Evidence for skeletal muscle fiber type-specific expressions of mechanosensors.
Abstract Mechanosensors govern muscle tissue integrity and constitute a subcellular structure known as costameres. Costameres physically link the muscle extracellular matrix to contractile and signaling 'hubs' inside muscle fibers mainly via integrins and are localized beneath sarcolemmas of muscle fibers. Costameres are the main mechanosensors converting mechanical cues into biological events. However, the fiber type-specific costamere architecture in muscles is unexplored. We hypothesized that fiber types differ in the expression of genes coding for costamere components. By coupling laser microdissection to a mu...
Source: Cellular and Molecular Life Sciences : CMLS - January 30, 2019 Category: Cytology Authors: Mathes S, Vanmunster M, Bloch W, Suhr F Tags: Cell Mol Life Sci Source Type: research

Dgcr8 knockout approaches to understand microRNA functions in vitro and in vivo.
Abstract Biologic function of the majority of microRNAs (miRNAs) is still unknown. Uncovering the function of miRNAs is hurdled by redundancy among different miRNAs. The deletion of Dgcr8 leads to the deficiency in producing all canonical miRNAs, therefore, overcoming the redundancy issue. Dgcr8 knockout strategy has been instrumental in understanding the function of miRNAs in a variety of cells in vitro and in vivo. In this review, we will first give a brief introduction about miRNAs, miRNA biogenesis pathway and the role of Dgcr8 in miRNA biogenesis. We will then summarize studies performed with Dgcr8 knockout c...
Source: Cellular and Molecular Life Sciences : CMLS - January 29, 2019 Category: Cytology Authors: Guo WT, Wang Y Tags: Cell Mol Life Sci Source Type: research

Non-obesogenic doses of fatty acids modulate the functionality of the circadian clock in the liver.
Abstract Saturated fatty acids, such as palmitate, lead to circadian disruption in cell culture. Moreover, information regarding the effects of unsaturated fatty acids on circadian parameters is scarce. We aimed at studying the effects of low doses of saturated as well as unsaturated fatty acids on circadian metabolism in vivo and at deciphering the mechanism by which fatty acids convey their effect. Mice were fed non-obesogenic doses of palm or olive oil and hepatocytes were treated with palmitate and oleate. Mice fed non-obesogenic doses of palm oil showed increased signaling towards fatty acid synthesis, while ...
Source: Cellular and Molecular Life Sciences : CMLS - January 29, 2019 Category: Cytology Authors: Tal Y, Chapnik N, Froy O Tags: Cell Mol Life Sci Source Type: research

Determinants of stem cell lineage differentiation toward chondrogenesis versus adipogenesis.
Abstract Adult stem cells, also termed as somatic stem cells, are undifferentiated cells, detected among differentiated cells in a tissue or an organ. Adult stem cells can differentiate toward lineage specific cell types of the tissue or organ in which they reside. They also have the ability to differentiate into mature cells of mesenchymal tissues, such as cartilage, fat and bone. Despite the fact that the balance has been comprehensively scrutinized between adipogenesis and osteogenesis and between chondrogenesis and osteogenesis, few reviews discuss the relationship between chondrogenesis and adipogenesis. In t...
Source: Cellular and Molecular Life Sciences : CMLS - January 28, 2019 Category: Cytology Authors: Zhou S, Chen S, Jiang Q, Pei M Tags: Cell Mol Life Sci Source Type: research

Link between the unfolded protein response and dysregulation of mitochondrial bioenergetics in Alzheimer's disease.
Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting more than 47.5 million people worldwide. Metabolic impairments are common hallmarks of AD, and amyloid-β (Aβ) peptide and hyperphosphorylated tau protein-the two foremost histopathological signs of AD-have been implicated in mitochondrial dysfunction. Many neurodegenerative disorders, including AD, show excessive amounts of mis-/unfolded proteins leading to an activation of the unfolded protein response (UPR). In the present study, we aimed to characterize the link between ER stress and bioenergetics defects under nor...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Poirier Y, Grimm A, Schmitt K, Eckert A Tags: Cell Mol Life Sci Source Type: research

The HMG box transcription factor HBP1: a cell cycle inhibitor at the crossroads of cancer signaling pathways.
Abstract HMG box protein 1 (HBP1) is a transcription factor and a potent cell cycle inhibitor in normal and cancer cells. HBP1 activates or represses the expression of different cell cycle genes (such as CDKN2A, CDKN1A, and CCND1) through direct DNA binding, cofactor recruitment, chromatin remodeling, or neutralization of other transcription factors. Among these are LEF1, TCF4, and MYC in the WNT/beta-catenin pathway. HBP1 also contributes to oncogenic RAS-induced senescence and terminal cell differentiation. Collectively, these activities suggest a tumor suppressor function. However, HBP1 is not listed among freq...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Bollaert E, de Rocca Serra A, Demoulin JB Tags: Cell Mol Life Sci Source Type: research

