microRNA-122 target sites in the hepatitis C virus RNA NS5B coding region and 3' untranslated region: function in replication and influence of RNA secondary structure.
Niepmann M Abstract We have analyzed the binding of the liver-specific microRNA-122 (miR-122) to three conserved target sites of hepatitis C virus (HCV) RNA, two in the non-structural protein 5B (NS5B) coding region and one in the 3' untranslated region (3'UTR). miR-122 binding efficiency strongly depends on target site accessibility under conditions when the range of flanking sequences available for the formation of local RNA secondary structures changes. Our results indicate that the particular sequence feature that contributes most to the correlation between target site accessibility and binding strength varie...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2016 Category: Cytology Authors: Gerresheim GK, Dünnes N, Nieder-Röhrmann A, Shalamova LA, Fricke M, Hofacker I, Höner Zu Siederdissen C, Marz M, Niepmann M Tags: Cell Mol Life Sci Source Type: research

Regulation of mRNA decay in plant responses to salt and osmotic stress.
Abstract Plant acclimation to environmental stresses requires fast signaling to initiate changes in developmental and metabolic responses. Regulation of gene expression by transcription factors and protein kinases acting upstream are important elements of responses to salt and drought. Gene expression can be also controlled at the post-transcriptional level. Recent analyses on mutants in mRNA metabolism factors suggest their contribution to stress signaling. Here we highlight the components of mRNA decay pathways that contribute to responses to osmotic and salt stress. We hypothesize that phosphorylation state of ...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2016 Category: Cytology Authors: Kawa D, Testerink C Tags: Cell Mol Life Sci Source Type: research

Heritability of targeted gene modifications induced by plant-optimized CRISPR systems.
Abstract The Streptococcus-derived CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 (CRISPR-associated protein 9) system has emerged as a very powerful tool for targeted gene modifications in many living organisms including plants. Since the first application of this system for plant gene modification in 2013, this RNA-guided DNA endonuclease system has been extensively engineered to meet the requirements of functional genomics and crop trait improvement in a number of plant species. Given its short history, the emphasis of many studies has been the optimization of the technology to improve ...
Source: Cellular and Molecular Life Sciences : CMLS - September 27, 2016 Category: Cytology Authors: Mao Y, Botella JR, Zhu JK Tags: Cell Mol Life Sci Source Type: research

Assessing heterogeneity in oligomeric AAA+  machines.
Assessing heterogeneity in oligomeric AAA+ machines. Cell Mol Life Sci. 2016 Sep 26; Authors: Sysoeva TA Abstract ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanic...
Source: Cellular and Molecular Life Sciences : CMLS - September 26, 2016 Category: Cytology Authors: Sysoeva TA Tags: Cell Mol Life Sci Source Type: research

Profilin1 biology and its mutation, actin(g) in disease.
Abstract Profilins were discovered in the 1970s and were extensively studied for their significant physiological roles. Profilin1 is the most prominent isoform and has drawn special attention due to its role in the cytoskeleton, cell signaling, and its link to conditions such as cancer and vascular hypertrophy. Recently, multiple mutations in the profilin1 gene were linked to amyotrophic lateral sclerosis (ALS). In this review, we will discuss the physiological and pathological roles of profilin1. We will further highlight the cytoskeletal function and dysfunction caused by profilin1 dysregulation. Finally, we wil...
Source: Cellular and Molecular Life Sciences : CMLS - September 26, 2016 Category: Cytology Authors: Alkam D, Feldman EZ, Singh A, Kiaei M Tags: Cell Mol Life Sci Source Type: research

Mechanisms of ciliogenesis suppression in dividing cells.
Abstract The primary cilium is a non-motile and microtubule-enriched protrusion ensheathed by plasma membrane. Primary cilia function as mechano/chemosensors and signaling hubs and their disorders predispose to a wide spectrum of human diseases. Most types of cells assemble their primary cilia in response to cellular quiescence, whereas they start to retract the primary cilia upon cell-cycle reentry. The retardation of ciliary resorption process has been shown to delay cell-cycle progression to the S or M phase after cell-cycle reentry. Apart from this conventional concept of ciliary disassembly linked to cell-cyc...
Source: Cellular and Molecular Life Sciences : CMLS - September 26, 2016 Category: Cytology Authors: Goto H, Inaba H, Inagaki M Tags: Cell Mol Life Sci Source Type: research

Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells.
Abstract At sites of inflammation and tumor growth, the local concentration of extracellular adenosine rapidly increases and plays a role in controlling the immune responses of nearby cells. Adenosine deaminases ADA1 and ADA2 (ADAs) decrease the level of adenosine by converting it to inosine, which serves as a negative feedback mechanism. Mutations in the genes encoding ADAs lead to impaired immune function, which suggests a crucial role for ADAs in immune system regulation. It is not clear why humans and other mammals possess two enzymes with adenosine deaminase activity. Here, we found that ADA2 binds to neutrop...
Source: Cellular and Molecular Life Sciences : CMLS - September 23, 2016 Category: Cytology Authors: Kaljas Y, Liu C, Skaldin M, Wu C, Zhou Q, Lu Y, Aksentijevich I, Zavialov AV Tags: Cell Mol Life Sci Source Type: research

