bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hierarchical Matching Method for Vectorial Road Networks Using Delaunay Triangulation
Authors: Zuo Zejun , Yang Lin , An Xiaoya , Zhen Wenjie , Qian Haoyue , Dai Songling
Published: August 2020

The primary objective of vectorial road network matching is to identify homonymous roads from two different data sources. Previous methods usually focus on matching road networks with the same coordinate system but rarely with different or unknown coordinate systems, which may lead to nontrivial and nonsystematic deviations (e.g., rotation angle) between homonymous objects. To fill this gap, this study proposes a novel hierarchical road network matching method based on Delaunay triangulation (DTRM). First, the entire urban road network is divided into three levels (L1, L2, L3) by using the principle of stroke. Then, the triangular meshes are constructed from L2, and the minimum matching unit (MMU) in the triangular mesh is used instead of the traditional “node-arc” unit to measure the similarity for the matching of L2. Lastly, a hierarchical matching solution integrating the probabilistic relaxation method and MMU similarity is yielded to identify the matching relationships of the three-level road network. Experiments conducted in Wuhan, China, and Auckland, New Zealand, show that the MMU similarity metrics can effectively calculate the similarity value with different rotation angles, and DTRM has higher precision than the benchmark probability-relaxation-matching method (PRM) and can correctly identify the most matching-relationships with an average accuracy of 89.63%. This study provides a matching framework for road networks with different or even unknown coordinate systems and contributes to the integration and updating of urban road networks.
Phenolic Metabolites from Barley in Contribution to Phenome in soil Moisture Deficit
Authors: Piasecka Anna , Sawikowska Aneta , Kuczyńska Anetta , Ogrodowicz Piotr , Mikołajczak Krzysztof , Krajewski Paweł , Kachlicki Piotr
Published: August 2020

Eight barley varieties from Europe and Asia were subjected to moisture deficit at various development stages. At the seedling stage and the flag leaf stage combined stress was applied. The experiment was designed for visualization of the correlation between the dynamics of changes in phenolic compound profiles and the external phenome. The most significant increase of compound content in water deficiency was observed for chrysoeriol and apigenin glycoconjugates acylated with methoxylated hydroxycinnamic acids that enhanced the UV-protection effectiveness. Moreover, other good antioxidants such as derivatives of luteolin and hordatines were also induced by moisture deficit. The structural diversity of metabolites of the contents changed in response to water deficiency in barley indicates their multipath activities under stress. Plants exposed to moisture deficit at the seedling stage mobilized twice as many metabolites as plants exposed to this stress at the flag leaf stage. Specific metabolites such as methoxyhydroxycinnamic acids participated in the long-term acclimation. In addition, differences in phenolome mobilization in response to moisture deficit applied at the vegetative and generative phases were correlated with the phenotypical consequences. Observations of plant yield and biomass gave us the possibility to discuss the developmentally related consequences of moisture deficit for plants’ fitness.
The Association of dp-ucMGP with Cardiovascular Morbidity and Decreased Renal Function in Diabetic Chronic Kidney Disease
Authors: Roumeliotis Stefanos , Roumeliotis Athanasios , Stamou Aikaterini , Leivaditis Konstantinos , Kantartzi Konstantia , Panagoutsos Stylianos , Liakopoulos Vassilios
Published: August 2020

We aimed to investigate the possible association of the inactive, dephosphorylated, uncarboxylated matrix Gla protein (dp-ucMGP) with oxidized low-density lipoprotein (ox-LDL) and all-cause/cardiovascular (CV) mortality and renal function in diabetic chronic kidney disease (CKD). Ox-LDL and dp-ucMGP were determined in 66 diabetic CKD patients. All patients were prospectively followed for seven years, or until the occurrence of death, or a composite renal outcome of 30% estimated glomerular filtration rate (eGFR) reduction or progression to end-stage renal disease (ESRD) requiring dialysis occurred. Secondary outcomes were the occurrence of CV events. Kaplan–Meier curves showed that patients with plasma dp-ucMGP levels above the median (≥656 pM) had a significantly higher risk for all study endpoints. After adjustment for several well-known cofounders, multivariate Cox analysis showed that high plasma dp-ucMGP levels were associated with all-cause mortality (Hazard ratio-HR = 2.63, 95% Confidence Interval-CI = 1.17–5.94, p = 0.02), CV mortality (HR = 2.82, 95% CI = 1.07–7.49, p = 0.037) and progression of CKD (HR = 4.02, 95% CI = 1.20–13.46, p = 0.024). Circulating dp-ucMGP is associated with mortality and decreased renal function in diabetic CKD.
Transcriptomic Analysis of Short-Term Salt Stress Response in Watermelon Seedlings
Authors: Song Qiushuo , Joshi Madhumita , Joshi Vijay
Published: August 2020

Watermelon (Citrullus lanatus L.) is a widely popular vegetable fruit crop for human consumption. Soil salinity is among the most critical problems for agricultural production, food security, and sustainability. The transcriptomic and the primary molecular mechanisms that underlie the salt-induced responses in watermelon plants remain uncertain. In this study, the photosynthetic efficiency of photosystem II, free amino acids, and transcriptome profiles of watermelon seedlings exposed to short-term salt stress (300 mM NaCl) were analyzed to identify the genes and pathways associated with response to salt stress. We observed that the maximal photochemical efficiency of photosystem II decreased in salt-stressed plants. Most free amino acids in the leaves of salt-stressed plants increased many folds, while the percent distribution of glutamate and glutamine relative to the amino acid pool decreased. Transcriptome analysis revealed 7622 differentially expressed genes (DEGs) under salt stress, of which 4055 were up-regulated. The GO analysis showed that the molecular function term “transcription factor (TF) activity” was enriched. The assembled transcriptome demonstrated up-regulation of 240 and down-regulation of 194 differentially expressed TFs, of which the members of ERF, WRKY, NAC bHLH, and MYB-related families were over-represented. The functional significance of DEGs associated with endocytosis, amino acid metabolism, nitrogen metabolism, photosynthesis, and hormonal pathways in response to salt stress are discussed. The findings from this study provide novel insights into the salt tolerance mechanism in watermelon.
Lipopolysaccharide-Linked Enterobacterial Common Antigen (ECALPS) Occurs in Rough Strains of Escherichia coli R1, R2, and R4
Authors: Maciejewska Anna , Kaszowska Marta , Jachymek Wojciech , Lugowski Czeslaw , Lukasiewicz Jolanta
Published: August 2020

Enterobacterial common antigen (ECA) is a conserved surface antigen characteristic for Enterobacteriaceae. It is consisting of trisaccharide repeating unit, →3)-α-d-Fucp4NAc-(1→4)-β-d-ManpNAcA-(1→4)-α-d-GlcpNAc-(1→, where prevailing forms include ECA linked to phosphatidylglycerol (ECAPG) and cyclic ECA (ECACYC). Lipopolysaccharide (LPS)-associated form (ECALPS) has been proved to date only for rough Shigella sonnei phase II. Depending on the structure organization, ECA constitutes surface antigen (ECAPG and ECALPS) or maintains the outer membrane permeability barrier (ECACYC). The existence of LPS was hypothesized in the 1960–80s on the basis of serological observations. Only a few Escherichia coli strains (i.e., R1, R2, R3, R4, and K-12) have led to the generation of anti-ECA antibodies upon immunization, excluding ECAPG as an immunogen and conjecturing ECALPS as the only immunogenic form. Here, we presented a structural survey of ECALPS in E. coli R1, R2, R3, and R4 to correlate previous serological observations with the presence of ECALPS. The low yields of ECALPS were identified in the R1, R2, and R4 strains, where ECA occupied outer core residues of LPS that used to be substituted by O-specific polysaccharide in the case of smooth LPS. Previously published observations and hypotheses regarding the immunogenicity and biosynthesis of ECALPS were discussed and correlated with presented herein structural data.
Colonic Mucosal Microbiota and Association of Bacterial Taxa with the Expression of Host Antimicrobial Peptides in Pediatric Ulcerative Colitis
Authors: Jalanka Jonna , Cheng Jing , Hiippala Kaisa , Ritari Jarmo , Salojärvi Jarkko , Ruuska Tarja , Kalliomäki Marko , Satokari Reetta
Published: August 2020

Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n = 26) and non-IBD controls (n = 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA, p = 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC.
The Role of the Kynurenine Signaling Pathway in Different Chronic Pain Conditions and Potential Use of Therapeutic Agents
Authors: Jovanovic Filip , Candido Kenneth D. , Knezevic Nebojsa Nick
Published: August 2020

Tryptophan (TRP) is an essential, aromatic amino acid catabolized by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) enzymes into kynurenine. The IDO enzyme is expressed in peripheral tissues and the central nervous system. Another enzyme of interest in the kynurenine signaling pathway is kynurenine 3-monooxygenase (KMO). The purpose of this review is to discuss the role of TRP and the kynurenine signaling pathway in different chronic pain patients. The IDO-1, IDO-2, and KMO enzymes and the kynurenine metabolite have been shown to be involved in the pathogenesis of neuropathic pain and other painful conditions (migraine, cluster headache, etc.) as well as depressive behavior. We highlighted the analgesic potential of novel agents targeting the enzymes of the kynurenine signaling pathway to explore their efficacy in both future basic science and transitional studies. Upcoming studies conducted on animal models will need to take into consideration the differences in TRP metabolism between human and non-human species. Since chronic painful conditions and depression have common pathophysiological patterns, and the kynurenine signaling pathway is involved in both of them, future clinical studies should aim to have outcomes targeting not only pain, but also functionality, mood changes, and quality of life.
Emerging Gene-Editing Modalities for Osteoarthritis
Authors: Tanikella Alekya S. , Hardy Makenna J. , Frahs Stephanie M. , Cormier Aidan G. , Gibbons Kalin D. , Fitzpatrick Clare K. , Oxford Julia Thom
Published: August 2020

Osteoarthritis (OA) is a pathological degenerative condition of the joints that is widely prevalent worldwide, resulting in significant pain, disability, and impaired quality of life. The diverse etiology and pathogenesis of OA can explain the paucity of viable preventive and disease-modifying strategies to counter it. Advances in genome-editing techniques may improve disease-modifying solutions by addressing inherited predisposing risk factors and the activity of inflammatory modulators. Recent progress on technologies such as CRISPR/Cas9 and cell-based genome-editing therapies targeting the genetic and epigenetic alternations in OA offer promising avenues for early diagnosis and the development of personalized therapies. The purpose of this literature review was to concisely summarize the genome-editing options against chronic degenerative joint conditions such as OA with a focus on the more recently emerging modalities, especially CRISPR/Cas9. Future advancements in novel genome-editing therapies may improve the efficacy of such targeted treatments.
Microglia Implicated in Tauopathy in the Striatum of Neurodegenerative Disease Patients from Genotype to Phenotype
Authors: Li Huifangjie , Knight William C. , Yang Pengfei , Guo Yingqiu , Perlmutter Joel S. , Morris John C. , Bateman Randall J. , Benzinger Tammie L. S. , Xu Jinbin
Published: August 2020

