Loss of mutL homolog-1 (MLH1) expression promotes acquisition of oncogenic and inhibitor-resistant point mutations in tyrosine kinases.
Abstract Genomic instability drives cancer progression by promoting genetic abnormalities that allow for the multi-step clonal selection of cells with growth advantages. We previously reported that the IL-9-dependent TS1 cell line sequentially acquired activating substitutions in JAK1 and JAK3 upon successive selections for growth factor independent and JAK inhibitor-resistant cells, suggestive of a defect in mutation avoidance mechanisms. In the first part of this paper, we discovered that the gene encoding mutL homolog-1 (MLH1), a key component of the DNA mismatch repair system, is silenced by promoter methylati...
Source: Cellular and Molecular Life Sciences : CMLS - July 19, 2016 Category: Cytology Authors: Springuel L, Losdyck E, Saussoy P, Turcq B, Mahon FX, Knoops L, Renauld JC Tags: Cell Mol Life Sci Source Type: research

Erratum to: Preservation of positional identity in fetus-derived neural stem (NS) cells from different mouse central nervous system compartments.
PMID: 27405607 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 12, 2016 Category: Cytology Authors: Onorati M, Binetti M, Conti L, Camnasio S, Calabrese G, Albieri I, Di Febo F, Toselli M, Biella G, Martynoga B, Guillemot F, Consalez GG, Cattaneo E Tags: Cell Mol Life Sci Source Type: research

Searching for convergent pathways in autism spectrum disorders: insights from human brain transcriptome studies.
Abstract Autism spectrum disorder (ASD) is one of the most heritable neuropsychiatric conditions. The complex genetic landscape of the disorder includes both common and rare variants at hundreds of genetic loci. This marked heterogeneity has thus far hampered efforts to develop genetic diagnostic panels and targeted pharmacological therapies. Here, we give an overview of the current literature on the genetic basis of ASD, and review recent human brain transcriptome studies and their role in identifying convergent pathways downstream of the heterogeneous genetic variants. We also discuss emerging evidence on the in...
Source: Cellular and Molecular Life Sciences : CMLS - July 12, 2016 Category: Cytology Authors: Gokoolparsadh A, Sutton GJ, Charamko A, Green NF, Pardy CJ, Voineagu I Tags: Cell Mol Life Sci Source Type: research

The functional role for condensin in the regulation of chromosomal organization during the cell cycle.
Abstract In all organisms, the control of cell cycle progression is a fundamental process that is essential for cell growth, development, and survival. Through each cell cycle phase, the regulation of chromatin organization is essential for natural cell proliferation and maintaining cellular homeostasis. During mitosis, the chromatin morphology is dramatically changed to have a "thread-like" shape and the condensed chromosomes are segregated equally into two daughter cells. Disruption of the mitotic chromosome architecture physically impedes chromosomal behaviors, such as chromosome alignment and chromos...
Source: Cellular and Molecular Life Sciences : CMLS - July 11, 2016 Category: Cytology Authors: Kagami Y, Yoshida K Tags: Cell Mol Life Sci Source Type: research

The CB2 receptor and its role as a regulator of inflammation.
Abstract The CB2 receptor is the peripheral receptor for cannabinoids. It is mainly expressed in immune tissues, highlighting the possibility that the endocannabinoid system has an immunomodulatory role. In this respect, the CB2 receptor was shown to modulate immune cell functions, both in cellulo and in animal models of inflammatory diseases. In this regard, numerous studies have reported that mice lacking the CB2 receptor have an exacerbated inflammatory phenotype. This suggests that therapeutic strategies aiming at modulating CB2 signaling could be promising for the treatment of various inflammatory conditions....
Source: Cellular and Molecular Life Sciences : CMLS - July 11, 2016 Category: Cytology Authors: Turcotte C, Blanchet MR, Laviolette M, Flamand N Tags: Cell Mol Life Sci Source Type: research

Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action.
Abstract Efforts to reduce the global burden of bacterial disease and contend with escalating bacterial resistance are spurring innovation in antibacterial drug and biocide development and related technologies such as photodynamic therapy and photochemical disinfection. Elucidation of the mechanism of action of these new agents and processes can greatly facilitate their development, but it is a complex endeavour. One strategy that has been popular for many years, and which is garnering increasing interest due to recent technological advances in microscopy and a deeper understanding of the molecular events involved...
Source: Cellular and Molecular Life Sciences : CMLS - July 8, 2016 Category: Cytology Authors: Cushnie TP, O'Driscoll NH, Lamb AJ Tags: Cell Mol Life Sci Source Type: research

Mechanisms of viral mutation.
lap P Abstract The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, a...
Source: Cellular and Molecular Life Sciences : CMLS - July 8, 2016 Category: Cytology Authors: Sanjuán R, Domingo-Calap P Tags: Cell Mol Life Sci Source Type: research

