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https://www.readbyqxmd.com/read/28644814/learning-multimodal-parameters-a-bare-bones-niching-differential-evolution-approach
#1
Yue-Jiao Gong, Jun Zhang, Yicong Zhou
Most learning methods contain optimization as a substep, where the nondifferentiability and multimodality of objectives push forward the interplay of evolutionary optimization algorithms and machine learning models. The recently emerged evolutionary multimodal optimization (MMOP) technique enables the learning of diverse sets of effective parameters for the models simultaneously, providing new opportunities to the applications requiring both accuracy and diversity, such as ensemble, interactive, and interpretive learning...
June 20, 2017: IEEE Transactions on Neural Networks and Learning Systems
https://www.readbyqxmd.com/read/28641288/the-crista-fenestra-and-its-impact-on-the-surgical-approach-to-the-scala-tympani-during-cochlear-implantation
#2
Roberto D Angeli, Joel Lavinsky, Enio T Setogutti, Luiz Lavinsky
OBJECTIVE: The aim of this work was to describe the dimensions of the crista fenestra and determine its presence by means of high-resolution computed tomography (CT) for the purpose of cochlear implantation via the round window approach. METHODS: A series of 10 adult human temporal bones underwent high-resolution CT scanning and were further dissected for microscopic study of the round window niche. RESULTS: In all of the specimens, the round window membrane was fully visualized after the complete removal of bony overhangs...
June 23, 2017: Audiology & Neuro-otology
https://www.readbyqxmd.com/read/28640953/overview-of-transgenic-mouse-models-of-myeloproliferative-neoplasms-mpns
#3
Andrew Dunbar, Abbas Nazir, Ross Levine
Myeloproliferative neoplasms (MPNs) are a class of hematologic diseases characterized by aberrant proliferation of one or more myeloid lineages and progressive bone marrow fibrosis. In 2005, seminal work by multiple groups identified the JAK2V617F mutation in a significant fraction of MPN patients. Since that time, murine models of JAK2V617F have greatly enhanced the understanding of the role of aberrant JAK-STAT signaling in MPN pathogenesis and have provided an in vivo pre-clinical platform that can be used to develop novel therapies...
June 22, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/28639518/selective-laser-melting-enabled-electrospinning-introducing-complexity-within-electrospun-membranes
#4
Thomas E Paterson, Selina N Beal, Martin E Santocildes-Romero, Alfred T Sidambe, Paul V Hatton, Ilida Ortega Asencio
Additive manufacturing technologies enable the creation of very precise and well-defined structures that can mimic hierarchical features of natural tissues. In this article, we describe the development of a manufacturing technology platform to produce innovative biodegradable membranes that are enhanced with controlled microenvironments produced via a combination of selective laser melting techniques and conventional electrospinning. This work underpins the manufacture of a new generation of biomaterial devices that have significant potential for use as both basic research tools and components of therapeutic implants...
June 2017: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
https://www.readbyqxmd.com/read/28639326/bone-marrow-hematons-an-access-point-to-the-human-hematopoietic-niche
#5
Alexandre Janel, Juliette Berger, Céline Bourgne, Richard Lemal, Nathalie Boiret-Dupré, Frédérique Dubois-Galopin, Pierre Déchelotte, Charlotte Bothorel, Eric Hermet, Sara Chabi, Jacques-Olivier Bay, Céline Lambert, Bruno Pereira, Françoise Pflumio, Rima Haddad, Marc G Berger
To understand the complex interactions between hematopoietic stem cells and the bone marrow niche, a human experimental model is needed. Our hypothesis is that hematons are an appropriate ex vivo model of human bone marrow. We analyzed the hierarchical hematopoietic cell content and the tissue organization of single hematons from healthy donors. Most (>90%) hematons contained precursors of all cell lineages, myeloid progenitors, and LTC-ICs without preferential commitment. Approximately half of the hematons could generate significant levels of lympho-myeloid hematopoiesis after transplantation in an NSG mouse model, despite the low absolute numbers of transplanted CD34(+) cells...
