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Cellular and Molecular Life Sciences: CMLS

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https://www.readbyqxmd.com/read/30019215/eif2a-an-initiator-trna-carrier-refractory-to-eif2%C3%AE-kinases-functions-synergistically-with-eif5b
#1
Eunah Kim, Joon Hyun Kim, Keunhee Seo, Ka Young Hong, Seon Woo A An, Junyoung Kwon, Seung-Jae V Lee, Sung Key Jang
The initiator tRNA (Met-tRNA i Met ) at the P site of the small ribosomal subunit plays an important role in the recognition of an mRNA start codon. In bacteria, the initiator tRNA carrier, IF2, facilitates the positioning of Met-tRNA i Met on the small ribosomal subunit. Eukarya contain the Met-tRNA i Met carrier, eIF2 (unrelated to IF2), whose carrier activity is inhibited under stress conditions by the phosphorylation of its α-subunit by stress-activated eIF2α kinases. The stress-resistant initiator tRNA carrier, eIF2A, was recently uncovered and shown to load Met-tRNA i Met on the 40S ribosomal subunit associated with a stress-resistant mRNA under stress conditions...
July 17, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/30003270/targeting-epigenetics-using-synthetic-lethality-in-precision-medicine
#2
REVIEW
Ee Sin Chen
Technological breakthroughs in genomics have had a significant impact on clinical therapy for human diseases, allowing us to use patient genetic differences to guide medical care. The "synthetic lethal approach" leverages on cancer-specific genetic rewiring to deliver a therapeutic regimen that preferentially targets malignant cells while sparing normal cells. The utility of this system is evident in several recent studies, particularly in poor prognosis cancers with loss-of-function mutations that become "treatable" when two otherwise discrete and unrelated genes are targeted simultaneously...
July 12, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29992471/the-mesenchymoangioblast-mesodermal-precursor-for-mesenchymal-and-endothelial-cells
#3
REVIEW
Igor I Slukvin, Akhilesh Kumar
Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNR+ PDGFRα+ KDR+ mesoderm in human pluripotent stem cell cultures. MBs are identified based on their capacity to form FGF2-dependent compact spheroid colonies in a serum-free semisolid medium. MBs colonies are composed of PDGFRβ+ CD271+ EMCN+ DLK1+ CD73- primitive mesenchymal cells which are generated through endothelial/angioblastic intermediates (cores) formed during first 3-4 days of clonogenic cultures...
July 10, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29987362/a126-in-the-active-site-and-ti167-168-in-the-ti-loop-are-essential-determinants-of-the-substrate-specificity-of-pten
#4
Michael G Leitner, Kirstin Hobiger, Angeliki Mavrantoni, Anja Feuer, Johannes Oberwinkler, Dominik Oliver, Christian R Halaszovich
PTEN prevents tumor genesis by antagonizing the PI3 kinase/Akt pathway through D3 site phosphatase activity toward PI(3,4)P2 and PI(3,4,5)P3 . The structural determinants of this important specificity remain unknown. Interestingly, PTEN shares remarkable homology to voltage-sensitive phosphatases (VSPs) that dephosphorylate D5 and D3 sites of PI(4,5)P2 , PI(3,4)P2 , and PI(3,4,5)P3 . Since the catalytic center of PTEN and VSPs differ markedly only in TI/gating loop and active site motif, we wondered whether these differences explained the variation of their substrate specificity...
July 9, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29982847/voltage-gated-sodium-currents-in-cerebellar-purkinje-neurons-functional-and-molecular-diversity
#5
REVIEW
Joseph L Ransdell, Jeanne M Nerbonne
Purkinje neurons, the sole output of the cerebellar cortex, deliver GABA-mediated inhibition to the deep cerebellar nuclei. To subserve this critical function, Purkinje neurons fire repetitively, and at high frequencies, features that have been linked to the unique properties of the voltage-gated sodium (Nav) channels expressed. In addition to the rapidly activating and inactivating, or transient, component of the Nav current (INaT ) present in many types of central and peripheral neurons, Purkinje neurons, also expresses persistent (INaP ) and resurgent (INaR ) Nav currents...
