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https://read.qxmd.com/read/30771072/a-process-account-of-the-uncontrolled-manifold-structure-of-joint-space-variance-in-pointing-movements
#1
Valère Martin, Hendrik Reimann, Gregor Schöner
In many situations, the human movement system has more degrees of freedom than needed to achieve a given movement task. Martin et al. (Neural Comput 21(5):1371-1414, 2009) accounted for signatures of such redundancy like self-motion and motor equivalence in a process model in which a neural oscillator generated timed end-effector virtual trajectories that a neural dynamics transformed into joint virtual trajectories while decoupling task-relevant and task-irrelevant combinations of joint angles. Neural control of muscle activation and the biomechanical dynamics of the arm were taken into account...
February 15, 2019: Biological Cybernetics
https://read.qxmd.com/read/30770379/multiple-supporting-cell-subtypes-are-capable-of-spontaneous-hair-cell-regeneration-in-the-neonatal-mouse-cochlea
#2
Melissa M McGovern, Michelle R Randle, Candice L Cuppini, Kaley A Graves, Brandon C Cox
Supporting cells (SCs) are known to spontaneously regenerate hair cells (HCs) in the neonatal mouse cochlea, yet little is known about the relative contribution of distinct SC subtypes which differ in morphology and function. We have previously shown that HC regeneration is linked to Notch signaling, and some SC subtypes, but not others, lose expression of the Notch effector Hes5 Other work has demonstrated that Lgr5-positive SCs have an increased capacity to regenerate HCs; however, several SC subtypes express Lgr5...
February 15, 2019: Development
https://read.qxmd.com/read/30770246/human-fetal-tnf-%C3%AE-cytokine-producing-cd4-effector-memory-t-cells-promote-intestinal-development-and-mediate-inflammation-early-in-life
#3
Renée R C E Schreurs, Martin E Baumdick, Adrian F Sagebiel, Max Kaufmann, Michal Mokry, Paul L Klarenbeek, Nicola Schaltenberg, Fenja L Steinert, Jorik M van Rijn, Agata Drewniak, Sarah-May M L The, Roel Bakx, Joep P M Derikx, Niek de Vries, Willemijn E Corpeleijn, Steven T Pals, Nicola Gagliani, Manuel A Friese, Sabine Middendorp, Edward E S Nieuwenhuis, Konrad Reinshagen, Teunis B H Geijtenbeek, Johannes B van Goudoever, Madeleine J Bunders
Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α)+ CD4+ CD69+ T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4+ T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dose-dependent, TNF-α-mediated effect of fetal intestinal CD4+ T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation...
February 5, 2019: Immunity
https://read.qxmd.com/read/30769145/directional-tuning-for-eye-and-arm-movements-in-overlapping-regions-in-human-posterior-parietal-cortex
#4
Caterina Magri, Sara Fabbri, Alfonso Caramazza, Angelika Lingnau
A network of frontal and parietal regions is known to be recruited during the planning and execution of arm and eye movements. While movements of the two effectors are typically coupled with each other, it remains unresolved how information is shared between them. Here we aimed to identify regions containing neuronal populations that show directional tuning for both arm and eye movements. In two separate fMRI experiments, the same participants were scanned while performing a center-out arm or eye movement task...
February 12, 2019: NeuroImage
https://read.qxmd.com/read/30764544/early-pregnancy-human-decidua-is-enriched-with-activated-fully-differentiated-and-pro-inflammatory-gamma-delta-t-cells-with-diverse-tcr-repertoires
#5
Antonia Terzieva, Violeta Dimitrova, Lyubomir Djerov, Petya Dimitrova, Silvina Zapryanova, Iana Hristova, Ivaylo Vangelov, Tanya Dimova
Pregnancy is a state where high and stage-dependent plasticity of the maternal immune system is necessary in order to equilibrate between immunosuppression of harmful responses towards the fetus and ability to fight infections. TCR γδ cells have been implicated in the responses in infectious diseases, in the regulation of immune responses, and in tissue homeostasis and repair. The variety of functions makes γδ T cells a particularly interesting population during pregnancy. In this study, we investigated the proportion, phenotype and TCR γ and δ repertoires of γδ T cells at the maternal⁻fetal interface and in the blood of pregnant women using FACS, immunohistochemistry and spectratyping...