June 22, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28637883/niche-mediated-depletion-of-the-normal-hematopoietic-stem-cell-reservoir-by-flt3-itd-induced-myeloproliferation
#6
Adam J Mead, Wen Hao Neo, Nikolaos Barkas, Sahoko Matsuoka, Alice Giustacchini, Raffaella Facchini, Supat Thongjuea, Lauren Jamieson, Christopher A G Booth, Nicholas Fordham, Cristina Di Genua, Deborah Atkinson, Onima Chowdhury, Emmanouela Repapi, Nicki Gray, Shabnam Kharazi, Sally-Ann Clark, Tiphaine Bouriez, Petter Woll, Toshio Suda, Claus Nerlov, Sten Eirik W Jacobsen
Although previous studies suggested that the expression of FMS-like tyrosine kinase 3 (Flt3) initiates downstream of mouse hematopoietic stem cells (HSCs), FLT3 internal tandem duplications (FLT3 ITDs) have recently been suggested to intrinsically suppress HSCs. Herein, single-cell interrogation found Flt3 mRNA expression to be absent in the large majority of phenotypic HSCs, with a strong negative correlation between Flt3 and HSC-associated gene expression. Flt3-ITD knock-in mice showed reduced numbers of phenotypic HSCs, with an even more severe loss of long-term repopulating HSCs, likely reflecting the presence of non-HSCs within the phenotypic HSC compartment...
June 21, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28636974/sema3a-partially-reverses-vegf-effects-through-binding-to-neuropilin-1
#7
Bruna Palodetto, Adriana da Silva Santos Duarte, Matheus Rodrigues Lopes, Flavia Adolfo Corrocher, Fernanda Marconi Roversi, Fernanda Soares Niemann, Karla Priscila Vieira Ferro, Ana Leda Figueiredo Longhini, Paula Melo Campos, Patricia Favaro, Sara Teresinha Olalla Saad
Cross-talk between hematopoietic stem cells (HSCs) and bone marrow stromal cells (BMSCs) is essential for HSCs regulation and leukemogenesis. Studying bone marrow of myelodysplasia patients, a pre-leukemic condition, we found mRNA overexpression of vascular endothelial growth factor A (VEGFA) in CD34(+) HSCs and semaphorin 3A (SEMA3A) in BMSCs. To better understand the role of VEGFA and SEMA3A in leukemogenesis, we recruited 30 myelodysplastic syndrome (MDS) patients, 29 acute myeloid leukemia (6 secondary to MDS) patients and 12 controls...
June 3, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28627605/mesenchymal-stem-cells-promote-endothelial-progenitor-cell-proliferation-by-secreting-insulin%C3%A2-like-growth-factor%C3%A2-1
#8
Jixue Hou, Xinyu Peng, Jing Wang, Hongwei Zhang, Jie Xia, Quanhu Ge, Xiaoyi Wang, Xueling Chen, Xiangwei Wu
Bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) interact with each other. EPCs are able to promote the self‑renewal of MSCs as niche cells in murine bone marrow, and MSCs are able to promote EPC proliferation in vitro in a co‑culture system. It has previously been reported that MSCs can secrete insulin‑like growth factor‑1 (IGF‑1), which serves critical functions in EPC proliferation. However, the mechanism underlying the IGF‑1‑mediated proliferation of EPCs remains unclear...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28626366/current-developments-in-mobilization-of-hematopoietic-stem-and-progenitor-cells-and-their-interaction-with-niches-in-bone-marrow
#9
REVIEW
Rudolf Richter, Wolfgang Forssmann, Reinhard Henschler
The clinical application of hematopoietic stem and progenitor cells (HSPCs) has evolved from a highly experimental stage in the 1980s to a currently clinically established treatment for more than 20,000 patients annually who suffer from hematological malignancies and other severe diseases. Studies in numerous murine models have demonstrated that HSPCs reside in distinct niches within the bone marrow environment. Whereas transplanted HSPCs travel through the bloodstream and home to sites of hematopoiesis, HSPCs can be mobilized from these niches into the blood either physiologically or induced by pharmaceutical drugs...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28619982/jak1-2-and-bcl2-inhibitors-synergize-to-counteract-bone-marrow-stromal-cell-induced-protection-of-aml
#10
Riikka Karjalainen, Tea Pemovska, Mihaela Popa, Minxia Liu, Komal K Javarappa, Muntasir M Majumder, Bhagwan Yadav, David Tamborero, Jing Tang, Dmitrii Bychkov, Mika Kontro, Alun Parsons, Minna Suvela, Mireia Mayoral Safont, Kimmo Porkka, Tero Aittokallio, Olli Kallioniemi, Emmet McCormack, Bjørn T Gjertsen, Krister Wennerberg, Jonathan Knowles, Caroline A Heckman
The bone marrow (BM) provides a protective microenvironment to support the survival of leukemic cells and influence their response to therapeutic agents. In acute myeloid leukemia (AML), the high rate of relapse may in part be due to the inability of current treatment to effectively overcome the protective influence of the BM niche. To better understand the impact of the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhibitors, including approved and investigational agents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture conditions...
