bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality Characteristics of Two Populations in the Northern Mediterranean (Croatia) in the Period 1960–2012: An Ecological Study
Authors: Doričić Robert , Ćorić Tanja , Tomljenović Morana , Lakošeljac Danijela , Muzur Amir , Kolarić Branko
Published: November 2018

In the second half of the 20th century, the town of Bakar (Primorje-Gorski Kotar County, Croatia), where a coking plant was operational 1978–1994, experienced intensive industrialisation. The town of Mali Lošinj (Primorje-Gorski Kotar County, Croatia) in this period based its economy on non-industrial sectors. The study goal was comparing mortality characteristics of these populations in the northern Mediterranean for 1960–2012. An ecological study design was used. Data were analysed for 1960–2012 for the deceased with recorded place of residence in the study area. Data on the deceased for 1960–1993 were taken from death reports, for 1994–2012 from digital archives of the Teaching Institute of Public Health, Primorje-Gorski Kotar County. Data on causes of death for 1960–1994 were recoded to the three-digit code of underlying cause of death according to the International Classification of Diseases (ICD–10). Among studied populations significant difference was found among the causes of deaths coded within ICD–10 chapters: neoplasms (particularly stomach carcinoma), mental and behavioural disorders and diseases of the respiratory system (particularly chronic obstructive pulmonary disease, (COPD)). Increase in mortality from neoplasms, increase in respiratory diseases for the area exposed to industrial pollution, also stomach carcinoma and COPD particularly in the town Bakar require further research.
Long Working Hours and Job Quality in Europe: Gender and Welfare State Differences
Authors: Artazcoz Lucía , Cortès-Franch Imma , Escribà-Agüir Vicenta , López María , Benavides Fernando G.
Published: November 2018

Chronic extreme long working hours (LWH) have been found consistently associated with poor health status. However, the evidence for moderately LWH (41–60 h a week) is contradictory. Although poor job quality has been proposed as one of the mechanisms of this relationship, there are almost no studies about LWH and job quality. The objectives of this study were to analyze the association between moderately LWH and job quality in the EU27, as well as to examine differences by welfare regimes and gender. This is a cross-sectional study based on data from the 2010 European Working Conditions Survey. A subsample of employees from the EU27 aged 16–64 years who worked 30–60 h a week was selected (12,574 men and 8787 women). Overall, moderately LWH were not consistently associated with poor job quality except among women from Eastern European countries. Therefore, in the EU27 poor job quality does not seem to explain the relationship between moderately LWH and poor health status. The findings among women from Eastern European countries may be related to their weakened position in the labor market and to their work-family conflict resulting from a process of re-familisation that constrains their choices for a good job.
Changes in Metabolic Syndrome Severity Following Individualized Versus Standardized Exercise Prescription: A Feasibility Study
Authors: Weatherwax Ryan M. , Ramos Joyce S. , Harris Nigel K. , Kilding Andrew E. , Dalleck Lance C.
Published: November 2018

This study sought to investigate the efficacy of standardized versus individualized exercise intensity prescription on metabolic syndrome (MetS) severity following a 12-week exercise intervention. A total of 38 experimental participants (47.8 ± 12.2 yr, 170.7 ± 8.0 cm, 82.6 ± 18.7 kg, 26.9 ± 6.7 mL·k−1·min−1) were randomized to one of two exercise interventions (exercise intensity prescribed using heart rate reserve or ventilatory threshold). Following the 12-week intervention, MetS z-score was significantly improved for the standardized (−2.0 ± 3.1 to −2.8 ± 2.8 [p = 0.01]) and individualized (−3.3 ± 2.3 to −3.9 ± 2.2 [p = 0.04]) groups. When separating participants based on prevalence of MetS at baseline and MetS z-score responsiveness, there were six and three participants in the standardized and individualized groups, respectively, with three or more MetS risk factors. Of the six participants in the standardized group, 83% (5/6) of the participants were considered responders, whereas 100% (3/3) of the individualized participants were responders. Furthermore, only 17% (1/6) of the participants with MetS at baseline in the standardized group no longer had symptoms of MetS following the intervention. In the individualized group, 67% (2/3) of participants with baseline MetS were not considered to have MetS at week 12. These findings suggest that an individualized approach to the exercise intensity prescription may ameliorate the severity of MetS.
Remediating Potentially Toxic Metal and Organic Co-Contamination of Soil by Combining In Situ Solidification/Stabilization and Chemical Oxidation: Efficacy, Mechanism, and Evaluation
Authors: Ma Yan , Liu Zhenhai , Xu Yanqiu , Zhou Shengkun , Wu Yi , Wang Jin , Huang Zhanbin , Shi Yi
Published: November 2018

