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https://www.readbyqxmd.com/read/28088685/a-semi-interpenetrating-network-of-polyacrylamide-and-recombinant-basement-membrane-allows-pluripotent-cell-culture-in-a-soft-ligand-rich-microenvironment
#1
Andrew J Price, Eva Y Huang, Vittorio Sebastiano, Alexander R Dunn
The physical properties of the extracellular matrix play an essential role in guiding stem cell differentiation and tissue morphogenesis both in vivo and in vitro. Existing work to investigate the role of matrix mechanics in directing stem cell proliferation, self-renewal, and differentiation has been limited by the poor attachment and survival of human pluripotent cells cultured on soft matrices (Young's modulus E ≲ 1000 Pa). To address this limitation we developed a protocol for generating semi-interpenetrating networks of polyacrylamide and recombinant basement membrane...
December 9, 2016: Biomaterials
https://www.readbyqxmd.com/read/28088123/antibody-dependent-cellular-cytotoxicity-and-influenza-virus
#2
REVIEW
Hillary A Vanderven, Sinthujan Jegaskanda, Adam K Wheatley, Stephen J Kent
Antibodies are a key defence against influenza infection and disease, but neutralizing antibodies are often strain-specific and of limited utility against divergent or pandemic viruses. There is now considerable evidence that influenza-specific antibodies with Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can assist in the clearance of influenza infection in vitro and in animal models. Further, ADCC-mediating antibodies that recognize a broad array of influenza strains are common in humans, likely as a result of being regularly exposed to influenza infections...
January 11, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28087948/regulation-of-immunity-to-tuberculosis
#3
Susanna Brighenti, Diane J Ordway
Immunity against Mycobacterium tuberculosis requires a balance between adaptive immune responses to constrain bacterial replication and the prevention of potentially damaging immune activation. Regulatory T (Treg) cells express the transcription factor Foxp3+ and constitute an essential counterbalance of inflammatory Th1 responses and are required to maintain immune homeostasis. The first reports describing the presence of Foxp3-expressing CD4+ Treg cells in tuberculosis (TB) emerged in 2006. Different Treg cell subsets, most likely specialized for different tissues and microenvironments, have been shown to expand in both human TB and animal models of TB...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087941/interplay-between-myeloid-cells-and-humoral-innate-immunity
#4
Sébastien Jaillon, Eduardo Bonavita, Cecilia Garlanda, Alberto Mantovani
The innate immune system represents the first line of defense against pathogens and comprises both a cellular and a humoral arm. Fluid-phase pattern recognition molecules (PRMs), which include collectins, ficolins, and pentraxins, are key components of the humoral arm of innate immunity and are expressed by a variety of cells, including myeloid, epithelial, and endothelial cells, mainly in response to infectious and inflammatory conditions. Soluble PRMs share basic multifunctional properties including activation and regulation of the complement cascade, opsonization of pathogens and apoptotic cells, regulation of leukocyte extravasation, and fine-tuning of inflammation...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087939/dendritic-cells-in-the-immune-system-history-lineages-tissues-tolerance-and-immunity
#5
Jonathan M Austyn
The aim of this review is to provide a coherent framework for understanding dendritic cells (DCs). It has seven sections. The introduction provides an overview of the immune system and essential concepts, particularly for the nonspecialist reader. Next, the "History" section outlines the early evolution of ideas about DCs and highlights some sources of confusion that still exist today. The "Lineages" section then focuses on five different populations of DCs: two subsets of "classical" DCs, plasmacytoid DCs, monocyte-derived DCs, and Langerhans cells...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087938/the-role-and-function-of-fc%C3%AE-receptors-on-myeloid-cells
#6
Stylianos Bournazos, Taia T Wang, Jeffrey V Ravetch