Cellular responses to proteostasis perturbations reveal non-optimal feedback in chaperone networks.
Abstract The proteostasis network (PN) comprises a plethora of proteins that are dedicated to aid in protein folding and maintenance; some with overlapping functions. Despite this, there are multiple pathophysiological states associated with depletion of chaperones. This is counter-intuitive, assuming cells have the ability to re-program transcriptional outputs in accordance with its proteostasic limitations. Here, we have used S. cerevisiae to understand how cells respond to different types of proteostasis impairments. We monitored the proteostasis status and transcriptome of single deletions of fourteen differen...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Ghosh A, Gangadharan A, Verma M, Das S, Matai L, Dash DP, Dash D, Mapa K, Chakraborty K Tags: Cell Mol Life Sci Source Type: research

The functional roles of exosomal long non-coding RNAs in cancer.
Abstract Exosomes are extracellular membranous vesicles that are secreted by various cell types. Exosomes have become indispensable facilitators in the exchange of information between cells. More importantly, exosomes perform a crucial role in a variety of diseases including cancers. Long non-coding RNAs (lncRNAs) are over 200 nucleotides long transcripts that exhibit no or limited protein-coding potentials. LncRNAs are an emerging group of regulatory RNAs and can be selectively packaged into exosomes. Exosomal lncRNAs play a central role in carcinogenesis and cancer progression by modulating tumor growth, metasta...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Wang M, Zhou L, Yu F, Zhang Y, Li P, Wang K Tags: Cell Mol Life Sci Source Type: research

The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD).
ard P Abstract NAFLD is currently the main cause of chronic liver disease in developed countries, and the number of NAFLD patients is growing worldwide. NAFLD often has similar symptoms to other metabolic disorders, including type 2 diabetes and obesity. Recently, the role of the gut microbiota in the pathophysiology of many diseases has been revealed. Regarding NAFLD, experiments using gut microbiota transplants to germ-free animal models showed that fatty liver disease development is determined by gut bacteria. Moreover, the perturbation of the composition of the gut microbiota has been observed in patients suff...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2019 Category: Cytology Authors: Safari Z, Gérard P Tags: Cell Mol Life Sci Source Type: research

Orthologous CRISPR/Cas9 systems for specific and efficient degradation of covalently closed circular DNA of hepatitis B virus.
Abstract Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the major cause of viral persistence and chronic hepatitis B. CRISPR/Cas9 nucleases can specifically target HBV cccDNA for decay, but off-target effects of nucleases in the human genome limit their clinical utility. CRISPR/Cas9 systems from four different species were co-expressed in cell lines with guide RNAs targeting conserved regions of the HBV genome. CRISPR/Cas9 systems from Streptococcus pyogenes (Sp) and Streptococcus thermophilus (St) targeting conserved regions of the HBV genome blocked HBV replication and, most importantly, r...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2019 Category: Cytology Authors: Kostyushev D, Brezgin S, Kostyusheva A, Zarifyan D, Goptar I, Chulanov V Tags: Cell Mol Life Sci Source Type: research

The SEACIT complex is involved in the maintenance of vacuole-mitochondria contact sites and controls mitophagy.
Abstract The major signaling pathway that regulates cell growth and metabolism is under the control of the target of rapamycin complex 1 (TORC1). In Saccharomyces cerevisiae the SEA complex is one of the TORC1 upstream regulators involved in amino acid sensing and autophagy. Here, we performed analysis of the expression, interactions and localization of SEA complex proteins under different conditions, varying parameters such as sugar source, nitrogen availability and growth phase. Our results show that the SEA complex promotes mitochondria degradation either by mitophagy or by general autophagy. In addition, the S...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2019 Category: Cytology Authors: Ma Y, Moors A, Camougrand N, Dokudovskaya S Tags: Cell Mol Life Sci Source Type: research

Mitochondrial stress triggers a pro-survival response through epigenetic modifications of nuclear DNA.
In conclusion, mitochondrial dysfunction leads to a "pro-survival" adaptive state that seems to be triggered by the differential methylation of nuclear genes. PMID: 30673822 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2019 Category: Cytology Authors: Mayorga L, Salassa BN, Marzese DM, Loos MA, Eiroa HD, Lubieniecki F, García Samartino C, Romano PS, Roqué M Tags: Cell Mol Life Sci Source Type: research

Testicular germ cell tumor: a comprehensive review.
Abstract Testicular tumors are the most common tumors in adolescent and young men and germ cell tumors (TGCTs) account for most of all testicular cancers. Increasing incidence of TGCTs among males provides strong motivation to understand its biological and genetic basis. Gains of chromosome arm 12p and aneuploidy are nearly universal in TGCTs, but TGCTs have low point mutation rate. It is thought that TGCTs develop from premalignant intratubular germ cell neoplasia that is believed to arise from the failure of normal maturation of gonocytes during fetal or postnatal development. Progression toward invasive TG...
Source: Cellular and Molecular Life Sciences : CMLS - January 22, 2019 Category: Cytology Authors: Batool A, Karimi N, Wu XN, Chen SR, Liu YX Tags: Cell Mol Life Sci Source Type: research

