Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases.
Abstract Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging. The first catabolic step in KP is primarily controlled by indoleami...
Source: Cellular and Molecular Life Sciences : CMLS - March 17, 2017 Category: Cytology Authors: Song P, Ramprasath T, Wang H, Zou MH Tags: Cell Mol Life Sci Source Type: research

Integration of mRNP formation and export.
r L Abstract Expression of protein-coding genes in eukaryotes relies on the coordinated action of many sophisticated molecular machineries. Transcription produces precursor mRNAs (pre-mRNAs) and the active gene provides an environment in which the pre-mRNAs are processed, folded, and assembled into RNA-protein (RNP) complexes. The dynamic pre-mRNPs incorporate the growing transcript, proteins, and the processing machineries, as well as the specific protein marks left after processing that are essential for export and the cytoplasmic fate of the mRNPs. After release from the gene, the mRNPs move by diffusion within...
Source: Cellular and Molecular Life Sciences : CMLS - March 17, 2017 Category: Cytology Authors: Björk P, Wieslander L Tags: Cell Mol Life Sci Source Type: research

Development of anticancer agents targeting the Hedgehog signaling.
Abstract Hedgehog signaling is an evolutionarily conserved pathway which is essential in embryonic and postnatal development as well as adult organ homeostasis. Abnormal regulation of Hedgehog signaling is implicated in many diseases including cancer. Consequently, substantial efforts have made in the past to develop potential therapeutic agents that specifically target the Hedgehog signaling for cancer treatment. Here, we review the therapeutic agents for inhibition of the Hedgehog signaling and their clinical advances in cancer treatment. PMID: 28314894 [PubMed - as supplied by publisher] (Source: Cellular ...
Source: Cellular and Molecular Life Sciences : CMLS - March 17, 2017 Category: Cytology Authors: Zhang X, Tian Y, Yang Y, Hao J Tags: Cell Mol Life Sci Source Type: research

Impairment of systemic DHA synthesis affects macrophage plasticity and polarization: implications for DHA supplementation during inflammation.
son A Abstract Docosahexaenoic acid (DHA) is an omega-3 fatty acid obtained from the diet or synthesized from alpha-linolenic acid through the action of fatty acid elongases (ELOVL) and desaturases. DHA plays important roles in the central nervous system as well as in peripheral organs and is the precursor of several molecules that regulate resolution of inflammation. In the present study, we questioned whether impaired synthesis of DHA affected macrophage plasticity and polarization both in vitro and in vivo models. For this we investigated the activation status and inflammatory response of bone marrow-derived M1...
Source: Cellular and Molecular Life Sciences : CMLS - March 15, 2017 Category: Cytology Authors: Talamonti E, Pauter AM, Asadi A, Fischer AW, Chiurchiù V, Jacobsson A Tags: Cell Mol Life Sci Source Type: research

Transfection of primary brain capillary endothelial cells for protein synthesis and secretion of recombinant erythropoietin: a strategy to enable protein delivery to the brain.
In conclusion, non-viral gene therapy to RBECs leads to protein secretion and signifies a method for therapeutic proteins to target cells inside the CNS otherwise omitted due to the BBB. PMID: 28293718 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - March 14, 2017 Category: Cytology Authors: Burkhart A, Andresen TL, Aigner A, Thomsen LB, Moos T Tags: Cell Mol Life Sci Source Type: research

PTEN proteoforms in biology and disease.
te; V Abstract Proteoforms are specific molecular forms of protein products arising from a single gene that possess different structures and different functions. Therefore, a single gene can produce a large repertoire of proteoforms by means of allelic variations (mutations, indels, SNPs), alternative splicing and other pre-translational mechanisms, post-translational modifications (PTMs), conformational dynamics, and functioning. Resulting proteoforms that have different sizes, alternative splicing patterns, sets of post-translational modifications, protein-protein interactions, and protein-ligand interactions, m...
Source: Cellular and Molecular Life Sciences : CMLS - March 13, 2017 Category: Cytology Authors: Malaney P, Uversky VN, Davé V Tags: Cell Mol Life Sci Source Type: research

GPR120: a critical role in adipogenesis, inflammation, and energy metabolism in adipose tissue.
Abstract It is well known that adipose tissue has a critical role in the development of obesity and metabolic diseases and that adipose tissue acts as an endocrine organ to regulate lipid and glucose metabolism. Accumulating in the adipose tissue, fatty acids serve as a primary source of essential nutrients and act on intracellular and cell surface receptors to regulate biological events. G protein-coupled receptor 120 (GPR120) represents a promising target for the treatment of obesity-related metabolic disorders for its involvement in the regulation of adipogenesis, inflammation, glucose uptake, and insulin resis...
Source: Cellular and Molecular Life Sciences : CMLS - March 11, 2017 Category: Cytology Authors: Song T, Yang Y, Zhou Y, Wei H, Peng J Tags: Cell Mol Life Sci Source Type: research

