Mammalian haploid stem cells: establishment, engineering and applications.
Abstract Haploid embryonic stem cells (haESCs) contain only one set of genomes inherited from the sperm or egg and are termed AG- or PG-haESCs, respectively. Mammalian haESCs show genome-wide hypomethylation and dysregulated imprinting, whereas they can sustain genome integrity during derivation and long-term propagation. In addition, haESCs exhibit similar pluripotency to traditional diploid ESCs but are unique because they function as gametes and have been used to produce semi-cloned animals. More strikingly, unisexual reproduction has been achieved in mice by using haESCs. In combination with a gene editing or ...
Source: Cellular and Molecular Life Sciences : CMLS - March 19, 2019 Category: Cytology Authors: He W, Chen J, Gao S Tags: Cell Mol Life Sci Source Type: research

Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia.
Abstract Medial vascular calcification has emerged as a putative key factor contributing to the excessive cardiovascular mortality of patients with chronic kidney disease (CKD). Hyperphosphatemia is considered a decisive determinant of vascular calcification in CKD. A critical role in initiation and progression of vascular calcification during elevated phosphate conditions is attributed to vascular smooth muscle cells (VSMCs), which are able to change their phenotype into osteo-/chondroblasts-like cells. These transdifferentiated VSMCs actively promote calcification in the medial layer of the arteries by producing...
Source: Cellular and Molecular Life Sciences : CMLS - March 18, 2019 Category: Cytology Authors: Voelkl J, Lang F, Eckardt KU, Amann K, Kuro-O M, Pasch A, Pieske B, Alesutan I Tags: Cell Mol Life Sci Source Type: research

A critical role for miR-142 in alveolar epithelial lineage formation in mouse lung development.
We report that the activation of the glucocorticoid pathway in an in vitro alveolar epithelial lineage differentiation assay led to increased AT2 marker Sftpc and decreased miR-142 expression. Using miR-142 KO mice, we demonstrate an increase in the AT2/AT1 cell number ratio. Overexpression of miR-142 in alveolar progenitor cells in vivo led to the opposite effect. Examination of the KO lungs at E18.5 revealed enhanced expression of miR-142 targets Apc, Ep300 and Kras associated with increased β-catenin and p-Erk signaling. Silencing of miR-142 expression in lung explants grown in vitro triggers enhanced Sftpc express...
Source: Cellular and Molecular Life Sciences : CMLS - March 18, 2019 Category: Cytology Authors: Shrestha A, Carraro G, Nottet N, Vazquez-Armendariz AI, Herold S, Cordero J, Singh I, Wilhelm J, Barreto G, Morty R, El Agha E, Mari B, Chen C, Zhang JS, Chao CM, Bellusci S Tags: Cell Mol Life Sci Source Type: research

LION: a simple and rapid method to achieve CRISPR gene editing.
Abstract The RNA-guided CRISPR-Cas9 technology has paved the way for rapid and cost-effective gene editing. However, there is still a great need for effective methods for rapid generation and validation of CRISPR/Cas9 gRNAs. Previously, we have demonstrated that highly efficient generation of multiplexed CRISPR guide RNA (gRNA) expression array can be achieved with Golden Gate Assembly (GGA). Here, we present an optimized and rapid method for generation and validation in less than 1 day of CRISPR gene targeting vectors. The method (LION) is based on ligation of double-stranded gRNA oligos into CRISPR vectors ...
Source: Cellular and Molecular Life Sciences : CMLS - March 18, 2019 Category: Cytology Authors: Xiang X, Luo L, Nodzyński M, Li C, Han P, Dou H, Petersen TS, Liang X, Pan X, Qu K, Yang L, Dang Y, Liu X, Bolund L, Zhang X, Tong G, Xing Y, Luo Y, Lin L Tags: Cell Mol Life Sci Source Type: research

Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases.
Abstract The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. The common lncRNAs known to be modulated by phytochemicals include ROR, PVT1, HOTAIR, MALAT1, H19, MEG3, PCAT29, PANDAR, NEAT1, and GAS5. The phytochemicals such as curcumin, resveratrol, sulforaphane, berberine, EGCG, and gambogic acid have been ...
Source: Cellular and Molecular Life Sciences : CMLS - March 16, 2019 Category: Cytology Authors: Mishra S, Verma SS, Rai V, Awasthee N, Chava S, Hui KM, Kumar AP, Challagundla KB, Sethi G, Gupta SC Tags: Cell Mol Life Sci Source Type: research

Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis.
Abstract Many secreted peptides used for cell-cell communication require conversion of a C-terminal glycine to an amide for bioactivity. This reaction is catalyzed only by the integral membrane protein peptidylglycine α-amidating monooxygenase (PAM). PAM has been highly conserved and is found throughout the metazoa; PAM-like sequences are also present in choanoflagellates, filastereans, unicellular and colonial chlorophyte green algae, dinoflagellates and haptophytes. Recent studies have revealed that in addition to playing a key role in peptidergic signaling, PAM also regulates ciliogenesis in vertebrates, ...
Source: Cellular and Molecular Life Sciences : CMLS - March 16, 2019 Category: Cytology Authors: Kumar D, Mains RE, Eipper BA, King SM Tags: Cell Mol Life Sci Source Type: research

Proteins with calmodulin-like domains: structures and functional roles.
erchtold MW Abstract The appearance of modular proteins is a widespread phenomenon during the evolution of proteins. The combinatorial arrangement of different functional and/or structural domains within a single polypeptide chain yields a wide variety of activities and regulatory properties to the modular proteins. In this review, we will discuss proteins, that in addition to their catalytic, transport, structure, localization or adaptor functions, also have segments resembling the helix-loop-helix EF-hand motifs found in Ca2+-binding proteins, such as calmodulin (CaM). These segments are denoted CaM-like domains...
Source: Cellular and Molecular Life Sciences : CMLS - March 15, 2019 Category: Cytology Authors: Villalobo A, González-Muñoz M, Berchtold MW Tags: Cell Mol Life Sci Source Type: research

Cancer targeting peptides.
Abstract Despite continuing advances in the development of biomacromolecules for therapeutic purposes, successful application of these often large and hydrophilic molecules has been hindered by their inability to efficiently traverse the cellular plasma membrane. In recent years, cell-penetrating peptides (CPPs) have received considerable attention as a promising class of delivery vectors due to their ability to mediate the efficient import of a large number of cargoes in vitro and in vivo. However, the lack of target specificity of CPPs remains a major obstacle to their clinical development. To address this issue...
Source: Cellular and Molecular Life Sciences : CMLS - March 15, 2019 Category: Cytology Authors: Kalmouni M, Al-Hosani S, Magzoub M Tags: Cell Mol Life Sci Source Type: research

To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling.
Abstract Accumulating evidence has reached the consensus that the balance of phosphorylation state of signaling molecules is a pivotal point in the regulation of cell signaling. Therefore, characterizing elements (kinases-phosphatases) in the phosphorylation balance are at great importance. However, the role of phosphatase enzymes is less investigated than kinase enzymes. PP2A is a member of serine/threonine protein phosphatase that its imbalance has been reported in neurodegenerative diseases. Therefore, we reviewed the superfamily of phosphatases and more specifically PP2A, its regulation, and physiological func...
Source: Cellular and Molecular Life Sciences : CMLS - March 14, 2019 Category: Cytology Authors: Javadpour P, Dargahi L, Ahmadiani A, Ghasemi R Tags: Cell Mol Life Sci Source Type: research

Neutrophil pyroptosis: new perspectives on sepsis.
Abstract Pyroptosis is a caspase-1 or caspase-4/5/11-dependent programmed cell death associated with inflammation, which is initiated by inflammasomes or cytosolic LPS in innate immunity. Sepsis is a life-threatening organ dysfunction caused by an imbalance in the body's response to infection. It is a complex interaction between the pathogen and the host's immune system. Neutrophils play the role of a double-edged sword in sepsis, and a number of studies have previously shown that regulation of neutrophils is the most crucial part of sepsis treatment. Pyroptosis is one of the important forms for neutrophils to fun...
Source: Cellular and Molecular Life Sciences : CMLS - March 14, 2019 Category: Cytology Authors: Liu L, Sun B Tags: Cell Mol Life Sci Source Type: research

Phosphorylated and aggregated TDP-43 with seeding properties are induced upon mutant Huntingtin (mHtt) polyglutamine expression in human cellular models.
Abstract The Tar DNA-Binding Protein 43 (TDP-43) and its phosphorylated isoform (pTDP-43) are the major components associated with ubiquitin positive/Tau-negative inclusions found in neurons and glial cells of patients suffering of amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration-TDP-43 (FTLD-TDP). Many studies have revealed that TDP-43 is also in the protein inclusions associated with neurodegenerative conditions other than ALS and FTLD-TDP, thus suggesting that this protein may be involved in the pathogenesis of a variety of neurological disorders. In brains of Huntington-affected patient...
Source: Cellular and Molecular Life Sciences : CMLS - March 12, 2019 Category: Cytology Authors: Coudert L, Nonaka T, Bernard E, Hasegawa M, Schaeffer L, Leblanc P Tags: Cell Mol Life Sci Source Type: research

Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans.
Abstract Mitochondria are essential components of eukaryotic cells, carrying out critical physiological processes that include energy production and calcium buffering. Consequently, mitochondrial dysfunction is associated with a range of human diseases. Fundamental to their function is the ability to transition through fission and fusion states, which is regulated by several GTPases. Here, we have developed new methods for the non-subjective quantification of mitochondrial morphology in muscle and neuronal cells of Caenorhabditis elegans. Using these techniques, we uncover surprising tissue-specific differences in...
Source: Cellular and Molecular Life Sciences : CMLS - March 6, 2019 Category: Cytology Authors: Byrne JJ, Soh MS, Chandhok G, Vijayaraghavan T, Teoh JS, Crawford S, Cobham AE, Yapa NMB, Mirth CK, Neumann B Tags: Cell Mol Life Sci Source Type: research