P2Y2 receptor modulates shear stress-induced cell alignment and actin stress fibers in human umbilical vein endothelial cells.
e D Abstract Endothelial cells release ATP in response to fluid shear stress, which activates purinergic (P2) receptor-mediated signaling molecules including endothelial nitric oxide (eNOS), a regulator of vascular tone. While P2 receptor-mediated signaling in the vasculature is well studied, the role of P2Y2 receptors in shear stress-associated endothelial cell alignment, cytoskeletal alterations, and wound repair remains ill defined. To address these aspects, human umbilical vein endothelial cell (HUVEC) monolayers were cultured on gelatin-coated dishes and subjected to a shear stress of 1 Pa. HUVECs expose...
Source: Cellular and Molecular Life Sciences : CMLS - September 20, 2016 Category: Cytology Authors: Sathanoori R, Bryl-Gorecka P, Müller CE, Erb L, Weisman GA, Olde B, Erlinge D Tags: Cell Mol Life Sci Source Type: research

A historical and evolutionary perspective on the biological significance of circulating DNA and extracellular vesicles.
Abstract The discovery of quantitative and qualitative differences of the circulating DNA (cirDNA) between healthy and diseased individuals inclined researchers to investigate these molecules as potential biomarkers for non-invasive diagnosis and prognosis of various pathologies. However, except for some prenatal tests, cirDNA analyses have not been readily translated to clinical practice due to a lack of knowledge regarding its composition, function, and biological and evolutionary origins. We believe that, to fully grasp the nature of cirDNA and the extracellular vesicles (EVs) and protein complexes with which i...
Source: Cellular and Molecular Life Sciences : CMLS - September 20, 2016 Category: Cytology Authors: Aucamp J, Bronkhorst AJ, Badenhorst CP, Pretorius PJ Tags: Cell Mol Life Sci Source Type: research

Modulation of Kv7 channels and excitability in the brain.
Abstract Neuronal Kv7 channels underlie a voltage-gated non-inactivating potassium current known as the M-current. Due to its particular characteristics, Kv7 channels show pronounced control over the excitability of neurons. We will discuss various factors that have been shown to drastically alter the activity of this channel such as protein and phospholipid interactions, phosphorylation, calcium, and numerous neurotransmitters. Kv7 channels locate to key areas for the control of action potential initiation and propagation. Moreover, we will explore the dynamic surface expression of the channel modulated by neurot...
Source: Cellular and Molecular Life Sciences : CMLS - September 19, 2016 Category: Cytology Authors: Greene DL, Hoshi N Tags: Cell Mol Life Sci Source Type: research

Regulation of antibody effector functions through IgG Fc N-glycosylation.
JD Abstract Immunoglobulin gamma (IgG) antibodies are key effector proteins of the immune system. They recognize antigens with high specificity and are indispensable for immunological memory following pathogen exposure or vaccination. The constant, crystallizable fragment (Fc) of IgG molecules mediates antibody effector functions such as complement-dependent cytotoxicity, antibody-mediated cellular cytotoxicity, and antibody-dependent cell-mediated phagocytosis. These functions are regulated by a single N-linked, biantennary glycan of the heavy chain, which resides just below the hinge region, and the presence of...
Source: Cellular and Molecular Life Sciences : CMLS - September 17, 2016 Category: Cytology Authors: Quast I, Peschke B, Lünemann JD Tags: Cell Mol Life Sci Source Type: research

Schwann cell mitochondria as key regulators in the development and maintenance of peripheral nerve axons.
Abstract Formation of myelin sheaths by Schwann cells (SCs) enables rapid and efficient transmission of action potentials in peripheral axons, and disruption of myelination results in disorders that involve decreased sensory and motor functions. Given that construction of SC myelin requires high levels of lipid and protein synthesis, mitochondria, which are pivotal in cellular metabolism, may be potential regulators of the formation and maintenance of SC myelin. Supporting this notion, abnormal mitochondria are found in SCs of neuropathic peripheral nerves in both human patients and the relevant animal models. How...
Source: Cellular and Molecular Life Sciences : CMLS - September 16, 2016 Category: Cytology Authors: Ino D, Iino M Tags: Cell Mol Life Sci Source Type: research

Epigenetic dysregulation of brainstem nuclei in the pathogenesis of Alzheimer's disease: looking in the correct place at the right time?
Abstract Even though the etiology of Alzheimer's disease (AD) remains unknown, it is suggested that an interplay among genetic, epigenetic and environmental factors is involved. An increasing body of evidence pinpoints that dysregulation in the epigenetic machinery plays a role in AD. Recent developments in genomic technologies have allowed for high throughput interrogation of the epigenome, and epigenome-wide association studies have already identified unique epigenetic signatures for AD in the cortex. Considerable evidence suggests that early dysregulation in the brainstem, more specifically in the raphe nuclei ...
Source: Cellular and Molecular Life Sciences : CMLS - September 14, 2016 Category: Cytology Authors: Iatrou A, Kenis G, Rutten BP, Lunnon K, van den Hove DL Tags: Cell Mol Life Sci Source Type: research

Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4.
Abstract P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-&ka...
Source: Cellular and Molecular Life Sciences : CMLS - September 14, 2016 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, Oude Elferink RP, Paulusma CC Tags: Cell Mol Life Sci Source Type: research

Molecular pathways driving disease-specific alterations of intestinal epithelial cells.
eya I Abstract Due to the fact that chronic inflammation as well as tumorigenesis in the gut is crucially impacted by the fate of intestinal epithelial cells, our article provides a comprehensive overview of the composition, function, regulation and homeostasis of the gut epithelium. In particular, we focus on those aspects which were found to be altered in the context of inflammatory bowel diseases or colorectal cancer and also discuss potential molecular targets for a disease-specific therapeutic intervention. PMID: 27624395 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - September 13, 2016 Category: Cytology Authors: López-Posadas R, Neurath MF, Atreya I Tags: Cell Mol Life Sci Source Type: research

Dicer generates a regulatory microRNA network in smooth muscle cells that limits neointima formation during vascular repair.
Abstract MicroRNAs (miRNAs) coordinate vascular repair by regulating injury-induced gene expression in vascular smooth muscle cells (SMCs) and promote the transition of SMCs from a contractile to a proliferating phenotype. However, the effect of miRNA expression in SMCs on neointima formation is unclear. Therefore, we studied the role of miRNA biogenesis by Dicer in SMCs in vascular repair. Following wire-induced injury to carotid arteries of Apolipoprotein E knockout (Apoe (-/-)) mice, miRNA microarray analysis revealed that the most significantly regulated miRNAs, such as miR-222 and miR-21-3p, were upregulated....
Source: Cellular and Molecular Life Sciences : CMLS - September 12, 2016 Category: Cytology Authors: Zahedi F, Nazari-Jahantigh M, Zhou Z, Subramanian P, Wei Y, Grommes J, Offermanns S, Steffens S, Weber C, Schober A Tags: Cell Mol Life Sci Source Type: research

Multidrug-resistant cancer cells and cancer stem cells hijack cellular systems to circumvent systemic therapies, can natural products reverse this?
Abstract Chemotherapy is one of the most effective and broadly used approaches for cancer management and many modern regimes can eliminate the bulk of the cancer cells. However, recurrence and metastasis still remain a major obstacle leading to the failure of systemic cancer treatments. Therefore, to improve the long-term eradication of cancer, the cellular and molecular pathways that provide targets which play crucial roles in drug resistance should be identified and characterised. Multidrug resistance (MDR) and the existence of tumor-initiating cells, also referred to as cancer stem cells (CSCs), are two major c...
Source: Cellular and Molecular Life Sciences : CMLS - September 12, 2016 Category: Cytology Authors: Zhang Q, Feng Y, Kennedy D Tags: Cell Mol Life Sci Source Type: research

DNA repair mechanisms in embryonic stem cells.
Abstract Embryonic stem cells (ESCs) can undergo unlimited self-renewal and retain the pluripotency to differentiate into all cell types in the body. Therefore, as a renewable source of various functional cells in the human body, ESCs hold great promise for human cell therapy. During the rapid proliferation of ESCs in culture, DNA damage, such as DNA double-stranded breaks, will occur in ESCs. Therefore, to realize the potential of ESCs in human cell therapy, it is critical to understand the mechanisms how ESCs activate DNA damage response and DNA repair to maintain genomic stability, which is a prerequisite for t...
Source: Cellular and Molecular Life Sciences : CMLS - September 10, 2016 Category: Cytology Authors: Fu X, Cui K, Yi Q, Yu L, Xu Y Tags: Cell Mol Life Sci Source Type: research

SUMOylation regulates the intracellular fate of ZO-2.
r O Abstract The zonula occludens (ZO)-2 protein links tight junctional transmembrane proteins to the actin cytoskeleton and associates with splicing and transcription factors in the nucleus. Multiple posttranslational modifications control the intracellular distribution of ZO-2. Here, we report that ZO-2 is a target of the SUMOylation machinery and provide evidence on how this modification may affect its cellular distribution and function. We show that ZO-2 associates with the E2 SUMO-conjugating enzyme Ubc9 and with SUMO-deconjugating proteases SENP1 and SENP3. In line with this, modification of ZO-2 by endogeno...
Source: Cellular and Molecular Life Sciences : CMLS - September 7, 2016 Category: Cytology Authors: Wetzel F, Mittag S, Cano-Cortina M, Wagner T, Krämer OH, Niedenthal R, Gonzalez-Mariscal L, Huber O Tags: Cell Mol Life Sci Source Type: research

Biochemical alterations in the oocyte in support of early embryonic development.
Abstract Notwithstanding the enormous reproductive potential encapsulated within a mature mammalian oocyte, these cells present only a limited window for fertilization before defaulting to an apoptotic cascade known as post-ovulatory oocyte aging. The only cell with the capacity to rescue this potential is the fertilizing spermatozoon. Indeed, the union of these cells sets in train a remarkable series of events that endows the oocyte with the capacity to divide and differentiate into the trillions of cells that comprise a new individual. Traditional paradigms hold that, beyond the initial stimulation of fluctuatin...
Source: Cellular and Molecular Life Sciences : CMLS - September 7, 2016 Category: Cytology Authors: Martin JH, Bromfield EG, John Aitken R, Nixon B Tags: Cell Mol Life Sci Source Type: research