Tyrosine 842 in the activation loop is required for full transformation by the oncogenic mutant FLT3-ITD.
In this report, we show that Y842 is not important for FLT3 activation or ubiquitination but plays a critical role in regulating signaling downstream of the receptor as well as controlling receptor stability. We found that mutation of Y842 in the FLT3-ITD oncogenic mutant background reduced cell viability and increased apoptosis. Furthermore, the introduction of the Y842 mutation in the FLT3-ITD background led to a dramatic reduction in in vitro colony forming capacity. Additionally, mice injected with cells expressing FLT3-ITD/Y842F displayed a significant delay in tumor formation, compared to FLT3-ITD expressing cells. M...
Source: Cellular and Molecular Life Sciences : CMLS - March 7, 2017 Category: Cytology Authors: Kazi JU, Chougule RA, Li T, Su X, Moharram SA, Rupar K, Marhäll A, Gazi M, Sun J, Zhao H, Rönnstrand L Tags: Cell Mol Life Sci Source Type: research

Immunoregulatory properties of the cytokine IL-34.
gon I Abstract Interleukin-34 is a cytokine with only partially understood functions, described for the first time in 2008. Although IL-34 shares very little homology with CSF-1 (CSF1, M-CSF), they share a common receptor CSF-1R (CSF-1R) and IL-34 has also two distinct receptors (PTP-ζ) and CD138 (syndecan-1). To make the situation more complex, IL-34 has also been shown as pairing with CSF-1 to form a heterodimer. Until now, studies have demonstrated that this cytokine is released by some tissues that differ to those where CSF-1 is expressed and is involved in the differentiation and survival of macrophages,...
Source: Cellular and Molecular Life Sciences : CMLS - March 3, 2017 Category: Cytology Authors: Guillonneau C, Bézie S, Anegon I Tags: Cell Mol Life Sci Source Type: research

Epigenetics: a link between addiction and social environment.
Abstract The detrimental effects of drug abuse are apparently not limited to individuals but may also impact the vulnerability of their progenies to develop addictive behaviours. Epigenetic signatures, early life experience and environmental factors, converge to influence gene expression patterns in addiction phenotypes and consequently may serve as mediators of behavioural trait transmission between generations. The majority of studies investigating the role of epigenetics in addiction do not consider the influence of social interactions. This shortcoming in current experimental approaches necessitates developing...
Source: Cellular and Molecular Life Sciences : CMLS - March 2, 2017 Category: Cytology Authors: Ajonijebu DC, Abboussi O, Russell VA, Mabandla MV, Daniels WM Tags: Cell Mol Life Sci Source Type: research

Integrin signaling in atherosclerosis.
Abstract Atherosclerosis, a chronic lipid-driven inflammatory disease affecting large arteries, represents the primary cause of cardiovascular disease in the world. The local remodeling of the vessel intima during atherosclerosis involves the modulation of vascular cell phenotype, alteration of cell migration and proliferation, and propagation of local extracellular matrix remodeling. All of these responses represent targets of the integrin family of cell adhesion receptors. As such, alterations in integrin signaling affect multiple aspects of atherosclerosis, from the earliest induction of inflammation to the dev...
Source: Cellular and Molecular Life Sciences : CMLS - February 28, 2017 Category: Cytology Authors: Finney AC, Stokes KY, Pattillo CB, Orr AW Tags: Cell Mol Life Sci Source Type: research

Technical approaches to induce selective cell death of pluripotent stem cells.
Abstract Despite the recent promising results of clinical trials using human pluripotent stem cell (hPSC)-based cell therapies for age-related macular degeneration (AMD), the risk of teratoma formation resulting from residual undifferentiated hPSCs remains a serious and critical hurdle for broader clinical implementation. To mitigate the tumorigenic risk of hPSC-based cell therapy, a variety of approaches have been examined to ablate the undifferentiated hPSCs based on the unique molecular properties of hPSCs. In the present review, we offer a brief overview of recent attempts at selective elimination of undiffere...
Source: Cellular and Molecular Life Sciences : CMLS - February 28, 2017 Category: Cytology Authors: Jeong HC, Cho SJ, Lee MO, Cha HJ Tags: Cell Mol Life Sci Source Type: research

Deciphering the BAR code of membrane modulators.
Abstract The BAR domain is the eponymous domain of the "BAR-domain protein superfamily", a large and diverse set of mostly multi-domain proteins that play eminent roles at the membrane cytoskeleton interface. BAR domain homodimers are the functional units that peripherally associate with lipid membranes and are involved in membrane sculpting activities. Differences in their intrinsic curvatures and lipid-binding properties account for a large variety in membrane modulating properties. Membrane activities of BAR domains are further modified and regulated by intramolecular or inter-subunit domains, by inte...
Source: Cellular and Molecular Life Sciences : CMLS - February 27, 2017 Category: Cytology Authors: Salzer U, Kostan J, Djinović-Carugo K Tags: Cell Mol Life Sci Source Type: research

