Evidence for vibration coding of sliding tactile textures in auditory cortex

Introduction: Psychophysical studies suggest texture perception is mediated by spatial and vibration codes (duplex theory). Vibration coding, driven by relative motion between digit and stimulus, is involved in the perception of very fine gratings whereas coarse texture perception depends more on spatial coding, which does not require relative motion.Methods: We examined cortical activation, using functional Magnetic Resonance Imaging associated with fine and coarse tactile spatial gratings applied by sliding or touching (sliding vs. static contact) on the index finger pad.Results: We found regions, contralateral to the stimulated digit, in BA1 in S1, OP1, OP3, and OP4 in S2, and in auditory cortex, which were significantly more activated by sliding gratings but did not find this pattern in visual cortex. Regions in brain areas activated by vibrotactile stimuli (including auditory cortex) were also modulated by whether or not the gratings moved. In a control study we showed that this contrast persisted when the salience of the static condition was increased by using a double touch.Discussion: These findings suggest that vibration from sliding touch invokes multisensory cortical mechanisms in tactile processing of roughness. However, we did not find evidence of a separate visual region activated by static touch nor was there a dissociation between cortical response to fine vs. coarse gratings as might have been expected from duplex theory

Effects of physical activity on functional health of older adults: a systematic review

Reviews on the relationships between functional health and physical activity of general older adults have been well documented in literature. However, specific age range of older adults, in particular, older adults of 75 years or above, is currently under-examined. A systematic review was conducted to investigate the effects of physical activity on functional health older adults aged 75 years or above. The reviewed articles cover a variety range of functional health outcomes, including balance, muscle conditioning, joint range of motion, quadriceps strength, reaction time, gait speed, health-related quality of life, back and knee pain, muscle mass, and walking ability. In general, interventions of the reviewed articles had favourable effects on function health of older adults. While physical activity has been identified as an important determinant of functional health, the ways to engage in and accumulate sufficient daily physical activity warrant investigation. It is also important to explore interventions which enhance daily, self-driven physical activity of elderly, as normally supervised physical activity bears higher costs

The 3D Morphology of VY Canis Majoris. I The Kinematics of the Ejecta

Images of the complex circumstellar nebula associated with the famous red supergiant VY CMa show evidence for multiple and asymmetric mass loss events over the past 1000 yrs. Doppler velocities of the arcs and knots in the ejecta showed that they are not only spatially distinct but also kinematically separate from the surrounding diffuse material. In this paper we describe second epoch HST/WFPC2 images to measure the transverse motions which when combined with the radial motions provide a complete picture of the kinematics of the ejecta including the total space motions and directions of the outflows. Our results show that the arcs and clumps of knots are moving at different velocities, in different directions, and at different angles relative to the plane of the sky and to the star, confirming their origin from eruptions at different times and from physically separate regions on the star. We conclude that the morphology and kinematics of the arcs and knots are consistent with a history of mass ejections not aligned with any presumed axis of symmetry. The arcs and clumps represent relatively massive outflows and ejections of gas very likely associated with large -- scale convective activity and magnetic fields.Comment: 20 pages, 10 figures, 5 table

Antibody targeting of Cathepsin S induces antibody-dependent cellular cytotoxicity

<p>Abstract</p> <p>Background</p> <p>Proteolytic enzymes have been implicated in driving tumor progression by means of their cancer cell microenvironment activity where they promote proliferation, differentiation, apoptosis, migration, and invasion. Therapeutic strategies have focused on attenuating their activity using small molecule inhibitors, but the association of proteases with the cell surface during cancer progression opens up the possibility of targeting these using antibody dependent cellular cytotoxicity (ADCC). Cathepsin S is a lysosomal cysteine protease that promotes the growth and invasion of tumour and endothelial cells during cancer progression. Our analysis of colorectal cancer patient biopsies shows that cathepsin S associates with the cell membrane indicating a potential for ADCC targeting.</p> <p>Results</p> <p>Here we report the cell surface characterization of cathepsin S and the development of a humanized antibody (Fsn0503h) with immune effector function and a stable <it>in vivo </it>half-life of 274 hours. Cathepsin S is expressed on the surface of tumor cells representative of colorectal and pancreatic cancer (23%-79% positive expression). Furthermore the binding of Fsn0503h to surface associated cathepsin S results in natural killer (NK) cell targeted tumor killing. In a colorectal cancer model Fsn0503h elicits a 22% cytotoxic effect.</p> <p>Conclusions</p> <p>This data highlights the potential to target cell surface associated enzymes, such as cathepsin S, as therapeutic targets using antibodies capable of elicitingADCC in tumor cells.</p

How immunological profle drives clinical phenotype of primary Sjögren’s syndrome at diagnosis: analysis of 10,500 patients (Sjögren Big Data Project)

To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjögren´s syndrome (SjS).METHODS:The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays.RESULTS:By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti- La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglo-bulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for cryoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESS- DAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).CONCLUSIONS:We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.Fil: Brito Zerón, Pilar. Hospital Sanitas CIMA; España. Universidad de Barcelona; EspañaFil: Acar Denizli, Nihan. Mimar Sinan Fine Arts University; TurquíaFil: Ng, Wan Fai. University of Newcastle; Reino UnidoFil: Zeher, Margit. University of Debrecen; HungríaFil: Rasmussen, Astrid. Oklahoma Medical Research Foundation; Estados UnidosFil: Mandl, Thomas. Lund University; SueciaFil: Seror, Raphaele. Université Paris Sud; FranciaFil: Xiaolin, Li. Anhui Provincial Hospital; ChinaFil: Baldini, Chiara. Università degli Studi di Pisa; ItaliaFil: Gottenberg, Jaques. Université de Strasbourg; Francia. Centre National de la Recherche Scientifique; FranciaFil: Danda, Debashish. Christian Medical College & Hospital; IndiaFil: Quartuccio, Luca. University Hospital “Santa María della Misericordia”; ItaliaFil: Priori, Roberta. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Hernandez Molina, Gabriela. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; MéxicoFil: Armagan, Berkan. Hacettepe University. Faculty of Medicine.Department of Internal Medicine; TurquíaFil: Kruize, Aike. University Medical Center Utrecht; Países BajosFil: Kwok, Seung Ki. The Catholic University of Korea; Corea del SurFil: Kvarnström, Marika. Karolinska University Hospital.Department of Medicine.Unit of Rheumatology. Karolinska Institutet ; SueciaFil: Praprotnik, Sonja. University Medical Centre; EsloveniaFil: Sene, Damien. Université Paris Diderot - Paris 7; FranciaFil: Bartoloni, Elena. Università di Perugia; ItaliaFil: Solans, R.. Hospital Vall d’Hebron; ItaliaFil: Rischmueller, M.. University of Western Australia; AustraliaFil: Suzuki, Y.. Kanazawa University Hospital; JapónFil: Isenberg, D. A.. University College London; Estados UnidosFil: Valim, V.. Federal University of Espírito Santo; BrasilFil: Wiland, P.. Wroclaw Medical Hospital; PoloniaFil: Nordmark, G.. Uppsala Universitet; SueciaFil: Fraile, G.. Hospital Ramón y Cajal; EspañaFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Hospital Privado Centro Medico de Córdoba; Argentina; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment