Importance of footwear for preventing xerosis and hyperkeratosis in older people with psychiatric disorders living in an institution

Pocos estudios se han centrado en la relación entre el uso y las características del calzado y la presencia de lesiones en los pies en personas con trastornos psiquiátricos. En este trabajo se analiza la influencia de los diferentes hábitos de uso del calzado en la presencia de deformidades y patologías de las uñas y dérmicas del pie de las personas institucionalizadas con trastornos psiquiátricos en comparación con las personas sin estos trastornos. Se realizó un estudio transversal y observacional con 107 participantes, divididos en dos grupos que han utilizado diferentes tipos de calzado a lo largo de su vida. El grupo de control estuvo integrado por 63 personas autónomas que utilizan principalmente calzado de cuero y un grupo de estudio de 44 personas institucionalizadas con discapacidad intelectual y trastornos psiquiátricos que utilizan principalmente calzado textil. Hubo diferencias significativas entre las poblaciones. El grupo con trastornos psiquiátricos presentó más xerosis e hiperqueratosis. El calzado de características inadecuadas es un posible agente causal de alteraciones de la piel. El uso de calzado con parte superior textil de calidad, por ejemplo, de tela o fieltro, podría influir en la aparición de estas alteraciones. El calzado de cuero se recomienda a las personas institucionalizadas para reducir los síntomas de la xerosis y mejorar su calidad de vida.Few studies have focused on the relation between the use and characteristics of footwear and the presence of foot lesions in people with psychiatric disorders. This work analyzes the influence of different footwear habits on the presence of deformities and ungueal and dermal pathologies of the foot of institutionalized people with psychiatric disorders compared to people without these disorders. A transversal and observational study was conducted on 107 participants, divided into two groups who have used different types of shoes throughout their lives. The control group comprised 63 autonomous people who mainly use leather footwear and a study group of 44 institutionalized people with intellectual disabilities and psychiatric disorders who mainly use textile footwear. There were significant differences between populations. The group with psychiatric disorders presented more xerosis and hyperkeratosis. Footwear with inappropriate characteristics is a possible causal agent of skin alterations. Wearing footwear with quality textile uppers, e.g., fabric or felt, could influence the appearance of these alterations. Leather footwear is recommended for institutionalized people to reduce symptoms of xerosis and improve their quality of life.peerReviewe

Structural determinants of peptide-dependent TAP1-TAP2 transit passage targeted by viral proteins and altered by cancer-associated mutations

The TAP1-TAP2 complex transports antigenic peptide substrates into the endoplasmic reticulum (ER). In ER, the peptides are further processed and loaded on the major histocompatibility class (MHC) I molecules by the peptide loading complex (PLC). The TAP transporters are linked with the PLC; a target for cancers and viral immune evasion. But the mechanisms whereby the cancer-derived mutations in TAP1-TAP2 or viral factors targeting the PLC, interfere peptide transport are only emerging. This study describes that transit of peptides through TAP can take place via two different channels (4 or 8 helices) depending on peptide length and sequence. Molecular dynamics and binding affinity predictions of peptide-transporters demonstrated that smaller peptides (8–10 mers; e.g. AAGIGILTV, SIINFEKL) can transport quickly through the transport tunnel compared to longer peptides (15-mer; e.g. ENPVVHFFKNIVTPR). In line with a regulated and selective peptide transport by TAPs, the immunopeptidome upon IFN-γ treatment in melanoma cells induced the shorter length (9-mer) peptide presentation over MHC-I that exhibit a relatively weak binding affinity with TAP. A conserved distance between N and C terminus residues of the studied peptides in the transport tunnel were reported. Furthermore, by adversely interacting with the TAP transport passage or affecting TAPNBD domains tilt movement, the viral proteins and cancer-derived mutations in TAP1-TAP2 may induce allosteric effects in TAP that block conformation of the tunnel (closed towards ER lumen). Interestingly, some cancer-associated mutations (e.g. TAP1R372Q and TAP2R373H) can specifically interfere with selective transport channels (i.e. for longer-peptides). These results provide a model for how viruses and cancer-associated mutations targeting TAP interfaces can affect MHC-I antigen presentation, and how the IFN-γ pathway alters MHC-I antigen presentation via the kinetics of peptide transport