Mechanisms of collective cell movement lacking a leading or free front edge in vivo.
Abstract Collective cell movement is one of the strategies for achieving the complex shapes of tissues and organs. In this process, multiple cells within a group held together by cell-cell adhesion acquire mobility and move together in the same direction. In some well-studied models of collective cell movement, the mobility depends strongly on traction generated at the leading edge by cells located at the front. However, recent advances in live-imaging techniques have led to the discovery of other types of collective cell movement lacking a leading edge or even a free edge at the front, in a diverse array of morph...
Source: Cellular and Molecular Life Sciences : CMLS - February 27, 2017 Category: Cytology Authors: Uechi H, Kuranaga E Tags: Cell Mol Life Sci Source Type: research

Microbial carcinogenic toxins and dietary anti-cancer protectants.
Abstract Several toxins are known which account for the ability of some bacteria to initiate or promote carcinogenesis. These ideas are summarised and evidence is discussed for more specific mechanisms involving chymotrypsin and the bacterial chymotryptic enzyme subtilisin. Subtilisin and Bacillus subtilis are present in the gut and environment and both are used commercially in agriculture, livestock rearing and meat processing. The enzymes deplete cells of tumour suppressors such as deleted in colorectal cancer (DCC) and neogenin, so their potential presence in the food chain might represent an important link bet...
Source: Cellular and Molecular Life Sciences : CMLS - February 25, 2017 Category: Cytology Authors: Stone TW, Darlington LG Tags: Cell Mol Life Sci Source Type: research

Emerging Role of MicroRNAs in mTOR Signaling.
Abstract Mechanistic target of rapamycin (mTOR) is a conserved serine/threonine kinase that plays a critical role in the control of cellular growth and metabolism. Hyperactivation of mTOR pathway is common in human cancers, driving uncontrolled proliferation. MicroRNA (miRNA) is a class of short noncoding RNAs that regulate the expression of a wide variety of genes. Deregulation of miRNAs is a hallmark of cancer. Recent studies have revealed interplays between miRNAs and the mTOR pathway during cancer development. Such interactions appear to provide a fine-tuning of various cellular functions and contribute qualit...
Source: Cellular and Molecular Life Sciences : CMLS - February 25, 2017 Category: Cytology Authors: Zhang Y, Huang B, Wang HY, Chang A, Zheng XF Tags: Cell Mol Life Sci Source Type: research

Germline-specific dgcr8 knockout in zebrafish using a BACK approach.
In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development. Our findings establish that Cre/loxP-mediated tissue-specific gene knockout could be achieve...
Source: Cellular and Molecular Life Sciences : CMLS - February 21, 2017 Category: Cytology Authors: Liu Y, Zhu Z, Ho IH, Shi Y, Xie Y, Li J, Zhang Y, Chan MT, Cheng CH Tags: Cell Mol Life Sci Source Type: research

Nucleic acid sensing pattern recognition receptors in the development of colorectal cancer and colitis.
Abstract Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36). Activation of these receptors eventually leads to the release...
Source: Cellular and Molecular Life Sciences : CMLS - February 21, 2017 Category: Cytology Authors: He L, Chen Y, Wu Y, Xu Y, Zhang Z, Liu Z Tags: Cell Mol Life Sci Source Type: research

Effect of hypoxia on human adipose-derived mesenchymal stem cells and its potential clinical applications.
Abstract Human adipose-derived mesenchymal stem cells (hASCs) are an ideal cell source for regenerative medicine due to their capabilities of multipotency and the readily accessibility of adipose tissue. They have been found residing in a relatively low oxygen tension microenvironment in the body, but the physiological condition has been overlooked in most studies. In light of the escalating need for culturing hASCs under their physiological condition, this review summarizes the most recent advances in the hypoxia effect on hASCs. We first highlight the advantages of using hASCs in regenerative medicine and discus...
Source: Cellular and Molecular Life Sciences : CMLS - February 21, 2017 Category: Cytology Authors: Choi JR, Yong KW, Wan Safwani WK Tags: Cell Mol Life Sci Source Type: research

Considerations on mTOR regulation at serine 2448: implications for muscle metabolism studies.
In conclusion, it is recommended that Ser2448 is an inadequate measure and that preferential analysis of mTORC1 activation should focus on the downstream and effector proteins, including p70S6K and 4E-BP1, along mTOR protein partners that bind to mTOR protein to form the active complexes 1 and 2. PMID: 28220207 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2017 Category: Cytology Authors: Figueiredo VC, Markworth JF, Cameron-Smith D Tags: Cell Mol Life Sci Source Type: research