February 5, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30764482/inflammation-and-pancreatic-cancer-focus-on-metabolism-cytokines-and-immunity
#6
REVIEW
Andrea Padoan, Mario Plebani, Daniela Basso
Systemic and local chronic inflammation might enhance the risk of pancreatic ductal adenocarcinoma (PDAC), and PDAC-associated inflammatory infiltrate in the tumor microenvironment concurs in enhancing tumor growth and metastasis. Inflammation is closely correlated with immunity, the same immune cell populations contributing to both inflammation and immune response. In the PDAC microenvironment, the inflammatory cell infiltrate is unbalanced towards an immunosuppressive phenotype, with a prevalence of myeloid derived suppressor cells (MDSC), M2 polarized macrophages, and Treg , over M1 macrophages, dendritic cells, and effector CD4⁺ and CD8⁺ T lymphocytes...
February 5, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30763319/bmp-signaling-is-required-for-nkx2-3-positive-pharyngeal-pouch-progenitor-specification-in-zebrafish
#7
Linwei Li, Guozhu Ning, Shuyan Yang, Yifang Yan, Yu Cao, Qiang Wang
Pharyngeal pouches, a series of outpocketings that bud from the foregut endoderm, are essential to the formation of craniofacial skeleton as well as several important structures like parathyroid and thymus. However, whether pharyngeal pouch progenitors exist in the developing gut tube remains unknown. Here, taking advantage of cell lineage tracing and transgenic ablation technologies, we identified a population of nkx2.3+ pouch progenitors in zebrafish embryos and demonstrated an essential requirement of ectodermal BMP2b for their specification...
February 14, 2019: PLoS Genetics
https://read.qxmd.com/read/30760779/age-dependent-differences-in-learning-to-control-a-robot-arm-using-a-body-machine-interface
#8
Rajiv Ranganathan, Mei-Hua Lee, Malavika R Padmanabhan, Sanders Aspelund, Florian A Kagerer, Ranjan Mukherjee
Body-machine interfaces, i.e. interfaces that rely on body movements to control external assistive devices, have been proposed as a safe and robust means of achieving movement and mobility; however, how children learn these novel interfaces is poorly understood. Here we characterized the learning of a body-machine interface in young unimpaired adults, two groups of typically developing children (9-year and 12-year olds), and one child with congenital limb deficiency. Participants had to control the end-effector of a robot arm in 2D using movements of the shoulder and torso...
February 13, 2019: Scientific Reports
https://read.qxmd.com/read/30759969/segmented-filamentous-bacteria-induce-divergent-populations-of-antigen-specific-cd4-t-cells-in-the-small-intestine
#9
Jaeu Yi, Jisun Jung, Daehee Han, Charles D Surh, You Jeong Lee
CD4 T cells differentiate into RORγt/IL-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naïve precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naïve CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization...
February 8, 2019: Molecules and Cells
https://read.qxmd.com/read/30755607/costimulation-of-type-2-innate-lymphoid-cells-by-gitr-promotes-effector-function-and-ameliorates-type-2-diabetes
#10
Lauriane Galle-Treger, Ishwarya Sankaranarayanan, Benjamin P Hurrell, Emily Howard, Richard Lo, Hadi Maazi, Gavin Lewis, Homayon Banie, Alan L Epstein, Peisheng Hu, Virender K Rehan, Frank D Gilliland, Hooman Allayee, Pejman Soroosh, Arlene H Sharpe, Omid Akbari
Metabolic syndrome is characterized by disturbances in glucose homeostasis and the development of low-grade systemic inflammation, which increase the risk to develop type 2 diabetes mellitus (T2DM). Type-2 innate lymphoid cells (ILC2s) are a recently discovered immune population secreting Th2 cytokines. While previous studies show how ILC2s can play a critical role in the regulation of metabolic homeostasis in the adipose tissue, a therapeutic target capable of modulating ILC2 activation has yet to be identified...
February 12, 2019: Nature Communications
https://read.qxmd.com/read/30753825/distinct-immune-cell-populations-define-response-to-anti-pd-1-monotherapy-and-anti-pd-1-anti-ctla-4-combined-therapy
#11
Tuba N Gide, Camelia Quek, Alexander M Menzies, Annie T Tasker, Ping Shang, Jeff Holst, Jason Madore, Su Yin Lim, Rebecca Velickovic, Matthew Wongchenko, Yibing Yan, Serigne Lo, Matteo S Carlino, Alexander Guminski, Robyn P M Saw, Angel Pang, Helen M McGuire, Umaimainthan Palendira, John F Thompson, Helen Rizos, Ines Pires da Silva, Marcel Batten, Richard A Scolyer, Georgina V Long, James S Wilmott
Cancer immunotherapies provide survival benefits in responding patients, but many patients fail to respond. Identifying the biology of treatment response and resistance are a priority to optimize drug selection and improve patient outcomes. We performed transcriptomic and immune profiling on 158 tumor biopsies from melanoma patients treated with anti-PD-1 monotherapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57). These data identified activated T cell signatures and T cell populations in responders to both treatments...
