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Int. J. Mol. Sci., Volume 17, Issue 9 (September 2016)

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Cover Story (view full-size image) Cellulose Binding Domain-Driven Silk–Cellulose Nanomaterial Ordered Assembly Cellulose binding [...] Read more.
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Open AccessReview
New Phase of Growth for Xenogeneic-Based Bioartificial Organs
Int. J. Mol. Sci. 2016, 17(9), 1593; https://doi.org/10.3390/ijms17091593
Received: 30 June 2016 / Revised: 17 August 2016 / Accepted: 29 August 2016 / Published: 21 September 2016
Cited by 4 | Viewed by 1700 | PDF Full-text (978 KB) | HTML Full-text | XML Full-text
Abstract
In this article, we examine the advanced clinical development of bioartificial organs and describe the challenges to implementing such systems into patient care. The case for bioartificial organs is evident: they are meant to reduce patient morbidity and mortality caused by the persistent [...] Read more.
In this article, we examine the advanced clinical development of bioartificial organs and describe the challenges to implementing such systems into patient care. The case for bioartificial organs is evident: they are meant to reduce patient morbidity and mortality caused by the persistent shortage of organs available for allotransplantation. The widespread introduction and adoption of bioengineered organs, incorporating cells and tissues derived from either human or animal sources, would help address this shortage. Despite the decades of development, the variety of organs studied and bioengineered, and continuous progress in the field, only two bioengineered systems are currently commercially available: Apligraf® and Dermagraft® are both approved by the FDA to treat diabetic foot ulcers, and Apligraf® is approved to treat venous leg ulcers. Currently, no products based on xenotransplantation have been approved by the FDA. Risk factors include immunological barriers and the potential infectivity of porcine endogenous retrovirus (PERV), which is unique to xenotransplantation. Recent breakthroughs in gene editing may, however, mitigate risks related to PERV. Because of its primary role in interrupting progress in xenotransplantation, we present a risk assessment for PERV infection, and conclude that the formerly high risk has been reduced to a moderate level. Advances in gene editing, and more broadly in the field, may make it more likely than ever before that bioartificial organs will alleviate the suffering of patients with organ failure. Full article
(This article belongs to the Special Issue Advances in Cell Transplantation)
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Open AccessArticle
McDonald Criteria 2010 and 2005 Compared: Persistence of High Oligoclonal Band Prevalence Despite Almost Doubled Diagnostic Sensitivity
Int. J. Mol. Sci. 2016, 17(9), 1592; https://doi.org/10.3390/ijms17091592
Received: 28 July 2016 / Revised: 7 September 2016 / Accepted: 9 September 2016 / Published: 21 September 2016
Cited by 15 | Viewed by 1840 | PDF Full-text (404 KB) | HTML Full-text | XML Full-text
Abstract
The 2010 McDonald criteria were developed to allow a more rapid diagnosis of relapsing-remitting multiple sclerosis (MS) by only one MRI of the brain. Although cerebrospinal fluid (CSF) is not a mandatory part of the latest criteria, the evidence of an intrathecal humoral [...] Read more.
The 2010 McDonald criteria were developed to allow a more rapid diagnosis of relapsing-remitting multiple sclerosis (MS) by only one MRI of the brain. Although cerebrospinal fluid (CSF) is not a mandatory part of the latest criteria, the evidence of an intrathecal humoral immunoreaction in the form of oligoclonal bands (OCB) is crucial in the diagnostic workup. To date, the impact of the 2010 McDonald criteria on the prevalence of OCB has not been investigated. We retrospectively evaluated data of 325 patients with a clinical relapse suggestive of demyelination that were treated in a German university hospital between 2010 and 2015. One hundred thirty-six patients (42%) were diagnosed with MS and 189 patients with CIS when the criteria of 2010 were applied. The criteria of 2005 allowed only 70 patients (22%) to be designated as MS. In contrast, the prevalence of OCB was marginal affected in MS patients with 96% for the criteria of 2010 and 98.5% for the criteria of 2005. In conclusion, OCB are prevalent in most MS patients and reflect the chronic inflammatory nature of the disease. We recommend CSF examination to exclude alternative diagnoses and reevaluation of the diagnosis MS in patients with negative OCB. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis 2016)
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Open AccessReview
Structure-Based Reverse Vaccinology Failed in the Case of HIV Because it Disregarded Accepted Immunological Theory
Int. J. Mol. Sci. 2016, 17(9), 1591; https://doi.org/10.3390/ijms17091591
Received: 14 July 2016 / Revised: 30 August 2016 / Accepted: 7 September 2016 / Published: 21 September 2016
Cited by 9 | Viewed by 2263 | PDF Full-text (2095 KB) | HTML Full-text | XML Full-text
Abstract
Two types of reverse vaccinology (RV) should be distinguished: genome-based RV for bacterial vaccines and structure-based RV for viral vaccines. Structure-based RV consists in trying to generate a vaccine by first determining the crystallographic structure of a complex between a viral epitope and [...] Read more.
Two types of reverse vaccinology (RV) should be distinguished: genome-based RV for bacterial vaccines and structure-based RV for viral vaccines. Structure-based RV consists in trying to generate a vaccine by first determining the crystallographic structure of a complex between a viral epitope and a neutralizing monoclonal antibody (nMab) and then reconstructing the epitope by reverse molecular engineering outside the context of the native viral protein. It is based on the unwarranted assumption that the epitope designed to fit the nMab will have acquired the immunogenic capacity to elicit a polyclonal antibody response with the same protective capacity as the nMab. After more than a decade of intensive research using this type of RV, this approach has failed to deliver an effective, preventive HIV-1 vaccine. The structure and dynamics of different types of HIV-1 epitopes and of paratopes are described. The rational design of an anti-HIV-1 vaccine is shown to be a misnomer since investigators who claim that they design a vaccine are actually only improving the antigenic binding capacity of one epitope with respect to only one paratope and not the immunogenic capacity of an epitope to elicit neutralizing antibodies. Because of the degeneracy of the immune system and the polyspecificity of antibodies, each epitope studied by the structure-based RV procedure is only one of the many epitopes that the particular nMab is able to recognize and there is no reason to assume that this nMab must have been elicited by this one epitope of known structure. Recent evidence is presented that the trimeric Env spikes of the virus possess such an enormous plasticity and intrinsic structural flexibility that it is it extremely difficult to determine which Env regions are the best candidate vaccine immunogens most likely to elicit protective antibodies. Full article
(This article belongs to the Special Issue Reverse Vaccinology)
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Open AccessArticle
Involvement of Ca2+ Signaling in the Synergistic Effects between Muscarinic Receptor Antagonists and β2-Adrenoceptor Agonists in Airway Smooth Muscle
Int. J. Mol. Sci. 2016, 17(9), 1590; https://doi.org/10.3390/ijms17091590
Received: 1 August 2016 / Revised: 2 September 2016 / Accepted: 8 September 2016 / Published: 21 September 2016
Cited by 5 | Viewed by 3300 | PDF Full-text (3002 KB) | HTML Full-text | XML Full-text
Abstract
Long-acting muscarinic antagonists (LAMAs) and short-acting β2-adrenoceptor agonists (SABAs) play important roles in remedy for COPD. To propel a translational research for development of bronchodilator therapy, synergistic effects between SABAs with LAMAs were examined focused on Ca2+ signaling using simultaneous [...] Read more.
Long-acting muscarinic antagonists (LAMAs) and short-acting β2-adrenoceptor agonists (SABAs) play important roles in remedy for COPD. To propel a translational research for development of bronchodilator therapy, synergistic effects between SABAs with LAMAs were examined focused on Ca2+ signaling using simultaneous records of isometric tension and F340/F380 in fura-2-loaded tracheal smooth muscle. Glycopyrronium (3 nM), a LAMA, modestly reduced methacholine (1 μM)-induced contraction. When procaterol, salbutamol and SABAs were applied in the presence of glycopyrronium, relaxant effects of these SABAs are markedly enhanced, and percent inhibition of tension was much greater than the sum of those for each agent and those expected from the BI theory. In contrast, percent inhibition of F340/F380 was not greater than those values. Bisindolylmaleimide, an inhibitor of protein kinase C (PKC), significantly increased the relaxant effect of LAMA without reducing F340/F380. Iberiotoxin, an inhibitor of large-conductance Ca2+-activated K+ (KCa) channels, significantly suppressed the effects of these combined agents with reducing F340/F380. In conclusion, combination of SABAs with LAMAs synergistically enhances inhibition of muscarinic contraction via decreasing both Ca2+ sensitization mediated by PKC and Ca2+ dynamics mediated by KCa channels. PKC and KCa channels may be molecular targets for cross talk between β2-adrenoceptors and muscarinic receptors. Full article
(This article belongs to the collection G Protein-Coupled Receptor Signaling and Regulation)
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Open AccessArticle
Multiplex Gene Expression Profiling of 16 Target Genes in Neoplastic and Non-Neoplastic Canine Mammary Tissues Using Branched-DNA Assay
Int. J. Mol. Sci. 2016, 17(9), 1589; https://doi.org/10.3390/ijms17091589
Received: 8 August 2016 / Revised: 7 September 2016 / Accepted: 9 September 2016 / Published: 21 September 2016
Viewed by 1756 | PDF Full-text (588 KB) | HTML Full-text | XML Full-text
Abstract
Mammary gland tumors are one of the most common neoplasms in female dogs, and certain breeds are prone to develop the disease. The use of biomarkers in canines is still restricted to research purposes. Therefore, the necessity to analyze gene profiles in different [...] Read more.
Mammary gland tumors are one of the most common neoplasms in female dogs, and certain breeds are prone to develop the disease. The use of biomarkers in canines is still restricted to research purposes. Therefore, the necessity to analyze gene profiles in different mammary entities in large sample sets is evident in order to evaluate the strength of potential markers serving as future prognostic factors. The aim of the present study was to analyze the gene expression of 16 target genes (BRCA1, BRCA2, FOXO3, GATA4, HER2, HMGA1, HMGA2, HMGB1, MAPK1, MAPK3, MCL1, MYC, PFDN5, PIK3CA, PTEN, and TP53) known to be involved in human and canine mammary neoplasm development. Expression was analyzed in 111 fresh frozen (FF) and in 170 formalin-fixed, paraffin-embedded (FFPE) specimens of neoplastic and non-neoplastic canine mammary tissues using a multiplexed branched-DNA (b-DNA) assay. TP53, FOXO3, PTEN, and PFDN5 expression revealed consistent results with significant low expression in malignant tumors. The possibility of utilizing them as predictive factors as well as for assisting in the choice of an adequate gene therapy may help in the development of new and improved approaches in canine mammary tumors. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessArticle
Anthocyanin Attenuates Doxorubicin-Induced Cardiomyotoxicity via Estrogen Receptor-α/β and Stabilizes HSF1 to Inhibit the IGF-IIR Apoptotic Pathway
Int. J. Mol. Sci. 2016, 17(9), 1588; https://doi.org/10.3390/ijms17091588
Received: 24 June 2016 / Revised: 23 August 2016 / Accepted: 13 September 2016 / Published: 21 September 2016
Cited by 10 | Viewed by 2464 | PDF Full-text (3166 KB) | HTML Full-text | XML Full-text
Abstract
Doxorubicin (Dox) is extensively used for chemotherapy in different types of cancer, but its use is limited to because of its cardiotoxicity. Our previous studies found that doxorubicin-induced insulin-like growth factor II receptor (IGF-IIR) accumulation causes cardiomyocytes apoptosis via down-regulation of HSF1 pathway. [...] Read more.
Doxorubicin (Dox) is extensively used for chemotherapy in different types of cancer, but its use is limited to because of its cardiotoxicity. Our previous studies found that doxorubicin-induced insulin-like growth factor II receptor (IGF-IIR) accumulation causes cardiomyocytes apoptosis via down-regulation of HSF1 pathway. In these studies, we demonstrated a new mechanism through which anthocyanin protects cardiomyoblast cells against doxorubicin-induced injury. We found that anthocyanin decreased IGF-IIR expression via estrogen receptors and stabilized heat shock factor 1 (HSF1) to inhibit caspase 3 activation and apoptosis of cardiomyocytes. Therefore, the phytoestrogen from plants has been considered as another potential treatment for heart failure. It has been reported that the natural compound anthocyanin (ACN) has the ability to reduce the risk of cardiovascular disease (CVD). Here, we demonstrated that anthocyanin acts as a cardioprotective drug against doxorubicin-induced heart failure by attenuating cardiac apoptosis via estrogen receptors to stabilize HSF1 expression and down-regulated IGF-IIR-induced cardiomyocyte apoptosis. Full article
(This article belongs to the Special Issue Anthocyanins)
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Open AccessReview
Cancer Cell Fusion: Mechanisms Slowly Unravel
Int. J. Mol. Sci. 2016, 17(9), 1587; https://doi.org/10.3390/ijms17091587
Received: 28 July 2016 / Revised: 26 August 2016 / Accepted: 12 September 2016 / Published: 21 September 2016
Cited by 20 | Viewed by 2053 | PDF Full-text (411 KB) | HTML Full-text | XML Full-text
Abstract
Although molecular mechanisms and signaling pathways driving invasion and metastasis have been studied for many years, the origin of the population of metastatic cells within the primary tumor is still not well understood. About a century ago, Aichel proposed that cancer cell fusion [...] Read more.