Most soil remediation studies investigated single contaminants or multiple contaminants of the same type. However, in field conditions, soils are often contaminated with potentially both toxic metals and organic pollutants, posing a serious technical challenge. Here, batch experiments were conducted to evaluate the performance of combining in situ solidification/stabilization (ISS) and in situ chemical oxidation (ISCO) for the simultaneous removal of aniline (1000 mg/kg) and Cd (10 mg/kg). All four tested ISS amendments, especially quick lime and Portland cement, promoted in situ chemical oxidation with activated persulfate in contaminated soil. Combined ISS/ISCO remediation effectively removed aniline and reduced the bioavailable Cd content at optimal initial persulfate and ISS amendment concentrations of 1.08 mol/kg and 30 wt% with a seven-day curing time, and significantly reduced leaching. Persulfate inhibited the reduction of the bioavailable Cd content, and ISS amendment with persulfate did not synergistically remediate Cd in co-contaminated soil. Strong alkalinity and high temperature were the main mechanisms driving rapid pollutant removal and immobilization. The reaction of CaO with water released heat, and Ca(OH)2 formation increased the pH. The relative contributions of heat vs. alkaline activation, as well as the contaminant removal efficiency, increased with ISS amendment CaO content. Combined treatment altered the soil physicochemical properties, and significantly increased Ca and S contents. Activated persulfate-related reactions did not negatively impact unconfined compressive strength and hydraulic conductivity. This work improves the selection of persulfate activation methods for the treatment of soils co-contaminated with both potentially toxic metals and organic pollutants.
Deciphering Molecular and Phenotypic Changes Associated with Early Autoimmune Disease in the Aire-Deficient Mouse Model of Sjögren’s Syndrome
Authors: Chen Feeling YuTing , Gaylord Eliza , McNamara Nancy , Knox Sarah
Published: November 2018

Sjögren’s syndrome (SS) is characterized by extensive lymphocytic infiltration of the salivary and lacrimal gland (LG), resulting in acinar cell destruction and organ dysfunction. The underlying pathogenesis of SS remains largely unknown, and studies historically focus on defining late-stage disease. Here, we identify tissue programs associated with disease onset using transcriptomic and immunohistological analysis of LGs from 5- and 7-week-old mice deficient in autoimmune response element (Aire). At 5 weeks of age (wk), Aire-/- mice show minimal tissue dysfunction and destruction compared to 7 wk Aire-/-, which exhibit severe dry eye, poor tear secretion, extensive lymphocytic infiltration, reduced functional innervation, and increased vascularization. Despite this mild phenotype, 5 wk Aire-/- LGs were highly enriched for signaling pathways previously associated with SS, including interferon gamma (IFNγ), interleukin 1 beta (IL1β), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), toll-like receptor (TLR) signaling, and interleukin-6/signal transducer and activator of transcription 3 (IL6/STAT3) signaling. Novel signaling pathways such as the semaphorin–plexin pathway were also noted. Intriguingly, we found an expansion of the ductal network with increasing disease. Activated STAT3, a blocker of apoptosis, was restricted to the ductal system and also increased with damage, highlighting its potential as a promoter of ductal cell survival. These data demonstrate the early activation of signaling pathways regulating inflammation, innervation, and cell survival before the onset of clinical disease indicators, suggesting their potential value as diagnostic biomarkers.
Loss of Response Gene to Complement 32 (RGC-32) in Diabetic Mouse Retina Is Involved in Retinopathy Development
Authors: Liao Wen-Ling , Lin Jane-Ming , Liu Shih-Ping , Chen Shih-Yin , Lin Hui-Ju , Wang Yeh-Han , Lei Yu-Jie , Huang Yu-Chuen , Tsai Fuu-Jen
Published: November 2018

