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https://www.readbyqxmd.com/read/28822242/mucosal-immunity-of-the-postpartum-bovine-genital-tract
#1
REVIEW
Dinesh Dadarwal, Colin Palmer, Philip Griebel
In this review, mucosal immune defense mechanisms used to control infections in the bovine genital tract (vestibule, vagina, cervix, uterus and oviduct) during the postpartum period are reviewed. Knowledge gaps are highlighted to emphasize the need for further investigations. Physical barriers to the entry of microbes include vulvar sealing, vestibule-vaginal constriction, a narrow cervical opening and the mucosal epithelium along with the overlying mucus layer. Genital tract mucosal epithelial cells recognize damage-associated molecular patterns and pathogen-associated molecular patterns and respond by secreting antimicrobial peptides and cytokines to recruit and activate immune cells...
August 10, 2017: Theriogenology
https://www.readbyqxmd.com/read/28822225/altered-thymocyte-and-t-cell-development-in-neonatal-mice-with-hyperoxia-induced-lung-injury
#2
Sowmya Angusamy, Tamer Mansour, Mohammed Abdulmageed, Rachel Han, Brian C Schutte, John LaPres, Jack R Harkema, Said A Omar
BACKGROUND: The adaptive immune system of neonates is relatively underdeveloped. The thymus is an essential organ for adaptive T cell development and might be affected during the natural course of oxygen induced lung injury. The effect of prolonged hyperoxia on the thymus, thymocyte and T cell development, and its proliferation has not been studied extensively. METHODS: Neonatal mice were exposed to 85% oxygen (hyperoxia) or room air (normoxia) up to 28 days. Flow cytometry using surface markers were used to assay for thymocyte development and proliferation...
August 19, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28822058/immune-dysfunction-in-non-hodgkin-lymphoma-avenues-for-new-immunotherapy-based-strategies
#3
REVIEW
Lorenzo Falchi
PURPOSE OF THIS REVIEW: The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies. RECENT FINDINGS: In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28821990/upregulation-of-cd16-monocyte-subsets-in-systemic-lupus-erythematous-patients
#4
Ziyan Wu, Shulan Zhang, Lidan Zhao, Yunyun Fei, Li Wang, Jing Li, Xiaoting Wen, Xiaofeng Zeng, Fengchun Zhang, Yongzhe Li
Monocytes are an important component in the innate immune system. However, studies to date have failed to conclude whether their levels are altered in patients with systemic lupus erythematosus (SLE). We applied the cytodiff counting method and comprehensively measured the circulating levels of distinct white blood cell (WBC) subsets, including CD16+, CD16-, and total monocytes, in 61 SLE patients as well as in 203 age-matched healthy controls (HCs). The absolute number of CD16- monocytes, total monocytes, immature granulocytes, mature neutrophils, total neutrophils, and T cell blasts was significantly higher, that of non-cytotoxic T lymphocytes, cytotoxic T + NK lymphocytes, T + NK lymphocytes, total lymphocytes, basophils, and eosinophils significantly lower (all p < 0...
August 19, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28821924/-89-zr-labeled-nivolumab-for-imaging-of-t-cell-infiltration-in-a-humanized-murine-model-of-lung-cancer
#5
Christopher G England, Dawei Jiang, Emily B Ehlerding, Brian T Rekoske, Paul A Ellison, Reinier Hernandez, Todd E Barnhart, Douglas G McNeel, Peng Huang, Weibo Cai
PURPOSE: Nivolumab is a human monoclonal antibody specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response. Acting as an immune checkpoint inhibitor, nivolumab binds to PD-1 expressed on the surface of many immune cells and prevents ligation by its natural ligands. Nivolumab is only effective in a subset of patients, and there is limited evidence supporting its use for diagnostic, monitoring, or stratification purposes. METHODS: (89)Zr-Df-nivolumab was synthesized to map the biodistribution of PD-1-expressing tumor infiltrating T-cells in vivo using a humanized murine model of lung cancer...
