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https://www.readbyqxmd.com/read/28098771/breast-cancer-brain-metastases-clonal-evolution-in-clinical-context
#1
REVIEW
Jodi M Saunus, Amy E McCart Reed, Zhun Leong Lim, Sunil R Lakhani
Brain metastases are highly-evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely-held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28097054/hydrogel-scaffolds-promote-neural-gene-expression-and-structural-reorganization-in-human-astrocyte-cultures
#2
V Bleu Knight, Elba E Serrano
Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro. Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene...
2017: PeerJ
https://www.readbyqxmd.com/read/28096221/efficient-crispr-cas9-assisted-gene-targeting-enables-rapid-and-precise-genetic-manipulation-of-mammalian-neural-stem-cells
#3
Raul Bardini Bressan, Pooran Singh Dewari, Maria Kalantzaki, Ester Gangoso, Mantas Matjusaitis, Claudia Garcia-Diaz, Carla Blin, Vivien Grant, Harry Bulstrode, Sabine Gogolok, William C Skarnes, Steven M Pollard
Mammalian neural stem (NS) cell lines provide a tractable model for discovery across stem cell and developmental biology, regenerative medicine and neuroscience. They can be derived from foetal or adult germinal tissues and continuously propagated in vitro as adherent monolayers. NS cells are clonally expandable, genetically stable, and easily transfectable - experimental attributes compatible with targeted genetic manipulations. However, gene targeting - so critical for functional studies of embryonic stem cells - has not been exploited to date in NS cells...
January 17, 2017: Development
https://www.readbyqxmd.com/read/28094018/single-cell-analysis-reveals-a-close-relationship-between-differentiating-dopamine-and-subthalamic-nucleus-neuronal-lineages
#4
Nigel Kee, Nikolaos Volakakis, Agnete Kirkeby, Lina Dahl, Helena Storvall, Sara Nolbrant, Laura Lahti, Åsa K Björklund, Linda Gillberg, Eliza Joodmardi, Rickard Sandberg, Malin Parmar, Thomas Perlmann
Stem cell engineering and grafting of mesencephalic dopamine (mesDA) neurons is a promising strategy for brain repair in Parkinson's disease (PD). Refinement of differentiation protocols to optimize this approach will require deeper understanding of mesDA neuron development. Here, we studied this process using transcriptome-wide single-cell RNA sequencing of mouse neural progenitors expressing the mesDA neuron determinant Lmx1a. This approach resolved the differentiation of mesDA and neighboring neuronal lineages and revealed a remarkably close relationship between developing mesDA and subthalamic nucleus (STN) neurons, while also highlighting a distinct transcription factor set that can distinguish between them...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28092363/mouse-models-of-uv-induced-melanoma-genetics-pathology-and-clinical-relevance
#5
Chi-Ping Day, Rachel Marchalik, Glenn Merlino, Helen Michael
Melanocytes, a neural crest cell derivative, produce pigment to protect keratinocytes from ultraviolet radiation (UVR). Although melanocytic lesions such as nevi and cutaneous malignant melanomas are known to be associated with sun exposure, the role of UVR in oncogenesis is complex and has yet to be clearly elucidated. UVR appears to have a direct mutational role in inducing or promoting melanoma formation as well as an indirect role through microenvironmental changes. Recent advances in the modeling of human melanoma in animals have built platforms upon which prospective studies can begin to investigate these questions...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28089234/oncogenic-kras-induced-increase-in-fluid-phase-endocytosis-is-dependent-on-n-wasp-and-is-required-for-the-formation-of-pancreatic-preneoplastic-lesions
#6
Clara Lubeseder-Martellato, Katharina Alexandrow, Ana Hidalgo-Sastre, Irina Heid, Sophie Luise Boos, Thomas Briel, Roland M Schmid, Jens T Siveke
Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas(G12D) leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE...
December 24, 2016: EBioMedicine
https://www.readbyqxmd.com/read/28088484/optimal-trajectories-of-brain-state-transitions
#7
Shi Gu, Richard F Betzel, Marcelo G Mattar, Matthew Cieslak, Philip R Delio, Scott T Grafton, Fabio Pasqualetti, Danielle S Bassett
The complexity of neural dynamics stems in part from the complexity of the underlying anatomy. Yet how white matter structure constrains how the brain transitions from one cognitive state to another remains unknown. Here we address this question by drawing on recent advances in network control theory to model the underlying mechanisms of brain state transitions as elicited by the collective control of region sets. We find that previously identified attention and executive control systems are poised to affect a broad array of state transitions that cannot easily be classified by traditional engineering-based notions of control...