Diabetic retinopathy (DR) is a severe and recurrent microvascular complication in diabetes. The multifunctional response gene to complement 32 (RGC-32) is involved in the regulation of cell cycle, proliferation, and apoptosis. To investigate the role of RGC-32 in the development of DR, we used human retinal microvascular endothelial cells under high-glucose conditions and type 2 diabetes (T2D) mice (+Leprdb/ + Leprdb, db/db). The results showed that RGC-32 expression increased moderately in human retinal endothelial cells under hyperglycemic conditions. Histopathology and RGC-32 expression showed no significant changes between T2D and control mice retina at 16 and 24 weeks of age. However, RGC-32 expression was significantly decreased in T2D mouse retina compared to the control group at 32 weeks of age, which develop features of the early clinical stages of DR, namely reduced retinal thickness and increased ganglion cell death. Moreover, immunohistochemistry showed that RGC-32 was predominantly expressed in the photoreceptor inner segments of control mice, while the expression was dramatically lowered in the T2D retinas. Furthermore, we found that the level of anti-apoptotic protein Bcl-2 was decreased (approximately 2-fold) with a concomitant increase in cleaved caspase-3 (approximately 3-fold) in T2D retina compared to control. In summary, RGC-32 may lose its expression in T2D retina with features of DR, suggesting that it plays a critical role in DR pathogenesis.
Cystine/Glutamate Antiporter and Aripiprazole Compensate NMDA Antagonist-Induced Dysfunction of Thalamocortical L-Glutamatergic Transmission
Authors: Fukuyama Kouji , Hasegawa Toshiki , Okada Motohiro
Published: November 2018

To explore pathophysiology of schizophrenia, this study analyzed the regulation mechanisms that are associated with cystine/glutamate antiporter (Sxc), group-II (II-mGluR), and group-III (III-mGluR) metabotropic glutamate-receptors in thalamo-cortical glutamatergic transmission of MK801-induced model using dual-probe microdialysis. L-glutamate release in medial pre-frontal cortex (mPFC) was increased by systemic- and local mediodorsal thalamic nucleus (MDTN) administrations of MK801, but was unaffected by local administration into mPFC. Perfusion into mPFC of activators of Sxc, II-mGluR, and III-mGluR, and into the MDTN of activators of Sxc, II-mGluR, and GABAA receptor inhibited MK801-evoked L-glutamate release in mPFC. Perfusion of aripiprazole (APZ) into MDTN and mPFC also inhibited systemic MK801-evoked L-glutamate release in mPFC. Inhibition of II-mGluR in mPFC and MDTN blocked inhibitory effects of Sxc-activator and APZ on MK801-evoked L-glutamate release; however, their inhibitory effects were blocked by the inhibition of III-mGluR in mPFC but not in MDTN. These results indicate that reduced activation of the glutamate/NMDA receptor (NMDAR) in MDTN enhanced L-glutamate release in mPFC possibly through GABAergic disinhibition in MDTN. Furthermore, MDTN-mPFC glutamatergic transmission receives inhibitory regulation of Sxc/II-mGluR/III-mGluR functional complex in mPFC and Sxc/II-mGluR complex in MDTN. Established antipsychotic, APZ inhibits MK801-evoked L-glutamate release through the activation of Sxc/mGluRs functional complexes in both MDTN and mPFC.
Comparative Characterization of the Complete Mitochondrial Genomes of the Three Apple Snails (Gastropoda: Ampullariidae) and the Phylogenetic Analyses
Authors: Yang Huirong , Zhang Jia-en , Xia Jun , Yang Jinzeng , Guo Jing , Deng Zhixin , Luo Mingzhu
Published: November 2018