Epigenetic regulation of epithelial-mesenchymal transition.
Abstract Epithelial-mesenchymal transition (EMT) is an essential process for morphogenesis and organ development which reversibly enables polarized epithelial cells to lose their epithelial characteristics and to acquire mesenchymal properties. It is now evident that the aberrant activation of EMT is also a critical mechanism to endow epithelial cancer cells with migratory and invasive capabilities associated with metastatic competence. This dedifferentiation program is mediated by a small cohort of pleiotropic transcription factors which orchestrate a complex array of epigenetic mechanisms for the wide-spread cha...
Source: Cellular and Molecular Life Sciences : CMLS - July 8, 2016 Category: Cytology Authors: Sun L, Fang J Tags: Cell Mol Life Sci Source Type: research

Methylphenidate-triggered ROS generation promotes caveolae-mediated transcytosis via Rac1 signaling and c-Src-dependent caveolin-1 phosphorylation in human brain endothelial cells.
This study, therefore, identifies Rac1/NOX/c-Src-dependent signaling in MPH-induced increase in transendothelial permeability of brain endothelial cell monolayers via caveolae-mediated transcytosis. PMID: 27376435 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 4, 2016 Category: Cytology Authors: Coelho-Santos V, Socodato R, Portugal C, Leitão RA, Rito M, Barbosa M, Couraud PO, Romero IA, Weksler B, Minshall RD, Fontes-Ribeiro C, Summavielle T, Relvas JB, Silva AP Tags: Cell Mol Life Sci Source Type: research

Axial and limb muscle development: dialogue with the neighbourhood.
tir S Abstract Skeletal muscles are part of the musculoskeletal system which also includes nerves, tendons, connective tissue, bones and blood vessels. Here we review the development of axial and limb muscles in amniotes within the context of their surrounding tissues in vivo. We highlight the reciprocal dialogue mediated by signalling factors between cells of these adjacent tissues and developing muscles and also demonstrate its importance from the onset of muscle cell differentiation well into foetal development. Early embryonic tissues secrete factors which are important regulators of myogenesis. However, later...
Source: Cellular and Molecular Life Sciences : CMLS - June 25, 2016 Category: Cytology Authors: Deries M, Thorsteinsdóttir S Tags: Cell Mol Life Sci Source Type: research

Negative feedback regulation of the ERK1/2 MAPK pathway.
l;ller J Abstract The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the ex...
Source: Cellular and Molecular Life Sciences : CMLS - June 24, 2016 Category: Cytology Authors: Lake D, Corrêa SA, Müller J Tags: Cell Mol Life Sci Source Type: research

One protein, multiple pathologies: multifaceted involvement of amyloid β in neurodegenerative disorders of the brain and retina.
One protein, multiple pathologies: multifaceted involvement of amyloid β in neurodegenerative disorders of the brain and retina. Cell Mol Life Sci. 2016 Jun 22; Authors: Gupta V, Gupta VB, Chitranshi N, Gangoda S, Vander Wall R, Abbasi M, Golzan M, Dheer Y, Shah T, Avolio A, Chung R, Martins R, Graham S Abstract Accumulation of amyloid β (Aβ) and its aggregates in the ageing central nervous system is regarded synonymous to Alzheimer's disease (AD) pathology. Despite unquestionable advances in mechanistic and diagnostic aspects of the disease understanding, the primary cause of Aβ a...
Source: Cellular and Molecular Life Sciences : CMLS - June 22, 2016 Category: Cytology Authors: Gupta V, Gupta VB, Chitranshi N, Gangoda S, Vander Wall R, Abbasi M, Golzan M, Dheer Y, Shah T, Avolio A, Chung R, Martins R, Graham S Tags: Cell Mol Life Sci Source Type: research

Absent in melanoma 2 proteins in the development of cancer.
Abstract Recent studies utilizing chemical-induced colitis-associated and sporadic colon cancer in mouse models indicated a protective role for absent in melanoma 2 (Aim2) in colon epithelial cells. Accordingly, mutations in the human AIM2 gene have been found in colorectal cancer (CRC), and reduced expression of AIM2 in CRC is associated with its progression. Furthermore, the overexpression of AIM2 protein in human cancer cell lines inhibits cell proliferation. Interferon-inducible Aim2 and AIM2 are members of the PYHIN (PYRIN and HIN domain-containing) protein family and share ~57 % amino acid identity. The...
Source: Cellular and Molecular Life Sciences : CMLS - June 21, 2016 Category: Cytology Authors: Choubey D Tags: Cell Mol Life Sci Source Type: research

Neuropeptide substance P and the immune response.
Abstract Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an in...
Source: Cellular and Molecular Life Sciences : CMLS - June 17, 2016 Category: Cytology Authors: Mashaghi A, Marmalidou A, Tehrani M, Grace PM, Pothoulakis C, Dana R Tags: Cell Mol Life Sci Source Type: research