June 15, 2017: Blood
https://www.readbyqxmd.com/read/28617253/the-emerging-role-of-the-human-bone-marrow-as-a-privileged-developmental-niche-for-the-transmission-stages-of-the-malaria-parasite-plasmodium-falciparum-commentary
#11
Pietro Alano
The spread of malaria relies on the ability of the Plasmodium parasites to be transmitted from infected individuals to the Anopheles mosquito vectors. Recent work on the most lethal of the malaria parasites, Plasmodium falciparum, identified the infected human bone marrow as a preferential site for the localization and maturation of the parasite transmission stages, the gametocytes. These findings unveil a complex host parasite interplay and an unsuspected role of the bone marrow microenvironment in the successful transmission of the malaria parasite and have major implications in developing and targeting future interventions to block the transmission of P...
April 2017: Annali Dell'Istituto Superiore di Sanità
https://www.readbyqxmd.com/read/28616152/magnetically-levitated-mesenchymal-stem-cell-spheroids-cultured-with-a-collagen-gel-maintain-phenotype-and-quiescence
#12
Natasha S Lewis, Emily El Lewis, Margaret Mullin, Helen Wheadon, Matthew J Dalby, Catherine C Berry
Multicellular spheroids are an established system for three-dimensional cell culture. Spheroids are typically generated using hanging drop or non-adherent culture; however, an emerging technique is to use magnetic levitation. Herein, mesenchymal stem cell spheroids were generated using magnetic nanoparticles and subsequently cultured within a type I collagen gel, with a view towards developing a bone marrow niche environment. Cells were loaded with magnetic nanoparticles, and suspended beneath an external magnet, inducing self-assembly of multicellular spheroids...
January 2017: Journal of Tissue Engineering
https://www.readbyqxmd.com/read/28604734/adult-haematopoietic-stem-cell-niches
#13
REVIEW
Genevieve M Crane, Elise Jeffery, Sean J Morrison
Stem cell niches are specialized microenvironments that promote the maintenance of stem cells and regulate their function. Recent advances have improved our understanding of the niches that maintain adult haematopoietic stem cells (HSCs). These advances include new markers for HSCs and niche cells, systematic analyses of the expression patterns of niche factors, genetic tools for functionally identifying niche cells in vivo, and improved imaging techniques. Together, they have shown that HSC niches are perivascular in the bone marrow and spleen...
June 12, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28603948/limb-derived-cells-as-a-paradigm-for-engineering-self-assembling-skeletal-tissues
#14
Warnakulasuriya A Fernando, Ioannis Papantoniou, Luis F Mendes, Gabriella Nilsson Hall, Kathleen Bosmans, Wai L Tam, Liliana M Teixeira, Malcolm Moos, Liesbet Geris, Frank P Luyten
Mimicking developmental events has been proposed as a strategy to engineer tissue constructs for regenerative medicine. However, this approach has not yet been investigated for skeletal tissues. Here we demonstrate that ectopic implantation of mouse embryonic day 14.5 long bone anlagen, dissociated into single cells and randomly incorporated in a bioengineered construct, give rise to epiphyseal growth plate like structures, bone, and marrow, which share many morphological and molecular similarities to epiphyseal units that form after transplanting intact long bone anlage, demonstrating substantial robustness and autonomy of complex tissue self-assembly and the overall organogenesis process...
June 11, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28603714/defining-disease-diagnosis-and-translational-medicine-within-a-homeostatic-perturbation-paradigm-the-national-institutes-of-health-undiagnosed-diseases-program-experience
#15
Timothy Gall, Elise Valkanas, Christofer Bello, Thomas Markello, Christopher Adams, William P Bone, Alexander J Brandt, Jennifer M Brazill, Lynn Carmichael, Mariska Davids, Joie Davis, Zoraida Diaz-Perez, David Draper, Jeremy Elson, Elise D Flynn, Rena Godfrey, Catherine Groden, Cheng-Kang Hsieh, Roxanne Fischer, Gretchen A Golas, Jessica Guzman, Yan Huang, Megan S Kane, Elizabeth Lee, Chong Li, Amanda E Links, Valerie Maduro, May Christine V Malicdan, Fayeza S Malik, Michele Nehrebecky, Joun Park, Paul Pemberton, Katherine Schaffer, Dimitre Simeonov, Murat Sincan, Damian Smedley, Zaheer Valivullah, Colleen Wahl, Nicole Washington, Lynne A Wolfe, Karen Xu, Yi Zhu, William A Gahl, Cynthia J Tifft, Camillo Toro, David R Adams, Miao He, Peter N Robinson, Melissa A Haendel, R Grace Zhai, Cornelius F Boerkoel
