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https://www.readbyqxmd.com/read/29353456/in-vivo-transient-and-partial-cell-reprogramming-to-pluripotency-as-a-therapeutic-tool-for-neurodegenerative-diseases
#1
REVIEW
S Tamanini, G P Comi, S Corti
In theory, human diseases in which a specific cell type degenerates, such as neurodegenerative diseases, can be therapeutically addressed by replacement of the lost cells. The classical strategy for cell replacement is exogenous cell transplantation, but now, cell replacement can also be achieved with in situ reprogramming. Indeed, many of these disorders are age-dependent, and "rejuvenating" strategies based on cell epigenetic modifications are a possible approach to counteract disease progression. In this context, transient and/or partial reprogramming of adult somatic cells towards pluripotency can be a promising tool for neuroregeneration...
January 20, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29352755/a-mos1-transposase-in-vivo-assay-to-screen-new-hiv-1-integrase-inhibitors
#2
Mariana Cancian, Elgion L S Loreto
The integrase and transposase enzymes of retrovirus and transposons, respectively, share the catalytic DDE domain. In vitro assays showed that inhibitors of HIV-1 integrase generally inhibit the mariner Mos1 transposase. Using a Drosophila strain in which the mobilisation of the mariner element can be quantified by mosaic eyes, we showed that flies maintained in medium containing 210 µM to 4 mM of raltegravir, or 1 or 2 mM of dolutegravir, which are HIV-1 integrase inhibitor used in AIDS treatment, have 23-33% less somatic mobilisation in mosaic eyes when treated with raltegravir and 28-32% when treated with dolutegravir...
January 19, 2018: Genetica
https://www.readbyqxmd.com/read/29352464/origin-of-heterogeneous-spiking-patterns-from-continuously-distributed-ion-channel-densities-a-computational-study-in-spinal-dorsal-horn-neurons
#3
Arjun Balachandar, Steven A Prescott
Neurons are often classified by spiking pattern. Yet some neurons exhibit distinct patterns under subtly different test conditions, which suggests that they operate near an abrupt transition, or bifurcation. A set of such neurons may exhibit heterogeneous spiking patterns not because of qualitative differences in which ion channels they express, but rather because quantitative differences in expression levels cause neurons to operate on opposite sides of a bifurcation. Neurons in the spinal dorsal horn, for example, respond to somatic current injection with patterns that include tonic-, single-, gap-, delayed- and reluctant-spiking...
January 20, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29352118/pi3k-mtor-inhibition-promotes-the-regression-of-experimental-vascular-malformations-driven-by-pik3ca-activating-mutations
#4
Laura di Blasio, Alberto Puliafito, Paolo Armando Gagliardi, Valentina Comunanza, Desiana Somale, Giulia Chiaverina, Federico Bussolino, Luca Primo
Somatic activating mutations within the PIK3CA gene have been recently detected in sporadic lymphatic and venous malformations, and in vascular malformations (VM) associated to overgrowth syndromes, such as CLOVES and Klippel-Trenaunay syndrome. Although VM are often limited to specific tissue areas and can be well treated, in extended or recurrent lesions novel therapeutic approaches are needed. We generated a mouse model of VM by local expression of PIK3CA-activating mutation in endothelial cells. PIK3CA-driven lesions are characterized by large areas of hemorrhage, hyperplastic vessels, infiltrates of inflammatory cells, and elevated endothelial cell density...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29351913/the-rig-i-like-receptor-lgp2-inhibits-dicer-dependent-processing-of-long-double-stranded-rna-and-blocks-rna-interference-in-mammalian-cells
#5
Annemarthe G van der Veen, Pierre V Maillard, Jan Marten Schmidt, Sonia A Lee, Safia Deddouche-Grass, Annabel Borg, Svend Kjær, Ambrosius P Snijders, Caetano Reis E Sousa
In vertebrates, the presence of viral RNA in the cytosol is sensed by members of the RIG-I-like receptor (RLR) family, which signal to induce production of type I interferons (IFN). These key antiviral cytokines act in a paracrine and autocrine manner to induce hundreds of interferon-stimulated genes (ISGs), whose protein products restrict viral entry, replication and budding. ISGs include the RLRs themselves: RIG-I, MDA5 and, the least-studied family member, LGP2. In contrast, the IFN system is absent in plants and invertebrates, which defend themselves from viral intruders using RNA interference (RNAi)...