A disease causing ATLASTIN 3 mutation affects multiple endoplasmic reticulum-related pathways.
Abstract Atlastins (ATLs) are membrane-bound GTPases involved in shaping of the endoplasmic reticulum (ER). Mutations in ATL1 and ATL3 cause spastic paraplegia and hereditary sensory neuropathy. We here show that the sensory neuropathy causing ATL3 Y192C mutation reduces the complexity of the tubular ER-network. ATL3 Y192C delays ER-export by reducing the number of ER exit sites, reduces autophagy, fragments the Golgi and causes malformation of the nucleus. In cultured primary neurons, ATL3 Y192C does not localize to the growing axon, resulting in axon growth deficits. Patient-derived fibroblasts possess a tubular...
Source: Cellular and Molecular Life Sciences : CMLS - January 21, 2019 Category: Cytology Authors: Behrendt L, Kurth I, Kaether C Tags: Cell Mol Life Sci Source Type: research

Critical role of UQCRC1 in embryo survival, brain ischemic tolerance and normal cognition in mice.
Abstract Ubiquinol cytochrome c reductase core protein I (UQCRC1) is a component of the complex III in the respiratory chain. Its biological functions are unknown. Here, we showed that knockout of UQCRC1 led to embryonic lethality. Disrupting one UQCRC1 allele in mice (heterozygous mice) of both sexes did not affect their growth but reduced UQCRC1 mRNA and protein in the brain. These mice had decreased complex III formation, complex III activity and ATP content in the brain at baseline. They developed worsened neurological outcome after brain ischemia/hypoxia or focal brain ischemia compared with wild-type mice. T...
Source: Cellular and Molecular Life Sciences : CMLS - January 21, 2019 Category: Cytology Authors: Shan W, Li J, Xu W, Li H, Zuo Z Tags: Cell Mol Life Sci Source Type: research

A novel leptin receptor antagonist uncouples leptin's metabolic and immune functions.
Abstract Leptin links body energy stores to high energy demanding processes like reproduction and immunity. Based on leptin's role in autoimmune diseases and cancer, several leptin and leptin receptor (LR) antagonists have been developed, but these intrinsically lead to unwanted weight gain. Here, we report on the uncoupling of leptin's metabolic and immune functions based on the cross talk with the epidermal growth factor receptor (EGFR). We show that both receptors spontaneously interact and, remarkably, that this complex can partially overrule the lack of LR activation by a leptin antagonistic mutein. Moreover,...
Source: Cellular and Molecular Life Sciences : CMLS - January 18, 2019 Category: Cytology Authors: Zabeau L, Wauman J, Dam J, Van Lint S, Burg E, De Geest J, Rogge E, Silva A, Jockers R, Tavernier J Tags: Cell Mol Life Sci Source Type: research

The role of endogenous tissue-type plasminogen activator in neuronal survival after ischemic stroke: friend or foe?
Abstract Endogenous protease tissue-type plasminogen activator (tPA) has highly efficient fibrinolytic activity and its recombinant variants alteplase and tenecteplase are established as highly effective thrombolytic drugs for ischemic stroke. Endogenous tPA is constituted of five functional domains through which it interacts with a variety of substrates, binding proteins and receptors, thus having enzymatic and cytokine-like effects to act on all cell types of the brain. In the past 2 decades, numerous studies have explored the clinical relevance of endogenous tPA in neurological diseases, especially in isch...
Source: Cellular and Molecular Life Sciences : CMLS - January 17, 2019 Category: Cytology Authors: Zhu J, Wan Y, Xu H, Wu Y, Hu B, Jin H Tags: Cell Mol Life Sci Source Type: research

Monitoring activities of receptor tyrosine kinases using a universal adapter in genetically encoded split TEV assays.
Abstract Receptor tyrosine kinases (RTKs) play key roles in various aspects of cell biology, including cell-to-cell communication, proliferation and differentiation, survival, and tissue homeostasis, and have been implicated in various diseases including cancer and neurodevelopmental disorders. Ligand-activated RTKs recruit adapter proteins through a phosphotyrosine (p-Tyr) motif that is present on the RTK and a p-Tyr-binding domain, like the Src homology 2 (SH2) domain found in adapter proteins. Notably, numerous combinations of RTK/adapter combinations exist, making it challenging to compare receptor activities ...
Source: Cellular and Molecular Life Sciences : CMLS - January 8, 2019 Category: Cytology Authors: Wintgens JP, Wichert SP, Popovic L, Rossner MJ, Wehr MC Tags: Cell Mol Life Sci Source Type: research

Long non-coding RNA in stem cell pluripotency and lineage commitment: functions and evolutionary conservation.
Abstract LncRNAs have recently emerged as new and fundamental transcriptional and post-transcriptional regulators acting at multiple levels of gene expression. Indeed, lncRNAs participate in a wide variety of stem cell and developmental processes, acting in cis and/or in trans in the nuclear and/or in the cytoplasmic compartments, and generating an intricate network of interactions with RNAs, enhancers, and chromatin-modifier complexes. Given the versatility of these molecules to operate in different subcellular compartments, via different modes of action and with different target specificity, the interest in this...
Source: Cellular and Molecular Life Sciences : CMLS - January 3, 2019 Category: Cytology Authors: Fico A, Fiorenzano A, Pascale E, Patriarca EJ, Minchiotti G Tags: Cell Mol Life Sci Source Type: research

