Open AccessArticle
The Anti-Oxidant Defense System of the Marine Polar Ciliate Euplotes nobilii: Characterization of the MsrB Gene Family
Biology 2017, 6(1), 4; doi:10.3390/biology6010004 (registering DOI) -
Abstract
Organisms living in polar waters must cope with an extremely stressful environment dominated by freezing temperatures, high oxygen concentrations and UV radiation. To shed light on the genetic mechanisms on which the polar marine ciliate, Euplotes nobilii, relies to effectively cope with
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Organisms living in polar waters must cope with an extremely stressful environment dominated by freezing temperatures, high oxygen concentrations and UV radiation. To shed light on the genetic mechanisms on which the polar marine ciliate, Euplotes nobilii, relies to effectively cope with the oxidative stress, attention was focused on methionine sulfoxide reductases which repair proteins with oxidized methionines. A family of four structurally distinct MsrB genes, encoding enzymes specific for the reduction of the methionine-sulfoxide R-forms, were identified from a draft of the E. nobilii transcriptionally active (macronuclear) genome. The En-MsrB genes are constitutively expressed to synthesize proteins markedly different in amino acid sequence, number of CXXC motifs for zinc-ion binding, and presence/absence of a cysteine residue specific for the mechanism of enzyme regeneration. The En-MsrB proteins take different localizations in the nucleus, mitochondria, cytosol and endoplasmic reticulum, ensuring a pervasive protection of all the major subcellular compartments from the oxidative damage. These observations have suggested to regard the En-MsrB gene activity as playing a central role in the genetic mechanism that enables E. nobilii and ciliates in general to live in the polar environment. Full article
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Open AccessReview
Concerted Flexibility of Chromatin Structure, Methylome, and Histone Modifications along with Plant Stress Responses
Biology 2017, 6(1), 3; doi:10.3390/biology6010003 -
Abstract
The spatial organization of chromosome structure within the interphase nucleus, as well as the patterns of methylome and histone modifications, represent intersecting layers that influence genome accessibility and function. This review is focused on the plastic nature of chromatin structure and epigenetic marks
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The spatial organization of chromosome structure within the interphase nucleus, as well as the patterns of methylome and histone modifications, represent intersecting layers that influence genome accessibility and function. This review is focused on the plastic nature of chromatin structure and epigenetic marks in association to stress situations. The use of chemical compounds (epigenetic drugs) or T-DNA-mediated mutagenesis affecting epigenetic regulators (epi-mutants) are discussed as being important tools for studying the impact of deregulated epigenetic backgrounds on gene function and phenotype. The inheritability of epigenetic marks and chromatin configurations along successive generations are interpreted as a way for plants to “communicate” past experiences of stress sensing. A mechanistic understanding of chromatin and epigenetics plasticity in plant response to stress, including tissue- and genotype-specific epigenetic patterns, may help to reveal the epigenetics contributions for genome and phenotype regulation. Full article
Open AccessEditorial
Acknowledgement to Reviewers of Biology in 2016
Biology 2017, 6(1), 2; doi:10.3390/biology6010002 -
Abstract The editors of Biology would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...] Full article
Open AccessReview
Mechanisms to Avoid and Correct Erroneous Kinetochore-Microtubule Attachments
Biology 2017, 6(1), 1; doi:10.3390/biology6010001 -
Abstract
In dividing vertebrate cells multiple microtubules must connect to mitotic kinetochores in a highly stereotypical manner, with each sister kinetochore forming microtubule attachments to only one spindle pole. The exact sequence of events by which this goal is achieved varies considerably from cell
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In dividing vertebrate cells multiple microtubules must connect to mitotic kinetochores in a highly stereotypical manner, with each sister kinetochore forming microtubule attachments to only one spindle pole. The exact sequence of events by which this goal is achieved varies considerably from cell to cell because of the variable locations of kinetochores and spindle poles, and randomness of initial microtubule attachments. These chance encounters with the kinetochores nonetheless ultimately lead to the desired outcome with high fidelity and in a limited time frame, providing one of the most startling examples of biological self-organization. This chapter discusses mechanisms that contribute to accurate chromosome segregation by helping dividing cells to avoid and resolve improper microtubule attachments. Full article
