The effect of spike mutations on SARS-CoV-2 neutralization

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Reevaluating sponge diversity and distribution in the Mediterranean Sea

The aim of this paper was (1) to update sponge diversity and distribution in the Mediterranean and (2) to re-examine faunal relationships among the Mediterranean areas on the basis of their sponge fauna. The Mediterranean demosponge faunal list was updated to 629 species by taking into consideration recent data from previously poorly studied areas. The species lists of 14 Mediterranean areas were compared on the basis of their sponge species richness, species composition, and taxonomic relatedness of species using multivariate analyses and diversity measures, such as PD, Delta+, and Lambda+. The 14 Mediterranean areas examined for their diversity and affinities were assembled into four major zoogeographic groups: the northwestern, northeastern, the central zone, and southeastern areas. Richest in species numbers were the areas belonging to the two northern groups. The species richness comparisons and similarity analyses performed at the generic level showed that it can be safely used as a surrogate for sponge species diversity in the Mediterranean. The results of this study showed that the simple traditional division of the Mediterranean Sea into a western, central, and eastern basin cannot reliably describe the distribution of sponges in the area. Thus, the W to E faunal decline previously presented for several faunal groups shifts to a general NNW-SSE pattern when one examines separately the northern and the southern parts of the traditional basins. This gradient seems to be in agreement with differences in key environmental variables, such as latitude, salinity, temperature, and water circulation, besides the typically examined distance from Gibraltar. Handling editor: T. P. Crowe     

Presentation of ICAM-1 protein at the cell surface of oral keratinocytes in the presence of adrenomedullin and corticotrophin.

Increasing evidence suggests that adrenomedullin (AM) and corticotrophin (ACTH) are immunomodulatory. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes not only from peripheral blood into inflamed tissues but also into epithelia. We have investigated the effects of AM and ACTH on the expression of ICAM-1 by human oral keratinocytes. The human oral keratinocyte cell line H357 was incubated with either AM or ACTH for up to 8 hrs and ICAM-1 expression was measured by cell surface ELISA. ICAM-1 was up regulated by both peptides and this was attenuated by the adenylyl cyclase inhibitor SQ22,536 and the NF-kappaB inhibitor SN-50. H357 cells constitutively express ICAM-1 mRNA and expression of this gene was significantly modulated by AM and ACTH. Furthermore AM caused translocation of NF-kappaB from the cytoplasm to the nucleus. This is the first report describing up regulation of ICAM-1 in oral keratinocytes by AM and ACTH and the results suggest both cAMP and NF-kappaB may play a role. These results further suggest both peptides may have an immunostimulatory role in oral muocsa and skin.     

Multi-omic profiling reveals associations between the gut mucosal microbiome,the metabolome,and host DNA methylation associated gene expression in patients with colorectal cancer

Actinomyces oris is an early colonizer and has two types of fimbriae on its cell surface, type 1 fimbriae (FimP and FimQ) and type 2 fimbriae (FimA and FimB), which contribute to the attachment and coaggregation with other bacteria and the formation of biofilm on the tooth surface, respectively. Short-chain fatty acids (SCFAs) are metabolic products of oral bacteria including A. oris and regulate pH in dental plaques. To clarify the relationship between SCFAs and fimbrillins, effects of SCFAs on the initial attachment and colonization (INAC) assay using A. oris wild type and fimbriae mutants was investigated. INAC assays using A. oris MG1 strain cells were performed with SCFAs (acetic, butyric, propionic, valeric and lactic acids) or a mixture of them on human saliva-coated 6-well plates incubated in TSB with 0.25% sucrose for 1 h. The INAC was assessed by staining live and dead cells that were visualized with a confocal microscope. Among the SCFAs, acetic, butyric and propionic acids and a mixture of acetic, butyric and propionic acids induced the type 1 and type 2 fimbriae-dependent and independent INAC by live A. oris, but these cells did not interact with streptococci. The main effects might be dependent on the levels of the non-ionized acid forms of the SCFAs in acidic stress conditions. GroEL was also found to be a contributor to the FimA-independent INAC by live A. oris cells stimulated with non-ionized acid. SCFAs affect the INAC-associated activities of the A. oris fimbrillins and non-fimbrillins during ionized and non-ionized acid formations in the form of co-culturing with other bacteria in the dental plaque but not impact the interaction of A. oris with streptococci.     

DNA end resection: Many nucleases make light work

Double-strand breaks (DSBs) are deleterious DNA lesions and if left unrepaired result in severe genomic instability. Cells use two main pathways to repair DSBs: homologous recombination (HR) or non-homologous end joining (NHEJ) depending on the phase of the cell cycle and the nature of the DSB ends. A key step where pathway choice is exerted is in the ‘licensing’ of 5′–3′ resection of the ends to produce recombinogenic 3′ single-stranded tails. These tails are substrate for binding by Rad51 to initiate pairing and strand invasion with homologous duplex DNA. Moreover, the single-stranded DNA generated after end processing is important to activate the DNA damage response. The mechanism of end processing is the focus of this review and we will describe recent findings that shed light on this important initiating step for HR. The conserved MRX/MRN complex appears to be a major regulator of DNA end processing. Sae2/CtIP functions with the MRX complex, either to activate the Mre11 nuclease or via the intrinsic endonuclease, in an initial step to trim the DSB ends. In a second step, redundant systems remove long tracts of DNA to reveal extensive 3′ single-stranded tails. One system is dependent on the helicase Sgs1 and the nuclease Dna2, and the other on the 5′–3′ exonuclease Exo1.     

Successful treatment with the mTOR inhibitor everolimus in a patient with Perivascular epithelioid cell tumor

ABSTRACT: Perivascular epithelioid cell tumor (PEComa) is an extremely rare neoplasm that appears to arise most commonly at visceral (especially gastrointestinal and uterine), retroperitoneal, and abdominopelvic sites. Malignant PEComas exist but are very rare. These tumors represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. Metastatic PEComa is a rare form of sarcoma for which no effective therapy has been described previously and that has a uniformly fatal outcome. Although there is no known effective therapy, the molecular pathophysiology of aberrant mTOR signaling provides a scientific rationale to target this pathway therapeutically. The difficulty in determining optimal therapy, owing to the sparse literature available, led us to present this case. On this basis, we report a case of metastatic retroperitoneal PEComa treated with an oral mTOR inhibitor, with everolimus achieving significant clinical response.