January 19, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29351905/cancer-treatment-in-childhood-and-testicular-function-the-role-of-the-somatic-environment
#6
Jan-Bernd Stukenborg, Kirsi Jahnukainen, Marsida Hutka, Rod T Mitchell
Testicular function and future fertility may be affected by cancer treatment during childhood. Whilst survival of the germ (stem) cells is critical for ensuring the potential for fertility in these patients, the somatic cell populations also play a crucial role in providing a suitable environment to support germ cell maintenance and subsequent development. Regulation of the spermatogonial stem cell niche involves many signaling pathways with hormonal influence from the hypothalamo-pituitary-gonadal axis. In this review, we describe the somatic cell populations that comprise the testicular germ stem cell niche in human and how they may be affected by cancer treatment during childhood...
January 19, 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29351803/psychometric-properties-and-measurement-equivalence-of-the-multidimensional-fatigue-syndrome-inventory-short-form-mfsi-sf-amongst-breast-cancer-and-lymphoma-patients-in-singapore
#7
Alexandre Chan, Claire Lew, Xiao Jun Wang, Terence Ng, Jung-Woo Chae, Hui Ling Yeo, Maung Shwe, Yan Xiang Gan
BACKGROUND: Currently, several fatigue measurement instruments are available to evaluate and measure cancer-related fatigue. Amongst them, Multidimensional Fatigue Syndrome Inventory-Short Form (MFSI-SF) is a self-reported instrument and a multidimensional scale that aims to capture the global, somatic, affective, cognitive and behavioural symptoms of fatigue. This study examines the psychometric properties and measurement equivalence of the English and Chinese versions of MFSI-SF in breast cancer and lymphoma patients in Singapore...
January 19, 2018: Health and Quality of Life Outcomes
https://www.readbyqxmd.com/read/29351756/disability-due-to-knee-pain-and-somatising-tendency-in-japanese-adults
#8
Tomoko Fujii, Hiroyuki Oka, Junji Katsuhira, Juichi Tonosu, Satoshi Kasahara, Sakae Tanaka, Ko Matsudaira
BACKGROUND: Knee pain is common and related to knee osteoarthritis. However, there is a discrepancy between knee pain and radiographic osteoarthritis. In the general population, knee pain is associated with psychological and cognitive factors, which would be one explanation for the discrepancy. Limited evidence demonstrates that somatization is associated with knee pain. This study examined the association between disability due to knee pain and a high somatising tendency. METHODS: Japanese adults (aged 20-64 years) who had experienced knee pain in the past four weeks were included in this study (n = 14,695, 50% women)...
January 19, 2018: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29351486/different-physiological-roles-of-insulin-receptors-in-mediating-nutrient-metabolism-in-zebrafish
#9
Bin-Yuan Yang, Gang Zhai, Yu-Long Gong, Jing-Zhi Su, Xu-Yan Peng, Guo-Hui Shang, Dong Han, Jun-Yan Jin, Hao-Kun Liu, Zhen-Yu Du, Zhan Yin, Shou-Qi Xie
Insulin, the most potent anabolic hormone, is critical for somatic growth and metabolism in vertebrates. Type 2 diabetes, which is the primary cause of hyperglycemia, results from an inability of insulin to signal glycolysis and gluconeogenesis. Our previous study showed that double knockout of insulin receptor a (insra) and b (insrb) caused β-cell hyperplasia and lethality from 5 dpf to 16 dpf. In this study, we characterized the physiological roles of Insra and Insrb, in somatic growth and fueling metabolism, respectively...
December 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29351395/macrophage-colony-stimulating-factor-increases-hepatic-macrophage-content-liver-growth-and-lipid-accumulation-in-neonatal-rats
#10
Clare Pridans, Kristin A Sauter, Katharine M Irvine, Gemma M Davis, Lucas Lefevre, Anna Raper, Rocio Rojo, Ajit J Nirmal, Philippa Beard, Michael Cheeseman, David A Hume
Signaling via the colony stimulating factor 1 receptor (CSF1R) controls the survival, differentiation and proliferation of macrophages. Mutations in CSF1, or CSF1R in mice and rats have pleiotropic effects on postnatal somatic growth. We tested the possible application of CSF1-Fc as a therapy for low birth weight (LBW) at term, using a model based upon maternal dexamethasone treatment in rats. Neonatal CSF1-Fc treatment did not alter somatic growth, and did not increase the blood monocyte count. Instead, there was a substantial increase in the size of liver in both control and LBW rats, and the treatment greatly exacerbated the lipid droplet accumulation seen in the dexamethasone LBW model...
