implying both ancient organization and functional unity. Nonetheless, intriguing variation exists that speaks to the evolutionary forces that have shaped the endomembrane system in eukaryotes and highlights ways in which membrane trafficking in protists differs from that in our well-understood models of mammalian and yeast cells. Both parasites and free-living protists possess specialized trafficking organelles, some lineage specific, others more widely distributed — the evolution and function of these organelles begs exploration. Novel members of protein families are present across eukaryotes but have been lost in humans. These proteins may well hold clues to understanding differences in cellular function in organisms that are of pressing importance for planetary health.
In this review, More and colleagues explore the differences in membrane-trafficking organelles and protein families in the diversity of lineages descended from the last eukaryotic common ancestor (LECA).
Apicomplexa are obligate intracellular parasites that cause tremendous disease burden world-wide. They utilize a set of specialized secretory organelles in their invasive process that require ...delivery of components for their biogenesis and function, yet the precise mechanisms underpinning such processes remain unclear. One set of potentially important components is the multi-subunit tethering complexes (MTCs), factors increasingly implicated in all aspects of vesicle-target interactions. Prompted by the results of previous studies indicating a loss of membrane trafficking factors in Apicomplexa, we undertook a bioinformatic analysis of MTC conservation. Building on knowledge of the ancient presence of most MTC proteins, we demonstrate the near complete retention of MTCs in the newly available genomes for Guillardiatheta and Bigelowiellanatans. The latter is a key taxonomic sampling point as a basal sister taxa to the group including Apicomplexa. We also demonstrate an ancient origin of the CORVET complex subunits Vps8 and Vps3, as well as the TRAPPII subunit Tca17. Having established that the lineage leading to Apicomplexa did at one point possess the complete eukaryotic complement of MTC components, we undertook a deeper taxonomic investigation in twelve apicomplexan genomes. We observed excellent conservation of the VpsC core of the HOPS and CORVET complexes, as well as the core TRAPP subunits, but sparse conservation of TRAPPII, COG, Dsl1, and HOPS/CORVET-specific subunits. However, those subunits that we did identify appear to be expressed with similar patterns to the fully conserved MTC proteins, suggesting that they may function as minimal complexes or with analogous partners. Strikingly, we failed to identify any subunits of the exocyst complex in all twelve apicomplexan genomes, as well as the dinoflagellate Perkinsus marinus. Overall, we demonstrate reduction of MTCs in Apicomplexa and their ancestors, consistent with modification during, and possibly pre-dating, the move from free-living marine algae to deadly human parasites.
Background
Despite civilization and progress, burns occur frequently in the world. Remarkable discoveries of wound healing mechanisms have been reported. On the other hand, long-term outcomes from ...burn injuries represent a barrier to improvement of patients’ social, functional, and psychological condition. Lipofilling, described since the 1980s, currently is used for several clinical applications. This study aimed to verify whether lipofilling could ameliorate scar remodeling in three clinical cases.
Methods
Three adult patients with hemifacial hypertrophic scars and keloids resulting from severe burns 2 to 13 years previously were selected. The patients were treated by injection of adipose tissue harvested from abdominal subcutaneous fat and processed according to Coleman’s technique. Two injections (with a 13-month interval between) were administered at the dermohypodermal junction. Histologic examination of scar tissue punch biopsies (hematoxylin-eosin staining) before and after the treatment was performed as well as magnetic resonance scan with contrast.
Results
The clinical appearance and subjective patient feelings after a 6-month follow-up period suggest considerable improvement in the mimic features, skin texture, and thickness. Histologic examination shows patterns of new collagen deposition, local hypervascularity, and dermal hyperplasia in the context of new tissue, with high correspondence to the original.
Conclusions
The preliminary results show that lipofilling improves scar quality and suggest a tissue regeneration enhancing process.
Background
Despite civilization and progress, burns occur frequently in the world. Remarkable discoveries of wound healing mechanisms have been reported. On the other hand, long-term outcomes from ...burn injuries represent a barrier to improvement of patients' social, functional, and psychological condition. Lipofilling, described since the 1980s, currently is used for several clinical applications. This study aimed to verify whether lipofilling could ameliorate scar remodeling in three clinical cases.
Methods
Three adult patients with hemifacial hypertrophic scars and keloids resulting from severe burns 2 to 13 years previously were selected. The patients were treated by injection of adipose tissue harvested from abdominal subcutaneous fat and processed according to Coleman's technique. Two injections (with a 13-month interval between) were administered at the dermohypodermal junction. Histologic examination of scar tissue punch biopsies (hematoxylin-eosin staining) before and after the treatment was performed as well as magnetic resonance scan with contrast.