ABCB4 missense mutations D243A, K435T, G535D, I490T, R545C, and S978P significantly impair the lipid floppase and likely predispose to secondary pathologies in the human population.
Abstract Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the luminal space of the biliary tree by the bile salt export pump (BSEP), an ATP-binding cassette (ABC) transporter in the canalicular membrane. BSEP deficiency causes cytotoxic accumulation of bile salts in the hepatocyte that results in mild-to-severe forms of cholestasis. The resulting inflammation can also progress to hepatocellular cancer via a novel mechanism involving upregulation of proliferative signalling pathways. A second ABC transporter of the...
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2017 Category: Cytology Authors: Andress EJ, Nicolaou M, McGeoghan F, Linton KJ Tags: Cell Mol Life Sci Source Type: research

S-phase checkpoint regulations that preserve replication and chromosome integrity upon dNTP depletion.
Abstract DNA replication stress, an important source of genomic instability, arises upon different types of DNA replication perturbations, including those that stall replication fork progression. Inhibitors of the cellular pool of deoxynucleotide triphosphates (dNTPs) slow down DNA synthesis throughout the genome. Following depletion of dNTPs, the highly conserved replication checkpoint kinase pathway, also known as the S-phase checkpoint, preserves the functionality and structure of stalled DNA replication forks and prevents chromosome fragmentation. The underlying mechanisms involve pathways extrinsic to replica...
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2017 Category: Cytology Authors: Giannattasio M, Branzei D Tags: Cell Mol Life Sci Source Type: research

Interactions between mesenchymal stem cells and the immune system.
Abstract In addition to being multi-potent, mesenchymal stem cells (MSCs) possess immunomodulatory functions that have been investigated as potential treatments in various immune disorders. MSCs can robustly interact with cells of the innate and adaptive immune systems, either through direct cell-cell contact or through their secretome. In this review, we discuss current findings regarding the interplay between MSCs and different immune cell subsets. We also draw attention to the mechanisms involved. PMID: 28214990 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - February 18, 2017 Category: Cytology Authors: Li N, Hua J Tags: Cell Mol Life Sci Source Type: research

On glioblastoma and the search for a cure: where do we stand?
ier F Abstract Although brain tumours have been documented and recorded since the nineteenth century, 2016 marked 90 years since Percival Bailey and Harvey Cushing coined the term "glioblastoma multiforme". Since that time, although extensive developments in diagnosis and treatment have been made, relatively little improvement on prognosis has been achieved. The resilience of GBM thus makes treating this tumour one of the biggest challenges currently faced by neuro-oncology. Aggressive and robust development, coupled with difficulties of complete resection, drug delivery and therapeutic resistance t...
Source: Cellular and Molecular Life Sciences : CMLS - February 17, 2017 Category: Cytology Authors: Bianco J, Bastiancich C, Jankovski A, des Rieux A, Préat V, Danhier F Tags: Cell Mol Life Sci Source Type: research

Novel AIDS therapies based on gene editing.
Abstract HIV/AIDS remains a major public health issue. In 2014, it was estimated that 36.9 million people are living with HIV worldwide, including 2.6 million children. Since the advent of combination antiretroviral therapy (cART), in the 1990s, treatment has been so successful that in many parts of the world, HIV has become a chronic condition in which progression to AIDS has become increasingly rare. However, while people with HIV can expect to live a normal life span with cART, lifelong medication is required and cardiovascular, renal, liver, and neurologic diseases are still possible, which continues...
Source: Cellular and Molecular Life Sciences : CMLS - February 16, 2017 Category: Cytology Authors: Khalili K, White MK, Jacobson JM Tags: Cell Mol Life Sci Source Type: research

miRNAs target databases: developmental methods and target identification techniques with functional annotations.
CONCLUSION: miRNA target databases contain diverse experimentally and computationally predicted target through various algorithms. The comparison of various miRNA target database has been performed on various parameters. The computationally predicted target databases suffer from false positive information as there is no common theory for prediction of miRNA targets. The review conclusion emphasizes the need of more intelligent computational improvement for the miRNA target identification, their functional annotations and datasbase development. PMID: 28204845 [PubMed - as supplied by publisher] (Source: Cellular and Mo...
Source: Cellular and Molecular Life Sciences : CMLS - February 15, 2017 Category: Cytology Authors: Singh NK Tags: Cell Mol Life Sci Source Type: research

