bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyramiding Bacterial Blight Resistance Genes in Tainung82 for Broad-Spectrum Resistance Using Marker-Assisted Selection
Authors: Hsu Yu-Chia , Chiu Chih-Hao , Yap Ruishen , Tseng Yu-Chien , Wu Yong-Pei
Published: February 2020

Tainung82 (TNG82) is one of the most popular japonica varieties in Taiwan due to its relatively high yield and grain quality, however, TNG82 is susceptible to bacterial blight (BB) disease. The most economical and eco-friendly way to control BB disease in japonica is through the utilization of varieties that are resistant to the disease. In order to improve TNG82’s resistance to BB disease, five bacterial blight resistance genes (Xa4, xa5, Xa7, xa13 and Xa21) were derived from a donor parent, IRBB66 and transferred into TNG82 via marker-assisted backcrossing breeding. Five BB-resistant gene-linked markers were integrated into the backcross breeding program in order to identify individuals possessing the five identified BB-resistant genes (Xa4, xa5, Xa7, xa13 and Xa21). The polymorphic markers between the donor and recurrent parent were used for background selection. Plants having maximum contribution from the recurrent parent genome were selected in each generation and crossed with the recipient parent. Selected BC3F1 plants were selfed in order to generate homozygous BC3F2 plants. Nine pyramided plants, possessing all five BB-resistant genes, were obtained. These individuals displayed a high level of resistance against the BB strain, XF89-b. Different BB gene pyramiding lines were also inoculated against the BB pathogen, resulting in more than three gene pyramided lines that exhibited high levels of resistance. The five identified BB gene pyramided lines exhibited yield levels and other desirable agronomic traits, including grain quality and palatability, consistent with TNG82. Bacterial blight-resistant lines possessing the five identified BB genes exhibited not only higher levels of resistance to the disease, but also greater yield levels and grain quality. Pyramiding multiple genes with potential characteristics into a single genotype through marker-assisted selection can improve the efficiency of generating new crop varieties exhibiting disease resistance, as well as other desirable traits.
Cbx2, a PcG Family Gene, Plays a Regulatory Role in Medaka Gonadal Development
Authors: Chao Qinghe , Shen Fengfeng , Xue Yidong , Wu Jikui , Zhang Junling
Published: February 2020

Chromobox homolog 2 (CBX2), a key member of the polycomb group (PcG) family, is essential for gonadal development in mammals. A functional deficiency or genetic mutation in cbx2 can lead to sex reversal in mice and humans. However, little is known about the function of cbx2 in gonadal development in fish. In this study, the cbx2 gene was identified in medaka, which is a model species for the study of gonadal development in fish. Transcription of cbx2 was abundant in the gonads, with testicular levels relatively higher than ovarian levels. In situ hybridization (ISH) revealed that cbx2 mRNA was predominately localized in spermatogonia and spermatocytes, and was also observed in oocytes at stages I, II, and III. Furthermore, cbx2 and vasa (a marker gene) were co-localized in germ cells by fluorescent in situ hybridization (FISH). After cbx2 knockdown in the gonads by RNA interference (RNAi), the sex-related genes, including sox9 and foxl2, were influenced. These results suggest that cbx2 not only plays a positive role in spermatogenesis and oogenesis but is also involved in gonadal differentiation through regulating the expression levels of sex-related genes in fish.
Secondhand Smoke Induces Liver Steatosis through Deregulation of Genes Involved in Hepatic Lipid Metabolism
Authors: Tommasi Stella , Yoon Jae-In , Besaratinia Ahmad
Published: February 2020

We investigated the role of secondhand smoke (SHS) exposure, independently of diet, in the development of chronic liver disease. Standard diet-fed mice were exposed to SHS (5 h/day, 5 days/week for 4 months). Genome-wide gene expression analysis, together with molecular pathways and gene network analyses, and histological examination for lipid accumulation, inflammation, fibrosis, and glycogen deposition were performed on the liver of SHS-exposed mice and controls, upon termination of exposure and after one-month recovery in clean air. Aberrantly expressed transcripts were found in the liver of SHS-exposed mice both pre- and post-recovery in clean air (n = 473 vs. 222). The persistent deregulated transcripts (n = 210) predominantly affected genes and functional networks involved in lipid metabolism as well as in the regulation of the endoplasmic reticulum where manufacturing of lipids occurs. Significant hepatic fat accumulation (steatosis) was observed in the SHS-exposed mice, which progressively increased as the animals underwent recovery in clean air. Moderate increases in lobular inflammation infiltrates and collagen deposition as well as loss of glycogen were also detectable in the liver of SHS-exposed mice. A more pronounced phenotype, manifested as a disrupted cord-like architecture with foci of necrosis, apoptosis, inflammation, and macrovesicular steatosis, was observed in the liver of SHS-exposed mice post-recovery. The progressive accumulation of hepatic fat and other adverse histological changes in the SHS-exposed mice are highly consistent with the perturbation of key lipid genes and associated pathways in the corresponding animals. Our data support a role for SHS in the genesis and progression of metabolic liver disease through deregulation of genes and molecular pathways and functional networks involved in lipid homeostasis.
Comparative Analysis of Structural Variations Due to Genome Shuffling of Bacillus Subtilis VS15 for Improved Cellulase Production
Authors: Ega Soujanya Lakshmi , Drendel Gene , Petrovski Steve , Egidi Eleonora , Franks Ashley E. , Muddada Sudhamani
Published: February 2020

Cellulose is one of the most abundant and renewable biomass products used for the production of bioethanol. Cellulose can be efficiently hydrolyzed by Bacillus subtilis VS15, a strain isolate obtained from decomposing logs. A genome shuffling approach was implemented to improve the cellulase activity of Bacillus subtilis VS15. Mutant strains were created using ethyl methyl sulfonate (EMS), N-Methyl-N′ nitro-N-nitrosoguanidine (NTG), and ultraviolet light (UV) followed by recursive protoplast fusion. After two rounds of shuffling, the mutants Gb2, Gc8, and Gd7 were produced that had an increase in cellulase activity of 128%, 148%, and 167%, respectively, in comparison to the wild type VS15. The genetic diversity of the shuffled strain Gd7 and wild type VS15 was compared at whole genome level. Genomic-level comparisons identified a set of eight genes, consisting of cellulase and regulatory genes, of interest for further analyses. Various genes were identified with insertions and deletions that may be involved in improved celluase production in Gd7. Strain Gd7 maintained the capability of hydrolyzing wheatbran to glucose and converting glucose to ethanol by fermentation with Saccharomyces cerevisiae of the wild type VS17. This ability was further confirmed by the acidified potassium dichromate (K2Cr2O7) method.
Mdm2 and MdmX RING Domains Play Distinct Roles in the Regulation of p53 Responses: A Comparative Study of Mdm2 and MdmX RING Domains in U2OS Cells
Authors: Egorova Olga , Lau Heather HC , McGraphery Kate , Sheng Yi
Published: February 2020

Dysfunction of the tumor suppressor p53 occurs in most human cancers. Mdm2 and MdmX are homologous proteins from the Mdm (Murine Double Minute) protein family, which play a critical role in p53 inactivation and degradation. The two proteins interact with one another via the intrinsic RING (Really Interesting New Gene) domains to achieve the negative regulation of p53. The downregulation of p53 is accomplished by Mdm2-mediated p53 ubiquitination and proteasomal degradation through the ubiquitin proteolytic system and by Mdm2 and MdmX mediated inhibition of p53 transactivation. To investigate the role of the RING domain of Mdm2 and MdmX, an analysis of the distinct functionalities of individual RING domains of the Mdm proteins on p53 regulation was conducted in human osteosarcoma (U2OS) cell line. Mdm2 RING domain was observed mainly localized in the cell nucleus, contrasting the localization of MdmX RING domain in the cytoplasm. Mdm2 RING was found to possess an endogenous E3 ligase activity, whereas MdmX RING did not. Both Mdm2 and MdmX RING domains were able to dimerize with endogenous full-length Mdm2 and MdmX protein and affect their cellular function. The results showed that overexpression of the Mdm2 or MdmX RING domains interfered with the endogenous full-length Mdm2 and MdmX activity and resulted in p53 stabilization and p53 target gene activation. However, both Mdm RING domains showed oncogenic activity in a colony formation assay, suggesting that the Mdm RING domains possess p53-independent oncogenic properties. This study highlights the distinct structural and functional traits of the RING domain of Mdm2 and MdmX and characterized their role in cellular responses through interfering with p53 dependent signaling pathway.
IL-27Rα: A Novel Molecular Imaging Marker for Allograft Rejection
Authors: Zhao Shanshan , Shi Dai , Su Chen , Jiang Wen , Zhang Chao , Liang Ting , Hou Guihua
Published: February 2020

Non-invasively monitoring allogeneic graft rejection with a specific marker is of great importance for prognosis of patients. Recently, data revealed that IL-27Rα was up-regulated in alloreactive CD4+ T cells and participated in inflammatory diseases. Here, we evaluated whether IL-27Rα could be used in monitoring allogeneic graft rejection both in vitro and in vivo. Allogeneic (C57BL/6 donor to BALB/c recipient) and syngeneic (BALB/c both as donor and recipient) skin grafted mouse models were established. The expression of IL-27Rα in grafts was detected. The radio-probe, 125I-anti-IL-27Rα mAb, was prepared. Dynamic whole-body phosphor-autoradiography, ex vivo biodistribution and immunofluorescence staining were performed. The results showed that the highest expression of IL-27Rα was detected in allogeneic grafts on day 10 post transplantation (top period of allorejection). 125I-anti-IL-27Rα mAb was successfully prepared with higher specificity and affinity. Whole-body phosphor-autoradiography showed higher radioactivity accumulation in allogeneic grafts than syngeneic grafts on day 10. The uptake of 125I-anti-IL-27Rα mAb in allogeneic grafts could be almost totally blocked by pre-injection with excess unlabeled anti-IL-27Rα mAb. Interestingly, we found that 125I-anti-IL-27Rα mAb accumulated in allogeneic grafts, along with weaker inflammation earlier on day 6. The high uptake of 125I-anti-IL-27Rα mAb was correlated with the higher infiltrated IL-27Rα positive cells (CD3+/CD68+) in allogeneic grafts. In conclusion, IL-27Rα may be a novel molecular imaging marker to predict allorejection.
Role of microRNAs in the Regulation of Dendritic Cell Generation and Function
Authors: Scalavino Viviana , Liso Marina , Serino Grazia
Published: February 2020

Dendritic cells (DCs) are antigen-presenting cells with a key role in immune responses. They act as a link between the innate and adaptive systems and they can induce and maintain immunologic tolerance. DCs are subdivided into conventional and plasmacytoid DCs. These cell subsets originate from the same bone marrow precursors and their differentiation process is determined by several extrinsic and intrinsic factors, such as cytokines, transcription factors, and miRNAs. miRNAs are small non-coding RNAs that play a crucial role in modulating physiological and pathological processes mediated by DCs. miRNA deregulation affects many inflammatory conditions and diseases. The aim of this review was to underline the importance of miRNAs in inflammatory processes mediated by DCs in physiological and pathological conditions and to highlight their potential application for future therapies.
The Floral Repressor GmFLC-like Is Involved in Regulating Flowering Time Mediated by Low Temperature in Soybean
Authors: Lyu Jing , Cai Zhandong , Li Yonghong , Suo Haicui , Yi Rong , Zhang Shuai , Nian Hai
Published: February 2020

Soybean is an important crop that is grown worldwide. Flowering time is a critical agricultural trait determining successful reproduction and yields. For plants, light and temperature are important environmental factors that regulate flowering time. Soybean is a typical short-day (SD) plant, and many studies have elucidated the fine-scale mechanisms of how soybean responds to photoperiod. Low temperature can delay the flowering time of soybean, but little is known about the detailed mechanism of how temperature affects soybean flowering. In this study, we isolated GmFLC-like from soybean, which belongs to the FLOWERING LOCUS C clade of the MADS-box family and is intensely expressed in soybean leaves. Heterologous expression of GmFLC-like results in a delayed-flowering phenotype in Arabidopsis. Additional experiments revealed that GmFLC-like is involved in long-term low temperature-triggered late flowering by inhibiting FT gene expression. In addition, yeast one-hybrid, dual-luciferase reporter assay, and electrophoretic mobility shift assay revealed that the GmFLC-like protein could directly repress the expression of FT2a by physically interacting with its promoter region. Taken together, our results revealed that GmFLC-like functions as a floral repressor involved in flowering time during treatments with various low temperature durations. As the only the FLC gene in soybean, GmFLC-like was meaningfully retained in the soybean genome over the course of evolution, and this gene may play an important role in delaying flowering time and providing protective mechanisms against sporadic and extremely low temperatures.
Blood Metabolite Signatures of Metabolic Syndrome in Two Cross-Cultural Older Adult Cohorts
Authors: Mahajan Uma V. , Varma Vijay R. , Huang Chiung-Wei , An Yang , Tanaka Toshiko , Ferrucci Luigi , Takebayashi Toru , Harada Sei , Iida Miho , Legido-Quigley Cristina , Thambisetty Madhav
Published: February 2020

Metabolic syndrome (MetS) affects an increasing number of older adults worldwide. Cross-cultural comparisons can provide insight into how factors, including genetic, environmental, and lifestyle, may influence MetS prevalence. Metabolomics, which measures the biochemical products of cell processes, can be used to enhance a mechanistic understanding of how biological factors influence metabolic outcomes. In this study we examined associations between serum metabolite concentrations, representing a range of biochemical pathways and metabolic syndrome in two older adult cohorts: The Tsuruoka Metabolomics Cohort Study (TMCS) from Japan (n = 104) and the Baltimore Longitudinal Study of Aging (BLSA) from the United States (n = 146). We used logistic regression to model associations between MetS and metabolite concentrations. We found that metabolites from the phosphatidylcholines-acyl-alkyl, sphingomyelin, and hexose classes were significantly associated with MetS and risk factor outcomes in both cohorts. In BLSA, metabolites across all classes were uniquely associated with all outcomes. In TMCS, metabolites from the amino acid, biogenic amines, and free fatty acid classes were uniquely associated with MetS, and metabolites from the sphingomyelin class were uniquely associated with elevated triglycerides. The metabolites and metabolite classes we identified may be relevant for future studies exploring disease mechanisms and identifying novel precision therapy targets for individualized medicine.
Platelet Concentrates in Musculoskeletal Medicine
Authors: Mariani Erminia , Pulsatelli Lia
Published: February 2020

Platelet concentrates (PCs), mostly represented by platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are autologous biological blood-derived products that may combine plasma/platelet-derived bioactive components, together with fibrin-forming protein able to create a natural three-dimensional scaffold. These types of products are safely used in clinical applications due to the autologous-derived source and the minimally invasive application procedure. In this narrative review, we focus on three main topics concerning the use of platelet concentrate for treating musculoskeletal conditions: (a) the different procedures to prepare PCs, (b) the composition of PCs that is related to the type of methodological procedure adopted and (c) the clinical application in musculoskeletal medicine, efficacy and main limits of the different studies.
Current Perspectives on the Auxin-Mediated Genetic Network that Controls the Induction of Somatic Embryogenesis in Plants
Authors: Wójcik Anna M. , Wójcikowska Barbara , Gaj Małgorzata D.
Published: February 2020

