Open AccessFeature PaperReview
The Role of Hypoxia in Glioblastoma Invasion
Cells 2017, 6(4), 45; doi:10.3390/cells6040045 -
Abstract
Glioblastoma multiforme (GBM), a grade IV astrocytoma, is the most common and deadly type of primary malignant brain tumor, with a patient’s median survival rate ranging from 15 to 17 months. The current treatment for GBM involves tumor resection surgery based on MRI
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Glioblastoma multiforme (GBM), a grade IV astrocytoma, is the most common and deadly type of primary malignant brain tumor, with a patient’s median survival rate ranging from 15 to 17 months. The current treatment for GBM involves tumor resection surgery based on MRI image analysis, followed by radiotherapy and treatment with temozolomide. However, the gradual development of tumor resistance to temozolomide is frequent in GBM patients leading to subsequent tumor regrowth/relapse. For this reason, the development of more effective therapeutic approaches for GBM is of critical importance. Low tumor oxygenation, also known as hypoxia, constitutes a major concern for GBM patients, since it promotes cancer cell spreading (invasion) into the healthy brain tissue in order to evade this adverse microenvironment. Tumor invasion not only constitutes a major obstacle to surgery, radiotherapy, and chemotherapy, but it is also the main cause of death in GBM patients. Understanding how hypoxia triggers the GBM cells to become invasive is paramount to developing novel and more effective therapies against this devastating disease. In this review, we will present a comprehensive examination of the available literature focused on investigating how GBM hypoxia triggers an invasive cancer cell phenotype and the role of these invasive proteins in GBM progression. Full article
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Open AccessFeature PaperReview
Entamoeba histolytica under Oxidative Stress: What Countermeasure Mechanisms Are in Place?
Cells 2017, 6(4), 44; doi:10.3390/cells6040044 -
Abstract
Entamoeba histolytica is the causative agent of human amoebiasis; it affects 50 million people worldwide and causes approximately 100,000 deaths per year. Entamoeba histolytica is an anaerobic parasite that is primarily found in the colon; however, for unknown reasons, it can become invasive,
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Entamoeba histolytica is the causative agent of human amoebiasis; it affects 50 million people worldwide and causes approximately 100,000 deaths per year. Entamoeba histolytica is an anaerobic parasite that is primarily found in the colon; however, for unknown reasons, it can become invasive, breaching the gut barrier and migrating toward the liver causing amoebic liver abscesses. During the invasive process, it must maintain intracellular hypoxia within the oxygenated human tissues and cellular homeostasis during the host immune defense attack when it is confronted with nitric oxide and reactive oxygen species. But how? This review will address the described and potential mechanisms available to counter the oxidative stress generated during invasion and the possible role that E. histolytica’s continuous endoplasmic reticulum (Eh-ER) plays during these events. Full article
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Open AccessReview
Danger: High Voltage—The Role of Voltage-Gated Calcium Channels in Central Nervous System Pathology
Cells 2017, 6(4), 43; doi:10.3390/cells6040043 -
Abstract
Voltage-gated calcium channels (VGCCs) are widely distributed within the central nervous system (CNS) and presumed to play an important role in the pathophysiology of a broad spectrum of CNS disorders including Alzheimer’s and Parkinson’s disease as well as multiple sclerosis. Several calcium channel
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Voltage-gated calcium channels (VGCCs) are widely distributed within the central nervous system (CNS) and presumed to play an important role in the pathophysiology of a broad spectrum of CNS disorders including Alzheimer’s and Parkinson’s disease as well as multiple sclerosis. Several calcium channel blockers have been in clinical practice for many years so that their toxicity and side effects are well studied. However, these drugs are primarily used for the treatment of cardiovascular diseases and most if not all effects on brain functions are secondary to peripheral effects on blood pressure and circulation. While the use of calcium channel antagonists for the treatment of CNS diseases therefore still heavily depends on the development of novel strategies to specifically target different channels and channel subunits, this review is meant to provide an impulse to further emphasize the importance of future research towards this goal. Full article
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Open AccessFeature PaperArticle
Role of Scaffold Protein Proline-, Glutamic Acid-, and Leucine-Rich Protein 1 (PELP1) in the Modulation of Adrenocortical Cancer Cell Growth
Cells 2017, 6(4), 42; doi:10.3390/cells6040042 -
Abstract
PELP1 acts as an estrogen receptor (ER) coactivator that exerts an essential role in the ER’s functions. ER coregulators have a critical role in the progression and response to hormonal treatment of estrogen-dependent tumors. We previously demonstrated that, in adrenocortical carcinoma (ACC), ERα