Potentiation of a neuronal nicotinic receptor via pseudo-agonist site.
Abstract Neuronal nicotinic receptors containing α4 and β2 subunits assemble in two pentameric stoichiometries, (α4)3(β2)2 and (α4)2(β2)3, each with distinct pharmacological signatures; (α4)3(β2)2 receptors are strongly potentiated by the drug NS9283, whereas (α4)2(β2)3 receptors are unaffected. Despite this stoichiometry-selective pharmacology, the molecular identity of the target for NS9283 remains elusive. Here, studying (α4)3(β2)2 receptors, we show that mutations at either the principal face of the β2 subunit or the complementary face of t...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Mazzaferro S, Bermudez I, Sine SM Tags: Cell Mol Life Sci Source Type: research

Impairment of CFTR activity in cultured epithelial cells upregulates the expression and activity of LDH resulting in lactic acid hypersecretion.
ma TA Abstract Mutations in the gene encoding the CFTR chloride channel produce cystic fibrosis (CF). CF patients are more susceptible to bacterial infections in lungs. The most accepted hypothesis sustains that a reduction in the airway surface liquid (ASL) volume favor infections. Alternatively, it was postulated that a reduced HCO3- transport through CFTR leads to a decreased ASL pH, favoring bacterial colonization. The issue is controversial, since recent data from cultured primary cells and CF children showed normal pH values in the ASL. We have reported previously a decreased mitochondrial Complex I (mCx-I) ...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Valdivieso ÁG, Clauzure M, Massip-Copiz MM, Cancio CE, Asensio CJA, Mori C, Santa-Coloma TA Tags: Cell Mol Life Sci Source Type: research

Multiple endocannabinoid-mediated mechanisms in the regulation of energy homeostasis in brain and peripheral tissues.
Abstract The endocannabinoid (eCB) system is widely expressed in many central and peripheral tissues, and is involved in a plethora of physiological processes. Among these, activity of the eCB system promotes energy intake and storage, which, however, under pathophysiological conditions, can favour the development of obesity and obesity-related disorders. It is proposed that eCB signalling is evolutionary beneficial for survival under periods of scarce food resources. Remarkably, eCB signalling is increased both in hunger and in overnutrition conditions, such as obesity and type-2 diabetes. This apparent paradox s...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Ruiz de Azua I, Lutz B Tags: Cell Mol Life Sci Source Type: research

Mammalian class I odorant receptors exhibit a conserved vestibular-binding pocket.
Abstract Odorant receptors represent the largest family of mammalian G protein-coupled receptors. Phylogenetically, they are split into two classes (I and II). By analyzing the entire subclass I odorant receptors sequences, we identified two class I-specific and highly conserved motifs. These are predicted to face each other at the extra-cellular portion of the transmembrane domain, forming a vestibular site at the entrance to the orthosteric-binding cavity. Molecular dynamics simulation combined with site-directed mutagenesis and in vitro functional assays confirm the functional role of this vestibular site in li...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Bushdid C, de March CA, Topin J, Do M, Matsunami H, Golebiowski J Tags: Cell Mol Life Sci Source Type: research

Transcriptional repression of the ectodomain sheddase ADAM10 by TBX2 and potential implication for Alzheimer's disease.
CONCLUSION: Our results characterize TBX2 as a repressor of ADAM10 gene expression and suggest that this regulatory interaction is conserved across tissues and species. PMID: 30599067 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Reinhardt S, Schuck F, Stoye N, Hartmann T, Grimm MOW, Pflugfelder G, Endres K Tags: Cell Mol Life Sci Source Type: research

Cellular senescence is associated with reorganization of the microtubule cytoskeleton.
This study evaluated the cytoskeleton in two independent cellular models of kidney epithelium senescence. Our work identified multiple senescence-related alterations that impact microtubules and filamentous actin during interphase. Both filamentous systems reorganized profoundly when cells became senescent. As such, microtubule stability increased during senescence, making these filaments more resistant to disassembly in the cold or by nocodazole. Microtubule stabilization was accompanied by enhanced α-tubulin acetylation on lysine 40 and the depletion of HDAC6, the major deacetylase for α-tubulin lysine 40. Rh...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Moujaber O, Fishbein F, Omran N, Liang Y, Colmegna I, Presley JF, Stochaj U Tags: Cell Mol Life Sci Source Type: research

The dual face of glutamate: from a neurotoxin to a potential survival factor-metabolic implications in health and disease.
Abstract Glutamate is the major excitatory neurotransmitter in the central nervous system. Beyond this function, glutamate also plays a key role in intermediary metabolism in all organs and tissues, linking carbohydrate and amino acid metabolism via the tricarboxylic acid cycle. Under both physiological and pathological conditions, we have recently found that the ability of glutamate to fuel cell metabolism selectively relies on the activity of two main transporters: the sodium-calcium exchanger (NCX) and the sodium-dependent excitatory amino-acid transporters (EAATs). In ischemic settings, when glutamate is admin...
Source: Cellular and Molecular Life Sciences : CMLS - January 1, 2019 Category: Cytology Authors: Magi S, Piccirillo S, Amoroso S Tags: Cell Mol Life Sci Source Type: research