A key determinant for the survival of organisms is their capacity to recognize and respond efficiently to foreign antigens. This is largely accomplished by the orchestrated activity of the innate and adaptive branches of the immune system. Antibodies are specifically generated in response to foreign antigens, facilitating thereby the specific recognition of antigens of almost infinite diversity. Receptors specific for the Fc domain of antibodies, Fc receptors, are expressed on the surface of the various myeloid leukocyte populations and mediate the binding and recognition of antibodies by innate leukocytes...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087931/evolution-of-cell-autonomous-effector-mechanisms-in-macrophages-versus-non-immune-cells
#7
Ryan G Gaudet, Clinton J Bradfield, John D MacMicking
Specialized adaptations for killing microbes are synonymous with phagocytic cells including macrophages, monocytes, inflammatory neutrophils, and eosinophils. Recent genome sequencing of extant species, however, reveals that analogous antimicrobial machineries exist in certain non-immune cells and also within species that ostensibly lack a well-defined immune system. Here we probe the evolutionary record for clues about the ancient and diverse phylogenetic origins of macrophage killing mechanisms and how some of their properties are shared with cells outside the traditional bounds of immunity in higher vertebrates such as mammals...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087929/fungal-plant-pathogenesis-mediated-by-effectors
#8
Pierre J G M De Wit, Alison C Testa, Richard P Oliver
The interactions between fungi and plants encompass a spectrum of ecologies ranging from saprotrophy (growth on dead plant material) through pathogenesis (growth of the fungus accompanied by disease on the plant) to symbiosis (growth of the fungus with growth enhancement of the plant). We consider pathogenesis in this article and the key roles played by a range of pathogen-encoded molecules that have collectively become known as effectors.
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087830/recognition-of-the-magnaporthe-oryzae-effector-avr-pia-by-the-decoy-domain-of-the-rice-nlr-immune-receptor-rga5
#9
Diana Ortiz, Karine De Guillen, Stella Cesari, Véronique Chalvon, Jérome Gracy, André Padilla, Thomas Kroj
Nucleotide-binding domain and leucine-rich repeat proteins (NLRs) are important receptors in plant immunity that allow recognition of pathogen effectors. The rice NLR RGA5 recognizes the Magnaporthe oryzae effector AVR-Pia through direct interaction. Here, we gained detailed insights into the molecular and structural bases of AVR-Pia-RGA5 interaction and the role of the RATX1 decoy domain of RGA5. NMR titration combined with in vitro and in vivo protein-protein interaction analyses identified the AVR-Pia interaction surface that binds to the RATX1 domain...
January 13, 2017: Plant Cell
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#10
Julian Kwan, Anna Sczaniecka, Emad Heidary Arash, Liem Nguyen, Chia-Chun Chen, Srdjana Ratkovic, Olga Klezovitch, Liliana Attisano, Helen McNeill, Andrew Emili, Valeri Vasioukhin
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087668/the-threshold-of-protection-from-liver-stage-malaria-relies-on-a-fine-balance-between-the-number-of-infected-hepatocytes-and-effector-cd8-t-cells-present-in-the-liver
#11
Alexandra J Spencer, Rhea J Longley, Anita Gola, Marta Ulaszewska, Teresa Lambe, Adrian V S Hill
Since the demonstration of sterile protection afforded by injection of irradiated sporozoites, CD8(+) T cells have been shown to play a significant role in protection from liver-stage malaria. This is, however, dependent on the presence of an extremely high number of circulating effector cells, thought to be necessary to scan, locate, and kill infected hepatocytes in the short time that parasites are present in the liver. We used an adoptive transfer model to elucidate the kinetics of the effector CD8(+) T cell response in the liver following Plasmodium berghei sporozoite challenge...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087321/enteric-nervous-system-development-a-crest-cell-s-journey-from-neural-tube-to-colon
#12
REVIEW
Nandor Nagy, Allan M Goldstein
The enteric nervous system (ENS) is comprised of a network of neurons and glial cells that are responsible for coordinating many aspects of gastrointestinal (GI) function. These cells arise from the neural crest, migrate to the gut, and then continue their journey to colonize the entire length of the GI tract. Our understanding of the molecular and cellular events that regulate these processes has advanced significantly over the past several decades, in large part facilitated by the use of rodents, avians, and zebrafish as model systems to dissect the signals and pathways involved...