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PELP1 acts as an estrogen receptor (ER) coactivator that exerts an essential role in the ER’s functions. ER coregulators have a critical role in the progression and response to hormonal treatment of estrogen-dependent tumors. We previously demonstrated that, in adrenocortical carcinoma (ACC), ERα is upregulated and that estradiol activates the IGF-II/IGF1R signaling pathways defining the role of this functional cross-talk in H295R ACC cell proliferation. The aim of this study was to determine if PELP1 is expressed in ACC and may play a role in promoting the interaction between ERα and IGF1R allowing the activation of pathways important for ACC cell growth. The expression of PELP1 was detected by Western blot analysis in ACC tissues and in H295R cells. H295R cell proliferation decrease was assessed by A3-(4,5-Dimethylthiaoly)-2,5-diphenyltetrazolium bromide (MTT) assay and [3H] thymidine incorporation. PELP1 is expressed in ACC tissues and in H295R cells. Moreover, treatment of H295R with E2 or IGF-II induced a multiprotein complex formation consisting of PELP1, IGF1R, ERα, and Src that is involved in ERK1/2 rapid activation. PELP1/ER/IGF1R/c-Src complex identification as part of E2- and IGF-II-dependent signaling in ACC suggests PELP1 is a novel and more efficient potential target to reduce ACC growth. Full article
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Open AccessFeature PaperEditorial
What Makes Cells Different from Other Open Access Journals
Cells 2017, 6(4), 41; doi:10.3390/cells6040041 -
Abstract
In 2011, I was invited to serve as the Editor-In-Chief for Cells, which back then was a “new kid on the block” among open access (OA) journals.[...] Full article
Open AccessArticle
Dupuytren’s and Ledderhose Diseases in a Family with LMNA-Related Cardiomyopathy and a Novel Variant in the ASTE1 Gene
Cells 2017, 6(4), 40; doi:10.3390/cells6040040 -
Abstract
Dupuytren’s disease (palmar fibromatosis) involves nodules in fascia of the hand that leads to flexion contractures. Ledderhose disease (plantar fibromatosis) is similar with nodules of the foot. While clinical aspects are well-described, genetic mechanisms are unknown. We report a family with cardiac disease
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Dupuytren’s disease (palmar fibromatosis) involves nodules in fascia of the hand that leads to flexion contractures. Ledderhose disease (plantar fibromatosis) is similar with nodules of the foot. While clinical aspects are well-described, genetic mechanisms are unknown. We report a family with cardiac disease due to a heterozygous LMNA mutation (c.736C>T, p.Gln246Stop) with palmar/plantar fibromatosis and investigate the hypothesis that a second rare DNA variant increases the risk for fibrotic disease in LMNA mutation carriers. The proband and six family members were evaluated for the cardiac and hand/feet phenotypes and tested for the LMNA mutation. Fibroblast RNA studies revealed monoallelic expression of the normal LMNA allele and reduced lamin A/C mRNAs consistent with LMNA haploinsufficiency. A novel, heterozygous missense variant (c.230T>C, p.Val77Ala) in the Asteroid Homolog 1 (ASTE1) gene was identified as a potential risk factor in fibrotic disease using exome sequencing and family studies of five family members: four LMNA mutation carriers with fibromatosis and one individual without the LMNA mutation and no fibromatosis. With a possible role in epidermal growth factor receptor signaling, ASTE1 may contribute to the increased risk for palmar/plantar fibromatosis in patients with Lamin A/C haploinsufficiency. Full article
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Open AccessFeature PaperReview
Application of Sodium Selenite in the Prevention and Treatment of Cancers
Cells 2017, 6(4), 39; doi:10.3390/cells6040039 -
Abstract
Selenium is an essential trace element that occurs in nature, in both inorganic and organic forms. This element participates in numerous biochemical processes, including antioxidant potential, but the mechanism of its anti-cancer action is still not well known. It should be noted that
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Selenium is an essential trace element that occurs in nature, in both inorganic and organic forms. This element participates in numerous biochemical processes, including antioxidant potential, but the mechanism of its anti-cancer action is still not well known. It should be noted that the anti-cancer properties of selenium depends on its chemical form, therapeutic doses, and the tumor type. Higher nutritional doses of selenium can stimulate human immune system. There are several hypotheses concerning the anticancer activity of selenium, including oxidation of sulfhydryl groups in proteins causing their conformational alterations. Conformational changes in proteins have the ability to weaken the activity of enzymes involved in the metabolism of cancer cells. In case of human fibrinogen sodium selenite, but not selenate, it inhibits protein disulfide exchange reactions, thus preventing formation of a hydrophobic polymer termed parafibrin, circulatory accumulation, of which is associated with numerous degenerative diseases. Parafibrin can specifically form a protein coat around tumor cells that is completely resistant to degradation induced with lymphocyte protease. In this way, cancer cells become protected against destruction by the organism’s immune system. Other possible mechanisms of anticancer action of selenium are being still investigated. Full article
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Open AccessReview
Monitoring Autophagy in the Model Green Microalga Chlamydomonas reinhardtii
Cells 2017, 6(4), 36; doi:10.3390/cells6040036 -
Abstract
Autophagy is an intracellular catabolic system that delivers cytoplasmic constituents and organelles in the vacuole. This degradative process is mediated by a group of proteins coded by autophagy-related (ATG) genes that are widely conserved from yeasts to plants and mammals. Homologs
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Autophagy is an intracellular catabolic system that delivers cytoplasmic constituents and organelles in the vacuole. This degradative process is mediated by a group of proteins coded by autophagy-related (ATG) genes that are widely conserved from yeasts to plants and mammals. Homologs of ATG genes have been also identified in algal genomes including the unicellular model green alga Chlamydomonas reinhardtii. The development of specific tools to monitor autophagy in Chlamydomonas has expanded our current knowledge about the regulation and function of this process in algae. Recent findings indicated that autophagy is regulated by redox signals and the TOR network in Chlamydomonas and revealed that this process may play in important role in the control of lipid metabolism and ribosomal protein turnover in this alga. Here, we will describe the different techniques and approaches that have been reported to study autophagy and autophagic flux in Chlamydomonas. Full article
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Open AccessReview
Standard Assays for the Study of Autophagy in the Ex Vivo Retina
Cells 2017, 6(4), 37; doi:10.3390/cells6040037 -
Abstract
Autophagy is a catabolic pathway that mediates the degradation and recycling of intracellular components, and is a key player in a variety of physiological processes in cells and tissues. Recent studies of autophagy in the eye suggest that this pathway is fundamental for
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Autophagy is a catabolic pathway that mediates the degradation and recycling of intracellular components, and is a key player in a variety of physiological processes in cells and tissues. Recent studies of autophagy in the eye suggest that this pathway is fundamental for the preservation of retinal homeostasis. Given its accessible location outside the brain, the retina is an ideal organ in which to study the central nervous system and a wide range of neuronal processes, from development to neurodegeneration. Here we review several methods used to assess autophagy in the retina in both physiological and pathological conditions. Full article
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Open AccessArticle
Expression Profiling of Differentiating Emerin-Null Myogenic Progenitor Identifies Molecular Pathways Implicated in Their Impaired Differentiation
Cells 2017, 6(4), 38; doi:10.3390/cells6040038 -
Abstract
Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD), a disorder causing progressive skeletal muscle wasting, irregular heart rhythms and contractures of major tendons. RNA sequencing was performed on differentiating wildtype and emerin-null myogenic progenitors to identify molecular pathways implicated in
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Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD), a disorder causing progressive skeletal muscle wasting, irregular heart rhythms and contractures of major tendons. RNA sequencing was performed on differentiating wildtype and emerin-null myogenic progenitors to identify molecular pathways implicated in EDMD, 340 genes were uniquely differentially expressed during the transition from day 0 to day 1 in wildtype cells. 1605 genes were uniquely expressed in emerin-null cells; 1706 genes were shared among both wildtype and emerin-null cells. One thousand and forty-seven transcripts showed differential expression during the transition from day 1 to day 2. Four hundred and thirty-one transcripts showed altered expression in both wildtype and emerin-null cells. Two hundred and ninety-five transcripts were differentially expressed only in emerin-null cells and 321 transcripts were differentially expressed only in wildtype cells. DAVID, STRING and Ingenuity Pathway Analysis identified pathways implicated in impaired emerin-null differentiation, including cell signaling, cell cycle checkpoints, integrin signaling, YAP/TAZ signaling, stem cell differentiation, and multiple muscle development and myogenic differentiation pathways. Functional enrichment analysis showed biological functions associated with the growth of muscle tissue and myogenesis of skeletal muscle were inhibited. The large number of differentially expressed transcripts upon differentiation induction suggests emerin functions during transcriptional reprograming of progenitors to committed myoblasts. Full article