From neural crest cells to melanocytes: cellular plasticity during development and beyond.
Abstract Here, we review melanocyte development and how the embryonic melanoblast, although specified to become a melanocyte, is prone to cellular plasticity and is not fully committed to the melanocyte lineage. Even fully differentiated and pigment-producing melanocytes do not always have a stable phenotype. The gradual lineage restriction of neural crest cells toward the melanocyte lineage is determined by both cell-intrinsic and extracellular signals in which differentiation and pathfinding ability reciprocally influence each other. These signals are leveraged by subtle differences in timing and axial positioni...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2019 Category: Cytology Authors: Vandamme N, Berx G Tags: Cell Mol Life Sci Source Type: research

Rab18: new insights into the function of an essential protein.
Abstract Rab18 is one of the small number of conserved Rab proteins which have been traced to the last eukaryotic common ancestor. It is found in organisms ranging from humans to trypanosomes, and localizes to multiple organelles, including most notably endoplasmic reticulum and lipid droplets. In humans, absence of Rab18 leads to a severe illness known as Warburg-Micro syndrome. Despite this evidence that Rab18 is essential, its role in cells remains mysterious. However, recent studies identifying effectors and interactors of Rab18, are now shedding light on its mechanism of action, suggesting functions related t...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2019 Category: Cytology Authors: Dejgaard SY, Presley JF Tags: Cell Mol Life Sci Source Type: research

Rab6 regulates cell migration and invasion by recruiting Cdc42 and modulating its activity.
Abstract Rab proteins are master regulators of intracellular membrane trafficking, but they also contribute to cell division, signaling, polarization, and migration. The majority of the works describing the mechanisms used by Rab proteins to regulate cell motility involve intracellular transport of key molecules important for migration. Interestingly, a few studies indicate that Rabs can modulate the activity of Rho GTPases, important regulators for the cytoskeleton rearrangements, but the mechanisms behind this crosstalk are still poorly understood. In this work, we identify Rab6 as a negative regulator of cell m...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2019 Category: Cytology Authors: Vestre K, Kjos I, Guadagno NA, Borg Distefano M, Kohler F, Fenaroli F, Bakke O, Progida C Tags: Cell Mol Life Sci Source Type: research

Enhanced cerebral branched-chain amino acid metabolism in R6/2 mouse model of Huntington's disease.
petersen HS Abstract Huntington's disease (HD) is a hereditary and fatal disease causing profound neurodegeneration. Deficits in cerebral energy and neurotransmitter metabolism have been suggested to play a central role in the neuronal dysfunction and death associated with HD. The branched-chain amino acids (BCAAs), leucine, isoleucine and valine, are important for cerebral nitrogen homeostasis, neurotransmitter recycling and can be utilized as energy substrates in the tricarboxylic acid (TCA) cycle. Reduced levels of BCAAs in HD have been validated by several reports. However, it is still unknown how cerebral BCA...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2019 Category: Cytology Authors: Andersen JV, Skotte NH, Aldana BI, Nørremølle A, Waagepetersen HS Tags: Cell Mol Life Sci Source Type: research

Abnormalities in chemokine receptor recycling in chronic lymphocytic leukemia.
Abstract In addition to their modulation through de novo expression and degradation, surface levels of chemokine receptors are tuned by their ligand-dependent recycling to the plasma membrane, which ensures that engaged receptors become rapidly available for further rounds of signaling. Dysregulation of this process contributes to the pathogenesis of chronic lymphocytic leukemia (CLL) by enhancing surface expression of chemokine receptors, thereby favoring leukemic cell accumulation in the protective niche of lymphoid organs. In this review, we summarize our current understanding of the process of chemokine recept...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2019 Category: Cytology Authors: Patrussi L, Capitani N, Baldari CT Tags: Cell Mol Life Sci Source Type: research

LRSAM1 E3 ubiquitin ligase: molecular neurobiological perspectives linked with brain diseases.
Abstract Cellular protein quality control (PQC) plays a significant role in the maintenance of cellular homeostasis. Failure of PQC mechanism may lead to various neurodegenerative diseases due to accumulation of aberrant proteins. To avoid such fatal neuronal conditions PQC employs autophagy and ubiquitin proteasome system (UPS) to degrade misfolded proteins. Few quality control (QC) E3 ubiquitin ligases interplay an important role to specifically recognize misfolded proteins for their intracellular degradation. Leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1) is a really interesting new gene (RIN...
Source: Cellular and Molecular Life Sciences : CMLS - March 2, 2019 Category: Cytology Authors: Mishra R, Upadhyay A, Prajapati VK, Dhiman R, Poluri KM, Jana NR, Mishra A Tags: Cell Mol Life Sci Source Type: research