January 10, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28087239/on-going-mechanical-damage-from-mastication-drives-homeostatic-th17-cell-responses-at-the-oral-barrier
#13
Nicolas Dutzan, Loreto Abusleme, Hayley Bridgeman, Teresa Greenwell-Wild, Tamsin Zangerle-Murray, Mark E Fife, Nicolas Bouladoux, Holly Linley, Laurie Brenchley, Kelly Wemyss, Gloria Calderon, Bo-Young Hong, Timothy J Break, Dawn M E Bowdish, Michail S Lionakis, Simon A Jones, Giorgio Trinchieri, Patricia I Diaz, Yasmine Belkaid, Joanne E Konkel, Niki M Moutsopoulos
Immuno-surveillance networks operating at barrier sites are tuned by local tissue cues to ensure effective immunity. Site-specific commensal bacteria provide key signals ensuring host defense in the skin and gut. However, how the oral microbiome and tissue-specific signals balance immunity and regulation at the gingiva, a key oral barrier, remains minimally explored. In contrast to the skin and gut, we demonstrate that gingiva-resident T helper 17 (Th17) cells developed via a commensal colonization-independent mechanism...
January 6, 2017: Immunity
https://www.readbyqxmd.com/read/28087106/charge-variant-analysis-of-proposed-biosimilar-to-trastuzumab
#14
Pravinkumar Dakshinamurthy, Pavithra Mukunda, Bhargav Prasad Kodaganti, Bharath Ravindra Shenoy, Bairavabalakumar Natarajan, Amol Maliwalave, Vivek Halan, Sathyabalan Murugesan, Sunit Maity
Trastuzumab is a humanized monoclonal antibody (mAb) employed for the treatment of HER2 Positive Breast Cancer. A HER2 overexpressing tumor cell binds to Trastuzumab and attracts immune cells which lead to induction of Antibody Dependent Cellular Cytotoxicity (ADCC) by binding to Fc receptors (CD16a or FcγRIIIa) on an effector cell, such as natural killer (NK) cells. The most commonly expressed receptor on NK cell is CD16a which binds to the Fc portion of Trastuzumab. The ligand-independent HER2-HER3 dimerization is the most potent stimulator of downstream pathways for regulation of cell growth and survival...
January 10, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28086097/snapshot-class-2-crispr-cas-systems
#15
Kira S Makarova, Feng Zhang, Eugene V Koonin
Class 2 CRISPR-Cas systems are characterized by effector modules consisting of single, large, multidomain proteins that appear to have been derived from mobile genetic elements. Some Class 2 effector proteins, such as Cas9 and Cas12a (Cpf1), have been successfully repurposed for genome engineering.