February 11, 2019: Cancer Cell
https://read.qxmd.com/read/30744042/intestinal-mucosal-mast-cells-key-modulators-of-barrier-function-and-homeostasis
#12
REVIEW
Mercé Albert-Bayo, Irene Paracuellos, Ana M González-Castro, Amanda Rodríguez-Urrutia, María J Rodríguez-Lagunas, Carmen Alonso-Cotoner, Javier Santos, María Vicario
The gastrointestinal tract harbours the largest population of mast cells in the body; this highly specialised leukocyte cell type is able to adapt its phenotype and function to the microenvironment in which it resides. Mast cells react to external and internal stimuli thanks to the variety of receptors they express, and carry out effector and regulatory tasks by means of the mediators of different natures they produce. Mast cells are fundamental elements of the intestinal barrier as they regulate epithelial function and integrity, modulate both innate and adaptive mucosal immunity, and maintain neuro-immune interactions, which are key to functioning of the gut...
February 8, 2019: Cells
https://read.qxmd.com/read/30741320/a-novel-variant-of-gh_d02g0276-is-required-for-root-knot-nematode-resistance-on-chromosome-14-d02-in-upland-cotton
#13
Martin J Wubben, Gregory N Thyssen, Franklin E Callahan, David D Fang, Dewayne D Deng, Jack C McCarty, Ping Li, Md Sariful Islam, Johnie N Jenkins
MAGIC population sequencing and virus-induced gene silencing identify Gh_D02G0276 as a novel root-knot nematode resistance gene on chromosome 14 in Upland cotton. The southern root-knot nematode [RKN; Meloidogyne incognita (Kofoid & White)] remains the primary yield-limiting biotic stress to Upland cotton (Gossypium hirsutum L.) throughout the southeastern USA. While useful genetic markers have been developed for two major RKN resistance loci on chromosomes 11 (A11) and 14 (D02), these markers are not completely effective because the causative genes have not been identified...
February 11, 2019: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://read.qxmd.com/read/30739161/igg-fc-receptors-evolutionary-considerations
#14
Stylianos Bournazos
Immunoglobulins (Ig), a critical component of the adaptive immune system, are present in all jawed vertebrates and through sophisticated diversification mechanisms are able to recognize antigens of almost infinite diversity. During mammalian evolution, IgG has emerged as the predominant Ig isotype that is elicited upon antigenic challenge, representing the most abundant isotype present in circulation. Along with the IgG molecule, a family of specialized receptors has evolved in mammalian species that specifically recognize the Fc domain of IgG...
February 10, 2019: Current Topics in Microbiology and Immunology
https://read.qxmd.com/read/30737409/lymphocyte-innateness-defined-by-transcriptional-states-reflects-a-balance-between-proliferation-and-effector-functions
#15
Maria Gutierrez-Arcelus, Nikola Teslovich, Alex R Mola, Rafael B Polidoro, Aparna Nathan, Hyun Kim, Susan Hannes, Kamil Slowikowski, Gerald F M Watts, Ilya Korsunsky, Michael B Brenner, Soumya Raychaudhuri, Patrick J Brennan
How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover a continuous 'innateness gradient', with adaptive T cells at one end, followed by MAIT, iNKT, γδ T and natural killer cells at the other end. Single-cell RNA-seq reveals four broad states of innateness, and heterogeneity within canonical innate and adaptive populations...
February 8, 2019: Nature Communications
https://read.qxmd.com/read/30737273/new-insights-into-lymphocyte-differentiation-and-aging-from-telomere-length-and-telomerase-activity-measurements
#16
Tinhinane Fali, Laura Papagno, Charles Bayard, Yanis Mouloud, Jacques Boddaert, Delphine Sauce, Victor Appay
αβ CD8+ , γδ, and NK lymphocytes are fundamental effector cells against viruses and tumors. These cells can be divided into multiple subsets according to their phenotype. Based on progressive telomere attrition from naive to late effector memory cells, human CD8+ T cell subsets have been positioned along a pathway of differentiation, which is also considered as a process of lymphocyte aging or senescence. A similar categorization has not been clearly established for γδ and NK cell populations. Moreover, the distinction between the aging of these populations due to cellular differentiation or due to the chronological age of the donor has not been formally considered...