We found interactions between dopamine and oxidative damage in the striatum involved in advanced neurodegeneration, which probably change the microglial phenotype. We observed possible microglia dystrophy in the striatum of neurodegenerative brains. To investigate the interactions between oxidative damage and microglial phenotype, we quantified myeloperoxidase (MPO), poly (ADP-Ribose) (PAR), and triggering receptors expressed on myeloid cell 2 (TREM2) using enzyme-linked immunosorbent assay (ELISA). To test the correlations of microglia dystrophy and tauopathy, we quantified translocator protein (TSPO) and tau fibrils using autoradiography. We chose the caudate and putamen of Lewy body diseases (LBDs) (Parkinson’s disease, Parkinson’s disease dementia, and Dementia with Lewy body), Alzheimer’s disease (AD), and control brains and genotyped for TSPO, TREM2, and bridging integrator 1 (BIN1) genes using single nucleotide polymorphisms (SNP) assays. TREM2 gene variants were absent across all samples. However, associations between TSPO and BIN1 gene polymorphisms and TSPO, MPO, TREM2, and PAR level variations were found. PAR levels reduced significantly in the caudate of LBDs. TSPO density and tau fibrils decreased remarkably in the striatum of LBDs but increased in AD. Oxidative damage, induced by misfolded tau proteins and dopamine metabolism, causes microglia dystrophy or senescence during the late stage of LBDs. Consequently, microglia dysfunction conversely reduces tau propagation. The G allele of the BIN1 gene is a potential risk factor for tauopathy.
EVs and Bioengineering: From Cellular Products to Engineered Nanomachines
Authors: Villata Simona , Canta Marta , Cauda Valentina
Published: August 2020

Extracellular vesicles (EVs) are natural carriers produced by many different cell types that have a plethora of functions and roles that are still under discovery. This review aims to be a compendium on the current advancement in terms of EV modifications and re-engineering, as well as their potential use in nanomedicine. In particular, the latest advancements on artificial EVs are discussed, with these being the frontier of nanomedicine-based therapeutics. The first part of this review gives an overview of the EVs naturally produced by cells and their extraction methods, focusing on the possibility to use them to carry desired cargo. The main issues for the production of the EV-based carriers are addressed, and several examples of the techniques used to upload the cargo are provided. The second part focuses on the engineered EVs, obtained through surface modification, both using direct and indirect methods, i.e., engineering of the parental cells. Several examples of the current literature are proposed to show the broad variety of engineered EVs produced thus far. In particular, we also report the possibility to engineer the parental cells to produce cargo-loaded EVs or EVs displaying specific surface markers. The third and last part focuses on the most recent advancements based on synthetic and chimeric EVs and the methods for their production. Both top-down or bottom-up techniques are analyzed, with many examples of applications.
Identification and Functional Analysis of AopN, an Acidovorax Citrulli Effector that Induces Programmed Cell Death in Plants
Authors: Zhang Xiaoxiao , Zhao Mei , Jiang Jie , Yang Linlin , Yang Yuwen , Yang Shanshan , Walcott Ron , Qiu Dewen , Zhao Tingchang
Published: August 2020

Bacterial fruit blotch (BFB), caused by Acidovorax citrulli, seriously affects watermelon and other cucurbit crops, resulting in significant economic losses. However, the pathogenicity mechanism of A. citrulli is not well understood. Plant pathogenic bacteria often suppress the plant immune response by secreting effector proteins. Thus, identifying A. citrulli effector proteins and determining their functions may improve our understanding of the underlying pathogenetic mechanisms. In this study, a novel effector, AopN, which is localized on the cell membrane of Nicotiana benthamiana, was identified. The functional analysis revealed that AopN significantly inhibited the flg22-induced reactive oxygen species burst. AopN induced a programmed cell death (PCD) response. Unlike its homologous protein, the ability of AopN to induce PCD was dependent on two motifs of unknown functions (including DUP4129 and Cpta_toxin), but was not dependent on LXXLL domain. More importantly, the virulence of the aopN mutant of A. citrulli in N. benthamiana significantly decreased, indicating that it was a core effector. Further analysis revealed that AopN interacted with watermelon ClHIPP and ClLTP, which responds to A. citrulli strain Aac5 infection at the transcription level. Collectively, these findings indicate that AopN suppresses plant immunity and activates the effector-triggered immunity pathway.
Insights into the Role of Bioactive Food Ingredients and the Microbiome in Idiopathic Pulmonary Fibrosis
Authors: Mercader-Barceló Josep , Truyols-Vives Joan , Río Carlos , López-Safont Nora , Sala-Llinàs Ernest , Chaplin Alice
Published: August 2020

