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https://www.readbyqxmd.com/read/28741662/molecular-breakdown-a-comprehensive-view-of-anaplastic-lymphoma-kinase-alk-rearranged-non-small-cell-lung-cancer
#1
Ka-Won Noh, Mi-Sook Lee, Seung Eun Lee, Ji-Young Song, Hyun-Tae Shin, Yu Jin Kim, Doo Yi Oh, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Young Mog Shim, Jae Ill Zo, Jhingook Kim, Woong-Yang Park, Se-Hoon Lee, Yoon-La Choi
Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how Echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors...
July 25, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28738989/membrane-curvature-and-lipid-composition-synergize-to-regulate-n-ras-anchor-recruitment
#2
Jannik B Larsen, Celeste Kennard, Søren L Pedersen, Knud J Jensen, Mark J Uline, Nikos S Hatzakis, Dimitrios Stamou
Proteins anchored to membranes through covalently linked fatty acids and/or isoprenoid groups play crucial roles in all forms of life. Sorting and trafficking of lipidated proteins has traditionally been discussed in the context of partitioning to membrane domains of different lipid composition. We recently showed that membrane shape/curvature can in itself mediate the recruitment of lipidated proteins. However, exactly how membrane curvature and composition synergize remains largely unexplored. Here we investigated how three critical structural parameters of lipids, namely acyl chain saturation, headgroup size, and acyl chain length, modulate the capacity of membrane curvature to recruit lipidated proteins...
July 21, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28714104/chronic-inflammation-elicited-liver-progenitor-cell-conversion-to-liver-cancer-stem-cell-with-clinical-significance
#3
Xiao-Feng Li, Cheng Chen, Dai-Min Xiang, Le Qu, Wen Sun, Xin-Yuan Lu, Teng-Fei Zhou, Shu-Zhen Chen, Bei-Fang Ning, Zhuo Cheng, Ming-Yang Xia, Wei-Feng Shen, Wen Yang, Wen Wen, Terence Kin Wah Lee, Wen-Ming Cong, Hong-Yang Wang, Jin Ding
The substantial heterogeneity and hierarchical organization in liver cancer supports the theory of liver cancer stem cell (LCSC). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in NOD/SCID mice, suggesting the malignant transformation of LPC toward LCSC...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28709942/generation-time-and-fitness-tradeoffs-during-the-evolution-of-multicellularity
#4
Martin P Leslie, Deborah E Shelton, Richard E Michod
The evolution of multicellular organisms from their unicellular ancestors is an example of an evolutionary transition in individuality (ETI), i.e. a change in the units of selection and adaptation. The theory of ETIs poses particular challenges because, by definition, key theoretical constructs such as fitness are shifting during an ETI. Past work emphasized the importance of life history tradeoffs during ETIs in which lower level units form groups and become individuals at a higher level. In particular, it has been hypothesized that the convexity of the lower-level tradeoff between viability and fecundity changes with group size and determines the optimality of lower-level specialization in the fitness components of the group...
July 12, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28707890/immersion-depths-of-lipid-carbons-in-bicelles-measured-by-paramagnetic-relaxation-enhancement
#5
Jobst Liebau, Lena Mäler
Myriads of biological processes occur in or at cellular lipid membranes. Knowledge about the localization of proteins, lipids, and other molecules within biological membranes is thus crucial for the understanding of such processes. Here, we present a method to determine the immersion depths of lipid carbon atoms in membranes by paramagnetic relaxation enhancement (PRE) caused by the presence of doxylated lipids. As membrane mimetics, we employ small isotropic bicelles made of synthetic lipids and of natural Escherichia coli phospholipid extract...
July 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28702580/ploc-mplant-predict-subcellular-localization-of-multi-location-plant-proteins-by-incorporating-the-optimal-go-information-into-general-pseaac
#6
Xiang Cheng, Xuan Xiao, Kuo-Chen Chou
One of the fundamental goals in cellular biochemistry is to identify the functions of proteins in the context of compartments that organize them in the cellular environment. To realize this, it is indispensable to develop an automated method for fast and accurate identification of the subcellular locations of uncharacterized proteins. The current study is focused on plant protein subcellular location prediction based on the sequence information alone. Although considerable efforts have been made in this regard, the problem is far from being solved yet...
July 12, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28702424/epigenetics-linking-nutrition-to-molecular-mechanisms-in-aging
#7
REVIEW
Joo Hyun Park, Yeongran Yoo, Yoon Jung Park
Healthy aging has become a major goal of public health. Many studies have provided evidence and theories to explain molecular mechanisms of the aging process. Recent studies suggest that epigenetic mechanisms are responsible for life span and the progression of aging. Epigenetics is a fascinating field of molecular biology, which studies heritable modifications of DNA and histones that regulate gene expression without altering the DNA sequence. DNA methylation is a major epigenetic mark that shows progressive changes during aging...
