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Molecular cell biology

Ekaterina M Savelieva, Vladimir E Oslovsky, Dmitry S Karlov, Nikolay N Kurochkin, Irina A Getman, Sergey N Lomin, Georgy V Sidorov, Sergey N Mikhailov, Dmitry I Osolodkin, Georgy A Romanov
Biological effects of hormones in both plants and animals are based on high-affinity interaction with cognate receptors resulting in their activation. The signal of cytokinins, classical plant hormones, is perceived in Arabidopsis by three homologous membrane receptors: AHK2, AHK3, and CRE1/AHK4. To study the cytokinin-receptor interaction, we used 25 derivatives of potent cytokinin N6 -benzyladenine (BA) with substituents in the purine heterocycle and/or in the side chain. The study was focused primarily on individual cytokinin receptors from Arabidopsis...
March 12, 2018: Phytochemistry
Dilyana Filipova, Margit Henry, Tamara Rotshteyn, Anna Brunn, Mariana Carstov, Martina Deckert, Jürgen Hescheler, Agapios Sachinidis, Gabriele Pfitzer, Symeon Papadopoulos
In skeletal muscle the coordinated actions of two mechanically coupled Ca2+ channels-the 1,4-dihydropyridine receptor (Cav1.1) and the type 1 ryanodine receptor (RYR1)-underlie the molecular mechanism of rapid cytosolic [Ca2+] increase leading to contraction. While both [Ca2+]i and contractile activity have been implicated in the regulation of myogenesis, less is known about potential specific roles of Cav1.1 and RYR1 in skeletal muscle development. In this study, we analyzed the histology and the transcriptomic changes occurring at E14...
2018: PloS One
Dasa Cizkova, Veronika Cubinkova, Tomas Smolek, Adriana-Natalia Murgoci, Jan Danko, Katarina Vdoviakova, Filip Humenik, Milan Cizek, Jusal Quanico, Isabelle Fournier, Michel Salzet
It was recently shown that the conditioned medium (CM) of mesenchymal stem cells can enhance viability of neural and glial cell populations. In the present study, we have investigated a cell-free approach via CM from rat bone marrow stromal cells (MScCM) applied intrathecally (IT) for spinal cord injury (SCI) recovery in adult rats. Functional in vitro test on dorsal root ganglion (DRG) primary cultures confirmed biological properties of collected MScCM for production of neurosphere-like structures and axon outgrowth...
March 15, 2018: International Journal of Molecular Sciences
Allison M Weis, Raymond Soto, June L Round
The commensal microbiota influences many aspects of immune system regulation, including T cells, but molecular details of how this occurs are largely unknown. Here we review our findings that the microbiota regulates Erdr1, a secreted apoptotic factor, to control T cell survival. Erdr1 is highly upregulated in CD4+ T cells from germfree mice and antibiotic treated animals, and our study shows that Erdr1 is suppressed by the microbiota via Toll-like receptor signaling and MyD88 dependent pathways. Erdr1 functions in an autocrine fashion and promotes apoptosis through the FAS/FASL pathway...
March 15, 2018: Gut Microbes
Jinxu Gao, Adelphe Mfuh, Yuka Amako, Christina M Woo
Many therapeutics elicit cell-type specific polypharmacology that is executed by a network of molecular recognition events between a small molecule and the whole proteome. However, measurement of the structures that underpin the molecular associations between the proteome and even common therapeutics, such as the nonsteroidal anti-inflammatory drugs (NSAIDs), is limited by the inability to map the small molecule interactome. To address this gap, we developed a platform termed small molecule interactome mapping by photoaffinity labeling (SIM-PAL) and applied it to the in cellulo direct characterization of specific NSAID binding sites...
March 15, 2018: Journal of the American Chemical Society
James W Checco, Guo Zhang, Wangding Yuan, Ke Yu, Siyuan Yin, Rachel H Roberts-Galbraith, Peter M Yau, Elena V Romanova, Jian Jing, Jonathan V Sweedler
Neuropeptides in several animals undergo an unusual post-translational modification: the isomerization of an amino acid residue from the L-stereoisomer to the D-stereoisomer. The resulting D-amino acid-containing peptide (DAACP) often displays higher biological activity than its all-L-residue analogue, with the D-residue being critical for function in many cases. However, little is known about the full physiological roles played by DAACPs and few studies have examined the interaction of DAACPs with their cognate receptors...
March 15, 2018: ACS Chemical Biology
V Jung-Schroers, M Adamek, S Harris, H Syakuri, A Jung, I Irnazarow, D Steinhagen
The effect of dietary β-glucan on the bacterial community in the gut of common carp (Cyprinus carpio) was examined after oral application of Aeromonas hydrophila. Carp received either feed supplemented with 1% MacroGard® , a β-1,3/1,6-glucan, or a β-glucan-free diet. Fourteen days after feeding, half of the carp from each group were intubated with 109 colony-forming units (CFU) of a pathogenic strain of A. hydrophila. Gut samples were taken 12 hr to 7 days after application and analysed using microbiological and molecular biological techniques (NGS, RT-PCR-DGGE)...