August 19, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28821884/the-atopic-dermatitis-blood-signature-is-characterized-by-increases-in-inflammatory-and-cardiovascular-risk-proteins
#6
Patrick M Brunner, Mayte Suárez-Fariñas, Helen He, Kunal Malik, Huei-Chi Wen, Juana Gonzalez, Tom Chih-Chieh Chan, Yeriel Estrada, Xiuzhong Zheng, Saakshi Khattri, Nancy Dattola, James G Krueger, Emma Guttman-Yassky
Beyond classic "allergic"/atopic comorbidities, atopic dermatitis (AD) emerges as systemic disease with increased cardiovascular risk. To better define serum inflammatory and cardiovascular risk proteins, we used an OLINK high-throughput proteomic assay to analyze moderate-to-severe AD (n = 59) compared to psoriasis (n = 22) and healthy controls (n = 18). Compared to controls, 10 proteins were increased in serum of both diseases, including Th1 (IFN-γ, CXCL9, TNF-β) and Th17 (CCL20) markers. 48 proteins each were uniquely upregulated in AD and psoriasis...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821816/an-expandable-embryonic-stem-cell-derived-purkinje-neuron-progenitor-population-that-exhibits-in-vivo-maturation-in-the-adult-mouse-cerebellum
#7
Gustavo A Higuera, Grazia Iaffaldano, Meiwand Bedar, Guy Shpak, Robin Broersen, Shashini T Munshi, Catherine Dupont, Joost Gribnau, Femke M S de Vrij, Steven A Kushner, Chris I De Zeeuw
The directed differentiation of patient-derived induced pluripotent stem cells into cell-type specific neurons has inspired the development of therapeutic discovery for neurodegenerative diseases. Many forms of ataxia result from degeneration of cerebellar Purkinje cells, but thus far it has not been possible to efficiently generate Purkinje neuron (PN) progenitors from human or mouse pluripotent stem cells, let alone to develop a methodology for in vivo transplantation in the adult cerebellum. Here, we present a protocol to obtain an expandable population of cerebellar neuron progenitors from mouse embryonic stem cells...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821804/nos2-deficient-mice-with-hypoxic-necrotizing-lung-lesions-predict-outcomes-of-tuberculosis-chemotherapy-in-humans
#8
Martin Gengenbacher, Maria A Duque-Correa, Peggy Kaiser, Stefanie Schuerer, Doris Lazar, Ulrike Zedler, Stephen T Reece, Amit Nayyar, Stewart T Cole, Vadim Makarov, Clifton E Barry Iii, Véronique Dartois, Stefan H E Kaufmann
During active TB in humans a spectrum of pulmonary granulomas with central necrosis and hypoxia exists. BALB/c mice, predominantly used in TB drug development, do not reproduce this complex pathology thereby inaccurately predicting clinical outcome. We found that Nos2 (-/-) mice incapable of NO-production in immune cells as microbial defence uniformly develop hypoxic necrotizing lung lesions, widely observed in human TB. To study the impact of hypoxic necrosis on the efficacy of antimycobacterials and drug candidates, we subjected Nos2 (-/-) mice with TB to monotherapy before or after establishment of human-like pathology...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821664/differential-desensitization-observed-at-multiple-effectors-of-somatic-mu-opioid-receptors-underlies-sustained-agonist-mediated-inhibition-of-proopiomelanocortin-neuron-activity
#9
Philip D Fox, Shane T Hentges
Activation of somatic mu opioid receptors (MORs) in hypothalamic proopiomelanocortin (POMC) neurons leads to the activation of G-protein-coupled inward rectifier potassium (GIRK) channels and hyperpolarization, but in response to continued signaling, MORs undergo acute desensitization resulting in robust reduction in the peak GIRK current after minutes of agonist exposure. We hypothesized that the attenuation of the GIRK current would lead to a recovery of neuronal excitability whereby desensitization of the receptor would lead to a new steady-state of POMC neuron activity reflecting the sustained GIRK current observed after the initial decline from peak with continued agonist exposure...
August 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821631/6-methoxyethylamino-numonafide-inhibits-hepatocellular-carcinoma-xenograft-growth-as-a-single-agent-and-in-combination-with-sorafenib
#10
Yanning Liu, Guohua Lou, John T Norton, Chen Wang, Irawati Kandela, Shuai Tang, Nathaniel I Shank, Pankaj Gupta, Min Huang, Michael J Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821585/a-coronin-1-dependent-decision-switch-in-juvenile-mice-determines-the-population-of-the-peripheral-naive-t-cell-compartment
#11
Mathias Jakob Lang, Mayumi Mori, Julie Ruer-Laventie, Jean Pieters
Following thymic maturation, T cells egress as recent thymic emigrants to peripheral lymphoid organs where they undergo an additional maturation step to mature naive T cells that circulate through secondary lymphoid organs ready to be activated upon pathogenic challenges. Thymic maturation and peripheral T cell survival depend on several signaling cascades, but whether a dedicated mechanism exists that exclusively regulates homeostasis of mature naive T cells without affecting thymocytes and/or recent thymic emigrants remains unknown...
August 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28821547/cultivation-in-space-flight-produces-minimal-alterations-in-the-susceptibility-of-bacillus-subtilis-cells-to-72-different-antibiotics-and-growth-inhibiting-compounds
#12
Michael D Morrison, Patricia Fajardo-Cavazos, Wayne L Nicholson
Past results have suggested that bacterial antibiotic susceptibility is altered during space flight. To test this notion, Bacillus subtilis cells were cultivated in matched hardware, medium, and environmental conditions either in spaceflight microgravity on the International Space Station, termed Flight (FL) samples, or at Earth-normal gravity, termed Ground Control (GC) samples. Susceptibility of FL and GC samples was compared to 72 antibiotics and growth-inhibitory compounds using the Omnilog Phenotype Microarray (PM) system...
August 18, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28821484/measurement-and-mathematical-characterization-of-cell-level-pharmacokinetics-of-antibody-drug-conjugates-a-case-study-with-trastuzumab-vc-mmae
#13
Aman P Singh, Dhaval K Shah
The main objective of this work was to understand and mathematically characterize the cellular disposition of a tool ADC, trastuzumab-vc-MMAE (T-vc-MMAE). Towards this goal, three different analytical methods were developed to measure the concentrations of different ADC related analytes in the media and cell lysate. An LC-MS/MS method was developed to quantify unconjugated drug (i.e. MMAE) concentrations, a forced deconjugation method was developed to quantify total drug concentrations, and an ELISA method was developed to quantify total antibody (i...