Although molecular mechanisms and signaling pathways driving invasion and metastasis have been studied for many years, the origin of the population of metastatic cells within the primary tumor is still not well understood. About a century ago, Aichel proposed that cancer cell fusion was a mechanism of cancer metastasis. This hypothesis gained some support over the years, and recently became the focus of many studies that revealed increasing evidence pointing to the possibility that cancer cell fusion probably gives rise to the metastatic phenotype by generating widespread genetic and epigenetic diversity, leading to the emergence of critical populations needed to evolve resistance to the treatment and development of metastasis. In this review, we will discuss the clinical relevance of cancer cell fusion, describe emerging mechanisms of cancer cell fusion, address why inhibiting cancer cell fusion could represent a critical line of attack to limit drug resistance and to prevent metastasis, and suggest one new modality for doing so. Full article
(This article belongs to the Special Issue Cell Fusion in Cancer)
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Open AccessArticle
Differential Impact of Hyperglycemia in Critically Ill Patients: Significance in Acute Myocardial Infarction but Not in Sepsis?
Int. J. Mol. Sci. 2016, 17(9), 1586; https://doi.org/10.3390/ijms17091586
Received: 5 August 2016 / Revised: 4 September 2016 / Accepted: 12 September 2016 / Published: 21 September 2016
Cited by 5 | Viewed by 1983 | PDF Full-text (879 KB) | HTML Full-text | XML Full-text
Abstract
Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe [...] Read more.
Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses. From 2006 to 2009, 2551 patients 69 (58–77) years; 1544 male; 337 patients suffering from type 2 diabetes (T2DM)) who were admitted because of either AMI or sepsis to an ICU in a tertiary care hospital were investigated retrospectively. Follow-up of patients was performed between May 2013 and November 2013. In a Cox regression analysis, maximum glucose concentration at the day of admission was associated with mortality in the overall cohort (HR = 1.006, 95% CI: 1.004–1.009; p < 0.001) and in patients suffering from myocardial infarction (HR = 1.101, 95% CI: 1.075–1.127; p < 0.001) but only in trend in patients admitted to an ICU for sepsis (HR = 1.030, 95% CI: 0.998–1.062; p = 0.07). Severe hyperglycemia was associated with adverse intra-ICU mortality in the overall cohort (23% vs. 13%; p < 0.001) and patients admitted for AMI (15% vs. 5%; p < 0.001) but not for septic patients (39% vs. 40%; p = 0.48). A medical history of type 2 diabetes (n = 337; 13%) was not associated with increased intra-ICU mortality (15% vs. 15%; p = 0.93) but in patients with severe hyperglycemia and/or a known medical history of type 2 diabetes considered in combination, an increased mortality in AMI patients (intra-ICU 5% vs. 13%; p < 0.001) but not in septic patients (intra-ICU 38% vs. 41%; p = 0.53) could be evidenced. The presence of hyperglycemia in critically ill patients has differential impact within the different etiological groups. Hyperglycemia in AMI patients might identify a sicker patient collective suffering from pre-diabetes or undiagnosed diabetes with its’ known adverse consequences, especially in the long-term. Hyperglycemia in sepsis might be considered as adaptive survival mechanism to hypo-perfusion and consecutive lack of glucose in peripheral cells. AMI patients with hyperglycemic derailment during an ICU-stay should be closely followed-up and extensively screened for diabetes to improve patients’ outcome. Full article
(This article belongs to the Special Issue Diabetic Complications: Pathophysiology, Mechanisms, and Therapies)
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Open AccessReview
Protein Kinases and Parkinson’s Disease
Int. J. Mol. Sci. 2016, 17(9), 1585; https://doi.org/10.3390/ijms17091585
Received: 30 May 2016 / Revised: 9 August 2016 / Accepted: 1 September 2016 / Published: 20 September 2016
Cited by 8 | Viewed by 1958 | PDF Full-text (597 KB) | HTML Full-text | XML Full-text
Abstract
Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved [...] Read more.
Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson’s disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson’s disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules. Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2016)
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Open AccessReview
Neuroprotection, Growth Factors and BDNF-TrkB Signalling in Retinal Degeneration
Int. J. Mol. Sci. 2016, 17(9), 1584; https://doi.org/10.3390/ijms17091584
Received: 27 July 2016 / Revised: 1 September 2016 / Accepted: 14 September 2016 / Published: 20 September 2016
Cited by 57 | Viewed by 3691 | PDF Full-text (2008 KB) | HTML Full-text | XML Full-text
Abstract
Neurotrophic factors play key roles in the development and survival of neurons. The potent neuroprotective effects of neurotrophic factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF) and nerve growth factor (NGF), suggest that they are [...] Read more.
Neurotrophic factors play key roles in the development and survival of neurons. The potent neuroprotective effects of neurotrophic factors, including brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF) and nerve growth factor (NGF), suggest that they are good therapeutic candidates for neurodegenerative diseases. Glaucoma is a neurodegenerative disease of the eye that causes irreversible blindness. It is characterized by damage to the optic nerve, usually due to high intraocular pressure (IOP), and progressive degeneration of retinal neurons called retinal ganglion cells (RGCs). Current therapy for glaucoma focuses on reduction of IOP, but neuroprotection may also be beneficial. BDNF is a powerful neuroprotective agent especially for RGCs. Exogenous application of BDNF to the retina and increased BDNF expression in retinal neurons using viral vector systems are both effective in protecting RGCs from damage. Furthermore, induction of BDNF expression by agents such as valproic acid has also been beneficial in promoting RGC survival. In this review, we discuss the therapeutic potential of neurotrophic factors in retinal diseases and focus on the differential roles of glial and neuronal TrkB in neuroprotection. We also discuss the role of neurotrophic factors in neuroregeneration. Full article
(This article belongs to the Special Issue Neurotrophic Factors—Historical Perspective and New Directions)
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Open AccessArticle
Alterations in Serum Polyunsaturated Fatty Acids and Eicosanoids in Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)
Int. J. Mol. Sci. 2016, 17(9), 1583; https://doi.org/10.3390/ijms17091583
Received: 14 July 2016 / Revised: 6 September 2016 / Accepted: 13 September 2016 / Published: 20 September 2016
Cited by 6 | Viewed by 2759 | PDF Full-text (1761 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Smoking is a major risk factor for several diseases including chronic obstructive pulmonary disease (COPD). To better understand the systemic effects of cigarette smoke exposure and mild to moderate COPD—and to support future biomarker development—we profiled the serum lipidomes of healthy smokers, smokers [...] Read more.
