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Open AccessArticle
Human Globozoospermia-Related Gene Spata16 Is Required for Sperm Formation Revealed by CRISPR/Cas9-Mediated Mouse Models
Int. J. Mol. Sci. 2017, 18(10), 2208; doi:10.3390/ijms18102208 (registering DOI) -
Abstract
A recent genetic analysis of infertile globozoospermic patients identified causative mutations in three genes: a protein interacting with C kinase 1 (PICK1), dpy 19-like 2 (DPY19L2), and spermatogenesis associated 16 (SPATA16). Although mouse models have clarified the
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A recent genetic analysis of infertile globozoospermic patients identified causative mutations in three genes: a protein interacting with C kinase 1 (PICK1), dpy 19-like 2 (DPY19L2), and spermatogenesis associated 16 (SPATA16). Although mouse models have clarified the physiological functions of Pick1 and Dpy19l2 during spermatogenesis, Spata16 remains to be determined. Globozoospermic patients carried a homozygous point mutation in SPATA16 at 848G→A/R283Q. We generated CRISPR/Cas9-mediated mutant mice with the same amino acid substitution in the fourth exon of Spata16 to analyze the mutation site at R284Q, which corresponded with R283Q of mutated human SPATA16. We found that the point mutation in Spata16 was not essential for male fertility; however, deletion of the fourth exon of Spata16 resulted in infertile male mice due to spermiogenic arrest but not globozoospermia. This study demonstrates that Spata16 is indispensable for male fertility in mice, as well as in humans, as revealed by CRISPR/Cas9-mediated mouse models. Full article
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Open AccessArticle
The Operophtera brumata Nucleopolyhedrovirus (OpbuNPV) Represents an Early, Divergent Lineage within Genus Alphabaculovirus
Viruses 2017, 9(10), 307; doi:10.3390/v9100307 (registering DOI) -
Abstract
Operophtera brumata nucleopolyhedrovirus (OpbuNPV) infects the larvae of the winter moth, Operophtera brumata. As part of an effort to explore the pesticidal potential of OpbuNPV, an isolate of this virus from Massachusetts (USA)—OpbuNPV-MA—was characterized by electron microscopy of OpbuNPV occlusion bodies (OBs)
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Operophtera brumata nucleopolyhedrovirus (OpbuNPV) infects the larvae of the winter moth, Operophtera brumata. As part of an effort to explore the pesticidal potential of OpbuNPV, an isolate of this virus from Massachusetts (USA)—OpbuNPV-MA—was characterized by electron microscopy of OpbuNPV occlusion bodies (OBs) and by sequencing of the viral genome. The OBs of OpbuNPV-MA consisted of irregular polyhedra and contained virions consisting of a single rod-shaped nucleocapsid within each envelope. Presumptive cypovirus OBs were also detected in sections of the OB preparation. The OpbuNPV-MA genome assembly yielded a circular contig of 119,054 bp and was found to contain little genetic variation, with most polymorphisms occurring at a frequency of < 6%. A total of 130 open reading frames (ORFs) were annotated, including the 38 core genes of Baculoviridae, along with five homologous repeat (hr) regions. The results of BLASTp and phylogenetic analysis with selected ORFs indicated that OpbuNPV-MA is not closely related to other alphabaculoviruses. Phylogenies based on concatenated core gene amino acid sequence alignments placed OpbuNPV-MA on a basal branch lying outside other alphabaculovirus clades. These results indicate that OpbuNPV-MA represents a divergent baculovirus lineage that appeared early during the diversification of genus Alphabaculovirus. Full article
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Open AccessArticle
The Geometry of Large Tundra Lakes Observed in Historical Maps and Satellite Images
Remote Sens. 2017, 9(10), 1072; doi:10.3390/rs9101072 (registering DOI) -
Abstract
The climate of the Arctic is warming rapidly and this is causing major changes to the cycling of carbon and the distribution of permafrost in this region. Tundra lakes are key components of the Arctic climate system because they represent a source of
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The climate of the Arctic is warming rapidly and this is causing major changes to the cycling of carbon and the distribution of permafrost in this region. Tundra lakes are key components of the Arctic climate system because they represent a source of methane to the atmosphere. In this paper, we aim to analyze the geometry of the patterns formed by large (> 0.8 km2) tundra lakes in the Russian High Arctic. We have studied images of tundra lakes in historical maps from the State Hydrological Institute, Russia (date 1977; scale 0.21166 km/pixel) and in Landsat satellite images derived from the Google Earth Engine (G.E.E.; date 2016; scale 0.1503 km/pixel). The G.E.E. is a cloud-based platform for