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Open AccessFeature PaperArticle
Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells
Cells 2017, 6(4), 35; doi:10.3390/cells6040035 -
Abstract
We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and
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We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo. In this study, to investigate the mechanism of cell injury of cardiac myocytes and pancreatic β-cells involved in diabetes mellitus (DM), we analyzed plasma ORAIP levels in DM model rats and the role of ORAIP in high glucose-induced apoptosis of cardiac myocytes in vitro. We also examined whether recombinant-ORAIP induces apoptosis in pancreatic β-cells. Plasma ORAIP levels in DM rats during diabetic phase were about 18 times elevated as compared with non-diabetic phase. High glucose induced massive apoptosis in cardiac myocytes (66.2 ± 2.2%), which was 78% suppressed by neutralizing anti-ORAIP mAb in vitro. Furthermore, recombinant-ORAIP clearly induced apoptosis in pancreatic β-cells in vitro. These findings strongly suggested that ORAIP plays a pivotal role in hyperglycemia-induced myocardial injury and pancreatic β-cell injury in DM. ORAIP will be a biomarker and a critical therapeutic target for cardiac injury and progression of DM itself. Full article
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Open AccessFeature PaperArticle
Post-Translational Modification of Human Histone by Wide Tolerance of Acetylation
Cells 2017, 6(4), 34; doi:10.3390/cells6040034 -
Abstract
Histone acetylation adds an acetyl group on the lysine residue commonly found within the N-terminal tail protruding from the histone core of the nucleosome, and is important for chromosome structure and function in gene transcription and chromatin remodeling. Acetylation may also occur on
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Histone acetylation adds an acetyl group on the lysine residue commonly found within the N-terminal tail protruding from the histone core of the nucleosome, and is important for chromosome structure and function in gene transcription and chromatin remodeling. Acetylation may also occur on other residues additional to lysine, but have not been thoroughly investigated at the proteomics level. Here we report a wide tolerance acetylation study mimicking the addition of 42 ± 0.5 Da delta mass modification on undefined amino acid residues of histones by shotgun proteomics using liquid chromatography–tandem mass spectrometry. A multi-blind spectral alignment algorithm with a wide peptide tolerance revealed frequent occurrence of 42 ± 0.5 Da modifications at lysine (K), serine (S) and threonine (T) residues in human histones from kidney tissues. Precision delta mass analysis identified acetylation (42.011 ± 0.004 Da) and trimethylation (42.047 ± 0.002 Da) modifications within the delta mass range. A specific antibody was produced to validate the acetylated T22 of human histone H3 (H3T22ac) by immune assays. Thus, we demonstrated that the wide tolerance acetylation approach identified histone acetylation as well as modification variants commonly associated with acetylation at undefined residues additional to lysine. Full article
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Open AccessReview
A Perspective on the Experimental Techniques for Studying Lamins
Cells 2017, 6(4), 33; doi:10.3390/cells6040033 -
Abstract
Lamins are type V intermediate filaments that collectively form a meshwork underneath the inner nuclear membrane, called nuclear lamina. Furthermore, they are also present in the nucleoplasm. Lamins are experiencing a growing interest, since a wide range of diseases are induced by mutations
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Lamins are type V intermediate filaments that collectively form a meshwork underneath the inner nuclear membrane, called nuclear lamina. Furthermore, they are also present in the nucleoplasm. Lamins are experiencing a growing interest, since a wide range of diseases are induced by mutations in the gene coding for A-type lamins, globally known as laminopathies. Moreover, it has been demonstrated that lamins are involved in other pathological conditions, like cancer. The role of lamins has been studied from several perspectives, exploiting different techniques and procedures. This multidisciplinary approach has contributed to resolving the unique features of lamins and has provided a thorough insight in their role in living organisms. Yet, there are still many unanswered questions, which constantly generate research in the field. The present work is aimed to review some interesting experimental techniques performed so far to study lamins. Scientists can take advantage of this collection for their novel investigations, being aware of the already pursued and consolidated methodologies. Hopefully, advances in these research directions will provide insights to achieve better diagnostic procedures and effective therapeutic options. Full article
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Open AccessReview
How Can Elispot Add Information to Improve Knowledge on Tropical Diseases?