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Open AccessReview
A Brief History of Research on Mitotic Mechanisms
Biology 2016, 5(4), 55; doi:10.3390/biology5040055 -
Abstract
This chapter describes in summary form some of the most important research on chromosome segregation, from the discovery and naming of mitosis in the nineteenth century until around 1990. It gives both historical and scientific background for the nine chapters that follow, each
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This chapter describes in summary form some of the most important research on chromosome segregation, from the discovery and naming of mitosis in the nineteenth century until around 1990. It gives both historical and scientific background for the nine chapters that follow, each of which provides an up-to-date review of a specific aspect of mitotic mechanism. Here, we trace the fruits of each new technology that allowed a deeper understanding of mitosis and its underlying mechanisms. We describe how light microscopy, including phase, polarization, and fluorescence optics, provided descriptive information about mitotic events and also enabled important experimentation on mitotic functions, such as the dynamics of spindle fibers and the forces generated for chromosome movement. We describe studies by electron microscopy, including quantitative work with serial section reconstructions. We review early results from spindle biochemistry and genetics, coupled to molecular biology, as these methods allowed scholars to identify key molecular components of mitotic mechanisms. We also review hypotheses about mitotic mechanisms whose testing led to a deeper understanding of this fundamental biological event. Our goal is to provide modern scientists with an appreciation of the work that has laid the foundations for their current work and interests. Full article
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Open AccessReview
Multiple Forms of Glutamate Dehydrogenase in Animals: Structural Determinants and Physiological Implications
Biology 2016, 5(4), 53; doi:10.3390/biology5040053 -
Abstract
Glutamate dehydrogenase (GDH) of animal cells is usually considered to be a mitochondrial enzyme. However, this enzyme has recently been reported to be also present in nucleus, endoplasmic reticulum and lysosomes. These extramitochondrial localizations are associated with moonlighting functions of GDH, which include
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Glutamate dehydrogenase (GDH) of animal cells is usually considered to be a mitochondrial enzyme. However, this enzyme has recently been reported to be also present in nucleus, endoplasmic reticulum and lysosomes. These extramitochondrial localizations are associated with moonlighting functions of GDH, which include acting as a serine protease or an ATP-dependent tubulin-binding protein. Here, we review the published data on kinetics and localization of multiple forms of animal GDH taking into account the splice variants, post-translational modifications and GDH isoenzymes, found in humans and apes. The kinetic properties of human GLUD1 and GLUD2 isoenzymes are shown to be similar to those published for GDH1 and GDH2 from bovine brain. Increased functional diversity and specific regulation of GDH isoforms due to alternative splicing and post-translational modifications are also considered. In particular, these structural differences may affect the well-known regulation of GDH by nucleotides which is related to recent identification of thiamine derivatives as novel GDH modulators. The thiamine-dependent regulation of GDH is in good agreement with the fact that the non-coenzyme forms of thiamine, i.e., thiamine triphosphate and its adenylated form are generated in response to amino acid and carbon starvation. Full article
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Open AccessArticle
Critical Function of PRDM2 in the Neoplastic Growth of Testicular Germ Cell Tumors
Biology 2016, 5(4), 54; doi:10.3390/biology5040054 -
Abstract
Testicular germ cell tumors (TGCTs) derive from primordial germ cells. Their maturation is blocked at different stages, reflecting histological tumor subtypes. A common genetic alteration in TGCT is a deletion of the chromosome 1 short arm, where the PRDM2 gene, belonging to the