Idiopathic pulmonary fibrosis (IPF) is a chronic disease mainly associated with aging and, to date, its causes are still largely unknown. It has been shown that dietary habits can accelerate or delay the occurrence of aging-related diseases; however, their potential role in IPF development has been underestimated so far. The present review summarizes the evidence regarding the relationship between diet and IPF in humans, and in animal models of pulmonary fibrosis, in which we discuss the bioactivity of specific dietary food ingredients, including fatty acids, peptides, amino acids, carbohydrates, vitamins, minerals and phytochemicals. Interestingly, many animal studies reveal preventive and therapeutic effects of particular compounds. Furthermore, it has been recently suggested that the lung and gut microbiota could be involved in IPF, a relationship which may be linked to changes in immunological and inflammatory factors. Thus, all the evidence so far puts forward the idea that the gut-lung axis could be modulated by dietary factors, which in turn have an influence on IPF development. Overall, the data reviewed here support the notion of identifying food ingredients with potential benefits in IPF, with the ultimate aim of designing nutritional approaches as an adjuvant therapeutic strategy.
Molecular Basis and Clinical Application of Growth-Factor-Independent In Vitro Myeloid Colony Formation in Chronic Myelomonocytic Leukemia
Authors: Geissler Klaus , Jäger Eva , Barna Agnes , Gurbisz Michael , Graf Temeida , Graf Elmir , Nösslinger Thomas , Pfeilstöcker Michael , Machherndl-Spandl Sigrid , Stauder Reinhard , Zebisch Armin , Sill Heinz , Öhler Leopold , Kusec Rajko , Hörmann Gregor , Valent Peter
Published: August 2020

We have originally reported that colony-forming units granulocyte/macrophage (CFU-GM) formation is an in vitro feature of chronic myelomonocytic leukemia (CMML) and a strong predictor for short survival. Elucidation of the molecular basis underlying this in vitro phenomenon could be helpful to define molecular features that predict inferior outcome in patients. We studied the correlation between the mutational landscape and spontaneous colony formation in 164 samples from 125 CMML patients. As compared to wildtype samples, spontaneous in vitro CFU-GM formation was significantly increased in samples containing mutations in NRAS, CBL and EZH2 that were confirmed as independent stimulatory factors by multiple regression analysis. Inducible expression of mutated RAS but not JAK2 was able to induce growth factor independence of Ba/F3 cells. Whereas high colony CFU-GM growth was a strong unfavorable parameter for survival (p < 0.00001) and time to transformation (p = 0.01390), no single mutated gene had the power to significantly predict for both outcome parameters. A composite molecular parameter including NRAS/CBL/EZH2, however, was predictive for inferior survival (p = 0.00059) as well as for increased risk of transformation (p = 0.01429). In conclusion, we show that the composite molecular profile NRAS/CBL/EZH2 derived from its impact on spontaneous in vitro myeloid colony formation improves the predictive power over single molecular parameters in patients with CMML.
Precocious Downregulation of Krüppel-Homolog 1 in the Migratory Locust, Locusta migratoria, Gives Rise to An Adultoid Phenotype with Accelerated Ovarian Development but Disturbed Mating and Oviposition
Authors: Gijbels Marijke , Schellens Sam , Schellekens Tine , Bruyninckx Evert , Marchal Elisabeth , Vanden Broeck Jozef
Published: August 2020

Krüppel-homolog 1 (Kr-h1) is a zinc finger transcription factor maintaining the status quo in immature insect stages and promoting reproduction in adult insects through the transduction of the Juvenile Hormone (JH) signal. Knockdown studies have shown that precocious silencing of Kr-h1 in the immature stages results in the premature development of adult features. However, the molecular characteristics and reproductive potential of these premature adult insect stages are still poorly understood. Here we report on an adult-like or ‘adultoid’ phenotype of the migratory locust, Locusta migratoria, obtained after a premature metamorphosis induced by the silencing of LmKr-h1 in the penultimate instar. The freshly molted adultoid shows precocious development of adult features, corresponding with increased transcript levels of the adult specifier gene LmE93. Furthermore, accelerated ovarian maturation and vitellogenesis were observed in female adultoids, coinciding with elevated expression of LmCYP15A1 in corpora allata (CA) and LmKr-h1 and vitellogenin genes (LmVg) in fat body, whereas LmE93 and Methoprene-tolerant (LmMet) transcript levels decreased in fat body. In adultoid ovaries, expression of the Halloween genes, Spook (LmSpo) and Phantom (LmPhm), was elevated as well. In addition, the processes of mating and oviposition were severely disturbed in these females. L. migratoria is a well-known, swarm-forming pest insect that can destroy crops and harvests in some of the world’s poorest countries. As such, a better understanding of factors that are capable of significantly reducing the reproductive potential of this pest may be of crucial importance for the development of novel locust control strategies.
Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy
Authors: Raz Vered , Kroon Rosemarie H. M. J. M. , Mei Hailiang , Riaz Muhammad , Buermans Henk , Lassche Saskia , Horlings Corinne , Swart Bert De , Kalf Johanna , Harish Pradeep , Vissing John , Kielbasa Szymon , van Engelen Baziel G. M.
Published: August 2020