Regulation of end-binding protein EB1 in the control of microtubule dynamics.
ias C Abstract The regulation of microtubule dynamics is critical to ensure essential cell functions, such as proper segregation of chromosomes during mitosis or cell polarity and migration. End-binding protein 1 (EB1) is a plus-end-tracking protein (+TIP) that accumulates at growing microtubule ends and plays a pivotal role in the regulation of microtubule dynamics. EB1 autonomously binds an extended tubulin-GTP/GDP-Pi structure at growing microtubule ends and acts as a molecular scaffold that recruits a large number of regulatory +TIPs through interaction with CAP-Gly or SxIP motifs. While extensive studies have...
Source: Cellular and Molecular Life Sciences : CMLS - February 15, 2017 Category: Cytology Authors: Nehlig A, Molina A, Rodrigues-Ferreira S, Honoré S, Nahmias C Tags: Cell Mol Life Sci Source Type: research

Discovery and progress of direct cardiac reprogramming.
Abstract Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (G...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2017 Category: Cytology Authors: Kojima H, Ieda M Tags: Cell Mol Life Sci Source Type: research

Mechanisms controlling germline cyst breakdown and primordial follicle formation.
Abstract In fetal females, oogonia proliferate immediately after sex determination. The progress of mitosis in oogonia proceeds so rapidly that the incompletely divided cytoplasm of the sister cells forms cysts. The oogonia will then initiate meiosis and arrest at the diplotene stage of meiosis I, becoming oocytes. Within each germline cyst, oocytes with Balbiani bodies will survive after cyst breakdown (CBD). After CBD, each oocyte is enclosed by pre-granulosa cells to form a primordial follicle (PF). Notably, the PF pool formed perinatally will be the sole lifelong oocyte source of a female. Thus, elucidating th...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2017 Category: Cytology Authors: Wang C, Zhou B, Xia G Tags: Cell Mol Life Sci Source Type: research

Clearance of cerebral A β in Alzheimer's disease: reassessing the role of microglia and monocytes.
Clearance of cerebral Aβ in Alzheimer's disease: reassessing the role of microglia and monocytes. Cell Mol Life Sci. 2017 Feb 14;: Authors: Zuroff L, Daley D, Black KL, Koronyo-Hamaoui M Abstract Deficiency in cerebral amyloid β-protein (Aβ) clearance is implicated in the pathogenesis of the common late-onset forms of Alzheimer's disease (AD). Accumulation of misfolded Aβ in the brain is believed to be a net result of imbalance between its production and removal. This in turn may trigger neuroinflammation, progressive synaptic loss, and ultimately cognitive decline. Clearance of ce...
Source: Cellular and Molecular Life Sciences : CMLS - February 14, 2017 Category: Cytology Authors: Zuroff L, Daley D, Black KL, Koronyo-Hamaoui M Tags: Cell Mol Life Sci Source Type: research

The equilibrium of ubiquitination and deubiquitination at PLK1 regulates sister chromatid separation.
Abstract PLK1 regulates almost every aspect of mitotic events, including mitotic entry, spindle assembly, chromosome alignment, sister chromatid segregation, metaphase-anaphase transition, cytokinesis, etc. In regulating the chromosome alignment and sister chromatid segregation, PLK1 has to be localized to and removed from kinetochores at the right times, and the underlying mechanism that regulates PLK1 both spatially and temporally only became clearer recently. It has been found that deubiquitination and ubiquitination of PLK1 are responsible for its localization to and dissociation from the kinetochores, respect...
Source: Cellular and Molecular Life Sciences : CMLS - February 10, 2017 Category: Cytology Authors: Liu J, Zhang C Tags: Cell Mol Life Sci Source Type: research

MLL5 (KMT2E): structure, function, and clinical relevance.
Abstract The mixed lineage leukemia (MLL) family of genes, also known as the lysine N-methyltransferase 2 (KMT2) family, are homologous to the evolutionarily conserved trithorax group that plays critical roles in the regulation of homeotic gene (HOX) expression and embryonic development. MLL5, assigned as KMT2E on the basis of its SET domain homology, was initially categorized under MLL (KMT2) family together with other six SET methyltransferase domain proteins (KMT2A-2D and 2F-2G). However, emerging evidence suggests that MLL5 is distinct from the other MLL (KMT2) family members, and the protein it encodes appear...
Source: Cellular and Molecular Life Sciences : CMLS - February 10, 2017 Category: Cytology Authors: Zhang X, Novera W, Zhang Y, Deng LW Tags: Cell Mol Life Sci Source Type: research

Skeletal muscle secretome in Duchenne muscular dystrophy: a pivotal anti-inflammatory role of adiponectin.
CONCLUSION: ApN retains its beneficial properties in dystrophic muscles by activating the AdipoR1-AMPK-SIRT1-PGC-1α pathway, thereby inducing a shift in the secretion of downstream myokines toward a less inflammatory profile while upregulating utrophin. ApN, the early events of the cascade and downstream myokines may be therapeutic targets for the management of DMD. PMID: 28188344 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - February 10, 2017 Category: Cytology Authors: Lecompte S, Abou-Samra M, Boursereau R, Noel L, Brichard SM Tags: Cell Mol Life Sci Source Type: research

WIP1 phosphatase is a critical regulator of adipogenesis through dephosphorylating PPAR γ serine 112.
WIP1 phosphatase is a critical regulator of adipogenesis through dephosphorylating PPARγ serine 112. Cell Mol Life Sci. 2017 Feb 08;: Authors: Li D, Zhang L, Xu L, Liu L, He Y, Zhang Y, Huang X, Zhao T, Wu L, Zhao Y, Wu K, Li H, Yu X, Zhao T, Gong S, Fan M, Zhu L Abstract WIP1, as a critical phosphatase, plays many important roles in various physiological and pathological processes through dephosphorylating different substrate proteins. However, the functions of WIP1 in adipogenesis and fat accumulation are not clear. Here, we report that WIP1-deficient mice show impaired body weight growth, dra...
Source: Cellular and Molecular Life Sciences : CMLS - February 8, 2017 Category: Cytology Authors: Li D, Zhang L, Xu L, Liu L, He Y, Zhang Y, Huang X, Zhao T, Wu L, Zhao Y, Wu K, Li H, Yu X, Zhao T, Gong S, Fan M, Zhu L Tags: Cell Mol Life Sci Source Type: research

Erratum to: Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4.
PMID: 28175960 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - February 7, 2017 Category: Cytology Authors: van der Mark VA, Ghiboub M, Marsman C, Zhao J, van Dijk R, Hiralall JK, Ho-Mok KS, Castricum Z, de Jonge WJ, Elferink RP, Paulusma CC Tags: Cell Mol Life Sci Source Type: research

Revertant mosaicism in genodermatoses.
Abstract Inherited monogenic skin disorders include blistering disorders, inflammatory disorders, and disorders of differentiation or development. In most cases, the skin is broadly involved throughout the affected individual's lifetime, but rarely, appearance of normal skin clones has been described. In these cases of revertant mosaicism, cells undergo spontaneous correction to ameliorate the effects of genetic mutation. While targeted reversion of genetic mutation would have tremendous therapeutic value, the mechanisms of reversion in the skin are poorly understood. In this review, we provide an overview of geno...
Source: Cellular and Molecular Life Sciences : CMLS - February 6, 2017 Category: Cytology Authors: Lim YH, Fisher JM, Choate KA Tags: Cell Mol Life Sci Source Type: research

Crystal structure and biochemical characterization of the transmembrane PAP2 type phosphatidylglycerol phosphate phosphatase from Bacillus subtilis.
rff F Abstract Type 2 phosphatidic acid phosphatases (PAP2s) can be either soluble or integral membrane enzymes. In bacteria, integral membrane PAP2s play major roles in the metabolisms of glycerophospholipids, undecaprenyl-phosphate (C55-P) lipid carrier and lipopolysaccharides. By in vivo functional experiments and biochemical characterization we show that the membrane PAP2 coded by the Bacillus subtilis yodM gene is the principal phosphatidylglycerol phosphate (PGP) phosphatase of B. subtilis. We also confirm that this enzyme, renamed bsPgpB, has a weaker activity on C55-PP. Moreover, we solved the crystal stru...
Source: Cellular and Molecular Life Sciences : CMLS - February 6, 2017 Category: Cytology Authors: Ghachi ME, Howe N, Auger R, Lambion A, Guiseppi A, Delbrassine F, Manat G, Roure S, Peslier S, Sauvage E, Vogeley L, Rengifo-Gonzalez JC, Charlier P, Mengin-Lecreulx D, Foglino M, Touzé T, Caffrey M, Kerff F Tags: Cell Mol Life Sci Source Type: research

Fluid shear stress-induced TGF- β/ALK5 signaling in renal epithelial cells is modulated by MEK1/2.
Fluid shear stress-induced TGF-β/ALK5 signaling in renal epithelial cells is modulated by MEK1/2. Cell Mol Life Sci. 2017 Feb 06;: Authors: Kunnen SJ, Leonhard WN, Semeins C, Hawinkels LJ, Poelma C, Ten Dijke P, Bakker A, Hierck BP, Peters DJ Abstract Renal tubular epithelial cells are exposed to mechanical forces due to fluid flow shear stress within the lumen of the nephron. These cells respond by activation of mechano-sensors located at the plasma membrane or the primary cilium, having crucial roles in maintenance of cellular homeostasis and signaling. In this paper, we applied fluid shear str...
Source: Cellular and Molecular Life Sciences : CMLS - February 6, 2017 Category: Cytology Authors: Kunnen SJ, Leonhard WN, Semeins C, Hawinkels LJ, Poelma C, Ten Dijke P, Bakker A, Hierck BP, Peters DJ Tags: Cell Mol Life Sci Source Type: research

