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https://www.readbyqxmd.com/read/28101194/inhibition-of-nedd8-and-fat10-ligase-activities-through-the-degrading-enzyme-nedd8-ultimate-buster-1-a-potential-anticancer-approach
#1
Ka-Liong Tan, Francesco Pezzella
The capabilities of tumour cells to survive through deregulated cell cycles and evade apoptosis are hallmarks of cancer. The ubiquitin-like proteins (UBL) proteasome system is important in regulating cell cycles via signaling proteins. Deregulation of the proteasomal system can lead to uncontrolled cell proliferation. The Skp, Cullin, F-box containing complex (SCF complex) is the predominant E3 ubiquitin ligase, and has diverse substrates. The ubiquitin ligase activity of the SCF complexes requires the conjugation of neural precursor cell expressed, developmentally down-regulated 8 (NEDD8) to cullin proteins...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100644/multicellular-hypothesis-for-the-pathogenesis-of-alzheimer-s-disease
#2
Edward J Goetzl, Bruce L Miller
Extensive abnormal interactions among microglia, astrocytes, and neurons of the CNS have been observed in proteinopathic neurodegenerative dementias of the elderly. These multicellular interactions are initiated by insoluble tangles of phosphorylated tau protein and plaques of amyloid peptides. Most research has focused on these neurotoxic proteins, but much less is known about the pathogenic roles of the responding resident and recruited neural cells. Principal interactions among the major 3 sets of CNS cells are herein considered at several levels in relation to cellular phenotypic alterations, mechanisms of cellular communication, and extent of involvement in the pathogenesis of Alzheimer's disease and related proteinopathic dementias...
January 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28099961/perineural-invasion-is-associated-with-poor-survival-after-preoperative-chemoradiation-therapy-for-advanced-lower-rectal-cancer
#3
Shozo Yokoyama, Kenji Matsuda, Takashi Watanabe, Yasuyuki Mitani, Junji Ieda, Hiromitsu Iwamoto, Tsukasa Hotta, Katsunari Takifuji, Hiroki Yamaue
BACKGROUND: Preoperative chemoradiation therapy (pCRT) is a standard procedure for patients with advanced lower rectal cancer. It has been reported that pCRT cannot prolong the survival of patients with advanced lower rectal cancer. The aim of this study is to address the controllable and uncontrollable pathological factors of pCRT in predicting local and distant recurrences. METHODS: One hundred two patients with stages 2 and 3 cancer were consecutively enrolled to the study...
January 19, 2017: Digestive Surgery
https://www.readbyqxmd.com/read/28098771/breast-cancer-brain-metastases-clonal-evolution-in-clinical-context
#4
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/28096400/defining-recovery-neurobiology-of-injured-spinal-cord-by-synthetic-matrix-assisted-hmsc-implantation
#5
Alexander E Ropper, Devang K Thakor, InBo Han, Dou Yu, Xiang Zeng, Jamie E Anderson, Zaid Aljuboori, Soo-Woo Kim, Hongjun Wang, Richard L Sidman, Ross D Zafonte, Yang D Teng
Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096186/translation-reprogramming-is-an-evolutionarily-conserved-driver-of-phenotypic-plasticity-and-therapeutic-resistance-in-melanoma
#6
Paola Falletta, Luis Sanchez-Del-Campo, Jagat Chauhan, Maike Effern, Amy Kenyon, Christopher J Kershaw, Robert Siddaway, Richard Lisle, Rasmus Freter, Matthew J Daniels, Xin Lu, Thomas Tüting, Mark Middleton, Francesca M Buffa, Anne E Willis, Graham Pavitt, Ze'ev A Ronai, Tatjana Sauka-Spengler, Michael Hölzel, Colin R Goding
The intratumor microenvironment generates phenotypically distinct but interconvertible malignant cell subpopulations that fuel metastatic spread and therapeutic resistance. Whether different microenvironmental cues impose invasive or therapy-resistant phenotypes via a common mechanism is unknown. In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, and drug resistance. However, how MITF is suppressed in vivo and how MITF-low cells in tumors escape senescence are poorly understood...