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Testicular germ cell tumors (TGCTs) derive from primordial germ cells. Their maturation is blocked at different stages, reflecting histological tumor subtypes. A common genetic alteration in TGCT is a deletion of the chromosome 1 short arm, where the PRDM2 gene, belonging to the Positive Regulatory domain gene (PRDM) family, is located. Expression of PRDM2 gene is shifted in different human tumors, where the expression of the two principal protein forms coded by PRDM2 gene, RIZ1 and RIZ2, is frequently unbalanced. Therefore, PRDM2 is actually considered a candidate tumor suppressor gene in different types of cancer. Although recent studies have demonstrated that PRDM gene family members have a pivotal role during the early stages of testicular development, no information are actually available on the involvement of these genes in TGCTs. In this article we show by qRT-PCR analysis that PRDM2 expression level is modulated by proliferation and differentiation agents such as estradiol, whose exposure during fetal life is probably an important risk factor for TGCTs development in adulthood. Furthermore in normal and cancer germ cell lines, PRDM2 binds estradiol receptor α (ERα) and influences proliferation, survival and apoptosis, as previously reported using MCF-7 breast cancer cell line, suggesting a potential tumor-suppressor role in TGCT formation. Full article
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Open AccessArticle
Subjective Mood in Young Unmedicated Depressed Women under High and Low Sleep Pressure Conditions
Biology 2016, 5(4), 52; doi:10.3390/biology5040052 -
Abstract
Diurnal mood variations are one of the core symptoms in depression, and total sleep deprivation (SD) can induce rapid, short-lasting clinical improvement in depressed patients. Here, we investigated if differential sleep pressure conditions impact on subjective mood levels in young women with major
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Diurnal mood variations are one of the core symptoms in depression, and total sleep deprivation (SD) can induce rapid, short-lasting clinical improvement in depressed patients. Here, we investigated if differential sleep pressure conditions impact on subjective mood levels in young women with major depressive disorder (MDD) without sleep disturbances, and in healthy controls. Eight healthy and eight MDD women underwent 40-h SD (high sleep pressure) and 40-h multiple NAP (low sleep pressure) protocols under constant routine conditions during which subjective mood was assessed every 30-min. MDD women rated overall significantly worse mood than controls, with minimal values for both groups during the biological night (ca. 4 a.m.), under high and low sleep pressure conditions. During SD, nighttime mood ratings in MDD women were lower than in controls and partially recovered during the second day of SD, but never attained control levels. The degree of this diurnal time-course in mood under SD correlated positively with sleep quality in MDD women. Our data indicate that MDD women without sleep disturbances did not exhibit a SD-induced antidepressant response, suggesting that the mood enhancement response to sleep deprivation might be related to the co-existence of sleep disturbances, which is an association that remains to be fully established. Full article
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Open AccessReview
Anaphase B
Biology 2016, 5(4), 51; doi:10.3390/biology5040051 -
Abstract
Anaphase B spindle elongation is characterized by the sliding apart of overlapping antiparallel interpolar (ip) microtubules (MTs) as the two opposite spindle poles separate, pulling along disjoined sister chromatids, thereby contributing to chromosome segregation and the propagation of all cellular life. The major
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Anaphase B spindle elongation is characterized by the sliding apart of overlapping antiparallel interpolar (ip) microtubules (MTs) as the two opposite spindle poles separate, pulling along disjoined sister chromatids, thereby contributing to chromosome segregation and the propagation of all cellular life. The major biochemical “modules” that cooperate to mediate pole–pole separation include: (i) midzone pushing or (ii) braking by MT crosslinkers, such as kinesin-5 motors, which facilitate or restrict the outward sliding of antiparallel interpolar MTs (ipMTs); (iii) cortical pulling by disassembling astral MTs (aMTs) and/or dynein motors that pull aMTs outwards; (iv) ipMT plus end dynamics, notably net polymerization; and (v) ipMT minus end depolymerization manifest as poleward flux. The differential combination of these modules in different cell types produces diversity in the anaphase B mechanism. Combinations of antagonist modules can create a force balance that maintains the dynamic pre-anaphase B spindle at constant length. Tipping such a force balance at anaphase B onset can initiate and control the rate of spindle elongation. The activities of the basic motor filament components of the anaphase B machinery are controlled by a network of non-motor MT-associated proteins (MAPs), for example the key MT cross-linker, Ase1p/PRC1, and various cell-cycle kinases, phosphatases, and proteases. This review focuses on the molecular mechanisms of anaphase B spindle elongation in eukaryotic cells and briefly mentions bacterial DNA segregation systems that operate by spindle elongation. Full article
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Open AccessArticle