Traditionally, the use of genomic information for personalized medical decisions relies on prior discovery and validation of genotype-phenotype associations. This approach constrains care for patients presenting with undescribed problems. The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) hypothesized that defining disease as maladaptation to an ecological niche allows delineation of a logical framework to diagnose and evaluate such patients. Herein, we present the philosophical bases, methodologies, and processes implemented by the NIH UDP...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28600504/amphiregulin-contained-in-nsclc-exosomes-induces-osteoclast-differentiation-through-the-activation-of-egfr-pathway
#16
Simona Taverna, Marzia Pucci, Marco Giallombardo, Maria Antonietta Di Bella, Mariacarmela Santarpia, Pablo Reclusa, Ignacio Gil-Bazo, Christian Rolfo, Riccardo Alessandro
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. The majority of patients are diagnosed in advanced disease stage. Bone metastasis is the most frequent complication in NSCLC resulting in osteolytic lesions. The perfect balance between bone-resorbing osteoclasts and bone-forming osteoblasts activity is lost in bone metastasis, inducing osteoclastogenesis. In NSCLC, the epidermal growth factor receptor (EGFR) pathway is constitutively activated. EGFR binds Amphiregulin (AREG) that is overexpressed in several cancers such as colon, breast and lung...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596376/cre-lox-studies-identify-resident-macrophages-as-the-major-source-of-circulating-coagulation-factor-xiii-a
#17
Cora M L Beckers, Kingsley R Simpson, Kathryn J Griffin, Jane M Brown, Lih T Cheah, Kerrie A Smith, Jean Vacher, Paul A Cordell, Mark T Kearney, Peter J Grant, Richard J Pease
OBJECTIVE: To establish the cellular source of plasma factor (F)XIII-A. APPROACH AND RESULTS: A novel mouse floxed for the F13a1 gene, FXIII-A(flox/flox) (Flox), was crossed with myeloid- and platelet-cre-expressing mice, and cellular FXIII-A mRNA expression and plasma and platelet FXIII-A levels were measured. The platelet factor 4-cre.Flox cross abolished platelet FXIII-A and reduced plasma FXIII-A to 23±3% (P<0.001). However, the effect of platelet factor 4-cre on plasma FXIII-A was exerted outside of the megakaryocyte lineage because plasma FXIII-A was not reduced in the Mpl(-/-) mouse, despite marked thrombocytopenia...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28589100/microrna-21-limits-uptake-of-listeria-monocytogenes-by-macrophages-to-reduce-the-intracellular-niche-and-control-infection
#18
Daniel G W Johnston, Jay Kearney, Zbigniew Zasłona, Michelle A Williams, Luke A J O'Neill, Sinéad C Corr
MiRNAs are important post-transcriptional regulators of gene expression. MiRNA expression is a crucial part of host responses to bacterial infection, however there is limited knowledge of their impact on the outcome of infections. We investigated the influence of miR-21 on macrophage responses during infection with Listeria monocytogenes, which establishes an intracellular niche within macrophages. MiR-21 is induced following infection of bone marrow-derived macrophages (BMDMs) with Listeria. MiR-21(-/-) macrophages display an increased bacterial burden with Listeria at 30 min and 2 h post-infection...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28581488/osteoblast-derived-laminin-332-is-a-novel-negative-regulator-of-osteoclastogenesis-in-bone-microenvironments
#19
Norihisa Uehara, Akiko Kukita, Yukari Kyumoto-Nakamura, Takayoshi Yamaza, Hisataka Yasuda, Toshio Kukita
Laminin-332 (Lm-332), a major basement membrane protein, has been shown to provide a niche for some stem cells. Here, we found that Lm-332 was expressed in osteoblasts, and is implicated in the regulation of osteoclast differentiation. Immunofluorescence analysis of laminin-β3, a unique component of Lm-332, indicated specific expression of laminin-β3 in osteoblast-like cells localized on bone surface. RT-PCR analysis confirmed that α3, β3, and γ2 chains of Lm-332 were all expressed in primary osteoblasts prepared from mouse calvaria...
June 5, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28577070/heparan-sulfate-proteoglycans-as-key-regulators-of-the-mesenchymal-niche-of-hematopoietic-stem-cells
#20
Dulce Papy-Garcia, Patricia Albanese
The complex microenvironment that surrounds hematopoietic stem cells (HSCs) in the bone marrow niche involves different coordinated signaling pathways. The stem cells establish permanent interactions with distinct cell types such as mesenchymal stromal cells, osteoblasts, osteoclasts or endothelial cells and with secreted regulators such as growth factors, cytokines, chemokines and their receptors. These interactions are mediated through adhesion to extracellular matrix compounds also. All these signaling pathways are important for stem cell fates such as self-renewal, proliferation or differentiation, homing and mobilization, as well as for remodeling of the niche...
June 2017: Glycoconjugate Journal
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