Targeted deep sequencing revealed variants in cell-free DNA of hormone receptor-positive metastatic breast cancer patients.
Abstract Cell-free DNA (cfDNA) is described to mirror intratumoral heterogeneity and gives insight about clonal evolution for improved therapeutic decisions. We sequenced cfDNA of a hormone receptor-positive, HER2-negative metastatic breast cancer (MBC) cohort with a high coverage to examine the prevalence and relevance of any detected variant. cfDNA of 44 MBC patients was isolated, followed by library construction using a customized targeted DNA panel with integrated unique molecular indices analyzing AKT1, AR, BRCA1, BRCA2, EGFR, ERCC4, ERBB2, ERBB3, ESR1, FGFR1, KRAS, MUC16, PIK3CA, PIK3R1, PTEN, PTGFR, and TGF...
Source: Cellular and Molecular Life Sciences : CMLS - June 28, 2019 Category: Cytology Authors: Keup C, Benyaa K, Hauch S, Sprenger-Haussels M, Tewes M, Mach P, Bittner AK, Kimmig R, Hahn P, Kasimir-Bauer S Tags: Cell Mol Life Sci Source Type: research

Therapeutic potential of vitamin D in AGE/RAGE-related cardiovascular diseases.
This article provides a comprehensive review of the mechanistic insights into AGE/RAGE involvement in CVDs and the modulation of the AGE/RAGE signaling pathways by vitamin D. PMID: 31250032 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2019 Category: Cytology Authors: Lee TW, Kao YH, Chen YJ, Chao TF, Lee TI Tags: Cell Mol Life Sci Source Type: research

A novel seed plants gene regulates oxidative stress tolerance in Arabidopsis thaliana.
Abstract Oxidative stress can lead to plant growth retardation, yield loss, and death. The atr7 mutant of Arabidopsis thaliana exhibits pronounced tolerance to oxidative stress. Using positional cloning, confirmed by knockout and RNA interference (RNAi) lines, we identified the atr7 mutation and revealed that ATR7 is a previously uncharacterized gene with orthologs in other seed plants but with no homology to genes in lower plants, fungi or animals. Expression of ATR7-GFP fusion shows that ATR7 is a nuclear-localized protein. RNA-seq analysis reveals that transcript levels of genes encoding abiotic- and oxidative ...
Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2019 Category: Cytology Authors: Sujeeth N, Mehterov N, Gupta S, Qureshi MK, Fischer A, Proost S, Omidbakhshfard MA, Obata T, Benina M, Staykov N, Balazadeh S, Walther D, Fernie AR, Mueller-Roeber B, Hille J, Gechev TS Tags: Cell Mol Life Sci Source Type: research

Direct reprogramming into interneurons: potential for brain repair.
Abstract The brain tissue has only a limited capacity for generating new neurons. Therefore, to treat neurological diseases, there is a need of other cell sources for brain repair. Different sources of cells have been subject of intense research over the years, including cells from primary tissue, stem cell-derived cells and reprogrammed cells. As an alternative, direct reprogramming of resident brain cells into neurons is a recent approach that could provide an attractive method for treating brain injuries or diseases as it uses the patient's own cells for generating novel neurons inside the brain. In vivo reprog...
Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2019 Category: Cytology Authors: Pereira M, Birtele M, Rylander Ottosson D Tags: Cell Mol Life Sci Source Type: research

Bridging intestinal immunity and gut microbiota by metabolites.
Abstract The gastrointestinal tract is the site of nutrient digestion and absorption and is also colonized by diverse, highly mutualistic microbes. The intestinal microbiota has diverse effects on the development and function of the gut-specific immune system, and provides some protection from infectious pathogens. However, interactions between intestinal immunity and microorganisms are very complex, and recent studies have revealed that this intimate crosstalk may depend on the production and sensing abilities of multiple bioactive small molecule metabolites originating from direct produced by the gut microbiota ...
Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2019 Category: Cytology Authors: Wang G, Huang S, Wang Y, Cai S, Yu H, Liu H, Zeng X, Zhang G, Qiao S Tags: Cell Mol Life Sci Source Type: research

The keratin-desmosome scaffold: pivotal role of desmosomes for keratin network morphogenesis.
Abstract Desmosome-anchored keratin intermediate filaments (KFs) are essential for epithelial coherence. Yet, desmosomal KF attachment and network organization are still unexplored in vivo. We, therefore, monitored KF network morphogenesis in fluorescent keratin 8 knock-in murine embryos revealing keratin enrichment at newly formed desmosomes followed by KF formation, KF elongation and KF fusion. To examine details of this process and its coupling to desmosome formation, we studied fluorescent keratin and desmosomal protein reporter dynamics in the periphery of expanding HaCaT keratinocyte colonies. Less than 3&nb...
Source: Cellular and Molecular Life Sciences : CMLS - June 26, 2019 Category: Cytology Authors: Moch M, Schwarz N, Windoffer R, Leube RE Tags: Cell Mol Life Sci Source Type: research