Silencing transposable elements in the Drosophila germline.
Abstract Transposable elements or transposons are DNA pieces that can move around within the genome and are, therefore, potential threat to genome stability and faithful transmission of the genetic information in the germline. Accordingly, self-defense mechanisms have evolved in the metazoan germline to silence transposons, and the primary mechanism requires the germline-specific non-coding small RNAs, named Piwi-interacting RNA (piRNAs), which are in complex with Argonaute family of PIWI proteins (the piRNA-RISC complexes), to silence transposons. piRNA-mediated transposon silencing occurs at both transcriptional...
Source: Cellular and Molecular Life Sciences : CMLS - September 6, 2016 Category: Cytology Authors: Yang F, Xi R Tags: Cell Mol Life Sci Source Type: research

Back to the tubule: microtubule dynamics in Parkinson's disease.
vey K Abstract Cytoskeletal homeostasis is essential for the development, survival and maintenance of an efficient nervous system. Microtubules are highly dynamic polymers important for neuronal growth, morphology, migration and polarity. In cooperation with several classes of binding proteins, microtubules regulate long-distance intracellular cargo trafficking along axons and dendrites. The importance of a delicate interplay between cytoskeletal components is reflected in several human neurodegenerative disorders linked to abnormal microtubule dynamics, including Parkinson's disease (PD). Mounting evidence now su...
Source: Cellular and Molecular Life Sciences : CMLS - September 6, 2016 Category: Cytology Authors: Pellegrini L, Wetzel A, Grannó S, Heaton G, Harvey K Tags: Cell Mol Life Sci Source Type: research

Death receptor 3 mediates necroptotic cell death.
Abstract Death receptor 3 (DR3) was initially identified as a T cell co-stimulatory and pro-inflammatory molecule, but further studies revealed a more complex role of DR3 and its ligand TL1A. Although being a death receptor, DR3 gained to date predominantly attention as a contributor to inflammation-driven diseases. In our study, we investigated the cell death pathways associated with DR3. We show that in addition to apoptosis, DR3 can robustly trigger necroptotic cell death and provide evidence for TL1A-induced, DR3-mediated necrosome assembly. DR3-mediated necroptosis critically depends on receptor-interacting p...
Source: Cellular and Molecular Life Sciences : CMLS - September 3, 2016 Category: Cytology Authors: Bittner S, Knoll G, Ehrenschwender M Tags: Cell Mol Life Sci Source Type: research

The ubiquitin-proteasome system and chromosome 17 in cerebellar granule cells and medulloblastoma subgroups.
Abstract Chromosome 17 abnormalities are often observed in medulloblastomas (MBs), particularly those classified in the consensus Groups 3 and 4. Herein we review MB signature genes associated with chromosome 17 and the relationship of these signature genes to the ubiquitin-proteasome system. While clinical investigators have not focused on the ubiquitin-proteasome system in relation to MB, a substantial amount of data on the topic has been hidden in the form of supplemental datasets of gene expression. A supplemental dataset associated with the Thompson classification of MBs shows that a subgroup of MB with 17p d...
Source: Cellular and Molecular Life Sciences : CMLS - September 3, 2016 Category: Cytology Authors: Vriend J, Marzban H Tags: Cell Mol Life Sci Source Type: research

Preparing the lethal hit: interplay between exo- and endocytic pathways in cytotoxic T lymphocytes.
Abstract Cytotoxic T lymphocytes patrol our body in search for infected cells which they kill through the release of cytotoxic substances contained in cytotoxic granules. The fusion of cytotoxic granules occurs at a specially formed contact site, the immunological synapse, and is tightly controlled to ensure specificity. In this review, we discuss the contribution of two intracellular compartments, endosomes and cytotoxic granules, to the formation, function and disassembly of the immunological synapse. We highlight a recently proposed sequential process of fusion events at the IS upon target cell recognition. Fir...
Source: Cellular and Molecular Life Sciences : CMLS - September 1, 2016 Category: Cytology Authors: Chang HF, Bzeih H, Chitirala P, Ravichandran K, Sleiman M, Krause E, Hahn U, Pattu V, Rettig J Tags: Cell Mol Life Sci Source Type: research

How cancer cells dictate their microenvironment: present roles of extracellular vesicles.
Abstract Intercellular communication plays an important role in cancer initiation and progression through secretory molecules, including growth factors and cytokines. Recent advances have revealed that small membrane vesicles, termed extracellular vesicles (EVs), served as a regulatory agent in the intercellular communication of cancer. EVs enable the transfer of functional molecules, including proteins, mRNA and microRNAs (miRNAs), into recipient cells. Cancer cells utilize EVs to dictate the unique phenotype of surrounding cells, thereby promoting cancer progression. Against such "education" by cancer ...
Source: Cellular and Molecular Life Sciences : CMLS - August 31, 2016 Category: Cytology Authors: Naito Y, Yoshioka Y, Yamamoto Y, Ochiya T Tags: Cell Mol Life Sci Source Type: research

