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https://www.readbyqxmd.com/read/28323513/transmembrane-tnf-dependent-uptake-of-anti-tnf-antibodies
#1
Arun Deora, Subramanya Hegde, Jacqueline Lee, Chee-Ho Choi, Qing Chang, Cheryl Lee, Lucia Eaton, Hua Tang, Dongdong Wang, David Lee, Mark Michalak, Medha Tomlinson, Qingfeng Tao, Nidhi Gaur, Bohdan Harvey, Shaun McLoughlin, Boris Labkovsky, Tariq Ghayur
TNF-alpha (TNF), a pro-inflammatory cytokine is synthesized as a 26 kDa protein, anchors in the plasma membrane as transmembrane TNF (TmTNF), and is subjected to proteolysis by the TNF-alpha converting enzyme (TACE) to release the 15 kDa form of soluble TNF (sTNF). TmTNF and sTNF interact with two distinct receptors, TNF-R1 (p55) and TNF-R2 (p75), to mediate the multiple biological effects of TNF described to date. Several anti-TNF biologics that bind to both forms of TNF and block their interactions with the TNF receptors are now approved for the treatment of a variety of immune-mediated diseases...
March 21, 2017: MAbs
https://www.readbyqxmd.com/read/28318784/kinetics-of-endogenous-camkii-required-for-synaptic-plasticity-revealed-by-optogenetic-kinase-inhibitor
#2
Hideji Murakoshi, Myung Eun Shin, Paula Parra-Bueno, Erzsebet M Szatmari, Akihiro C E Shibata, Ryohei Yasuda
Elucidating temporal windows of signaling activity required for synaptic and behavioral plasticity is crucial for understanding molecular mechanisms underlying these phenomena. Here, we developed photoactivatable autocamtide inhibitory peptide 2 (paAIP2), a genetically encoded, light-inducible inhibitor of CaMKII activity. The photoactivation of paAIP2 in neurons for 1-2 min during the induction of LTP and structural LTP (sLTP) of dendritic spines inhibited these forms of plasticity in hippocampal slices of rodents...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28318197/-generalized-eruptive-histiocytosis-juvenile-xanthogranuloma-clinical-spectrum-in-a-pediatric-patient
#3
Ruth Alperovich, Pedro T Grassino, Raúl Asial, Luis Pasteris, María Del Carmen Boente
Both, generalized eruptive histiocytosis and juvenile xanthogranuloma are dendritic histiocytic disorders (also known as non-Langerhans cells histiocytosis) that share clinicopathological and immunohistiochemical characteristics. We present a 3-year-old female patient with skin lesions that were clinically compatible with generalized eruptive histiocytosis, confirmed by histopathological and immunohistochemical studies. During her development the disorder compromised the central nervous system, and surgical intervention of one symptomatic lesion was needed...
April 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28317871/insights-into-molecular-therapy-of-glioma-current-challenges-and-next-generation-blueprint
#4
REVIEW
Y Rajesh, Ipsita Pal, Payel Banik, Sandipan Chakraborty, Sachin A Borkar, Goutam Dey, Ahona Mukherjee, Mahitosh Mandal
Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28303764/recent-progress-in-gm-csf-based-cancer-immunotherapy
#5
Wan-Lun Yan, Kuan-Yin Shen, Chun-Yuan Tien, Yu-An Chen, Shih-Jen Liu
Cancer immunotherapy is a growing field. GM-CSF, a potent cytokine promoting the differentiation of myeloid cells, can also be used as an immunostimulatory adjuvant to elicit antitumor immunity. Additionally, GM-CSF is essential for the differentiation of dendritic cells, which are responsible for processing and presenting tumor antigens for the priming of antitumor cytotoxic T lymphocytes. Some strategies have been developed for GM-CSF-based cancer immunotherapy in clinical practice: GM-CSF monotherapy, GM-CSF-secreting cancer cell vaccines, GM-CSF-fused tumor-associated antigen protein-based vaccines, GM-CSF-based DNA vaccines and GM-CSF combination therapy...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28302385/primary-cutaneous-interdigitating-dendritic-cell-sarcoma-is-a-morphologic-and-phenotypic-simulator-of-poorly-differentiated-metastatic-melanoma-a-report-of-2-cases-and-review-of-the-literature
#6
REVIEW
Cynthia M Magro, Luke C Olson, Gerard Nuovo, Garron J Solomon
Interdigitating dendritic cell sarcoma (IDS) is a rare form of hematologic malignancy associated with an aggressive clinical course. Only 4 prior cases have been described as originating in the skin. We encountered two male patients ages 47 and 61years of age who presented with solitary cutaneous neoplasms diagnosed as IDS. Histologic exam showed a coalescing nested and multinodular proliferation of large pleomorphic epithelioid cells. In one case an initial diagnosis of melanoma was rendered. A recurrence 8months later was then interpreted as a primary cutaneous IDS...