A cellular reporter to evaluate CRM1 nuclear export activity: functional analysis of the cancer-related mutant E571K.
S, Rodríguez JA Abstract The exportin CRM1 binds nuclear export signals (NESs), and mediates active transport of NES-bearing proteins from the nucleus to the cytoplasm. Structural and biochemical analyses have uncovered the molecular mechanisms underlying CRM1/NES interaction. CRM1 binds NESs through a hydrophobic cleft, whose open or closed conformation facilitates NES binding and release. Several cofactors allosterically modulate the conformation of the NES-binding cleft through intramolecular interactions involving an acidic loop and a C-terminal helix in CRM1. This current model of CRM1-mediated nuclea...
Source: Cellular and Molecular Life Sciences : CMLS - June 16, 2016 Category: Cytology Authors: García-Santisteban I, Arregi I, Alonso-Mariño M, Urbaneja MA, Garcia-Vallejo JJ, Bañuelos S, Rodríguez JA Tags: Cell Mol Life Sci Source Type: research

Control of Candida albicans morphology and pathogenicity by post-transcriptional mechanisms.
Abstract Candida albicans is a major human fungal pathogen responsible for both systemic and mucosal infections in a wide variety of immunocompromised individuals. Because the ability of C. albicans to undergo a reversible morphological transition from yeast to filaments is important for virulence, significant research efforts have focused on mechanisms that control this transition. While transcriptional and post-translational mechanisms have been well-studied, considerably less is known about the role of post-transcriptional mechanisms. However, in recent years several discoveries have begun to shed light on this...
Source: Cellular and Molecular Life Sciences : CMLS - June 16, 2016 Category: Cytology Authors: Kadosh D Tags: Cell Mol Life Sci Source Type: research

Metabolic control of the proteotoxic stress response: implications in diabetes mellitus and neurodegenerative disorders.
Abstract Proteome homeostasis, or proteostasis, is essential to maintain cellular fitness and its disturbance is associated with a broad range of human health conditions and diseases. Cells are constantly challenged by various extrinsic and intrinsic insults, which perturb cellular proteostasis and provoke proteotoxic stress. To counter proteomic perturbations and preserve proteostasis, cells mobilize the proteotoxic stress response (PSR), an evolutionarily conserved transcriptional program mediated by heat shock factor 1 (HSF1). The HSF1-mediated PSR guards the proteome against misfolding and aggregation. In addi...
Source: Cellular and Molecular Life Sciences : CMLS - June 11, 2016 Category: Cytology Authors: Su KH, Dai C Tags: Cell Mol Life Sci Source Type: research

Asymmetric cell division in plants: mechanisms of symmetry breaking and cell fate determination.
Abstract Asymmetric cell division is a fundamental mechanism that generates cell diversity while maintaining self-renewing stem cell populations in multicellular organisms. Both intrinsic and extrinsic mechanisms underpin symmetry breaking and differential daughter cell fate determination in animals and plants. The emerging picture suggests that plants deal with the problem of symmetry breaking using unique cell polarity proteins, mobile transcription factors, and cell wall components to influence asymmetric divisions and cell fate. There is a clear role for altered auxin distribution and signaling in distinguishi...
Source: Cellular and Molecular Life Sciences : CMLS - June 10, 2016 Category: Cytology Authors: Pillitteri LJ, Guo X, Dong J Tags: Cell Mol Life Sci Source Type: research

Striated muscle function, regeneration, and repair.
Abstract As the only striated muscle tissues in the body, skeletal and cardiac muscle share numerous structural and functional characteristics, while exhibiting vastly different size and regenerative potential. Healthy skeletal muscle harbors a robust regenerative response that becomes inadequate after large muscle loss or in degenerative pathologies and aging. In contrast, the mammalian heart loses its regenerative capacity shortly after birth, leaving it susceptible to permanent damage by acute injury or chronic disease. In this review, we compare and contrast the physiology and regenerative potential of native ...
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2016 Category: Cytology Authors: Shadrin IY, Khodabukus A, Bursac N Tags: Cell Mol Life Sci Source Type: research

Novel nuclear hENT2 isoforms regulate cell cycle progression via controlling nucleoside transport and nuclear reservoir.
a M, Coe IR Abstract Nucleosides participate in many cellular processes and are the fundamental building blocks of nucleic acids. Nucleoside transporters translocate nucleosides across plasma membranes although the mechanism by which nucleos(t)ides are translocated into the nucleus during DNA replication is unknown. Here, we identify two novel functional splice variants of equilibrative nucleoside transporter 2 (ENT2), which are present at the nuclear envelope. Under proliferative conditions, these splice variants are up-regulated and recruit wild-type ENT2 to the nuclear envelope to translocate nucleosides into t...
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2016 Category: Cytology Authors: Grañé-Boladeras N, Spring CM, Hanna WJ, Pastor-Anglada M, Coe IR Tags: Cell Mol Life Sci Source Type: research

Cytokine responses and epithelial function in the intestinal mucosa.
Abstract Inflammatory diseases of mucosal organs are significantly influenced by the microenvironment in which they reside. Cytokines found within this microenvironment contribute significantly to endpoint functions of the mucosa. Studies dating back to the 1990s have revealed that epithelial cells are both a source as well as a target for numerous cytokines and that such signaling can substantially influence the outcome of mucosal disease, such as inflammatory bowel disease. Here, we will review literature regarding intestinal epithelial cells as sources and responders to cytokines found in the intestinal milieu....
Source: Cellular and Molecular Life Sciences : CMLS - June 6, 2016 Category: Cytology Authors: Onyiah JC, Colgan SP Tags: Cell Mol Life Sci Source Type: research

Erratum to: Unique carbohydrate binding platforms employed by the glucan phosphatases.
PMID: 27262704 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - June 4, 2016 Category: Cytology Authors: Emanuelle S, Kathryn Brewer M, Meekins DA, Gentry MS Tags: Cell Mol Life Sci Source Type: research

Evolution of the archaeal and mammalian information processing systems: towards an archaeal model for human disease.
Abstract Current evolutionary models suggest that Eukaryotes originated from within Archaea instead of being a sister lineage. To test this model of ancient evolution, we review recent studies and compare the three major information processing subsystems of replication, transcription and translation in the Archaea and Eukaryotes. Our hypothesis is that if the Eukaryotes arose within the archaeal radiation, their information processing systems will appear to be one of kind and not wholly original. Within the Eukaryotes, the mammalian or human systems are emphasized because of their importance in understanding healt...
Source: Cellular and Molecular Life Sciences : CMLS - June 3, 2016 Category: Cytology Authors: Lyu Z, Whitman WB Tags: Cell Mol Life Sci Source Type: research

Modeling simple repeat expansion diseases with iPSC technology.
Abstract A number of human genetic disorders, including Huntington's disease, myotonic dystrophy type 1, C9ORF72 form of amyotrophic lateral sclerosis and several spinocerebellar ataxias, are caused by the expansion of various microsatellite sequences in single implicated genes. The neurodegenerative and neuromuscular nature of the repeat expansion disorders considerably limits the access of researchers to appropriate cellular models of these diseases. This limitation, however, can be overcome by the application of induced pluripotent stem cell (iPSC) technology. In this paper, we review the current knowledge on t...
Source: Cellular and Molecular Life Sciences : CMLS - June 3, 2016 Category: Cytology Authors: Jaworska E, Kozlowska E, Switonski PM, Krzyzosiak WJ Tags: Cell Mol Life Sci Source Type: research

Erratum to: Controlling the response to DNA damage by the APC/C-Cdh1.
PMID: 27251328 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - June 1, 2016 Category: Cytology Authors: de Boer HR, Llobet SG, van Vugt MA Tags: Cell Mol Life Sci Source Type: research

Synthetic combinations of missense polymorphic genetic changes underlying Down syndrome susceptibility.
Abstract Single nucleotide polymorphisms (SNPs) are important biomolecular markers in health and disease. Down syndrome, or Trisomy 21, is the most frequently occurring chromosomal abnormality in live-born children. Here, we highlight associations between SNPs in several important enzymes involved in the one-carbon folate metabolic pathway and the elevated maternal risk of having a child with Down syndrome. Our survey highlights that the combination of SNPs may be a more reliable predictor of the Down syndrome phenotype than single SNPs alone. We also describe recent links between SNPs in p53 and its related pathw...
Source: Cellular and Molecular Life Sciences : CMLS - May 31, 2016 Category: Cytology Authors: Jackson RA, Nguyen ML, Barrett AN, Tan YY, Choolani MA, Chen ES Tags: Cell Mol Life Sci Source Type: research

Mitochondrial cAMP signaling.
Abstract Cyclic adenosine 3, 5'-monophosphate (cAMP) is a ubiquitous second messenger regulating many biological processes, such as cell migration, differentiation, proliferation and apoptosis. cAMP signaling functions not only on the plasma membrane, but also in the nucleus and in organelles such as mitochondria. Mitochondrial cAMP signaling is an indispensable part of the cytoplasm-mitochondrion crosstalk that maintains mitochondrial homeostasis, regulates mitochondrial dynamics, and modulates cellular stress responses and other signaling pathways. Recently, the compartmentalization of mitochondrial cAMP signali...
Source: Cellular and Molecular Life Sciences : CMLS - May 28, 2016 Category: Cytology Authors: Zhang F, Zhang L, Qi Y, Xu H Tags: Cell Mol Life Sci Source Type: research