The assembly of succinate dehydrogenase: a key enzyme in bioenergetics.
Abstract Succinate dehydrogenase (SDH) also known as complex II or succinate:quinone oxidoreductase is an enzyme involved in both oxidative phosphorylation and tricarboxylic acid cycle; the processes that generate energy. SDH is a multi-subunit enzyme which requires a series of proteins for its proper assembly at several steps. This enzyme has medical significance as there is a broad range of human diseases from cancers to neurodegeneration related to SDH malfunction. Some of these disorders have recently been linked to defective assembly factors, reinvigorating further research in this area. Apart from that this ...
Source: Cellular and Molecular Life Sciences : CMLS - June 24, 2019 Category: Cytology Authors: Moosavi B, Berry EA, Zhu XL, Yang WC, Yang GF Tags: Cell Mol Life Sci Source Type: research

Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous system.
SF Abstract 'A disintegrin and metalloproteases' (ADAMs) are a family of transmembrane proteins with diverse functions in multicellular organisms. About half of the ADAMs are active metalloproteases and cleave numerous cell surface proteins, including growth factors, receptors, cytokines and cell adhesion proteins. The other ADAMs have no catalytic activity and function as adhesion proteins or receptors. Some ADAMs are ubiquitously expressed, others are expressed tissue specifically. This review highlights functions of ADAMs in the mammalian nervous system, including their links to diseases. The non-proteolytic A...
Source: Cellular and Molecular Life Sciences : CMLS - June 24, 2019 Category: Cytology Authors: Hsia HE, Tüshaus J, Brummer T, Zheng Y, Scilabra SD, Lichtenthaler SF Tags: Cell Mol Life Sci Source Type: research

Rational design of agonists for bitter taste receptor TAS2R14: from modeling to bench and back.
MY Abstract Human bitter taste receptors (TAS2Rs) are a subfamily of 25 G protein-coupled receptors that mediate bitter taste perception. TAS2R14 is the most broadly tuned bitter taste receptor, recognizing a range of chemically diverse agonists with micromolar-range potency. The receptor is expressed in several extra-oral tissues and is suggested to have physiological roles related to innate immune responses, male fertility, and cancer. Higher potency ligands are needed to investigate TAS2R14 function and to modulate it for future clinical applications. Here, a structure-based modeling approach is described for ...
Source: Cellular and Molecular Life Sciences : CMLS - June 24, 2019 Category: Cytology Authors: Di Pizio A, Waterloo LAW, Brox R, Löber S, Weikert D, Behrens M, Gmeiner P, Niv MY Tags: Cell Mol Life Sci Source Type: research

Polyamines in mammalian pathophysiology.
da L, Urdiales JL Abstract Polyamines (PAs) are essential organic polycations for cell viability along the whole phylogenetic scale. In mammals, they are involved in the most important physiological processes: cell proliferation and viability, nutrition, fertility, as well as nervous and immune systems. Consequently, altered polyamine metabolism is involved in a series of pathologies. Due to their pathophysiological importance, PA metabolism has evolved to be a very robust metabolic module, interconnected with the other essential metabolic modules for gene expression and cell proliferation/differentiation. Two dif...
Source: Cellular and Molecular Life Sciences : CMLS - June 21, 2019 Category: Cytology Authors: Sánchez-Jiménez F, Medina MÁ, Villalobos-Rueda L, Urdiales JL Tags: Cell Mol Life Sci Source Type: research

Isorhapontigenin (ISO) inhibits stem cell-like properties and invasion of bladder cancer cell by attenuating CD44 expression.
Abstract Cancer stem cells (CSC) are highly associated with poor prognosis in cancer patients. Our previous studies report that isorhapontigenin (ISO) down-regulates SOX2-mediated cyclin D1 induction and stem-like cell properties in glioma stem-like cells. The present study revealed that ISO could inhibit stem cell-like phenotypes and invasivity of human bladder cancer (BC) by specific attenuation of expression of CD44 but not SOX-2, at both the protein transcription and degradation levels. On one hand, ISO inhibited cd44 mRNA expression through decreases in Sp1 direct binding to its promoter region-binding site, ...
Source: Cellular and Molecular Life Sciences : CMLS - June 20, 2019 Category: Cytology Authors: Luo Y, Tian Z, Hua X, Huang M, Xu J, Li J, Huang H, Cohen M, Huang C Tags: Cell Mol Life Sci Source Type: research

The molecular clock in the skin, its functionality, and how it is disrupted in cutaneous melanoma: a new pharmacological target?
Abstract The skin is the interface between the organism and the external environment, acting as its first barrier. Thus, this organ is constantly challenged by physical stimuli such as UV and infrared radiation, visible light, and temperature as well as chemicals and pathogens. To counteract the deleterious effects of the above-mentioned stimuli, the skin has complex defense mechanisms such as: immune and neuroendocrine systems; shedding of epidermal squamous layers and apoptosis of damaged cells; DNA repair; and pigmentary system. Here we have reviewed the current knowledge regarding which stimuli affect the mole...
Source: Cellular and Molecular Life Sciences : CMLS - June 20, 2019 Category: Cytology Authors: de Assis LVM, Moraes MN, de Lauro Castrucci AM Tags: Cell Mol Life Sci Source Type: research