Small non-coding microRNAs (miRNAs) are involved in the regulation of mRNA stability. Their features, including high stability and secretion to biofluids, make them attractive as potential biomarkers for diverse pathologies. This is the first study reporting miRNA as potential biomarkers for oculopharyngeal muscular dystrophy (OPMD), an adult-onset myopathy. We hypothesized that miRNA that is differentially expressed in affected muscles from OPMD patients is secreted to biofluids and those miRNAs could be used as biomarkers for OPMD. We first identified candidate miRNAs from OPMD-affected muscles and from muscles from an OPMD mouse model using RNA sequencing. We then compared the OPMD-deregulated miRNAs to the literature and, subsequently, we selected a few candidates for expression studies in serum and saliva biofluids using qRT-PCR. We identified 126 miRNAs OPMD-deregulated in human muscles, but 36 deregulated miRNAs in mice only (pFDR < 0.05). Only 15 OPMD-deregulated miRNAs overlapped between the in humans and mouse studies. The majority of the OPMD-deregulated miRNAs showed opposite deregulation direction compared with known muscular dystrophies miRNAs (myoMirs), which are associated. In contrast, similar dysregulation direction was found for 13 miRNAs that are common between OPMD and aging muscles. A significant age-association (p < 0.05) was found for 17 OPMD-deregulated miRNAs (13.4%), whereas in controls, only six miRNAs (1.4%) showed a significant age-association, suggesting that miRNA expression in OPMD is highly age-associated. miRNA expression in biofluids revealed that OPMD-associated deregulation in saliva was similar to that in muscles, but not in serum. The same as in muscle, miRNA expression levels in saliva were also found to be associated with age (p < 0.05). Moreover, the majority of OPMD-miRNAs were found to be associated with dysphagia as an initial symptom. We suggest that levels of specific miRNAs in saliva can mark muscle degeneration in general and dysphagia in OPMD.
Sperm Proteome after Interaction with Reproductive Fluids in Porcine: From the Ejaculation to the Fertilization Site
Authors: Luongo Chiara , González-Brusi Leopoldo , Cots-Rodríguez Paula , Izquierdo-Rico Mª José , Avilés Manuel , García-Vázquez Francisco Alberto
Published: August 2020

Ejaculated sperm are exposed to different environments before encountering the oocyte. However, how the sperm proteome changes during this transit remains unsolved. This study aimed to identify proteomic changes in boar sperm after incubation with male (seminal plasma, SP) and/or female (uterine fluid, UF; and oviductal fluid, OF) reproductive fluids. The following experimental groups were analyzed: (1) SP: sperm + 20% SP; (2) UF: sperm + 20% UF; (3) OF: sperm + 20% OF; (4) SP + UF: sperm + 20% SP + 20% UF; and (5) SP+OF: sperm + 20% SP + 20% OF. The proteome analysis, performed by HPLC-MS/MS, allowed the identification of 265 proteins. A total of 69 proteins were detected in the UF, SP, and SP + UF groups, and 102 proteins in the OF, SP, and SP + OF groups. Our results showed a higher number of proteins when sperm were incubated with only one fluid than when they were co-incubated with two fluids. Additionally, the number of sperm-interacting proteins from the UF group was lower than the OF group. In conclusion, the interaction of sperm with reproductive fluids alters its proteome. The description of sperm-interacting proteins in porcine species after co-incubation with male and/or female reproductive fluids may be useful to understand sperm transport, selection, capacitation, or fertilization phenomena.
AvrA Exerts Inhibition of NF-κB Pathway in Its Naïve Salmonella Serotype through Suppression of p-JNK and Beclin-1 Molecules
Authors: Yin Chao , Liu Zijian , Xian Honghong , Jiao Yang , Yuan Yu , Li Yang , Li Qiuchun , Jiao Xinan
Published: August 2020

Avian salmonellosis caused by Salmonella enterica serovar Enteritidis (S. Enteritidis) and Pullorum (S. Pullorum) remains a big threat to the poultry industry and public hygiene. AvrA is an effector involved in inhibiting inflammation. Compared to AvrA from S. Enteritidis (SE-AvrA), the AvrA from S. Pullorum (SP-AvrA) lacks ten amino acids at the C-terminal. In this study, we compared the anti-inflammatory response induced by SP-AvrA to that of SE-AvrA. Transient expression of SP-AvrA in epithelial cells resulted in significantly weaker inhibition of NF-κB pathway activation when treated with TNF-α compared to the inhibition by SE-AvrA. SP-AvrA expression in the S. Enteritidis resulted in weaker suppression of NF-κB pathway in infected HeLa cells compared to SE-AvrA expression in the cells, while SP-AvrA expressed in S. Pullorum C79-13 suppressed NF-κB activation in infected HeLa and Caco 2 BBE cells to a greater extent than did SE-AvrA because of the higher expression of SP-AvrA than SE-AvrA in S. Pullorum. Further analysis demonstrated that the inhibition of NF-κB pathway in Salmonella-infected cells corresponded to the downregulation of the p-JNK and Beclin-1 protein molecules. Our study reveals that AvrA modifies the anti-inflammatory response in a manner dependent on the Salmonella serotype through inhibition of NF-κB pathway.
Direct Comparison of Therapeutic Effects on Diabetic Polyneuropathy between Transplantation of Dental Pulp Stem Cells and Administration of Dental Pulp Stem Cell-Secreted Factors
Authors: Kanada Saki , Makino Eriko , Nakamura Nobuhisa , Miyabe Megumi , Ito Mizuho , Hata Masaki , Yamauchi Taisuke , Sawada Noritaka , Kondo Shun , Saiki Tomokazu , Minato Tomomi , Miyazawa Ken , Goto Shigemi , Matsubara Tatsuaki , Naruse Keiko
Published: August 2020