Exosome Proteome of U-87MG Glioblastoma Cells
Biology 2016, 5(4), 50; doi:10.3390/biology5040050 -
Abstract
Exosomes are small membrane vesicles between 30 and 100 nm in diameter secreted by many cell types, and are associated with a wide range of physiological and/or pathological processes. Exosomes containing proteins, lipids, mRNA, and microRNA contribute to cell-to-cell communication and cell-to-environment regulation,
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Exosomes are small membrane vesicles between 30 and 100 nm in diameter secreted by many cell types, and are associated with a wide range of physiological and/or pathological processes. Exosomes containing proteins, lipids, mRNA, and microRNA contribute to cell-to-cell communication and cell-to-environment regulation, however, their biological functions are not yet fully understood. In this report, exosomes in the glioblastoma cell line, U-87MG, were isolated and the proteome was investigated. In addition, exosome proteome changes in U-87MG cells exposed to a low temperature were investigated to elucidate whether the exosome proteome could respond to an external stimulus. Cell culture medium was collected, and exosomes were isolated by continuous centrifugation eliminating cell debris, nucleic acids, and other particles. The morphology of exosomes was observed by cryo-tunneling electron microscopy. According to 2-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, certain proteins including collagen type VI alpha 1, putative RNA-binding protein 15B chain A, substrate induced remodeling of the active site regulates HTRA1, coatomer protein complex-subunit beta 2, myosin-heavy chain 1, and keratin-type I cytoskeletal 9 showed differences between the control proteome and the low temperature-exposed proteome. Full article
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Open AccessArticle
Decreased STAT3 Phosphorylation Mediates Cell Swelling in Ammonia-Treated Astrocyte Cultures
Biology 2016, 5(4), 48; doi:10.3390/biology5040048 -
Abstract
Brain edema, due largely to astrocyte swelling, and the subsequent increase in intracranial pressure and brain herniation, are major complications of acute liver failure (ALF). Elevated level of brain ammonia has been strongly implicated in the development of astrocyte swelling associated with ALF.
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Brain edema, due largely to astrocyte swelling, and the subsequent increase in intracranial pressure and brain herniation, are major complications of acute liver failure (ALF). Elevated level of brain ammonia has been strongly implicated in the development of astrocyte swelling associated with ALF. The means by which ammonia brings about astrocyte swelling, however, is incompletely understood. Recently, oxidative/nitrosative stress and associated signaling events, including activation of mitogen-activated protein kinases (MAPKs), as well as activation of the transcription factor, nuclear factor-kappaB (NF-κB), have been implicated in the mechanism of ammonia-induced astrocyte swelling. Since these signaling events are known to be regulated by the transcription factor, signal transducer and activator of transcription 3 (STAT3), we examined the state of STAT3 activation in ammonia-treated cultured astrocytes, and determined whether altered STAT3 activation and/or protein expression contribute to the ammonia-induced astrocyte swelling. STAT3 was found to be dephosphorylated (inactivated) at Tyrosine705 in ammonia-treated cultured astrocytes. Total STAT3 protein level was also reduced in ammonia-treated astrocytes. We also found a significant increase in protein tyrosine phosphatase receptor type-1 (PTPRT-1) protein expression in ammonia-treated cultured astrocytes, and that inhibition of PTPRT-1 enhanced the phosphorylation of STAT3 after ammonia treatment. Additionally, exposure of cultured astrocytes to inhibitors of protein tyrosine phosphatases diminished the ammonia-induced cell swelling, while cultured astrocytes over-expressing STAT3 showed a reduction in the astrocyte swelling induced by ammonia. Collectively, these studies strongly suggest that inactivation of STAT3 represents a critical event in the mechanism of the astrocyte swelling associated with acute liver failure. Full article
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Open AccessArticle
Protein Phosphatase-1 Regulates Expression of Neuregulin-1
Biology 2016, 5(4), 49; doi:10.3390/biology5040049 -
Abstract
Protein phosphatase 1 (PP1), a cellular serine/threonine phosphatase, is targeted to cellular promoters by its major regulatory subunits, PP1 nuclear targeting subunit, nuclear inhibitor of PP1 (NIPP1) and RepoMan. PP1 is also targeted to RNA polymerase II (RNAPII) by NIPP1 where it can