July 7, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29980799/dsg2-via-src-mediated-transactivation-shapes-egfr-signaling-towards-cell-adhesion
#6
Hanna Ungewiß, Vera Rötzer, Michael Meir, Christina Fey, Markus Diefenbacher, Nicolas Schlegel, Jens Waschke
Rapidly renewing epithelial tissues such as the intestinal epithelium require precise tuning of intercellular adhesion and proliferation to preserve barrier integrity. Here, we provide evidence that desmoglein 2 (Dsg2), an adhesion molecule of desmosomes, controls cell adhesion and proliferation via epidermal growth factor receptor (EGFR) signaling. Dsg2 is required for EGFR localization at intercellular junctions as well as for Src-mediated EGFR activation. Src binds to EGFR and is required for localization of EGFR and Dsg2 to cell-cell contacts...
July 6, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29974127/crosstalk-between-metabolism-and-epigenetic-modifications-in-autoimmune-diseases-a-comprehensive-overview
#7
REVIEW
Zijun Wang, Hai Long, Christopher Chang, Ming Zhao, Qianjin Lu
Little information is available regarding mechanistic links between epigenetic modifications and autoimmune diseases. It seems plausible to surmise that aberrant gene expression and energy metabolism would disrupt immune tolerance, which could ultimately result in autoimmune responses. Metaboloepigenetics is an emerging paradigm that defines the interrelationships between metabolism and epigenetics. Epigenetic modifications, such as the methylation/demethylation of DNA and histone proteins and histone acetylation/deacetylation can be dynamically produced and eliminated by a group of enzymes that consume several metabolites derived from various physiological pathways...
July 4, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29961157/trans-spliced-long-non-coding-rna-an-emerging-regulator-of-pluripotency
#8
REVIEW
Chun-Ying Yu, Ching-Yu Chuang, Hung-Chih Kuo
With dual capacities for unlimited self-renewal and pluripotent differentiation, pluripotent stem cells (PSCs) give rise to many cell types in our body and PSC culture systems provide an unparalleled opportunity to study early human development and disease. Accumulating evidence indicates that the molecular mechanisms underlying pluripotency maintenance in PSCs involve many factors. Among these regulators, recent studies have shown that long non-coding RNAs (lncRNAs) can affect the pluripotency circuitry by cooperating with master pluripotency-associated factors...
June 30, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29959459/transcriptional-regulation-of-murine-natural-killer-cell-development-differentiation-and-maturation
#9
REVIEW
Werner Held, Beena Jeevan-Raj, Mélanie Charmoy
Natural killer (NK) cells are innate cytotoxic effector cells that play important protective roles against certain pathogens as well as against pathogen-infected and transformed host cells. NK cells continuously arise from adult bone marrow-resident haematopoietic progenitors. Their generation can be sub-divided into three phases. The early NK cell development phase from multipotent common lymphoid progenitors occurs at least in part in common with that of additional members of a family of innate lymphoid cells, for which NK cells are the founding member...
June 29, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29955905/inhibition-of-src-family-kinases-facilitates-anti-ctla4-immunotherapy-in-head-and-neck-squamous-cell-carcinoma
#10
Guang-Tao Yu, Liang Mao, Lei Wu, Wei-Wei Deng, Lin-Lin Bu, Jian-Feng Liu, Lei Chen, Lei-Lei Yang, Hao Wu, Wen-Feng Zhang, Zhi-Jun Sun
The immune system plays a critical role in the establishment, development, and progression of head and neck squamous cell carcinoma (HNSCC). As treatment with single-immune checkpoint agent results in a lower response rate in patients, it is important to investigate new strategies to maintain favorable anti-tumor immune response. Herein, the combination immunotherapeutic value of CTLA4 blockade and SFKs inhibition was assessed in transgenic HNSCC mouse model. Our present work showed that tumor growth was not entirely controlled when HNSCC model mice were administered anti-CTLA4 chemotherapeutic treatment...