Anti-inflammatory cytokines in endometriosis.
Abstract Although the pathogenesis of endometriosis is not fully understood, it is often considered to be an inflammatory disease. An increasing number of studies suggest that differential expression of anti-inflammatory cytokines (e.g., interleukin-4 and -10, and transforming growth factor-β1) occurs in women with endometriosis, including in serum, peritoneal fluid and ectopic lesions. These anti-inflammatory cytokines also have indispensable roles in the progression of endometriosis, including by promoting survival, growth, invasion, differentiation, angiogenesis, and immune escape of the endometriotic...
Source: Cellular and Molecular Life Sciences : CMLS - March 2, 2019 Category: Cytology Authors: Zhou WJ, Yang HL, Shao J, Mei J, Chang KK, Zhu R, Li MQ Tags: Cell Mol Life Sci Source Type: research

Establishment and depletion of the ovarian reserve: physiology and impact of environmental chemicals.
In conclusion, evidences exist that exposure to RTECs can compromise a woman's reproductive health. However, human exposures may date back to the developmental stage, while the adverse effects are usually diagnosed decades later, thus making it difficult to determine the association between RTECs exposure and human reproductive health. Therefore, epidemiological surveys and more experimental investigation on humans, or alternatively primates, are needed to determine the direct and indirect effects caused by RTECs exposure on the ovary function, and to characterize their action mechanisms. PMID: 30810760 [PubMed - as s...
Source: Cellular and Molecular Life Sciences : CMLS - February 27, 2019 Category: Cytology Authors: Ge W, Li L, Dyce PW, De Felici M, Shen W Tags: Cell Mol Life Sci Source Type: research

Comprehensive analysis of circular RNAs in pathological states: biogenesis, cellular regulation, and therapeutic relevance.
Abstract Circular RNAs (circRNAs) are members of the non-coding transcriptome; however, some of them are translated into proteins. These transcripts have important roles in both physiological and pathological mechanisms due to their ability to directly influence cellular signaling pathways. Specifically, circRNAs are regulators of transcription, translation, protein interaction, and signal transduction. An increased knowledge within their area is observed over the last few years, concomitant with the development of next-generation sequencing techniques. circRNAs are mostly tissue and disease specific with the abil...
Source: Cellular and Molecular Life Sciences : CMLS - February 25, 2019 Category: Cytology Authors: Braicu C, Zimta AA, Gulei D, Olariu A, Berindan-Neagoe I Tags: Cell Mol Life Sci Source Type: research

Expression and purification of recombinant extracellular sulfatase HSulf-2 allows deciphering of enzyme sub-domain coordinated role for the binding and 6-O-desulfation of heparan sulfate.
In this study, we unlock this critical bottleneck, by reporting an efficient expression and purification system of recombinant HSulf-2 in mammalian HEK293 cells. This novel source of enzyme enabled us to investigate the way the enzyme domain organization dictates its functional properties. By generating mutants, we confirmed previous studies that HSulf-2 catalytic (CAT) domain was sufficient to elicit arylsulfatase activity and that its hydrophilic (HD) domain was necessary for the enzyme 6-O-endosulfatase activity. However, we demonstrated for the first time that high-affinity binding of HS substrates occurred through the...
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2019 Category: Cytology Authors: Seffouh A, El Masri R, Makshakova O, Gout E, Hassoun ZEO, Andrieu JP, Lortat-Jacob H, Vivès RR Tags: Cell Mol Life Sci Source Type: research

Presynaptic NMDA receptors control nociceptive transmission at the spinal cord level in neuropathic pain.
Abstract Chronic neuropathic pain is a debilitating condition that remains challenging to treat. Glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been used to treat neuropathic pain, but the exact sites of their actions have been unclear until recently. Although conventionally postsynaptic, NMDARs are also expressed presynaptically, particularly at the central terminals of primary sensory neurons, in the spinal dorsal horn. However, presynaptic NMDARs in the spinal cord are normally quiescent and are not actively involved in physiological nociceptive transmission. In this review, we describe the em...
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2019 Category: Cytology Authors: Deng M, Chen SR, Pan HL Tags: Cell Mol Life Sci Source Type: research

RDH1 suppresses adiposity by promoting brown adipose adaptation to fasting and re-feeding.
Abstract RDH1 is one of the several enzymes that catalyze the first of the two reactions to convert retinol into all-trans-retinoic acid (atRA). Here, we show that Rdh1-null mice fed a low-fat diet gain more weight as adiposity (17% males, 13% females) than wild-type mice by 20 weeks old, despite neither consuming more calories nor decreasing activity. Glucose intolerance and insulin resistance develop following increased adiposity. Despite the increase in white fat pads, epididymal white adipose does not express Rdh1, nor does muscle. Brown adipose tissue (BAT) and liver express Rdh1 at relatively high level...
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2019 Category: Cytology Authors: Krois CR, Vuckovic MG, Huang P, Zaversnik C, Liu CS, Gibson CE, Wheeler MR, Obrochta KM, Min JH, Herber CB, Thompson AC, Shah ID, Gordon SP, Hellerstein MK, Napoli JL Tags: Cell Mol Life Sci Source Type: research