February 20, 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28301408/k-cl-cotransporter-2-mediated-cl-extrusion-determines-developmental-stage-dependent-impact-of-propofol-anesthesia-on-dendritic-spines
#7
Martin Puskarjov, Hubert Fiumelli, Adrian Briner, Timea Bodogan, Kornel Demeter, Claudia-Marvine Lacoh, Martina Mavrovic, Peter Blaesse, Kai Kaila, Laszlo Vutskits
BACKGROUND: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABAA)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2)...
March 16, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28300196/recombinant-mycobacterium-smegmatis-with-a-pmyong2-vector-expressing-human-immunodeficiency-virus-type-i-gag-can-induce-enhanced-virus-specific-immune-responses
#8
Byoung-Jun Kim, Jeong-Ryeol Gong, Ga-Na Kim, Bo-Ram Kim, So-Young Lee, Yoon-Hoh Kook, Bum-Joon Kim
Recently, we have developed a novel Mycobacterium-Escherichia coli shuttle vector system using pMyong2, which can provide an enhanced expression of heterologous genes in recombinant Mycobacterium smegmatis (rSmeg). To investigate the usefulness of rSmeg using pMyong2 in vaccine application, we vaccinated M. smegmatis with pMyong2 system expressing Human Immunodeficiency Virus Type I (HIV-1) Gag p24 antigen (rSmeg-pMyong2-p24) into mice and examined its cellular and humoral immune responses against HIV gag protein...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28299466/development-of-oral-cancer-vaccine-using-recombinant-bifidobacterium-displaying-wilms-tumor-1-protein
#9
Koichi Kitagawa, Tsugumi Oda, Hiroki Saito, Ayame Araki, Reina Gonoi, Katsumi Shigemura, Yoshiko Hashii, Takane Katayama, Masato Fujisawa, Toshiro Shirakawa
Several types of vaccine-delivering tumor-associated antigens (TAAs) have been developed in basic and clinical research. Wilms' tumor 1 (WT1), identified as a gene responsible for pediatric renal neoplasm, is one of the most promising TAA for cancer immunotherapy. Peptide and dendritic cell-based WT1 cancer vaccines showed some therapeutic efficacy in clinical and pre-clinical studies but as yet no oral WT1 vaccine can be administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying WT1 protein...