A clinical and biological perspective of human myeloid-derived suppressor cells in cancer.
Abstract Considering the large number of studies focused on myeloid-derived suppressor cells (MDSCs) to date, only a handful of well-defined relationships in human cancer have been established. The difficulty of assessing the impact of MDSCs in human cancer is partly due to the relatively small number of studies performed in humans. This is compounded in the literature by a common lack of clear indication of which species is being referred to for each characteristic described. These aspects may result in inappropriate extrapolation of animal studies to those in the human setting. This is especially the case for st...
Source: Cellular and Molecular Life Sciences : CMLS - May 28, 2016 Category: Cytology Authors: Shipp C, Speigl L, Janssen N, Martens A, Pawelec G Tags: Cell Mol Life Sci Source Type: research

Post-translational modifications in mitochondria: protein signaling in the powerhouse.
Abstract There is an intimate interplay between cellular metabolism and the pathophysiology of disease. Mitochondria are essential to maintaining and regulating metabolic function of cells and organs. Mitochondrial dysfunction is implicated in diverse diseases, such as cardiovascular disease, diabetes and metabolic syndrome, neurodegeneration, cancer, and aging. Multiple reversible post-translational protein modifications are located in the mitochondria that are responsive to nutrient availability and redox conditions, and which can act in protein-protein interactions to modify diverse mitochondrial functions. Inc...
Source: Cellular and Molecular Life Sciences : CMLS - May 27, 2016 Category: Cytology Authors: Stram AR, Payne RM Tags: Cell Mol Life Sci Source Type: research

Hes1: the maestro in neurogenesis.
Abstract The process of neurogenesis is well orchestrated by the harmony of multiple cues in a spatiotemporal manner. In this review, we focus on how a dynamic gene, Hes1, is involved in neurogenesis with the view of its regulation and functional implications. Initially, we have reviewed the immense functional significance drawn by this maestro during neural development in a context-dependent manner. How this indispensable role of Hes1 in conferring the competency for neural differentiation partly relies on the direct/indirect mode of repression mediated by very specific structural and functional arms of this prot...
Source: Cellular and Molecular Life Sciences : CMLS - May 27, 2016 Category: Cytology Authors: Dhanesh SB, Subashini C, James J Tags: Cell Mol Life Sci Source Type: research

Axonal localization and mitochondrial association of precursor microRNA 338.
In this study, we investigated the axonal localization of pre-miR-338. Using proteomic and biochemical approaches, we provide evidence for the localization of pre-miR-338 to distal neuronal compartments and identify several constituents of the pre-miR-338 ribonucleoprotein complex. Furthermore, we found that pre-miR-338 is associated with the mitochondria in axons of superior cervical ganglion (SCG) neurons. The maintenance of mitochondrial function within axons requires the precise spatiotemporal synthesis of nuclear-encoded mRNAs, some of which are regulated by miR-338. Therefore, the association of pre-miR-338 with axon...
Source: Cellular and Molecular Life Sciences : CMLS - May 26, 2016 Category: Cytology Authors: Vargas JN, Kar AN, Kowalak JA, Gale JR, Aschrafi A, Chen CY, Gioio AE, Kaplan BB Tags: Cell Mol Life Sci Source Type: research

A structural perspective of RNA recognition by intrinsically disordered proteins.
Abstract Protein-RNA recognition is essential for gene expression and its regulation, which is indispensable for the survival of the living organism at one hand, on the other hand, misregulation of this recognition may lead to their extinction. Polymorphic conformation of both the interacting partners is a characteristic feature of such molecular recognition that promotes the assembly. Many RNA binding proteins (RBP) or regions in them are found to be intrinsically disordered, and this property helps them to play a central role in the regulatory processes. Sequence composition and the length of the flexible linker...
Source: Cellular and Molecular Life Sciences : CMLS - May 26, 2016 Category: Cytology Authors: Basu S, Bahadur RP Tags: Cell Mol Life Sci Source Type: research

Vitamin D interferes with glucocorticoid responsiveness in human peripheral blood mononuclear target cells.
Vitamin D interferes with glucocorticoid responsiveness in human peripheral blood mononuclear target cells. Cell Mol Life Sci. 2016 May 24; Authors: Kassi E, Nasiri-Ansari N, Spilioti E, Kalotychou V, Apostolou PE, Moutsatsou P, Papavassiliou AG Abstract Glucocorticoids (GCs) are widely used in the treatment of inflammatory and autoimmune diseases; however, patients are often resistant to GC effects. Current studies indicate that vitamin D reduces the risk or modifies the course of autoimmune diseases posing vitamin D supplementation as a prevention or therapeutic option. Herein, we investigated ...
Source: Cellular and Molecular Life Sciences : CMLS - May 24, 2016 Category: Cytology Authors: Kassi E, Nasiri-Ansari N, Spilioti E, Kalotychou V, Apostolou PE, Moutsatsou P, Papavassiliou AG Tags: Cell Mol Life Sci Source Type: research