Age-related macular degeneration, glaucoma and Alzheimer's disease: amyloidogenic diseases with the same glymphatic background?
PMID: 27572287 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - August 29, 2016 Category: Cytology Authors: Wostyn P, De Groot V, Van Dam D, Audenaert K, Killer HE, De Deyn PP Tags: Cell Mol Life Sci Source Type: research

Endothelial epsins as regulators and potential therapeutic targets of tumor angiogenesis.
Abstract VEGF-driven tumor angiogenesis has been validated as a central target in several tumor types deserving of continuous and further considerations to improve the efficacy and selectivity of the current therapeutic paradigms. Epsins, a family of endocytic clathrin adaptors, have been implicated in regulating endothelial cell VEGFR2 signaling, where its inactivation leads to nonproductive leaky neo-angiogenesis and, therefore, impedes tumor development and progression. Targeting endothelial epsins is of special significance due to its lack of affecting other angiogenic-signaling pathways or disrupting normal q...
Source: Cellular and Molecular Life Sciences : CMLS - August 29, 2016 Category: Cytology Authors: Song K, Wu H, Rahman HN, Dong Y, Wen A, Brophy ML, Wong S, Kwak S, Bielenberg DR, Chen H Tags: Cell Mol Life Sci Source Type: research

Interplay of mitochondrial metabolism and microRNAs.
Abstract Mitochondria are important organelles in cellular metabolism. Several crucial metabolic pathways such as the energy producing electron transport chain or the tricarboxylic acid cycle are hosted inside the mitochondria. The proper function of mitochondria depends on the import of proteins, which are encoded in the nucleus and synthesized in the cytosol. Micro-ribonucleic acids (miRNAs) are short non-coding ribonucleic acid (RNA) molecules with the ability to prevent messenger RNA (mRNA)-translation or to induce the degradation of mRNA-transcripts. Although miRNAs are mainly located in the cytosol or the nu...
Source: Cellular and Molecular Life Sciences : CMLS - August 25, 2016 Category: Cytology Authors: Geiger J, Dalgaard LT Tags: Cell Mol Life Sci Source Type: research

Selenoproteins and oxidative stress-induced inflammatory tumorigenesis in the gut.
Abstract Selenium is an essential micronutrient that is incorporated into at least 25 selenoproteins encoded by the human genome, many of which serve antioxidant functions. Because patients with inflammatory bowel disease (IBD) demonstrate nutritional deficiencies and are at increased risk for colon cancer due to heightened inflammation and oxidative stress, selenoprotein dysfunction may contribute to disease progression. Over the years, numerous studies have analyzed the effects of selenoprotein loss and shown that they are important mediators of intestinal inflammation and carcinogenesis. In particular, recent w...
Source: Cellular and Molecular Life Sciences : CMLS - August 25, 2016 Category: Cytology Authors: Barrett CW, Short SP, Williams CS Tags: Cell Mol Life Sci Source Type: research

Aptamer and its applications in neurodegenerative diseases.
Abstract Aptamers are small single-stranded DNA or RNA oligonucleotide fragments or small peptides, which can bind to targets by high affinity and specificity. Because aptamers are specific, non-immunogenic and non-toxic, they are ideal materials for clinical applications. Neurodegenerative disorders are ravaging the lives of patients. Even though the mechanism of these diseases is still elusive, they are mainly characterized by the accumulation of misfolded proteins in the central nervous system. So it is essential to develop potential measures to slow down or prevent the onset of these diseases. With the advance...
Source: Cellular and Molecular Life Sciences : CMLS - August 25, 2016 Category: Cytology Authors: Qu J, Yu S, Zheng Y, Zheng Y, Yang H, Zhang J Tags: Cell Mol Life Sci Source Type: research

Convergent evolution of defensin sequence, structure and function.
Abstract Defensins are a well-characterised group of small, disulphide-rich, cationic peptides that are produced by essentially all eukaryotes and are highly diverse in their sequences and structures. Most display broad range antimicrobial activity at low micromolar concentrations, whereas others have other diverse roles, including cell signalling (e.g. immune cell recruitment, self/non-self-recognition), ion channel perturbation, toxic functions, and enzyme inhibition. The defensins consist of two superfamilies, each derived from an independent evolutionary origin, which have subsequently undergone extensive dive...
Source: Cellular and Molecular Life Sciences : CMLS - August 24, 2016 Category: Cytology Authors: Shafee TM, Lay FT, Phan TK, Anderson MA, Hulett MD Tags: Cell Mol Life Sci Source Type: research