Regulation of the H(+)-ATP synthase by IF1: a role in mitohormesis.
va JM Abstract The mitochondrial H(+)-ATP synthase is a primary hub of cellular homeostasis by providing the energy required to sustain cellular activity and regulating the production of signaling molecules that reprogram nuclear activity needed for adaption to changing cues. Herein, we summarize findings regarding the regulation of the activity of the H(+)-ATP synthase by its physiological inhibitor, the ATPase inhibitory factor 1 (IF1) and their functional role in cellular homeostasis. First, we outline the structure and the main molecular mechanisms that regulate the activity of the enzyme. Next, we describe th...
Source: Cellular and Molecular Life Sciences : CMLS - February 6, 2017 Category: Cytology Authors: Esparza-Moltó PB, Nuevo-Tapioles C, Cuezva JM Tags: Cell Mol Life Sci Source Type: research

Comparing the rules of engagement of androgen and glucocorticoid receptors.
Abstract Despite the diverse physiological activities of androgens and glucocorticoids, the corresponding receptors are very close members of the nuclear-receptor super family. Their action mechanisms show striking similarities, since both receptors recognize very similar DNA-response elements and recruit the same coactivators to their target genes. The specificity of the responses lies mainly in the tissue-specific expression of the receptors and in their ligand specificity. In cells, where both receptors are expressed, the mechanisms leading to the difference in target genes are less obvious. They lie in part in...
Source: Cellular and Molecular Life Sciences : CMLS - February 6, 2017 Category: Cytology Authors: Claessens F, Joniau S, Helsen C Tags: Cell Mol Life Sci Source Type: research

Silencing of endogenous retroviruses by heterochromatin.
Abstract Endogenous retroviruses (ERV) are an abundant class of repetitive elements in mammalian genomes. To ensure genomic stability, ERVs are largely transcriptionally silent. However, these elements also feature physiological roles in distinct developmental contexts, under which silencing needs to be partially relieved. ERV silencing is mediated through a heterochromatic structure, which is established by histone modification and DNA methylation machineries. This heterochromatic structure is largely refractory to transcriptional stimulation, however, challenges to the heterochromatic state, such as DNA replicat...
Source: Cellular and Molecular Life Sciences : CMLS - February 3, 2017 Category: Cytology Authors: Groh S, Schotta G Tags: Cell Mol Life Sci Source Type: research

Actin dynamics in the regulation of endothelial barrier functions and neutrophil recruitment during endotoxemia and sepsis.
ock A Abstract Sepsis is a leading cause of death worldwide. Increased vascular permeability is a major hallmark of sepsis. Dynamic alterations in actin fiber formation play an important role in the regulation of endothelial barrier functions and thus vascular permeability. Endothelial integrity requires a delicate balance between the formation of cortical actin filaments that maintain endothelial cell contact stability and the formation of actin stress fibers that generate pulling forces, and thus compromise endothelial cell contact stability. Current research has revealed multiple molecular pathways that regulat...
Source: Cellular and Molecular Life Sciences : CMLS - February 2, 2017 Category: Cytology Authors: Schnoor M, García Ponce A, Vadillo E, Pelayo R, Rossaint J, Zarbock A Tags: Cell Mol Life Sci Source Type: research

Characterization of a nuclear pore protein sheds light on the roles and composition of the Toxoplasma gondii nuclear pore complex.
Abstract The nuclear pore is a key structure in eukaryotes regulating nuclear-cytoplasmic transport as well as a wide range of cellular processes. Here, we report the characterization of the first Toxoplasma gondii nuclear pore protein, named TgNup302, which appears to be the orthologue of the mammalian Nup98-96 protein. We produced a conditional knock-down mutant that expresses TgNup302 under the control of an inducible tetracycline-regulated promoter. Under ATc treatment, a substantial decrease of TgNup302 protein in inducible knock-down (iKD) parasites was observed, causing a delay in parasite proliferation. Mo...
Source: Cellular and Molecular Life Sciences : CMLS - January 30, 2017 Category: Cytology Authors: Courjol F, Mouveaux T, Lesage K, Saliou JM, Werkmeister E, Bonabaud M, Rohmer M, Slomianny C, Lafont F, Gissot M Tags: Cell Mol Life Sci Source Type: research

Membrane-traversing mechanism of thyroid hormone transport by monocarboxylate transporter 8.
Abstract Monocarboxylate transporter 8 (MCT8) mediates thyroid hormone (TH) transport across the plasma membrane in many cell types. In order to better understand its mechanism, we have generated three new MCT8 homology models based on sugar transporters XylE in the intracellular opened (PDB ID: 4aj4) and the extracellular partly occluded (PDB ID: 4gby) conformations as well as FucP (PDB ID: 3o7q) and GLUT3 (PDB ID: 4zwc) in the fully extracellular opened conformation. T3-docking studies from both sides revealed interactions with His192, His415, Arg445 and Asp498 as previously identified. Selected mutations reveal...
Source: Cellular and Molecular Life Sciences : CMLS - January 28, 2017 Category: Cytology Authors: Protze J, Braun D, Hinz KM, Bayer-Kusch D, Schweizer U, Krause G Tags: Cell Mol Life Sci Source Type: research

