Co-option of Neutrophil Fates by Tissue Environments.

Classically considered short-lived and purely defensive leukocytes, neutrophils are unique in their fast and moldable response to stimulation. This plastic behavior may underlie variable and even antagonistic functions during inflammation or cancer, yet the full spectrum of neutrophil properties as they enter healthy tissues remains unexplored. Using a new model to track neutrophil fates, we found short but variable lifetimes across multiple tissues. Through analysis of the receptor, transcriptional, and chromatin accessibility landscapes, we identify varying neutrophil states and assign non-canonical functions, including vascular repair and hematopoietic homeostasis. Accordingly, depletion of neutrophils compromised angiogenesis during early age, genotoxic injury, and viral infection, and impaired hematopoietic recovery after irradiation. Neutrophils acquired these properties in target tissues, a process that, in the lungs, occurred in CXCL12-rich areas and relied on CXCR4. Our results reveal that tissues co-opt neutrophils en route for elimination to induce programs that support their physiological demands.This study was supported byIntramural grants from the Severo Ochoa program (IGP-SO), a grant from Fundacio la Marato de TV3 (120/C/2015-20153032), grant SAF2015-65607-R fromMinisterio de Ciencia e Innovacion (MICINN) with co-funding by Fondo Eu-ropeo de Desarrollo Regional (FEDER), RTI2018-095497-B-I00 from MICINN,HR17_00527 from Fundacion La Caixa, and Transatlantic Network of Excel-lence (TNE-18CVD04) from the Leducq Foundation to A.H. I.B. is supportedby fellowship MSCA-IF-EF-748381 and EMBO short-term fellowship 8261.A.R.-P. is supported by a fellowship (BES-2016-076635) and J.A.N.-A. byfellowship SVP-2014-068595 from MICINN. R.O. is supported by ERC startinggrant 759532, Italian Telethon Foundation SR-Tiget grant award F04, ItalianMoH grant GR-201602362156, AIRC MFAG 20247, Cariplo Foundation grant2015-0990, and the EU Infect-ERA 126. C.S. is supported by the SFB 1123,project A07, as well as by the DZHK (German Centre for Cardiovascular Research) and the BMBF (German Ministry of Education and Research) grant81Z0600204. L.G.N. is supported by SIgN core funding from A*STAR. The CNIC is supported by the MICINN and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MICINN award SEV-2015-0505). G.F.-C. issupported by the Spanish Ministerio de Ciencia e Innovacio ́n (grantPID2019-110895RB-100) and Junta de Comunidades de Castilla-La Mancha(grant SBPLY/19/180501/000211). C.R. received funding from the BoehingerIngelheim Foundation (consortium grant ‘‘Novel and Neglected CardiovascularRisk Factors’’) and German Federal Ministry of Education and Research(BMBF 01EO1503) and is a Fellow of the Gutenberg Research College (GFK)at the Johannes Gutenberg-University MainzS

The BioMart community portal: an innovative alternative to large, centralized data repositories.

The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations

Ving-cinq ans après

En mai 2016, un colloque international était l’occasion de célébrer, à l’École française de Rome, le XXVe anniversaire de la parution de l’Histoire des femmes en Occident et le XXe anniversaire de la publication de la Storia delle donne in Italia, deux entreprises collectives dont l’éditeur italien Laterza avait été à l’origine. Le livre collectif issu de cette rencontre revient sur la genèse de ces ouvrages pionniers, leur réception et la solidité des acquis historiographiques dont ils sont le fruit en donnant tout d’abord la parole à Michelle Perrot et à quelques-unes des éditrices d’alors ; il s’efforce ensuite de rendre compte de l’extraordinaire évolution d’un champ d’études qui s’est enrichi en suivant les parcours déjà balisés par ces œuvres majeures, mais également en empruntant des directions plus inattendues. Plus de vingt éminent-e-s spécialistes font ainsi le point sur les thématiques les plus significatives qui, de nos jours, sont au cœur des questionnements de l’histoire des femmes et du genre, inscrite désormais dans une dimension globale : circulations, migrations et métissages, lois et droits, identités personnelles, familles et masculinités, économies et cultures matérielles

A multinational consensus on dysphagia in Parkinson's disease:screening, diagnosis and prognostic value

Background: Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD. Objective: To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients. Methods: A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. Results: Eighty-five papers were used to inform the Panel\u2019s statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions. Conclusions: The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD

IL-1β+ macrophages fuel pathogenic inflammation in pancreatic cancer

: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with high resistance to therapies1. Inflammatory and immunomodulatory signals co-exist in the pancreatic tumour microenvironment, leading to dysregulated repair and cytotoxic responses. Tumour-associated macrophages (TAMs) have key roles in PDAC2, but their diversity has prevented therapeutic exploitation. Here we combined single-cell and spatial genomics with functional experiments to unravel macrophage functions in pancreatic cancer. We uncovered an inflammatory loop between tumour cells and interleukin-1β (IL-1β)-expressing TAMs, a subset of macrophages elicited by a local synergy between prostaglandin E2 (PGE2) and tumour necrosis factor (TNF). Physical proximity with IL-1β+ TAMs was associated with inflammatory reprogramming and acquisition of pathogenic properties by a subset of PDAC cells. This occurrence was an early event in pancreatic tumorigenesis and led to persistent transcriptional changes associated with disease progression and poor outcomes for patients. Blocking PGE2 or IL-1β activity elicited TAM reprogramming and antagonized tumour cell-intrinsic and -extrinsic inflammation, leading to PDAC control in vivo. Targeting the PGE2-IL-1β axis may enable preventive or therapeutic strategies for reprogramming of immune dynamics in pancreatic cancer

Consensus on the treatment of dysphagia in Parkinson's disease

Background: Dysphagia is common in Parkinson's disease (PD). The effects of antiparkinsonian drugs on dysphagia are controversial. Several treatments for dysphagia are available but there is no consensus on their efficacy in PD. Objective: To conduct a systematic review of the literature and to define consensus statements on the treatment of dysphagia in PD and related nutritional management. Methods: A multinational group of experts in the field of neurogenic dysphagia and/or Parkinson's disease conducted a systematic evaluation of the literature and reported the results according to PRISMA guidelines. The evidence from the retrieved studies was analyzed and discussed in a consensus conference organized in Pavia, Italy, and the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. Results: The literature review retrieved 64 papers on treatment and nutrition of patients with PD and dysphagia, mainly of Class IV quality. Based on the literature and expert opinion in cases where the evidence was limited or lacking, 26 statements were developed. Conclusions: The statements developed by the Consensus panel provide a guidance for a multi-disciplinary treatment of dysphagia in patients with PD, involving neurologists, otorhinolaryngologists, gastroenterologists, phoniatricians, speech-language pathologists, dieticians, and clinical nutritionists