February 8, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
https://read.qxmd.com/read/30737226/anti-baff-r-antibody-vay-736-demonstrates-promising-preclinical-activity-in-cll-and-enhances-effectiveness-of-ibrutinib
#17
Emily M McWilliams, Christopher R Lucas, Timothy Chen, Bonnie K Harrington, Ronni Wasmuth, Amanda Campbell, Kerry A Rogers, Carolyn M Cheney, Xiaokui Mo, Leslie A Andritsos, Farrukh T Awan, Jennifer Woyach, William E Carson, Jonathan Butchar, Susheela Tridandapani, Erin Hertlein, Carlos E Castro, Natarajan Muthusamy, John C Byrd
The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib has transformed chronic lymphocytic leukemia (CLL) therapy but requires continuous administration. These factors have spurred interest in combination treatments. Unlike with chemotherapy, CD20-directed antibody therapy has not improved the outcome of BTKi treatment. Whereas CD20 antigen density on CLL cells decreases during ibrutinib treatment, the B-cell activating factor (BAFF) and its receptor (BAFF-R) remain elevated. Furthermore, BAFF signaling via noncanonical NF-κB remains elevated with BTKi treatment...
February 12, 2019: Blood Advances
https://read.qxmd.com/read/30732586/the-genome-of-the-soybean-cyst-nematode-heterodera-glycines-reveals-complex-patterns-of-duplications-involved-in-the-evolution-of-parasitism-genes
#18
Rick Masonbrink, Tom R Maier, Usha Muppirala, Arun S Seetharam, Etienne Lord, Parijat S Juvale, Jeremy Schmutz, Nathan T Johnson, Dmitry Korkin, Melissa G Mitchum, Benjamin Mimee, Sebastian Eves-van den Akker, Matthew Hudson, Andrew J Severin, Thomas J Baum
BACKGROUND: Heterodera glycines, commonly referred to as the soybean cyst nematode (SCN), is an obligatory and sedentary plant parasite that causes over a billion-dollar yield loss to soybean production annually. Although there are genetic determinants that render soybean plants resistant to certain nematode genotypes, resistant soybean cultivars are increasingly ineffective because their multi-year usage has selected for virulent H. glycines populations. The parasitic success of H. glycines relies on the comprehensive re-engineering of an infection site into a syncytium, as well as the long-term suppression of host defense to ensure syncytial viability...
February 7, 2019: BMC Genomics
https://read.qxmd.com/read/30724014/proteomics-in-drug-development-the-dawn-of-a-new-era
#19
REVIEW
Maria Frantzi, Agnieszka Latosinska, Harald Mischak
Mass spectrometry offers the potential of acquiring high resolution data depicting the functional status of a group of healthy or disease individuals, according to the different conditions. As most of the drugs are currently targeting proteins, proteomics has a dual value, both in the discovery of new molecules as therapeutic targets, but also as a methodology to perform high throughput drug profiling. As there is an evident need for drugs to be improved in terms of efficacy, a mechanistic insight for downstream effectors can be valuable in order to predict side effects and resistance mechanisms...
February 5, 2019: Proteomics. Clinical Applications
https://read.qxmd.com/read/30719702/%C3%AE-1-integrin-is-essential-for-fascin-mediated-breast-cancer-stem-cell-function-and-disease-progression
#20
Rayanah Barnawi, Samiyah Al-Khaldi, Dilek Colak, Asma Tulbah, Taher Al-Tweigeri, Mohannad Fallatah, Dorota Monies, Hazem Ghebeh, Monther Al-Alwan
Breast cancer remains the second cause of tumor-related mortality in women worldwide mainly due to chemoresistance and metastasis. The chemoresistance and metastasis are attributed to a rare subpopulation with enriched stem-like characteristics, thus called Cancer Stem Cells (CSCs). We have previously reported aberrant expression of the actin-bundling protein (fascin) in breast cancer cells, which enhances their chemoresistance, metastasis and enriches CSC population. The intracellular mechanisms that link fascin with its downstream effectors are not fully elucidated...
February 4, 2019: International Journal of Cancer. Journal International du Cancer
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