June 2017: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/28702123/the-evolution-of-life-a-metadarwinian-integrative-approach
#8
Arnold De Loof
It is undeniably very logical to first formulate an unambiguous definition of "Life" before engaging in defining the parameters instrumental to Life's evolution. Because nearly everybody assumes, erroneously in my opinion, that catching Life's essence in a single sentence is impossible, this way of thinking remained largely unexplored in evolutionary theory. Upon analyzing what exactly happens at the transition from "still alive" to "just dead," the following definition emerged. What we call "Life" (L) is an activity...
2017: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/28702078/anticancer-activities-and-mechanisms-of-heat-clearing-and-detoxicating-traditional-chinese-herbal-medicine
#9
REVIEW
Yulin Zhang, Yeer Liang, Chengwei He
In traditional Chinese medicine (TCM) theory, pathogenic heat and toxins, which are akin to the inflammatory factors, are the causes of cancer and could promote its virulent development. Therefore, heat-clearing and detoxicating (HCD) herbs are essential components of TCM formulas for cancer treatment. An increasing interest has been focused on the study of HCD herbs and accumulated evidences have shown that HCD herbs or HCD herbs-based formulas exhibited remarkable anticancer effects when used alone or combined with other therapeutic approaches...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/28698549/a-tissue-engineered-model-of-aging-interdependence-and-cooperative-effects-in-failing-tissues
#10
A Acun, D C Vural, P Zorlutuna
Aging remains a fundamental open problem in modern biology. Although there exist a number of theories on aging on the cellular scale, nearly nothing is known about how microscopic failures cascade to macroscopic failures of tissues, organs and ultimately the organism. The goal of this work is to bridge microscopic cell failure to macroscopic manifestations of aging. We use tissue engineered constructs to control the cellular-level damage and cell-cell distance in individual tissues to establish the role of complex interdependence and interactions between cells in aging tissues...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698152/novel-functions-of-ccm1-delimit-the-relationship-of-ptb-ph-domains
#11
Jun Zhang, Pallavi Dubey, Akhil Padarti, Aileen Zhang, Rinkal Patel, Vipulkumar Patel, David Cistola, Ahmed Badr
BACKGROUND: Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (pH) domains were recognized as structurally related but functionally distinct domains. METHODS: By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, pH and FERM domain(s)...
July 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28675929/red-yellow-and-blue-luminescence-by-graphene-quantum-dots-syntheses-mechanism-and-cellular-imaging
#12
Tian Gao, Xi Wang, Li-Yun Yang, Huan He, Xiao-Xu Ba, Jie Zhao, Feng-Lei Jiang, Yi Liu
Owing to their excellent photoluminescence (PL) properties, good biocompatibility, and low toxicity, graphene quantum dots (GQDs) are widely applied in bioimaging, biosensing, and so forth. However, further development of GQDs is limited by their synthetic methodology and unclear PL mechanism. Therefore, it is urgent to find efficient and universal methods for the synthesis of GQDs with high stability, controllable surface properties, and tunable PL emission wavelength. By coating with polyethyleneimine (PEI) of different molecular weights, blue-, yellow-, and red-emitting GQDs were successfully prepared...
July 12, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28673574/ldl-c-levels-in-older-people-cholesterol-homeostasis-and-the-free-radical-theory-of-ageing-converge
#13
Mark T Mc Auley, Kathleen M Mooney
The cardiovascular disease (CVD) risk factor, low density lipoprotein cholesterol (LDL-C) increases with age, up until the midpoint of life in males and females. However, LDL-C can decrease with age in older men and women. Intriguingly, a recent systematic review also revealed an inverse association between LDL-C levels and cardiovascular mortality in older people; low levels of LDL-C were associated with reduced risk of mortality. Such findings are puzzling and require a biological explanation. In this paper a hypothesis is proposed to explain these observations...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28672876/novel-thiazolo-5-4-b-phenothiazine-derivatives-synthesis-structural-characterization-and-in-vitro-evaluation-of-antiproliferative-activity-against-human-leukaemia
#14
Balazs Brem, Emese Gal, Luiza Găină, Luminiţa Silaghi-Dumitrescu, Eva Fischer-Fodor, Ciprian Ionuţ Tomuleasa, Adriana Grozav, Valentin Zaharia, Lorena Filip, Castelia Cristea
The molecular frame of the reported series of new polyheterocyclic compounds was intended to combine the potent phenothiazine and benzothiazole pharmacophoric units. The synthetic strategy applied was based on oxidative cyclization of N-(phenothiazin-3-yl)-thioamides and it was validated by the preparation of new 2-alkyl- and 2-aryl-thiazolo[5,4-b]phenothiazine derivatives. Optical properties of the series were experimentally emphasized by UV-Vis absorption/emission spectroscopy and structural features were theoretically modelled using density functional theory (DFT)...