A phylogenetic study of covid-19 data from Aragon and Catalonia over a year: learning bioinformatics during a world pandemic

Presentamos aquí un análisis de variabilidad durante un año del virus SARS-CoV-2 en el área de Aragón, comparándolo con la vecina Cataluña y centrándonos en la variante del Reino Unido. La investigación se realizó dentro de un curso de Bioinformática. Se extrajeron tanto una evaluación detallada sobre el valor de esta metodología como conclusiones novedosas de la investigación

Emergent Role of IFITM1/3 towards Splicing Factor (SRSF1) and Antigen-Presenting Molecule (HLA-B) in Cervical Cancer

The IFITM restriction factors play a role in cancer cell progression through undefined mechanisms. We investigate new protein–protein interactions for IFITM1/3 in the context of cancer that would shed some light on how IFITM1/3 attenuate the expression of targeted proteins such as HLA-B. SBP-tagged IFITM1 protein was used to identify an association of IFITM1 protein with the SRSF1 splicing factor and transporter of mRNA to the ribosome. Using in situ proximity ligation assays, we confirmed a predominant cytosolic protein–protein association for SRSF1 and IFITM1/3. Accordingly, IFITM1/3 interacted with HLA-B mRNA in response to IFNγ stimulation using RNA–protein proximity ligation assays. In addition, RT-qPCR assays in IFITM1/IFITM3 null cells and wt-SiHa cells indicated that HLA-B gene expression at the mRNA level does not account for lowered HLA-B protein synthesis in response to IFNγ. Complementary, shotgun RNA sequencing did not show major transcript differences between IFITM1/IFITM3 null cells and wt-SiHa cells. Furthermore, ribosome profiling using sucrose gradient sedimentation identified a reduction in 80S ribosomal fraction an IFITM1/IFITM3 null cells compared to wild type. It was partially reverted by IFITM1/3 complementation. Our data link IFITM1/3 proteins to HLA-B mRNA and SRSF1 and, all together, our results begin to elucidate how IFITM1/3 catalyze the synthesis of target proteins. IFITMs are widely studied for their role in inhibiting viruses, and multiple studies have associated IFITMs with cancer progression. Our study has identified new proteins associated with IFITMs which support their role in mediating protein expression; a pivotal function that is highly relevant for viral infection and cancer progression. Our results suggest that IFITM1/3 affect the expression of targeted proteins; among them, we identified HLA-B. Changes in HLA-B expression could impact the presentation and recognition of oncogenic antigens on the cell surface by cytotoxic T cells and, ultimately, limit tumor cell eradication. In addition, the role of IFITMs in mediating protein abundance is relevant, as it has the potential for regulating the expression of viral and oncogenic proteins

Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site

An important stage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) life cycle is the binding of the spike (S) protein to the angiotensin converting enzyme-2 (ACE2) host cell receptor. Therefore, to explore conserved features in spike protein dynamics and to identify potentially novel regions for drugging, we measured spike protein variability derived from 791 viral genomes and studied its properties by molecular dynamics (MD) simulation. The findings indicated that S2 subunit (heptad-repeat 1 (HR1), central helix (CH), and connector domain (CD) domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the receptor binding domain (RBD) domain, which is typically targeted in drug discovery programs, exhibits more sequence variability and flexibility. Interpretations from MD simulations suggest that the monomer form of spike protein is in constant motion showing transitions between an “up” and “down” state. In addition, the trimer cavity may function as a “bouncing spring” that may facilitate the homotrimer spike protein interactions with the ACE2 receptor. The feasibility of the trimer cavity as a potential drug target was examined by structure based virtual screening. Several hits were identified that have already been validated or suggested to inhibit the SARS-CoV-2 virus in published cell models. In particular, the data suggest an action mechanism for molecules including Chitosan and macrolides such as the mTOR (mammalian target of Rapamycin) pathway inhibitor Rapamycin. These findings identify a novel small molecule binding-site formed by the spike protein oligomer, that might assist in future drug discovery programs aimed at targeting the coronavirus (CoV) family of viruses