March 15, 2018: Journal of Fish Diseases
David R Glenn, Dominik B Bucher, Junghyun Lee, Mikhail D Lukin, Hongkun Park, Ronald L Walsworth
Quantum systems that consist of solid-state electronic spins can be sensitive detectors of nuclear magnetic resonance (NMR) signals, particularly from very small samples. For example, nitrogen-vacancy centres in diamond have been used to record NMR signals from nanometre-scale samples, with sensitivity sufficient to detect the magnetic field produced by a single protein. However, the best reported spectral resolution for NMR of molecules using nitrogen-vacancy centres is about 100 hertz. This is insufficient to resolve the key spectral identifiers of molecular structure that are critical to NMR applications in chemistry, structural biology and materials research, such as scalar couplings (which require a resolution of less than ten hertz) and small chemical shifts (which require a resolution of around one part per million of the nuclear Larmor frequency)...
March 14, 2018: Nature
Margarita Villar, Lourdes Mateos-Hernandez, Jose de la Fuente
BACKGROUND: Why an autoimmune disease that is the main cause of the acute neuromuscular paralysis worldwide has not yet a well-characterized cause or an effective treatment? The existence of different clinical variants for the Guillain-Barré syndrome (GBS) coupled with the fact that a high number of pathogens can cause an infection that sometimes, but not always, precedes the development of the syndrome, confers a high degree of uncertainty for both prognosis and treatment. In the post-genomic era, the development of omics technologies for the high-throughput analysis of biological molecules is allowing the characterization of biological systems in a degree of depth unimaginable before...
March 14, 2018: Current Medicinal Chemistry
Julie E Maguire, Aakarsha Pandey, Yushi Wu, Anna Di Gregorio
Ascidian embryos have been employed as model systems for studies of developmental biology for well over a century, owing to their desirable blend of experimental advantages, which include their rapid development, traceable cell lineage, and evolutionarily conserved morphogenetic movements. Two decades ago, the development of a streamlined electroporation method drastically reduced the time and cost of transgenic experiments, and, along with the elucidation of the complete genomic sequences of several ascidian species, propelled these simple chordates to the forefront of the model organisms available for studies of regulation of gene expression...
2018: Advances in Experimental Medicine and Biology
Paulino Alvarez, Alexandros Briasoulis
PURPOSE OF REVIEW: Immune system activation plays a central role in heart failure progression. Large-scale immune modulatory clinical trials targeting tumor necrosis factor-α and broad spectrum immune modulation have been negative. The objective of this review is to highlight past, present, and what is in the horizon for the immunomodulation in heart failure with a focus of biologics. RECENT FINDINGS: Strategies targeting interleukin-1 pathway are currently undergoing clinical evaluation and data from pilot studies are promising...
March 15, 2018: Current Treatment Options in Cardiovascular Medicine
Doron Feinsilber, Roberto J Leoni, Duminda Siripala, Julianne Leuck, Katrina A Mears
The pharmacological and medical management of complex chemotherapy regimens are vast and complex, requiring an intimate understanding of physiology, particularly when novel biologic agents are utilized with commonly used regimens. The molecular classification in patients with diffuse large B-cell lymphoma (DLBCL) is multifaceted, particularly with the expansion of novel molecular targets. The pharmacological and medical management of hematologic malignancies with a tendency to have central nervous system (CNS) involvement is complex and requires an understanding of physiology and pharmacology...
January 8, 2018: Curēus
Conglin Ye, Xiaolong Yu, Xuqiang Liu, Min Dai, Bin Zhang
MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules involved in cancer initiation and progression. The present study aimed to determine the effect of miRNA-30d (miR-30d) on the growth, malignant phenotype, and apoptosis of Ewing's sarcoma (ES) SK-ES-1 cells, and to elucidate the underlying molecular mechanism and signaling pathway involved. Cell proliferation, invasion, migration, morphological changes, cell cycle distribution and apoptosis were investigated. Furthermore, the expression of matrix metalloproteinase (MMP)-2, MMP-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3 and poly (ADP-ribose) polymerase (PARP) were examined, as was the activity of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt pathways...