Auxin contributes to almost every aspect of plant development and metabolism as well as the transport and signalling of auxin-shaped plant growth and morphogenesis in response to endo- and exogenous signals including stress conditions. Consistently with the common belief that auxin is a central trigger of developmental changes in plants, the auxin treatment of explants was reported to be an indispensable inducer of somatic embryogenesis (SE) in a large number of plant species. Treating in vitro-cultured tissue with auxins (primarily 2,4-dichlorophenoxyacetic acid, which is a synthetic auxin-like plant growth regulator) results in the extensive reprogramming of the somatic cell transcriptome, which involves the modulation of numerous SE-associated transcription factor genes (TFs). A number of SE-modulated TFs that control auxin metabolism and signalling have been identified, and conversely, the regulators of the auxin-signalling pathway seem to control the SE-involved TFs. In turn, the different expression of the genes encoding the core components of the auxin-signalling pathway, the AUXIN/INDOLE-3-ACETIC ACIDs (Aux/IAAs) and AUXIN RESPONSE FACTORs (ARFs), was demonstrated to accompany SE induction. Thus, the extensive crosstalk between the hormones, in particular, auxin and the TFs, was revealed to play a central role in the SE-regulatory network. Accordingly, LEAFY COTYLEDON (LEC1 and LEC2), BABY BOOM (BBM), AGAMOUS-LIKE15 (AGL15) and WUSCHEL (WUS) were found to constitute the central part of the complex regulatory network that directs the somatic plant cell towards embryogenic development in response to auxin. The revealing picture shows a high degree of complexity of the regulatory relationships between the TFs of the SE-regulatory network, which involve direct and indirect interactions and regulatory feedback loops. This review examines the recent advances in studies on the auxin-controlled genetic network, which is involved in the mechanism of SE induction and focuses on the complex regulatory relationships between the down- and up-stream targets of the SE-regulatory TFs. In particular, the outcomes from investigations on Arabidopsis, which became a model plant in research on genetic control of SE, are presented.
Regulatory Mechanisms of Mitochondrial Function and Cardiac Aging
Authors: Lin Ruizhu , Kerkelä Risto
Published: February 2020

Aging is a major risk factor for cardiovascular diseases (CVDs), the major cause of death worldwide. Cardiac myocytes, which hold the most abundant mitochondrial population, are terminally differentiated cells with diminished regenerative capacity in the adult. Cardiomyocyte mitochondrial dysfunction is a characteristic feature of the aging heart and one out of the nine features of cellular aging. Aging and cardiac pathologies are also associated with increased senescence in the heart. However, the cause and consequences of cardiac senescence during aging or in cardiac pathologies are mostly unrecognized. Further, despite recent advancement in anti-senescence therapy, the targeted cell type and the effect on cardiac structure and function have been largely overlooked. The unique cellular composition of the heart, and especially the functional properties of cardiomyocytes, need to be considered when designing therapeutics to target cardiac aging. Here we review recent findings regarding key factors regulating cell senescence, mitochondrial health as well as cardiomyocyte rejuvenation.
Characterization of Glyceollins as Novel Aryl Hydrocarbon Receptor Ligands and Their Role in Cell Migration
Authors: Pham Thu Ha , Lecomte Sylvain , Le Guevel Remy , Lardenois Aurélie , Evrard Bertrand , Chalmel Frédéric , Ferriere François , Balaguer Patrick , Efstathiou Theo , Pakdel Farzad
Published: February 2020

Recent studies strongly support the use of the aryl hydrocarbon receptor (AhR) as a therapeutic target in breast cancer. Glyceollins, a group of soybean phytoalexins, are known to exert therapeutic effects in chronic human diseases and also in cancer. To investigate the interaction between glyceollin I (GI), glyceollin II (GII) and AhR, a computational docking analysis, luciferase assays, immunofluorescence and transcriptome analyses were performed with different cancer cell lines. The docking experiments predicted that GI and GII can enter into the AhR binding pocket, but their interactions with the amino acids of the binding site differ, in part, from those interacting with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Both GI and GII were able to weakly and partially activate AhR, with GII being more potent. The results from the transcriptome assays showed that approximately 10% of the genes regulated by TCDD were also modified by both GI and GII, which could have either antagonistic or synergistic effects upon TCDD activation. In addition, we report here, on the basis of phenotype, that GI and GII inhibit the migration of triple-negative (ER-, PgR-, HER2NEU-) MDA-MB-231 breast cancer cells, and that they inhibit the expression of genes which code for important regulators of cell migration and invasion in cancer tissues. In conclusion, GI and GII are AhR ligands that should be further investigated to determine their usefulness in cancer treatments.
The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF
Authors: Miao Zhuang , Wang Yan , Sun Zhongsheng
Published: February 2020

Brain-derived neurotrophic factor (BDNF), a critical member of the neurotrophic family, plays an important role in multiple stress-related mental disorders. Although alterations in BDNF in multiple brain regions of individuals experiencing stress have been demonstrated in previous studies, it appears that a set of elements are involved in the complex regulation. In this review, we summarize the specific brain regions with altered BDNF expression during stress exposure. How various environmental factors, including both physical and psychological stress, affect the expression of BDNF in specific brain regions are further summarized. Moreover, epigenetic regulation of BDNF, including DNA methylation, histone modification, and noncoding RNA, in response to diverse types of stress, as well as sex differences in the sensitivity of BDNF to the stress response, is also summarized. Clarification of the underlying role of BDNF in the stress process will promote our understanding of the pathology of stress-linked mental disorders and provide a potent target for the future treatment of stress-related illness.
Potential Therapeutic Approaches Against Brain Diseases Associated with Cytomegalovirus Infections
Authors: Wang Shao-Cheng , Chen Shiu-Jau , Chen Yuan-Chuan
Published: February 2020