Mechanisms protecting host cells against bacterial pore-forming toxins.
Abstract Pore-forming toxins (PFTs) are key virulence determinants produced and secreted by a variety of human bacterial pathogens. They disrupt the plasma membrane (PM) by generating stable protein pores, which allow uncontrolled exchanges between the extracellular and intracellular milieus, dramatically disturbing cellular homeostasis. In recent years, many advances were made regarding the characterization of conserved repair mechanisms that allow eukaryotic cells to recover from mechanical disruption of the PM membrane. However, the specificities of the cell recovery pathways that protect host cells against PFT...
Source: Cellular and Molecular Life Sciences : CMLS - December 27, 2018 Category: Cytology Authors: Brito C, Cabanes D, Sarmento Mesquita F, Sousa S Tags: Cell Mol Life Sci Source Type: research

Immune responses in cardiac repair and regeneration: a comparative point of view.
r DYR Abstract Immediately after cardiac injury, the immune system plays major roles in repair and regeneration as it becomes involved in a number of processes including damage-associated signaling, inflammation, revascularization, cardiomyocyte dedifferentiation and replenishment, and fibrotic scar formation/resolution. Recent studies have revealed that different immune responses occur in the various experimental models capable or incapable of cardiac regeneration, and that harnessing these immune responses might improve cardiac repair. In light of this concept, this review analyzes current knowledge about the im...
Source: Cellular and Molecular Life Sciences : CMLS - December 21, 2018 Category: Cytology Authors: Lai SL, Marín-Juez R, Stainier DYR Tags: Cell Mol Life Sci Source Type: research

The contribution of environmental exposure to the etiology of autism spectrum disorder.
This article reviews our current understanding of environmental risk factors of ASD and their presumed adverse physiological mechanisms. It comprehensively maps the significance of parental age, teratogenic compounds, perinatal risks, medication, smoking and alcohol use, nutrition, vaccination, toxic exposures, as well as the role of extreme psychosocial factors. Further, we consider the role of potential protective factors such as folate and fatty acid intake. Evidence indicates an increased offspring vulnerability to ASD through advanced maternal and paternal age, valproate intake, toxic chemical exposure, maternal diabe...
Source: Cellular and Molecular Life Sciences : CMLS - December 20, 2018 Category: Cytology Authors: Bölte S, Girdler S, Marschik PB Tags: Cell Mol Life Sci Source Type: research

Endothelial cell apoptosis and the role of endothelial cell-derived extracellular vesicles in the progression of atherosclerosis.
Abstract To maintain physiological homeostasis, cell turnover occurs every day in the body via a form of programmed cell death called apoptosis. During apoptosis, cells undergo distinct morphological changes culminating in the disassembly of the dying cell into smaller fragments known as apoptotic bodies (ApoBDs). Dysregulation of apoptosis is associated with diseases including infection, cancer and atherosclerosis. Although the development of atherosclerosis is largely attributed to the accumulation of lipids and inflammatory debris in vessel walls, it is also associated with apoptosis of macrophages, smooth musc...
Source: Cellular and Molecular Life Sciences : CMLS - December 19, 2018 Category: Cytology Authors: Paone S, Baxter AA, Hulett MD, Poon IKH Tags: Cell Mol Life Sci Source Type: research

Meiotic spindle assembly checkpoint and aneuploidy in males versus females.
Abstract The production of gametes (sperm and eggs in mammals) involves two sequential cell divisions, meiosis I and meiosis II. In meiosis I, homologous chromosomes segregate to different daughter cells, and meiosis II resembles mitotic divisions in that sister chromatids separate. While in principle the process is identical in males and females, the time frame and susceptibility to chromosomal defects, including achiasmy and cohesion weakening, and the response to mis-segregating chromosomes are not. In this review, we compare and contrast meiotic spindle assembly checkpoint function and aneuploidy in the two se...
Source: Cellular and Molecular Life Sciences : CMLS - December 18, 2018 Category: Cytology Authors: Lane S, Kauppi L Tags: Cell Mol Life Sci Source Type: research

How many cadherins do human endothelial cells express?
án J Abstract The vasculature is the paradigm of a compartment generated by parallel cellular barriers that aims to transport oxygen, nutrients and immune cells in complex organisms. Vascular barrier dysfunction leads to fatal acute and chronic inflammatory diseases. The endothelial barrier lines the inner side of vessels and is the main regulator of vascular permeability. Cadherins comprise a superfamily of 114 calcium-dependent adhesion proteins that contain conserved cadherin motifs and form cell-cell junctions in metazoans. In mature human endothelial cells, only VE (vascular endothelial)-cadherin and N...
Source: Cellular and Molecular Life Sciences : CMLS - December 14, 2018 Category: Cytology Authors: Colás-Algora N, Millán J Tags: Cell Mol Life Sci Source Type: research