Immunosenescence: the potential role of myeloid-derived suppressor cells (MDSC) in age-related immune deficiency.
Abstract The aging process is associated with chronic low-grade inflammation in both humans and rodents, commonly called inflammaging. At the same time, there is a gradual decline in the functional capacity of adaptive and innate immune systems, i.e., immunosenescence, a process not only linked to the aging process, but also encountered in several pathological conditions involving chronic inflammation. The hallmarks of immunosenescence include a decline in the numbers of naïve CD4+ and CD8+ T cells, an imbalance in the T cell subsets, and a decrease in T cell receptor (TCR) repertoire and signaling. Correspon...
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2019 Category: Cytology Authors: Salminen A, Kaarniranta K, Kauppinen A Tags: Cell Mol Life Sci Source Type: research

Helicobacter pylori infection and gastric cancer biology: tempering a double-edged sword.
Abstract Helicobacter pylori (H. pylori) infection affects an estimated 4.4 billion people globally. Moreover, H. pylori presents the most significant risk factor for gastric cancer and low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, and it is the first example of bacterial infection linked to carcinogenesis. Here, we contend that H. pylori research, which focuses on a cancer-causing pathogen resident in a relatively accessible organ, the stomach, could constitute an exemplar for microbial-related carcinogenesis in less tractable organs, such as the pancreas and lung. In this context, molecular biolog...
Source: Cellular and Molecular Life Sciences : CMLS - February 19, 2019 Category: Cytology Authors: Mentis AA, Boziki M, Grigoriadis N, Papavassiliou AG Tags: Cell Mol Life Sci Source Type: research

Protein S-nitrosylation in programmed cell death in plants.
Abstract Programmed cell death (PCD) is associated with different phases of plant life and provides resistance to different kinds of biotic or abiotic stress. The redox molecule nitric oxide (NO) is usually produced during the stress response and exerts dual effects on PCD regulation. S-nitrosylation, which NO attaches to the cysteine thiol of proteins, is a vital posttranslational modification and is considered as an essential way for NO to regulate cellular redox signaling. In recent years, a great number of proteins have been identified as targets of S-nitrosylation in plants, especially during PCD. S-nitrosyla...
Source: Cellular and Molecular Life Sciences : CMLS - February 19, 2019 Category: Cytology Authors: Huang D, Huo J, Zhang J, Wang C, Wang B, Fang H, Liao W Tags: Cell Mol Life Sci Source Type: research

Integrin-independent support of cancer drug resistance by tetraspanin CD151.
Abstract Tetraspanin protein CD151 has typically been studied as binding partner and functional regulator of laminin-binding integrins. However, we show here that CD151 supports anti-cancer drug resistance independent of integrins. CD151 ablation sensitized multiple tumor cell types to several anti-cancer drugs (e.g., gefitinib and camptothecin), thus increasing apoptosis, as seen using cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), annexin V, and propidium iodide staining assays. Drug sensitization due to CD151 ablation is integrin-independent, because, (1) effects occurred in cells when integrin...
Source: Cellular and Molecular Life Sciences : CMLS - February 18, 2019 Category: Cytology Authors: Hwang S, Takimoto T, Hemler ME Tags: Cell Mol Life Sci Source Type: research

Targeting angiogenesis in Duchenne muscular dystrophy.
Abstract Duchenne muscular dystrophy (DMD) represents one of the most devastating types of muscular dystrophies which affect boys already at early childhood. Despite the fact that the primary cause of the disease, namely the lack of functional dystrophin is known already for more than 30 years, DMD still remains an incurable disease. Thus, an enormous effort has been made during recent years to reveal novel mechanisms that could provide therapeutic targets for DMD, especially because glucocorticoids treatment acts mostly symptomatic and exerts many side effects, whereas the effectiveness of genetic approaches...
Source: Cellular and Molecular Life Sciences : CMLS - February 15, 2019 Category: Cytology Authors: Podkalicka P, Mucha O, Dulak J, Loboda A Tags: Cell Mol Life Sci Source Type: research