June 28, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29946805/response-of-vascular-mesenchymal-stem-progenitor-cells-to-hyperlipidemia
#11
REVIEW
Ting Chen, Yutao Wu, Wenduo Gu, Qingbo Xu
Hyperlipidemia is a risk factor for atherosclerosis that is characterized by lipid accumulation, inflammatory cell infiltration, and smooth muscle cell proliferation. It is well known that hyperlipidemia is a stimulator for endothelial dysfunction and smooth muscle cell migration during vascular disease development. Recently, it was found that vessel wall contains a variable number of mesenchymal stem cells (MSCs) that are quiescent in physiological conditions, but can be activated by a variety of stimuli, e...
June 26, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29943076/pivotal-role-of-lbd16-in-root-and-root-like-organ-initiation
#12
REVIEW
Wu Liu, Jie Yu, Yachao Ge, Peng Qin, Lin Xu
In the post-embryonic stage of Arabidopsis thaliana, roots can be initiated from the vascular region of the existing roots or non-root organs; they are designated as lateral roots (LRs) and adventitious roots (ARs), respectively. Some root-like organs can also be initiated from the vasculature. In tissue culture, auxin-induced callus, which is a group of pluripotent root-primordium-like cells, is formed via the rooting pathway. The formation of feeding structures from the vasculature induced by root-knot nematodes also borrows the rooting pathway...
June 25, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29938386/neuronal-gap-porf-2-transduces-ephb1-signaling-to-brake-axon-growth
#13
Guo-Hui Huang, Lin Guo, Liang Zhu, Xian-Dong Liu, Zhao-Liang Sun, Hong-Jiang Li, Nan-Jie Xu, Dong-Fu Feng
Axonal outgrowth and guidance require numerous extracellular cues and intracellular mediators that transduce signals in the growth cone to regulate cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron-expressed RhoGTPase-activating protein, plays an essential role in the inhibition of initial axon growth by restricting the expansion of the growth cone in a cell-autonomous manner. Furthermore, the EphB1 receptor is identified as an upstream controller that binds and regulates Porf-2 specifically upon extracellular ephrin-B stimulation...
June 25, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29936596/molecular-mechanisms-of-hepatic-lipid-accumulation-in-non-alcoholic-fatty-liver-disease
#14
REVIEW
David Højland Ipsen, Jens Lykkesfeldt, Pernille Tveden-Nyborg
Non-alcoholic fatty liver disease (NAFLD) is currently the world's most common liver disease, estimated to affect up to one-fourth of the population. Hallmarked by hepatic steatosis, NAFLD is associated with a multitude of detrimental effects and increased mortality. This narrative review investigates the molecular mechanisms of hepatic steatosis in NAFLD, focusing on the four major pathways contributing to lipid homeostasis in the liver. Hepatic steatosis is a consequence of lipid acquisition exceeding lipid disposal, i...
June 23, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29934665/galectin-8-induces-functional-disease-markers-in-human-osteoarthritis-and-cooperates-with-galectins-1-and-3
#15
Daniela Weinmann, Michael Kenn, Sebastian Schmidt, Katy Schmidt, Sonja M Walzer, Bernd Kubista, Reinhard Windhager, Wolfgang Schreiner, Stefan Toegel, Hans-Joachim Gabius
The reading of glycan-encoded signals by tissue lectins is considered a major route of the flow of biological information in many (patho)physiological processes. The arising challenge for current research is to proceed from work on a distinct protein to family-wide testing of lectin function. Having previously identified homodimeric galectin-1 and chimera-type galectin-3 as molecular switches in osteoarthritis progression, we here provide proof-of-principle evidence for an intra-network cooperation of galectins with three types of modular architecture...
