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https://www.readbyqxmd.com/read/28346818/regulation-of-low-temperature-stress-in-plants-by-micrornas
#1
REVIEW
Swati Megha, Urmila Basu, Nat N V Kav
Low temperature is one of the most common environmental stresses that seriously affects the growth and development of plants. However, plants have the plasticity in their defense mechanisms enabling them to tolerate and, sometimes, even survive adverse environmental conditions. MicroRNAs (miRNAs) are small non-coding RNAs, approximately 19-21 nucleotides in length, and are being increasingly recognized as regulators of gene expression at the post-transcriptional level and have the ability to influence a broad range of biological processes...
March 27, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28346802/metabolome-profiling-of-partial-and-fully-reprogrammed-induced-pluripotent-stem-cells
#2
Soon-Jung Park, Sang A Lee, Nutan Prasain, Daekyeong Bae, Hyunsu Kang, Taewon Ha, Jong Soo Kim, Ki-Sung Hong, Charlie Mantel, Sung-Hwan Moon, Hal E Broxmeyer, Man Ryul Lee
Acquisition of proper metabolomic fate is required to convert somatic cells toward fully reprogrammed pluripotent stem cells. The majority of induced pluripotent stem cells (iPSCs) are partially reprogrammed and have a transcriptome different from that of the pluripotent stem cells. The metabolomic profile and mitochondrial metabolic functions required to achieve full reprogramming of somatic cells to iPSC status have not yet been elucidated. Clarification of the metabolites underlying reprogramming mechanisms should enable further optimization to enhance the efficiency of obtaining fully reprogrammed iPSCs...
March 27, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28346653/how-successful-is-the-fitting-of-digital-hearing-aids-implications-for-the-allocation-of-resources-within-national-health-systems
#3
Petros V Vlastarakos, Alastair I Cameron, Thomas P Nikolopoulos
We conducted a retrospective study to determine the success rate of initial fittings in digital hearing aid (DHA) users. We also addressed the implications of national health systems' continuing to provide access to these devices. We identified 1,597 consecutively presenting adults who had undergone a first fitting or a new fitting (i.e., an upgrade from an analogue hearing aid in the first or second ear) of a behind-the-ear DHA during the previous year. We further sought to identify all nominal reprogram appointments that had taken place within 6 months after the first or new fitting; we found 460 such appointments (28...
March 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28346452/purine-synthesis-promotes-maintenance-of-brain-tumor-initiating-cells-in-glioma
#4
Xiuxing Wang, Kailin Yang, Qi Xie, Qiulian Wu, Stephen C Mack, Yu Shi, Leo J Y Kim, Briana C Prager, William A Flavahan, Xiaojing Liu, Meromit Singer, Christopher G Hubert, Tyler E Miller, Wenchao Zhou, Zhi Huang, Xiaoguang Fang, Aviv Regev, Mario L Suvà, Tae Hyun Hwang, Jason W Locasale, Shideng Bao, Jeremy N Rich
Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake active normally in neurons to maintain energy demands. Here we link metabolic dysregulation in human BTICs to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28346404/chemical-screening-identifies-atm-as-a-target-for-alleviating-senescence
#5
Hyun Tae Kang, Joon Tae Park, Kobong Choi, Yongsub Kim, Hyo Jei Claudia Choi, Chul Won Jung, Young-Sam Lee, Sang Chul Park
Senescence, defined as irreversible cell-cycle arrest, is the main driving force of aging and age-related diseases. Here, we performed high-throughput screening to identify compounds that alleviate senescence and identified the ataxia telangiectasia mutated (ATM) inhibitor KU-60019 as an effective agent. To elucidate the mechanism underlying ATM's role in senescence, we performed a yeast two-hybrid screen and found that ATM interacted with the vacuolar ATPase V1 subunits ATP6V1E1 and ATP6V1G1. Specifically, ATM decreased E-G dimerization through direct phosphorylation of ATP6V1G1...