Results
The clinical appearance and subjective patient feelings after a 6-month follow-up period suggest considerable improvement in the mimic features, skin texture, and thickness. Histologic examination shows patterns of new collagen deposition, local hypervascularity, and dermal hyperplasia in the context of new tissue, with high correspondence to the original.
Conclusions
The preliminary results show that lipofilling improves scar quality and suggest a tissue regeneration enhancing process.
Plastids are supported by a wide range of proteins encoded within the nucleus and imported from the cytoplasm. These plastid-targeted proteins may originate from the endosymbiont, the host, or other ...sources entirely. Here, we identify and characterise 770 plastid-targeted proteins that are conserved across the ochrophytes, a major group of algae including diatoms, pelagophytes and kelps, that possess plastids derived from red algae. We show that the ancestral ochrophyte plastid proteome was an evolutionary chimera, with 25% of its phylogenetically tractable nucleus-encoded proteins deriving from green algae. We additionally show that functional mixing of host and plastid proteomes, such as through dual-targeting, is an ancestral feature of plastid evolution. Finally, we detect a clear phylogenetic signal from one ochrophyte subgroup, the lineage containing pelagophytes and dictyochophytes, in plastid-targeted proteins from another major algal lineage, the haptophytes. This may represent a possible serial endosymbiosis event deep in eukaryotic evolutionary history.
Abstract
First released in 2006, DrugBank (https://go.drugbank.com) has grown to become the ‘gold standard’ knowledge resource for drug, drug–target and related pharmaceutical information. DrugBank ...is widely used across many diverse biomedical research and clinical applications, and averages more than 30 million views/year. Since its last update in 2018, we have been actively enhancing the quantity and quality of the drug data in this knowledgebase. In this latest release (DrugBank 6.0), the number of FDA approved drugs has grown from 2646 to 4563 (a 72% increase), the number of investigational drugs has grown from 3394 to 6231 (a 38% increase), the number of drug–drug interactions increased from 365 984 to 1 413 413 (a 300% increase), and the number of drug–food interactions expanded from 1195 to 2475 (a 200% increase). In addition to this notable expansion in database size, we have added thousands of new, colorful, richly annotated pathways depicting drug mechanisms and drug metabolism. Likewise, existing datasets have been significantly improved and expanded, by adding more information on drug indications, drug–drug interactions, drug–food interactions and many other relevant data types for 11 891 drugs. We have also added experimental and predicted MS/MS spectra, 1D/2D-NMR spectra, CCS (collision cross section), RT (retention time) and RI (retention index) data for 9464 of DrugBank's 11 710 small molecule drugs. These and other improvements should make DrugBank 6.0 even more useful to a much wider research audience ranging from medicinal chemists to metabolomics specialists to pharmacologists.
Graphical Abstract
Graphical Abstract
Polyomavirus BK (BKV)‐associated nephropathy causes premature kidney transplant (KT) failure. BKV viruria and viremia are biomarkers of disease progression, but associated risk factors are ...controversial. A total of 682 KT patients receiving basiliximab, mycophenolic acid (MPA), corticosteroids were randomized 1:1 to cyclosporine (CsA) or tacrolimus (Tac). Risk factors were analyzed in 629 (92.2%) patients having at least 2 BKV measurements until month 12 posttransplant. Univariate analysis associated CsA‐MPA with lower rates of viremia than Tac‐MPA at month 6 (10.6% vs. 16.3%, p = 0.048) and 12 (4.8% vs. 12.1%, p = 0.004) and lower plasma BKV loads at month 12 (3.9 vs. 5.1 log10 copies/mL; p = 0.028). In multivariate models, CsA‐MPA remained associated with less viremia than Tac‐MPA at month 6 (OR 0.60; 95% CI 0.36–0.99) and month 12 (OR 0.33; 95% CI 0.16–0.68). Viremia at month 6 was also independently associated with higher steroid exposure until month 3 (OR 1.19 per 1 g), and with male gender (OR 2.49) and recipient age (OR 1.14 per 10 years) at month 12. The data suggest a dynamic risk factor evolution of BKV viremia consisting of higher corticosteroids until month 3, Tac‐MPA compared to CsA‐MPA at month 6 and Tac‐MPA, older age, male gender at month 12 posttransplant.
In a study of kidney transplant recipients randomized 1:1 to receive either cyclosporine‐A or tacrolimus together with a common backbone of basiliximab induction, mycophenolate and steroids, higher steroid exposure, tacrolimus, male gender and older age are identified as independent risk factors for BK virus in the first year posttransplant. See a related manuscript by Theodoropoulos et al on page 197.
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