April 2018: Oncology Letters
Zhengting Chen, Xinyi Cai, Li Chang, Yaoxiong Xia, Li Wang, Yu Hou, Lan Li, Dingguo Pan, Furong Li, Shan Liu, Wei Xiong, Wenhui Li
Concurrent radiotherapy and chemotherapy is a widely used, comprehensive treatment for rectal cancer. By studying the impact of concurrent chemoradiotherapy on the invasion and migration of colorectal cancer (CRC) cells and researching the associated molecular mechanisms, the present study aimed to provide a novel method to improve the therapeutic effect of this treatment against CRC. Human HCT116 and HT29 CRC cells were simultaneously treated with 4 Gy of 6 MV X-rays and 10 µmol/l 5-fluorouracil to establish a residual cell model...
April 2018: Oncology Letters
Boaz Palterer, Gianfranco Vitiello, Alessia Carraresi, Maria Grazia Giudizi, Daniele Cammelli, Paola Parronchi
Idiopathic inflammatory myopathies represent a heterogeneous group of autoimmune diseases with systemic involvement. Even though numerous specific autoantibodies have been recognized, they have not been included, with the only exception of anti-Jo-1, into the 2017 Classification Criteria, thus perpetuating a clinical-serologic gap. The lack of homogeneous grouping based on the antibody profile deeply impacts the diagnostic approach, therapeutic choices and prognostic stratification of these patients. This review is intended to highlight the comprehensive scenario regarding myositis-related autoantibodies, from the molecular characterization and biological significance to target antigens, from the detection tools, with a special focus on immunofluorescence patterns on HEp-2 cells, to their relative prevalence and ethnic diversity, from the clinical presentation to prognosis...
2018: Clinical and Molecular Allergy: CMA
Tatsuya Yamada, Makoto Nishiyama, Shigeyuki Oba, Henri Claver Jimbo, Kazushi Ikeda, Shin Ishii, Kyonsoo Hong, Yuichi Sakumura
Biological cells express intracellular biomolecular information to the extracellular environment as various physical responses. We show a novel computational approach to estimate intracellular biomolecular pathways from growth cone electrophysiological responses. Previously, it was shown that cGMP signaling regulates membrane potential (MP) shifts that control the growth cone turning direction during neuronal development. We present here an integrated deterministic mathematical model and Bayesian reversed-engineering framework that enables estimation of the molecular signaling pathway from electrical recordings and considers both the system uncertainty and cell-to-cell variability...
March 14, 2018: Scientific Reports
Yi-Shu Huang, Nien-Yi Chiang, Gin-Wen Chang, Hsi-Hsien Lin
The evolutionarily conserved adhesion G protein-coupled receptors (aGPCRs) play critical roles in biological processes as diverse as brain development, cell polarity and innate immune functions. A defining feature of aGPCRs is the GPCR autoproteolysis inducing (GAIN) domain capable of self-catalytic cleavage, resulting in the generation of an extracellular N-terminal fragment (NTF) and a seven-transmembrane C-terminal fragment (CTF) involved in the cellular adhesion and signaling functions, respectively. Interestingly, two different NTF subtypes have previously been identified, namely an NTF that couples non-covalently with the CTF and a membrane-associated NTF that tethers on cell surface independently...
March 14, 2018: Scientific Reports
Ryosuke Koyama, Wataru Hakamata, Takako Hirano, Toshiyuki Nishio
Three Golgi mannosidases (GMs), namely Golgi α-mannosidases IA, IB, and IC, remove mannose residues from N-glycans and regulate the quality control and transportation of nascent proteins. GM inhibitors regulate several biological events such as cell-cell communication, differentiation, and apoptosis in cancer cells. As a result, GM inhibitor-based therapies have gained significant attention for cancer treatment. However, to date, no GM inhibitor has been approved and none is in clinical development for anti-cancer treatment...
March 13, 2018: Chemical & Pharmaceutical Bulletin
Michael Cleary-Gaffney, Andrew N Coogan
Circadian rhythms are recurring patterns in a range of behavioural, physiological and molecular parameters that display periods of near 24 h, and are underpinned by an endogenous biological timekeeping system. Circadian clocks are increasingly recognised as being key for health. Environmental light is the key stimulus that synchronises the internal circadian system with the external time cues. There are emergent health concerns regarding increasing worldwide prevalence of electric lighting, especially man-made light-at-night, and light's impact on the circadian system may be central to these effects...
March 11, 2018: Physiology & Behavior
Min Sha, Mei Lin, Jia Wang, Jun Ye, Jie Xu, Ning Xu, Junxing Huang
BACKGROUND: The objective of this study was to investigate the role and mechanism of long non-coding RNA MIAT in gastric cancer (GC). METHODS: Real-time PCR was used to determine MIAT level in 120 GC tissues, and in two gastric cancer cell lines. The clinicopathological characteristics of MIAT in GC patients were analyzed. Small interfering RNA specific for MIAT (si-MIAT) and lentivector for si-MIAT was performed to down-regulate MIAT expression in GC cells and in animal tumor model, respectively...
March 14, 2018: Journal of Experimental & Clinical Cancer Research: CR
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