March 27, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28346230/glutaminase-and-poly-adp-ribose-polymerase-inhibitors-suppress-pyrimidine-synthesis-and-vhl-deficient-renal-cancers
#6
Arimichi Okazaki, Paulo A Gameiro, Danos Christodoulou, Laura Laviollette, Meike Schneider, Frances Chaves, Anat Stemmer-Rachamimov, Stephanie A Yazinski, Richard Lee, Gregory Stephanopoulos, Lee Zou, Othon Iliopoulos
Many cancer-associated mutations that deregulate cellular metabolic responses to hypoxia also reprogram carbon metabolism to promote utilization of glutamine. In renal cell carcinoma (RCC), cells deficient in the von Hippel-Lindau (VHL) tumor suppressor gene use glutamine to generate citrate and lipids through reductive carboxylation (RC) of α-ketoglutarate (αKG). Glutamine can also generate aspartate, the carbon source for pyrimidine biosynthesis, and glutathione for redox balance. Here we have shown that VHL-/- RCC cells rely on RC-derived aspartate to maintain de novo pyrimidine biosynthesis...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345955/smoking-dependent-distal-to-proximal-repatterning-of-the-adult-human-small-airway-epithelium
#7
Jing Yang, Wu-Lin Zuo, Tomoya Fukui, IonWa Chao, Kazunori Gomi, Busub Lee, Michelle R Staudt, Robert J Kaner, Yael Strulovici-Barel, Jacqueline Salit, Ronald G Crystal, Renat Shaykhiev
RATIONALE: Small airways are the primary site of pathologic changes in chronic obstructive pulmonary disease (COPD), the major smoking-induced lung disorder. OBJECTIVES: Based on the concept of proximal-distal patterning that determines regional specialization of the airway epithelium during lung development, we hypothesized that a similar program operates in the adult human lung being altered by smoking leading to decreased regional identity of the small airway epithelium (SAE)...
March 27, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28345605/extracellular-matrix-protein-reelin-promotes-myeloma-progression-by-facilitating-tumor-cell-proliferation-and-glycolysis
#8
Xiaodan Qin, Liang Lin, Li Cao, Xinwei Zhang, Xiao Song, Jie Hao, Yan Zhang, Risheng Wei, Xiaojun Huang, Jin Lu, Qing Ge
Reelin is an extracellular matrix protein that is crucial for neuron migration, adhesion, and positioning. We examined the expression of Reelin in a large cohort of multiple myeloma patients recorded in Gene Expression Omnibus (GEO) database and used over-expression and siRNA knockdown of Reelin to investigate the role of Reelin in myeloma cell growth. We find that Reelin expression is negatively associated with myeloma prognosis. Reelin promotes myeloma cell proliferation in vitro as well as in vivo. The Warburg effect, evidenced by increased glucose uptake and lactate production, is also enhanced in Reelin-expressing cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344995/global-manufacturing-of-car-t-cell-therapy
#9
REVIEW
Bruce L Levine, James Miskin, Keith Wonnacott, Christopher Keir
Immunotherapy using chimeric antigen receptor-modified T cells has demonstrated high response rates in patients with B cell malignancies, and chimeric antigen receptor T cell therapy is now being investigated in several hematologic and solid tumor types. Chimeric antigen receptor T cells are generated by removing T cells from a patient's blood and engineering the cells to express the chimeric antigen receptor, which reprograms the T cells to target tumor cells. As chimeric antigen receptor T cell therapy moves into later-phase clinical trials and becomes an option for more patients, compliance of the chimeric antigen receptor T cell manufacturing process with global regulatory requirements becomes a topic for extensive discussion...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344054/the-role-of-cardiac-energy-metabolism-in-cardiac-hypertrophy-and-failure
#10
REVIEW
Tomi Tuomainen, Pasi Tavi
In mammalian heart, incessant production of cellular energy is vital for maintaining continuous mechanical pumping function providing the body for oxygen and nutrients. To ensure this essential function, cardiac muscle adapt to increased energy demand or compromised energy supply by reprogramming the network of genes whose products are necessary to match the production of energy to consumption. Failure in this regulation leads to severe cardiac dysfunction and has been associated with cardiac pathogenesis including cardiac hypertrophy, failure and diabetes...
