Mechanisms of stretch-mediated skin expansion at single-cell resolution.

The ability of the skin to grow in response to stretching has been exploited in reconstructive surgery1. Although the response of epidermal cells to stretching has been studied in vitro2,3, it remains unclear how mechanical forces affect their behaviour in vivo. Here we develop a mouse model in which the consequences of stretching on skin epidermis can be studied at single-cell resolution. Using a multidisciplinary approach that combines clonal analysis with quantitative modelling and single-cell RNA sequencing, we show that stretching induces skin expansion by creating a transient bias in the renewal activity of epidermal stem cells, while a second subpopulation of basal progenitors remains committed to differentiation. Transcriptional and chromatin profiling identifies how cell states and gene-regulatory networks are modulated by stretching. Using pharmacological inhibitors and mouse mutants, we define the step-by-step mechanisms that control stretch-mediated tissue expansion at single-cell resolution in vivo.Wellcome Trust Royal Societ

Linear and Branched Glyco-Lipopeptide Vaccines Follow Distinct Cross-Presentation Pathways and Generate Different Magnitudes of Antitumor Immunity

Glyco-lipopeptides, a form of lipid-tailed glyco-peptide, are currently under intense investigation as B- and T-cell based vaccine immunotherapy for many cancers. However, the cellular and molecular mechanisms of glyco-lipopeptides (GLPs) immunogenicity and the position of the lipid moiety on immunogenicity and protective efficacy of GLPs remain to be determined.We have constructed two structural analogues of HER-2 glyco-lipopeptide (HER-GLP) by synthesizing a chimeric peptide made of one universal CD4(+) epitope (PADRE) and one HER-2 CD8(+) T-cell epitope (HER(420-429)). The C-terminal end of the resulting CD4-CD8 chimeric peptide was coupled to a tumor carbohydrate B-cell epitope, based on a regioselectively addressable functionalized templates (RAFT), made of four alpha-GalNAc molecules. The resulting HER glyco-peptide (HER-GP) was then linked to a palmitic acid moiety, attached either at the N-terminal end (linear HER-GLP-1) or in the middle between the CD4+ and CD8+ T cell epitopes (branched HER-GLP-2). We have investigated the uptake, processing and cross-presentation pathways of the two HER-GLP vaccine constructs, and assessed whether the position of linkage of the lipid moiety would affect the B- and T-cell immunogenicity and protective efficacy. Immunization of mice revealed that the linear HER-GLP-1 induced a stronger and longer lasting HER(420-429)-specific IFN-gamma producing CD8(+) T cell response, while the branched HER-GLP-2 induced a stronger tumor-specific IgG response. The linear HER-GLP-1 was taken up easily by dendritic cells (DCs), induced stronger DCs maturation and produced a potent TLR- 2-dependent T-cell activation. The linear and branched HER-GLP molecules appeared to follow two different cross-presentation pathways. While regression of established tumors was induced by both linear HER-GLP-1 and branched HER-GLP-2, the inhibition of tumor growth was significantly higher in HER-GLP-1 immunized mice (p<0.005).These findings have important implications for the development of effective GLP based immunotherapeutic strategies against cancers

Tools for comprehensive evaluation of sexual function in patients with multiple sclerosis

Introduction: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that affects young adults, causing a variety of symptoms (motor alterations, visual alterations, loss of sphincter control, gait alterations) that impair the patient’s functional status. However, other symptoms, such as sexual dysfunction, can also have an effect on quality of life. Development: Sexual dysfunction can occur at any time during the course of the disease; its prevalence varies between 50% and 90%, and it can be secondary to demyelinating lesions in the spinal cord and/or brain or caused by symptoms that do not directly involve the nervous system (fatigue; psychological, social, and cultural factors; etc.). Although its prevalence and impact on quality of life are well known, sexual dysfunction is still frequently underestimated. Therefore, in this article we review the different scales for assessing presence or severity of sexual dysfunction, in order to offer early multidisciplinary management. Conclusion: We evaluated 5 questionnaires that could identify the presence of sexual dysfunction in patients with MS and determine its aetiology, assisting in treatment decision making. MS must be understood as a complex disease that encompasses and compromises different aspects of patients’ health, and goes beyond simply measuring disability. Resumen: Introducción: La esclerosis múltiple (EM) es una enfermedad desmielinizante del sistema nervioso central (SNC) que afecta a adultos jóvenes, ocasionando una variedad de síntomas (motores, visuales, control de esfínteres, alteraciones de la marcha) que impactan la funcionalidad del paciente; sin embargo, otros síntomas, como la disfunción sexual (DS), también pueden tener un efecto sobre la calidad de vida. Desarrollo: La DS puede presentarse en cualquier momento del curso de la enfermedad, su prevalencia varía entre 50 y 90%, puede ser secundaria a lesiones desmielinizantes en médula espinal y/o cerebro, ocasionada por síntomas que no incluyen directamente el sistema nervioso —fatiga, aspectos psicológicos, sociales y culturales—. Si bien se ha logrado establecer su prevalencia y su impacto sobre la calidad de vida, la DS todavía es una condición frecuentemente subestimada, razón por la cual en este artículo se revisan las diferentes escalas que ayudan a evaluar la presencia o la severidad de esta para dar un manejo multidisciplinario temprano, según corresponda. Conclusión: Cinco cuestionarios han sido evaluados y/o dise˜nados para pacientes con EM, los cuales podrían identificar la presencia de DS, su etiología y, con esto, determinar posibilidades de tratamiento. La EM debe ser comprendida como una enfermedad compleja que abarca y compromete diferentes aspectos de la salud de los pacientes, y va más allá de solo medir escalas de discapacidad

Stretch exercises for stem cells expand the skin

Responses of epidermal stem cells to stretch in a living organism. Stretching the skin of mice reveals that mechanical strain is communicated by a subpopulation of stem cells that proliferate and promote mechanical resistance, and so generate extra skin

El CoLaboratorio de la Oceanografía Social: Espacio Plural para la Conservación Integral de los Mares y las Sociedades Costera

Este ensayo revisa los alcances de la oceanografía social tal como fue presentada y discutida en la Primera Reunión de Oceanografía Social organizada en el Centro de Estudios en Geografía Humana de El Colegio de Michoacán en septiembre de 2017. La oceanografía social es un campo innovador e híbrido de estudio, situado en el umbral entre las ciencias naturales y sociales que abarca el estudio de las relaciones e interacciones de las sociedades humanas, presentes y pasadas, con el ambiente costero/marino. Dividimos el ensayo en dos secciones. Primero, describimos crono-lógicamente el surgimiento y evolución de la disciplina, así como un panorama contemporáneo del quehacer del oceanógrafo social y la imperante necesidad de expandir esta aproximación a todas las esferas de los estudios marinos. Finalmente, ofrecemos una síntesis de las fortalezas y retos que ofrece la oceanografía social y de cómo nos proponemos enfrentarlos a partir de la formación de un CoLaboratorio. Abstract This essay reviews the scope and aims of Social Oceanography as presented and discussed at the First Social Oceanography Meeting held at the Center for Human Geography Studies of El Colegio de Michoacán in September 2017. Social Oceanography is a hybrid field of study at the interface between the natural and social sciences focused on understanding the relationships and interactions of past and present human societies, and the coastal/marine environment. We present our argument in three sections. First, we describe the chronological development and evolution of the discipline. Second, we offer a contemporary overview of the sphere of action of social oceanogra-phers and the pressing need to extend this approach to all spheres of marine studies. Lastly, we summarize the strengths and challenges of Social Oceanography and the ways we will deal with them through the creation of a CoLaboratory