Disruption of calcitonin gene-related peptide signaling accelerates muscle denervation and dampens cytotoxic neuroinflammation in SOD1 mutant mice.
z B Abstract Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Neuronal vacuolization and glial activation are pathologic hallmarks in the superoxide dismutase 1 (SOD1) mouse model of ALS. Previously, we found the neuropeptide calcitonin gene-related peptide (CGRP) associated with vacuolization and astrogliosis in the spinal cord of these mice. We now show that CGRP abundance positively correlated with the severity of astrogliosis, but not vacuolization, in several motor and non-motor areas throughout the brain. SOD1 mice harboring a genetic depletion of the βCGRP isoform showed reduced CGR...
Source: Cellular and Molecular Life Sciences : CMLS - August 23, 2016 Category: Cytology Authors: Ringer C, Tune S, Bertoune MA, Schwarzbach H, Tsujikawa K, Weihe E, Schütz B Tags: Cell Mol Life Sci Source Type: research

Toxin bioportides: exploring toxin biological activity and multifunctionality.
; Junior PL Abstract Toxins have been shown to have many biological functions and to constitute a rich source of drugs and biotechnological tools. We focus on toxins that not only have a specific activity, but also contain residues responsible for transmembrane penetration, which can be considered bioportides-a class of cell-penetrating peptides that are also intrinsically bioactive. Bioportides are potential tools in pharmacology and biotechnology as they help deliver substances and nanoparticles to intracellular targets. Bioportides characterized so far are peptides derived from human proteins, such as cytochrom...
Source: Cellular and Molecular Life Sciences : CMLS - August 23, 2016 Category: Cytology Authors: Kerkis I, de Brandão Prieto da Silva AR, Pompeia C, Tytgat J, de Sá Junior PL Tags: Cell Mol Life Sci Source Type: research

The role of Epac in the heart.
Abstract As one of the most important second messengers, 3',5'-cyclic adenosine monophosphate (cAMP) mediates various extracellular signals including hormones and neurotransmitters, and induces appropriate responses in diverse types of cells. Since cAMP was formerly believed to transmit signals through only two direct target molecules, protein kinase A and the cyclic nucleotide-gated channel, the sensational discovery in 1998 of another novel direct effecter of cAMP [exchange proteins directly activated by cAMP (Epac)] attracted a great deal of scientific interest in cAMP signaling. Numerous studies on Epac have s...
Source: Cellular and Molecular Life Sciences : CMLS - August 22, 2016 Category: Cytology Authors: Fujita T, Umemura M, Yokoyama U, Okumura S, Ishikawa Y Tags: Cell Mol Life Sci Source Type: research

Nuclear receptor function in skin health and disease: therapeutic opportunities in the orphan and adopted receptor classes.
Abstract The skin forms a vital barrier between an organism's external environment, providing protection from pathogens and numerous physical and chemical threats. Moreover, the intact barrier is essential to prevent water and electrolyte loss without which terrestrial life could not be maintained. Accordingly, acute disruption of the skin through physical or chemical trauma needs to be repaired timely and efficiently as sustained skin pathologies ranging from mild irritations and inflammation through to malignancy impact considerably on morbidity and mortality. The Nuclear Hormone Receptor Family of transcription...
Source: Cellular and Molecular Life Sciences : CMLS - August 20, 2016 Category: Cytology Authors: Yin K, Smith AG Tags: Cell Mol Life Sci Source Type: research

Gnotobiotic mouse model's contribution to understanding host-pathogen interactions.
Abstract This brief review is dedicated to the legacy of Prof. Jaroslav Šterzl and his colleagues, who laid the foundation for gnotobiology in the former Czechoslovakia 55 years. Prof. Sterzl became one of the founders of modern Czechoslovak immunology, which was characterized by work on a wide range of problems needing to be solved. While examining the mechanisms of innate immunity, he focused his studies on the induction of antibody production by immunocompetent cells involved in adaptive immune transmission while using the model of pig fetuses and germ-free piglets and characterizing immunoglobulins...
Source: Cellular and Molecular Life Sciences : CMLS - August 20, 2016 Category: Cytology Authors: Kubelkova K, Benuchova M, Kozakova H, Sinkora M, Krocova Z, Pejchal J, Macela A Tags: Cell Mol Life Sci Source Type: research

Metabolic and redox signaling in the retina.
el JA Abstract Visual perception by photoreceptors relies on the interaction of incident photons from light with a derivative of vitamin A that is covalently linked to an opsin molecule located in a special subcellular structure, the photoreceptor outer segment. The photochemical reaction produced by the photon is optimal when the opsin molecule, a seven-transmembrane protein, is embedded in a lipid bilayer of optimal fluidity. This is achieved in vertebrate photoreceptors by a high proportion of lipids made with polyunsaturated fatty acids, which have the detrimental property of being oxidized and damaged by ligh...
Source: Cellular and Molecular Life Sciences : CMLS - August 20, 2016 Category: Cytology Authors: Léveillard T, Sahel JA Tags: Cell Mol Life Sci Source Type: research