Increases in cytosolic Ca2+ induce dynamin- and calcineurin-dependent internalisation of CFTR.
Abstract The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated, apical anion channel that regulates ion and fluid transport in many epithelia including the airways. We have previously shown that cigarette smoke (CS) exposure to airway epithelia causes a reduction in plasma membrane CFTR expression which correlated with a decrease in airway surface hydration. The effect of CS on CFTR was dependent on an increase in cytosolic Ca2+. However, the underlying mechanism for this Ca2+-dependent, internalisation of CFTR is unknown. To gain a better understanding of the effect of Ca2+ on CFTR, w...
Source: Cellular and Molecular Life Sciences : CMLS - December 13, 2018 Category: Cytology Authors: Patel W, Moore PJ, Sassano MF, Lopes-Pacheco M, Aleksandrov AA, Amaral MD, Tarran R, Gray MA Tags: Cell Mol Life Sci Source Type: research

Intricate role of mitochondrial lipid in mitophagy and mitochondrial apoptosis: its implication in cancer therapeutics.
Abstract The efficacy of chemotherapy is mostly restricted by the drug resistance developed during the course of cancer treatment. Mitophagy, as a pro-survival mechanism, crucially maintains mitochondrial homeostasis and it is one of the mechanisms that cancer cells adopt for their progression. On the other hand, mitochondrial apoptosis, a precisely regulated form of cell death, acts as a tumor-suppressive mechanism by targeting cancer cells. Mitochondrial lipids, such as cardiolipin, ceramide, and sphingosine-1-phosphate, act as a mitophageal signal for the clearance of damaged mitochondria by interacting with mi...
Source: Cellular and Molecular Life Sciences : CMLS - December 11, 2018 Category: Cytology Authors: Praharaj PP, Naik PP, Panigrahi DP, Bhol CS, Mahapatra KK, Patra S, Sethi G, Bhutia SK Tags: Cell Mol Life Sci Source Type: research

HIF-1 α-derived cell-penetrating peptides inhibit ERK-dependent activation of HIF-1 and trigger apoptosis of cancer cells under hypoxia.
HIF-1α-derived cell-penetrating peptides inhibit ERK-dependent activation of HIF-1 and trigger apoptosis of cancer cells under hypoxia. Cell Mol Life Sci. 2018 Dec 10;: Authors: Karagiota A, Kourti M, Simos G, Mylonis I Abstract Hypoxia is frequently encountered in the microenvironment of solid tumors. Hypoxia-inducible factors (HIFs), the main effectors of cell response to hypoxia, promote cancer cell survival and progression. HIF-1α, the oxygen-regulated subunit of HIF-1, is often correlated with oncogenesis and represents an attractive therapeutic target. We have previously reported tha...
Source: Cellular and Molecular Life Sciences : CMLS - December 10, 2018 Category: Cytology Authors: Karagiota A, Kourti M, Simos G, Mylonis I Tags: Cell Mol Life Sci Source Type: research

Adaptive responses to low doses of radiation or chemicals: their cellular and molecular mechanisms.
This article reviews the current knowledge on the mechanisms of adaptive response to low doses of ionizing radiation or chemical exposure. A better knowledge of these mechanisms is needed to improve our understanding of health risks at low levels of environmental or occupational exposure and their involvement in cancer or non-cancer diseases. This response is orchestrated through a multifaceted cellular program involving the concerted action of diverse stress response pathways. These evolutionary highly conserved defense mechanisms determine the cellular response to chemical and physical aggression. They include DNA damage...
Source: Cellular and Molecular Life Sciences : CMLS - December 8, 2018 Category: Cytology Authors: Guéguen Y, Bontemps A, Ebrahimian TG Tags: Cell Mol Life Sci Source Type: research

Hindbrain induction and patterning during early vertebrate development.
Abstract The hindbrain is a key relay hub of the central nervous system (CNS), linking the bilaterally symmetric half-sides of lower and upper CNS centers via an extensive network of neural pathways. Dedicated neural assemblies within the hindbrain control many physiological processes, including respiration, blood pressure, motor coordination and different sensations. During early development, the hindbrain forms metameric segmented units known as rhombomeres along the antero-posterior (AP) axis of the nervous system. These compartmentalized units are highly conserved during vertebrate evolution and act as the tem...
Source: Cellular and Molecular Life Sciences : CMLS - December 5, 2018 Category: Cytology Authors: Frank D, Sela-Donenfeld D Tags: Cell Mol Life Sci Source Type: research

Coupling factors involved in preserving bone balance.
Abstract Coupling during bone remodeling refers to the spatial and temporal coordination of bone resorption with bone formation. Studies have assessed the subtle interactions between osteoclasts and osteoblasts to preserve bone balance. Traditionally, coupling research related to osteoclast function has focused on bone resorption activity causing the release of growth factors embedded in the bone matrix. However, considerable evidence from in vitro, animal, and human studies indicates the importance of the osteoclasts themselves in coupling phenomena, and many osteoclast-derived coupling factors have been identifi...
Source: Cellular and Molecular Life Sciences : CMLS - December 4, 2018 Category: Cytology Authors: Kim BJ, Koh JM Tags: Cell Mol Life Sci Source Type: research