XPF knockout via CRISPR/Cas9 reveals that ERCC1 is retained in the cytoplasm without its heterodimer partner XPF.
Abstract The XPF/ERCC1 heterodimeric complex is essentially involved in nucleotide excision repair (NER), interstrand crosslink (ICL), and double-strand break repair. Defects in XPF lead to severe diseases like xeroderma pigmentosum (XP). Up until now, XP-F patient cells have been utilized for functional analyses. Due to the multiple roles of the XPF/ERCC1 complex, these patient cells retain at least one full-length allele and residual repair capabilities. Despite the essential function of the XPF/ERCC1 complex for the human organism, we successfully generated a viable immortalised human XPF knockout cell line wit...
Source: Cellular and Molecular Life Sciences : CMLS - January 27, 2017 Category: Cytology Authors: Lehmann J, Seebode C, Smolorz S, Schubert S, Emmert S Tags: Cell Mol Life Sci Source Type: research

Defective germinal center B-cell response and reduced arthritic pathology in microRNA-29a-deficient mice.
Abstract MicroRNA (miR) are short non-coding RNA sequences of 19-24 nucleotides that regulate gene expression by binding to mRNA target sequences. The miR-29 family of miR (miR-29a, b-1, b-2 and c) is a key player in T-cell differentiation and effector function, with deficiency causing thymic involution and a more inflammatory T-cell profile. However, the relative roles of different miR-29 family members in these processes have not been dissected. We studied the immunological role of the individual members of the miR-29 family using mice deficient for miR-29a/b-1 or miR-29b-2/c in homeostasis and during collagen-i...
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2017 Category: Cytology Authors: van Nieuwenhuijze A, Dooley J, Humblet-Baron S, Sreenivasan J, Koenders M, Schlenner SM, Linterman M, Liston A Tags: Cell Mol Life Sci Source Type: research

The multi-faceted role of retinoid X receptor in bone remodeling.
P, Ricote M Abstract Retinoid X receptors (RXRs) form a unique subclass within the nuclear receptor (NR) superfamily of ligand-dependent transcription factors. RXRs are obligatory partners for a number of other NRs, placing RXRs in a coordinating role at the crossroads of multiple signaling pathways. In addition, RXRs can function as self-sufficient homodimers. Recent advances have revealed RXRs as novel regulators of osteoclastogenesis and bone remodeling. This review outlines the versatility of RXR action in the control of transcription of bone-forming osteoblasts and bone-resorbing osteoclasts, both through het...
Source: Cellular and Molecular Life Sciences : CMLS - January 19, 2017 Category: Cytology Authors: Menéndez-Gutiérrez MP, Ricote M Tags: Cell Mol Life Sci Source Type: research

Innate and intrinsic antiviral immunity in Drosophila.
Abstract The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducibl...
Source: Cellular and Molecular Life Sciences : CMLS - January 19, 2017 Category: Cytology Authors: Mussabekova A, Daeffler L, Imler JL Tags: Cell Mol Life Sci Source Type: research

The role of neuropeptides in adverse myocardial remodeling and heart failure.
Abstract In addition to traditional neurotransmitters of the sympathetic and parasympathetic nervous systems, the heart also contains numerous neuropeptides. These neuropeptides not only modulate the effects of neurotransmitters, but also have independent effects on cardiac function. While in most cases the physiological actions of these neuropeptides are well defined, their contributions to cardiac pathology are less appreciated. Some neuropeptides are cardioprotective, some promote adverse cardiac remodeling and heart failure, and in the case of others their functions are unclear. Some have both cardioprotective...
Source: Cellular and Molecular Life Sciences : CMLS - January 17, 2017 Category: Cytology Authors: Widiapradja A, Chunduri P, Levick SP Tags: Cell Mol Life Sci Source Type: research

Mitochondrial dynamics as regulators of cancer biology.
Abstract Mitochondria are dynamic organelles that supply energy required to drive key cellular processes, such as survival, proliferation, and migration. Critical to all of these processes are changes in mitochondrial architecture, a mechanical mechanism encompassing both fusion and fragmentation (fission) of the mitochondrial network. Changes to mitochondrial shape, size, and localization occur in a regulated manner to maintain energy and metabolic homeostasis, while deregulation of mitochondrial dynamics is associated with the onset of metabolic dysfunction and disease. In cancers, oncogenic signals that drive e...
Source: Cellular and Molecular Life Sciences : CMLS - January 12, 2017 Category: Cytology Authors: Trotta AP, Chipuk JE Tags: Cell Mol Life Sci Source Type: research