Vps13b is required for acrosome biogenesis through functions in Golgi dynamic and membrane trafficking.
omb L Abstract The sperm acrosome is a lysosome-related organelle that develops using membrane trafficking from the Golgi apparatus as well as the endolysosomal compartment. How vesicular trafficking is regulated in spermatids to form the acrosome remains to be elucidated. VPS13B, a RAB6-interactor, was recently shown involved in endomembrane trafficking. Here, we report the generation of the first Vps13b-knockout mouse model and show that male mutant mice are infertile due to oligoasthenoteratozoospermia. This phenotype was explained by a failure of Vps13b deficient spermatids to form an acrosome. In wild-type sp...
Source: Cellular and Molecular Life Sciences : CMLS - June 19, 2019 Category: Cytology Authors: Da Costa R, Bordessoules M, Guilleman M, Carmignac V, Lhussiez V, Courot H, Bataille A, Chlémaire A, Bruno C, Fauque P, Thauvin C, Faivre L, Duplomb L Tags: Cell Mol Life Sci Source Type: research

Progress in the emerging role of selenoproteins in cardiovascular disease: focus on endoplasmic reticulum-resident selenoproteins.
In conclusion, selenoproteins could represent valuable targets to treat and diagnose cardiovascular diseases secondary to oxidative stress, opening a new avenue in the field of related therapeutic strategies. PMID: 31218451 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - June 19, 2019 Category: Cytology Authors: Rocca C, Pasqua T, Boukhzar L, Anouar Y, Angelone T Tags: Cell Mol Life Sci Source Type: research

The role of polarisation of circulating tumour cells in cancer metastasis.
Abstract Metastasis is the spread of cancer cells from a primary tumour to a distant site of the body. Metastasising tumour cells have to survive and readjust to different environments, such as heterogeneous solid tissues and liquid phase in lymph- or blood circulation, which they achieve through a high degree of plasticity that renders them adaptable to varying conditions. One defining characteristic of the metastatic process is the transition of tumour cells between different polarised phenotypes, ranging from differentiated epithelial polarity to migratory front-rear polarity. Here, we review the polarisation t...
Source: Cellular and Molecular Life Sciences : CMLS - June 19, 2019 Category: Cytology Authors: Heikenwalder M, Lorentzen A Tags: Cell Mol Life Sci Source Type: research

Protein methylation functions as the posttranslational modification switch to regulate autophagy.
Abstract Studies over the past decades have elucidated the critical role of autophagy in human health and diseases. Although the processes of autophagy in the cytoplasm have been well studied, the posttranscriptional and epigenetic regulation mechanisms of autophagy are still poorly understood. Protein methylation, including histone methylation and non-histone protein methylation, is the most important type of posttranscriptional and epigenetic modification. Recent studies have shown that protein methylation is associated with effects on autophagosome formation, autophagy-related protein expression, and signaling ...
Source: Cellular and Molecular Life Sciences : CMLS - June 19, 2019 Category: Cytology Authors: Li R, Wei X, Jiang DS Tags: Cell Mol Life Sci Source Type: research

MiR-17 and miR-19 cooperatively promote skeletal muscle cell differentiation.
Abstract Skeletal myogenesis is a highly coordinated process that involves cell proliferation, differentiation and fusion controlled by a complex gene regulatory network. The microRNA gene cluster miR-17-92 has been shown to be related to this process; however, the exact role of each cluster member remains unclear. Here, we show that miR-17 and miR-20a could effectively promote the differentiation of both C2C12 myoblasts and primary bovine satellite cells. In contrast, miR-18a might play a negative role in C2C12 cell differentiation, while miR-19 and miR-92a had little influence. Transcriptome and target analyses ...
Source: Cellular and Molecular Life Sciences : CMLS - June 18, 2019 Category: Cytology Authors: Kong D, He M, Yang L, Zhou R, Yan YQ, Liang Y, Teng CB Tags: Cell Mol Life Sci Source Type: research

Degradome of soluble ADAM10 and ADAM17 metalloproteases.
Abstract Disintegrin and metalloproteinases (ADAMs) 10 and 17 can release the extracellular part of a variety of membrane-bound proteins via ectodomain shedding important for many biological functions. So far, substrate identification focused exclusively on membrane-anchored ADAM10 and ADAM17. However, besides known shedding of ADAM10, we identified ADAM8 as a protease capable of releasing the ADAM17 ectodomain. Therefore, we investigated whether the soluble ectodomains of ADAM10/17 (sADAM10/17) exhibit an altered substrate spectrum compared to their membrane-bound counterparts. A mass spectrometry-based N-termino...
Source: Cellular and Molecular Life Sciences : CMLS - June 17, 2019 Category: Cytology Authors: Scharfenberg F, Helbig A, Sammel M, Benzel J, Schlomann U, Peters F, Wichert R, Bettendorff M, Schmidt-Arras D, Rose-John S, Moali C, Lichtenthaler SF, Pietrzik CU, Bartsch JW, Tholey A, Becker-Pauly C Tags: Cell Mol Life Sci Source Type: research

The molecular foundations of zygosis.
Abstract Zygosis is the generation of new biological individuals by the sexual fusion of gamete cells. Our current understanding of eukaryotic phylogeny indicates that sex is ancestral to all extant eukaryotes. Although sexual development is extremely diverse, common molecular elements have been retained. HAP2-GCS1, a protein that promotes the fusion of gamete cell membranes that is related in structure to certain viral fusogens, is conserved in many eukaryotic lineages, even though gametes vary considerably in form and behaviour between species. Similarly, although zygotes have dramatically different forms and fa...
Source: Cellular and Molecular Life Sciences : CMLS - June 15, 2019 Category: Cytology Authors: Bloomfield G Tags: Cell Mol Life Sci Source Type: research