January 17, 2017: Genes & Development
https://www.readbyqxmd.com/read/28094811/brain-connectivity-changes-occurring-following-cognitive-behavioural-therapy-for-psychosis-predict-long-term-recovery
#7
L Mason, E Peters, S C Williams, V Kumari
Little is known about the psychobiological mechanisms of cognitive behavioural therapy for psychosis (CBTp) and which specific processes are key in predicting favourable long-term outcomes. Following theoretical models of psychosis, this proof-of-concept study investigated whether the long-term recovery path of CBTp completers can be predicted by the neural changes in threat-based social affective processing that occur during CBTp. We followed up 22 participants who had undergone a social affective processing task during functional magnetic resonance imaging along with self-report and clinician-administered symptom measures, before and after receiving CBTp...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28094018/single-cell-analysis-reveals-a-close-relationship-between-differentiating-dopamine-and-subthalamic-nucleus-neuronal-lineages
#8
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/28093705/manipulation-of-oxygen-and-endoplasmic-reticulum-stress-factors-as-possible-interventions-for-treatment-of-multiple-sclerosis-evidence-for-and-against
#9
Paul Eggleton, Gary R Smerdon, Janet E Holley, Nicholas J Gutowski
Multiple sclerosis (MS) is normally considered a chronic inflammatory disease of the central nervous system (CNS), where T-cells breaching the blood brain barrier react against proteins of the axonal myelin sheaths, leading to focal plaques and demyelination in the brain and spinal cord. Many current therapies are immunosuppressive in nature and are designed to target the immune system at an early stage of the disease. But there is no cure and MS may evolve into a neurodegenerative disease, where immunomodulatory treatments appear less effective...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28091786/a-new-look-at-the-drug-resistance-investigation-of-uropathogenic-e-coli-strains
#10
Wioletta Adamus-Białek, Łukasz Lechowicz, Anna B Kubiak-Szeligowska, Monika Wawszczak, Ewelina Kamińska, Magdalena Chrapek
Bacterial drug resistance and uropathogenic tract infections are among the most important issues of current medicine. Uropathogenic Escherichia coli strains are the primary factor of this issue. This article is the continuation of the previous study, where we used Kohonen relations to predict the direction of drug resistance. The characterized collection of uropathogenic E. coli strains was used for microbiological (the disc diffusion method for antimicrobial susceptibility testing), chemical (ATR/FT-IR) and mathematical (artificial neural networks, Ward's hierarchical clustering method, the analysis of distributions of inhibition zone diameters for antibiotics, Cohen's kappa measure of agreement) analysis...
January 13, 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28089669/exposure-to-gdnf-enhances-the-ability-of-enteric-neural-progenitors-to%C3%A2-generate-an-enteric-nervous-system
#11
Sonja J McKeown, Mitra Mohsenipour, Annette J Bergner, Heather M Young, Lincon A Stamp
Cell therapy is a promising approach to generate an enteric nervous system (ENS) and treat enteric neuropathies. However, for translation to the clinic, it is highly likely that enteric neural progenitors will require manipulation prior to transplantation to enhance their ability to migrate and generate an ENS. In this study, we examine the effects of exposure to several factors on the ability of ENS progenitors, grown as enteric neurospheres, to migrate and generate an ENS. Exposure to glial-cell-line-derived neurotrophic factor (GDNF) resulted in a 14-fold increase in neurosphere volume and a 12-fold increase in cell number...
January 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28089606/parasacral-transcutaneous-electrical-neural-stimulation-ptens-once-a-week-for-the-treatment-of-overactive-bladder-in-children-a-randomized-controlled-trial
#12
Lidyanne Ilidia da Silva de Paula, Liliana Fajardo de Oliveira, Brysa Paiva Cruz, Dayana Maria de Oliveira, Laís Maini Miranda, Mauro de Moraes Ribeiro, Raphaela Ornellas Duque, André Avarese de Figueiredo, José de Bessa, José Murillo Bastos Netto
INTRODUCTION: Overactive bladder (OAB) is the most prevalent voiding disorder in childhood, and its main manifestation is urinary urgency. In general, urotherapy and anticholinergics are the first choices of treatment. Parasacral Transcutaneous Electrical Neural Stimulation (PTENS) was introduced as an alternative for the treatment of detrusor overactivity in children, but treatment protocols described to date require several sessions per week or long-lasting sessions, making it difficult for the child to adhere to the treatment...
December 21, 2016: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/28087763/circadian-kinetics-of-cell-cycle-progression-in-adult-neurogenic-niches-of-a-diurnal-vertebrate
#13
Veronica Akle, Alexander J Stankiewicz, Vasili Kharchenko, Lili Yu, Peter V Kharchenko, Irina V Zhdanova
: The circadian system may regulate adult neurogenesis via intracellular molecular clock mechanisms or by modifying the environment of neurogenic niches, with daily variation in growth factors or nutrients depending on the animal's diurnal or nocturnal life-style. In a diurnal vertebrate, zebrafish, we studied circadian distribution of immunohistochemical markers of the cell division cycle (CDC) in five of the sixteen neurogenic niches of adult brain, the dorsal telencephalon, habenula, preoptic area, hypothalamus and cerebellum...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28079995/effects-of-cell-cycle-phases-on-the-induction-of-dental-pulp-stem-cells-toward-dopaminergic-like-cells
#14
Nareshwaran Gnanasegaran, Vijayendran Govindasamy, Premasangery Kathirvaloo, Sabri Musa, Noor Hayaty Abu Kasim
Parkinson's disease (PD) is characterized by tremors and cognitive issues, and is due to the death of dopaminergic (DA-ergic) neurons in brain circuits that are responsible for producing neurotransmitter dopamine (DA). Currently, cell replacement therapies are underway to overcome existing therapeutic approaches such as drug treatments and electrical stimulation. Among the widely available sources, dental pulp stem cells from deciduous teeth (DPSC) have gained popularity due to their neural crest origin and inherent propensity toward neuronal lineage...