Cells 2017, 6(4), 31; doi:10.3390/cells6040031 -
Abstract
Elispot has been used as an important tool for detecting immune cells’ products and functions and has facilitated the understanding of host-pathogen interaction. Despite the incredible diversity of possibilities, two main approaches have been developed: the immunopathogenesis and diagnosis/prognosis of infectious diseases as
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Elispot has been used as an important tool for detecting immune cells’ products and functions and has facilitated the understanding of host-pathogen interaction. Despite the incredible diversity of possibilities, two main approaches have been developed: the immunopathogenesis and diagnosis/prognosis of infectious diseases as well as cancer research. Much has been described on the topics of allergy, autoimmune diseases, and HIV-Aids, however, Elispot can also be applied to other infectious diseases, mainly leishmaniasis, malaria, some viruses, helminths and mycosis usually classified as tropical diseases. The comprehension of the function, concentration and diversity of the immune response in the infectious disease is pointed out as crucial to the development of infection or disease in humans and animals. In this review we will describe the knowledge already obtained using Elispot as a method for accessing the profile of immune response as well as the recent advances in information about host-pathogen interaction in order to better understand the clinical outcome of a group of tropical and neglected diseases. Full article
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Open AccessReview
Use of Human Neurons Derived via Cellular Reprogramming Methods to Study Host-Parasite Interactions of Toxoplasma gondii in Neurons
Cells 2017, 6(4), 32; doi:10.3390/cells6040032 -
Abstract
Toxoplasma gondii is an intracellular protozoan parasite, with approximately one-third of the worlds’ population chronically infected. In chronically infected individuals, the parasite resides in tissue cysts in neurons in the brain. The chronic infection in immunocompetant individuals has traditionally been considered to be
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Toxoplasma gondii is an intracellular protozoan parasite, with approximately one-third of the worlds’ population chronically infected. In chronically infected individuals, the parasite resides in tissue cysts in neurons in the brain. The chronic infection in immunocompetant individuals has traditionally been considered to be asymptomatic, but increasing evidence indicates that chronic infection is associated with diverse neurological disorders such as schizophrenia, cryptogenic epilepsy, and Parkinson’s Disease. The mechanisms by which the parasite exerts affects on behavior and other neuronal functions are not understood. Human neurons derived from cellular reprogramming methods offer the opportunity to develop better human neuronal models to study T. gondii in neurons. Results from two studies using human neurons derived via cellular reprogramming methods indicate these human neuronal models provide better in vitro models to study the effects of T. gondii on neurons and neurological functions. In this review, an overview of the current neural reprogramming methods will be given, followed by a summary of the studies using human induced pluripotent stem cell (hiPSC)-derived neurons and induced neurons (iNs) to study T. gondii in neurons. The potential of these neural reprogramming methods for further study of the host-parasite interactions of T. gondii in neurons will be discussed. Full article
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Open AccessReview
Assessing Autophagy in Sciatic Nerves of a Rat Model that Develops Inflammatory Autoimmune Peripheral Neuropathies
Cells 2017, 6(3), 30; doi:10.3390/cells6030030 -
Abstract
The rat sciatic nerve has attracted widespread attention as an excellent model system for studying autophagy alterations in peripheral neuropathies. In our laboratory, we have developed an original rat model, which we used currently in routine novel drug screening and to evaluate treatment