June 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28669456/biphasic-modeling-of-mitochondrial-metabolism-dysregulation-during-aging
#15
REVIEW
Darren J Baker, Shahaf Peleg
Organismal aging is classically viewed as a gradual decline of cellular functions and a systemic deterioration of tissues that leads to an increased mortality rate in older individuals. According to the prevailing theory, aging is accompanied by a continuous and progressive decline in mitochondrial metabolic activity in cells. However, the most robust approaches to extending healthy lifespan are frequently linked with reduced energy intake or with lowering of mitochondrial activity. While these observations appear contradictory, recent work and technological advances demonstrate that metabolic deregulation during aging is potentially biphasic...
June 29, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28660894/proteostasis-in-cardiac-health-and-disease
#16
REVIEW
Robert H Henning, Bianca J J M Brundel
The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing. Prevailing theories about the mechanisms of ageing feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of protein quality control as central factors. In the heart, loss of protein patency, owing to flaws in genetically-determined design or because of environmentally-induced 'wear and tear', can overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac ageing...
June 29, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28659382/domain-cell-theory-supports-the-independent-evolution-of-the-eukarya-bacteria-and-archaea-and-the-nuclear-compartment-commonality-hypothesis
#17
James T Staley
In 2015, the Royal Society of London held a meeting to discuss the various hypotheses regarding the origin of the Eukarya. Although not all participants supported a hypothesis, the proposals that did fit into two broad categories: one group favoured 'Prokaryotes First' hypotheses and another addressed 'Eukaryotes First' hypotheses. Those who proposed Prokaryotes First hypotheses advocated either a fusion event between a bacterium and an archaeon that produced the first eukaryote or the direct evolution of the Eukarya from the Archaea...
June 2017: Open Biology
https://www.readbyqxmd.com/read/28655711/long-noncoding-rna-foxd3-as1-regulates-oxidative-stress-induced-apoptosis-via-sponging-microrna-150
#18
Duo Zhang, Heedoo Lee, Jeffrey A Haspel, Yang Jin
The function of most human long noncoding RNAs (lncRNAs) remains unclear. Our studies identified a highly up-regulated mammalian lncRNA, FOXD3-AS1, known as linc1623 in mouse, in the setting of hyperoxia/reactive oxygen species (ROS)-induced lung injury. We found that ROS induced a robust expression of FOXD3-AS1 in mouse lung tissue. Functionally, FOXD3-AS1 promoted oxidative stress-induced lung epithelial cell death. In human lung epithelial cells, the microRNA-150 (miR-150) was identified to interact with FOXD3-AS1; this finding was confirmed using the luciferase reporter assays...
June 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28655149/neuromodulation-of-axon-terminals
#19
Darpan Chakraborty, Dennis Q Truong, Marom Bikson, Hanoch Kaphzan
Understanding which cellular compartments are influenced during neuromodulation underpins any rational effort to explain and optimize outcomes. Axon terminals have long been speculated to be sensitive to polarization, but experimentally informed models for CNS stimulation are lacking. We conducted simultaneous intracellular recording from the neuron soma and axon terminal (blebs) during extracellular stimulation with weak sustained (DC) uniform electric fields in mouse cortical slices. Use of weak direct current stimulation (DCS) allowed isolation and quantification of changes in axon terminal biophysics, relevant to both suprathreshold (e...
June 24, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28648877/a-rare-presentation-a-case-report-of-osseous-metaplasia-and-mature-bone-formation-in-a-follicular-adenoma-of-the-thyroid
#20
Nadia Aurora, Insia Hashmi, Subhasis Misra, Nail Aydin
INTRODUCTION: Cases of multinodular goiter, thyroid hyperplasia, follicular adenoma, papillary thyroid carcinoma, and anaplastic thyroid carcinoma have been reported with histopathologic findings of osseous metaplasia (OM), bone marrow metaplasia (BMM), ectopic bone formation (EBF), ossification, and extramedullary hematopoiesis (EMH). To date no report of a follicular adenoma with OM and mature EBF in the absence of EMH has been reported in the English language. PRESENTATION OF CASE: 63-year-old woman with an incidental finding of thyroid nodule unable to be biopsied...
June 17, 2017: International Journal of Surgery Case Reports
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