SWI/SNF-directed stem cell lineage specification: dynamic composition regulates specific stages of skeletal myogenesis.
Abstract SWI/SNF chromatin-remodeling complexes are key regulators of the epigenetic modifications that determine whether stem cells maintain pluripotency or commit toward specific lineages through development and during postnatal life. Dynamic combinatorial assembly of multiple variants of SWI/SNF subunits is emerging as the major determinant of the functional versatility of SWI/SNF. Here, we summarize the current knowledge on the structural and functional properties of the alternative SWI/SNF complexes that direct stem cell fate toward skeletal muscle lineage and control distinct stages of skeletal myogenesis. I...
Source: Cellular and Molecular Life Sciences : CMLS - May 20, 2016 Category: Cytology Authors: Toto PC, Puri PL, Albini S Tags: Cell Mol Life Sci Source Type: research

A single point in protein trafficking by Plasmodium falciparum determines the expression of major antigens on the surface of infected erythrocytes targeted by human antibodies.
Abstract Antibodies to blood-stage antigens of Plasmodium falciparum play a pivotal role in human immunity to malaria. During parasite development, multiple proteins are trafficked from the intracellular parasite to the surface of P. falciparum-infected erythrocytes (IEs). However, the relative importance of different proteins as targets of acquired antibodies, and key pathways involved in trafficking major antigens remain to be clearly defined. We quantified antibodies to surface antigens among children, adults, and pregnant women from different malaria-exposed regions. We quantified the importance of antigens as...
Source: Cellular and Molecular Life Sciences : CMLS - May 19, 2016 Category: Cytology Authors: Chan JA, Howell KB, Langer C, Maier AG, Hasang W, Rogerson SJ, Petter M, Chesson J, Stanisic DI, Duffy MF, Cooke BM, Siba PM, Mueller I, Bull PC, Marsh K, Fowkes FJ, Beeson JG Tags: Cell Mol Life Sci Source Type: research

Inhibitory interneurons in visual cortical plasticity.
Abstract For proper maturation of the neocortex and acquisition of specific functions and skills, exposure to sensory stimuli is vital during critical periods of development when synaptic connectivity is highly malleable. To preserve reliable cortical processing, it is essential that these critical periods end after which learning becomes more conditional and active interaction with the environment becomes more important. How these age-dependent forms of plasticity are regulated has been studied extensively in the primary visual cortex. This has revealed that inhibitory innervation plays a crucial role and that a ...
Source: Cellular and Molecular Life Sciences : CMLS - May 18, 2016 Category: Cytology Authors: van Versendaal D, Levelt CN Tags: Cell Mol Life Sci Source Type: research

Polyglutamine androgen receptor-mediated neuromuscular disease.
Abstract An expanded polyglutamine (polyQ) tract at the amino-terminus of the androgen receptor (AR) confers toxic properties responsible for neuronal and non-neuronal degeneration in spinal and bulbar muscular atrophy (SBMA), one of nine polyQ expansion diseases. Both lower motor neurons and peripheral tissues, including skeletal muscle, are affected, supporting the notion that SBMA is not a pure motor neuron disease but a degenerative disorder of the neuromuscular system. Here, we review experimental evidence demonstrating both nerve and muscle degeneration in SBMA model systems and patients. We propose that pol...
Source: Cellular and Molecular Life Sciences : CMLS - May 17, 2016 Category: Cytology Authors: Giorgetti E, Lieberman AP Tags: Cell Mol Life Sci Source Type: research

Stress transgenerationally programs metabolic pathways linked to altered mental health.
Abstract Stress is among the primary causes of mental health disorders, which are the most common reason for disability worldwide. The ubiquity of these disorders, and the costs associated with them, lends a sense of urgency to the efforts to improve prediction and prevention. Down-stream metabolic changes are highly feasible and accessible indicators of pathophysiological processes underlying mental health disorders. Here, we show that remote and cumulative ancestral stress programs central metabolic pathways linked to mental health disorders. The studies used a rat model consisting of a multigenerational stress ...
Source: Cellular and Molecular Life Sciences : CMLS - May 17, 2016 Category: Cytology Authors: Kiss D, Ambeskovic M, Montina T, Metz GA Tags: Cell Mol Life Sci Source Type: research

Transition from inflammation to proliferation: a critical step during wound healing.
ring;hle M Abstract The ability to rapidly restore the integrity of a broken skin barrier is critical and is the ultimate goal of therapies for hard-to-heal-ulcers. Unfortunately effective treatments to enhance healing and reduce scarring are still lacking. A deeper understanding of the physiology of normal repair and of the pathology of delayed healing is a prerequisite for the development of more effective therapeutic interventions. Transition from the inflammatory to the proliferative phase is a key step during healing and accumulating evidence associates a compromised transition with wound healing disorders. T...
Source: Cellular and Molecular Life Sciences : CMLS - May 14, 2016 Category: Cytology Authors: Landén NX, Li D, Ståhle M Tags: Cell Mol Life Sci Source Type: research