January 11, 2017: NeuroImage
https://www.readbyqxmd.com/read/28079187/a-spiking-neural-network-model-of-3d-perception-for-event-based-neuromorphic-stereo-vision-systems
#8
Marc Osswald, Sio-Hoi Ieng, Ryad Benosman, Giacomo Indiveri
Stereo vision is an important feature that enables machine vision systems to perceive their environment in 3D. While machine vision has spawned a variety of software algorithms to solve the stereo-correspondence problem, their implementation and integration in small, fast, and efficient hardware vision systems remains a difficult challenge. Recent advances made in neuromorphic engineering offer a possible solution to this problem, with the use of a new class of event-based vision sensors and neural processing devices inspired by the organizing principles of the brain...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065938/efficient-implementation-of-a-real-time-estimation-system-for-thalamocortical-hidden-parkinsonian-properties
#9
Shuangming Yang, Bin Deng, Jiang Wang, Huiyan Li, Chen Liu, Chris Fietkiewicz, Kenneth A Loparo
Real-time estimation of dynamical characteristics of thalamocortical cells, such as dynamics of ion channels and membrane potentials, is useful and essential in the study of the thalamus in Parkinsonian state. However, measuring the dynamical properties of ion channels is extremely challenging experimentally and even impossible in clinical applications. This paper presents and evaluates a real-time estimation system for thalamocortical hidden properties. For the sake of efficiency, we use a field programmable gate array for strictly hardware-based computation and algorithm optimization...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28060704/segnet-a-deep-convolutional-encoder-decoder-architecture-for-scene-segmentation
#10
Vijay Badrinarayanan, Alex Kendall, Roberto Cipolla
We present a novel and practical deep fully convolutional neural network architecture for semantic pixel-wise segmentation termed SegNet. This core trainable segmentation engine consists of an encoder network, a corresponding decoder network followed by a pixel-wise classification layer. The architecture of the encoder network is topologically identical to the 13 convolutional layers in the VGG16 network [1]. The role of the decoder network is to map the low resolution encoder feature maps to full input resolution feature maps for pixel-wise classification...
January 2, 2017: IEEE Transactions on Pattern Analysis and Machine Intelligence
https://www.readbyqxmd.com/read/28058503/genetic-manipulation-of-specific-neural-circuits-by-use-of-a-viral-vector-system
#11
REVIEW
Kenta Kobayashi, Shigeki Kato, Kazuto Kobayashi
To understand the mechanisms underlying higher brain functions, we need to analyze the roles of specific neuronal pathways or cell types forming the complex neural networks. In the neuroscience field, the transgenic approach has provided a useful gene engineering tool for experimental studies of neural functions. The conventional transgenic technique requires the appropriate promoter regions that drive a neuronal type-specific gene expression, but the promoter sequences specifically functioning in each neuronal type are limited...
January 5, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28057438/oncogenic-kras-induced-increase-in-fluid-phase-endocytosis-is-dependent-on-n-wasp-and-is-required-for-the-formation-of-pancreatic-preneoplastic-lesions
#12
Clara Lubeseder-Martellato, Katharina Alexandrow, Ana Hidalgo-Sastre, Irina Heid, Sophie Luise Boos, Thomas Briel, Roland M Schmid, Jens T Siveke
Fluid-phase endocytosis is a homeostatic process with an unknown role in tumor initiation. The driver mutation in pancreatic ductal adenocarcinoma (PDAC) is constitutively active KRas(G12D), which induces neoplastic transformation of acinar cells through acinar-to-ductal metaplasia (ADM). We have previously shown that KRas(G12D)-induced ADM is dependent on RAC1 and EGF receptor (EGFR) by a not fully clarified mechanism. Using three-dimensional mouse and human acinar tissue cultures and genetically engineered mouse models, we provide evidence that (i) KRas(G12D) leads to EGFR-dependent sustained fluid-phase endocytosis (FPE) during acinar metaplasia; (ii) variations in plasma membrane tension increase FPE and lead to ADM in vitro independently of EGFR; and (iii) that RAC1 regulates ADM formation partially through actin-dependent regulation of FPE...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28054637/salidroside-promotes-peripheral-nerve-regeneration-based-on-tissue-engineering-strategy-using-schwann-cells-and-plga-in-vitro-and-in-vivo
#13
Hui Liu, Peizhen Lv, Yongjia Zhu, Huayu Wu, Kun Zhang, Fuben Xu, Li Zheng, Jinmin Zhao
Salidriside (SDS), a phenylpropanoid glycoside derived from Rhodiola rosea L, has been shown to be neuroprotective in many studies, which may be promising in nerve recovery. In this study, the neuroprotective effects of SDS on engineered nerve constructed by Schwann cells (SCs) and Poly (lactic-co-glycolic acid) (PLGA) were studied in vitro. We further investigated the effect of combinational therapy of SDS and PLGA/SCs based tissue engineering on peripheral nerve regeneration based on the rat model of nerve injury by sciatic transection...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28052540/engineered-neural-tissue-with-schwann-cell-differentiated-human-dental-pulp-stem-cells-potential-for-peripheral-nerve-repair
#14
Kathleen Sanen, Wendy Martens, Melanie Georgiou, Marcel Ameloot, Ivo Lambrichts, James Phillips
Despite the spontaneous regenerative capacity of the peripheral nervous system, large gap peripheral nerve injuries (PNIs) require bridging strategies. The limitations and suboptimal results obtained with autografts or hollow nerve conduits in the clinic urge the need for alternative treatments. Recently, we have described promising neuroregenerative capacities of Schwann cells derived from differentiated human dental pulp stem cells (d-hDPSCs) in vitro. Here, we extended the in vitro assays to show the pro-angiogenic effects of d-hDPSCs, such as enhanced endothelial cell proliferation, migration and differentiation...
