TP63 links chromatin remodeling and enhancer reprogramming to epidermal differentiation and squamous cell carcinoma development.
Abstract Squamous cell carcinoma (SCC) is an aggressive malignancy that can originate from various organs. TP63 is a master regulator that plays an essential role in epidermal differentiation. It is also a lineage-dependent oncogene in SCC. ΔNp63α is the prominent isoform of TP63 expressed in epidermal cells and SCC, and overexpression promotes SCC development through a variety of mechanisms. Recently, ΔNp63α was highlighted to act as an epidermal-specific pioneer factor that binds closed chromatin and enhances chromatin accessibility at epidermal enhancers. ΔNp63α coordinates c...
Source: Cellular and Molecular Life Sciences : CMLS - May 23, 2020 Category: Cytology Authors: Yi M, Tan Y, Wang L, Cai J, Li X, Zeng Z, Xiong W, Li G, Li X, Tan P, Xiang B Tags: Cell Mol Life Sci Source Type: research

Studies of ApoD-/- and ApoD-/-ApoE-/- mice uncover the APOD significance for retinal metabolism, function, and status of chorioretinal blood vessels.
Abstract Apolipoprotein D (APOD) is an atypical apolipoprotein with unknown significance for retinal structure and function. Conversely, apolipoprotein E (APOE) is a typical apolipoprotein with established roles in retinal cholesterol transport. Herein, we immunolocalized APOD to the photoreceptor inner segments and conducted ophthalmic characterizations of ApoD-/- and ApoD-/-ApoE-/- mice. ApoD-/- mice had normal levels of retinal sterols but changes in the chorioretinal blood vessels and impaired retinal function. The whole-body glucose disposal was impaired in this genotype but the retinal glucose metabolism was...
Source: Cellular and Molecular Life Sciences : CMLS - May 21, 2020 Category: Cytology Authors: El-Darzi N, Mast N, Petrov AM, Dao T, Astafev AA, Saadane A, Prendergast E, Schwarz E, Bederman I, Pikuleva IA Tags: Cell Mol Life Sci Source Type: research

TGF- β1 promotes epithelial-to-mesenchymal transition and stemness of prostate cancer cells by inducing PCBP1 degradation and alternative splicing of CD44.
TGF-β1 promotes epithelial-to-mesenchymal transition and stemness of prostate cancer cells by inducing PCBP1 degradation and alternative splicing of CD44. Cell Mol Life Sci. 2020 May 21;: Authors: Chen Q, Gu M, Cai ZK, Zhao H, Sun SC, Liu C, Zhan M, Chen YB, Wang Z Abstract CD44 is a marker of cancer stem cell (CSC) in many types of tumors. Alternative splicing of its 20 exons generates various CD44 isoforms that have different tissue specific expression and functions, including the CD44 standard isoform (CD44s) encoded by the constant exons and the CD44 variant isoforms (CD44v) with variant exon...
Source: Cellular and Molecular Life Sciences : CMLS - May 21, 2020 Category: Cytology Authors: Chen Q, Gu M, Cai ZK, Zhao H, Sun SC, Liu C, Zhan M, Chen YB, Wang Z Tags: Cell Mol Life Sci Source Type: research

Functional circuits and signal processing in the enteric nervous system.
Abstract The enteric nervous system (ENS) is an extensive network comprising millions of neurons and glial cells contained within the wall of the gastrointestinal tract. The major functions of the ENS that have been most studied include the regulation of local gut motility, secretion, and blood flow. Other areas that have been gaining increased attention include its interaction with the immune system, with the gut microbiota and its involvement in the gut-brain axis, and neuro-epithelial interactions. Thus, the enteric circuitry plays a central role in intestinal homeostasis, and this becomes particularly evident ...
Source: Cellular and Molecular Life Sciences : CMLS - May 18, 2020 Category: Cytology Authors: Fung C, Vanden Berghe P Tags: Cell Mol Life Sci Source Type: research

miRNA regulation of social and anxiety-related behaviour.
Abstract Neuropsychiatric disorders, including autism spectrum disorders (ASD) and anxiety disorders are characterized by a complex range of symptoms, including social behaviour and cognitive deficits, depression and repetitive behaviours. Although the mechanisms driving pathophysiology are complex and remain largely unknown, advances in the understanding of gene association and gene networks are providing significant clues to their aetiology. In recent years, small noncoding RNA molecules known as microRNA (miRNA) have emerged as a new gene regulatory layer in the pathophysiology of mental illness. These small RN...
Source: Cellular and Molecular Life Sciences : CMLS - May 14, 2020 Category: Cytology Authors: Narayanan R, Schratt G Tags: Cell Mol Life Sci Source Type: research

Staphylococcus aureus impairs cutaneous wound healing by activating the expression of a gap junction protein, connexin-43 in keratinocytes.
Abstract Chronic wounds have been considered as major medical problems that may result in expensive healthcare. One of the common causes of chronic wounds is bacterial contamination that leads to persistent inflammation and unbalanced host cell immune responses. Among the bacterial strains that have been identified from chronic wounds, Staphylococcus aureus is the most common strain. We previously observed that S. aureus impaired mouse cutaneous wound healing by delaying re-epithelialization. Here, we investigated the mechanism of delayed re-epithelialization caused by S. aureus infection. With the presence of S. ...
Source: Cellular and Molecular Life Sciences : CMLS - May 14, 2020 Category: Cytology Authors: Xu W, Dielubanza E, Maisel A, Leung K, Mustoe T, Hong S, Galiano R Tags: Cell Mol Life Sci Source Type: research

