Opa1 Overexpression Protects from Early-Onset Mpv17−/−-Related Mouse Kidney Disease

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First report of Mortierella wolfii causing fungal keratitis from a tertiary eye hospital in India

A young 33 year old male presented with non-resolving corneal infiltrate for 2 month duration in the right eye. KOH/ Calcoflour wet mount revealed sparsely septate fungal hyphae. Post therapeutic penetrating keratoplasty 3 doses of intracameral voriconazole(100μg/0.1ml) was administered suspecting recurrence. Fungal culture revealed non sporulating mould on SDA. PCR based DNA sequencing targeting the ITS region identified the fungal isolate as Mortierella wolfii (M. wolfii) belonging to zygomycetes. To the best of our knowledge, this is the first report of human fungal keratitis caused by M. wolfii.     

Tracking myeloma tumor DNA in peripheral blood

Over the past years, the emergence of liquid biopsy technologies has dramatically expanded our ability to assess multiple myeloma without the need for invasive sampling. Interrogation of cell-free DNA from the peripheral blood recapitulates the mutational landscape at excellent concordance with matching bone marrow aspirates. It can quantify disease burden and identify previously undetected resistance mechanisms which may inform clinical management in real-time. The convenience of sample acquisition and storage provides strong procedural benefits over currently available testing. Further investigations will have to define the role of cell-free DNA as a diagnostic measure by determining clinically relevant tumor thresholds in comparison to existing routine parameters. This review presents an overview of currently available assays and discusses the clinical value, potential and limitations of cell-free DNA technologies for the assessment of this challenging disease.     

含DNA嵌入基团的抗肿瘤铂类配合物研究进展

铂类抗肿瘤药物因其独特的抗肿瘤作用机制、显著的抗肿瘤效果以及抗肿瘤谱广等特点，被广泛应用于临床治疗中。而已上市的铂类药物在治疗过程中出现的不良反应、耐药性和交叉耐药性等缺点限制了其进一步扩大应用。铂类配合物结构中引入DNA嵌入基团，其抗肿瘤作用机制与经典铂类药物不同，在克服经典铂类抗肿瘤药物缺点上具有独到的优势。含DNA嵌入基团的铂类配合物以其所含DNA嵌入基团不同可分为6大类:含吲哚嵌入基团的铂类配合物、含吖啶嵌入基团的铂类配合物、含喹啉嵌入基团的铂类配合物、含萘酰亚胺嵌入基团的铂类配合物、含蒽醌嵌入基团的铂类配合物、含其他类嵌入基团的铂类配合物。本文总结了近几年含DNA嵌入基团铂类配合物的抗肿瘤活性研究进展。     

Human infections due to Schizophyllum commune: Case report and review of the literature

Schizophyllum commune is an environmental basidiomycetous fungus, causing occasional, predominantly respiratory, infections in humans. Although S. commune is considered an emerging pathogen, some authors pointed out the possibility that the increase in the diagnosed cases may be also due to recent advances in diagnostic technologies now allowing a more prompt and precise identification at the species level. Here we describe the first Italian case of chronic non-invasive fungal rhinosinusitis due to S. commune in an immunocompetent subject and update the literature review on S. commune sinusitis published between 2012–2019. A timely diagnosis is important to avoid local and systemic complications due to infection with this fungus. In our case, prompt identification at species level was only possible with the use of MALDI-TOF mass spectrometry and confirmed by sequence analysis of ribosomal DNA ITS regions, due to the difficulty in achieving a correct and rapid identification using routine morphological analysis.     

Understanding the importance of low-molecular weight (ethylene oxide- and propylene oxide-induced) DNA adducts and mutations in risk assessment: Insights from 15 years of research and collaborative discussions

The interpretation and significance of DNA adduct data, their causal relationship to mutations, and their role in risk assessment have been debated for many years. An extended effort to identify key questions and collect relevant data to address them was focused on the ubiquitous low MW N7-alkyl/hydroxyalkylguanine adducts. Several academic, governmental, and industrial laboratories collaborated to gather new data aimed at better understanding the role and potential impact of these adducts in quantifiable genotoxic events (gene mutations/micronucleus). This review summarizes and evaluates the status of dose–response data for DNA adducts and mutations from recent experimental work with standard mutagenic agents and ethylene oxide and propylene oxide, and the importance for risk assessment. This body of evidence demonstrates that small N7-alkyl/hydroxyalkylguanine adducts are not pro-mutagenic and, therefore, adduct formation alone is not adequate evidence to support a mutagenic mode of action. Quantitative methods for dose–response analysis and derivation of thresholds, benchmark dose (BMD), or other points-of-departure (POD) for genotoxic events are now available. Integration of such analyses of genetox data is necessary to properly assess any role for DNA adducts in risk assessment. Regulatory acceptance and application of these insights remain key challenges that only the regulatory community can address by applying the many learnings from recent research. The necessary tools, such as BMDs and PODs, and the example datasets, are now available and sufficiently mature for use by the regulatory community. Environ. Mol. Mutagen. 60: 100–121, 2019. © 2018 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.