The apple snails Pomacea canaliculata, Pomacea diffusa and Pomacea maculate (Gastropoda: Caenogastropoda: Ampullariidae) are invasive pests causing massive economic losses and ecological damage. We sequenced and characterized the complete mitochondrial genomes of these snails to conduct phylogenetic analyses based on comparisons with the mitochondrial protein coding sequences of 47 Caenogastropoda species. The gene arrangements, distribution and content were canonically identical and consistent with typical Mollusca except for the tRNA-Gln absent in P. diffusa. An identifiable control region (d-loop) was absent. Bayesian phylogenetic analysis indicated that all the Ampullariidae species clustered on the same branch. The genus Pomacea clustered together and then with the genus Marisa. The orders Architaenioglossa and Sorbeoconcha clustered together and then with the order Hypsogastropoda. Furthermore, the intergenic and interspecific taxonomic positions were defined. Unexpectedly, Ceraesignum maximum, Dendropoma gregarium, Eualetes tulipa and Thylacodes squamigerus, traditionally classified in order Hypsogastropoda, were isolated from the order Hypsogastropoda in the most external branch of the Bayesian inference tree. The divergence times of the Caenogastropoda indicated that their evolutionary process covered four geological epochs that included the Quaternary, Neogene, Paleogene and Cretaceous periods. This study will facilitate further investigation of species identification to aid in the implementation of effective management and control strategies of these invasive species.
Natural Killer Cell Dysfunction in Hepatocellular Carcinoma: Pathogenesis and Clinical Implications
Authors: Sung Pil Soo , Jang Jeong Won
Published: November 2018

Hepatocellular carcinoma (HCC) is currently the third leading cause of malignancy-related mortalities worldwide. Natural killer (NK) cells are involved in the critical role of first line immunological defense against cancer development. Defects in NK cell functions are recognized as important mechanisms for immune evasion of tumor cells. NK cell function appears to be attenuated in HCC, and many previous reports suggested that NK cells play a critical role in controlling HCC, suggesting that boosting the activity of dysfunctional NK cells can enhance tumor cell killing. However, the detailed mechanisms of NK cell dysfunction in tumor microenvironment of HCC remain largely unknown. A better understanding of the mechanisms of NK cell dysfunction in HCC will help in the NK cell-mediated eradication of cancer cells and prolong patient survival. In this review, we describe the various mechanisms underlying human NK cell dysfunction in HCC. Further, we summarize current advances in the approaches to enhance endogenous NK cell function and in adoptive NK cell therapies, to cure this difficult-to-treat cancer.
Lactate Promotes Myoblast Differentiation and Myotube Hypertrophy via a Pathway Involving MyoD In Vitro and Enhances Muscle Regeneration In Vivo
Authors: Tsukamoto Sakuka , Shibasaki Ayako , Naka Ayano , Saito Hazuki , Iida Kaoruko
Published: November 2018

Lactate is a metabolic substrate mainly produced in muscles, especially during exercise. Recently, it was reported that lactate affects myoblast differentiation; however, the obtained results are inconsistent and the in vivo effect of lactate remains unclear. Our study thus aimed to evaluate the effects of lactate on myogenic differentiation and its underlying mechanism. The differentiation of C2C12 murine myogenic cells was accelerated in the presence of lactate and, consequently, myotube hypertrophy was achieved. Gene expression analysis of myogenic regulatory factors showed significantly increased myogenic determination protein (MyoD) gene expression in lactate-treated cells compared with that in untreated ones. Moreover, lactate enhanced gene and protein expression of myosin heavy chain (MHC). In particular, lactate increased gene expression of specific MHC isotypes, MHCIIb and IId/x, in a dose-dependent manner. Using a reporter assay, we showed that lactate increased promoter activity of the MHCIIb gene and that a MyoD binding site in the promoter region was necessary for the lactate-induced increase in activity. Finally, peritoneal injection of lactate in mice resulted in enhanced regeneration and fiber hypertrophy in glycerol-induced regenerating muscles. In conclusion, physiologically high lactate concentrations modulated muscle differentiation by regulating MyoD-associated networks, thereby enhancing MHC expression and myotube hypertrophy in vitro and, potentially, in vivo.
Mycobacterium tuberculosis ClpC1 N-Terminal Domain Is Dispensable for Adaptor Protein-Dependent Allosteric Regulation
Authors: Marsee Justin D. , Ridings Amy , Yu Tao , Miller Justin M.
Published: November 2018