January 12, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28079471/pre-implant-modeling-of-depth-lead-placement-in-white-matter-for-maximizing-the-extent-of-cortical-activation-during-direct-neurostimulation-therapy
#15
Leopoldo Cendejas Zaragoza, Richard W Byrne, Marvin A Rossi
INTRODUCTION: The objective of this work was to predict preoperatively the maximum extent to which direct stimulation therapy can propagate through an epileptic circuit for stabilizing refractory focal-onset epilepsy. A pre-surgical workflow is presented which comprises a computationally intensive process for calculating the volume of cortical activation (VOCA) surrounding cylindrical depth contacts virtually placed in white matter. The process employs an activation function (AF) derived from cable modeling of an axon...
January 12, 2017: Neurological Research
https://www.readbyqxmd.com/read/28077715/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#16
Amber L Alhadeff, Ruby A Holland, Huiyuan Zheng, Linda Rinaman, Harvey J Grill, Bart C De Jonghe
: Cisplatin chemotherapy is commonly used to treat cancer despite severe energy balance side effects. In rats, cisplatin activates nucleus tractus solitarius (NTS) projections to the lateral parabrachial nucleus (lPBN) and calcitonin-gene related peptide (CGRP) projections from the lPBN to the central nucleus of the amygdala (CeA). We demonstrated previously that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we used neuroanatomical tracing, immunofluorescence, and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections coexpress vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28076702/lasmiditan-for-the-treatment-of-migraine
#17
Matilde Capi, Fernando de Andrés, Luana Lionetto, Giovanna Gentile, Fabiola Cipolla, Marina Borro, Paolo Martelletti, Martina Curto
Migraine is one of the most common diseases in the world, with high economical and subjective burden. Migraine acute therapy is nowadays based on specific and non-specific drugs but up to 40% of episodic migraineurs still have unmet treatment needs and over 35% do not benefit from triptans administration. Serotonin-1F receptors have been identified in trigeminal system and became an ideal target for anti-migraine drug development as potential trigeminal neural inhibitors. Lasmiditan, a novel serotonin1F receptor agonist, showed specific affinity in vitro for the receptor with any vasoconstrictive action and inhibited markers associated with electrical stimulation of trigeminal ganglion in migraine animal models...
January 11, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28076681/computational-modeling-of-neurotransmitter-release-evoked-by-electrical-stimulation-non-linear-approaches-to-predicting-stimulation-evoked-dopamine-release
#18
James K Trevathan, Ali Yousefi, Hyung Ook Park, John J Bartoletta, Kip A Ludwig, Kendall H Lee, J Luis Lujan
Neurochemical changes evoked by electrical stimulation of the nervous system have been linked to both therapeutic and undesired effects of neuromodulation therapies used to treat obsessive-compulsive disorder, depression, epilepsy, Parkinson's disease, stroke, hypertension, tinnitus, and many other indications. In fact, interest in better understanding the role of neurochemical signaling in neuromodulation therapies has been a focus of recent government- and industry-sponsored programs whose ultimate goal is to usher in an era of personalized medicine by creating neuromodulation therapies that respond to real-time changes in patient status...
January 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28073086/human-neural-progenitors-derived-from-integration-free-ipscs-for-sci-therapy
#19
Ying Liu, Yiyan Zheng, Shenglan Li, Haipeng Xue, Karl Schmitt, Georgene W Hergenroeder, Jiaqian Wu, Yuanyuan Zhang, Dong H Kim, Qilin Cao
As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28069687/adaptive-resistance-of-melanoma-cells-to-raf-inhibition-via-reversible-induction-of-a-slowly-dividing-de-differentiated-state
#20
Mohammad Fallahi-Sichani, Verena Becker, Benjamin Izar, Gregory J Baker, Jia-Ren Lin, Sarah A Boswell, Parin Shah, Asaf Rotem, Levi A Garraway, Peter K Sorger
Treatment of BRAF-mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live-cell imaging, single-cell analysis, and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest, and the remainder adapt to drug. Drug-adapted cells up-regulate markers of the neural crest (e.g., NGFR), a melanocyte precursor, and grow slowly...
January 9, 2017: Molecular Systems Biology
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