March 24, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28344037/methods-for-decoding-cas9-protospacer-adjacent-motif-pam-sequences-a-brief-overview
#11
REVIEW
Tautvydas Karvelis, Giedrius Gasiunas, Virginijus Siksnys
Recently the Cas9, an RNA guided DNA endonuclease, emerged as a powerful tool for targeted genome manipulations. Cas9 protein can be reprogrammed to cleave, bind or nick any DNA target by simply changing crRNA sequence, however a short nucleotide sequence, termed PAM, is required to initiate crRNA hybridization to the DNA target. PAM sequence is recognized by Cas9 protein and must be determined experimentally for each Cas9 variant. Exploration of Cas9 orthologs could offer a diversity of PAM sequences and novel biochemical properties that may be beneficial for genome editing applications...
March 23, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28344001/inducible-and-deterministic-forward-programming-of-human-pluripotent-stem-cells-into-neurons-skeletal-myocytes-and-oligodendrocytes
#12
Matthias Pawlowski, Daniel Ortmann, Alessandro Bertero, Joana M Tavares, Roger A Pedersen, Ludovic Vallier, Mark R N Kotter
The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs has compromised efficiencies of forward programming approaches. We have systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy. This approach provides a powerful platform for the generation of human cell types by forward programming...
March 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28343982/single-cell-5-formylcytosine-landscapes-of-mammalian-early-embryos-and-escs-at-single-base-resolution
#13
Chenxu Zhu, Yun Gao, Hongshan Guo, Bo Xia, Jinghui Song, Xinglong Wu, Hu Zeng, Kehkooi Kee, Fuchou Tang, Chengqi Yi
Active DNA demethylation in mammals involves ten-eleven translocation (TET) family protein-mediated oxidation of 5-methylcytosine (5mC). However, base-resolution landscapes of 5-formylcytosine (5fC) (an oxidized derivative of 5mC) at the single-cell level remain unexplored. Here, we present "CLEVER-seq" (chemical-labeling-enabled C-to-T conversion sequencing), which is a single-cell, single-base resolution 5fC-sequencing technology, based on biocompatible, selective chemical labeling of 5fC and subsequent C-to-T conversion during amplification and sequencing...
March 15, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28343578/untranslated-regions-utrs-orchestrate-translation-reprogramming-in-cellular-stress-responses
#14
REVIEW
Basavaraj Sajjanar, Rajib Deb, Susheel Kumar Raina, Sachin Pawar, Manoj P Brahmane, Avinash V Nirmale, Nitin P Kurade, Gundallahalli B Manjunathareddy, Santanu Kumar Bal, Narendra Pratap Singh
Stress is the result of an organism's interaction with environmental challenges. Regulations of gene expression including translation modulations are critical for adaptation and survival under stress. Untranslated regions (UTRs) of the transcripts play significant roles in translation regulation and continue to raise many intriguing questions in our understanding of cellular stress physiology. IRES (Internal ribosome entry site) and uORF (upstream open reading frame) mediated alternative translation initiations are emerging as unique mechanisms...
April 2017: Journal of Thermal Biology
https://www.readbyqxmd.com/read/28343015/systemic-delivery-of-the-tumor-necrosis-factor-gene-to-tumors-by-a-novel-dual-dna-nanocomplex-in-a-nanoparticle-system
#15
Vasundhara Shukla, Manu Dalela, Manika Vij, Munia Ganguli, Ralph Weichselbaum, Surender Kharbanda, Donald Kufe, Harpal Singh
Many cancers fail to respond to immunotherapy as a result of immune suppression by the tumor microenvironment. The exogenous expression of immune cytokines to reprogram the tumor microenvironment represents an approach to circumvent this suppression. The present studies describe the development of a novel dual nanoparticle (DNP) system for driving DNA expression vectors encoding inflammatory cytokines in tumor cells. The DNP system consists of a DNA expression vector-cationic nanocomplex (NC) surrounded by a diblock polymeric NP...