TET3 controls the expression of the H3K27me3 demethylase Kdm6b during neural commitment.
F, Arnaud P Abstract The acquisition of cell identity is associated with developmentally regulated changes in the cellular histone methylation signatures. For instance, commitment to neural differentiation relies on the tightly controlled gain or loss of H3K27me3, a hallmark of polycomb-mediated transcriptional gene silencing, at specific gene sets. The KDM6B demethylase, which removes H3K27me3 marks at defined promoters and enhancers, is a key factor in neurogenesis. Therefore, to better understand the epigenetic regulation of neural fate acquisition, it is important to determine how Kdm6b expression is regulated...
Source: Cellular and Molecular Life Sciences : CMLS - May 14, 2020 Category: Cytology Authors: Montibus B, Cercy J, Bouschet T, Charras A, Maupetit-Méhouas S, Nury D, Gonthier-Guéret C, Chauveau S, Allegre N, Chariau C, Hong CC, Vaillant I, Marques CJ, Court F, Arnaud P Tags: Cell Mol Life Sci Source Type: research

Correction to: CX3CR1 positively regulates BCR signaling coupled with cell metabolism via negatively controlling actin remodeling.
Abstract In the original published version of the article, the red squares in the figures which indicated the corrections. PMID: 32405720 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - May 13, 2020 Category: Cytology Authors: Li N, Jiang P, Chen A, Luo X, Jing Y, Yang L, Kang D, Chen Q, Liu J, Chang J, Jellusova J, Miller H, Westerberg L, Wang CY, Gong Q, Liu C Tags: Cell Mol Life Sci Source Type: research

Yolk sac hematopoiesis: does it contribute to the adult hematopoietic system?
Abstract In most vertebrates, the yolk sac (YS) represents the very first tissue where blood cells are detected. Therefore, it was thought for a long time that it generated all the blood cells present in the embryo. This model was challenged using different animal models, and we now know that YS hematopoietic precursors are mostly transient although their contribution to the adult system cannot be excluded. In this review, we aim at properly define the different waves of blood progenitors that are produced by the YS and address the fate of each of them. Indeed, in the last decade, many evidences have emphasized th...
Source: Cellular and Molecular Life Sciences : CMLS - May 13, 2020 Category: Cytology Authors: Wittamer V, Bertrand JY Tags: Cell Mol Life Sci Source Type: research

The role of essential fatty acids in cystic fibrosis and normalizing effect of fenretinide.
Abstract Cystic fibrosis (CF) is the most common autosomal-recessive disease in Caucasians caused by mutations in the CF transmembrane regulator (CFTR) gene. Patients are usually diagnosed in infancy and are burdened with extensive medical treatments throughout their lives. One of the first documented biochemical defects in CF, which predates the cloning of CFTR gene for almost three decades, is an imbalance in the levels of polyunsaturated fatty acids (PUFAs). The principal hallmarks of this imbalance are increased levels of arachidonic acid and decreased levels of docosahexaenoic acids (DHA) in CF. This pro-infl...
Source: Cellular and Molecular Life Sciences : CMLS - May 11, 2020 Category: Cytology Authors: Garić D, Dumut DC, Shah J, De Sanctis JB, Radzioch D Tags: Cell Mol Life Sci Source Type: research

The secreted inhibitor of invasive cell growth CREG1 is negatively regulated by cathepsin proteases.
l T Abstract Previous clinical and experimental evidence strongly supports a breast cancer-promoting function of the lysosomal protease cathepsin B. However, the cathepsin B-dependent molecular pathways are not completely understood. Here, we studied the cathepsin-mediated secretome changes in the context of the MMTV-PyMT breast cancer mouse model. Employing the cell-conditioned media from tumor-macrophage co-cultures, as well as tumor interstitial fluid obtained by a novel strategy from PyMT mice with differential cathepsin B expression, we identified an important proteolytic and lysosomal signature, highlighting...
Source: Cellular and Molecular Life Sciences : CMLS - May 8, 2020 Category: Cytology Authors: Gomez-Auli A, Hillebrand LE, Christen D, Günther SC, Biniossek ML, Peters C, Schilling O, Reinheckel T Tags: Cell Mol Life Sci Source Type: research

The metalloproteinase ADAM10 requires its activity to sustain surface expression.
udwig A Abstract The metalloproteinase ADAM10 critically contributes to development, inflammation, and cancer and can be controlled by endogenous or synthetic inhibitors. Here, we demonstrate for the first time that loss of proteolytic activity of ADAM10 by either inhibition or loss of function mutations induces removal of the protease from the cell surface and the whole cell. This process is temperature dependent, restricted to mature ADAM10, and associated with an increased internalization, lysosomal degradation, and release of mature ADAM10 in extracellular vesicles. Recovery from this depletion requires de nov...
Source: Cellular and Molecular Life Sciences : CMLS - May 5, 2020 Category: Cytology Authors: Seifert A, Düsterhöft S, Wozniak J, Koo CZ, Tomlinson MG, Nuti E, Rossello A, Cuffaro D, Yildiz D, Ludwig A Tags: Cell Mol Life Sci Source Type: research