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The rat sciatic nerve has attracted widespread attention as an excellent model system for studying autophagy alterations in peripheral neuropathies. In our laboratory, we have developed an original rat model, which we used currently in routine novel drug screening and to evaluate treatment strategies for chronic inflammatory demyelinating polyneuropathy (CIDP) and other closely related diseases. Lewis rats injected with the S-palmitoylated P0(180-199) peptide develop a chronic, sometimes relapsing-remitting type of disease. Our model fulfills electrophysiological criteria of demyelination with axonal degeneration, confirmed by immunohistopathology and several typical features of CIDP. We have set up a series of techniques that led us to examine the failures of autophagy pathways in the sciatic nerve of these model rats and to follow the possible improvement of these defects after treatment. Based on these newly introduced methods, a novel area of investigation is now open and will allow us to more thoroughly examine important features of certain autophagy pathways occurring in sciatic nerves. Full article
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Open AccessArticle
Delayed Activation Kinetics of Th2- and Th17 Cells Compared to Th1 Cells
Cells 2017, 6(3), 29; doi:10.3390/cells6030029 -
Abstract
During immune responses, different classes of T cells arise: Th1, Th2, and Th17. Mobilizing the right class plays a critical role in successful host defense and therefore defining the ratios of Th1/Th2/Th17 cells within the antigen-specific T cell repertoire is critical for immune
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During immune responses, different classes of T cells arise: Th1, Th2, and Th17. Mobilizing the right class plays a critical role in successful host defense and therefore defining the ratios of Th1/Th2/Th17 cells within the antigen-specific T cell repertoire is critical for immune monitoring purposes. Antigen-specific Th1, Th2, and Th17 cells can be detected by challenging peripheral blood mononuclear cells (PBMC) with antigen, and establishing the numbers of T cells producing the respective lead cytokine, IFN-γ and IL-2 for Th1 cells, IL-4 and IL-5 for Th2, and IL-17 for Th-17 cells, respectively. Traditionally, these cytokines are measured within 6 h in flow cytometry. We show here that 6 h of stimulation is sufficient to detect peptide-induced production of IFN-γ, but 24 h are required to reveal the full frequency of protein antigen-specific Th1 cells. Also the detection of IL-2 producing Th1 cells requires 24 h stimulation cultures. Measurements of IL-4 producing Th2 cells requires 48-h cultures and 96 h are required for frequency measurements of IL-5 and IL-17 secreting T cells. Therefore, accounting for the differential secretion kinetics of these cytokines is critical for the accurate determination of the frequencies and ratios of antigen-specific Th1, Th2, and Th17 cells. Full article
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Open AccessReview
Lamin B Receptor: Interplay between Structure, Function and Localization
Cells 2017, 6(3), 28; doi:10.3390/cells6030028 -
Abstract
Lamin B receptor (LBR) is an integral protein of the inner nuclear membrane, containing a hydrophilic N-terminal end protruding into the nucleoplasm, eight hydrophobic segments that span the membrane and a short, nucleoplasmic C-terminal tail. Two seemingly unrelated functions have been
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Lamin B receptor (LBR) is an integral protein of the inner nuclear membrane, containing a hydrophilic N-terminal end protruding into the nucleoplasm, eight hydrophobic segments that span the membrane and a short, nucleoplasmic C-terminal tail. Two seemingly unrelated functions have been attributed to LBR. Its N-terminal domain tethers heterochromatin to the nuclear periphery, thus contributing to the shape of interphase nuclear architecture, while its transmembrane domains exhibit sterol reductase activity. Mutations within the transmembrane segments result in defects in cholesterol synthesis and are associated with diseases such as the Pelger–Huët anomaly and Greenberg skeletal dysplasia, whereas no such harmful mutations related to the anchoring properties of LBR have been reported so far. Recent evidence suggests a dynamic regulation of LBR expression levels, structural organization, localization and function, in response to various signals. The molecular mechanisms underlying this dynamic behavior have not yet been fully unraveled. Here, we provide an overview of the current knowledge of the interplay between the structure, function and localization of LBR, and hint at the interconnection of the two distinct functions of LBR. Full article
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Open AccessReview
Approaches for Studying Autophagy in Caenorhabditis elegans
Cells 2017, 6(3), 27; doi:10.3390/cells6030027 -