Identification Of Actionable Genetic Targets In Primary Cardiac Sarcomas

Background: Primary cardiac tumors are extremely rare; most are myxomas with a benign prognosis. However, primary sarcomas are highly aggressive and treatment options are limited. Radical surgery is often not feasible and conventional therapies provide only modest results. Due to the rare nature of primary cardiac tumors, there are no proper randomized studies to guide treatment. Their complexity requires alternative approaches in order to improve treatment efficacy. Methods: We isolated DNA from 5 primary cardiac sarcomas; the quality of DNA from 3 of them was sufficient to perform high-resolution single nucleotide polymorphism (SNP) array analysis. Results: In the present study, molecular karyotyping revealed numerous segmental chromosomal alterations and amplifications affecting actionable genes that may be involved in disease initiation and/or progression. These include chromosomal break flanking AKT2 in undifferentiated pleomorphic rhabdomyosarcoma, chromosomal break in promoter of TERT, and gain of CDK4 and amplification of MDM2 in inflammatory myofibroblastic tumor. We detected segmental break flanking MOS in high-grade myxofibrosarcoma. In addition, the high number of chromosomal aberrations in high-grade myxofibrosarcoma may cause multiple tumor-specific epitopes, supporting the study of immunotherapy treatment in this type of aggressive tumor. Conclusion: Our results provide a genetic rationale that supports an alternative, personalized therapeutic management of primary cardiac sarcomas

Gorham-Stout case report: a multi-omic analysis reveals recurrent fusions as new potential drivers of the disease

BACKGROUND: Gorham-Stout disease is a rare condition characterized by vascular proliferation and the massive destruction of bone tissue. With less than 400 cases in the literature of Gorham-Stout syndrome, we performed a unique study combining whole-genome sequencing and RNA-Seq to probe the genomic features and differentially expressed pathways of a presented case, revealing new possible drivers and biomarkers of the disease. CASE PRESENTATION: We present a case report of a white 45-year-old female patient with marked bone loss of the left humerus associated with vascular proliferation, diagnosed with Gorham-Stout disease. The analysis of whole-genome sequencing showed a dominance of large structural DNA rearrangements. Particularly, rearrangements in chromosomes seven, twelve, and twenty could contribute to the development of the disease, especially a gene fusion involving ATG101 that could affect macroautophagy. The study of RNA-sequencing data from the patient uncovered the PI3K/AKT/mTOR pathway as the most affected signaling cascade in the Gorham-Stout lesional tissue. Furthermore, M2 macrophage infiltration was detected using immunohistochemical staining and confirmed by deconvolution of the RNA-seq expression data. CONCLUSIONS: The way that DNA and RNA aberrations lead to Gorham-Stout disease is poorly understood due to the limited number of studies focusing on this rare disease. Our study provides the first glimpse into this facet of the disease, exposing new possible therapeutic targets and facilitating the clinicopathological diagnosis of Gorham-Stout disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-022-01277-x

A phylogenetic study of covid-19 data from Aragon and Catalonia over a year: learning Bioinformatics during a world pandemic

We present here a one year variability analysis of SARS-CoV-2 virus in the Aragon area, comparing it to neighboring Catalonia and focusing on the UK-variant. Research was performed within a Bioinformatics course. Both a detailed assessment on the value of this methodology and novel research conclusions were extracted.Presentamos aquí un análisis de variabilidad durante un año del virus SARS-CoV-2 en el área de Aragón, comparándolo con la vecina Cataluña y centrándonos en la variante del Reino Unido. La investigación se realizó dentro de un curso de Bioinformática. Se extrajeron tanto una evaluación detallada sobre el valor de esta metodología como conclusiones novedosas de la investigación