Dissecting the initiation of female meiosis in the mouse at single-cell resolution.
Abstract Meiosis is one of the most finely orchestrated events during gametogenesis with distinct developmental patterns in males and females. However, the molecular mechanisms involved in this process remain not well known. Here, we report detailed transcriptome analyses of cell populations present in the mouse female gonadal ridges (E11.5) and the embryonic ovaries from E12.5 to E14.5 using single-cell RNA sequencing (scRNA seq). These periods correspond with the initiation and progression of meiosis throughout the first stage of prophase I. We identified 13 transcriptionally distinct cell populations and 7 tran...
Source: Cellular and Molecular Life Sciences : CMLS - May 4, 2020 Category: Cytology Authors: Ge W, Wang JJ, Zhang RQ, Tan SJ, Zhang FL, Liu WX, Li L, Sun XF, Cheng SF, Dyce PW, De Felici M, Shen W Tags: Cell Mol Life Sci Source Type: research

Vaccination against the Epstein-Barr virus.
ml;nz C Abstract Epstein-Barr virus (EBV) was the first human tumor virus being discovered and remains to date the only human pathogen that can transform cells in vitro. 55 years of EBV research have now brought us to the brink of an EBV vaccine. For this purpose, recombinant viral vectors and their heterologous prime-boost vaccinations, EBV-derived virus-like particles and viral envelope glycoprotein formulations are explored and are discussed in this review. Even so, cell-mediated immune control by cytotoxic lymphocytes protects healthy virus carriers from EBV-associated malignancies, antibodies might be ab...
Source: Cellular and Molecular Life Sciences : CMLS - May 4, 2020 Category: Cytology Authors: Rühl J, Leung CS, Münz C Tags: Cell Mol Life Sci Source Type: research

Activation of stress response axis as a key process in environment-induced sex plasticity in fish.
rnandino JI Abstract The determination of sex is an important hallmark in the life cycle of organisms, in which the fate of gonads and then the individual sex are defined. In gonochoristic teleost fish, this process is characterized by a high plasticity, considering that in spite of genotypic sex many environmental factors can cause shifts from one to another molecular pathway, resulting in organisms with mismatching genotypic and phenotypic sexes. Interestingly, in most instances, both female-to-male or male-to-female sex-reversed individuals develop functional gonads with normal gametogenesis and respective prog...
Source: Cellular and Molecular Life Sciences : CMLS - May 4, 2020 Category: Cytology Authors: Hattori RS, Castañeda-Cortés DC, Arias Padilla LF, Strobl-Mazzulla PH, Fernandino JI Tags: Cell Mol Life Sci Source Type: research

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations.
Abstract Cystic fibrosis (CF) is one of the most common life-limiting recessive genetic disorders in Caucasians, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CF is a multi-organ disease that involves the lungs, pancreas, sweat glands, digestive and reproductive systems and several other tissues. This debilitating condition is associated with recurrent lower respiratory tract bacterial and viral infections, as well as inflammatory complications that may eventually lead to pulmonary failure. Immune cells play a crucial role in protecting the organs against opportunistic infe...
Source: Cellular and Molecular Life Sciences : CMLS - May 4, 2020 Category: Cytology Authors: Lara-Reyna S, Holbrook J, Jarosz-Griffiths HH, Peckham D, McDermott MF Tags: Cell Mol Life Sci Source Type: research

Akirin proteins in development and disease: critical roles and mechanisms of action.
We describe data supporting the hypothesis that Akirins act as a "bridge" between a variety of transcription factors and major chromatin remodeling complexes, and discuss several important questions remaining to be addressed. In little more than a decade, Akirin proteins have gone from being completely unknown to being increasingly recognized as evolutionarily conserved mediators of gene expression programs essential for the formation and function of animals. PMID: 32361777 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - May 2, 2020 Category: Cytology Authors: Bosch PJ, Peek SL, Smolikove S, Weiner JA Tags: Cell Mol Life Sci Source Type: research

The multifaceted role of reactive oxygen species in tumorigenesis.
Abstract Redox homeostasis is an essential requirement of the biological systems for performing various normal cellular functions including cellular growth, differentiation, senescence, survival and aging in humans. The changes in the basal levels of reactive oxygen species (ROS) are detrimental to cells and often lead to several disease conditions including cardiovascular, neurological, diabetes and cancer. During the last two decades, substantial research has been done which clearly suggests that ROS are essential for the initiation, progression, angiogenesis as well as metastasis of cancer in several ways. Duri...
Source: Cellular and Molecular Life Sciences : CMLS - May 1, 2020 Category: Cytology Authors: Kirtonia A, Sethi G, Garg M Tags: Cell Mol Life Sci Source Type: research

Growth regulation by amino acid transporters in Drosophila larvae.
ean Y Abstract Drosophila larvae need to adapt their metabolism to reach a critical body size to pupate. This process needs food resources and has to be tightly adjusted to control metamorphosis timing and adult size. Nutrients such as amino acids either directly present in the food or obtained via protein digestion play key regulatory roles in controlling metabolism and growth. Amino acids act especially on two organs, the fat body and the brain, to control larval growth, body size developmental timing and pupariation. The expression of specific amino acid transporters in fat body cells, and in the brain through ...
Source: Cellular and Molecular Life Sciences : CMLS - May 1, 2020 Category: Cytology Authors: Manière G, Alves G, Berthelot-Grosjean M, Grosjean Y Tags: Cell Mol Life Sci Source Type: research