Cerebrospinal fluid biomarkers for understanding multiple aspects of Alzheimer's disease pathogenesis.
Abstract Alzheimer's disease (AD) is a multifactorial age-related brain disease. Numerous pathological events run forth in the brain leading to AD. There is an initial long, dormant phase before the clinical symptoms become evident. There is a need to diagnose the disease at the preclinical stage since therapeutic interventions are most likely to be effective if initiated early. Undoubtedly, the core cerebrospinal fluid (CSF) biomarkers have a good diagnostic accuracy and have been used in clinical trials as end point measures. However, looking into the multifactorial nature of AD and the overlapping pathology wit...
Source: Cellular and Molecular Life Sciences : CMLS - February 15, 2019 Category: Cytology Authors: Dhiman K, Blennow K, Zetterberg H, Martins RN, Gupta VB Tags: Cell Mol Life Sci Source Type: research

Functional high-throughput screening reveals miR-323a-5p and miR-342-5p as new tumor-suppressive microRNA for neuroblastoma.
A, Gallego S, Segura MF Abstract Current therapies for most non-infectious diseases are directed at or affect functionality of the human translated genome, barely 2% of all genetic information. By contrast, the therapeutic potential of targeting the transcriptome, ~ 70% of the genome, remains largely unexplored. RNA therapeutics is an emerging field that widens the range of druggable targets and includes elements such as microRNA. Here, we sought to screen for microRNA with tumor-suppressive functions in neuroblastoma, an aggressive pediatric tumor of the sympathetic nervous system that requires the developme...
Source: Cellular and Molecular Life Sciences : CMLS - February 15, 2019 Category: Cytology Authors: Soriano A, Masanas M, Boloix A, Masiá N, París-Coderch L, Piskareva O, Jiménez C, Henrich KO, Roma J, Westermann F, Stallings RL, Sábado C, de Toledo JS, Santamaria A, Gallego S, Segura MF Tags: Cell Mol Life Sci Source Type: research

Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria.
Abstract Oxygen is required for the survival of the majority of eukaryotic organisms, as it is important for many cellular processes. Eukaryotic cells utilize oxygen for the production of biochemical energy in the form of adenosine triphosphate (ATP) generated from the catabolism of carbon-rich fuels such as glucose, lipids and glutamine. The intracellular sites of oxygen consumption-coupled ATP production are the mitochondria, double-membraned organelles that provide a dynamic and multifaceted role in cell signalling and metabolism. Highly evolutionarily conserved molecular mechanisms exist to sense and respond t...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2019 Category: Cytology Authors: Thomas LW, Ashcroft M Tags: Cell Mol Life Sci Source Type: research

Nuclear pore protein TPR associates with lamin B1 and affects nuclear lamina organization and nuclear pore distribution.
nberková M, Čapek M, Fišer K, Hozák P Abstract The organization of the nuclear periphery is crucial for many nuclear functions. Nuclear lamins form dense network at the nuclear periphery and play a substantial role in chromatin organization, transcription regulation and in organization of nuclear pore complexes (NPCs). Here, we show that TPR, the protein located preferentially within the nuclear baskets of NPCs, associates with lamin B1. The depletion of TPR affects the organization of lamin B1 but not lamin A/C within the nuclear lamina as shown by stimulated emission depletion microscopy. F...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2019 Category: Cytology Authors: Fišerová J, Maninová M, Sieger T, Uhlířová J, Šebestová L, Efenberková M, Čapek M, Fišer K, Hozák P Tags: Cell Mol Life Sci Source Type: research

Contribution of the eighth transmembrane segment to the function of the CFTR chloride channel pore.
Abstract Our molecular understanding of the cystic fibrosis transmembrane conductance regulator (CFTR)-the chloride channel that is mutated in cystic fibrosis-has been greatly enhanced by a number of recent atomic-level structures of the protein in different conformations. One surprising aspect of these structures was the finding that the eighth of CFTR's 12 membrane-spanning segments (TM8) appeared close to the channel pore. Although functional evidence supports a role for other TMs in forming the pore, such a role for TM8 has not previously been reported. Here, we use patch-clamp recording to investigate the fun...
Source: Cellular and Molecular Life Sciences : CMLS - February 13, 2019 Category: Cytology Authors: Negoda A, Hogan MS, Cowley EA, Linsdell P Tags: Cell Mol Life Sci Source Type: research

Establishment and maintenance of blood-lymph separation.
Abstract Hippocratic Corpus, a collection of Greek medical literature, described the functional anatomy of the lymphatic system in the fifth century B.C. Subsequent studies in cadavers and surgical patients firmly established that lymphatic vessels drain extravasated interstitial fluid, also known as lymph, into the venous system at the bilateral lymphovenous junctions. Recent advances revealed that lymphovenous valves and platelet-mediated hemostasis at the lymphovenous junctions maintain life-long separation of the blood and lymphatic vascular systems. Here, we review murine models that exhibit failure of blood-...
Source: Cellular and Molecular Life Sciences : CMLS - February 13, 2019 Category: Cytology Authors: Janardhan HP, Trivedi CM Tags: Cell Mol Life Sci Source Type: research