Roles of extracellular nucleotides and P2 receptors in ectodomain shedding.
Abstract Ectodomain shedding of integral membrane receptors results in the release of soluble molecules and modification of the transmembrane portions to mediate or modulate extracellular and intracellular signalling. Ectodomain shedding is stimulated by a variety of mechanisms, including the activation of P2 receptors by extracellular nucleotides. This review describes in detail the roles of extracellular nucleotides and P2 receptors in the shedding of various cell surface molecules, including amyloid precursor protein, CD23, CD62L, and members of the epidermal growth factor, immunoglobulin and tumour necrosis fa...
Source: Cellular and Molecular Life Sciences : CMLS - May 14, 2016 Category: Cytology Authors: Pupovac A, Sluyter R Tags: Cell Mol Life Sci Source Type: research

Golden Gate Assembly of CRISPR gRNA expression array for simultaneously targeting multiple genes.
Abstract The engineered CRISPR/Cas9 technology has developed as the most efficient and broadly used genome editing tool. However, simultaneously targeting multiple genes (or genomic loci) in the same individual cells using CRISPR/Cas9 remain one technical challenge. In this article, we have developed a Golden Gate Assembly method for the generation of CRISPR gRNA expression arrays, thus enabling simultaneous gene targeting. Using this method, the generation of CRISPR gRNA expression array can be accomplished in 2 weeks, and contains up to 30 gRNA expression cassettes. We demonstrated in the study that si...
Source: Cellular and Molecular Life Sciences : CMLS - May 13, 2016 Category: Cytology Authors: Vad-Nielsen J, Lin L, Bolund L, Nielsen AL, Luo Y Tags: Cell Mol Life Sci Source Type: research

Starch-degrading polysaccharide monooxygenases.
Abstract Polysaccharide degradation by hydrolytic enzymes glycoside hydrolases (GHs) is well known. More recently, polysaccharide monooxygenases (PMOs, also known as lytic PMOs or LPMOs) were found to oxidatively degrade various polysaccharides via a copper-dependent hydroxylation. PMOs were previously thought to be either GHs or carbohydrate binding modules (CBMs), and have been re-classified in carbohydrate active enzymes (CAZY) database as auxiliary activity (AA) families. These enzymes include cellulose-active fungal PMOs (AA9, formerly GH61), chitin- and cellulose-active bacterial PMOs (AA10, formerly CBM33),...
Source: Cellular and Molecular Life Sciences : CMLS - May 12, 2016 Category: Cytology Authors: Vu VV, Marletta MA Tags: Cell Mol Life Sci Source Type: research

Liposarcoma: molecular targets and therapeutic implications.
Abstract Liposarcoma (LPS) is the most common soft tissue sarcoma and accounts for approximately 20 % of all adult sarcomas. Current treatment modalities (surgery, chemotherapy, and radiotherapy) all have limitations; therefore, molecularly driven studies are needed to improve the identification and increased understanding of genetic and epigenetic deregulations in LPS if we are to successfully target specific tumorigenic drivers. It can be anticipated that such biology-driven therapeutics will improve treatments by selectively deleting cancer cells while sparing normal tissues. This review will focus on seve...
Source: Cellular and Molecular Life Sciences : CMLS - May 12, 2016 Category: Cytology Authors: Bill KL, Casadei L, Prudner BC, Iwenofu H, Strohecker AM, Pollock RE Tags: Cell Mol Life Sci Source Type: research

mTORC1-S6K1 inhibition or mTORC2 activation improves hippocampal synaptic plasticity and learning in Angelman syndrome mice.
Abstract Emerging evidence is implicating abnormal activation of the mechanistic target of rapamycin (mTOR) pathway in several monogenetic neuropsychiatric disorders, including Angelman syndrome (AS), which is caused by deficiency in maternally inherited UBE3A. Using an AS mouse model, we show that semi-chronic rapamycin treatment improves long-term potentiation (LTP) and actin polymerization in hippocampal slices, spine morphology, and fear-conditioning learning. Activity of mTORC1 and of its downstream substrate, S6K1, was increased in hippocampus of AS mice. However, mTORC2 activity, as reflected by PKCα ...
Source: Cellular and Molecular Life Sciences : CMLS - May 12, 2016 Category: Cytology Authors: Sun J, Liu Y, Tran J, O'Neal P, Baudry M, Bi X Tags: Cell Mol Life Sci Source Type: research