March 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28342985/mast-cells-are-directly-activated-by-contact-with-cancer-cells-by-a-mechanism-involving-autocrine-formation-of-adenosine-and-autocrine-paracrine-signaling-of-the-adenosine-a3-receptor
#16
Yaara Gorzalczany, Eyal Akiva, Ofir Klein, Ofer Merimsky, Ronit Sagi-Eisenberg
Mast cells (MCs) constitute an important part of the tumor microenvironment (TME). However, their underlying mechanisms of activation within the TME remain poorly understood. Here we show that recapitulating cell-to-cell contact interactions by exposing MCs to membranes derived from a number of cancer cell types, results in MC activation, evident by the increased phosphorylation of the ERK1/2 MAP kinases and Akt, in a phosphatidylinositol 3-kinase dependent fashion. Activation is unidirectional since MC derived membranes do not activate cancer cells...
March 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28342867/gsk3%C3%AE-attenuates-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-and-metabolic-alterations-in-arpe-19-cells
#17
Li Huang, Cheng Zhang, Li Su, Zhengyu Song
While TGF-β1 is known to induce epithelial-mesenchymal transition (EMT), a major factor in the pathogenesis of proliferative vitreoretinopathy (PVR), in ARPE-19 cells. The molecular pathways involved in EMT formation have not yet to be fully characterized. In this study, we have found that TGF-β1-mediated induction of EMT in ARPE-19 cells varied in a dose- and time-dependent manner. Specifically, TGF-β1 inhibited GSK-3β by accelerating phosphorylation at ser9. GSK-3β inhibitor or knockdown of GSK-3β resulted in enhanced TGF-β1-mediated EMT, migration and collagen contraction in ARPE-19 cells, which were then abrogated by GSK-3β overexpression and PI3K/AKT inhibitor...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28341962/tumour-suppressor-ep300-a-modulator-of-paclitaxel-resistance-and-stemness-is-downregulated-in-metaplastic-breast-cancer
#18
Muhammad Asaduzzaman, Stephanie Constantinou, Haoxiang Min, John Gallon, Meng-Lay Lin, Poonam Singh, Selina Raguz, Simak Ali, Sami Shousha, R Charles Coombes, Eric W-F Lam, Yunhui Hu, Ernesto Yagüe
PURPOSE: We have previously described a novel pathway controlling drug resistance, epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer cells. Upstream in the pathway, three miRs (miR-106b, miR-93 and miR-25) target EP300, a transcriptional activator of E-cadherin. Upregulation of these miRs leads to the downregulation of EP300 and E-cadherin with initiation of an EMT. However, miRs regulate the expression of many genes, and the contribution to EMT by miR targets other than EP300 cannot be ruled out...
March 24, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28341870/influences-of-the-gut-microbiota-on-dna-methylation-and-histone-modification
#19
REVIEW
Jianzhong Ye, Wenrui Wu, Yating Li, Lanjuan Li
The gut microbiota is a vast ensemble of microorganisms inhabiting the mammalian gastrointestinal tract that can impact physiologic and pathologic processes. However, our understanding of the underlying mechanism for the dynamic interaction between host and gut microbiota is still in its infancy. The highly evolved epigenetic modifications allow hosts to reprogram the genome in response to environmental stimuli, which may play a key role in triggering multiple human diseases. In spite of increasing studies in gut microbiota and epigenetic modifications, the correlation between them has not been well elaborated...
March 24, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28341222/the-science-and-ethics-of-cell-based-therapies-for-parkinson-s-disease
#20
REVIEW
C R Towns
Parkinson's Disease (PD) is an age-related, disabling neurodegenerative disorder. Although sufferers usually respond to dopamine agonists for extended periods, the disease remains progressive and adverse drug effects can compromise effective long term treatment. Cell-based therapies have been the subject of much hype and optimism with regard to PD. Proof of principle was provided in the 1980s with fetal tissue transplantation trials demonstrating successful graft survival. Embryonic stem cells and reprogrammed or transdifferentiated somatic cells may provide alternative sources of tissue with the potential to overcome the material shortages and technical difficulties that have hindered fetal neural transplants...
January 2017: Parkinsonism & related Disorders
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