Stem cell transplantation is a potential novel therapy for diabetic polyneuropathy. Dental pulp stem cells (DPSCs) are attractive stem cell sources because DPSCs can be isolated from extracted teeth and cryopreserved while retaining viability. In this study, we directly compared the efficacy of the transplantation of DPSCs and the administration of the secreted factors from DPSCs (DPSC-SFs) on diabetic polyneuropathy. Eight weeks after streptozotocin injection, DPSCs (1.0 × 106 cells/rat) or DPSC-SFs (1.0 mL/rat) were administered into the unilateral hindlimb skeletal muscles of diabetic Sprague–Dawley rats. DPSC transplantation and DPSC-SF administration did not affect blood glucose levels and body weights in the diabetic rats. Both DPSC transplantation and DPSC-SF administration significantly ameliorated sciatic nerve conduction velocity and sciatic nerve blood flow, accompanied by increases in muscle bundle size, vascular density in the skeletal muscles and intraepidermal nerve fiber density in the diabetic rats, while there was no difference between the results for DPSCs and DPSC-SFs. These results suggest that the efficacy of both DPSC transplantation and DPSC-SF administration for diabetic polyneuropathy four weeks after transplantation/administration was mainly due to the multiple secretomes secreted from transplanted DPSCs or directly injected DPSC-SFs in the early phase of transplantation/administration.
Long-Term Impact of Chemical and Alternative Fungicides Applied to Grapevine cv Nebbiolo on Berry Transcriptome
Authors: Balestrini Raffaella , Ghignone Stefano , Quiroga Gabriela , Fiorilli Valentina , Romano Irene , Gambino Giorgio
Published: August 2020

Viticulture is one of the horticultural systems in which antifungal treatments can be extremely frequent, with substantial economic and environmental costs. New products, such as biofungicides, resistance inducers and biostimulants, may represent alternative crop protection strategies respectful of the environmental sustainability and food safety. Here, the main purpose was to evaluate the systemic molecular modifications induced by biocontrol products as laminarin, resistance inducers (i.e., fosetyl-Al and potassium phosphonate), electrolyzed water and a standard chemical fungicide (i.e., metiram), on the transcriptomic profile of ‘Nebbiolo’ grape berries at harvest. In addition to a validation of the sequencing data through real-time polymerase chain reaction (PCR), for the first-time the expression of some candidate genes in different cell-types of berry skin (i.e., epidermal and hypodermal layers) was evaluated using the laser microdissection approach. Results showed that several considered antifungal treatments do not strongly affect the berry transcriptome profile at the end of season. Although some treatments do not activate long lasting molecular defense priming features in berry, some compounds appear to be more active in long-term responses. In addition, genes differentially expressed in the two-cell type populations forming the berry skin were found, suggesting a different function for the two-cell type populations.
Exploring Antifouling Activity of Biosurfactants Producing Marine Bacteria Isolated from Gulf of California
Authors: Alemán-Vega Monserrat , Sánchez-Lozano Ilse , Hernández-Guerrero Claudia J. , Hellio Claire , Quintana Erika T.
Published: August 2020

Biofouling causes major problems and economic losses to marine and shipping industries. In the search for new antifouling agents, marine bacteria with biosurfactants production capability can be an excellent option, due to the amphipathic surface-active characteristic that confers antimicrobial and antibiofilm activities. The aim of this study was to evaluate the antifouling activity of biosurfactants producing marine bacteria from the Gulf of California. The cell free culture supernatant (CFCS) of Bacillus niabensis (S-69), Ralstonia sp. (S-74) (isolated from marine sediment) and of B. niabensis (My-30) (bacteria associated to the sponge Mycale ramulosa) were screened for production of biosurfactants (using hemolysis and drop collapse test, oil displacement and emulsifying activity). The toxicity and antifouling activity were evaluated against biofoulers (bacteria forming biofilm and macrofoulers) both in laboratory and field assays. The results indicate that all bacteria were biosurfactant producers, but the higher capability was shown by B. niabensis (My-30) with high emulsifying properties (E24) of 71%. The CFCS showed moderate toxicity but were considered non-toxic against Artemia franciscana at low concentrations. In the antifouling assay, the CFCS of both strains of B. niabensis showed the best results for the reduction of the biofilm formation (up 50%) against all Gram-positive bacteria and most Gram-negative bacteria with low concentrations. In the field assay, the CFCS of B. niabensis (My-30) led to the reduction of 30% of biofouling compared to the control. The results indicate that the biosurfactant produced by B. niabensis (My-30) has promising antifouling activity.
The Endosomal Recycling Pathway—At the Crossroads of the Cell
Authors: O’Sullivan Mary J. , Lindsay Andrew J.
Published: August 2020

The endosomal recycling pathway lies at the heart of the membrane trafficking machinery in the cell. It plays a central role in determining the composition of the plasma membrane and is thus critical for normal cellular homeostasis. However, defective endosomal recycling has been linked to a wide range of diseases, including cancer and some of the most common neurological disorders. It is also frequently subverted by many diverse human pathogens in order to successfully infect cells. Despite its importance, endosomal recycling remains relatively understudied in comparison to the endocytic and secretory transport pathways. A greater understanding of the molecular mechanisms that support transport through the endosomal recycling pathway will provide deeper insights into the pathophysiology of disease and will likely identify new approaches for their detection and treatment. This review will provide an overview of the normal physiological role of the endosomal recycling pathway, describe the consequences when it malfunctions, and discuss potential strategies for modulating its activity.
Farnesoid X Receptor Activation Stimulates Organic Cations Transport in Human Renal Proximal Tubular Cells
Authors: Wongwan Teerasak , Chatsudthipong Varanuj , Soodvilai Sunhapas
Published: August 2020