Smoking is a major risk factor for several diseases including chronic obstructive pulmonary disease (COPD). To better understand the systemic effects of cigarette smoke exposure and mild to moderate COPD—and to support future biomarker development—we profiled the serum lipidomes of healthy smokers, smokers with mild to moderate COPD (GOLD stages 1 and 2), former smokers, and never-smokers (n = 40 per group) (ClinicalTrials.gov registration: NCT01780298). Serum lipidome profiling was conducted with untargeted and targeted mass spectrometry-based lipidomics. Guided by weighted lipid co-expression network analysis, we identified three main trends comparing smokers, especially those with COPD, with non-smokers: a general increase in glycero(phospho)lipids, including triglycerols; changes in fatty acid desaturation (decrease in ω-3 polyunsaturated fatty acids, and an increase in monounsaturated fatty acids); and an imbalance in eicosanoids (increase in 11,12- and 14,15-DHETs (dihydroxyeicosatrienoic acids), and a decrease in 9- and 13-HODEs (hydroxyoctadecadienoic acids)). The lipidome profiles supported classification of study subjects as smokers or non-smokers, but were not sufficient to distinguish between smokers with and without COPD. Overall, our study yielded further insights into the complex interplay between smoke exposure, lung disease, and systemic alterations in serum lipid profiles. Full article
(This article belongs to the Section Molecular Toxicology)
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Open AccessArticle
Salinity-Induced Variation in Biochemical Markers Provides Insight into the Mechanisms of Salt Tolerance in Common (Phaseolus vulgaris) and Runner (P. coccineus) Beans
Int. J. Mol. Sci. 2016, 17(9), 1582; https://doi.org/10.3390/ijms17091582
Received: 5 August 2016 / Revised: 7 September 2016 / Accepted: 12 September 2016 / Published: 20 September 2016
Cited by 11 | Viewed by 1937 | PDF Full-text (2253 KB) | HTML Full-text | XML Full-text
Abstract
The evaluation of biochemical markers is important for the understanding of the mechanisms of tolerance to salinity of Phaseolus beans. We have evaluated several growth parameters in young plants of three Phaseolus vulgaris cultivars subjected to four salinity levels (0, 50, 100, and [...] Read more.
The evaluation of biochemical markers is important for the understanding of the mechanisms of tolerance to salinity of Phaseolus beans. We have evaluated several growth parameters in young plants of three Phaseolus vulgaris cultivars subjected to four salinity levels (0, 50, 100, and 150 mM NaCl); one cultivar of P. coccineus, a closely related species reported as more salt tolerant than common bean, was included as external reference. Biochemical parameters evaluated in leaves of young plants included the concentrations of ions (Na+, K+, and Cl), osmolytes (proline, glycine betaine, and total soluble sugars), and individual soluble carbohydrates. Considerable differences were found among cultivars, salinity levels, and in their interaction for most traits. In general, the linear component of the salinity factor for the growth parameters and biochemical markers was the most important. Large differences in the salinity response were found, with P. vulgaris cultivars “The Prince” and “Maxidor” being, respectively, the most susceptible and tolerant ones. Our results support that salt stress tolerance in beans is mostly based on restriction of Na+ (and, to a lesser extent, also of Cl) transport to shoots, and on the accumulation of myo-inositol for osmotic adjustment. These responses to stress during vegetative growth appear to be more efficient in the tolerant P. vulgaris cultivar “Maxidor”. Proline accumulation is a reliable marker of the level of salt stress affecting Phaseolus plants, but does not seem to be directly related to stress tolerance mechanisms. These results provide useful information on the responses to salinity of Phaseolus. Full article
(This article belongs to the Special Issue Pulses)
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Open AccessArticle
Candida antarctica Lipase B Immobilized onto Chitin Conjugated with POSS® Compounds: Useful Tool for Rapeseed Oil Conversion
Int. J. Mol. Sci. 2016, 17(9), 1581; https://doi.org/10.3390/ijms17091581
Received: 28 July 2016 / Revised: 8 September 2016 / Accepted: 9 September 2016 / Published: 20 September 2016
Cited by 9 | Viewed by 2067 | PDF Full-text (2141 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new method is proposed for the production of a novel chitin-polyhedral oligomeric silsesquioxanes (POSS) enzyme support. Analysis by such techniques as X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy confirmed the effective functionalization of the chitin surface. The resulting hybrid carriers were used [...] Read more.
A new method is proposed for the production of a novel chitin-polyhedral oligomeric silsesquioxanes (POSS) enzyme support. Analysis by such techniques as X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy confirmed the effective functionalization of the chitin surface. The resulting hybrid carriers were used in the process of immobilization of the lipase type b from Candida antarctica (CALB). Fourier transform infrared spectroscopy (FTIR) confirmed the effective immobilization of the enzyme. The tests of the catalytic activity showed that the resulting support-biocatalyst systems remain hydrolytically active (retention of the hydrolytic activity up to 87% for the chitin + Methacryl POSS® cage mixture (MPOSS) + CALB after 24 h of the immobilization), as well as represents good thermal and operational stability, and retain over 80% of its activity in a wide range of temperatures (30–60 °C) and pH (6–9). Chitin-POSS-lipase systems were used in the transesterification processes of rapeseed oil at various reaction conditions. Produced systems allowed the total conversion of the oil to fatty acid methyl esters (FAME) and glycerol after 24 h of the process at pH 10 and a temperature 40 °C, while the Methacryl POSS® cage mixture (MPOSS) was used as a chitin-modifying agent. Full article
(This article belongs to the Special Issue Frontiers of Marine Biomaterials)
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Open AccessReview
Clinical Application of Circulating Tumour Cells in Prostate Cancer: From Bench to Bedside and Back
Int. J. Mol. Sci. 2016, 17(9), 1580; https://doi.org/10.3390/ijms17091580
Received: 2 July 2016 / Revised: 5 September 2016 / Accepted: 9 September 2016 / Published: 20 September 2016
Cited by 7 | Viewed by 2509 | PDF Full-text (549 KB) | HTML Full-text | XML Full-text
Abstract
Prostate cancer is the most common cancer in men worldwide. To improve future drug development and patient management, surrogate biomarkers associated with relevant outcomes are required. Circulating tumour cells (CTCs) are tumour cells that can enter the circulatory system, and are principally responsible [...] Read more.
Prostate cancer is the most common cancer in men worldwide. To improve future drug development and patient management, surrogate biomarkers associated with relevant outcomes are required. Circulating tumour cells (CTCs) are tumour cells that can enter the circulatory system, and are principally responsible for the development of metastasis at distant sites. In recent years, interest in detecting CTCs as a surrogate biomarker has ghiiukjrown. Clinical studies have revealed that high levels of CTCs in the blood correlate with disease progression in patients with prostate cancer; however, their predictive value for monitoring therapeutic response is less clear. Despite the important progress in CTC clinical development, there are critical requirements for the implementation of their analysis as a routine oncology tool. The goal of the present review is to provide an update on the advances in the clinical validation of CTCs as a surrogate biomarker and to discuss the principal obstacles and main challenges to their inclusion in clinical practice. Full article
(This article belongs to the Special Issue Circulating Tumor Cells)
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Open AccessCommunication
Pre-Analytical Considerations for Successful Next-Generation Sequencing (NGS): Challenges and Opportunities for Formalin-Fixed and Paraffin-Embedded Tumor Tissue (FFPE) Samples
Int. J. Mol. Sci. 2016, 17(9), 1579; https://doi.org/10.3390/ijms17091579
Received: 8 August 2016 / Revised: 8 September 2016 / Accepted: 13 September 2016 / Published: 20 September 2016
Cited by 12 | Viewed by 2256 | PDF Full-text (721 KB) | HTML Full-text | XML Full-text
Abstract
In cancer drug discovery, it is important to investigate the genetic determinants of response or resistance to cancer therapy as well as factors that contribute to adverse events in the course of clinical trials. Despite the emergence of new technologies and the ability [...] Read more.