Free fatty acid G-protein coupled receptor signaling in M1 skewed white adipose tissue macrophages.
Abstract Obesity is associated with the establishment and maintenance of a low grade, chronically inflamed state in the white adipose tissue (WAT) of the body. The WAT macrophage population is a major cellular participant in this inflammatory process that significantly contributes to the pathophysiology of the disease, with the adipose depots of obese individuals, relative to lean counterparts, having an elevated number of macrophages that are skewed towards a pro-inflammatory phenotype. Alterations in the WAT lipid micro-environment, and specifically the availability of free fatty acids, are believed to contribut...
Source: Cellular and Molecular Life Sciences : CMLS - May 12, 2016 Category: Cytology Authors: Vieira WA, Sadie-Van Gijsen H, Ferris WF Tags: Cell Mol Life Sci Source Type: research

Formation of starch in plant cells.
Abstract Starch-rich crops form the basis of our nutrition, but plants have still to yield all their secrets as to how they make this vital substance. Great progress has been made by studying both crop and model systems, and we approach the point of knowing the enzymatic machinery responsible for creating the massive, insoluble starch granules found in plant tissues. Here, we summarize our current understanding of these biosynthetic enzymes, highlighting recent progress in elucidating their specific functions. Yet, in many ways we have only scratched the surface: much uncertainty remains about how these components...
Source: Cellular and Molecular Life Sciences : CMLS - May 11, 2016 Category: Cytology Authors: Pfister B, Zeeman SC Tags: Cell Mol Life Sci Source Type: research

Hepatitis B virus inhibits insulin receptor signaling and impairs liver regeneration via intracellular retention of the insulin receptor.
This study aims to investigate the impact of HBV on liver regeneration and hepatic insulin receptor signaling. After carbon tetrachloride-induced liver injury, liver regeneration is delayed in HBV transgenic mice. These mice show diminished hepatocyte proliferation and increased expression of fibrosis markers. This is in accordance with a reduced activation of the insulin receptor although HBV induces expression of the insulin receptor via activation of NF-E2-related factor 2. This leads to increased intracellular amounts of insulin receptor in HBV expressing hepatocytes. However, intracellular retention of the receptor si...
Source: Cellular and Molecular Life Sciences : CMLS - May 7, 2016 Category: Cytology Authors: Barthel SR, Medvedev R, Heinrich T, Büchner SM, Kettern N, Hildt E Tags: Cell Mol Life Sci Source Type: research

Quality control of chemically damaged RNA.
Abstract The "central dogma" of molecular biology describes how information contained in DNA is transformed into RNA and finally into proteins. In order for proteins to maintain their functionality in both the parent cell and subsequent generations, it is essential that the information encoded in DNA and RNA remains unaltered. DNA and RNA are constantly exposed to damaging agents, which can modify nucleic acids and change the information they encode. While much is known about how cells respond to damaged DNA, the importance of protecting RNA has only become appreciated over the past decade. Modification ...
Source: Cellular and Molecular Life Sciences : CMLS - May 7, 2016 Category: Cytology Authors: Simms CL, Zaher HS Tags: Cell Mol Life Sci Source Type: research

Structure-function relationships of family GH70 glucansucrase and 4,6-α-glucanotransferase enzymes, and their evolutionary relationships with family GH13 enzymes.
Structure-function relationships of family GH70 glucansucrase and 4,6-α-glucanotransferase enzymes, and their evolutionary relationships with family GH13 enzymes. Cell Mol Life Sci. 2016 May 7; Authors: Meng X, Gangoiti J, Bai Y, Pijning T, Van Leeuwen SS, Dijkhuizen L Abstract Lactic acid bacteria (LAB) are known to produce large amounts of α-glucan exopolysaccharides. Family GH70 glucansucrase (GS) enzymes catalyze the synthesis of these α-glucans from sucrose. The elucidation of the crystal structures of representative GS enzymes has advanced our understanding of their reaction me...
Source: Cellular and Molecular Life Sciences : CMLS - May 7, 2016 Category: Cytology Authors: Meng X, Gangoiti J, Bai Y, Pijning T, Van Leeuwen SS, Dijkhuizen L Tags: Cell Mol Life Sci Source Type: research

Modeling head and neck cancer stem cell-mediated tumorigenesis.
JE Abstract A large body of literature has emerged supporting the importance of cancer stem cells (CSCs) in the pathogenesis of head and neck cancers. CSCs are a subpopulation of cells within a tumor that share the properties of self-renewal and multipotency with stem cells from normal tissue. Their functional relevance to the pathobiology of cancer arises from the unique properties of tumorigenicity, chemotherapy resistance, and their ability to metastasize and invade distant tissues. Several molecular profiles have been used to discriminate a stem cell from a non-stem cell. CSCs can be grown for study and furth...
Source: Cellular and Molecular Life Sciences : CMLS - May 5, 2016 Category: Cytology Authors: Pearson AT, Jackson TL, Nör JE Tags: Cell Mol Life Sci Source Type: research