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Protein phosphatase 1 (PP1), a cellular serine/threonine phosphatase, is targeted to cellular promoters by its major regulatory subunits, PP1 nuclear targeting subunit, nuclear inhibitor of PP1 (NIPP1) and RepoMan. PP1 is also targeted to RNA polymerase II (RNAPII) by NIPP1 where it can dephosphorylate RNAPII and cycle-dependent kinase 9 (CDK9). Here, we show that treatment of cells with a small molecule activator of PP1 increases the abundance of a neuregulin-1 (NRG-1)-derived peptide. NRG-1 mRNA and protein levels were increased in the cells stably or transiently expressing mutant NIPP1 (mNIPP1) that does not bind PP1, but not in the cells expressing NIPP1. Expression of mNIPP1 also activated the NRG-1 promoter in an NF-κB-dependent manner. Analysis of extracts from mNIPP1 expressing cells by glycerol gradient centrifugation showed a redistribution of PP1 and CDK9 between large and small molecular weight complexes, and increased CDK9 Thr-186 phosphorylation. This correlated with the increased CDK9 activity. Further, RNAPII co-precipitated with mNIPP1, and phosphorylation of RNAPII C-terminal domain (CTD) Ser-2 residues was greater in cells expressing mNIPP1. In mNIPP1 expressing cells, okadaic acid, a cell-permeable inhibitor of PP1, did not increase Ser-2 CTD phosphorylation inhibited by flavopiridol, in contrast to the NIPP1 expressing cells, suggesting that PP1 was no longer involved in RNAPII dephosphorylation. Finally, media conditioned with mNIPP1 cells induced the proliferation of wild type 84-31 cells, consistent with a role of neuregulin-1 as a growth promoting factor. Our study indicates that deregulation of PP1/NIPP1 holoenzyme activates NRG-1 expression through RNAPII and CDK9 phosphorylation in a NF-κB dependent manner. Full article
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Open AccessArticle
Optimization of Cyanine Dye Stability and Analysis of FRET Interaction on DNA Microarrays
Biology 2016, 5(4), 47; doi:10.3390/biology5040047 -
Abstract
The application of DNA microarrays for high throughput analysis of genetic regulation is often limited by the fluorophores used as markers. The implementation of multi-scan techniques is limited by the fluorophores’ susceptibility to photobleaching when exposed to the scanner laser light. This paper
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The application of DNA microarrays for high throughput analysis of genetic regulation is often limited by the fluorophores used as markers. The implementation of multi-scan techniques is limited by the fluorophores’ susceptibility to photobleaching when exposed to the scanner laser light. This paper presents combined mechanical and chemical strategies which enhance the photostability of cyanine 3 and cyanine 5 as part of solid state DNA microarrays. These strategies are based on scanning the microarrays while the hybridized DNA is still in an aqueous solution with the presence of a reductive/oxidative system (ROXS). Furthermore, the experimental setup allows for the analysis and eventual normalization of Förster-resonance-energy-transfer (FRET) interaction of cyanine-3/cyanine-5 dye combinations on the microarray. These findings constitute a step towards standardization of microarray experiments and analysis and may help to increase the comparability of microarray experiment results between labs. Full article
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Open AccessArticle
Thermal Resilience of Feeding Kinematics May Contribute to the Spread of Invasive Fishes in Light of Climate Change
Biology 2016, 5(4), 46; doi:10.3390/biology5040046 -
Abstract
As a consequence of global warming, tropical invasive species are expected to expand their range pole-ward, extending their negative impacts to previously undisturbed, high-latitude ecosystems. Investigating the physiological responses of invasive species to environmental temperature is important because the coupled effects of climate
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As a consequence of global warming, tropical invasive species are expected to expand their range pole-ward, extending their negative impacts to previously undisturbed, high-latitude ecosystems. Investigating the physiological responses of invasive species to environmental temperature is important because the coupled effects of climate change and species invasion on ecosystems could be more alarming than the effects of each phenomenon independently. Especially in poikilotherms, the rate of motion in muscle-driven biomechanical systems is expected to double for every 10 °C increase in temperature. In this study, we address the question, “How does temperature affect the speed of jaw-movement during prey-capture in invasive fishes?” Kinematic analysis of invasive-fish prey-capture behavior revealed that (1) movement velocities of key components of the feeding mechanism did not double as water temperature increased from 20 °C to 30 °C; and (2) thermal sensitivity (Q10 values) for gape, hyoid, lower-jaw rotation, and cranial rotation velocities at 20 °C and 30 °C ranged from 0.56 to 1.44 in all three species. With the exception of lower-jaw rotation, Q10 values were significantly less than the expected Q10 = 2.0, indicating that feeding kinematics remains consistent despite the change in environmental temperature. It is conceivable that the ability to maintain peak performance at different temperatures helps facilitate the spread of invasive fishes globally. Full article