Tumor-associated macrophages: a short compendium.
Abstract Macrophages play an important role in tissue development and homeostasis. They serve as a nexus between adaptive and innate immunity, and employ considerable plasticity. In cancer, they play a pivotal role in chronic inflammation and tumor growth either by directly stimulating the proliferation of cancer cells or by producing angiogenic and lymphangiogenic factors. Although numerous immune cells play an important role in the tumor microenvironment, tumor-associated macrophages (TAMs) are by far the most extensively studied. A better understanding of the role of TAMs in mediating chemo- and radiotherapy re...
Source: Cellular and Molecular Life Sciences : CMLS - February 12, 2019 Category: Cytology Authors: Prenen H, Mazzone M Tags: Cell Mol Life Sci Source Type: research

The structure and function of Iristatin, a novel immunosuppressive tick salivary cystatin.
We present the crystal structure of Iristatin at 1.76 Å resolution. Purified recombinant Iristatin inhibited the proteolytic activity of cathepsins L and C and diminished IL-2, IL-4, IL-9, and IFN-γ production by different T-cell populations, IL-6 and IL-9 production by mast cells, and nitric oxide production by macrophages. Furthermore, Iristatin inhibited OVA antigen-induced CD4+ T-cell proliferation and leukocyte recruitment in vivo and in vitro. Our results indicate that Iristatin affects wide range of anti-tick immune responses in the vertebrate host and may be exploitable as an immunotherapeutic. ...
Source: Cellular and Molecular Life Sciences : CMLS - February 12, 2019 Category: Cytology Authors: Kotál J, Stergiou N, Buša M, Chlastáková A, Beránková Z, Řezáčová P, Langhansová H, Schwarz A, Calvo E, Kopecký J, Mareš M, Schmitt E, Chmelař J, Kotsyfakis M Tags: Cell Mol Life Sci Source Type: research

The coming-of-age of nucleocytoplasmic transport in motor neuron disease and neurodegeneration.
Abstract The nuclear pore is the gatekeeper of nucleocytoplasmic transport and signaling through which a vast flux of information is continuously exchanged between the nuclear and cytoplasmic compartments to maintain cellular homeostasis. A unifying and organizing principle has recently emerged that cements the notion that several forms of amyotrophic lateral sclerosis (ALS), and growing number of other neurodegenerative diseases, co-opt the dysregulation of nucleocytoplasmic transport and that this impairment is a pathogenic driver of neurodegeneration. The understanding of shared pathomechanisms that underpin ne...
Source: Cellular and Molecular Life Sciences : CMLS - February 11, 2019 Category: Cytology Authors: Ferreira PA Tags: Cell Mol Life Sci Source Type: research

N-acetylglucosaminyltransferases and nucleotide sugar transporters form multi-enzyme-multi-transporter assemblies in golgi membranes in vivo.
Abstract Branching and processing of N-glycans in the medial-Golgi rely both on the transport of the donor UDP-N-acetylglucosamine (UDP-GlcNAc) to the Golgi lumen by the SLC35A3 nucleotide sugar transporter (NST) as well as on the addition of the GlcNAc residue to terminal mannoses in nascent N-glycans by several linkage-specific N-acetyl-glucosaminyltransferases (MGAT1-MGAT5). Previous data indicate that the MGATs and NSTs both form higher order assemblies in the Golgi membranes. Here, we investigate their specific and mutual interactions using high-throughput FRET- and BiFC-based interaction screens. We show tha...
Source: Cellular and Molecular Life Sciences : CMLS - February 8, 2019 Category: Cytology Authors: Khoder-Agha F, Sosicka P, Escriva Conde M, Hassinen A, Glumoff T, Olczak M, Kellokumpu S Tags: Cell Mol Life Sci Source Type: research

Characterization of functional subgroups among genetically identified cholinergic neurons in the pedunculopontine nucleus.
ml;cs P, Pál B Abstract The pedunculopontine nucleus (PPN) is a part of the reticular activating system which is composed of cholinergic, glutamatergic and GABAergic neurons. Early electrophysiological studies characterized and grouped PPN neurons based on certain functional properties (i.e., the presence or absence of the A-current, spike latency, and low threshold spikes). Although other electrophysiological characteristics of these neurons were also described (as high threshold membrane potential oscillations, great differences in spontaneous firing rate and the presence or absence of the M-current), sys...
Source: Cellular and Molecular Life Sciences : CMLS - February 8, 2019 Category: Cytology Authors: Baksa B, Kovács A, Bayasgalan T, Szentesi P, Kőszeghy Á, Szücs P, Pál B Tags: Cell Mol Life Sci Source Type: research