What microRNAs could tell us about the human X chromosome.
Abstract MicroRNAs (miRNA) are small-non coding RNAs endowed with great regulatory power, thus playing key roles not only in almost all physiological pathways, but also in the pathogenesis of several diseases. Surprisingly, genomic distribution analysis revealed the highest density of miRNA sequences on the X chromosome; this evolutionary conserved mammalian feature equips females with a larger miRNA machinery than males. However, miRNAs contribution to some X-related conditions, properties or functions is still poorly explored. With the aim to support and focus research in the field, this review analyzes the lite...
Source: Cellular and Molecular Life Sciences : CMLS - April 30, 2020 Category: Cytology Authors: Di Palo A, Siniscalchi C, Salerno M, Russo A, Gravholt CH, Potenza N Tags: Cell Mol Life Sci Source Type: research

Noncoding RNAs in Duchenne and Becker muscular dystrophies: role in pathogenesis and future prognostic and therapeutic perspectives.
Abstract Noncoding RNAs (ncRNAs), such as miRNAs and long noncoding RNAs, are key regulators of gene expression at the post-transcriptional level and represent promising therapeutic targets and biomarkers for several human diseases, including Duchenne and Becker muscular dystrophies (DMD/BMD). A role for ncRNAs in the pathogenesis of muscular dystrophies has been suggested, even if it is still incompletely understood. Here, we discuss current progress leading towards the clinical utility of ncRNAs for DMD/BMD. Long and short noncoding RNAs are differentially expressed in DMD/BMD and have a mechanism of action via ...
Source: Cellular and Molecular Life Sciences : CMLS - April 29, 2020 Category: Cytology Authors: Brusa R, Magri F, Bresolin N, Comi GP, Corti S Tags: Cell Mol Life Sci Source Type: research

Transcriptional regulation of Treg homeostasis and functional specification.
Abstract CD4+Foxp3+ regulatory T (Treg) cells are key players in keeping excessive inflammation in check. Mounting evidence has shown that Treg cells exert much more diverse functions in both immunological and non-immunological processes. The development, maintenance and functional specification of Treg cells are regulated by multilayered factors, including antigens and TCR signaling, cytokines, epigenetic modifiers and transcription factors (TFs). In the review, we will focus on TFs by summarizing their unique and redundant roles in Treg cells under physiological and pathophysiological conditions. We will also di...
Source: Cellular and Molecular Life Sciences : CMLS - April 29, 2020 Category: Cytology Authors: Wang K, Fu W Tags: Cell Mol Life Sci Source Type: research

What turns CREB on? And off? And why does it matter?
Abstract Altered expression and function of the transcription factor cyclic AMP response-binding protein (CREB) has been identified to play an important role in cancer and is associated with the overall survival and therapy response of tumor patients. This review focuses on the expression and activation of CREB under physiologic conditions and in tumors of distinct origin as well as the underlying mechanisms of CREB regulation by diverse stimuli and inhibitors. In addition, the clinical relevance of CREB is summarized, including its use as a prognostic and/or predictive marker as well as a therapeutic target. ...
Source: Cellular and Molecular Life Sciences : CMLS - April 28, 2020 Category: Cytology Authors: Steven A, Friedrich M, Jank P, Heimer N, Budczies J, Denkert C, Seliger B Tags: Cell Mol Life Sci Source Type: research

Fucosidases from the human gut symbiont Ruminococcus gnavus.
Abstract The availability and repartition of fucosylated glycans within the gastrointestinal tract contributes to the adaptation of gut bacteria species to ecological niches. To access this source of nutrients, gut bacteria encode α-L-fucosidases (fucosidases) which catalyze the hydrolysis of terminal α-L-fucosidic linkages. We determined the substrate and linkage specificities of fucosidases from the human gut symbiont Ruminococcus gnavus. Sequence similarity network identified strain-specific fucosidases in R. gnavus ATCC 29149 and E1 strains that were further validated enzymatically against a range ...
Source: Cellular and Molecular Life Sciences : CMLS - April 24, 2020 Category: Cytology Authors: Wu H, Rebello O, Crost EH, Owen CD, Walpole S, Bennati-Granier C, Ndeh D, Monaco S, Hicks T, Colvile A, Urbanowicz PA, Walsh MA, Angulo J, Spencer DIR, Juge N Tags: Cell Mol Life Sci Source Type: research

Circulating tumor cells as Trojan Horse for understanding, preventing, and treating cancer: a critical appraisal.
Abstract Circulating tumor cells (CTCs) are regarded as harbingers of metastases. Their ability to predict response to therapy, relapse, and resistance to treatment has proposed their value as putative diagnostic and prognostic indicators. CTCs represent one of the zeniths of cancer evolution in terms of cell survival; however, the triggers of CTC generation, the identification of potentially metastatic CTCs, and the mechanisms contributing to their heterogeneity and aggressiveness represent issues not yet fully deciphered. Thus, prior to enabling liquid biopsy applications to reach clinical prime time, understand...
Source: Cellular and Molecular Life Sciences : CMLS - April 24, 2020 Category: Cytology Authors: Mentis AA, Grivas PD, Dardiotis E, Romas NA, Papavassiliou AG Tags: Cell Mol Life Sci Source Type: research