Regulation of the alternative β-secretase meprin β by ADAM-mediated shedding.
Regulation of the alternative β-secretase meprin β by ADAM-mediated shedding. Cell Mol Life Sci. 2019 Jun 14;: Authors: Scharfenberg F, Armbrust F, Marengo L, Pietrzik C, Becker-Pauly C Abstract Alzheimer's Disease (AD) is the sixth-leading cause of death in industrialized countries. Neurotoxic amyloid-β (Aβ) plaques are one of the pathological hallmarks in AD patient brains. Aβ accumulates in the brain upon sequential, proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretases. However, so far disease-modifying drugs targeting β- and ...
Source: Cellular and Molecular Life Sciences : CMLS - June 14, 2019 Category: Cytology Authors: Scharfenberg F, Armbrust F, Marengo L, Pietrzik C, Becker-Pauly C Tags: Cell Mol Life Sci Source Type: research

Mechanisms of synovial joint and articular cartilage development.
Abstract Articular cartilage is formed at the end of epiphyses in the synovial joint cavity and permanently contributes to the smooth movement of synovial joints. Most skeletal elements develop from transient cartilage by a biological process known as endochondral ossification. Accumulating evidence indicates that articular and growth plate cartilage are derived from different cell sources and that different molecules and signaling pathways regulate these two kinds of cartilage. As the first sign of joint development, the interzone emerges at the presumptive joint site within a pre-cartilage tissue. After that, jo...
Source: Cellular and Molecular Life Sciences : CMLS - June 14, 2019 Category: Cytology Authors: Chijimatsu R, Saito T Tags: Cell Mol Life Sci Source Type: research

Adamts17 is involved in skeletogenesis through modulation of BMP-Smad1/5/8 pathway.
Abstract Fibrillin microfibrils are ubiquitous elements of extracellular matrix assemblies that play crucial roles in regulating the bioavailability of growth factors of the transforming growth factor beta superfamily. Recently, several "a disintegrin and metalloproteinase with thrombospondin motifs" (ADAMTS) proteins were shown to regulate fibrillin microfibril function. Among them, ADAMTS17 is the causative gene of Weill-Marchesani syndrome (WMS) and Weill-Marchesani-like syndrome, of which common symptoms are ectopia lentis and short stature. ADAMTS17 has also been linked to height variation in humans...
Source: Cellular and Molecular Life Sciences : CMLS - June 14, 2019 Category: Cytology Authors: Oichi T, Taniguchi Y, Soma K, Oshima Y, Yano F, Mori Y, Chijimatsu R, Kim-Kaneyama JR, Tanaka S, Saito T Tags: Cell Mol Life Sci Source Type: research

Demystifying the extracellular matrix and its proteolytic remodeling in the brain: structural and functional insights.
Abstract The extracellular matrix (ECM) plays diverse roles in several physiological and pathological conditions. In the brain, the ECM is unique both in its composition and in functions. Furthermore, almost all the cells in the central nervous system contribute to different aspects of this intricate structure. Brain ECM, enriched with proteoglycans and other small proteins, aggregate into distinct structures around neurons and oligodendrocytes. These special structures have cardinal functions in the normal functioning of the brain, such as learning, memory, and synapse regulation. In this review, we have compiled...
Source: Cellular and Molecular Life Sciences : CMLS - June 13, 2019 Category: Cytology Authors: Krishnaswamy VR, Benbenishty A, Blinder P, Sagi I Tags: Cell Mol Life Sci Source Type: research

Metalloproteinases and their tissue inhibitors in Alzheimer's disease and other neurodegenerative disorders.
Baranger K Abstract As life expectancy increases worldwide, age-related neurodegenerative diseases will increase in parallel. The lack of effective treatment strategies may soon lead to an unprecedented health, social and economic crisis. Any attempt to halt the progression of these diseases requires a thorough knowledge of the pathophysiological mechanisms involved to facilitate the identification of new targets and the application of innovative therapeutic strategies. The metzincin superfamily of metalloproteinases includes matrix metalloproteinases (MMP), a disintegrin and metalloproteinase (ADA...
Source: Cellular and Molecular Life Sciences : CMLS - June 13, 2019 Category: Cytology Authors: Rivera S, García-González L, Khrestchatisky M, Baranger K Tags: Cell Mol Life Sci Source Type: research

Open reading frame mining identifies a TLR4 binding domain in the primary sequence of ECRG4.
Abstract The embedding of small peptide ligands within large inactive pre-pro-precursor proteins encoded by orphan open reading frames (ORFs) makes them difficult to identify and study. To address this problem, we generated oligonucleotide ( 1200 amino acid EGF precursor protein or the orphan ECRG4 ORF, that encodes a 148 amino acid Esophageal Cancer Related Gene 4 (ECRG4), a putative cytokine precursor protein of up to eight ligands. After phage display and 3-4 rounds of biopanning for phage internalization into prostate cancer epithelial cells, sequencing identified the 53-amino acid EGF ligand encoded by...
Source: Cellular and Molecular Life Sciences : CMLS - June 12, 2019 Category: Cytology Authors: Dang X, Coimbra R, Mao L, Podvin S, Li X, Yu H, Costantini TW, Zeng X, Larocca D, Eliceiri BP, Baird A Tags: Cell Mol Life Sci Source Type: research