Farnesoid X receptor (FXR) is a ligand-activated transcription factor highly expressed in the liver and kidneys. Activation of FXR decreases organic cation transporter (OCT) 1-mediated clearance of organic cation compounds in hepatocytes. The present study investigated FXR regulation of renal clearance of organic cations by OCT2 modulation and multidrug and toxin extrusion proteins (MATEs). The role of FXR in OCT2 and MATEs functions was investigated by monitoring the flux of 3H–MPP+, a substrate of OCT2 and MATEs. FXR agonists chenodeoxycholic acid (CDCA) and GW4064 stimulated OCT2-mediated 3H–MPP+ uptake in human renal proximal tubular cells (RPTEC/TERT1 cells) and OCT2-CHO-K1 cells. The stimulatory effect of CDCA (20 µM) was abolished by an FXR antagonist, Z-guggulsterone, indicating an FXR-dependent mechanism. CDCA increased OCT2 transport activity via an increased maximal transport rate of MPP+. Additionally, 24 h CDCA treatment increased MATEs-mediated 3H-MPP+ uptake. Moreover, CDCA treatment increased the expression of OCT2, MATE1, and MATE2-K mRNA compared with that of the control. OCT2 protein expression was also increased following CDCA treatment. FXR activation stimulates renal OCT2- and MATE1/2-K-mediated cation transports in proximal tubules, demonstrating that FXR plays a role in the regulation of OCT2 and MATEs in renal proximal tubular cells.
The Role of Chloroplast Gene Expression in Plant Responses to Environmental Stress
Authors: Zhang Yi , Zhang Aihong , Li Xiuming , Lu Congming
Published: August 2020

Chloroplasts are plant organelles that carry out photosynthesis, produce various metabolites, and sense changes in the external environment. Given their endosymbiotic origin, chloroplasts have retained independent genomes and gene-expression machinery. Most genes from the prokaryotic ancestors of chloroplasts were transferred into the nucleus over the course of evolution. However, the importance of chloroplast gene expression in environmental stress responses have recently become more apparent. Here, we discuss the emerging roles of the distinct chloroplast gene expression processes in plant responses to environmental stresses. For example, the transcription and translation of psbA play an important role in high-light stress responses. A better understanding of the connection between chloroplast gene expression and environmental stress responses is crucial for breeding stress-tolerant crops better able to cope with the rapidly changing environment.
Improved Autophagic Flux in Escapers from Doxorubicin-Induced Senescence/Polyploidy of Breast Cancer Cells
Authors: Bojko Agnieszka , Staniak Karolina , Czarnecka-Herok Joanna , Sunderland Piotr , Dudkowska Magdalena , Śliwińska Małgorzata Alicja , Salmina Kristine , Sikora Ewa
Published: August 2020

The induction of senescence/polyploidization and their role in cancer recurrence is still a poorly explored issue. We showed that MDA-MB-231 and MCF-7 breast cancer cells underwent reversible senescence/polyploidization upon pulse treatment with doxorubicin (dox). Subsequently, senescent/polyploid cells produced progeny (escapers) that possessed the same amount of DNA as parental cells. In a dox-induced senescence/polyploidization state, the accumulation of autophagy protein markers, such as LC3B II and p62/SQSTM1, was observed. However, the senescent cells were characterized by a very low rate of new autophagosome formation and degradation, estimated by autophagic index. In contrast to senescent cells, escapers had a substantially increased autophagic index and transcription factor EB activation, but a decreased level of an autophagy inhibitor, Rubicon, and autophagic vesicles with non-degraded cargo. These results strongly suggested that autophagy in escapers was improved, especially in MDA-MB-231 cells. The escapers of both cell lines were also susceptible to dox-induced senescence. However, MDA-MB-231 cells which escaped from senescence were characterized by a lower number of γH2AX foci and a different pattern of interleukin synthesis than senescent cells. Thus, our studies showed that breast cancer cells can undergo senescence uncoupled from autophagy status, but autophagic flux resumption may be indispensable in cancer cell escape from senescence/polyploidy.
Integrated Dissection of lncRNA-Perturbated Triplets Reveals Novel Prognostic Signatures Across Cancer Types
Authors: Wei Yunzhen , Zhou Limeng , Huang Yingzhang , Guo Dianjing
Published: August 2020

Long noncoding RNA (lncRNA)/microRNA(miRNA)/mRNA triplets contribute to cancer biology. However, identifying significative triplets remains a major challenge for cancer research. The dynamic changes among factors of the triplets have been less understood. Here, by integrating target information and expression datasets, we proposed a novel computational framework to identify the triplets termed as “lncRNA-perturbated triplets”. We applied the framework to five cancer datasets in The Cancer Genome Atlas (TCGA) project and identified 109 triplets. We showed that the paired miRNAs and mRNAs were widely perturbated by lncRNAs in different cancer types. LncRNA perturbators and lncRNA-perturbated mRNAs showed significantly higher evolutionary conservation than other lncRNAs and mRNAs. Importantly, the lncRNA-perturbated triplets exhibited high cancer specificity. The pan-cancer perturbator OIP5-AS1 had higher expression level than that of the cancer-specific perturbators. These lncRNA perturbators were significantly enriched in known cancer-related pathways. Furthermore, among the 25 lncRNA in the 109 triplets, lncRNA SNHG7 was identified as a stable potential biomarker in lung adenocarcinoma (LUAD) by combining the TCGA dataset and two independent GEO datasets. Results from cell transfection also indicated that overexpression of lncRNA SNHG7 and TUG1 enhanced the expression of the corresponding mRNA PNMA2 and CDC7 in LUAD. Our study provides a systematic dissection of lncRNA-perturbated triplets and facilitates our understanding of the molecular roles of lncRNAs in cancers.
Histone Demethylase LSD1 Regulates Kidney Cancer Progression by Modulating Androgen Receptor Activity
Authors: Lee Kyoung-Hwa , Kim Byung-Chan , Jeong Seung-Hwan , Jeong Chang Wook , Ku Ja Hyeon , Kwak Cheol , Kim Hyeon Hoe
Published: August 2020