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Open AccessReview
Fish Immunoglobulins
Biology 2016, 5(4), 45; doi:10.3390/biology5040045 -
Abstract
The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or
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The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or cDNA sequence data, but where appropriate draw upon protein, immunization, affinity and structural studies. Work from major aquatic model organisms and less studied comparative species are both included to define what is the rule for an immunoglobulin isotype or taxonomic group and what exemplifies an exception. Full article
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Open AccessReview
A Cell Biological Perspective on Past, Present and Future Investigations of the Spindle Assembly Checkpoint
Biology 2016, 5(4), 44; doi:10.3390/biology5040044 -
Abstract
The spindle assembly checkpoint (SAC) is a quality control mechanism that ensures accurate chromosome segregation during cell division. It consists of a mechanochemical signal transduction mechanism that senses the attachment of chromosomes to the spindle, and a signaling cascade that inhibits cell division
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The spindle assembly checkpoint (SAC) is a quality control mechanism that ensures accurate chromosome segregation during cell division. It consists of a mechanochemical signal transduction mechanism that senses the attachment of chromosomes to the spindle, and a signaling cascade that inhibits cell division if one or more chromosomes are not attached. Extensive investigations of both these component systems of the SAC have synthesized a comprehensive understanding of the underlying molecular mechanisms. This review recounts the milestone results that elucidated the SAC, compiles a simple model of the complex molecular machinery underlying the SAC, and highlights poorly understood facets of the biochemical design and cell biological operation of the SAC that will drive research forward in the near future. Full article
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Open AccessArticle
Use of a Fluorescent Aptamer RNA as an Exonic Sequence to Analyze Self-Splicing Ability of a Group I Intron from Structured RNAs
Biology 2016, 5(4), 43; doi:10.3390/biology5040043 -
Abstract
Group I self-splicing intron constitutes an important class of functional RNA molecules that can promote chemical transformation. Although the fundamental mechanism of the auto-excision from its precursor RNA has been established, convenient assay systems for its splicing activity are still useful for a
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Group I self-splicing intron constitutes an important class of functional RNA molecules that can promote chemical transformation. Although the fundamental mechanism of the auto-excision from its precursor RNA has been established, convenient assay systems for its splicing activity are still useful for a further understanding of its detailed mechanism and of its application. Because some host RNA sequences, to which group I introns inserted form stable three-dimensional (3D) structures, the effects of the 3D structures of exonic elements on the splicing efficiency of group I introns are important but not a fully investigated issue. We developed an assay system for group I intron self-splicing by employing a fluorescent aptamer RNA (spinach RNA) as a model exonic sequence inserted by the Tetrahymena group I intron. We investigated self-splicing of the intron from spinach RNA, serving as a model exonic sequence with a 3D structure. Full article
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Open AccessReview
The Potential of Non-Provitamin A Carotenoids for the Prevention and Treatment of Non-Alcoholic Fatty Liver Disease
Biology 2016, 5(4), 42; doi:10.3390/biology5040042 -
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated spectrum of comorbidities defined by the presence of metabolic dysfunction, oxidative stress, inflammation, and fibrosis in the liver. If left untreated, NAFLD can progress to cirrhosis, liver failure, or hepatocellular carcinoma. NAFLD is recognized as