ClpC1 hexamers couple the energy of ATP hydrolysis to unfold and, subsequently, translocate specific protein substrates into the associated ClpP protease. Substrate recognition by ATPases associated with various cellular activities (AAA+) proteases is driven by the ATPase component, which selectively determines protein substrates to be degraded. The specificity of these unfoldases for protein substrates is often controlled by an adaptor protein with examples that include MecA regulation of Bacillus subtilis ClpC or ClpS-mediated control of Escherichia coli ClpA. No adaptor protein-mediated control has been reported for mycobacterial ClpC1. Using pulldown and stopped-flow fluorescence methods, we report data demonstrating that Mycobacterium tuberculosis ClpC1 catalyzed unfolding of an SsrA-tagged protein is negatively impacted by association with the ClpS adaptor protein. Our data indicate that ClpS-dependent inhibition of ClpC1 catalyzed SsrA-dependent protein unfolding does not require the ClpC1 N-terminal domain but instead requires the presence of an interaction surface located in the ClpC1 Middle Domain. Taken together, our results demonstrate for the first time that mycobacterial ClpC1 is subject to adaptor protein-mediated regulation in vitro.
Investigating the Role of MicroRNA and Transcription Factor Co-regulatory Networks in Multiple Sclerosis Pathogenesis
Authors: Nuzziello Nicoletta , Vilardo Laura , Pelucchi Paride , Consiglio Arianna , Liuni Sabino , Trojano Maria , Liguori Maria
Published: November 2018

MicroRNAs (miRNAs) and transcription factors (TFs) play key roles in complex multifactorial diseases like multiple sclerosis (MS). Starting from the miRNomic profile previously associated with a cohort of pediatric MS (PedMS) patients, we applied a combined molecular and computational approach in order to verify published data in patients with adult-onset MS (AOMS). Six out of the 13 selected miRNAs (miR-320a, miR-125a-5p, miR-652-3p, miR-185-5p, miR-942-5p, miR-25-3p) were significantly upregulated in PedMS and AOMS patients, suggesting that they may be considered circulating biomarkers distinctive of the disease independently from age. A computational and unbiased miRNA-based screening of target genes not necessarily associated to MS was then performed in order to provide an extensive view of the genetic mechanisms underlying the disease. A comprehensive MS-specific miRNA-TF co-regulatory network was hypothesized; among others, SP1, RELA, NF-κB, TP53, AR, MYC, HDAC1, and STAT3 regulated the transcription of 61 targets. Interestingly, NF-κB and STAT3 cooperatively regulate the expression of immune response genes and control the cross-talk between inflammatory and immune cells. Further functional analysis will be performed on the identified critical hubs. Above all, in our view, this approach supports the need of multidisciplinary strategies for shedding light into the pathogenesis of MS.
STE20/PAKA Protein Kinase Gene Releases an Autoinhibitory Domain through Pre-mRNA Alternative Splicing in the Dermatophyte Trichophyton rubrum
Authors: Gomes Eriston V. , Bortolossi Julio C. , Sanches Pablo R. , Mendes Niege S. , Martinez-Rossi Nilce M. , Rossi Antonio
Published: November 2018

Signaling pathways are highly diverse in filamentous fungi, allowing the cells to receive and process ambient information. Interaction of components from different pathways results in signaling networks. The mitogen-activated protein kinase (MAPK) pathway is dependent on phosphorylation that is accomplished by kinase proteins. Thus, the STE/PAK protein kinase family plays essential roles in MAPK signal transduction, regulating several cellular functions. The STE/PAK protein displays an autoinhibitory (Cdc42/Rac interactive binding—CRIB) domain on its N-terminal portion, which interacts with the C-terminal catalytic kinase domain. Based on current knowledge, for the STE/PAK kinase to be activated, molecular signals (e.g., interaction with the activated form of Rac1 and Cdc42 proteins) or proteolytic cleavage by caspase 3 is necessary. Both mechanisms release the kinase domain from the CRIB interaction. Here, we hypothesize a novel molecular mechanism for the activation of STE20/PAKA kinase in Trichophyton rubrum based on an alternative pre-mRNA splicing process. Our data suggest that, because of the retention of intron 1 of this gene, it is theoretically possible that the translation of STE20/PAKA kinase will be free of its autoinhibitory CRIB domain. These findings indicate a rapid response system to environmental changes. Furthermore, STE20/PAKA may be a potential T. rubrum virulence factor and an interesting target for new drugs against dermatophytes.
Sub-Toxic Human Amylin Fragment Concentrations Promote the Survival and Proliferation of SH-SY5Y Cells via the Release of VEGF and HspB5 from Endothelial RBE4 Cells
Authors: Caruso Giuseppe , Fresta Claudia G. , Lazzarino Giacomo , Distefano Donatella A. , Parlascino Paolo , Lunte Susan M. , Lazzarino Giuseppe , Caraci Filippo
Published: November 2018

Human amylin is a 37-residue peptide hormone (hA1-37) secreted by β-cells of the pancreas and, along with insulin, is directly associated with type 2 diabetes mellitus (T2DM). Amyloid deposits within the islets of the pancreas represent a hallmark of T2DM. Additionally, amylin aggregates have been found in blood vessels and/or brain of patients with Alzheimer’s disease, alone or co-deposited with β-amyloid. The purpose of this study was to investigate the neuroprotective potential of human amylin in the context of endothelial-neuronal “cross-talk”. We initially performed dose-response experiments to examine cellular toxicity (quantified by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT assay) of different hA17–29 concentrations in endothelial cells (RBE4). In the culture medium of these cells, we also measured heat shock protein B5 (HspB5) levels by ELISA, finding that even a sub-toxic concentration of hA17–29 (3 µM) produced an increase of HspB5. Using a cell medium of untreated and RBE4 challenged for 48 h with a sub-toxic concentration of hA17–29, we determined the potential beneficial effect of their addition to the medium of neuroblastoma SH-SY5Y cells. These cells were subsequently incubated for 48 h with a toxic concentration of hA17–29 (20 µM). We found a complete inhibition of hA17–29 toxicity, potentially related to the presence in the conditioned medium not only of HspB5, but also of vascular endothelial growth factor (VEGF). Pre-treating SH-SY5Y cells with the anti-Flk1 antibody, blocking the VEGF receptor 2 (VEGFR2), significantly decreased the protective effects of the conditioned RBE4 medium. These data, obtained by indirectly measuring VEGF activity, were strongly corroborated by the direct measurement of VEGF levels in conditioned RBE4 media as detected by ELISA. Altogether, these findings highlighted a novel role of sub-toxic concentrations of human amylin in promoting the secretion of proteic factors by endothelial cells (HspB5 and VEGF) that support the survival and proliferation of neuron-like cells.
Hsp90 Stabilizes SIRT1 Orthologs in Mammalian Cells and C. elegans
Authors: Nguyen Minh Tu , Somogyvári Milán , Sőti Csaba
Published: November 2018

Sirtuin 1 (SIRT1) othologs are ubiquitous NAD+-dependent deacetylases that act as nutrient sensors and modulate metabolism and stress responses in diverse organisms. Both mammalian SIRT1 and Caenorhabditis elegans SIR-2.1 have been implicated in dietary restriction, longevity, and healthspan. Hsp90 is an evolutionarily conserved molecular chaperone that stabilizes a plethora of signaling ’client’ proteins and regulates fundamental biological processes. Here we report that Hsp90 is required for conformational stabilization of SIRT1 and SIR-2.1. We find that inhibition of Hsp90 by geldanamycin (GA) induces the depletion of mammalian SIRT1 protein in a concentration and time dependent manner in COS-7 and HepG2 cells. In contrast to SIRT1, SIRT2 level remains unchanged by GA treatment, reflecting a specific Hsp90 SIRT1 interaction. Hsp90 inhibition leads to the destabilization and proteasomal degradation of SIRT1. Moreover, we observe a GA-sensitive physical interaction between SIRT1 and Hsp90 by immunoprecipitation. We also demonstrate that hsp-90 gene silencing also induces SIR-2.1 protein depletion and proteasomal degradation in C. elegans. Our findings identify metazoan SIRT1 orthologs as Hsp90 clients and reveal a novel crosstalk between the proteostasis and nutrient signaling networks, which may have implications in various age related diseases.
The Pub1 and Upf1 Proteins Act in Concert to Protect Yeast from Toxicity of the [PSI+] Prion
Authors: Urakov Valery , Mitkevich Olga , Dergalev Alexander , Ter-Avanesyan Michael
Published: November 2018