January 4, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28045049/mir-218-induces-neuronal-differentiation-of-ascs-in-a-temporally-sequential-manner-with-fibroblast-growth-factor-by-regulation-of-the-wnt-signaling-pathway
#15
Feihu Hu, Bo Sun, Peng Xu, Yanliang Zhu, Xian-Hui Meng, Gao-Jun Teng, Zhong-Dang Xiao
Differentiation of neural lineages from mesenchymal stem cells has raised the hope of generating functional cells as seed cells for nerve tissue engineering. As important gene regulators, microRNAs (miRNAs) have been speculated to play a vital role in accelerating stem cell differentiation and repairing neuron damage. However, miRNA roles in directing differentiation of stem cells in current protocols are underexplored and the mechanisms of miRNAs as regulators of neuronal differentiation remain ambiguous. In this study, we have determined that miR-218 serves as crucial constituent regulator in neuronal differentiation of adipose stem cells (ASCs) through Wnt signaling pathway based on comprehensive annotation of miRNA sequencing data...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28040687/de-identification-of-patient-notes-with-recurrent-neural-networks
#16
Franck Dernoncourt, Ji Young Lee, Ozlem Uzuner, Peter Szolovits
OBJECTIVE: Patient notes in electronic health records (EHRs) may contain critical information for medical investigations. However, the vast majority of medical investigators can only access de-identified notes, in order to protect the confidentiality of patients. In the United States, the Health Insurance Portability and Accountability Act (HIPAA) defines 18 types of protected health information that needs to be removed to de-identify patient notes. Manual de-identification is impractical given the size of electronic health record databases, the limited number of researchers with access to non-de-identified notes, and the frequent mistakes of human annotators...
December 30, 2016: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/28032743/sustained-local-release-of-ngf-from-a-chitosan-sericin-composite-scaffold-for-treating-chronic-nerve-compression
#17
Lei Zhang, Wen Yang, Kaixiong Tao, Yu Song, Hongjian Xie, Jian Wang, Xiaolin Li, Xiaoming Shuai, Jinbo Gao, Panpan Chang, Guobin Wang, Zheng Wang, Lin Wang
Chronic nerve compression (CNC), such as carpal tunnel syndrome (CTS), is a common cause of peripheral nerve dysfunction and chronic peripheral nerve pain. Current available treatments for CNC are ineffective as they usually aim to alleviate symptoms at the acute phase with limited capability towards restoring injured nerve function. New approaches for effective recovery of CNC injury are highly desired. Here we report for the first time a tissue-engineered approach for the repair of CNC. A genipin cross-linked chitosan-sericin 3D scaffold for delivering nerve growth factor (NGF) was designed and fabricated...
December 29, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28024405/boosting-docking-based-virtual-screening-with-deep-learning
#18
Janaina Cruz Pereira, Ernesto Raúl Caffarena, Cicero Nogueira Dos Santos
In this work, we propose a deep learning approach to improve docking-based virtual screening. The deep neural network that is introduced, DeepVS, uses the output of a docking program and learns how to extract relevant features from basic data such as atom and residues types obtained from protein-ligand complexes. Our approach introduces the use of atom and amino acid embeddings and implements an effective way of creating distributed vector representations of protein-ligand complexes by modeling the compound as a set of atom contexts that is further processed by a convolutional layer...
December 27, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28005222/effects-of-nerve-growth-factor-and-basic-fibroblast-growth-factor-promote-human-dental-pulp-stem-cells-to-neural-differentiation
#19
Jinlong Zhang, Min Lian, Peipei Cao, Guofeng Bao, Guanhua Xu, Yuyu Sun, Lingling Wang, Jiajia Chen, Yi Wang, Guijuan Feng, Zhiming Cui
Dental pulp stem cells (DPSCs) were the most widely used seed cells in the field of neural regeneration and bone tissue engineering, due to their easily isolation, lack of ethical controversy, low immunogenicity and low rates of transplantation rejection. The purpose of this study was to investigate the role of basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) on neural differentiation of DPSCs in vitro. DPSCs were cultured in neural differentiation medium containing NGF and bFGF alone or combination for 7 days...
December 22, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27998214/fabrication-of-a-highly-aligned-neural-scaffold-via-a-table-top-stereolithography-3d-printing-and-electrospinning
#20
Se-Jun Lee, Margaret Nowicki, Brent Harris, Lijie Grace Zhang
Three-dimensional (3D) bioprinting is a rapidly emerging technique in the field of tissue engineering to fabricate extremely intricate and complex biomimetic scaffolds in the range of micrometers. Such customized 3D printed constructs can be used for the regeneration of complex tissues such as cartilage, vessels, and nerves. However, the 3D printing techniques often offer limited control over the resolution and compromised mechanical properties due to short selection of printable inks. To address these limitations, we combined stereolithography and electrospinning techniques to fabricate a novel 3D biomimetic neural scaffold with a tunable porous structure and embedded aligned fibers...
January 11, 2017: Tissue Engineering. Part A
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