Melanoma-associated fibroblasts impair CD8+  T cell function and modify expression of immune checkpoint regulators via increased arginase activity.
This study shows that melanoma-associated fibroblasts (MAFs) suppress cytotoxic T lymphocyte (CTL) activity and reveals a pivotal role played by arginase in this phenomenon. MAFs and normal dermal fibroblasts (DFs) were isolated from surgically resected melanomas and identified as Melan-A-/gp100-/FAP+ cells. CTLs of healthy blood donors were activated in the presence of MAF- and DF-conditioned media (CM). Markers of successful CTL activation, cytotoxic degranulation, killing activity and immune checkpoint regulation were evaluated by flow cytometry, ELISPOT, and redirected killing assays. Soluble mediators responsib...
Source: Cellular and Molecular Life Sciences : CMLS - April 23, 2020 Category: Cytology Authors: Érsek B, Silló P, Cakir U, Molnár V, Bencsik A, Mayer B, Mezey E, Kárpáti S, Pós Z, Németh K Tags: Cell Mol Life Sci Source Type: research

Receptor-mediated endocytosis 8 (RME-8)/DNAJC13 is a novel positive modulator of autophagy and stabilizes cellular protein homeostasis.
Abstract The cellular protein homeostasis (proteostasis) network responds effectively to insults. In a functional screen in C. elegans, we recently identified the gene receptor-mediated endocytosis 8 (rme-8; human ortholog: DNAJC13) as a component of the proteostasis network. Accumulation of aggregation-prone proteins, such as amyloid-β 42 (Aβ), α-synuclein, or mutant Cu/Zn-superoxide dismutase (SOD1), were aggravated upon the knockdown of rme-8/DNAJC13 in C. elegans and in human cell lines, respectively. DNAJC13 is involved in endosomal protein trafficking and associated with the retromer and the ...
Source: Cellular and Molecular Life Sciences : CMLS - April 22, 2020 Category: Cytology Authors: Besemer AS, Maus J, Ax MDA, Stein A, Vo S, Freese C, Nalbach K, von Hilchen C, Pfalzgraf IF, Koziollek-Drechsler I, Silva B, Huesmann H, Boukhallouk F, Florin L, Kern A, Behl C, Clement AM Tags: Cell Mol Life Sci Source Type: research

P53 vs NF- κB: the role of nuclear factor-kappa B in the regulation of p53 activity and vice versa.
P53 vs NF-κB: the role of nuclear factor-kappa B in the regulation of p53 activity and vice versa. Cell Mol Life Sci. 2020 Apr 22;: Authors: Carrà G, Lingua MF, Maffeo B, Taulli R, Morotti A Abstract The onco-suppressor p53 is a transcription factor that regulates a wide spectrum of genes involved in various cellular functions including apoptosis, cell cycle arrest, senescence, autophagy, DNA repair and angiogenesis. p53 and NF-κB generally have opposing effects in cancer cells. While p53 activity is associated with apoptosis induction, the stimulation of NF-κB has been demons...
Source: Cellular and Molecular Life Sciences : CMLS - April 22, 2020 Category: Cytology Authors: Carrà G, Lingua MF, Maffeo B, Taulli R, Morotti A Tags: Cell Mol Life Sci Source Type: research

Centromere targeting of Mis18 requires the interaction with DNA and H2A-H2B in fission yeast.
Abstract Faithful chromosome segregation during mitosis requires the correct assembly of kinetochore on the centromere. CENP-A is a variant of histone H3, which specializes the centromere region on chromatin and mediates the kinetochore assembly. The Mis18 complex plays a critical role in initiating the centromere loading of the newly-synthesized CENP-A. However, it remains unclear how Mis18 complex (spMis18, spMis16 and spMis19) is located to the centromere to license the recruitment of Cnp1CENP-A in Schizosaccharomyces pombe. We found that spMis18 directly binds to nucleosomal DNA through its extreme C-terminus ...
Source: Cellular and Molecular Life Sciences : CMLS - April 21, 2020 Category: Cytology Authors: Zhang M, Zheng F, Xiong Y, Shao C, Wang C, Wu M, Niu X, Dong F, Zhang X, Fu C, Zang J Tags: Cell Mol Life Sci Source Type: research

A chromatin perspective on metabolic and genotoxic impacts on hematopoietic stem and progenitor cells.
Abstract Fate determination in self-renewal and differentiation of hematopoietic stem and progenitor cells (HSCs and HPCs) is ultimately controlled by gene expression, which is profoundly influenced by the global and local chromatin state. Cellular metabolism directly influences the chromatin state through the dynamic regulation of the enzymatic activities that modify DNA and histones, but also generates genotoxic metabolites that can damage DNA and thus pose threat to the genome integrity. On the other hand, mechanisms modulating the chromatin state impact metabolism by regulating the expression and activities of...
Source: Cellular and Molecular Life Sciences : CMLS - April 21, 2020 Category: Cytology Authors: Yang Z, Jiang H Tags: Cell Mol Life Sci Source Type: research