Cytomegalovirus (CMV) is one of the major human health threats worldwide, especially for immunologically comprised patients. CMV may cause opportunistic infections, congenital infections, and brain diseases (e.g., mental retardation and glioblastoma). The etiology of brain diseases associated with human CMV (HCMV) infections is usually complex and it is particularly difficult to treat because HCMV has a life-long infection in its hosts, high mutation rate, and latent infections. Moreover, it is almost impossible to eradicate latent viruses in humans. Although there has been progress in drug discovery recently, current drugs used for treating active CMV infections are still limited in efficacy due to side effects, toxicity, and viral resistance. Fortunately, letermovir which targets the HCMV terminase complex rather than DNA polymerase with fewer adverse reactions has been approved to treat CMV infections in humans. The researchers are focusing on developing approaches against both productive and latent infections of CMV. The gene or RNA targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) are being investigated to remove acute and/or latent CMV infections. For the treatment of glioblastoma, vaccine therapy through targeting specific CMV antigens has improved patients’ survival outcomes significantly and immunotherapy has also emerged as an alternative modality. The advanced research for developing anti-CMV agents and approaches is promising to obtain significant outcomes and expecting to have a great impact on the therapy of brain diseases associated with CMV infections.
Autoantibody Biomarkers in Rheumatic Diseases
Authors: Kang Eun Ha , Ha You-Jung , Lee Yun Jong
Published: February 2020

Autoantibodies encountered in patients with systemic rheumatic diseases bear clinical significance as a biomarker to help or predict diagnosis, clinical phenotypes, prognosis, and treatment decision-making. Furthermore, evidence has accumulated regarding the active involvement of disease-specific or disease-associated autoantibodies in the pathogenic process beyond simple association with the disease, and such knowledge has become essential for us to better understand the clinical value of autoantibodies as a biomarker. This review will focus on the current update on the autoantibodies of four rheumatic diseases (rheumatoid arthritis, myositis, systemic sclerosis, and anti-neutrophil cytoplasmic antibody associated vasculitis) where there has been a tremendous progress in our understanding on their biological effects and clinical use.
Absence of Dx2 at Glu-D1 Locus Weakens Gluten Quality Potentially Regulated by Expression of Nitrogen Metabolism Enzymes and Glutenin-Related Genes in Wheat
Authors: Song Lijun , Li Liqun , Zhao Liye , Liu Zhenzhen , Xie Tingting , Li Xuejun
Published: February 2020

Absence of high-molecular-weight glutenin subunit (HMW-GS) Dx2 weakens the gluten quality, but it is unclear how the absence of Dx2 has these effects. Thus, we investigated the gluten quality in terms of cytological, physicochemical, and transcriptional characteristics using two near-isogenic lines with Dx2 absent or present at Glu-D1 locus. Cytological observations showed that absence of Dx2 delayed and decreased the accumulation of protein bodies (PBs), where fewer and smaller PBs formed in the endosperm. The activity and gene expression levels of nitrogen assimilation and proteolysis enzymes were lower in HMW-D1a without Dx2 than HMW-D1p with Dx2, and thus less amino acid was transported for protein synthesis in the grains. The expression pattern of genes encoding Glu-1Dx2+1Dy12 was similar to those of three transcription factors, where these genes were significantly down-regulated in HMW-D1a than HMW-D1p. Three genes involving with glutenin polymerization were also down-regulated in HMW-D1a. These results may explain the changes in the glutenin and glutenin macropolymer (GMP) levels during grain development. Therefore, we suggest that the lower nitrogen metabolism capacity and expression levels of glutenin synthesis-related genes in HMW-D1a accounted for the lower accumulation of glutenin, GMP, and PBs, thereby weakening the structural‒thermal properties of gluten.
TUBB Variants Underlying Different Phenotypes Result in Altered Vesicle Trafficking and Microtubule Dynamics
Authors: Sferra Antonella , Petrini Stefania , Bellacchio Emanuele , Nicita Francesco , Scibelli Francesco , Dentici Maria Lisa , Alfieri Paolo , Cestra Gianluca , Bertini Enrico Silvio , Zanni Ginevra
Published: February 2020

Tubulinopathies are rare neurological disorders caused by alterations in tubulin structure and function, giving rise to a wide range of brain abnormalities involving neuronal proliferation, migration, differentiation and axon guidance. TUBB is one of the ten β-tubulin encoding genes present in the human genome and is broadly expressed in the developing central nervous system and the skin. Mutations in TUBB are responsible for two distinct pathological conditions: the first is characterized by microcephaly and complex structural brain malformations and the second, also known as “circumferential skin creases Kunze type” (CSC-KT), is associated to neurological features, excess skin folding and growth retardation. We used a combination of immunocytochemical and cellular approaches to explore, on patients’ derived fibroblasts, the functional consequences of two TUBB variants: the novel mutation (p.N52S), associated with basal ganglia and cerebellar dysgenesis, and the previously reported variant (p.M73T), linked to microcephaly, corpus callosum agenesis and CSC-KT skin phenotype. Our results demonstrate that these variants impair microtubule (MT) function and dynamics. Most importantly, our studies show an altered epidermal growth factor (EGF) and transferrin (Tf) intracellular vesicle trafficking in both patients’ fibroblasts, suggesting a specific role of TUBB in MT-dependent vesicular transport.
Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models
Authors: Ceci Claudia , Atzori Maria Grazia , Lacal Pedro Miguel , Graziani Grazia
Published: February 2020