June 22, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29934664/histones-and-heart-failure-in-diabetes
#16
REVIEW
Veera Ganesh Yerra, Andrew Advani
Although heart failure is now accepted as being a major long-term complication of diabetes, many of the recent advances in our understanding of the pathobiology of diabetes complications have come about through the study of more traditional microvascular or macrovascular diseases. This has been the case, for example, in the evolving field of the epigenetics of diabetes complications and, in particular, the post-translational modification of histone proteins. However, histone modifications also occur in human heart failure and their perturbation also occurs in diabetic hearts...
June 22, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29947928/coordination-of-microtubule-acetylation-and-the-actin-cytoskeleton-by-formins
#17
REVIEW
Jaime Fernández-Barrera, Miguel A Alonso
The acetylation of the lysine 40 residue of α-tubulin was described more than 30 years ago and has been the subject of intense research ever since. Although the exact function of this covalent modification of tubulin in the cell remains unknown, it has been established that tubulin acetylation confers resilience to mechanical stress on the microtubules. Formins have a dual role in the fate of the actin and tubulin cytoskeletons. On the one hand, they catalyze the formation of actin filaments, and on the other, they bind microtubules, act on their stability, and regulate their acetylation and alignment with actin fibers...
June 15, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29947927/mechanisms-of-protein-toxicity-in-neurodegenerative-diseases
#18
REVIEW
Chang Geon Chung, Hyosang Lee, Sung Bae Lee
Protein toxicity can be defined as all the pathological changes that ensue from accumulation, mis-localization, and/or multimerization of disease-specific proteins. Most neurodegenerative diseases manifest protein toxicity as one of their key pathogenic mechanisms, the details of which remain unclear. By systematically deconstructing the nature of toxic proteins, we aim to elucidate and illuminate some of the key mechanisms of protein toxicity from which therapeutic insights may be drawn. In this review, we focus specifically on protein toxicity from the point of view of various cellular compartments such as the nucleus and the mitochondria...
June 12, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29947926/osbp-related-protein-2-orp2-a-novel-akt-effector-that-controls-cellular-energy-metabolism
#19
Henriikka Kentala, Annika Koponen, Helena Vihinen, Juho Pirhonen, Gerhard Liebisch, Zoltan Pataj, Annukka Kivelä, Shiqian Li, Leena Karhinen, Eeva Jääskeläinen, Robert Andrews, Leena Meriläinen, Silke Matysik, Elina Ikonen, You Zhou, Eija Jokitalo, Vesa M Olkkonen
ORP2 is a ubiquitously expressed OSBP-related protein previously implicated in endoplasmic reticulum (ER)-lipid droplet (LD) contacts, triacylglycerol (TG) metabolism, cholesterol transport, adrenocortical steroidogenesis, and actin-dependent cell dynamics. Here, we characterize the role of ORP2 in carbohydrate and lipid metabolism by employing ORP2-knockout (KO) hepatoma cells (HuH7) generated by CRISPR-Cas9 gene editing. The ORP2-KO and control HuH7 cells were subjected to RNA sequencing, analyses of Akt signaling, carbohydrate and TG metabolism, the extracellular acidification rate, and the lipidome, as well as to transmission electron microscopy...
June 12, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29947925/targeting-nrf-2-is-a-promising-intervention-approach-for-the-prevention-of-ethanol-induced-liver-disease
#20
REVIEW
Ning Zhao, Fang-Fang Guo, Ke-Qin Xie, Tao Zeng
Alcoholic liver disease (ALD) remains to be a worldwide health problem. It is generally accepted that oxidative stress plays critical roles in the pathogenesis of ALD, and antioxidant therapy represents a logical strategy for the prevention and treatment of ALD. Nuclear factor erythroid-derived 2-like 2 (NFE2L2 or Nrf-2) is essential for the antioxidant responsive element (ARE)-mediated induction of endogenous antioxidant enzymes such as heme oxygenase 1 (HO-1) and glutamate-cysteine ligase [GCL, the rate-limiting enzyme in the synthesis of glutathione (GSH)]...
June 11, 2018: Cellular and Molecular Life Sciences: CMLS
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