Primary renal lymphoma masquerading as metastasis in a patient with primary breast cancer and systemic lupus erythematosus.

We describe a case of a 56-year-old woman with systemic lupus erythematosus (SLE) who presented with breast mass, axillary lymphadenopathy, and renal mass. The breast lesion was diagnosed as infiltrating ductal carcinoma. However, the renal mass evaluation was suggestive of a primary lymphoma. Primary renal lymphoma (PRL) with breast cancer in an SLE patient has rarely been reported.

Pleural fluid cytology in prompt diagnosis of pleuro-pulmonary nocardiosis masquerading as COVID-19.

Introduction: There are few reports of nocardial infections among the Indian population. We report this case because of its rarity and unique presentation and to highlight the role of cytology in diagnosis. Case Details: A 74-year-old woman presented with fever and chest pain of a duration of 15 days. In view of the coronavirus disease (COVID) pandemic, she was given steroids. She developed breathlessness and was referred to a tertiary care hospital. Her pleural fluid cytology showed filamentous bacteria. A diagnosis of nocardia was confirmed by culture. Discussion: Nocardiosis refers to the localized or disseminated infection caused by filamentous aerobic bacteria of the genus Nocardia. The clinical presentation of nocardiosis is highly variable. In our case, clinical misdiagnosis as COVID-19 and steroid treatment would have caused deterioration of nocardiosis. Conclusion: All patients with pulmonary symptoms should be thoroughly evaluated before considering a diagnosis of COVID-19. Pleural fluid cytology can be of help in the diagnosis of nocardiosis.

ß-Strand-mediated interactions of protein domains.

Protein domains exist by themselves or in combination with other domains to form complex multidomain proteins. Defining domain boundaries in proteins is essential for understanding their evolution and function but is not trivial. More specifically, partitioning domains that interact by forming a single ß-sheet is known to be particularly troublesome for automatic structure-based domain decomposition pipelines. Here, we study edge-to-edge ß-strand interactions between domains in a protein chain, to help define the boundaries for some more difficult cases where a single ß-sheet spanning over two domains gives an appearance of one. We give a number of examples where ß-strands belonging to a single ß-sheet do not belong to a single domain and highlight the difficulties of automatic domain parsers on these examples. This work can be used as a baseline for defining domain boundaries in homologous proteins or proteins with similar domain interactions in the future.

Recent advances suggest increased influence of selective pressure in allostery.

Allosteric regulation of protein functions is ubiquitous in organismal biology, but the principles governing its evolution are not well understood. Here we discuss recent studies supporting the large-scale existence of latent allostery in ancestor proteins of superfamilies. As suggested, the evolution of allostery could be driven by the need for specificity in paralogs of slow evolving protein complexes with conserved active sites. The same slow evolution is displayed by purifying selection exhibited in allosteric proteins with somatic mutations involved in cancer, where disease-associated mutations are enriched in both orthosteric and allosteric sites. Consequently, disease-associated variants can be used to identify druggable allosteric sites that are specific for paralogs in protein superfamilies with otherwise similar functions.

Author Correction: Interaction between the microbiome and TP53 in human lung cancer.

Following publication of the original paper [1], the authors submitted a new Additional file 5 to replace the one containing formatting issues. The updated Additional file 5 is published in this correction.

Predicting Sequence Features, Function, and Structure of Proteins Using MESSA.

MEta-Server for protein Sequence Analysis (MESSA) is a tool that facilitates widespread protein sequence analysis by gathering structural (local sequence properties and three-dimensional structure) and functional (annotations from SWISS-PROT, Gene Ontology terms, and enzyme classification) predictions for a query protein of interest. MESSA uses multiple well-established tools to offer consensus-based predictions on important aspects of protein sequence analysis. Being freely available for noncommercial users and with a user-friendly interface, MESSA serves as an umbrella platform that overcomes the absence of a comprehensive tool for predictive protein analysis. This article reveals how to access MESSA via the Web and shows how to input a protein sequence to analyze using the MESSA web server. It also includes a detailed explanation of the output from MESSA to aid in better interpretation of results. © 2019 by John Wiley & Sons, Inc.

Species-level bacterial community profiling of the healthy sinonasal microbiome using Pacific Biosciences sequencing of full-length 16S rRNA genes.

BACKGROUND: Pan-bacterial 16S rRNA microbiome surveys performed with massively parallel DNA sequencing technologies have transformed community microbiological studies. Current 16S profiling methods, however, fail to provide sufficient taxonomic resolution and accuracy to adequately perform species-level associative studies for specific conditions. This is due to the amplification and sequencing of only short 16S rRNA gene regions, typically providing for only family- or genus-level taxonomy. Moreover, sequencing errors often inflate the number of taxa present. Pacific Biosciences' (PacBio's) long-read technology in particular suffers from high error rates per base. Herein, we present a microbiome analysis pipeline that takes advantage of PacBio circular consensus sequencing (CCS) technology to sequence and error correct full-length bacterial 16S rRNA genes, which provides high-fidelity species-level microbiome data. RESULTS: Analysis of a mock community with 20 bacterial species demonstrated 100% specificity and sensitivity with regard to taxonomic classification. Examination of a 250-plus species mock community demonstrated correct species-level classification of > 90% of taxa, and relative abundances were accurately captured. The majority of the remaining taxa were demonstrated to be multiply, incorrectly, or incompletely classified. Using this methodology, we examined the microgeographic variation present among the microbiomes of six sinonasal sites, by both swab and biopsy, from the anterior nasal cavity to the sphenoid sinus from 12 subjects undergoing trans-sphenoidal hypophysectomy. We found greater variation among subjects than among sites within a subject, although significant within-individual differences were also observed. Propiniobacterium acnes (recently renamed Cutibacterium acnes) was the predominant species throughout, but was found at distinct relative abundances by site. CONCLUSIONS: Our microbial composition analysis pipeline for single-molecule real-time 16S rRNA gene sequencing (MCSMRT, https://github.com/jpearl01/mcsmrt ) overcomes deficits of standard marker gene-based microbiome analyses by using CCS of entire 16S rRNA genes to provide increased taxonomic and phylogenetic resolution. Extensions of this approach to other marker genes could help refine taxonomic assignments of microbial species and improve reference databases, as well as strengthen the specificity of associations between microbial communities and dysbiotic states.

Interaction between the microbiome and TP53 in human lung cancer.

BACKGROUND: Lung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort. RESULTS: Overall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas. CONCLUSIONS: The results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection.