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 20, 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 20, 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 19, 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 17, 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 17, 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 17, 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 12, 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 12, 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 9, 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 9, 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 7, 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 5, 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 3, 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 3, 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 - March 31, 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 30, 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 29, 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 25, 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 20, 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 18, 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 18, 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 18, 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

The Map3k12 (Dlk)/JNK3 signaling pathway is required for pancreatic beta-cell proliferation during postnatal development.
In conclusion, we find that activation of Jnk3 signalling by Dlk could be a key mechanism for adapting islet beta-cell mass during postnatal development and weight gain. PMID: 32189007 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - March 17, 2020 Category: Cytology Authors: Tenenbaum M, Plaisance V, Boutry R, Pawlowski V, Jacovetti C, Sanchez-Parra C, Ezanno H, Bourry J, Beeler N, Pasquetti G, Gmyr V, Dalle S, Kerr-Conte J, Pattou F, Hirai SI, Regazzi R, Bonnefond A, Froguel P, Abderrahmani A Tags: Cell Mol Life Sci Source Type: research

Building sophisticated sensors of extracellular cues that enable mammalian cells to work as "doctors" in the body.
Building sophisticated sensors of extracellular cues that enable mammalian cells to work as "doctors" in the body. Cell Mol Life Sci. 2020 Mar 17;: Authors: Kojima R, Aubel D, Fussenegger M Abstract Mammalian cells are inherently capable of sensing extracellular environmental signals and activating complex biological functions on demand. Advances in synthetic biology have made it possible to install additional capabilities, which can allow cells to sense the presence of custom biological molecules and provide defined outputs on demand. When implanted/infused in patients, such engineered cell...
Source: Cellular and Molecular Life Sciences : CMLS - March 16, 2020 Category: Cytology Authors: Kojima R, Aubel D, Fussenegger M Tags: Cell Mol Life Sci Source Type: research

Molecular and circuit mechanisms regulating cocaine memory.
Abstract Risk of relapse is a major challenge in the treatment of substance use disorders. Several types of learning and memory mechanisms are involved in substance use and have implications for relapse. Associative memories form between the effects of drugs and the surrounding environmental stimuli, and exposure to these stimuli during abstinence causes stress and triggers drug craving, which can lead to relapse. Understanding the neural underpinnings of how these associations are formed and maintained will inform future advances in treatment practices. A large body of research has expanded our knowledge of how a...
Source: Cellular and Molecular Life Sciences : CMLS - March 13, 2020 Category: Cytology Authors: Bender BN, Torregrossa MM Tags: Cell Mol Life Sci Source Type: research

Bitter taste receptors stimulate phagocytosis in human macrophages through calcium, nitric oxide, and cyclic-GMP signaling.
We examined mechanisms of T2R signaling in primary human monocyte-derived unprimed (M0) macrophages (M[Formula: see text]s) using live cell imaging techniques. Known bitter compounds and bacterial T2R agonists activated low-level calcium signals through a pertussis toxin (PTX)-sensitive, phospholipase C-dependent, and inositol trisphosphate receptor-dependent calcium release pathway. These calcium signals activated low-level nitric oxide (NO) production via endothelial and neuronal NO synthase (NOS) isoforms. NO production increased cellular cGMP and enhanced acute phagocytosis ~ threefold over 30-60 min...
Source: Cellular and Molecular Life Sciences : CMLS - March 13, 2020 Category: Cytology Authors: Gopallawa I, Freund JR, Lee RJ Tags: Cell Mol Life Sci Source Type: research

Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis.
Abstract eIF4E plays key roles in protein synthesis and tumorigenesis. It is phosphorylated by the kinases MNK1 and MNK2. Binding of MNKs to eIF4G enhances their ability to phosphorylate eIF4E. Here, we show that mTORC1, a key regulator of mRNA translation and oncogenesis, directly phosphorylates MNK2 on Ser74. This suppresses MNK2 activity and impairs binding of MNK2 to eIF4G. These effects provide a novel mechanism by which mTORC1 signaling impairs the function of MNK2 and thereby decreases eIF4E phosphorylation. MNK2[S74A] knock-in cells show enhanced phosphorylation of eIF4E and S6K1 (i.e., increased mTORC1 si...
Source: Cellular and Molecular Life Sciences : CMLS - March 12, 2020 Category: Cytology Authors: Xie J, Shen K, Jones AT, Yang J, Tee AR, Shen MH, Yu M, Irani S, Wong D, Merrett JE, Lenchine RV, De Poi S, Jensen KB, Trim PJ, Snel MF, Kamei M, Martin SK, Fitter S, Tian S, Wang X, Butler LM, Zannettino ACW, Proud CG Tags: Cell Mol Life Sci Source Type: research

Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors.
This study aimed to delineate the cellular heterogeneity and possible functional role of endogenous vascular SPCs in large vessels. Using single-cell RNA-sequencing (scRNA-seq) and genetic lineage tracing mouse models, we uncovered the cellular heterogeneity of SPCs, i.e., c-Kit+ cells in the mouse aorta, and found that endogenous c-Kit+ cells acquire endothelial cell fate in the aorta under both physiological and pathological conditions. While c-Kit+ cells contribute to aortic endothelial turnover in the atheroprone regions during homeostasis, recipient c-Kit+ cells of nonbone marrow source replace both luminal and microv...
Source: Cellular and Molecular Life Sciences : CMLS - March 12, 2020 Category: Cytology Authors: Deng J, Ni Z, Gu W, Chen Q, Nowak WN, Chen T, Issa Bhaloo S, Zhang Z, Hu Y, Zhou B, Zhang L, Xu Q Tags: Cell Mol Life Sci Source Type: research

Update on SLC6A14 in lung and gastrointestinal physiology and physiopathology: focus on cystic fibrosis.
, Guillot L Abstract The solute carrier family 6 member 14 (SLC6A14) protein imports and concentrates all neutral amino acids as well as the two cationic acids lysine and arginine into the cytoplasm of different cell types. Primarily described as involved in several cancer and colonic diseases physiopathological mechanisms, the SLC6A14 gene has been more recently identified as a genetic modifier of cystic fibrosis (CF) disease severity. It was indeed shown to have a pleiotropic effect, modulating meconium ileus occurrence, lung disease severity, and precocity of P. aeruginosa airway infection. The biological mecha...
Source: Cellular and Molecular Life Sciences : CMLS - March 11, 2020 Category: Cytology Authors: Ruffin M, Mercier J, Calmel C, Mésinèle J, Bigot J, Sutanto EN, Kicic A, Corvol H, Guillot L Tags: Cell Mol Life Sci Source Type: research

Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue.
Abstract Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipo...
Source: Cellular and Molecular Life Sciences : CMLS - March 10, 2020 Category: Cytology Authors: Caputo T, Tran VDT, Bararpour N, Winkler C, Aguileta G, Trang KB, Giordano Attianese GMP, Wilson A, Thomas A, Pagni M, Guex N, Desvergne B, Gilardi F Tags: Cell Mol Life Sci Source Type: research

The SF3b complex: splicing and beyond.
Abstract The SF3b complex is an intrinsic component of the functional U2 small nuclear ribonucleoprotein (snRNP). As U2 snRNP enters nuclear pre-mRNA splicing, SF3b plays key roles in recognizing the branch point sequence (BPS) and facilitating spliceosome assembly and activation. Since the discovery of SF3b, substantial progress has been made in elucidating its molecular mechanism during splicing. In addition, numerous recent studies indicate that SF3b and its components are engaged in various molecular and cellular events that are beyond the canonical role in splicing. This review summarizes the current knowledg...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2020 Category: Cytology Authors: Sun C Tags: Cell Mol Life Sci Source Type: research

Crystal structures of human NSDHL and development of its novel inhibitor with the potential to suppress EGFR activity.
In this study, we reported two X-ray crystal structures of human NSDHL, which revealed a detailed description of the coenzyme-binding site and the unique conformational change upon the binding of a coenzyme. A structure-based virtual screening and biochemical evaluation were performed and identified a novel inhibitor for NSDHL harboring suppressive activity towards EGFR. In EGFR-driven human cancer cells, treatment with the potent NSDHL inhibitor enhanced the antitumor effect of an EGFR kinase inhibitor. Overall, these findings could serve as good platforms for the development of therapeutic agents against NSDHL-related di...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2020 Category: Cytology Authors: Kim DG, Cho S, Lee KY, Cheon SH, Yoon HJ, Lee JY, Kim D, Shin KS, Koh CH, Koo JS, Choi Y, Lee HH, Oh YK, Jeong YS, Chung SJ, Baek M, Jung KY, Lim HJ, Kim HS, Park SJ, Lee JY, Lee SJ, Lee BJ Tags: Cell Mol Life Sci Source Type: research

Isotope metallomics approaches for medical research.
Abstract Metallomics is a rapidly evolving field of bio-metal research that integrates techniques and perspectives from other "-omics" sciences (e.g. genomics, proteomics) and from research vocations further afield. Perhaps the most esoteric of this latter category has been the recent coupling of biomedicine with element and isotope geochemistry, commonly referred to as isotope metallomics. Over the course of less than two decades, isotope metallomics has produced numerous benchmark studies highlighting the use of stable metal isotope distribution in developing disease diagnostics-e.g. cancer, neurodegen...
Source: Cellular and Molecular Life Sciences : CMLS - March 3, 2020 Category: Cytology Authors: Mahan B, Chung RS, Pountney DL, Moynier F, Turner S Tags: Cell Mol Life Sci Source Type: research

Regulation of B-cell function by NF-kappaB c-Rel in health and disease.
Abstract B cells mediate humoral immune response and contribute to the regulation of cellular immune response. Members of the Nuclear Factor kappaB (NF-κB) family of transcription factors play a major role in regulating B-cell functions. NF-κB subunit c-Rel is predominantly expressed in lymphocytes, and in B cells, it is required for survival, proliferation, and antibody production. Dysregulation of c-Rel expression and activation alters B-cell homeostasis and is associated with B-cell lymphomas and autoimmune pathologies. Based on its essential roles, c-Rel may serve as a potential prognostic and ther...
Source: Cellular and Molecular Life Sciences : CMLS - March 3, 2020 Category: Cytology Authors: Basavarajappa SC, Ramakrishnan P Tags: Cell Mol Life Sci Source Type: research

Apelin/APJ system: an emerging therapeutic target for respiratory diseases.
Abstract Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney, especially in lung tissue. A growing body of evidence suggests that apelin/APJ system is closely related to the development of respiratory diseases. Therefore, in this review, we focus on the role of apelin/APJ system in respiratory diseases, including pulmonary arterial hypertension (PAH), pulmonary embolism (PE), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), obstructive sleep apnoea syndrome (OSAS), non-small cell lung cancer (NSCLC), pulmo...
Source: Cellular and Molecular Life Sciences : CMLS - March 2, 2020 Category: Cytology Authors: Yan J, Wang A, Cao J, Chen L Tags: Cell Mol Life Sci Source Type: research

Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1).
The objectives of this review are to discuss the current understanding of SMARD1 through a summary of the presently known information regarding its clinical presentation and pathogenesis and to discuss emerging therapeutic approaches. Advances in clinical care management have significantly extended the lives of individuals affected by SMARD1 and research into the molecular mechanisms that lead to the disease has identified potential strategies for intervention that target the underlying causes of SMARD1. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to halt or poss...
Source: Cellular and Molecular Life Sciences : CMLS - March 1, 2020 Category: Cytology Authors: Perego MGL, Galli N, Nizzardo M, Govoni A, Taiana M, Bresolin N, Comi GP, Corti S Tags: Cell Mol Life Sci Source Type: research

Cellular uptake of collagens and implications for immune cell regulation in disease.
Madsen DH Abstract As the dominant constituent of the extracellular matrix (ECM), collagens of different types are critical for the structural properties of tissues and make up scaffolds for cellular adhesion and migration. Importantly, collagens also directly modulate the phenotypic state of cells by transmitting signals that influence proliferation, differentiation, polarization, survival, and more, to cells of mesenchymal, epithelial, or endothelial origin. Recently, the potential of collagens to provide immune regulatory signals has also been demonstrated, and it is believed that pathological changes in the EC...
Source: Cellular and Molecular Life Sciences : CMLS - February 24, 2020 Category: Cytology Authors: Jürgensen HJ, van Putten S, Nørregaard KS, Bugge TH, Engelholm LH, Behrendt N, Madsen DH Tags: Cell Mol Life Sci Source Type: research

The neglected part of early embryonic development: maternal protein degradation.
Abstract The degradation of maternally provided molecules is a very important process during early embryogenesis. However, the vast majority of studies deals with mRNA degradation and protein degradation is only a very little explored process yet. The aim of this article was to summarize current knowledge about the protein degradation during embryogenesis of mammals. In addition to resuming of known data concerning mammalian embryogenesis, we tried to fill the gaps in knowledge by comparison with facts known about protein degradation in early embryos of non-mammalian species. Maternal protein degradation seems to ...
Source: Cellular and Molecular Life Sciences : CMLS - February 23, 2020 Category: Cytology Authors: Toralova T, Kinterova V, Chmelikova E, Kanka J Tags: Cell Mol Life Sci Source Type: research

Regulation of branched-chain amino acid metabolism by hypoxia-inducible factor in glioblastoma.
Abstract Hypoxia-inducible factors (HIFs) mediate metabolic reprogramming in response to hypoxia. However, the role of HIFs in branched-chain amino acid (BCAA) metabolism remains unknown. Here we show that hypoxia upregulates mRNA and protein levels of the BCAA transporter LAT1 and the BCAA metabolic enzyme BCAT1, but not their paralogs LAT2-4 and BCAT2, in human glioblastoma (GBM) cell lines as well as primary GBM cells. Hypoxia-induced LAT1 protein upregulation is mediated by both HIF-1 and HIF-2 in GBM cells. Although both HIF-1α and HIF-2α directly bind to the hypoxia response element at the first ...
Source: Cellular and Molecular Life Sciences : CMLS - February 21, 2020 Category: Cytology Authors: Zhang B, Chen Y, Shi X, Zhou M, Bao L, Hatanpaa KJ, Patel T, DeBerardinis RJ, Wang Y, Luo W Tags: Cell Mol Life Sci Source Type: research

Functional mosaic organization of neuroligins in neuronal circuits.
Abstract Complex brain circuitry with feedforward and feedback systems regulates neuronal activity, enabling neural networks to process and drive the entire spectrum of cognitive, behavioral, sensory, and motor functions. Simultaneous orchestration of distinct cells and interconnected neural circuits is underpinned by hundreds of synaptic adhesion molecules that span synaptic junctions. Dysfunction of a single molecule or molecular interaction at synapses can lead to disrupted circuit activity and brain disorders. Neuroligins, a family of cell adhesion molecules, were first identified as postsynaptic-binding partn...
Source: Cellular and Molecular Life Sciences : CMLS - February 19, 2020 Category: Cytology Authors: Qin L, Guo S, Han Y, Wang X, Zhang B Tags: Cell Mol Life Sci Source Type: research