March 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28298884/physical-exercise-restores-the-generation-of-newborn-neurons-in-an-animal-model-of-chronic-epilepsy
#10
Fabricio N Mendonça, Luiz E C Santos, Antônio M Rodrigues, Sérgio Gomes da Silva, Ricardo M Arida, Gilcélio A da Silveira, Fulvio A Scorza, Antônio-Carlos G Almeida
Neurogenesis impairment is associated with the chronic phase of the epilepsy in humans and also observed in animal models. Recent studies with animal models have shown that physical exercise is capable of improving neurogenesis in adult subjects, alleviating cognitive impairment and depression. Here, we show that there is a reduction in the generation of newborn granule cells in the dentate gyrus of adult rats subjected to a chronic model of epilepsy during the postnatal period of brain development. We also show that the physical exercise was capable to restore the number of newborn granule cells in this animals to the level observed in the control group...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28297673/%C3%AE-protocadherins-interact-with-neuroligin-1-and-negatively-regulate-dendritic-spine-morphogenesis
#11
Michael J Molumby, Rachel M Anderson, Dillan J Newbold, Norah K Koblesky, Andrew M Garrett, Dietmar Schreiner, Jason J Radley, Joshua A Weiner
The 22 γ-Protocadherin (γ-Pcdh) cell adhesion molecules are critical for the elaboration of complex dendritic arbors in the cerebral cortex. Here, we provide evidence that the γ-Pcdhs negatively regulate synapse development by inhibiting the postsynaptic cell adhesion molecule, neuroligin-1 (Nlg1). Mice lacking all γ-Pcdhs in the forebrain exhibit significantly increased dendritic spine density in vivo, while spine density is significantly decreased in mice overexpressing one of the 22 γ-Pcdh isoforms...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28296555/the-screening-of-a-microrna-expression-during-development-of-human-macrophages-and-mouse-dendritic-cells
#12
Eui Young So, Trisha Winchester, Toru Ouchi
There is increasing evidence showing specific roles of microRNA in cell differentiation and cancer progression. Here we examine miRNA profiles during maturation of monocytes and bone marrow-derived dendritic cells (BMDCs) in human and mouse, respectively. We have identified significant changes of various miRNA expression during monocyte and BMDC monocyte development via miRNA microarrays, confirmed by quantitative PCR. Increases in miR155 expression positively correlated with increasing maturity of monocyte and BMDC in both mouse and human microarrays, indicating its importance in development...
March 15, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28296000/novel-application-of-localized-nanodelivery-of-anti-il6-protects-organ-transplant-from-ischemia-reperfusion-injuries
#13
Zhabiz Solhjou, Mayuko Uehara, Baharak Bahmani, Omar H Maarouf, Takaharu Ichimura, Craig R Brooks, Wanlong Xu, Mine Yilmaz, Abdala Elkhal, Stefan G Tullius, Indira Guleria, Martina McGrath, Reza Abdi
Ischemia reperfusion injury (IRI) evokes intra-graft inflammatory responses, which markedly augment alloimmune responses against the graft. Understanding the mechanisms underlying these responses is fundamental to develop therapeutic regimens to prevent/ameliorate organ IRI. Here, we demonstrate that IRI results in a marked increase in mitochondrial damage and autophagy in dendritic cells (DC). While autophagy is a survival mechanism for ischemic DC, it also augments their production of IL6. Allograft derived dendritic cells (ADDC) lacking autophagy related gene 5 (Atg5) showed higher death rates post-transplantation...
March 12, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28295967/fervent-hype-behind-magnesium-batteries-an-open-call-to-synthetic-chemists-electrolytes-and-cathodes-needed
#14
John Muldoon, Claudiu B Bucur, Thomas Gregory
Magnesium metal is an ideal anode which has double the volumetric capacity of lithium metal and has a negative reduction potential of -2.37V vs. the standard hydrogen electrode. The major advantage of magnesium is the apparent lack of dendritic formation during charging which is one of the major concerns of using a lithium metal anode. In this review, we highlight the major research in the development of electrolytes and cathodes and discuss some of the major challenges which must be overcome in realizing a practical magnesium battery...
March 10, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28295344/connectomics-of-synaptic-microcircuits-lessons-from-the-outer-retina
#15
Luke Edward Rogerson, Christian Behrens, Thomas Euler, Philipp Berens, Timm Schubert
Photoreceptors form a sophisticated synaptic complex with bipolar and horizontal cells, transmitting the signals generated by the phototransduction cascade to downstream retinal circuitry. The cone photoreceptor synapse shows several characteristic anatomical connectivity motifs that shape signal transfer: Typically, ON-cone bipolar cells receive photoreceptor input through invaginating synapses; OFF-cone bipolar cells form basal synapses with photoreceptors. Both ON- and OFF-cone bipolar cells are believed to sample from all cone photoreceptors within their dendritic span...