December 21, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29351154/predictors-of-health-related-quality-of-life-in-irritable-bowel-syndrome-patients-compared-with-healthy-individuals
#11
Raymond Addante, Bruce Naliboff, Wendy Shih, Angela P Presson, Kirsten Tillisch, Emeran A Mayer, Lin Chang
BACKGROUND: Irritable bowel syndrome (IBS) reduces health-related quality of life (HRQOL). It is unclear how having IBS modifies the impact of gastrointestinal (GI), psychosocial, and somatic symptom variables on HRQOL compared with healthy controls (HCs). AIMS: (1) Determine psychosocial, somatic, and physical status variables most predictive of HRQOL in IBS and HCs and (2) determine if IBS status modifies relationships between predictive factors and HRQOL. METHODS: IBS patients and HCs completed validated questionnaires measuring GI symptoms, psychosocial/somatic variables, and physical [physical component score (PCS)] and mental [mental component score (MCS)] HRQOL via the Short-Form-36...
January 18, 2018: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29350802/cellular-reprogramming-a-new-way-to-understand-aging-mechanisms
#12
REVIEW
Burcu Yener Ilce, Umut Cagin, Acelya Yilmazer
Increased life expectancy, due to the rise in life quality and the decline in mortality rates, is leading to a society in which the population aged 60 and over is growing more rapidly than the entire population. Although various models and model organisms have been employed to investigate the mechanism of aging, induced pluripotent stem cells (iPSCs) are useful candidates to study human aging and age-related human diseases. This work discusses how iPSCs can be used as an alternative to the model organisms such as yeast, Caenorhabditis elegans, Drosophila melanogaster, or the mouse...
January 19, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/29350438/astrocytic-glutamine-synthetase-is-expressed-in-the-neuronal-somatic-layers-and-down-regulated-proportionally-to-neuronal-loss-in-the-human-epileptic-hippocampus
#13
Ismini E Papageorgiou, Nektarios A Valous, Bernd Lahrmann, Hana Janova, Zin-Juan Klaft, Arend Koch, Ulf C Schneider, Peter Vajkoczy, Frank L Heppner, Niels Grabe, Niels Halama, Uwe Heinemann, Oliver Kann
Human mesial temporal lobe epilepsy (MTLE) features subregion-specific hippocampal neurodegeneration and reactive astrogliosis, including up-regulation of the glial fibrillary acidic protein (GFAP) and down-regulation of glutamine synthetase (GS). However, the regional astrocytic expression pattern of GFAP and GS upon MTLE-associated neurodegeneration still remains elusive. We assessed GFAP and GS expression in strict correlation with the local neuronal number in cortical and hippocampal surgical specimens from 16 MTLE patients using immunohistochemistry, stereology and high-resolution image analysis for digital pathology and whole-slide imaging...
January 19, 2018: Glia
https://www.readbyqxmd.com/read/29350289/small-rna-pathways-responsible-for-non-cell-autonomous-regulation-of-plant-reproduction
#14
REVIEW
Ken-Ichi Nonomura
In angiosperms, germline precursors and germ cells are always attached to or engulfed within somatic companion cells until just before fertilization. This is because sperm and egg cells develop as part of the multicellular gametophyte. Thus, the non-cell-autonomous regulation by somatic companions plays important roles in efficient reproduction, in addition to the cell-autonomous regulation. Epigenetic silencing of transposable elements is one of the central events by which the germline transmits the error-free genome to the next generation...