In cancer drug discovery, it is important to investigate the genetic determinants of response or resistance to cancer therapy as well as factors that contribute to adverse events in the course of clinical trials. Despite the emergence of new technologies and the ability to measure more diverse analytes (e.g., circulating tumor cell (CTC), circulating tumor DNA (ctDNA), etc.), tumor tissue is still the most common and reliable source for biomarker investigation. Because of its worldwide use and ability to preserve samples for many decades at ambient temperature, formalin-fixed, paraffin-embedded tumor tissue (FFPE) is likely to be the preferred choice for tissue preservation in clinical practice for the foreseeable future. Multiple analyses are routinely performed on the same FFPE samples (such as Immunohistochemistry (IHC), in situ hybridization, RNAseq, DNAseq, TILseq, Methyl-Seq, etc.). Thus, specimen prioritization and optimization of the isolation of analytes is critical to ensure successful completion of each assay. FFPE is notorious for producing suboptimal DNA quality and low DNA yield. However, commercial vendors tend to request higher DNA sample mass than what is actually required for downstream assays, which restricts the breadth of biomarker work that can be performed. We evaluated multiple genomics service laboratories to assess the current state of NGS pre-analytical processing of FFPE. Significant differences in pre-analytical capabilities were observed. Key aspects are highlighted and recommendations are made to improve the current practice in translational research. Full article
(This article belongs to the Special Issue Next-Generation Sequencing for Clinical Application)
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Open AccessReview
Recent Advances in Antimicrobial Polymers: A Mini-Review
Int. J. Mol. Sci. 2016, 17(9), 1578; https://doi.org/10.3390/ijms17091578
Received: 21 July 2016 / Revised: 6 September 2016 / Accepted: 14 September 2016 / Published: 20 September 2016
Cited by 66 | Viewed by 2952 | PDF Full-text (1562 KB) | HTML Full-text | XML Full-text
Abstract
Human safety and well-being is threatened by microbes causing numerous infectious diseases resulting in a large number of deaths every year. Despite substantial progress in antimicrobial drugs, many infectious diseases remain difficult to treat. Antimicrobial polymers offer a promising antimicrobial strategy for fighting [...] Read more.
Human safety and well-being is threatened by microbes causing numerous infectious diseases resulting in a large number of deaths every year. Despite substantial progress in antimicrobial drugs, many infectious diseases remain difficult to treat. Antimicrobial polymers offer a promising antimicrobial strategy for fighting pathogens and have received considerable attention in both academic and industrial research. This mini-review presents the advances made in antimicrobial polymers since 2013. Antimicrobial mechanisms exhibiting either passive or active action and polymer material types containing bound or leaching antimicrobials are introduced. This article also addresses the applications of these antimicrobial polymers in the medical, food, and textile industries. Full article
(This article belongs to the Special Issue Antimicrobial Polymers 2016)
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Open AccessReview
Reactivities of Quinone Methides versus o-Quinones in Catecholamine Metabolism and Eumelanin Biosynthesis
Int. J. Mol. Sci. 2016, 17(9), 1576; https://doi.org/10.3390/ijms17091576
Received: 18 August 2016 / Revised: 8 September 2016 / Accepted: 12 September 2016 / Published: 20 September 2016
Cited by 20 | Viewed by 3498 | PDF Full-text (5100 KB) | HTML Full-text | XML Full-text
Abstract
Melanin is an important biopolymeric pigment produced in a vast majority of organisms. Tyrosine and its hydroxylated product, dopa, form the starting material for melanin biosynthesis. Earlier studies by Raper and Mason resulted in the identification of dopachrome and dihydroxyindoles as important intermediates [...] Read more.
Melanin is an important biopolymeric pigment produced in a vast majority of organisms. Tyrosine and its hydroxylated product, dopa, form the starting material for melanin biosynthesis. Earlier studies by Raper and Mason resulted in the identification of dopachrome and dihydroxyindoles as important intermediates and paved way for the establishment of well-known Raper–Mason pathway for the biogenesis of brown to black eumelanins. Tyrosinase catalyzes the oxidation of tyrosine as well as dopa to dopaquinone. Dopaquinone thus formed, undergoes intramolecular cyclization to form leucochrome, which is further oxidized to dopachrome. Dopachrome is either converted into 5,6-dihydroxyindole by decarboxylative aromatization or isomerized into 5,6-dihydroxyindole-2-carboxylic acid. Oxidative polymerization of these two dihydroxyindoles eventually produces eumelanin pigments via melanochrome. While the role of quinones in the biosynthetic pathway is very well acknowledged, that of isomeric quinone methides, however, remained marginalized. This review article summarizes the key role of quinone methides during the oxidative transformation of a vast array of catecholamine derivatives and brings out the importance of these transient reactive species during the melanogenic process. In addition, possible reactions of quinone methides at various stages of melanogenesis are discussed. Full article
(This article belongs to the Special Issue Biochemistry and Mechanisms of Melanogenesis)
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Open AccessReview
Molecular Pathogenesis of NASH
Int. J. Mol. Sci. 2016, 17(9), 1575; https://doi.org/10.3390/ijms17091575
Received: 14 July 2016 / Revised: 5 September 2016 / Accepted: 7 September 2016 / Published: 20 September 2016
Cited by 40 | Viewed by 3656 | PDF Full-text (1048 KB) | HTML Full-text | XML Full-text
Abstract
Nonalcoholic steatohepatitis (NASH) is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as [...] Read more.
Nonalcoholic steatohepatitis (NASH) is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression. Full article
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Open AccessArticle
Alliin Attenuated RANKL-Induced Osteoclastogenesis by Scavenging Reactive Oxygen Species through Inhibiting Nox1
Int. J. Mol. Sci. 2016, 17(9), 1516; https://doi.org/10.3390/ijms17091516
Received: 16 June 2016 / Revised: 21 August 2016 / Accepted: 6 September 2016 / Published: 20 September 2016
Cited by 8 | Viewed by 2012 | PDF Full-text (3450 KB) | HTML Full-text | XML Full-text
Abstract
The healthy skeleton requires a perfect coordination of the formation and degradation of bone. Metabolic bone disease like osteoporosis is resulted from the imbalance of bone formation and/or bone resorption. Osteoporosis also reflects lower level of bone matrix, which is contributed by up-regulated [...] Read more.
