Identification of Cytoplasmic Chaperone Networks Relevant for Respiratory Syncytial Virus Replication.

RNA viruses have limited coding capacity and must therefore successfully subvert cellular processes to facilitate their replication. A fundamental challenge faced by both viruses and their hosts is the ability to achieve the correct folding and assembly of their proteome while avoiding misfolding and aggregation. In cells, this process is facilitated by numerous chaperone systems together with a large number of co-chaperones.

Adoptive transfer of ex vivo expanded SARS-CoV-2-specific cytotoxic lymphocytes: A viable strategy for COVID-19 immunosuppressed patients?

Cellular and humoral response to acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is on focus of research. We evaluate herein the feasibility of expanding virus-specific T cells (VST) against SARS-CoV-2 ex vivo through a standard protocol proven effective for other viruses. The experiment was performed in three different donors' scenarios: (a) SARS-CoV-2 asymptomatic infection/negative serology, (b) SARS-CoV-2 symptomatic infection/positive serology, and (c) no history of SARS-CoV-2 infection/negative serology.

Globally defining the effects of mutations in a picornavirus capsid.

The capsids of non-enveloped viruses are highly multimeric and multifunctional protein assemblies that play key roles in viral biology and pathogenesis. Despite their importance, a comprehensive understanding of how mutations affect viral fitness across different structural and functional attributes of the capsid is lacking. To address this limitation, we globally define the effects of mutations across the capsid of a human picornavirus.

Inference of SARS-CoV-2 spike-binding neutralizing antibody titers in sera from hospitalized COVID-19 patients by using commercial enzyme and chemiluminescent immunoassays.

Whether antibody levels measured by commercially available enzyme or chemiluminescent immunoassays targeting the SARS-CoV-2 spike (S) protein can act as a proxy for serum neutralizing activity remains to be established for many of these assays. We evaluated the degree of correlation between neutralizing antibodies (NtAb) binding the SARS-CoV-2 spike (S) protein and SARS-CoV-2-S-IgG levels measured by four commercial immunoassays in sera drawn from hospitalized COVID-19 patients. Ninety sera from 51 hospitalized COVID-19 patients were tested by a pseudotyped virus neutralization assay, the LIAISON SARS-CoV-2 S1/S2 IgG, the Euroimmun SARS-CoV-2 IgG ELISA, the MAGLUMI 2019-nCoV IgG, and the COVID-19 ELISA IgG assays.

HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation.

Gene expression programs determine cell fate in embryonic development and their dysregulation results in disease. Transcription factors (TFs) control gene expression by binding to enhancers, but how TFs select and activate their target enhancers is still unclear. HOX TFs share conserved homeodomains with highly similar sequence recognition properties, yet they impart the identity of different animal body parts.

Suitability of two rapid lateral flow immunochromatographic assays for predicting SARS-CoV-2 neutralizing activity of sera.

Assessment of commercial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoassays for their capacity to provide reliable information on sera neutralizing activity is an emerging need. We evaluated the performance of two commercially available lateral flow immunochromatographic assays (LFIC; Wondfo SARS-CoV-2 Antibody test and the INNOVITA 2019-nCoV Ab test) in comparison with a SARS-CoV-2 neutralization pseudotyped assay for coronavirus disease 2019 (COVID-19) diagnosis in hospitalized patients and investigate whether the intensity of the test band in LFIC associates with neutralizing antibody (NtAb) titers. Ninety sera were included from 51 patients with moderate to severe COVID-19.

SARS-CoV-2 antibodies, serum inflammatory biomarkers and clinical severity of hospitalized COVID-19 patients.

Background: The involvement of SARS-CoV-2 antibodies in mediating immunopathogenetic events in COVID-19 patients has been suggested. By using several experimental approaches, we investigated the potential association between SARS-CoV-2 IgGs recognizing the spike (S) protein receptor-binding domain (RBD), neutralizing antibodies (NtAb) targeting S, and COVID-19 severity.

Patients And Methods: This unicenter, retrospective, observational study included 51 hospitalized patients (24 at the intensive care unit; ICU).

Chaperoning the : Current Knowledge and Future Directions.

The order harbors numerous viruses of significant relevance to human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses, and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread.

A tissue-specific, Gata6-driven transcriptional program instructs remodeling of the mature arterial tree.