Abstract
Macroautophagy (hereafter referred to as autophagy) is an intracellular degradative process, well conserved among eukaryotes. By engulfing cytoplasmic constituents into the autophagosome for degradation, this process is involved in the maintenance of cellular homeostasis. Autophagy induction triggers the formation of a cup-shaped double
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Macroautophagy (hereafter referred to as autophagy) is an intracellular degradative process, well conserved among eukaryotes. By engulfing cytoplasmic constituents into the autophagosome for degradation, this process is involved in the maintenance of cellular homeostasis. Autophagy induction triggers the formation of a cup-shaped double membrane structure, the phagophore, which progressively elongates and encloses materials to be removed. This double membrane vesicle, which is called an autophagosome, fuses with lysosome and forms the autolysosome. The inner membrane of the autophagosome, along with engulfed compounds, are degraded by lysosomal enzymes, which enables the recycling of carbohydrates, amino acids, nucleotides, and lipids. In response to various factors, autophagy can be induced for non-selective degradation of bulk cytoplasm. Autophagy is also able to selectively target cargoes and organelles such as mitochondria or peroxisome, functioning as a quality control system. The modification of autophagy flux is involved in developmental processes such as resistance to stress conditions, aging, cell death, and multiple pathologies. So, the use of animal models is essential for understanding these processes in the context of different cell types throughout the entire lifespan. For almost 15 years, the nematode Caenorhabditis elegans has emerged as a powerful model to analyze autophagy in physiological or pathological contexts. This review presents a rapid overview of physiological processes involving autophagy in Caenorhabditis elegans, the different assays used to monitor autophagy, their drawbacks, and specific tools for the analyses of selective autophagy. Full article
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Open AccessReview
Assessment of Autophagy in Neurons and Brain Tissue
Cells 2017, 6(3), 25; doi:10.3390/cells6030025 -
Abstract
Autophagy is a complex process that controls the transport of cytoplasmic components into lysosomes for degradation. This highly conserved proteolytic system involves dynamic and complex processes, using similar molecular elements and machinery from yeast to humans. Moreover, autophagic dysfunction may contribute to a
[...] Read more.
Autophagy is a complex process that controls the transport of cytoplasmic components into lysosomes for degradation. This highly conserved proteolytic system involves dynamic and complex processes, using similar molecular elements and machinery from yeast to humans. Moreover, autophagic dysfunction may contribute to a broad spectrum of mammalian diseases. Indeed, in adult tissues, where the capacity for regeneration or cell division is low or absent (e.g., in the mammalian brain), the accumulation of proteins/peptides that would otherwise be recycled or destroyed may have pathological implications. Indeed, such changes are hallmarks of pathologies, like Alzheimer’s, Prion or Parkinson’s disease, known as proteinopathies. However, it is still unclear whether such dysfunction is a cause or an effect in these conditions. One advantage when analysing autophagy in the mammalian brain is that almost all the markers described in different cell lineages and systems appear to be present in the brain, and even in neurons. By contrast, the mixture of cell types present in the brain and the differentiation stage of such neurons, when compared with neurons in culture, make translating basic research to the clinic less straightforward. Thus, the purpose of this review is to describe and discuss the methods available to monitor autophagy in neurons and in the mammalian brain, a process that is not yet fully understood, focusing primarily on mammalian macroautophagy. We will describe some general features of neuronal autophagy that point to our focus on neuropathologies in which macroautophagy may be altered. Indeed, we centre this review around the hypothesis that enhanced autophagy may be able to provide therapeutic benefits in some brain pathologies, like Alzheimer’s disease, considering this pathology as one of the most prevalent proteinopathies. Full article
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