planetary-scale geospatial analysis on over four decades of Landsat data. We developed an image-processing algorithm to segment these maps and images, measure the area and perimeter of each lake, and compute the fractal dimension of the lakes in the images we have studied. Our results indicate that as lake size increases, their fractal dimension bifurcates. For lakes observed in historical maps, this bifurcation occurs among lakes larger than 100 km2 (fractal dimension 1.43 to 1.87). For lakes observed in satellite images this bifurcation occurs among lakes larger than ∼100 km2 (fractal dimension 1.31 to 1.95). Tundra lakes with a fractal dimension close to 2 have a tendency to be self-similar with respect to their area–perimeter relationships. Area–perimeter measurements indicate that lakes with a length scale greater than 70 km2 are power-law distributed. Preliminary analysis of changes in lake size over time in paired lakes (lakes that were visually matched in both the historical map and the satellite imagery) indicate that some lakes in our study region have increased in size over time, whereas others have decreased in size over time. Lake size change during this 39-year time interval can be up to half the size of the lake as recorded in the historical map. Full article
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Open AccessArticle
Inhibitory Effects of Siegesbeckia orientalis Extracts on Advanced Glycation End Product Formation and Key Enzymes Related to Metabolic Syndrome
Molecules 2017, 22(10), 1785; doi:10.3390/molecules22101785 (registering DOI) -
Abstract
Metabolic syndrome typically includes Type 2 diabetes associated with hyperglycemia, central obesity, dyslipidemia and hypertension. It is highly related to oxidative stress, formation of advanced glycated end products (AGEs) and key enzymes, such as carbohydrate digesting enzymes like pancreatic α-amylase and intestinal α-glucosidase,
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Metabolic syndrome typically includes Type 2 diabetes associated with hyperglycemia, central obesity, dyslipidemia and hypertension. It is highly related to oxidative stress, formation of advanced glycated end products (AGEs) and key enzymes, such as carbohydrate digesting enzymes like pancreatic α-amylase and intestinal α-glucosidase, pancreatic lipase and angiotensin I-converting enzyme (ACE). This study used an in vitro approach to assess the potential of four extracts of Siegesbeckia orientalis linne on key enzymes relevant to metabolic syndrome. In this research, S. orientailis was firstly extracted by ethanol. The ethanol extract (SE) was then partitioned sequentially with hexane, ethyl acetate and methanol, and these extracts were named SE-Hex, SE-EA and SE-MeOH, respectively. The experimental results showed that SE-EA had the highest total phenolic content (TPC, 76.9 ± 1.8 mg/g) and the total flavonoids content (TFC, 5.3 ± 0.3 mg/g). This extract exhibited the most significant antioxidant activities, including DPPH radical-scavenging capacity (IC50 = 161.8 ± 2.4 μg/mL), ABTS radical-scavenging capacity (IC50 = 13.9 ± 1.5 μg/mL) and reducing power. For anti-glycation activities, SE-EA showed the best results in the inhibition of AGEs, as well as inhibitory activities against α-glucosidase (IC50 = 362.3 ± 9.2 μg/mL) and α-amylase (IC50 = 119.0 ± 17.7 μg/mL). For anti-obesity activities, SE-EA indicated the highest suppression effect on pancreatic lipase (IC50 = 3.67 ± 0.52 mg/mL). Finally, for anti-hypertension activity, SE-EA also demonstrated the strongest inhibitory activity on ACE (IC50 = 626.6 ± 15.0 μg/mL). Close relationships were observed among the parameters of TPC, antioxidant activities, inhibitory activities on α-amylase, α-glucosidase, lipase and ACE (R > 0.9). Moderate correlations were found among the parameters of TFC, antioxidant activities, and suppression of dicarbonyl compounds formation (R = 0.5–0.9). Taken together these in vitro studies reveal the therapeutic potential of SE-EA extract in the prevention and treatment of metabolic disorders. Full article
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Open AccessReview
Gammaherpesviral Tegument Proteins, PML-Nuclear Bodies and the Ubiquitin-Proteasome System
Viruses 2017, 9(10), 308; doi:10.3390/v9100308 (registering DOI) -
Abstract
Gammaherpesviruses like Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) subvert the ubiquitin proteasome system for their own benefit in order to facilitate viral gene expression and replication. In particular, viral tegument proteins that share sequence homology to the formylglycineamide ribonucleotide amidotransferase (FGARAT,