Ca(2+) signals, cell membrane disintegration, and activation of TMEM16F during necroptosis.
Abstract Activated receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain like (MLKL) are essential components of the necroptotic pathway. Phosphorylated MLKL (pMLKL) is thought to induce membrane leakage, leading to cell swelling and disintegration of the cell membrane. However, the molecular identity of the necroptotic membrane pore remains unclear, and the role of pMLKL for membrane permeabilization is currently disputed. We observed earlier that the phospholipid scramblase and ion channel TMEM16F/anoctamin 6 cause large membrane currents, cell swelling, and cell death when activated by a...
Source: Cellular and Molecular Life Sciences : CMLS - August 17, 2016 Category: Cytology Authors: Ousingsawat J, Cabrita I, Wanitchakool P, Sirianant L, Krautwald S, Linkermann A, Schreiber R, Kunzelmann K Tags: Cell Mol Life Sci Source Type: research

The crystal structure of the AgamOBP1 •Icaridin complex reveals alternative binding modes and stereo-selective repellent recognition.
The crystal structure of the AgamOBP1•Icaridin complex reveals alternative binding modes and stereo-selective repellent recognition. Cell Mol Life Sci. 2016 Aug 17; Authors: Drakou CE, Tsitsanou KE, Potamitis C, Fessas D, Zervou M, Zographos SE Abstract Anopheles gambiae Odorant Binding Protein 1 in complex with the most widely used insect repellent DEET, was the first reported crystal structure of an olfactory macromolecule with a repellent, and paved the way for OBP1-structure-based approaches for discovery of new host-seeking disruptors. In this work, we performed STD-NMR experiments to direct...
Source: Cellular and Molecular Life Sciences : CMLS - August 17, 2016 Category: Cytology Authors: Drakou CE, Tsitsanou KE, Potamitis C, Fessas D, Zervou M, Zographos SE Tags: Cell Mol Life Sci Source Type: research

Vascular smooth muscle cells in Marfan syndrome aneurysm: the broken bricks in the aortic wall.
Abstract Marfan syndrome (MFS) is a connective tissue disorder with multiple organ manifestations. The genetic cause of this syndrome is the mutation of the FBN1 gene, encoding the extracellular matrix (ECM) protein fibrillin-1. This genetic alteration leads to the degeneration of microfibril structures and ECM integrity in the tunica media of the aorta. Indeed, thoracic aortic aneurysm and dissection represent the leading cause of death in MFS patients. To date, the most effective treatment option for this pathology is the surgical substitution of the damaged aorta. To highlight novel therapeutic targets, we revi...
Source: Cellular and Molecular Life Sciences : CMLS - August 17, 2016 Category: Cytology Authors: Perrucci GL, Rurali E, Gowran A, Pini A, Antona C, Chiesa R, Pompilio G, Nigro P Tags: Cell Mol Life Sci Source Type: research

Breast cancer stem cell: the roles and therapeutic implications.
Abstract Breast cancers have been increasingly recognized as malignancies displaying frequent inter- and intra-tumor heterogeneity. This heterogeneity is represented by diverse subtypes and complexity within tumors, and impinges on response to therapy, metastasis, and prognosis. Cancer stem cells (CSCs), a subpopulation of cancer cells endowed with self-renewal and differentiation capacity, have been suggested to contribute to tumor heterogeneity. The CSC concept posits a hierarchical organization of tumors, at the apex of which are stem cells that drive tumor initiation, progression, and recurrence. In breast can...
Source: Cellular and Molecular Life Sciences : CMLS - August 16, 2016 Category: Cytology Authors: Yang F, Xu J, Tang L, Guan X Tags: Cell Mol Life Sci Source Type: research

Is hepatic lipogenesis fundamental for NAFLD/NASH? A focus on the nuclear receptor coactivator PGC-1 β.
Is hepatic lipogenesis fundamental for NAFLD/NASH? A focus on the nuclear receptor coactivator PGC-1β. Cell Mol Life Sci. 2016 Aug 13; Authors: Ducheix S, Vegliante MC, Villani G, Napoli N, Sabbà C, Moschetta A Abstract Non-alcoholic fatty liver diseases are the hepatic manifestation of metabolic syndrome. According to the classical pattern of NAFLD progression, de novo fatty acid synthesis has been incriminated in NAFLD progression. However, this hypothesis has been challenged by the re-evaluation of NAFLD development mechanisms together with the description of the role of lipogenic genes...
Source: Cellular and Molecular Life Sciences : CMLS - August 13, 2016 Category: Cytology Authors: Ducheix S, Vegliante MC, Villani G, Napoli N, Sabbà C, Moschetta A Tags: Cell Mol Life Sci Source Type: research

Expanding role of molecular chaperones in regulating α-synuclein misfolding; implications in Parkinson's disease.
Expanding role of molecular chaperones in regulating α-synuclein misfolding; implications in Parkinson's disease. Cell Mol Life Sci. 2016 Aug 13; Authors: Sharma SK, Priya S Abstract Protein misfolding under stressful environmental conditions cause several cellular problems owing to the disturbed cellular protein homeostasis, which may further lead to neurological disorders like Parkinson's disease (PD), Alzheimer's disease (AD), Amyloid lateral sclerosis and Huntington disease (HD). The presence of cellular defense mechanisms like molecular chaperones and proteasomal degradation systems prevent...
Source: Cellular and Molecular Life Sciences : CMLS - August 13, 2016 Category: Cytology Authors: Sharma SK, Priya S Tags: Cell Mol Life Sci Source Type: research