Metalloproteinases mediate diabetes-induced retinal neuropathy and vasculopathy.
Abstract Matrix metalloproteinases (MMPs) and related metalloproteinases with a disintegrin domain (ADAMs) have become interesting probes and targets in eye diseases, including diabetic retinopathy. We here summarize recent data about MMPs and ADAMs in retinopathies. Retinal diseases range from rare genetic afflictions to diabetic retinopathy, the latter of which is reaching epidemic proportions. MMPs and ADAMs play roles in normal eye development and in disease states, not only in local proteolysis but also signaling functions mediated by specific protein domains, interacting with cell surface receptors. In proli...
Source: Cellular and Molecular Life Sciences : CMLS - June 10, 2019 Category: Cytology Authors: Opdenakker G, Abu El-Asrar A Tags: Cell Mol Life Sci Source Type: research

Introduction to the multi-author review on methylation in cellular physiology.
Abstract Protein post-translational modifications (PTMs) have long been a topic of intensive investigation. Covalent additions to the 20 genetically encoded amino acids can alter protein interactions and can even change enzymatic function. In eukarya, PTMs can amplify both the complexity and functional paradigms of the cellular environment. Therefore, PTMs have been of substantial research interest, both for understanding fundamental mechanisms and to provide insight into drug design. Indeed, targeting proteins involved in writing, reading, and erasing PTMs important for human pathologies are some of the most frui...
Source: Cellular and Molecular Life Sciences : CMLS - June 8, 2019 Category: Cytology Authors: Shechter D Tags: Cell Mol Life Sci Source Type: research

Requirement of NPHP5 in the hierarchical assembly of basal feet associated with basal bodies of primary cilia.
Abstract During ciliogenesis, the mother centriole transforms into a basal body competent to nucleate a cilium. The mother centriole and basal body possess sub-distal appendages (SDAs) and basal feet (BF), respectively. SDAs and BF are thought to be equivalent structures. In contrast to SDA assembly, little is known about the players involved in BF assembly and its assembly order. Furthermore, the contribution of BF to ciliogenesis is not understood. Here, we found that SDAs are distinguishable from BF and that the protein NPHP5 is a novel SDA and BF component. Remarkably, NPHP5 is specifically required for BF ass...
Source: Cellular and Molecular Life Sciences : CMLS - June 8, 2019 Category: Cytology Authors: Hossain D, Barbelanne M, Tsang WY Tags: Cell Mol Life Sci Source Type: research

Codon selection reduces GC content bias in nucleic acids encoding for intrinsically disordered proteins.
Abstract Protein-coding nucleic acids exhibit composition and codon biases between sequences coding for intrinsically disordered regions (IDRs) and those coding for structured regions. IDRs are regions of proteins that are folding self-insufficient and which function without the prerequisite of folded structure. Several authors have investigated composition bias or codon selection in regions encoding for IDRs, primarily in Eukaryota, and concluded that elevated GC content is the result of the biased amino acid composition of IDRs. We substantively extend previous work by examining GC content in regions encoding ID...
Source: Cellular and Molecular Life Sciences : CMLS - June 7, 2019 Category: Cytology Authors: Oldfield CJ, Peng Z, Uversky VN, Kurgan L Tags: Cell Mol Life Sci Source Type: research

Metalloproteinases in nervous system function and pathology: introduction.
Abstract This multi-author review in CMLS includes ten articles that provide an update of current knowledge on the role of metalloproteinases in the physiology and pathology of the central nervous system. The collection covers a wide range of situations in which matrix metalloproteinases, adamalysins and meprins are regulated and in turn regulate substrates or signalling pathways involved in: nervous system development, learning and memory, neuroinflammation, degeneration and repair after traumatic and ischemic injury or neurodegenerative mechanisms underlying retinopathies, psychiatric and neurodegenerative disor...
Source: Cellular and Molecular Life Sciences : CMLS - June 7, 2019 Category: Cytology Authors: Rivera S Tags: Cell Mol Life Sci Source Type: research

Matrix metalloproteinase signals following neurotrauma are right on cue.
Abstract Neurotrauma, a term referencing both traumatic brain and spinal cord injuries, is unique to neurodegeneration in that onset is clearly defined. From the perspective of matrix metalloproteinases (MMPs), there is opportunity to define their temporal participation in injury and recovery beginning at the level of the synapse. Here we examine the diverse roles of MMPs in the context of targeted insults (optic nerve lesion and hippocampal and olfactory bulb deafferentation), and clinically relevant focal models of traumatic brain and spinal cord injuries. Time-specific MMP postinjury signaling is critical to sy...
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2019 Category: Cytology Authors: Trivedi A, Noble-Haeusslein LJ, Levine JM, Santucci AD, Reeves TM, Phillips LL Tags: Cell Mol Life Sci Source Type: research

MMPs in learning and memory and neuropsychiatric disorders.
Abstract Matrix metalloproteinases (MMPs) are a group of over twenty proteases, operating chiefly extracellularly to cleave components of the extracellular matrix, cell adhesion molecules as well as cytokines and growth factors. By virtue of their expression and activity patterns in animal models and clinical investigations, as well as functional studies with gene knockouts and enzyme inhibitors, MMPs have been demonstrated to play a paramount role in many physiological and pathological processes in the brain. In particular, they have been shown to influence learning and memory processes, as well as major neuropsy...
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2019 Category: Cytology Authors: Beroun A, Mitra S, Michaluk P, Pijet B, Stefaniuk M, Kaczmarek L Tags: Cell Mol Life Sci Source Type: research