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086085/two-distant-catalytic-sites-are-responsible-for-c2c2-rnase-activities
#16
Liang Liu, Xueyan Li, Jiuyu Wang, Min Wang, Peng Chen, Maolu Yin, Jiazhi Li, Gang Sheng, Yanli Wang
C2c2, the effector of type VI CRISPR-Cas systems, has two RNase activities-one for cutting its RNA target and the other for processing the CRISPR RNA (crRNA). Here, we report the structures of Leptotrichia shahii C2c2 in its crRNA-free and crRNA-bound states. While C2c2 has a bilobed structure reminiscent of all other Class 2 effectors, it also exhibits different structural characteristics. It contains the REC lobe with a Helical-1 domain and the NUC lobe with two HEPN domains. The two RNase catalytic pockets responsible for cleaving pre-crRNA and target RNA are independently located on Helical-1 and HEPN domains, respectively...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28085915/sequential-targeting-of-cd52-and-tnf-allows-early-minimization-therapy-in-kidney-transplantation-from-a-biomarker-to-targeting-in-a-proof-of-concept-trial
#17
Ondrej Viklicky, Petra Hruba, Stefan Tomiuk, Sabrina Schmitz, Bernhard Gerstmayer, Birgit Sawitzki, Patrick Miqueu, Petra Mrazova, Irena Tycova, Eva Svobodova, Eva Honsova, Uwe Janssen, Hans-Dieter Volk, Petra Reinke
BACKGROUND: There is high medical need for safe long-term immunosuppression monotherapy in kidney transplantation. Selective targeting of post-transplant alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global T cell depletion may allow safe drug minimization, however, it is unsolved what might be the best maintenance monotherapy. METHODS: In this open, prospective observational single-centre trial, 20 primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by 5 mg/kg Infliximab (d2)...
2017: PloS One
https://www.readbyqxmd.com/read/28085879/acylation-of-the-type-3-secretion-system-translocon-using-a-dedicated-acyl-carrier-protein
#18
Julie P M Viala, Valérie Prima, Rémy Puppo, Rym Agrebi, Mickaël J Canestrari, Sabrina Lignon, Nicolas Chauvin, Stéphane Méresse, Tâm Mignot, Régine Lebrun, Emmanuelle Bouveret
Bacterial pathogens often deliver effectors into host cells using type 3 secretion systems (T3SS) the extremity of which forms a translocon that perforates the host plasma membrane. The T3SS encoded by Salmonella pathogenicity island 1 (SPI-1) is genetically associated with an acyl carrier protein, IacP, whose role has remained enigmatic. In this study, using tandem affinity purification, we identify a direct protein-protein interaction between IacP and the translocon protein SipB. We show, by mass spectrometry and radiolabelling, that SipB is acylated, which provides evidence for a modification of the translocon that has not been described before...
January 13, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28085634/an-interleukin-12-adjuvanted-herpes-simplex-virus-2-dna-vaccine-is-more-protective-than-a-glycoprotein-d-subunit-vaccine-in-a-high-dose-murine-challenge-model
#19
Kenneth C Bagley, Jennifer A Schwartz, Hanne Andersen, John H Eldridge, Rong Xu, Ayuko Ota-Setlik, Joshua J Geltz, William P Halford, Timothy R Fouts
Vaccination is a proven intervention against human viral diseases; however, success against Herpes Simplex Virus 2 (HSV-2) remains elusive. Most HSV-2 vaccines tested in humans to date contained just one or two immunogens, such as the virion attachment receptor glycoprotein D (gD) and/or the envelope fusion protein, glycoprotein B (gB). At least three factors may have contributed to the failures of subunit-based HSV-2 vaccines. First, immune responses directed against one or two viral antigens may lack sufficient antigenic breadth for efficacy...
January 13, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28085492/mucosal-type-2-innate-lymphoid-cells-are-a-key-component-of-the-allergic-response-to-aeroallergen
#20
Jaideep Dhariwal, Aoife Cameron, Maria-Belen Trujillo-Torralbo, Ajerico Del Rosario, Eteri Bakhsoliani, Malte Paulsen, David J Jackson, Michael R Edwards, Batika M J Rana, David J Cousins, Trevor T Hansel, Sebastian L Johnston, Ross P Walton
RATIONALE: Newly characterised type 2 innate lymphoid cells display potent type 2 effector functionality, however their contribution to allergic airways inflammation and asthma is poorly understood. Mucosal biopsy used to characterise the airway mucosa is invasive, poorly tolerated and does not allow sequential sampling. OBJECTIVES: To assess the role of type 2 innate lymphoid cells during nasal allergen challenge in subjects with allergic rhinitis, using novel non-invasive methodology...
January 13, 2017: American Journal of Respiratory and Critical Care Medicine
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