The healthy skeleton requires a perfect coordination of the formation and degradation of bone. Metabolic bone disease like osteoporosis is resulted from the imbalance of bone formation and/or bone resorption. Osteoporosis also reflects lower level of bone matrix, which is contributed by up-regulated osteoclast-mediated bone resorption. It is reported that monocytes/macrophage progenitor cells or either hematopoietic stem cells (HSCs) gave rise to multinucleated osteoclasts. Thus, inhibition of osteoclastic bone resorption generally seems to be a predominant therapy for treating osteoporosis. Recently, more and more natural compounds have been discovered, which have the ability of inhibiting osteoclast differentiation and fusion. Alliin (S-allyl-l-cysteine sulfoxides, SACSO) is the major component of aged garlic extract (AGE), bearing broad-spectrum natural antioxidant properties. However, its effects on bone health have not yet been explored. Hence, we designed the current study to explore its effects and role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast fusion and differentiation. It was revealed that alliin had an inhibitory effect in osteoclasteogenesis with a dose-dependent manner via blocking the c-Fos-NFATc1 signaling pathway. In addition, alliin decreased the generation of reactive oxygen species (ROS) and down-regulated the expression of NADPH oxidase 1 (Nox1). The overall results revealed that alliin could be a potential therapeutic agent in the treatment of osteoporosis. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention)
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Open AccessArticle
Effect of Thyrotropin on Osteopontin, Integrin αvβ3, and VCAM-1 in the Endothelium via Activation of Akt
Int. J. Mol. Sci. 2016, 17(9), 1484; https://doi.org/10.3390/ijms17091484
Received: 26 July 2016 / Revised: 23 August 2016 / Accepted: 31 August 2016 / Published: 20 September 2016
Cited by 2 | Viewed by 2006 | PDF Full-text (4770 KB) | HTML Full-text | XML Full-text
Abstract
Numerous epidemiological studies have shown that subclinical hypothyroidism (SCH) can impair endothelial function and cause dyslipidemia. Studies have evaluated the effects of thyroid stimulating hormone (TSH) on endothelial cells, but the mechanism underlying the proatherosclerotic effect of increased TSH levels remains unclear. In [...] Read more.
Numerous epidemiological studies have shown that subclinical hypothyroidism (SCH) can impair endothelial function and cause dyslipidemia. Studies have evaluated the effects of thyroid stimulating hormone (TSH) on endothelial cells, but the mechanism underlying the proatherosclerotic effect of increased TSH levels remains unclear. In the present study, SCH rat models were established in thyroidectomized Wistar rats that were given ʟ-T4 daily. The results showed that in vivo, the expression of osteopontin (OPN) vascular cell adhesion molecule (VCAM-1), and levels of integrin αvβ3 in the aortic tissue in SCH and Hypothyroidism (CH) groups was higher than in the control group. However, the effect in the SCH group was higher than in the CH group. In vitro, results showed that different concentration and time gradients of TSH stimulation could increase the expression of OPN, VCAM-1, and integrin αvβ3, and this was accompanied by extracellular signal regulated kinase 1/2 (Erk1/2) and Akt activation in human umbilical vein endothelial cells (HUVECs). TSH induced elevation of these proatherosclerotic factors was partially suppressed by a specific Akt inhibitor but not by a specific Erk inhibitor. Findings suggested that the endothelial dysfunction caused by SCH was related to increased proatherosclerotic factors induced by TSH via Akt activation. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
Metabolomics Analysis of the Larval Head of the Silkworm, Bombyx mori
Int. J. Mol. Sci. 2016, 17(9), 1460; https://doi.org/10.3390/ijms17091460
Received: 23 July 2016 / Revised: 25 August 2016 / Accepted: 26 August 2016 / Published: 20 September 2016
Cited by 5 | Viewed by 2034 | PDF Full-text (1036 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The head, which performs many biological functions, is the most complicated structure of an insect. Development, locomotor behavior, food intake, environmental sensing, and signal transduction are all controlled by the insect’s head. As a well-studied insect in Lepidoptera, the silkworm head has an [...] Read more.
The head, which performs many biological functions, is the most complicated structure of an insect. Development, locomotor behavior, food intake, environmental sensing, and signal transduction are all controlled by the insect’s head. As a well-studied insect in Lepidoptera, the silkworm head has an additional function of spinning silk fibers. To understand which molecules are involved in these physiological activities, we performed a metabolomics analysis of silkworm heads. By integrating GC-MS and LC-MS/MS, 90 metabolites were identified in the larval heads of silkworms. These were classified into 13 categories, including amino acids, sugars, organic acids, nucleotides, alcohols, and fatty acids. Informatics analysis revealed that these metabolites are involved in cellular processes, environmental information processing, genetic information processing, human diseases, metabolism, organismal systems, and other pathways. The identified metabolites and pathways are involved in biological processes such as signal transduction, carbohydrate metabolism, endocrine activities, and sensory activities; reflecting the functions of various organs in silkworm heads. Thus, our findings provide references which elucidate the potential functions of the silkworm head and will be of great value for the metabolomics research of silkworms and other insects. Full article
(This article belongs to the Section Biochemistry)
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Open AccessCorrection
Correction: G. Bradley Schaefer. Clinical Genetic Aspects of ASD Spectrum Disorders. Int. J. Mol. Sci. 2016, 17, 180
Int. J. Mol. Sci. 2016, 17(9), 1572; https://doi.org/10.3390/ijms17091572
Received: 7 September 2016 / Accepted: 16 September 2016 / Published: 19 September 2016
Cited by 2 | Viewed by 1187 | PDF Full-text (139 KB) | HTML Full-text | XML Full-text
Abstract
The author wishes to make a change to the published paper [1].[...] Full article
Open AccessArticle
DNA Interaction Studies of Selected Polyamine Conjugates
Int. J. Mol. Sci. 2016, 17(9), 1560; https://doi.org/10.3390/ijms17091560
Received: 7 July 2016 / Revised: 9 September 2016 / Accepted: 9 September 2016 / Published: 19 September 2016
Cited by 5 | Viewed by 1474 | PDF Full-text (2281 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The interaction of polyamine conjugates with DNA double helix has been studied. Binding properties were examined by ethidium bromide (EtBr) displacement and DNA unwinding/topoisomerase I/II (Topo I/II) activity assays, as well as dsDNA thermal stability studies and circular dichroism spectroscopy. Genotoxicity of the [...] Read more.
The interaction of polyamine conjugates with DNA double helix has been studied. Binding properties were examined by ethidium bromide (EtBr) displacement and DNA unwinding/topoisomerase I/II (Topo I/II) activity assays, as well as dsDNA thermal stability studies and circular dichroism spectroscopy. Genotoxicity of the compounds was estimated by a comet assay. It has been shown that only compound 2a can interact with dsDNA via an intercalative binding mode as it displaced EtBr from the dsDNA-dye complex, with Kapp = 4.26 × 106 M−1; caused an increase in melting temperature; changed the circular dichroism spectrum of dsDNA; converted relaxed plasmid DNA into a supercoiled molecule in the presence of Topo I and reduced the amount of short oligonucleotide fragments in the comet tail. Furthermore, preliminary theoretical study has shown that interaction of the discussed compounds with dsDNA depends on molecule linker length and charge distribution over terminal aromatic chromophores. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
Spider Silk-CBD-Cellulose Nanocrystal Composites: Mechanism of Assembly
Int. J. Mol. Sci. 2016, 17(9), 1573; https://doi.org/10.3390/ijms17091573
Received: 30 June 2016 / Revised: 22 August 2016 / Accepted: 8 September 2016 / Published: 18 September 2016
Cited by 4 | Viewed by 2966 | PDF Full-text (7183 KB) | HTML Full-text | XML Full-text
Abstract
The fabrication of cellulose-spider silk bio-nanocomposites comprised of cellulose nanocrystals (CNCs) and recombinant spider silk protein fused to a cellulose binding domain (CBD) is described. Silk-CBD successfully binds cellulose, and unlike recombinant silk alone, silk-CBD self-assembles into microfibrils even in the absence of [...] Read more.