August 18, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28821013/rictor-positively-regulates-b-cell-receptor-signaling-by-modulating-actin-reorganization-via-ezrin
#14
Lu Huang, Yongjie Zhang, Chenguang Xu, Xiaomei Gu, Linlin Niu, Jinzhi Wang, Xiaoyu Sun, Xiaoming Bai, Xingtian Xuan, Qubei Li, Chunwei Shi, Bing Yu, Heather Miller, Gangyi Yang, Lisa S Westerberg, Wanli Liu, Wenxia Song, Xiaodong Zhao, Chaohong Liu
As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28820319/a-to-i-rna-editing-thinking-beyond-the-single-nucleotide
#15
Nabeel S Ganem, Ayelet T Lamm
Adenosine-to-inosine RNA editing is a conserved process, which is performed by ADAR enzymes. By changing nucleotides in coding regions of genes and altering codons, ADARs expand the cell's protein repertoire. This function of the ADAR enzymes is essential for human brain development. However, most of the known editing sites are in non-coding repetitive regions in the transcriptome and the purpose of editing in these regions is unclear. Recent studies, which have shown that editing levels of transcripts vary between tissues and developmental stages in many organisms, suggest that the targeted RNA and ADAR editing are both regulated...
August 18, 2017: RNA Biology
https://www.readbyqxmd.com/read/28820196/on-the-mobility-of-carriers-at-semi-coherent-oxide-heterointerfaces
#16
Pratik P Dholabhai, Enrique Martínez, Nicholas T Brown, Blas Pedro Uberuaga
In the quest to develop new materials with enhanced ionic conductivity for battery and fuel cell applications, nano-structured oxides have attracted attention. Experimental reports indicate that oxide heterointerfaces can lead to enhanced ionic conductivity, but these same reports cannot elucidate the origin of this enhancement, often vaguely referring to pipe diffusion at misfit dislocations as a potential explanation. However, this highlights the need to understand the role of misfit dislocation structure at semi-coherent oxide heterointerfaces in modifying carrier mobilities...
August 18, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28820075/t-regulatory-cell-subsets-in-children-with-type-1-diabetes-mellitus-relation-to-control-of-the-disease
#17
Mabrouk Ghonaim, Rawhia El-Edel, Wafaa Abo El Fotoh, Samar Kamal Eldein, Samar Salman
BACKGROUND: Type 1 diabetes mellitus described as a chronic metabolic disorder characterized by aggressive immune β-cell destruction. There are numbers of varied immune mechanisms for sustaining self-tolerance in opposition to the autoimmune disorders. A recessive tolerance accomplished by thymic gland via a negative assortment of different clones while a dominant tolerance accomplished by the regulatory T cells (Treg) in the periphery. Treg (CD4+CD25+FOXP3+) are subsets of T cells which have an essential role in maintaining tolerance...
August 17, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28819864/molecular-processes-involved-in-b-cell-acute-lymphoblastic-leukaemia
#18
REVIEW
Camille Malouf, Katrin Ottersbach
B cell leukaemia is one of the most frequent malignancies in the paediatric population, but also affects a significant proportion of adults in developed countries. The majority of infant and paediatric cases initiate the process of leukaemogenesis during foetal development (in utero) through the formation of a chromosomal translocation or the acquisition/deletion of genetic material (hyperdiploidy or hypodiploidy, respectively). This first genetic insult is the major determinant for the prognosis and therapeutic outcome of patients...
August 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28819773/tlr9-gene-polymorphism-1486t-c-rs187084-is-associated-with-uterine-cervical-neoplasm-in-mexican-female-population
#19
Cecilia Martínez-Campos, Margarita Bahena-Román, Kirvis Torres-Poveda, Ana I Burguete-García, Vicente Madrid-Marina
PURPOSE: The aim of this work was to evaluate the association of single nucleotide polymorphisms in TLR9 (-1486 T/C [rs187084], -1237T/C [rs5743836] and G2848A [rs352140]) with HPV infection, squamous intraepithelial lesions, and uterine cervical neoplasm in a Mexican population. Additionally, the peripheral expression of TLR9 was evaluated to evaluate the differences in the TLR9 expression associated with every genotype in the locus -1486 of the TLR9 gene. The serum concentration of TLR9 was evaluated in a randomly selected subsample...
August 17, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28819723/guselkumab-first-global-approval
#20
Anthony Markham
Guselkumab (Tremfya™) is a human monoclonal IgG1λ antibody being developed by Janssen Biotech, Inc. that has been approved in the USA as a treatment for moderate-to-severe plaque psoriasis. Guselkumab inhibits the binding of interleukin 23 (IL-23) to its cell surface receptor, disrupting the type 17 helper T cell/IL-17 pathway. This article summarizes the milestones in the development of guselkumab leading to this first approval for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy...
August 17, 2017: Drugs
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