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Gammaherpesviruses like Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) subvert the ubiquitin proteasome system for their own benefit in order to facilitate viral gene expression and replication. In particular, viral tegument proteins that share sequence homology to the formylglycineamide ribonucleotide amidotransferase (FGARAT, or PFAS), an enzyme in the cellular purine biosynthesis, are important for disrupting the intrinsic antiviral response associated with Promyelocytic Leukemia (PML) protein-associated nuclear bodies (PML-NBs) by proteasome-dependent and independent mechanisms. In addition, all herpesviruses encode for a potent ubiquitin protease that can efficiently remove ubiquitin chains from proteins and thereby interfere with several different cellular pathways. In this review, we discuss mechanisms and functional consequences of virus-induced ubiquitination and deubiquitination for early events in gammaherpesviral infection. Full article
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Open AccessArticle
Dynamic Modeling and Simulation of Deep Geothermal Electric Submersible Pumping Systems
Energies 2017, 10(10), 1659; doi:10.3390/en10101659 (registering DOI) -
Abstract
Deep geothermal energy systems employ electric submersible pumps (ESPs) in order to lift geothermal fluid from the production well to the surface. However, rough downhole conditions and high flow rates impose heavy strain on the components, leading to frequent failures of the pump
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Deep geothermal energy systems employ electric submersible pumps (ESPs) in order to lift geothermal fluid from the production well to the surface. However, rough downhole conditions and high flow rates impose heavy strain on the components, leading to frequent failures of the pump system. As downhole sensor data is limited and often unrealible, a detailed and dynamical model system will serve as basis for deeper understanding and analysis of the overall system behavior. Furthermore, it allows to design model-based condition monitoring and fault detection systems, and to improve controls leading to a more robust and efficient operation. In this paper, a detailed state-space model of the complete ESP system is derived, covering the electrical, mechanical and hydraulic subsystems. Based on the derived model, the start-up phase of an exemplary yet realistic ESP system in the Megawatt range—located at a setting depth of 950 m and producing geothermal fluid of 140 C temperature at a rate of 0.145 m3s1—is simulated in MATLAB/Simulink. The simulation results show that the system reaches a stable operating point with realistic values. Furthermore, the effect of self-excitation between the filter capacitor and the motor inductor can clearly be observed. A full set of parameters is provided, allowing for direct model implementation and reproduction of the presented results. Full article
Open AccessReview
The Roles of Matricellular Proteins in Oncogenic Virus-Induced Cancers and Their Potential Utilities as Therapeutic Targets
Int. J. Mol. Sci. 2017, 18(10), 2198; doi:10.3390/ijms18102198 (registering DOI) -
Abstract
Matricellular proteins differ from other classical extracellular matrix proteins; for instance, they are transiently expressed as soluble proteins rather than being constitutively expressed in pathological conditions, such as acute viral infections. Accumulating studies have revealed that matricellular proteins, including osteopontin and tenascin-C, both
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Matricellular proteins differ from other classical extracellular matrix proteins; for instance, they are transiently expressed as soluble proteins rather than being constitutively expressed in pathological conditions, such as acute viral infections. Accumulating studies have revealed that matricellular proteins, including osteopontin and tenascin-C, both of which interact with integrin heterodimers, are involved in inflammatory diseases, autoimmune disorders, and cancers. The concentrations of these matricellular proteins are elevated in the plasma of patients with certain types of cancers, indicating that they play important roles in oncogenesis. Chronic viral infections are associated with certain cancers, which are distinct from non-viral cancers. Viral oncogenes play critical roles in the development and progression of such cancers. It is vital to investigate the mechanisms of tumorigenesis and, particularly, the mechanism by which viral proteins induce tumor progression. Viral proteins have been shown to influence not only the viral-infected cancer cells, but also the stromal cells and matricellular proteins that constitute the extracellular matrix that surrounds tumor tissues. In this review, we summarize the recent progress on the involvement of matricellular proteins in oncogenic virus-induced cancers to elucidate the mechanism of oncogenesis and consider the possible role of matricellular proteins as therapeutic targets in virus-induced cancers. Full article
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Open AccessArticle