Pancreatic beta cells persistently infected with coxsackievirus B4 are targets of NK cell-mediated cytolytic activity.
Abstract It has been suggested that the persistence of coxsackieviruses-B (CV-B) in pancreatic beta cells plays a role in the pathogenesis of type 1 diabetes (T1D). Yet, immunological effectors, especially natural killer (NK) cells, are supposed to clear virus-infected cells. Therefore, an evaluation of the response of NK cells to pancreatic beta cells persistently infected with CV-B4 was conducted. A persistent CV-B4 infection was established in 1.1B4 pancreatic beta cells. Infectious particles were found in supernatants throughout the culture period. The proportion of cells containing viral protein VP1 was low (
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2019 Category: Cytology Authors: Nekoua MP, Bertin A, Sane F, Alidjinou EK, Lobert D, Trauet J, Hober C, Engelmann I, Moutairou K, Yessoufou A, Hober D Tags: Cell Mol Life Sci Source Type: research

Regulation of AMPK activity by type 10 adenylyl cyclase: contribution to the mitochondrial biology, cellular redox and energy homeostasis.
In this study, sAC expression and activity were manipulated in H9C2 cells, adult rat cardiomyocytes or endothelial cells. sAC knockdown depleted the cellular cAMP content and decreased AMPK activity in an EPAC-dependent manner. Functionally, sAC knockdown reduced cellular ATP content, increased mitochondrial ROS formation and led to mitochondrial depolarization. Furthermore, sAC downregulation led to EPAC-dependent mitophagy disturbance, indicated by an increased mitochondrial mass and unaffected mitochondrial biogenesis. Consistently, sAC overexpression or stimulation with bicarbonate significantly increased AMPK activity...
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2019 Category: Cytology Authors: Jayarajan V, Appukuttan A, Aslam M, Reusch P, Regitz-Zagrosek V, Ladilov Y Tags: Cell Mol Life Sci Source Type: research

MMPs and ADAMs in neurological infectious diseases and multiple sclerosis.
Abstract Metalloproteinases-such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs)-are involved in various diseases of the nervous system but also contribute to nervous system development, synaptic plasticity and neuroregeneration upon injury. MMPs and ADAMs proteolytically cleave many substrates including extracellular matrix components but also signaling molecules and receptors. During neuroinfectious disease with associated neuroinflammation, MMPs and ADAMs regulate blood-brain barrier breakdown, bacterial invasion, neutrophil infiltration and cytokine signaling. Specific and ...
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2019 Category: Cytology Authors: Muri L, Leppert D, Grandgirard D, Leib SL Tags: Cell Mol Life Sci Source Type: research

PGAM5 is a key driver of mitochondrial dysfunction in experimental lung fibrosis.
CONCLUSIONS: Our study identifies PGAM5 as an important regulator of mitochondrial homeostasis in pulmonary fibrosis. Our data further indicate PGAM5-mediated mitophagy itself as a pivotal gateway event in the mediation of self-sustaining mitochondrial damage and membrane depolarization. Our work hereby highlights the importance of mitochondrial dynamics and identifies a potential therapeutic target that warrants further studies. Toxic agents lead to mitochondrial damage resulting in depolarization of the mitochondrial membrane potential (ΔΨ) which is a gateway event for the initiation of PGAM5-mediated mitophagy...
Source: Cellular and Molecular Life Sciences : CMLS - June 5, 2019 Category: Cytology Authors: Ganzleben I, He GW, Günther C, Prigge ES, Richter K, Rieker RJ, Mougiakakos D, Neurath MF, Becker C Tags: Cell Mol Life Sci Source Type: research

Matrix metalloproteinases and ADAMs in stroke.
ell A Abstract Stroke is a leading cause of death and disability worldwide. However, after years of in-depth research, the pathophysiology of stroke is still not fully understood. Increasing evidence shows that matrix metalloproteinases (MMPs) and "a disintegrin and metalloproteinase" (ADAMs) participate in the neuro-inflammatory cascade that is triggered during stroke but also in recovery phases of the disease. This review covers the involvement of these proteins in brain injury following cerebral ischemia which has been widely studied in recent years, with efforts to modulate this group of proteins in ...
Source: Cellular and Molecular Life Sciences : CMLS - June 5, 2019 Category: Cytology Authors: Montaner J, Ramiro L, Simats A, Hernández-Guillamon M, Delgado P, Bustamante A, Rosell A Tags: Cell Mol Life Sci Source Type: research