A central role of the endoplasmic reticulum in the cell emerges from its functional contact sites with multiple organelles.
Abstract Early eukaryotic cells emerged from the compartmentalization of metabolic processes into specific organelles through the development of an endomembrane system (ES), a precursor of the endoplasmic reticulum (ER), which was essential for their survival. Recently, substantial evidence emerged on how organelles communicate among themselves and with the plasma membrane (PM) through contact sites (CSs). From these studies, the ER-the largest single structure in eukaryotic cells-emerges as a central player communicating with all organelles to coordinate cell functions and respond to external stimuli to maintain ...
Source: Cellular and Molecular Life Sciences : CMLS - April 20, 2020 Category: Cytology Authors: Almeida C, Amaral MD Tags: Cell Mol Life Sci Source Type: research

Prognostic models for prolonged disorders of consciousness: an integrative review.
Abstract Disorders of consciousness (DoC) are acquired conditions of severe altered consciousness. During the past decades, some prognostic models for DoC have been explored on the basis of a variety of predictors, including demographics, neurological examinations, clinical diagnosis, neurophysiology and brain images. In this article, a systematic review of pertinent literature was conducted. We identified and evaluated 21 prognostic models involving a total of 1201 DoC patients. In terms of the reported accuracies of predicting the prognosis of DoC, these 21 models vary widely, ranging from 60 to 90%. Using impro...
Source: Cellular and Molecular Life Sciences : CMLS - April 18, 2020 Category: Cytology Authors: Song M, Yang Y, Yang Z, Cui Y, Yu S, He J, Jiang T Tags: Cell Mol Life Sci Source Type: research

Pathogenic mechanisms underlying spinocerebellar ataxia type 1.
Abstract The family of hereditary cerebellar ataxias is a large group of disorders with heterogenous clinical manifestations and genetic etiologies. Among these, over 30 autosomal dominantly inherited subtypes have been identified, collectively referred to as the spinocerebellar ataxias (SCAs). Generally, the SCAs are characterized by a progressive gait impairment with classical cerebellar features, and in a subset of SCAs, accompanied by extra-cerebellar features. Beyond the common gait impairment and cerebellar atrophy, the wide range of additional clinical features observed across the SCAs is likely explained b...
Source: Cellular and Molecular Life Sciences : CMLS - April 18, 2020 Category: Cytology Authors: Tejwani L, Lim J Tags: Cell Mol Life Sci Source Type: research

Genome-wide analysis of CCHC-type zinc finger (ZCCHC) proteins in yeast, Arabidopsis, and humans.
Abstract The diverse eukaryotic proteins that contain zinc fingers participate in many aspects of nucleic acid metabolism, from DNA transcription to RNA degradation, post-transcriptional gene silencing, and small RNA biogenesis. These proteins can be classified into at least 30 types based on structure. In this review, we focus on the CCHC-type zinc fingers (ZCCHC), which contain an 18-residue domain with the CX2CX4HX4C sequence, where C is cysteine, H is histidine, and X is any amino acid. This motif, also named the "zinc knuckle", is characteristic of the retroviral Group Antigen protein and occurs alo...
Source: Cellular and Molecular Life Sciences : CMLS - April 18, 2020 Category: Cytology Authors: Aceituno-Valenzuela U, Micol-Ponce R, Ponce MR Tags: Cell Mol Life Sci Source Type: research

Alteration of the late endocytic pathway in Charcot-Marie-Tooth type 2B disease.
Abstract The small GTPase RAB7A regulates late stages of the endocytic pathway and plays specific roles in neurons, controlling neurotrophins trafficking and signaling, neurite outgrowth and neuronal migration. Mutations in the RAB7A gene cause the autosomal dominant Charcot-Marie-Tooth type 2B (CMT2B) disease, an axonal peripheral neuropathy. As several neurodegenerative diseases are caused by alterations of endocytosis, we investigated whether CMT2B-causing mutations correlate with changes in this process. To this purpose, we studied the endocytic pathway in skin fibroblasts from healthy and CMT2B individuals. W...
Source: Cellular and Molecular Life Sciences : CMLS - April 13, 2020 Category: Cytology Authors: Romano R, Rivellini C, De Luca M, Tonlorenzi R, Beli R, Manganelli F, Nolano M, Santoro L, Eskelinen EL, Previtali SC, Bucci C Tags: Cell Mol Life Sci Source Type: research

Relevance of humanized three-dimensional tumor tissue models: a descriptive systematic literature review.
Abstract Despite numerous advances in tumor screening, diagnosis, and treatment, to date, tumors remain one of the leading causes of death, principally due to metastasis and the physiological damage produced by tumor growth. Among the main limits related to the study of tumor physiology there is the complex and heterogeneity nature of its environment and the absence of relevant, simple and inexpensive models able to mimic the biological processes occurring in patients allowing the correct clinical translation of results. To enhance the understanding of the mechanisms of tumors and to develop and evaluate new thera...
Source: Cellular and Molecular Life Sciences : CMLS - April 13, 2020 Category: Cytology Authors: Contartese D, Salamanna F, Veronesi F, Fini M Tags: Cell Mol Life Sci Source Type: research