Comprehensive Evaluation of the Sustainable Development of Power Grid Enterprises Based on the Model of Fuzzy Group Ideal Point Method and Combination Weighting Method with Improved Group Order Relation Method and Entropy Weight Method
Sustainability 2017, 9(10), 1900; doi:10.3390/su9101900 (registering DOI) -
Abstract
As an important implementing body of the national energy strategy, grid enterprises bear the important responsibility of optimizing the allocation of energy resources and serving the economic and social development, and their levels of sustainable development have a direct impact on the national
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As an important implementing body of the national energy strategy, grid enterprises bear the important responsibility of optimizing the allocation of energy resources and serving the economic and social development, and their levels of sustainable development have a direct impact on the national economy and social life. In this paper, the model of fuzzy group ideal point method and combination weighting method with improved group order relation method and entropy weight method is proposed to evaluate the sustainable development of power grid enterprises. Firstly, on the basis of consulting a large amount of literature, the important criteria of the comprehensive evaluation of the sustainable development of power grid enterprises are preliminarily selected. The opinions of the industry experts are consulted and fed back for many rounds through the Delphi method and the evaluation criteria system for sustainable development of power grid enterprises is determined, then doing the consistent and non dimensional processing of the evaluation criteria. After that, based on the basic order relation method, the weights of each expert judgment matrix are synthesized to construct the compound matter elements. By using matter element analysis, the subjective weights of the criteria are obtained. And entropy weight method is used to determine the objective weights of the preprocessed criteria. Then, combining the subjective and objective information with the combination weighting method based on the subjective and objective weighted attribute value consistency, a more comprehensive, reasonable and accurate combination weight is calculated. Finally, based on the traditional TOPSIS method, the triangular fuzzy numbers are introduced to better realize the scientific processing of the data information which is difficult to quantify, and the queuing indication value of each object and the ranking result are obtained. A numerical example is taken to prove that the model of fuzzy group ideal point method and combination weighting method with improved group order relation method and entropy weight method is feasible and effective for evaluating the sustainable development of power grid enterprises. Full article
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Open AccessFeature PaperArticle
Comparing Markov Chain Samplers for Molecular Simulation
Entropy 2017, 19(10), 561; doi:10.3390/e19100561 (registering DOI) -
Abstract
Markov chain Monte Carlo sampling propagators, including numerical integrators for stochastic dynamics, are central to the calculation of thermodynamic quantities and determination of structure for molecular systems. Efficiency is paramount, and to a great extent, this is determined by the integrated autocorrelation time
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Markov chain Monte Carlo sampling propagators, including numerical integrators for stochastic dynamics, are central to the calculation of thermodynamic quantities and determination of structure for molecular systems. Efficiency is paramount, and to a great extent, this is determined by the integrated autocorrelation time (IAcT). This quantity varies depending on the observable that is being estimated. It is suggested that it is the maximum of the IAcT over all observables that is the relevant metric. Reviewed here is a method for estimating this quantity. For reversible propagators (which are those that satisfy detailed balance), the maximum IAcT is determined by the spectral gap in the forward transfer operator, but for irreversible propagators, the maximum IAcT can be far less than or greater than what might be inferred from the spectral gap. This is consistent with recent theoretical results (not to mention past practical experience) suggesting that irreversible propagators generally perform better if not much better than reversible ones. Typical irreversible propagators have a parameter controlling the mix of ballistic and diffusive movement. To gain insight into the effect of the damping parameter for Langevin dynamics, its optimal value is obtained here for a multidimensional quadratic potential energy function. Full article
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