January 19, 2018: Plant Reproduction
https://www.readbyqxmd.com/read/29350171/the-dna-copy-number-landscape-of-a-collision-tumor
#15
Hugh Kearney, Jane B Cryan, Seamus Looby, Francesca M Brett, Michael A Farrell, Patrick G Buckley
Intracranial collision tumors are composed of two histologically distinct but merging components, and are rare. Their genetic profile has rarely been described. Comparative genome hybridization of a combined meningioma and oligodendroglioma demonstrated deletion of chromosome 22q and of 19q in both tumors. Somatic deletion of chromosome 22q and 19q is associated with development of an intracranial collision tumor.
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January 19, 2018: Clinical Neuropathology
https://www.readbyqxmd.com/read/29349598/phase-ib-study-evaluating-safety-and-clinical-activity-of-the-anti-her3-antibody-lumretuzumab-combined-with-the-anti-her2-antibody-pertuzumab-and-paclitaxel-in-her3-positive-her2-low-metastatic-breast-cancer
#16
Andreas Schneeweiss, Tjoung-Won Park-Simon, Joan Albanell, Ulrik Lassen, Javier Cortés, Veronique Dieras, Marcus May, Christoph Schindler, Frederik Marmé, Juan Miguel Cejalvo, Maria Martinez-Garcia, Iria Gonzalez, Jose Lopez-Martin, Anja Welt, Christelle Levy, Florence Joly, Francesca Michielin, Wolfgang Jacob, Céline Adessi, Annie Moisan, Georgina Meneses-Lorente, Tomas Racek, Ian James, Maurizio Ceppi, Max Hasmann, Martin Weisser, Andrés Cervantes
Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m2 weekly in all cohorts)...
January 19, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29348566/phosphorylation-of-ulk1-by-ampk-is-essential-for-mouse-embryonic-stem-cell-self-renewal-and-pluripotency
#17
Jiaqi Gong, Haifeng Gu, Lin Zhao, Liang Wang, Pinglei Liu, Fuping Wang, Haoyu Xu, Tongbiao Zhao
Autophagy is a catabolic process to degrade both damaged organelles and aggregated proteins in somatic cells. We have recently identified that autophagy is an executor for mitochondrial homeostasis in embryonic stem cell (ESC), and thus contribute to stemness regulation. However, the regulatory and functional mechanisms of autophagy in ESC are still largely unknown. Here we have shown that activation of ULK1 by AMPK is essential for ESC self-renewal and pluripotency. Dysfunction of Ulk1 decreases the autophagic flux in ESC, leading to compromised self-renewal and pluripotency...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348113/genetics-in-endocrinology-the-expanding-genetic-horizon-of-primary-aldosteronism
#18
Silvia Monticone, Fabrizio Buffolo, Martina Tetti, Franco Veglio, Barbara Pasini, Paolo Mulatero
Aldosterone is the main mineralocorticoid hormone in humans and plays a key role in maintaining water and electrolyte homeostasis. Primary aldosteronism (PA), characterized by autonomous aldosterone overproduction by the adrenal glands, affects 6% of the general hypertensive population and can be either sporadic or familial. Aldosterone producing adenoma (APA) and bilateral adrenal hyperplasia (BAH) are the two most frequent subtypes of sporadic PA, and 4 forms of familial hyperaldosteronism (FH-I to FH-IV) have been identified...
January 18, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29347918/somatic-evolutionary-timings-of-driver-mutations
#19
Karen Gomez, Sayaka Miura, Louise A Huuki, Brianna S Spell, Jeffrey P Townsend, Sudhir Kumar
BACKGROUND: A unified analysis of DNA sequences from hundreds of tumors concluded that the driver mutations primarily occur in the earliest stages of cancer formation, with relatively few driver mutation events detected in the late-arising subclones. However, emerging evidence from the sequencing of multiple tumors and tumor regions per individual suggests that late-arising subclones with additional driver mutations are underestimated in single-sample analyses. METHODS: To test whether driver mutations generally map to early tumor development, we examined multi-regional tumor sequencing data from 101 individuals reported in 11 published studies...
January 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29347847/combining-cell-and-gene-therapy-to-advance-cardiac-regeneration
#20
Pina Marotta, Eleonora Cianflone, Iolanda Aquila, Carla Vicinanza, Mariangela Scalise, Fabiola Marino, Teresa Mancuso, Michele Torella, Ciro Indolfi, Daniele Torella
The characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration. Areas covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial...
January 19, 2018: Expert Opinion on Biological Therapy
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