A holistic view on plant effector-triggered immunity presented as an iceberg model.
Abstract The immune system of plants is highly complex. It involves pattern-triggered immunity (PTI), which is signaled and manifested through branched multi-step pathways. To counteract this, pathogen effectors target and inhibit individual PTI steps. This in turn can cause specific plant cytosolic nucleotide-binding leucine-rich repeat (NLR) receptors to activate effector-triggered immunity (ETI). Plants and pathogens have many genes encoding NLRs and effectors, respectively. Yet, only a few segregate genetically as resistance (R) genes and avirulence (Avr) effector genes in wild-type populations. In an attempt ...
Source: Cellular and Molecular Life Sciences : CMLS - April 10, 2020 Category: Cytology Authors: Thordal-Christensen H Tags: Cell Mol Life Sci Source Type: research

Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury.
Abstract The great plasticity of Schwann cells (SCs), the myelinating glia of the peripheral nervous system (PNS), is a critical feature in the context of peripheral nerve regeneration following traumatic injuries and peripheral neuropathies. After a nerve damage, SCs are rapidly activated by injury-induced signals and respond by entering the repair program. During the repair program, SCs undergo dynamic cell reprogramming and morphogenic changes aimed at promoting nerve regeneration and functional recovery. SCs convert into a repair phenotype, activate negative regulators of myelination and demyelinate the damage...
Source: Cellular and Molecular Life Sciences : CMLS - April 10, 2020 Category: Cytology Authors: Nocera G, Jacob C Tags: Cell Mol Life Sci Source Type: research

High-throughput synthetic rescue for exhaustive characterization of suppressor mutations in human genes.
Abstract Inherited or acquired mutations can lead to pathological outcomes. However, in a process defined as synthetic rescue, phenotypic outcome created by primary mutation is alleviated by suppressor mutations. An exhaustive characterization of these mutations in humans is extremely valuable to better comprehend why patients carrying the same detrimental mutation exhibit different pathological outcomes or different responses to treatment. Here, we first review all known suppressor mutations' mechanisms characterized by genetic screens on model species like yeast or flies. However, human suppressor mutations are ...
Source: Cellular and Molecular Life Sciences : CMLS - April 8, 2020 Category: Cytology Authors: Kobaisi F, Fayyad N, Sulpice E, Badran B, Fayyad-Kazan H, Rachidi W, Gidrol X Tags: Cell Mol Life Sci Source Type: research

Mechanisms of larynx and vocal fold development and pathogenesis.
Abstract The larynx and vocal folds sit at the crossroad between digestive and respiratory tracts and fulfill multiple functions related to breathing, protection and phonation. They develop at the head and trunk interface through a sequence of morphogenetic events that require precise temporo-spatial coordination. We are beginning to understand some of the molecular and cellular mechanisms that underlie critical processes such as specification of the laryngeal field, epithelial lamina formation and recanalization as well as the development and differentiation of mesenchymal cell populations. Nevertheless, many gap...
Source: Cellular and Molecular Life Sciences : CMLS - April 6, 2020 Category: Cytology Authors: Lungova V, Thibeault SL Tags: Cell Mol Life Sci Source Type: research

Melanocortin 5 receptor signaling pathway in health and disease.
Abstract Melanocortin hormone system plays a key role in maintaining the homeostasis of our body via their neuro-immune-endocrine activities and regulates a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion. The pathobiologic actions of all melanocortins are conveyed by melanocortin receptors. As the last melanocortin receptor to be cloned and characterized, melanocortin receptor 5 (MC5R) is widely expressed in both central nervous system and a numb...
Source: Cellular and Molecular Life Sciences : CMLS - April 4, 2020 Category: Cytology Authors: Xu Y, Guan X, Zhou R, Gong R Tags: Cell Mol Life Sci Source Type: research

Emerging roles of infiltrating granulocytes and monocytes in homeostasis.
Abstract The infiltration of naïve tissues by myeloid cells has been long related to their clearance and the physiological cell turnover, however, increasing evidence shows that they can additionally fulfill specific, non-immune functions in different tissues. There is also growing evidence to support that infiltrated granulocytes and monocytes respond to different environments by modulating gene expression and cytokine production, which in turn contribute to the normal function of the host tissue. This review will address the roles of immigrated myeloid cells in different tissues and their crosstalk wit...
Source: Cellular and Molecular Life Sciences : CMLS - April 4, 2020 Category: Cytology Authors: Groeneweg L, Hidalgo A, A-Gonzalez N Tags: Cell Mol Life Sci Source Type: research

HOX gene cluster (de)regulation in brain: from neurodevelopment to malignant glial tumours.
ta BM Abstract HOX genes encode a family of evolutionarily conserved homeodomain transcription factors that are crucial both during development and adult life. In humans, 39 HOX genes are arranged in four clusters (HOXA, B, C, and D) in chromosomes 7, 17, 12, and 2, respectively. During embryonic development, particular epigenetic states accompany their expression along the anterior-posterior body axis. This tightly regulated temporal-spatial expression pattern reflects their relative chromosomal localization, and is critical for normal embryonic brain development when HOX genes are mainly expressed in the hindbra...
Source: Cellular and Molecular Life Sciences : CMLS - April 1, 2020 Category: Cytology Authors: Gonçalves CS, Le Boiteux E, Arnaud P, Costa BM Tags: Cell Mol Life Sci Source Type: research

Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype.
Abstract Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models. However, little is known about their O-glycome and the differences in glycan biosynthesis in different cell types. To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed. The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization...
Source: Cellular and Molecular Life Sciences : CMLS - March 31, 2020 Category: Cytology Authors: Madunić K, Zhang T, Mayboroda OA, Holst S, Stavenhagen K, Jin C, Karlsson NG, Lageveen-Kammeijer GSM, Wuhrer M Tags: Cell Mol Life Sci Source Type: research