Modulation of miRNA function by natural and synthetic RNA-binding proteins in cancer.
Abstract RNA-binding proteins (RBPs) and microRNAs (miRNAs) are the most important regulators of mRNA stability and translation in eukaryotic cells; however, the complex interplay between these systems is only now coming to light. RBPs and miRNAs regulate a unique set of targets in either a positive or negative manner and their regulation is mainly opposed to each other on overlapping targets. In some cases, the levels of RBPs or miRNAs regulate the cellular levels of one another and decreased levels of either results in changes in translation of their targets. There is growing evidence that these regulatory circu...
Source: Cellular and Molecular Life Sciences : CMLS - June 4, 2019 Category: Cytology Authors: Vos PD, Leedman PJ, Filipovska A, Rackham O Tags: Cell Mol Life Sci Source Type: research

pH and male fertility: making sense on pH homeodynamics throughout the male reproductive tract.
Abstract In the male reproductive tract, ionic equilibrium is essential to maintain normal spermatozoa production and, hence, the reproductive potential. Among the several ions, HCO3- and H+ have a central role, mainly due to their role on pH homeostasis. In the male reproductive tract, the major players in pH regulation and homeodynamics are carbonic anhydrases (CAs), HCO3- membrane transporters (solute carrier 4-SLC4 and solute carrier 26-SLC26 family transporters), Na+-H+ exchangers (NHEs), monocarboxylate transporters (MCTs) and voltage-gated proton channels (Hv1). CAs and these membrane transporters are widel...
Source: Cellular and Molecular Life Sciences : CMLS - June 4, 2019 Category: Cytology Authors: Bernardino RL, Carrageta DF, Sousa M, Alves MG, Oliveira PF Tags: Cell Mol Life Sci Source Type: research

Matrix metalloproteinases in the CNS: interferons get nervous.
Abstract Matrix metalloproteinases (MMPs) have been investigated in context of chronic inflammatory diseases and demonstrated to degrade multiple components of the extracellular matrix (ECM). However, following several disappointing MMP clinical trials, recent studies have demonstrated unexpected novel functions of MMPs in viral infections and autoimmune inflammatory diseases in unanticipated locations. Thus, MMPs play additional functions in inflammation than just ECM degradation. They can regulate the activity of chemokines and cytokines of the immune response by precise proteolytic processing resulting in activ...
Source: Cellular and Molecular Life Sciences : CMLS - June 4, 2019 Category: Cytology Authors: Chopra S, Overall CM, Dufour A Tags: Cell Mol Life Sci Source Type: research

Evolutionary analyses of NIN-like proteins in plants and their roles in nitrate signaling.
Abstract Nitrogen (N) is one of the most important essential macro-elements for plant growth and development, and nitrate represents the most abundant inorganic form of N in soils. The nitrate uptake and assimilation processes are finely tuned according to the available nitrate in the surroundings as well as by the internal finely coordinated signaling pathways. The NIN-like proteins (NLPs) harbor both RWP-RK, and Phox and Bem1 (PB1) domains, and they belong to the well-characterized plant-specific RWP-RK transcription factor gene family. NLPs are known to be involved in the nitrate signaling pathway by activating...
Source: Cellular and Molecular Life Sciences : CMLS - June 3, 2019 Category: Cytology Authors: Mu X, Luo J Tags: Cell Mol Life Sci Source Type: research

Elmo1 function, linked to Rac1 activity, regulates peripheral neuronal numbers and myelination in zebrafish.
Abstract Peripheral nervous system development involves a tight coordination of neuronal birth and death and a substantial remodelling of the myelinating glia cytoskeleton to achieve myelin wrapping of its projecting axons. However, how these processes are coordinated through time is still not understood. We have identified engulfment and cell motility 1, Elmo1, as a novel component that regulates (i) neuronal numbers within the Posterior Lateral Line ganglion and (ii) radial sorting of axons by Schwann cells (SC) and myelination in the PLL system in zebrafish. Our results show that neuronal and myelination defect...
Source: Cellular and Molecular Life Sciences : CMLS - June 3, 2019 Category: Cytology Authors: Mikdache A, Fontenas L, Albadri S, Revenu C, Loisel-Duwattez J, Lesport E, Degerny C, Del Bene F, Tawk M Tags: Cell Mol Life Sci Source Type: research

PGC-1 α induced browning promotes involution and inhibits lactation in mammary glands.
PGC-1α induced browning promotes involution and inhibits lactation in mammary glands. Cell Mol Life Sci. 2019 Jun 01;: Authors: Piccinin E, Morgano A, Peres C, Contursi A, Bertrand-Michel J, Arconzo M, Guillou H, Villani G, Moschetta A Abstract The PPARγ coactivator 1α (PGC-1α) is a transcriptional regulator of mitochondrial biogenesis and oxidative metabolism. Recent studies have highlighted a fundamental role of PGC-1α in promoting breast cancer progression and metastasis, but the physiological role of this coactivator in the development of mammary glands is still unkno...
Source: Cellular and Molecular Life Sciences : CMLS - June 1, 2019 Category: Cytology Authors: Piccinin E, Morgano A, Peres C, Contursi A, Bertrand-Michel J, Arconzo M, Guillou H, Villani G, Moschetta A Tags: Cell Mol Life Sci Source Type: research

Understanding histone H3 lysine 36 methylation and its deregulation in disease.
Abstract Methylation of histone H3 lysine 36 (H3K36) plays crucial roles in the partitioning of chromatin to distinctive domains and the regulation of a wide range of biological processes. Trimethylation of H3K36 (H3K36me3) demarcates body regions of the actively transcribed genes, providing signals for modulating transcription fidelity, mRNA splicing and DNA damage repair; and di-methylation of H3K36 (H3K36me2) spreads out within large intragenic regions, regulating distribution of histone H3 lysine 27 trimethylation (H3K27me3) and possibly DNA methylation. These H3K36 methylation-mediated events are biologically...
Source: Cellular and Molecular Life Sciences : CMLS - May 30, 2019 Category: Cytology Authors: Li J, Ahn JH, Wang GG Tags: Cell Mol Life Sci Source Type: research