The carotid body: a physiologically relevant germinal niche in the adult peripheral nervous system.
Abstract Oxygen constitutes a vital element for the survival of every single cell in multicellular aerobic organisms like mammals. A complex homeostatic oxygen-sensing system has evolved in these organisms, including detectors and effectors, to guarantee a proper supply of the element to every cell. The carotid body represents the most important peripheral arterial chemoreceptor organ in mammals and informs about hypoxemic situations to the effectors at the brainstem cardiorespiratory centers. To optimize organismal adaptation to maintained hypoxemic situations, the carotid body has evolved containing a niche of a...
Source: Cellular and Molecular Life Sciences : CMLS - November 29, 2018 Category: Cytology Authors: Sobrino V, Annese V, Navarro-Guerrero E, Platero-Luengo A, Pardal R Tags: Cell Mol Life Sci Source Type: research

Applications of PNA-laden nanoparticles for hematological disorders.
Abstract Safe and efficient genome editing has been an unmitigated goal for biomedical researchers since its inception. The most prevalent strategy for gene editing is the use of engineered nucleases that induce DNA damage and take advantage of cellular DNA repair machinery. This includes meganucleases, zinc-finger nucleases, transcription activator-like effector nucleases, and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) systems. However, the clinical viability of these nucleases is marred by their off-target cleavage activity (≥ 50% in RNA-guided endonucleases). In addition, ...
Source: Cellular and Molecular Life Sciences : CMLS - November 29, 2018 Category: Cytology Authors: Malik S, Oyaghire S, Bahal R Tags: Cell Mol Life Sci Source Type: research

Identification of CD36 as a new interaction partner of membrane NEU1: potential implication in the pro-atherogenic effects of the elastin receptor complex.
Abstract In addition to its critical role in lysosomes for catabolism of sialoglycoconjugates, NEU1 is expressed at the plasma membrane and regulates a myriad of receptors by desialylation, playing a key role in many pathophysiological processes. Here, we developed a proteomic approach dedicated to the purification and identification by LC-MS/MS of plasma membrane NEU1 interaction partners in human macrophages. Already known interaction partners were identified as well as several new candidates such as the class B scavenger receptor CD36. Interaction between NEU1 and CD36 was confirmed by complementary approaches....
Source: Cellular and Molecular Life Sciences : CMLS - November 29, 2018 Category: Cytology Authors: Kawecki C, Bocquet O, Schmelzer CEH, Heinz A, Ihling C, Wahart A, Romier B, Bennasroune A, Blaise S, Terryn C, Linton KJ, Martiny L, Duca L, Maurice P Tags: Cell Mol Life Sci Source Type: research

The inflammatory function of human IgA.
Abstract The prevailing concept regarding the immunological function of immunoglobulin A (IgA) is that it binds to and neutralizes pathogens to prevent infection at mucosal sites of the body. However, recently, it has become clear that in humans IgA is also able to actively contribute to the initiation of inflammation, both at mucosal and non-mucosal sites. This additional function of IgA is initiated by the formation of immune complexes, which trigger Fc alpha Receptor I (FcαRI) to synergize with various other receptors to amplify inflammatory responses. Recent findings have demonstrated that co-stimulation...
Source: Cellular and Molecular Life Sciences : CMLS - November 29, 2018 Category: Cytology Authors: Hansen IS, Baeten DLP, den Dunnen J Tags: Cell Mol Life Sci Source Type: research

Targeting autophagy using metallic nanoparticles: a promising strategy for cancer treatment.
cute; Abstract Despite the extensive genetic and phenotypic variations present in the different tumors, they frequently share common metabolic alterations, such as autophagy. Autophagy is a self-degradative process in response to stresses by which damaged macromolecules and organelles are targeted by autophagic vesicles to lysosomes and then eliminated. It is known that autophagy dysfunctions can promote tumorigenesis and cancer development, but, interestingly, its overstimulation by cytotoxic drugs may also induce cell death and chemosensitivity. For this reason, the possibility to modulate autophagy may represen...
Source: Cellular and Molecular Life Sciences : CMLS - November 27, 2018 Category: Cytology Authors: Cordani M, Somoza Á Tags: Cell Mol Life Sci Source Type: research

H19X-encoded miR-424(322)/-503 cluster: emerging roles in cell differentiation, proliferation, plasticity and metabolism.
Abstract miR-424(322)/-503 are mammal-specific members of the extended miR-15/107 microRNA family. They form a co-expression network with the imprinted lncRNA H19 in tetrapods. miR-424(322)/-503 regulate fundamental cellular processes including cell cycle, epithelial-to-mesenchymal transition, hypoxia and other stress response. They control tissue differentiation (cardiomyocyte, skeletal muscle, monocyte) and remodeling (mammary gland involution), and paradoxically participate in tumor initiation and progression. Expression of miR-424(322)/-503 is governed by unique mechanisms involving sex hormones. Here, we summ...
Source: Cellular and Molecular Life Sciences : CMLS - November 24, 2018 Category: Cytology Authors: Wang F, Liang R, Tandon N, Matthews ER, Shrestha S, Yang J, Soibam B, Yang J, Liu Y Tags: Cell Mol Life Sci Source Type: research