Mutation of a single amino acid of pregnane X receptor switches an antagonist to agonist by altering AF-2 helix positioning.
Abstract Pregnane X receptor (PXR) is activated by chemicals to transcriptionally regulate drug disposition and possibly decrease drug efficacy and increase resistance, suggesting therapeutic value for PXR antagonists. We previously reported the antagonist SPA70 and its analog SJB7, which unexpectedly is an agonist. Here, we describe another unexpected observation: mutating a single residue (W299A) within the PXR ligand-binding domain converts SPA70 to an agonist. After characterizing wild-type and W299A PXR activity profiles, we used molecular dynamics simulations to reveal that in wild-type PXR, agonists stabili...
Source: Cellular and Molecular Life Sciences : CMLS - March 30, 2020 Category: Cytology Authors: Huber AD, Wright WC, Lin W, Majumder K, Low JA, Wu J, Buchman CD, Pintel DJ, Chen T Tags: Cell Mol Life Sci Source Type: research

Long non-coding RNA NEAT1-centric gene regulation.
Abstract Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA that is widely expressed in a variety of mammalian cell types. An increasing number of studies have demonstrated that NEAT1 plays key roles in various biological and pathological processes; therefore, it is important to understand how its expression is regulated and how it regulates the expression of its target genes. Recently, we found that NEAT1 expression could be regulated by signal transducer and activator of transcription 3 and that altered NEAT1 expression epigenetically regulates downstream gene transcription during herpes ...
Source: Cellular and Molecular Life Sciences : CMLS - March 26, 2020 Category: Cytology Authors: Wang Z, Li K, Huang W Tags: Cell Mol Life Sci Source Type: research

Controversies in TWEAK-Fn14 signaling in skeletal muscle atrophy and regeneration.
Abstract Skeletal muscle is one of the largest functional tissues in the human body; it is highly plastic and responds dramatically to anabolic and catabolic stimuli, including weight training and malnutrition, respectively. Excessive loss of muscle mass, or atrophy, is a common symptom of many disease states with severe impacts on prognosis and quality of life. TNF-like weak inducer of apoptosis (TWEAK) and its cognate receptor, fibroblast growth factor-inducible 14 (Fn14) are an emerging cytokine signaling pathway in the pathogenesis of muscle atrophy. Upregulation of TWEAK and Fn14 has been described in a numbe...
Source: Cellular and Molecular Life Sciences : CMLS - March 21, 2020 Category: Cytology Authors: Pascoe AL, Johnston AJ, Murphy RM Tags: Cell Mol Life Sci Source Type: research

Plant vascular development: mechanisms and environmental regulation.
te;zquez MA Abstract Plant vascular development is a complex process culminating in the generation of xylem and phloem, the plant transporting conduits. Xylem and phloem arise from specialized stem cells collectively termed (pro)cambium. Once developed, xylem transports mainly water and mineral nutrients and phloem transports photoassimilates and signaling molecules. In the past few years, major advances have been made to characterize the molecular, genetic and physiological aspects that govern vascular development. However, less is known about how the environment re-shapes the process, which molecular mechanisms ...
Source: Cellular and Molecular Life Sciences : CMLS - March 19, 2020 Category: Cytology Authors: Agustí J, Blázquez MA Tags: Cell Mol Life Sci Source Type: research

Biological roles of LSD1 beyond its demethylase activity.
Abstract It is well-established that Lysine-specific demethylase 1 (LSD1, also known as KDM1A) roles as a lysine demethylase canonically acting on H3K4me1/2 and H3K9me1/2 for regulating gene expression. Though the discovery of non-histone substrates methylated by LSD1 has largely expanded the functions of LSD1 as a typical demethylase, recent groundbreaking studies unveiled its non-catalytic functions as a second life for this demethylase. We and others found that LSD1 is implicated in the interaction with a line of proteins to exhibit additional non-canonical functions in a demethylase-independent manner. Here, w...
Source: Cellular and Molecular Life Sciences : CMLS - March 19, 2020 Category: Cytology Authors: Gu F, Lin Y, Wang Z, Wu X, Ye Z, Wang Y, Lan H Tags: Cell Mol Life Sci Source Type: research

Xist attenuates acute inflammatory response by female cells.
Abstract Biological sex influences inflammatory response, as there is a greater incidence of acute inflammation in men and chronic inflammation in women. Here, we report that acute inflammation is attenuated by X-inactive specific transcript (Xist), a female cell-specific nuclear long noncoding RNA crucial for X-chromosome inactivation. Lipopolysaccharide-mediated acute inflammation increased Xist levels in the cytoplasm of female mouse J774A.1 macrophages and human AML193 monocytes. In both cell types, cytoplasmic Xist colocalizes with the p65 subunit of NF-κB. This interaction was associated with reduced N...
Source: Cellular and Molecular Life Sciences : CMLS - March 19, 2020 Category: Cytology Authors: Shenoda BB, Ramanathan S, Gupta R, Tian Y, Jean-Toussaint R, Alexander GM, Addya S, Somarowthu S, Sacan A, Ajit SK Tags: Cell Mol Life Sci Source Type: research