The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta growth factor (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, and metastasis formation. Although VEGF-A can activate both VEGFR-1 and VEGFR-2 membrane receptors, PlGF and VEGF-B exclusively interact with VEGFR-1. Differently from VEGFR-2, which is involved both in physiological and pathological angiogenesis, in the adult VEGFR-1 is required only for pathological angiogenesis. Besides this role in tumor endothelium, ligand-mediated stimulation of VEGFR-1 expressed in tumor cells may directly induce cell chemotaxis and extracellular matrix invasion. Furthermore, VEGFR-1 activation in myeloid progenitors and tumor-associated macrophages favors cancer immune escape through the release of immunosuppressive cytokines. These properties have prompted a number of preclinical and clinical studies to analyze VEGFR-1 involvement in the metastatic process. The aim of the present review is to highlight the contribution of VEGFs/VEGFR-1 signaling in the progression of different tumor types and to provide an overview of the therapeutic approaches targeting VEGFR-1 currently under investigation.
Study on CO2 Capture Characteristics and Kinetics of Modified Potassium-Based Adsorbents
Authors: Guo Baihe , Wang Yanlin , Shen Xin , Qiao Xiaolei , Jia Li , Xiang Jun , Jin Yan
Published: February 2020

In this paper, a silica aerogel support was prepared by two-step sol–gel method, and the active component K2CO3 was supported on the support by wet loading to obtain a modified potassium-based CO2 adsorbent. As the influences of reaction conditions on the CO2 capture characteristics of modified potassium-based adsorbents, the reaction temperature (50 °C, 60 °C, 70 °C, 80 °C), water vapor concentration (10%, 15%, 20%), CO2 concentration (5%, 10%, 12.5%, 15%), and total gas flow rate (400 mL/min, 500 mL/min, 600 mL/min) were studied in a self-designed fixed-bed reactor. At the same time, the low-temperature nitrogen adsorption experiment, scanning electron microscope, and X-ray diffractometer were used to study the microscopic characteristics of modified potassium-based adsorbents before and after the reaction. The results show that the silica aerogel prepared by the two-step sol–gel method has an excellent microstructure, and its specific surface area and specific pore volume are as high as 838.9 m2/g and 0.85 cm3/g, respectively. The microstructure of K2CO3 loaded on the support is improved, which promotes the CO2 adsorption performance of potassium-based adsorbents. The adsorption of CO2 by potassium-based adsorbents can be better described by the Avrami fractional kinetic model and the modified Avrami fractional kinetic model, and it is a complex multi-path adsorption process, which is related to the adsorption site and activity. The optimal adsorption temperature, water vapor concentration, CO2 concentration, and total gas volume were 60 °C, 15%, 12.5%, and 500 mL/min, respectively.
Study of the Forming Characteristics of Small-Caliber Ammunition with Circumferential MEFP
Authors: Ma Guangsong , He Guanglin , Liu Yukuan , Guo Yachao
Published: February 2020

To study the influence of the structural parameters of the ammunition liner of small-caliber ammunition on the forming characteristics of the projectile, an integrated circumferential multiple explosively formed projectile (MEFP) warhead with an integrated shell and the liner was initially designed, and the wall thickness of the liner is variable. LS-DYNA finite-element software is used to simulate the integral circumferential MEFP of the preliminary design, based on the numerical simulation results, the influence of the thickness at the center of the liner, and the curvature radius of the liner on the shape and velocity of the formed projectile. The numerical simulation results show that when the thickness of the center of the liner is constant and the curvature radius increases gradually, the velocity of the formed projectile decreases and the length: Diameter ratio of formed projectile decreases gradually. When the curvature radius of the liner remains unchanged, the velocity of the formed projectile decreases with the increase of the thickness of the center of the liner, and the shape of the formed projectile does not change significantly. The results show that when the design of integrating the shell and the liner was adopted for the integral circumferential MEFP warhead, the shape of the formed projectile is greatly affected by the curvature radius of the liner (curvature radius of inner and outer walls of the liner), but less by the thickness of the center of the liner. The velocity of the formed projectile is affected by the curvature radius of the inner and outer walls of the liner and the thickness of the center of the liner. Moreover, the influence of the thickness of the center of the liner on the velocity of the formed projectile is greater than that of the curvature radius of the outer wall of the liner.
Understanding the patient voice in gout: a quantitative study conducted in Europe
Authors: De Meulemeester Marc , Mateus Elsa , Wieberneit-Tolman Hilda , Betteridge Neil , Ireland Lucy , Petersen Gudula , Maske Nina Jeanette , Jansen Tim L , Perez-Ruiz Fernando
Published: February 2020

Background

Although commonly diagnosed, gout often remains a poorly managed disease. This is partially due to a lack of awareness of the long-term effect of gout among patients and healthcare professionals.

Aim

To understand unmet needs for patients and provide insight into achieving better treatment.

Design & setting

A quantitative online questionnaire collected from 1100 people with gout from 14 countries within Europe.

Method

Patients were recruited to complete an online survey via healthcare professional (HCP) referral, patient associations, or market research panels. Patients were included if they had been diagnosed with gout by a physician. Prior to commencement, patients were made aware that this study was sponsored by Grünenthal. The responses collected were collated and analyses were performed.

Results

Patients had an average of 2.9 gout flares within a 12-month period. Although 79% of patients were satisfied with treatment, inadequate gout control was also reported by 71% of patients. Furthermore, 84% experienced moderate-to-severe pain with their most recent flare. Of those who acknowledged treatment dissatisfaction, only 24% discussed other options with their GP. Most patients reported irregular follow-up and serum uric acid (sUA) monitoring. In addition, loss of belief that more can be done was a key barrier for patients.