Revisiting cellular immune response to oncogenic Marek's disease virus: the rising of avian T-cell immunity.
Abstract Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes deadly T-cell lymphomas and serves as a natural virus-induced tumor model in chickens. Although Marek's disease (MD) is well controlled by current vaccines, the evolution of MDV field viruses towards increasing virulence is concerning as a better vaccine to combat very virulent plus MDV is still lacking. Our understanding of molecular and cellular immunity to MDV and its immunopathogenesis has significantly improved, but those findings about cellular immunity to MDV are largely out-of-date, hampering the development of more eff...
Source: Cellular and Molecular Life Sciences : CMLS - February 19, 2020 Category: Cytology Authors: Yang Y, Dong M, Hao X, Qin A, Shang S Tags: Cell Mol Life Sci Source Type: research

Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation.
PA Abstract Zinc is required for the regulation of proliferation, metabolism, and cell signaling. It is an intracellular second messenger, and the cellular level of ionic, mobile zinc is strictly controlled by zinc transporters. In mammals, zinc homeostasis is primarily regulated by ZIP and ZnT zinc transporters. The importance of these transporters is underscored by the list of diseases resulting from changes in transporter expression and activity. However, despite numerous structural studies of the transporters revealing both zinc binding sites and motifs important for transporter function, the exact molecular ...
Source: Cellular and Molecular Life Sciences : CMLS - February 18, 2020 Category: Cytology Authors: Thingholm TE, Rönnstrand L, Rosenberg PA Tags: Cell Mol Life Sci Source Type: research

Reductive stress in striated muscle cells.
Abstract Reductive stress is defined as a condition of sustained increase in cellular glutathione/glutathione disulfide and NADH/NAD+ ratios. Reductive stress is emerging as an important pathophysiological event in several diseased states, being as detrimental as is oxidative stress. Occurrence of reductive stress has been documented in several cardiomyopathies and is an important pathophysiological factor particularly in coronary artery disease and myocardial infarction. Excess activation of the transcription factor, Nrf2-the master regulator of the antioxidant response-, consequent in most cases to defective aut...
Source: Cellular and Molecular Life Sciences : CMLS - February 17, 2020 Category: Cytology Authors: Bellezza I, Riuzzi F, Chiappalupi S, Arcuri C, Giambanco I, Sorci G, Donato R Tags: Cell Mol Life Sci Source Type: research

Targets for protection and mitigation of radiation injury.
Abstract Protection of normal tissues against toxic effects of ionizing radiation is a critical issue in clinical and environmental radiobiology. Investigations in recent decades have suggested potential targets that are involved in the protection against radiation-induced damages to normal tissues and can be proposed for mitigation of radiation injury. Emerging evidences have been shown to be in contrast to an old dogma in radiation biology; a major amount of reactive oxygen species (ROS) production and cell toxicity occur during some hours to years after exposure to ionizing radiation. This can be attributed to ...
Source: Cellular and Molecular Life Sciences : CMLS - February 17, 2020 Category: Cytology Authors: Khodamoradi E, Hoseini-Ghahfarokhi M, Amini P, Motevaseli E, Shabeeb D, Musa AE, Najafi M, Farhood B Tags: Cell Mol Life Sci Source Type: research

The Rab5 activator RME-6 is required for amyloid precursor protein endocytosis depending on the YTSI motif.
Abstract Endocytosis of the amyloid precursor protein (APP) is critical for generation of β-amyloid, aggregating in Alzheimer's disease. APP endocytosis depending on the intracellular NPTY motif is well investigated, whereas involvement of the YTSI (also termed BaSS) motif remains controversial. Here, we show that APP lacking the YTSI motif (ΔYTSI) displays reduced localization to early endosomes and decreased internalization rates, similar to APP ΔNPTY. Additionally, we show that the YTSI-binding protein, PAT1a interacts with the Rab5 activator RME-6, as shown by several independent assays. ...
Source: Cellular and Molecular Life Sciences : CMLS - February 16, 2020 Category: Cytology Authors: Eggert S, Gruebl T, Rajender R, Rupp C, Sander B, Heesch A, Zimmermann M, Hoepfner S, Zentgraf H, Kins S Tags: Cell Mol Life Sci Source Type: research

Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases.
bry L Abstract Over the last three decades, the scaffold proteins prohibitins-1 and -2 (PHB1/2) have emerged as key signaling proteins regulating a myriad of signaling pathways in health and diseases. Small molecules targeting PHBs display promising effects against cancers, osteoporosis, inflammatory, cardiac and neurodegenerative diseases. This review provides an updated overview of the various classes of PHB ligands, with an emphasis on their mechanism of action and therapeutic potential. We also describe how these ligands have been used to explore PHB signaling in different physiological and pathological settin...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2020 Category: Cytology Authors: Wang D, Tabti R, Elderwish S, Abou-Hamdan H, Djehal A, Yu P, Yurugi H, Rajalingam K, Nebigil CG, Désaubry L Tags: Cell Mol Life Sci Source Type: research

Founder cells for hepatocytes during liver regeneration: from identification to application.
Abstract Liver regeneration (LR) capacity in vertebrates developed through natural selection over a hundred million years of evolution. To maintain homeostasis or recover from various injuries, liver cells must regenerate; this process includes the renewal of parenchymal and nonparenchymal cells as well as the formation of liver structures. The cellular origin of newly grown tissue is one of the critical questions in this area and has been a subject of prolonged debate. The regenerative tissue may derive from either hepatocyte self-duplication or liver stem/progenitor cells (LSPCs). Recently, hepatocyte subpopulat...
Source: Cellular and Molecular Life Sciences : CMLS - February 13, 2020 Category: Cytology Authors: Wei S, Tang J, Cai X Tags: Cell Mol Life Sci Source Type: research

Dynamics of kinetochore structure and its regulations during mitotic progression.
Abstract Faithful chromosome segregation during mitosis in eukaryotes requires attachment of the kinetochore, a large protein complex assembled on the centromere of each chromosome, to the spindle microtubules. The kinetochore is a structural interface for the microtubule attachment and provides molecular surveillance mechanisms that monitor and ensure the precise microtubule attachment as well, including error correction and spindle assembly checkpoint. During mitotic progression, the kinetochore undergoes dynamic morphological changes that are observable through electron microscopy as well as through fluorescenc...
Source: Cellular and Molecular Life Sciences : CMLS - February 11, 2020 Category: Cytology Authors: Hara M, Fukagawa T Tags: Cell Mol Life Sci Source Type: research

Physiological functions of SPP/SPPL intramembrane proteases.
r B Abstract Intramembrane proteolysis describes the cleavage of substrate proteins within their hydrophobic transmembrane segments. Several families of intramembrane proteases have been identified including the aspartyl proteases Signal peptide peptidase (SPP) and its homologues, the SPP-like (SPPL) proteases SPPL2a, SPPL2b, SPPL2c and SPPL3. As presenilin homologues, they employ a similar catalytic mechanism as the well-studied γ-secretase. However, SPP/SPPL proteases cleave transmembrane proteins with a type II topology. The characterisation of SPP/SPPL-deficient mouse models has highlighted a still ...
Source: Cellular and Molecular Life Sciences : CMLS - February 11, 2020 Category: Cytology Authors: Mentrup T, Cabrera-Cabrera F, Fluhrer R, Schröder B Tags: Cell Mol Life Sci Source Type: research

Prevalence and significance of the commonest phosphorylated motifs in the human proteome: a global analysis.
Abstract Protein phosphorylation is the most frequent post-translational modification by which the properties of eukaryotic proteins can be reversibly modified. In humans, over 500 protein kinases generate a huge phosphoproteome including more than 200,000 individual phosphosites, a figure which is still continuously increasing. The in vivo selectivity of protein kinases is the outcome of a multifaceted and finely tuned process where numerous factors play an integrated role. To gain information about the actual contribution to this process of local features that reflect the interaction of the protein targets with ...
Source: Cellular and Molecular Life Sciences : CMLS - February 11, 2020 Category: Cytology Authors: Cesaro L, Pinna LA Tags: Cell Mol Life Sci Source Type: research