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Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated spectrum of comorbidities defined by the presence of metabolic dysfunction, oxidative stress, inflammation, and fibrosis in the liver. If left untreated, NAFLD can progress to cirrhosis, liver failure, or hepatocellular carcinoma. NAFLD is recognized as the most common liver disease in the United States, affecting around 30% of the population. Identification of dietary components capable of reducing or preventing NAFLD is therefore essential to battle this condition. Dietary carotenoids including astaxanthin, lycopene, lutein, and zeaxanthin have been demonstrated to be potent antioxidants as well as to exhibit anti-inflammatory effects. Many studies report the protective effect(s) of these carotenoids against different conditions such as atherosclerosis, diabetic complications, age-related macular degeneration, and liver diseases. In this review, we will focus on the effects of these carotenoids in the prevention or reduction of NAFLD as seen in epidemiological observations and clinical trials, as well as the suggested mechanism of action derived from animal and cell studies. Full article
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Open AccessArticle
X-ray Diffraction Evidence for Low Force Actin-Attached and Rigor-Like Cross-Bridges in the Contractile Cycle
Biology 2016, 5(4), 41; doi:10.3390/biology5040041 -
Abstract
Defining the structural changes involved in the myosin cross-bridge cycle on actin in active muscle by X-ray diffraction will involve recording of the whole two dimensional (2D) X-ray diffraction pattern from active muscle in a time-resolved manner. Bony fish muscle is the most
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Defining the structural changes involved in the myosin cross-bridge cycle on actin in active muscle by X-ray diffraction will involve recording of the whole two dimensional (2D) X-ray diffraction pattern from active muscle in a time-resolved manner. Bony fish muscle is the most highly ordered vertebrate striated muscle to study. With partial sarcomere length (SL) control we show that changes in the fish muscle equatorial A-band (10) and (11) reflections, along with (10)/(11) intensity ratio and the tension, are much more rapid than without such control. Times to 50% change with SL control were 19.5 (±2.0) ms, 17.0 (±1.1) ms, 13.9 (±0.4) ms and 22.5 (±0.8) ms, respectively, compared to 25.0 (±3.4) ms, 20.5 (±2.6) ms, 15.4 (±0.6) ms and 33.8 (±0.6) ms without control. The (11) intensity and the (10)/(11) intensity ratio both still change ahead of tension, supporting the likelihood of the presence of a head population close to or on actin, but producing little or no force, in the early stages of the contractile cycle. Higher order equatorials (e.g., (30), (31), and (32)), more sensitive to crossbridge conformation and distribution, also change very rapidly and overshoot their tension plateau values by a factor of around two, well before the tension plateau has been reached, once again indicating an early low-force cross-bridge state in the contractile cycle. Modelling of these intensity changes suggests the presence of probably two different actin-attached myosin head structural states (mainly low-force attached and rigor-like). No more than two main attached structural states are necessary and sufficient to explain the observations. We find that 48% of the heads are off actin giving a resting diffraction pattern, 20% of heads are in the weak binding conformation and 32% of the heads are in the strong (rigor-like) state. The strong states account for 96% of the tension at the tetanus plateau. Full article
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Open AccessReview
Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis
Biology 2016, 5(4), 40; doi:10.3390/biology5040040 -
Abstract
Glutamine synthetase (GS) is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency
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Glutamine synthetase (GS) is a cytosolic enzyme that produces glutamine, the most abundant free amino acid in the human body. Glutamine is a major substrate for various metabolic pathways, and is thus an important factor for the functioning of many organs; therefore, deficiency of glutamine due to a defect in GS is incompatible with normal life. Mutations in the human GLUL gene (encoding for GS) can cause an ultra-rare recessive inborn error of metabolism—congenital glutamine synthetase deficiency. This disease was reported until now in only three unrelated patients, all of whom suffered from neonatal onset severe epileptic encephalopathy. The hallmark of GS deficiency in these patients was decreased levels of glutamine in body fluids, associated with chronic hyperammonemia. This review aims at recapitulating the clinical history of the three known patients with congenital GS deficiency and summarizes the findings from studies done along with the work-up of these patients. It is the aim of this paper to convince the reader that (i) this disorder is possibly underdiagnosed, since decreased concentrations of metabolites do not receive the attention they deserve; and (ii) early detection of GS deficiency may help to improve the outcome of patients who could be treated early with metabolites that are lacking in this condition. Full article
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