Connection of the heart to the systemic circulation is a critical developmental event that requires selective preservation of embryonic vessels (aortic arches). However, why some aortic arches regress while others are incorporated into the mature aortic tree remains unclear. By microdissection and deep sequencing in mouse, we find that neural crest (NC) only differentiates into vascular smooth muscle cells (SMCs) around those aortic arches destined for survival and reorganization, and identify the transcription factor Gata6 as a crucial regulator of this process.

Dysfunctional Skin-Derived Glucocorticoid Synthesis Is a Pathogenic Mechanism of Psoriasis.

Glucocorticoids (GC) are the primary steroids that regulate inflammation and have been exploited therapeutically in inflammatory skin diseases. Despite the broad-spectrum therapeutic use of GC, the biochemical rationale for locally treating inflammatory skin conditions is poorly understood, as systemic GC production remains largely functional in these patients. GC synthesis has been well characterized in healthy skin, but the pathological consequence has not been examined.

A distal 594 bp ECR specifies Hmx1 expression in pinna and lateral facial morphogenesis and is regulated by the Hox-Pbx-Meis complex.

Hmx1 encodes a homeodomain transcription factor expressed in the developing lateral craniofacial mesenchyme, retina and sensory ganglia. Mutation or mis-regulation of Hmx1 underlies malformations of the eye and external ear in multiple species. Deletion or insertional duplication of an evolutionarily conserved region (ECR) downstream of Hmx1 has recently been described in rat and cow, respectively.

Glucocorticoid receptor and Klf4 co-regulate anti-inflammatory genes in keratinocytes.

The glucocorticoid (GC) receptor (GR) and Kruppel-like factor Klf4 are transcription factors that play major roles in skin homeostasis. However, whether these transcription factors cooperate in binding genomic regulatory regions in epidermal keratinocytes was not known. Here, we show that in dexamethasone-treated keratinocytes GR and Klf4 are recruited to genomic regions containing adjacent GR and KLF binding motifs to control transcription of the anti-inflammatory genes Tsc22d3 and Zfp36.

Selective ablation of glucocorticoid receptor in mouse keratinocytes increases susceptibility to skin tumorigenesis.

We recently demonstrated that mice lacking the epidermal glucocorticoid (GC) receptor (GR) (GR epidermal knockout (GR(EKO)) mice) have developmental defects and sensitivity to epidermal challenge in adulthood. We examined the susceptibility of GR(EKO) mice to skin chemical carcinogenesis. GR(EKO) mice treated with a low dose of 12-dimethylbenz(a) anthracene (DMBA) followed by phorbol 12-myristate 13-acetate (PMA) promotion exhibited earlier papilloma formation with higher incidence and multiplicity relative to control littermates (CO).

Epidermal inactivation of the glucocorticoid receptor triggers skin barrier defects and cutaneous inflammation.

The glucocorticoid (GC) receptor (GR) mediates the effects of physiological and pharmacological GC ligands and has a major role in cutaneous pathophysiology. To dissect the epithelial versus mesenchymal contribution of GR in developing and adult skin, we generated mice with keratinocyte-restricted GR inactivation (GR epidermal knockout or GR(EKO) mice). Developing and early postnatal GR(EKO) mice exhibited impaired epidermal barrier formation, abnormal keratinocyte differentiation, hyperproliferation, and stratum corneum (SC) fragility.

Keratinocyte-targeted overexpression of the glucocorticoid receptor delays cutaneous wound healing.

Delayed wound healing is one of the most common secondary adverse effects associated to the therapeutic use of glucocorticoid (GC) analogs, which act through the ligand-dependent transcription factor GC-receptor (GR). GR function is exerted through DNA-binding-dependent and -independent mechanisms, classically referred to as transactivation (TA) and transrepression (TR). Currently both TA and TR are thought to contribute to the therapeutical effects mediated by GR; however their relative contribution to unwanted side effects such as delayed wound healing is unknown.

Glucocorticoid receptor regulates overlapping and differential gene subsets in developing and adult skin.

We have previously shown that the glucocorticoid receptor (GR) is required for skin homeostasis and epidermal barrier competence. To understand the transcriptional program by which GR regulates skin development, we performed a microarray analysis using the skin of GR(-/-) and GR(+/+) mice of embryonic d 18.5 and identified 442 differentially expressed genes.