Conclusion

Patients reported severe pain and social burden, coupled with low treatment expectation and lack of awareness of target sUA. Education around knowing and reaching sUA target is needed so that patients can receive and GPs can deliver higher quality management.
SMS GATEWAY KANNEL SEBAGAI SARANA PENUNJANG INFORMASI AKADEMIK
Authors: Suryana Taryana a Author
Published: February 2020

SMS Gateway merupakan pintu gerbang bagi penyebaran Informasi dengan menggunakan SMS. Anda dapat menyebarkan informasi atau meminta informasi melalui server SMS tersebut. Selain itu dengan adanya SMS Gateway anda dapat mengcustomisasi keyword dan informasi apa saja yang ingin dikirimkan. Ada beberapa metode pengiriman dan penerimaan SMS (protocol) yang didukung oleh Kannel SMS gateway yaitu protocol CIMD 1.3, CIMD 2.0, SMPP 3.4, UCP/EMI 4.0. juga SEMA SMS2000 OIS protocol for SMS centers over Radiopad dan X.25
PEMBANGUNAN VIRTUAL MIRROR EYEGLASSES MENGGUNAKAN TEKNOLOGI AUGMENTED REALITY
Authors: Arham Zaid
Published: February 2020

Perkembangan teknologi augmented realitymenjadi sangat populer saat ini. Hal ini dikarenakanpenggunaan augmented reality sangat menarik dantelah banyak digunakan dalam kehidupan kita.Salah satu contohnya seperti pada strategipemasaran dan pengenalan produk kepadakonsumen melalui aplikasi virtual mirror eyeglassesyang berbasis web. Biasanya konsumen kesulitanjika ingin mencoba sebuah produk kacamata, merekabiasanya hanya bisa mencoba ketika akan membelikacamata dengan mendatangi langsung toko optikyang ada, jadi dengan begitu akan sangat membuangwaktu konsumen, tidak praktis, dan juga mengurangiminat konsumen terhadap produk yang ditawarkan.Dengan aplikasi kacamata virtual ini diharapkandapat menarik minat konsumen dan mengenalkanproduk-produk yang ditawarkan kepada konsumen.Virtual mirror eyeglasses adalah sebuah aplikasidimana konsumen dapat memakai kacamata secaravirtual menggunakan teknik face detection sepertisedang mencoba di depan cermin. Aplikasi inimensimulasikan model kacamata sehingga penggunaseakan-akan sedang menggunakan kacamata secarareal-time. Metode face detection yang digunakanadalah haar cascades classifier. Metode inimenggunakan haar feature yang banyak dandiorganisir dalam cascade classifier. Apabila tiapsubcitra berhasil melewati seluruh filter yang adamaka citra tersebut terdeteksi sebagai wajah. Melalui proses inilah wajah pengguna dapat terdeteksi
ANALISIS DATA MART UNTUK VIRTUALISASI TRAFFIC MONITORING INSIDEN DI ID-SIRTII/CC
Authors: Sabariah Mira Kania , Kustiani Fiska Mekas
Published: February 2020

Id-SIRTII/CC (Indonesia Security Incident Response Team on Internet Infrastructure/Coordination Center) merupakan pertahanan pertama untuk melindungi para pengguna di Indonesia dari kejahatan yang mungkin terjadi di dunia maya berupa sebuah tim yang bertugas untuk menjaga keamanan informasi data di Indonesia, terutama dari serangan cracker yang banyak menyerang web dan server internet di Indonesia. Berdasarkan hasil wawancara terhadap staf Laboratorium Data Mining Deputy of Researh and Development Id-SIRTII/CC, untuk mengolah insiden web yang telah disusupi oleh peretas, staf mencari informasi di situs Zone-h (http://www.zone-h.org dan Indonesian Defacer (http://indonesiandefacer.org). Data tersebut digunakan untuk traffic monitoring insiden. Adapun tujuan dilakukan traffic monitoring adalah untuk mempermudah melihat website berdomain Indonesia yang telah disusupi oleh peretas. Saat ini, proses penyajian data masih dilakukan secara manual dan belum tervirtualisasi dengan baik, sehingga pada saat proses monitoring mengalami kesulitan saat akan melakukan analisis insiden dari berbagai kondisi.
Galilée et le principe du chasseur
Authors: Gapaillard Jacques
Published: February 2020

The inconsistency of a few pages in the Second Day of Galileo ’s Dialogo reflects the difficulties encountered by Galileo when he wanted to conclude that mechanical phenomena at the Earth’s surface are indifferent to the possible rotation of the Earth. For Galileo was moreover fully conscious that the diurnal motion of the Earth must slightly deflect the apparent paths of projectiles. Consequently he did his best to find reasons to neglect these small deviations, which led him in particular to compute accurately one of them.
La notion d' «agrégat d'indivisibles» dans la constitution de la cinématique galiléenne : Cavalieri, Galilée, Torricelli
Authors: Festa Egidio
Published: February 2020

The interest in indivisibles in studies of the motion of freely falling bodies was confirmed in Galileo’s use of indivisibles from 1604 onwards. Beginning in 1621, Bonaventura Cavalieri worked out a new geometrical method that played an important part in clarifying the empirical use of indivisibles in this field. In a demonstration published in 1632 in the Dialogo, Galileo showed clearly the way in which the «total speed » is generated as an aggregate of «degrees of speed. » Some months later, Cavalieri gave, in Lo Specchio Ustorio, his own demonstration of the result obtained by Galileo, specifying the role played by the aggregate of indivisibles. This use of the aggregate of indivisibles is present in Galileo’s Discorsi, published in 1638, and in some of Torricelli’s writings.
Estudos sobre o currículo para a formação humana plena
Authors: Dulcina Platt Adreana
Published: February 2020