Transcription factor Ptf1a in development, diseases and reprogramming.
Abstract The transcription factor Ptf1a is a crucial helix-loop-helix (bHLH) protein selectively expressed in the pancreas, retina, spinal cord, brain, and enteric nervous system. Ptf1a is preferably assembled into a transcription trimeric complex PTF1 with an E protein and Rbpj (or Rbpjl). In pancreatic development, Ptf1a is indispensable in controlling the expansion of multipotent progenitor cells as well as the specification and maintenance of the acinar cells. In neural tissues, Ptf1a is transiently expressed in the post-mitotic cells and specifies the inhibitory neuronal cell fates, mostly mediated by downstr...
Source: Cellular and Molecular Life Sciences : CMLS - November 23, 2018 Category: Cytology Authors: Jin K, Xiang M Tags: Cell Mol Life Sci Source Type: research

Heparan sulfate proteoglycan (HSPG) can take part in cell division: inside and outside.
Abstract Prior to the cytokinesis, the cell-matrix interactions should be disrupted, and the mitotic cells round up. Prerequisite of mitosis, the centrosomes duplicate, spindle fibers are generated and move away from each other to opposite sides of the cells marking the cell poles. Later, an invagination in the plasma membrane is formed a few minutes after anaphase. This furrow ingression is driven by a contractile actomyosin ring, whose assembly is regulated by RhoA GTPase. At the completion of cytokinesis, the two daughter cells are still connected by a thin intercellular bridge, which is subjected to abscission...
Source: Cellular and Molecular Life Sciences : CMLS - November 21, 2018 Category: Cytology Authors: Ughy B, Schmidthoffer I, Szilak L Tags: Cell Mol Life Sci Source Type: research

Modeling elastin-associated vasculopathy with patient induced pluripotent stem cells and tissue engineering.
Abstract Elastin-associated vasculopathies are life-threatening conditions of blood vessel dysfunction. The extracellular matrix protein elastin endows the recoil and compliance required for physiologic arterial function, while disruption of function can lead to aberrant vascular smooth muscle cell proliferation manifesting through stenosis, aneurysm, or vessel dissection. Although research efforts have been informative, they remain incomplete as no viable therapies exist outside of a heart transplant. Induced pluripotent stem cell technology may be uniquely suited to address current obstacles as these present a r...
Source: Cellular and Molecular Life Sciences : CMLS - November 20, 2018 Category: Cytology Authors: Ellis MW, Luo J, Qyang Y Tags: Cell Mol Life Sci Source Type: research

Developmental and functional characteristics of the thoracic aorta perivascular adipocyte.
Abstract Thoracic aorta perivascular adipose tissue (T-PVAT) has critical roles in regulating vascular homeostasis. However, the developmental characteristics and cellular lineage of adipocyte in the T-PVAT remain unclear. We show that T-PVAT contains three long strip-shaped fat depots, anterior T-PVAT (A-T-PVAT), left lateral T-PVAT (LL-T-PVAT), and right lateral T-PVAT (RL-T-PVAT). A-T-PVAT displays a distinct transcriptional profile and developmental origin compared to the two lateral T-PVATs (L-T-PVAT). Lineage tracing studies indicate that A-T-PVAT adipocytes are primarily derived from SM22α+ progenitor...
Source: Cellular and Molecular Life Sciences : CMLS - November 17, 2018 Category: Cytology Authors: Ye M, Ruan CC, Fu M, Xu L, Chen D, Zhu M, Zhu D, Gao P Tags: Cell Mol Life Sci Source Type: research

Bardet-Biedl Syndrome proteins regulate cilia disassembly during tissue maturation.
HL Abstract Primary cilia are conserved organelles that mediate cellular communication crucial for organogenesis and homeostasis in numerous tissues. The retinal pigment epithelium (RPE) is a ciliated monolayer in the eye that borders the retina and is vital for visual function. Maturation of the RPE is absolutely critical for visual function and the role of the primary cilium in this process has been largely ignored to date. We show that primary cilia are transiently present during RPE development and that as the RPE matures, primary cilia retract, and gene expression of ciliary disassembly components decline. W...
Source: Cellular and Molecular Life Sciences : CMLS - November 16, 2018 Category: Cytology Authors: Patnaik SR, Kretschmer V, Brücker L, Schneider S, Volz AK, Oancea-Castillo LDR, May-Simera HL Tags: Cell Mol Life Sci Source Type: research

Structural disorder in the proteome and interactome of Alkhurma virus (ALKV).
Abstract Infection by the Alkhurma virus (ALKV) leading to the Alkhurma hemorrhagic fever is a common thread in Saudi Arabia, with no efficient treatment or prevention available as of yet. Although the rational drug design traditionally uses information on known 3D structures of viral proteins, intrinsically disordered proteins (i.e., functional proteins that do not possess unique 3D structures), with their multitude of disorder-dependent functions, are crucial for the biology of viruses. Here, viruses utilize disordered regions in their invasion of the host organisms and in hijacking and repurposing of different ...
Source: Cellular and Molecular Life Sciences : CMLS - November 15, 2018 Category: Cytology Authors: Redwan EM, AlJaddawi AA, Uversky VN Tags: Cell Mol Life Sci Source Type: research