March 10, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28295265/card9-controls-dectin-1-induced-t-cell-cytotoxicity-and-tumor-growth-in-mice
#16
Haas Tobias, Heidegger Simon, Wintges Alexander, Bscheider Michael, Bek Sarah, Fischer Julius C, Eisenkolb Gabriel, Schmickl Martina, Spoerl Silvia, Peschel Christian, Poeck Hendrik, Ruland Jürgen
Activation of the C-type lectin receptor Dectin-1 by β-glucans triggers multiple signals within dendritic cells (DCs) that result in activation of innate immunity. While these mechanisms can potently prime CD8(+) cytotoxic T cell (CTL) responses without additional adjuvants, the Dectin-1 effector pathways that control CTL induction remain unclear. Here we demonstrate that Dectin-1-induced CTL cross-priming in mice does not require inflammasome activation but strictly depends on the adapter protein Card9 in vitro...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295231/deficiency-in-irak4-activity-attenuates-manifestations-of-murine-lupus
#17
Michael Murphy, Goutham Pattabiraman, Tissa T Manavalan, Andrei E Medvedev
Interleukin-1 receptor-associated kinase (IRAK) 4 mediates host defense against infections. As an active kinase, IRAK4 elicits full spectra of myeloid differentiation primary response protein (MyD) 88-dependent responses, while kinase-inactive IRAK4 induces a subset of cytokines and negative regulators whose expression is not regulated by mRNA stability. IRAK4 kinase activity is critical for resistance against Streptococcus pneumonia, but its involvement in autoimmunity is incompletely understood. In this study, we determined the role of IRAK4 kinase activity in murine lupus...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28292736/increased-metalloproteinase-activity-in-the-hippocampus-following-status-epilepticus
#18
Deepti Dubey, Paulette A McRae, Elyse K Rankin-Gee, Esther Baranov, Luke Wandrey, Stephanie Rogers, Brenda E Porter
Increased neuronal plasticity and neuronal cell loss has been implicated in the development of epilepsy following injury. Parvalbumin fast spiking inhibitory interneurons have a robust extracellular matrix coating their cell bodies and the proximal dendrites called the perineuronal net (PNN). The role of the PNN is not clear but it has been implicated in closing of the critical period, altering seizure thresholds and providing neuronal protection from oxidative stress. The PNN is susceptible to degradation following a prolonged seizure and there is an increase in proteolytic-fragments of the PNN enriched proteoglycan aggrecan (Dzwonek et al...
March 1, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28291548/the-role-of-interleukin-17a-in-the-pathogenesis-of-kidney-diseases
#19
REVIEW
Charlotte Cortvrindt, Reinhart Speeckaert, Alena Moerman, Joris R Delanghe, Marijn M Speeckaert
Being a member of the IL-17 family, comprising six structurally related ligands, IL-17A is a cytokine, produced by multiple cell types, such as CD4(+)αβ T cells, γδ T cells, natural killer cells, neutrophils, macrophages, dendritic cells, lymphoid tissue inducer cells, mast cells and plasma cells. IL-17A participates in tissue inflammation by inducing the expression of chemokines, proinflammatory cytokines and matrix metalloproteases. Besides its role in host defence against infectious diseases, IL-17A is involved in different autoimmune and inflammatory diseases...
March 10, 2017: Pathology
https://www.readbyqxmd.com/read/28290050/micellar-nano-carriers-for-the-delivery-of-stat3-dimerization-inhibitors-to-melanoma
#20
Amir H Soleimani, Shyam M Garg, Igor M Paiva, Mohammad R Vakili, Abdulraheem Alshareef, Yung-Hsing Huang, Ommoleila Molavi, Raymond Lai, Afsaneh Lavasanifar
The objective of this research was to develop polymeric micellar formulations of inhibitors of signal transducer and activator of transcription 3 (STAT3) dimerization, i.e., S3I-1757 and S3I-201, and evaluate the activity of successful formulations in B16-F10 melanoma, a STAT3 hyperactive cancer model, in vitro and in vivo. STAT3 inhibitory agents were encapsulated in methoxy poly(ethylene oxide)-b-poly(ε-caprolactone) (PEO114-b-PCL22) and methoxy poly(ethylene oxide)-b-poly(α-benzyl carboxylate-ε-caprolactone) (PEO114-b-PBCL20) micelles using co-solvent evaporation...
March 13, 2017: Drug Delivery and Translational Research
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