Neste estudo procuraremos destacar conceitualmente as categorias que consideramos imprescindíveis aos fundamentos da discussão curricular e formação humana plena. Entendemos o currículo de formação humana a partir da filosofia da práxis. Coadunando com nossas perspectivas epistemológicas, concordamos com a leitura de Semeraro (2001), quando aponta que Gramsci melhor desvela o processo de elaboração da filosofia da práxis a partir de novas relações sociais; ou seja, desligado das puras abstrações, o filósofo italiano observa na “unidade das tensões dualistas e as contradições ricas e complexas” (“entre teoria/prática, intelectuais/massa, organização/espontaneidade, sociedade política/sociedade civil, ocidente/oriente, norte/sul, história do mundo/história particular”), a articulação para o desenvolvimento da atividade humana plena. A partir destes pressupostos colocados aqui, enquanto premissas para a sistematização de nossos estudos, nos debruçaremos sobre dois grandes objetivos: (1) compreender o processo de humanização a partir da esfera das objetivações sociais e (2) a constituição do currículo de formação humana atrelado aos diferentes modos de produção, uma vez que demanda em diferentes formações sociais.
Pesquisa em educação e arte: a consolidação de um campo interminável
Authors: Villela Pereira Marcos
Published: February 2020

O objetivo deste artigo é explorar algumas considerações acerca da educação, da arte e da relação entre elas, de modo a mostrar a condição interminável desse campo de estudo e investigação. Tomando como horizonte a formação de professores, reitero-me no entrecruzamento dos processos de subjetivação e do entendimento estético: a estética da existência como tema clássico na história da humanidade e a formação como um complexo e multifacetado processo de produção de subjetividade – formar os outros e formar a si mesmo como uma intrincada arte de existir. O lugar da arte na educação, a relação entre arte e educação, o lugar da arte na vida, o sentido da educação, as implicações entre a vida, a arte e a educação, quem vem antes, quem vem depois, quem depende de quem, quem se serve de quem: não tanto o conteúdo dessa problematização, não tanto as respostas, mas é o próprio movimento de perguntar que interessa ser problematizado. Como corpus de problematização, tomaram-se quatro textos da importante arte-educadora brasileira Noêmia Varela, professora da Escolinha de Arte do Recife: «Criatividade na escola e formação do professor», de 1972; «Movimento Escolinhas de Arte: imagens e ideias», de 1973; «O desafio da formação de recursos humanos para a educação através da arte», de 1977; e «A formação do arte-educador no Brasil», de 1984. O material será confrontado com categorias contemporâneas do campo da educação e da arte, buscando-se especular seu potencial infinito de investigação.
A arte como mediadora na apropriação do conhecimento
Authors: Martins Piccolo Gustavo
Published: February 2020

Atualmente vivemos em um processo de crise do próprio entendimento do ser humano como produtor de sua história, fato que implica, inequivocamente, um contexto de crise também na esfera artística. Tais tensões têm gerado um empobrecimento subjetivo na forma de a humanidade perceber sua objetividade histórica. Exatamente em tal contexto, quando mais vilipendiada parece estar em seu compromisso social de emancipação política, a arte é vista como caminho crucial ao se estabelecer um novo processo de humanização. Devido a isto, são diversas as tentativas de tentar se introduzir a apropriação da arte como elemento crucial no currículo escolar, almejando qualificar o processo de ensino e aprendizagem realizado nestas instituições. Mas uma pergunta emerge de tais questionamentos: De que tipo de arte estamos falando? Arte para que e para quem? Qual é a sua relação com a educação? Tal trabalho pretende responder algumas destas questões, mediante um processo de revisão literária ancorado nos cânones do materialismo histórico e, principalmente, a partir das contribuições de Lukács.
Arte, educación y posmodernidad. Un ensayo pragmático-educativo a partir del arte en el Instituto de Ciencias de la Educación de la UABJO
Authors: Bautista Gómez Juan Jorge
Published: February 2020

El artículo Arte, educación y posmodernidad. Un ensayo pragmático-educativo en el Instituto de Ciencias de la Educación de la UABJO. Devela la vitalidad del arte en el proceso educativo, mostrando como por medio del método de proyectos, dirigido a actividades artísticas, se puede llevar a los estudiantes de educación superior a una experiencia de orden artístico que acarrea consecuencias conceptuales, valorales y actitudinales, evidenciando, finalmente, cómo el estudiante tiene en el arte un referente fundamental para lograr una formación más compleja e integral.
Políticas de avaliação e avaliação de políticas: o caso português no contexto ibero-americano
Authors: Abrantes Pedro
Published: February 2020

Com base em vários estudos em que o autor participou nos últimos anos, o presente artigo discute o desenvolvimento recente dos dispositivos de avaliação e a sua relação com o contexto político-mediático, no quadro ibero-americano, aprofundando o caso português durante a última legislatura (2005-2009). Durante este período, além da importância central que representaram as provas nacionais e internacionais de alunos no desenho das políticas educativas, foram implementados sistemas nacionais de avaliação das escolas e dos professores, tornando-se assim um locus privilegiado de observação. Desta análise, é possível reconhecer tendências ibero-americanas, mas também a influência de pressões europeias e particularidades nacionais. Se os dispositivos de avaliação surgem condicionados pelas orientações político-ideológicas das forças que os promovem e sustentam, sendo a apropriação pública dos seus resultados também altamente filtrada por maniqueísmos retóricos que reflectem interesses particulares, não deixam de providenciar informações que interpelam os diversos actores educativos, alimentando o debate público e a abertura dos sistemas, numa dialéctica permanente entre políticas de avaliação e avaliação de políticas.