Immunological properties of oxygen-transport proteins: hemoglobin, hemocyanin and hemerythrin.
Abstract It is now well documented that peptides with enhanced or alternative functionality (termed cryptides) can be liberated from larger, and sometimes inactive, proteins. A primary example of this phenomenon is the oxygen-transport protein hemoglobin. Aside from respiration, hemoglobin and hemoglobin-derived peptides have been associated with immune modulation, hematopoiesis, signal transduction and microbicidal activities in metazoans. Likewise, the functional equivalents to hemoglobin in invertebrates, namely hemocyanin and hemerythrin, act as potent immune effectors under certain physiological conditions. T...
Source: Cellular and Molecular Life Sciences : CMLS - August 12, 2016 Category: Cytology Authors: Coates CJ, Decker H Tags: Cell Mol Life Sci Source Type: research

The estrogen-related receptors (ERRs): potential targets against bone loss.
Abstract Bone loss and the resulting skeletal fragility is induced by several pathological or natural conditions, the most prominent of which being aging as well as the decreased levels of circulating estrogens in post-menopause females. To date, most treatments against bone loss aim at preventing excess bone resorption. We here summarize data indicating that the estrogen-related receptors (ERRs) α and γ prevent bone formation. Inhibiting these receptors may thus constitute an anabolic approach by increasing bone formation. PMID: 27514376 [PubMed - as supplied by publisher] (Source: Cellular and M...
Source: Cellular and Molecular Life Sciences : CMLS - August 11, 2016 Category: Cytology Authors: Zhang L, Wong J, Vanacker JM Tags: Cell Mol Life Sci Source Type: research

Quantitative analysis of mucosal oxygenation using ex vivo imaging of healthy and inflamed mammalian colon tissue.
Abstract Colonic inflammation is associated with decreased tissue oxygenation, significantly affecting gut homeostasis. However, the crosstalk between O2 consumption and supply in the inflamed tissue are not fully understood. Using a murine model of colitis, we analysed O2 in freshly prepared samples of healthy and inflamed colon tissue. We developed protocols for efficient ex vivo staining of mouse distal colon mucosa with a cell-penetrating O2 sensitive probe Pt-Glc and high-resolution imaging of O2 concentration in live tissue by confocal phosphorescence lifetime-imaging microscopy (PLIM). Microscopy analysis r...
Source: Cellular and Molecular Life Sciences : CMLS - August 10, 2016 Category: Cytology Authors: Zhdanov AV, Okkelman IA, Golubeva AV, Doerr B, Hyland NP, Melgar S, Shanahan F, Cryan JF, Papkovsky DB Tags: Cell Mol Life Sci Source Type: research

Liver X receptors: from cholesterol regulation to neuroprotection-a new barrier against neurodegeneration in amyotrophic lateral sclerosis?
Abstract Cholesterol plays a central role in numerous nervous system functions. Cholesterol is the major constituent of myelin sheaths, is essential for synapse and dendrite formation, axon guidance as well as neurotransmission. Among regulators of cholesterol homeostasis, liver X receptors (LXRs), two members of the nuclear receptor superfamily, play a determinant role. LXRs act as cholesterol sensors and respond to high intracellular cholesterol concentration by decreasing plasmatic and intracellular cholesterol content. Beyond their cholesterol-lowering role, LXRs have been proposed as regulators of immunity an...
Source: Cellular and Molecular Life Sciences : CMLS - August 10, 2016 Category: Cytology Authors: Mouzat K, Raoul C, Polge A, Kantar J, Camu W, Lumbroso S Tags: Cell Mol Life Sci Source Type: research

Intracellular localization of DR5 and related regulatory pathways as a mechanism of resistance to TRAIL in cancer.
Abstract TNF-related apoptosis-inducing ligand (TRAIL) is a prominent cytokine capable of inducing apoptosis. It can bind to five different cognate receptors, through which diverse intracellular pathways can be activated. TRAIL's ability to preferentially kill transformed cells makes it a promising potential weapon for targeted tumor therapy. However, recognition of several resistance mechanisms to TRAIL-induced apoptosis has indicated that a thorough understanding of the details of TRAIL biology is still essential before this weapon can be confidently unleashed. Critical to this aim is revealing the functions and...
Source: Cellular and Molecular Life Sciences : CMLS - August 10, 2016 Category: Cytology Authors: Mert U, Sanlioglu AD Tags: Cell Mol Life Sci Source Type: research

Nuclear receptors as pharmacological targets, where are we now?
Abstract Knowledge of integrative physiology is a major challenge for scientists, as even small deregulation could lead to diseases. Cells communicate with each other to control many processes such as growth, migration, survival, or differentiation. Such interaction could be achieved via several mechanisms either through cell-cell interactions and/or through the signaling of molecules that bind to receptors on the membrane or in the target cells. The produced molecules could have either autocrine, paracrine stimulations, or even act on distant organs (endocrine signaling). PMID: 27506618 [PubMed - as supplied...
Source: Cellular and Molecular Life Sciences : CMLS - August 9, 2016 Category: Cytology Authors: Volle DH Tags: Cell Mol Life Sci Source Type: research