Exosomes: from carcinogenesis and metastasis to diagnosis and treatment of gastric cancer.
Abstract Exosomes represent an important group of extracellular vesicles with a defined size between 40 and 150 nm and cup-shaped construction which have a pivotal role in elimination of intracellular debris and intercellular signaling networks. A line of evidence revealed the impact of different types of exosomes in initiation, progression, and metastasis of gastric cancer (GC). These bioactive vesicles mediate tumor and stromal communication network through modulation of cell signaling for carcinogenesis and pre-metastatic niche formation in distant organs. Exosomes contain various cargos including DNAs (mi...
Source: Cellular and Molecular Life Sciences : CMLS - February 8, 2019 Category: Cytology Authors: Kahroba H, Hejazi MS, Samadi N Tags: Cell Mol Life Sci Source Type: research

Alternative polyadenylation coordinates embryonic development, sexual dimorphism and longitudinal growth in Xenopus tropicalis.
Abstract RNA alternative polyadenylation contributes to the complexity of information transfer from genome to phenome, thus amplifying gene function. Here, we report the first X. tropicalis resource with 127,914 alternative polyadenylation (APA) sites derived from embryos and adults. Overall, APA networks play central roles in coordinating the maternal-zygotic transition (MZT) in embryos, sexual dimorphism in adults and longitudinal growth from embryos to adults. APA sites coordinate reprogramming in embryos before the MZT, but developmental events after the MZT due to zygotic genome activation. The APA transcript...
Source: Cellular and Molecular Life Sciences : CMLS - February 7, 2019 Category: Cytology Authors: Zhou X, Zhang Y, Michal JJ, Qu L, Zhang S, Wildung MR, Du W, Pouchnik DJ, Zhao H, Xia Y, Shi H, Ji G, Davis JF, Smith GD, Griswold MD, Harland RM, Jiang Z Tags: Cell Mol Life Sci Source Type: research

Tight junction proteins at the blood-brain barrier: far more than claudin-5.
In conclusion, this complete Cldn/TAMP profile demonstrates the presence of up to a dozen TJ proteins in brain capillaries. Mouse and human share a similar and complex TJ profile in vivo, but this complexity is widely lost under in vitro conditions. PMID: 30734065 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - February 7, 2019 Category: Cytology Authors: Berndt P, Winkler L, Cording J, Breitkreuz-Korff O, Rex A, Dithmer S, Rausch V, Blasig R, Richter M, Sporbert A, Wolburg H, Blasig IE, Haseloff RF Tags: Cell Mol Life Sci Source Type: research

IGFBP-3 interacts with NONO and SFPQ in PARP-dependent DNA damage repair in triple-negative breast cancer.
Abstract Women with triple-negative breast cancer (TNBC) are generally treated by chemotherapy but their responsiveness may be blunted by DNA double-strand break (DSB) repair. We previously reported that IGFBP-3 forms nuclear complexes with EGFR and DNA-dependent protein kinase (DNA-PKcs) to modulate DSB repair by non-homologous end-joining (NHEJ) in TNBC cells. To discover IGFBP-3 binding partners involved in chemoresistance through stimulation of DSB repair, we analyzed the IGFBP-3 interactome by LC-MS/MS and confirmed interactions by coimmunoprecipitation and proximity ligation assay. Functional effects were de...
Source: Cellular and Molecular Life Sciences : CMLS - February 6, 2019 Category: Cytology Authors: de Silva HC, Lin MZ, Phillips L, Martin JL, Baxter RC Tags: Cell Mol Life Sci Source Type: research

Therapeutic potential of menstrual blood-derived endometrial stem cells in cardiac diseases.
Abstract Despite significant developments in medical and surgical strategies, cardiac diseases remain the leading causes of morbidity and mortality worldwide. Numerous studies involving preclinical and clinical trials have confirmed that stem cell transplantation can help improve cardiac function and regenerate damaged cardiac tissue, and stem cells isolated from bone marrow, heart tissue, adipose tissue and umbilical cord are the primary candidates for transplantation. During the past decade, menstrual blood-derived endometrial stem cells (MenSCs) have gradually become a promising alternative for stem cell-based ...
Source: Cellular and Molecular Life Sciences : CMLS - February 5, 2019 Category: Cytology Authors: Liu Y, Niu R, Li W, Lin J, Stamm C, Steinhoff G, Ma N Tags: Cell Mol Life Sci Source Type: research

Role of bone marrow adipocytes in leukemia and chemotherapy challenges.
Abstract Adipose tissue (AT) is an extramedullary reservoir of normal hematopoietic stem cells (HSCs). Adipocytes prevent the production of normal HSCs via secretion of inflammatory factors, and adipocyte-derived free fatty acids may contribute to the development and progression of leukemia via providing energy for leukemic cells. In addition, adipocytes are able to metabolize and inactivate therapeutic agents, reducing the concentrations of active drugs in adipocyte-rich microenvironments. The aim of this study was to detect the role of adipocytes in the progression and treatment of leukemia. Relevant literature ...
Source: Cellular and Molecular Life Sciences : CMLS - February 4, 2019 Category: Cytology Authors: Samimi A, Ghanavat M, Shahrabi S, Azizidoost S, Saki N Tags: Cell Mol Life Sci Source Type: research

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