Microbiome-metabolomics reveals gut microbiota associated with glycine-conjugated metabolites and polyamine metabolism in chronic kidney disease.
Abstract Dysbiosis of the gut microbiome and related metabolites in chronic kidney disease (CKD) have been intimately associated with the prevalence of cardiovascular diseases. Unfortunately, thus far, there is a paucity of sufficient knowledge of gut microbiome and related metabolites on CKD progression partly due to the severely limited investigations. Using a 5/6 nephrectomized (NX) rat model, we carried out 16S rRNA sequence and untargeted metabolomic analyses to explore the relationship between colon's microbiota and serum metabolites. Marked decline in microbial diversity and richness was...
Source: Cellular and Molecular Life Sciences : CMLS - May 30, 2019 Category: Cytology Authors: Feng YL, Cao G, Chen DQ, Vaziri ND, Chen L, Zhang J, Wang M, Guo Y, Zhao YY Tags: Cell Mol Life Sci Source Type: research

Deregulated miRNAs in osteoporosis: effects in bone metastasis.
Abstract Starting from their role exerted on osteoblast and osteoclast differentiation and activity pathways, microRNAs (miRNAs) have been recently identified as regulators of different processes in bone homeostasis. For this purpose, in a recent review, we highlighted, as deregulated miRNAs could be involved in different bone diseases such as osteoporosis. In addition, recent studies supported the concept that osteoporosis-induced bone alterations might offer a receptive site for cancer cells to form bone metastases, However, to date, no data on specific-shared miRNAs between osteoporosis and bone metastases have...
Source: Cellular and Molecular Life Sciences : CMLS - May 30, 2019 Category: Cytology Authors: Bellavia D, Salamanna F, Raimondi L, De Luca A, Carina V, Costa V, Alessandro R, Fini M, Giavaresi G Tags: Cell Mol Life Sci Source Type: research

Therapeutic perspectives for structural and functional abnormalities of cilia.
Abstract Ciliopathies are a group of hereditary disorders that result from structural or functional abnormalities of cilia. Recent intense research efforts have uncovered the genetic bases of ciliopathies, and our understanding of the assembly and functions of cilia has been improved significantly. Although mechanism-specific therapies for ciliopathies have not yet received regulatory approval, the use of innovative therapeutic modalities such as oligonucleotide therapy, gene replacement therapy, and gene editing in addition to symptomatic treatments are expected to provide valid treatment options in the near futu...
Source: Cellular and Molecular Life Sciences : CMLS - May 30, 2019 Category: Cytology Authors: Kim YJ, Kim J Tags: Cell Mol Life Sci Source Type: research

Death for life: a path from apoptotic signaling to tissue-scale effects of apoptotic epithelial extrusion.
We describe how apoptosis can control epithelial homeostasis though epithelial extrusion, a highly orchestrated process based on high- order actomyosin structures and on the coordination between the apoptotic and the neighboring cells. Finally, we describe how the synergy among forces generated by multiple apoptotic cells can shape epithelia in embryo development. PMID: 31143959 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - May 29, 2019 Category: Cytology Authors: Gagliardi PA, Primo L Tags: Cell Mol Life Sci Source Type: research

N(6)-Methyladenine in eukaryotes.
Abstract DNA modifications are a major form of epigenetic regulation that eukaryotic cells utilize in concert with histone modifications. While much work has been done elucidating the role of 5-methylcytosine over the past several decades, only recently has it been recognized that N(6)-methyladenine (N6-mA) is present in quantifiable and biologically active levels in the DNA of eukaryotic cells. Unlike prokaryotes which utilize N6-mA to recognize "self" from "foreign" DNA, eukaryotes have been found to use N6-mA in varying ways, from regulating transposable elements to gene regulation in respon...
Source: Cellular and Molecular Life Sciences : CMLS - May 29, 2019 Category: Cytology Authors: Alderman MH, Xiao AZ Tags: Cell Mol Life Sci Source Type: research

No imprinted XIST expression in pigs: biallelic XIST expression in early embryos and random X inactivation in placentas.
Abstract Dosage compensation, which is achieved by X-chromosome inactivation (XCI) in female mammals, ensures balanced X-linked gene expression levels between the sexes. Although eutherian mammals commonly display random XCI in embryonic and adult tissues, imprinted XCI has also been identified in extraembryonic tissues of mouse, rat, and cow. Little is known about XCI in pigs. Here, we sequenced the porcine XIST gene and identified an insertion/deletion mutation between Asian- and Western-origin pig breeds. Allele-specific analysis revealed biallelic XIST expression in porcine ICSI blastocysts. To investigate the...
Source: Cellular and Molecular Life Sciences : CMLS - May 28, 2019 Category: Cytology Authors: Zou H, Yu D, Du X, Wang J, Chen L, Wang Y, Xu H, Zhao Y, Zhao S, Pang Y, Liu Y, Hao H, Zhao X, Du W, Dai Y, Li N, Wu S, Zhu H Tags: Cell Mol Life Sci Source Type: research