The fabrication of cellulose-spider silk bio-nanocomposites comprised of cellulose nanocrystals (CNCs) and recombinant spider silk protein fused to a cellulose binding domain (CBD) is described. Silk-CBD successfully binds cellulose, and unlike recombinant silk alone, silk-CBD self-assembles into microfibrils even in the absence of CNCs. Silk-CBD-CNC composite sponges and films show changes in internal structure and CNC alignment related to the addition of silk-CBD. The silk-CBD sponges exhibit improved thermal and structural characteristics in comparison to control recombinant spider silk sponges. The glass transition temperature (Tg) of the silk-CBD sponge was higher than the control silk sponge and similar to native dragline spider silk fibers. Gel filtration analysis, dynamic light scattering (DLS), small angle X-ray scattering (SAXS) and cryo-transmission electron microscopy (TEM) indicated that silk-CBD, but not the recombinant silk control, formed a nematic liquid crystalline phase similar to that observed in native spider silk during the silk spinning process. Silk-CBD microfibrils spontaneously formed in solution upon ultrasonication. We suggest a model for silk-CBD assembly that implicates CBD in the central role of driving the dimerization of spider silk monomers, a process essential to the molecular assembly of spider-silk nanofibers and silk-CNC composites. Full article
(This article belongs to the Special Issue Silk-Based Materials: From Production to Characterization)
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Open AccessArticle
Immunoglobulin Tau Heavy Chain (IgT) in Flounder, Paralichthys olivaceus: Molecular Cloning, Characterization, and Expression Analyses
Int. J. Mol. Sci. 2016, 17(9), 1571; https://doi.org/10.3390/ijms17091571
Received: 22 July 2016 / Revised: 12 September 2016 / Accepted: 12 September 2016 / Published: 17 September 2016
Cited by 8 | Viewed by 2112 | PDF Full-text (4973 KB) | HTML Full-text | XML Full-text
Abstract
Immunoglobulin tau (IgT) is a new teleost immunoglobulin isotype, and its potential function in adaptive immunity is not very clear. In the present study, the membrane-bound and secreted IgT (mIgT and sIgT) heavy chain genes were cloned for the first time and characterized [...] Read more.
Immunoglobulin tau (IgT) is a new teleost immunoglobulin isotype, and its potential function in adaptive immunity is not very clear. In the present study, the membrane-bound and secreted IgT (mIgT and sIgT) heavy chain genes were cloned for the first time and characterized in flounder (Paralichthys olivaceus), and found the nucleic acid sequence were exactly same in the Cτ1–Cτ4 constant domains of mIgT and sIgT, but different in variable regions and the C-terminus. The amino acid sequence of mIgT shared higher similarity with Bovichtus diacanthus (51.2%) and Dicentrarchus labrax (45.0%). Amino acid of flounder IgT, IgM, and IgD heavy chain was compared and the highest similarity was found between IgT Cτ1 and IgM Cμ1 (38%). In healthy flounder, the transcript levels of IgT mRNA were the highest in gill, spleen, and liver, and higher in peripheral blood leucocytes, skin, and hindgut. After infection and vaccination with Edwardsiella tarda via intraperitoneal injection and immersion, the qRT-PCR analysis demonstrated that the IgT mRNA level was significantly upregulated in all tested tissues, with similar dynamic tendency that increased firstly and then decreased, and higher in gill, skin, hindgut, liver, and stomach in immersion than in the injection group, but no significant difference existed in spleen and head kidney between immersion and injection groups. These results revealed that IgT responses could be simultaneously induced in both mucosal and systemic tissues after infection/vaccination via injection and immersion route, but IgT might play a more important role in mucosal immunity than in systemic immunity. Full article
(This article belongs to the Section Biochemistry)
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Open AccessReview
Biology, Pest Status, Microbiome and Control of Kudzu Bug (Hemiptera: Heteroptera: Plataspidae): A New Invasive Pest in the U.S.
Int. J. Mol. Sci. 2016, 17(9), 1570; https://doi.org/10.3390/ijms17091570
Received: 15 July 2016 / Revised: 3 September 2016 / Accepted: 9 September 2016 / Published: 16 September 2016
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Abstract
Soybean is an important food crop, and insect integrated pest management (IPM) is critical to the sustainability of this production system. In recent years, the introduction into the United States of the kudzu bug currently identified as Megacopta cribraria (F.), poses a threat [...] Read more.
Soybean is an important food crop, and insect integrated pest management (IPM) is critical to the sustainability of this production system. In recent years, the introduction into the United States of the kudzu bug currently identified as Megacopta cribraria (F.), poses a threat to soybean production. The kudzu bug was first discovered in the state of Georgia, U.S. in 2009 and since then has spread to most of the southeastern states. Because it was not found in the North American subcontinent before this time, much of our knowledge of this insect comes from research done in its native habitat. However, since the U.S. introduction, studies have been undertaken to improve our understanding of the kudzu bug basic biology, microbiome, migration patterns, host selection and management in its expanding new range. Researchers are not only looking at developing IPM strategies for the kudzu bug in soybean, but also at its unique relationship with symbiotic bacteria. Adult females deposit bacterial packets with their eggs, and the neonates feed on these packets to acquire the bacteria, Candidatus Ishikawaella capsulata. The kudzu bug should be an informative model to study the co-evolution of insect function and behavior with that of a single bacteria species. We review kudzu bug trapping and survey methods, the development of bioassays for insecticide susceptibility, insecticide efficacy, host preferences, impact of the pest on urban environments, population expansion, and the occurrence of natural enemies. The identity of the kudzu bug in the U.S. is not clear. We propose that the kudzu bug currently accepted as M. cribraria in the U.S. is actually Megacopta punctatissima, with more work needed to confirm this hypothesis. Full article
(This article belongs to the Special Issue Plant-Insect Interactions)
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Open AccessArticle
Molecular Characterization and Growth Association of Two Apolipoprotein A-Ib Genes in Common Carp (Cyprinus carpio)
Int. J. Mol. Sci. 2016, 17(9), 1569; https://doi.org/10.3390/ijms17091569
Received: 16 May 2016 / Revised: 1 September 2016 / Accepted: 1 September 2016 / Published: 16 September 2016
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Abstract
Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is [...] Read more.
Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is relatively conserved within cyprinid fishes. During embryonic development, C. carpio apoA-Ib was first expressed at the stage of multi-cells, and the highest mRNA level was observed at the stage of optic vesicle. A ubiquitous expression pattern was detected in various tissues with extreme predominance in the liver. Significantly different expression levels were observed between light and heavy body weight groups and also in the compensatory growth test. Seventeen and eight single-nucleotide polymorphisms (SNPs) were identified in matured mRNA of the C. carpio apoA-Ib.1 and apoA-Ib.2, respectively. Two of these SNPs (apoA-Ib.2-g.183A>T and apoA-Ib.2-g.1753C>T) were significantly associated with body weight and body length in two populations of common carp. These results indicate that apoA-Ib may play an important role in the modulation of growth and development in common carp. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
Advanced Glycation End-Products Induce Apoptosis of Vascular Smooth Muscle Cells: A Mechanism for Vascular Calcification
Int. J. Mol. Sci. 2016, 17(9), 1567; https://doi.org/10.3390/ijms17091567
Received: 17 May 2016 / Revised: 27 July 2016 / Accepted: 8 September 2016 / Published: 16 September 2016
Cited by 12 | Viewed by 4282 | PDF Full-text (3221 KB) | HTML Full-text | XML Full-text
Abstract
Vascular calcification, especially medial artery calcification, is associated with cardiovascular death in patients with diabetes mellitus and chronic kidney disease (CKD). To determine the underlying mechanism of vascular calcification, we have demonstrated in our previous report that advanced glycation end-products (AGEs) stimulated calcium [...] Read more.
Vascular calcification, especially medial artery calcification, is associated with cardiovascular death in patients with diabetes mellitus and chronic kidney disease (CKD). To determine the underlying mechanism of vascular calcification, we have demonstrated in our previous report that advanced glycation end-products (AGEs) stimulated calcium deposition in vascular smooth muscle cells (VSMCs) through excessive oxidative stress and phenotypic transition into osteoblastic cells. Since AGEs can induce apoptosis, in this study we investigated its role on VSMC apoptosis, focusing mainly on the underlying mechanisms. A rat VSMC line (A7r5) was cultured, and treated with glycolaldehyde-derived AGE-bovine serum albumin (AGE3-BSA). Apoptotic cells were identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. To quantify apoptosis, an enzyme-linked immunosorbent assay (ELISA) for histone-complexed DNA fragments was employed. Real-time PCR was performed to determine the mRNA levels. Treatment of A7r5 cells with AGE3-BSA from 100 µg/mL concentration markedly increased apoptosis, which was suppressed by Nox inhibitors. AGE3-BSA significantly increased the mRNA expression of NAD(P)H oxidase components including Nox4 and p22phox, and these findings were confirmed by protein levels using immunofluorescence. Dihydroethidisum assay showed that compared with cBSA, AGE3-BSA increased reactive oxygen species level in A7r5 cells. Furthermore, AGE3-induced apoptosis was significantly inhibited by siRNA-mediated knockdown of Nox4 or p22phox. Double knockdown of Nox4 and p22phox showed a similar inhibitory effect on apoptosis as single gene silencing. Thus, our results demonstrated that NAD(P)H oxidase-derived oxidative stress are involved in AGEs-induced apoptosis of VSMCs. These findings might be important to understand the pathogenesis of vascular calcification in diabetes and CKD. Full article
(This article belongs to the collection Programmed Cell Death and Apoptosis)
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Open AccessReview
The Role of Galectin-1 in Cancer Progression, and Synthetic Multivalent Systems for the Study of Galectin-1
Int. J. Mol. Sci. 2016, 17(9), 1566; https://doi.org/10.3390/ijms17091566
Received: 23 June 2016 / Revised: 24 August 2016 / Accepted: 5 September 2016 / Published: 16 September 2016
Cited by 22 | Viewed by 2924 | PDF Full-text (2564 KB) | HTML Full-text | XML Full-text
Abstract
This review discusses the role of galectin-1 in the tumor microenvironment. First, the structure and function of galectin-1 are discussed. Galectin-1, a member of the galectin family of lectins, is a functionally dimeric galactoside-binding protein. Although galectin-1 has both intracellular and extracellular functions, [...] Read more.
This review discusses the role of galectin-1 in the tumor microenvironment. First, the structure and function of galectin-1 are discussed. Galectin-1, a member of the galectin family of lectins, is a functionally dimeric galactoside-binding protein. Although galectin-1 has both intracellular and extracellular functions, the defining carbohydrate-binding role occurs extracellularly. In this review, the extracellular roles of galectin-1 in cancer processes are discussed. In particular, the importance of multivalent interactions in galectin-1 mediated cellular processes is reviewed. Multivalent interactions involving galectin-1 in cellular adhesion, mobility and invasion, tumor-induced angiogenesis, and apoptosis are presented. Although the mechanisms of action of galectin-1 in these processes are still not well understood, the overexpression of galectin-1 in cancer progression indicates that the role of galectin-1 is significant. To conclude this review, synthetic frameworks that have been used to modulate galectin-1 processes are reviewed. Small molecule oligomers of carbohydrates, carbohydrate-functionalized pseudopolyrotaxanes, cyclodextrins, calixarenes, and glycodendrimers are presented. These synthetic multivalent systems serve as important tools for studying galectin-1 mediated cancer cellular functions. Full article
(This article belongs to the Special Issue Glycan–Receptor Interaction)
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Open AccessCommunication
Plant-to-Plant Variability in Root Metabolite Profiles of 19 Arabidopsis thaliana Accessions Is Substance-Class-Dependent
Int. J. Mol. Sci. 2016, 17(9), 1565; https://doi.org/10.3390/ijms17091565
Received: 30 June 2016 / Revised: 8 September 2016 / Accepted: 12 September 2016 / Published: 16 September 2016
Cited by 4 | Viewed by 2099 | PDF Full-text (1531 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Natural variation of secondary metabolism between different accessions of Arabidopsis thaliana (A. thaliana) has been studied extensively. In this study, we extended the natural variation approach by including biological variability (plant-to-plant variability) and analysed root metabolic patterns as well as their [...] Read more.
Natural variation of secondary metabolism between different accessions of Arabidopsis thaliana (A. thaliana) has been studied extensively. In this study, we extended the natural variation approach by including biological variability (plant-to-plant variability) and analysed root metabolic patterns as well as their variability between plants and naturally occurring accessions. To screen 19 accessions of A. thaliana, comprehensive non-targeted metabolite profiling of single plant root extracts was performed using ultra performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) and gas chromatography/electron ionization quadrupole mass spectrometry (GC/EI-QMS). Linear mixed models were applied to dissect the total observed variance. All metabolic profiles pointed towards a larger plant-to-plant variability than natural variation between accessions and variance of experimental batches. Ratios of plant-to-plant to total variability were high and distinct for certain secondary metabolites. None of the investigated accessions displayed a specifically high or low biological variability for these substance classes. This study provides recommendations for future natural variation analyses of glucosinolates, flavonoids, and phenylpropanoids and also reference data for additional substance classes. Full article
(This article belongs to the Special Issue Metabolomics in the Plant Sciences)
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