Kidney cancer is one of the most difficult cancers to treat by targeted and radiation therapy. Therefore, identifying key regulators in this cancer is especially important for finding new drugs. We focused on androgen receptor (AR) regulation by its epigenetic co-regulator lysine-specific histone demethylase 1 (LSD1) in kidney cancer development. LSD1 knock-down in kidney cancer cells decreased expression of AR target genes. Moreover, the binding of AR to target gene promoters was reduced and histone methylation status was changed in LSD1 knock-down kidney cancer cells. LSD1 knock-down also slowed growth and decreased the migration ability of kidney cancer cells. We found that pargyline, known as a LSD1 inhibitor, can reduce AR activity in kidney cancer cells. The treatment of kidney cancer cells with pargyline delayed growth and repressed epithelial–mesenchymal transition (EMT) markers. These effects were additively enhanced by co-treatment with the AR inhibitor enzalutamide. Down-regulation of LSD1 in renal cancer cells (RCC) attenuated in vivo tumor growth in a xenograft mouse model. These results provide evidence that LSD1 can regulate kidney cancer cell growth via epigenetic control of AR transcription factors and that LSD1 inhibitors may be good candidate drugs for treating kidney cancer.
Metabolic Changes in Polycystic Kidney Disease as a Potential Target for Systemic Treatment
Authors: Haumann Sophie , Müller Roman-Ulrich , Liebau Max C.
Published: August 2020

Autosomal recessive and autosomal dominant polycystic kidney disease (ARPKD, ADPKD) are systemic disorders with pronounced hepatorenal phenotypes. While the main underlying genetic causes of both ARPKD and ADPKD have been well-known for years, the exact molecular mechanisms resulting in the observed clinical phenotypes in the different organs, remain incompletely understood. Recent research has identified cellular metabolic changes in PKD. These findings are of major relevance as there may be an immediate translation into clinical trials and potentially clinical practice. Here, we review important results in the field regarding metabolic changes in PKD and their modulation as a potential target of systemic treatment.
Na+ Transporter SvHKT1;1 from a Halophytic Turf Grass Is Specifically Upregulated by High Na+ Concentration and Regulates Shoot Na+ Concentration
Authors: Kawakami Yuki , Imran Shahin , Katsuhara Maki , Tada Yuichi
Published: August 2020

We characterized an Na+ transporter SvHKT1;1 from a halophytic turf grass, Sporobolus virginicus. SvHKT1;1 mediated inward and outward Na+ transport in Xenopus laevis oocytes and did not complement K+ transporter-defective mutant yeast. SvHKT1;1 did not complement athkt1;1 mutant Arabidopsis, suggesting its distinguishable function from other typical HKT1 transporters. The transcript was abundant in the shoots compared with the roots in S. virginicus and was upregulated by severe salt stress (500 mM NaCl), but not by lower stress. SvHKT1;1-expressing Arabidopsis lines showed higher shoot Na+ concentrations and lower salt tolerance than wild type (WT) plants under nonstress and salt stress conditions and showed higher Na+ uptake rate in roots at the early stage of salt treatment. These results suggested that constitutive expression of SvHKT1;1 enhanced Na+ uptake in root epidermal cells, followed by increased Na+ transport to shoots, which led to reduced salt tolerance. However, Na+ concentrations in phloem sap of the SvHKT1;1 lines were higher than those in WT plants under salt stress. Based on this result, together with the induction of the SvHKT1;1 transcription under high salinity stress, it was suggested that SvHKT1;1 plays a role in preventing excess shoot Na+ accumulation in S. virginicus.
Structural and Functional Maturation of Rat Primary Motor Cortex Layer V Neurons
Authors: Benedetti Bruno , Dannehl Dominik , Janssen Jan Maximilian , Corcelli Corinna , Couillard-Després Sébastien , Engelhardt Maren
Published: August 2020

Rodent neocortical neurons undergo prominent postnatal development and maturation. The process is associated with structural and functional maturation of the axon initial segment (AIS), the site of action potential initiation. In this regard, cell size and optimal AIS length are interconnected. In sensory cortices, developmental onset of sensory input and consequent changes in network activity cause phasic AIS plasticity that can also control functional output. In non-sensory cortices, network input driving phasic events should be less prominent. We, therefore, explored the relationship between postnatal functional maturation and AIS maturation in principal neurons of the primary motor cortex layer V (M1LV), a non-sensory area of the rat brain. We hypothesized that a rather continuous process of AIS maturation and elongation would reflect cell growth, accompanied by progressive refinement of functional output properties. We found that, in the first two postnatal weeks, cell growth prompted substantial decline of neuronal input resistance, such that older neurons needed larger input current to reach rheobase and fire action potentials. In the same period, we observed the most prominent AIS elongation and significant maturation of functional output properties. Alternating phases of AIS plasticity did not occur, and changes in functional output properties were largely justified by AIS elongation. From the third postnatal week up to five months of age, cell growth, AIS elongation, and functional output maturation were marginal. Thus, AIS maturation in M1LV is a continuous process that attunes the functional output of pyramidal neurons and associates with early postnatal development to counterbalance increasing electrical leakage due to cell growth.