The [PSI+] nonsense-suppressor determinant of Saccharomyces cerevisiae is based on the formation of heritable amyloids of the Sup35 (eRF3) translation termination factor. [PSI+] amyloids have variants differing in amyloid structure and in the strength of the suppressor phenotype. The appearance of [PSI+], its propagation and manifestation depend primarily on chaperones. Besides chaperones, the Upf1/2/3, Siw14 and Arg82 proteins restrict [PSI+] formation, while Sla2 can prevent [PSI+] toxicity. Here, we identify two more non-chaperone proteins involved in [PSI+] detoxification. We show that simultaneous lack of the Pub1 and Upf1 proteins is lethal to cells harboring [PSI+] variants with a strong, but not with a weak, suppressor phenotype. This lethality is caused by excessive depletion of the Sup45 (eRF1) termination factor due to its sequestration into Sup35 polymers. We also show that Pub1 acts to restrict excessive Sup35 prion polymerization, while Upf1 interferes with Sup45 binding to Sup35 polymers. These data allow consideration of the Pub1 and Upf1 proteins as a novel [PSI+] detoxification system.
An Enrichment Analysis for Cardiometabolic Traits Suggests Non-Random Assignment of Genes to microRNAs
Authors: Mustafa Rima , Ghanbari Mohsen , Evangelou Marina , Dehghan Abbas
Published: November 2018

MicroRNAs (miRNAs) regulate the expression of the majority of genes. However, it is not known whether they regulate genes in random or are organized according to their function. To this end, we chose cardiometabolic disorders as an example and investigated whether genes associated with cardiometabolic disorders are regulated by a random set of miRNAs or a limited number of them. Single-nucleotide polymorphisms (SNPs) reaching genome-wide level significance were retrieved from most recent genome-wide association studies on cardiometabolic traits, which were cross-referenced with Ensembl to identify related genes and combined with miRNA target prediction databases (TargetScan, miRTarBase, or miRecords) to identify miRNAs that regulate them. We retrieved 520 SNPs, of which 355 were intragenic, corresponding to 304 genes. While we found a higher proportion of genes reported from all GWAS that were predicted targets for miRNAs in comparison to all protein-coding genes (75.1%), the proportion was even higher for cardiometabolic genes (80.6%). Enrichment analysis was performed within each database. We found that cardiometabolic genes were over-represented in target genes for 29 miRNAs (based on TargetScan) and 3 miRNAs (miR-181a, miR-302d and miR-372) (based on miRecords) after Benjamini-Hochberg correction for multiple testing. Our work provides evidence for non-random assignment of genes to miRNAs and supports the idea that miRNAs regulate sets of genes that are functionally related.
Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor β
Authors: Tsubakihara Yutaro , Moustakas Aristidis
Published: November 2018

Metastasis of tumor cells from primary sites of malignancy to neighboring stromal tissue or distant localities entails in several instances, but not in every case, the epithelial-mesenchymal transition (EMT). EMT weakens the strong adhesion forces between differentiated epithelial cells so that carcinoma cells can achieve solitary or collective motility, which makes the EMT an intuitive mechanism for the initiation of tumor metastasis. EMT initiates after primary oncogenic events lead to secondary secretion of cytokines. The interaction between tumor-secreted cytokines and oncogenic stimuli facilitates EMT progression. A classic case of this mechanism is the cooperation between oncogenic Ras and the transforming growth factor β (TGFβ). The power of TGFβ to mediate EMT during metastasis depends on versatile signaling crosstalk and on the regulation of successive waves of expression of many other cytokines and the progressive remodeling of the extracellular matrix that facilitates motility through basement membranes. Since metastasis involves many organs in the body, whereas EMT affects carcinoma cell differentiation locally, it has frequently been debated whether EMT truly contributes to metastasis. Despite controversies, studies of circulating tumor cells, studies of acquired chemoresistance by metastatic cells, and several (but not all) metastatic animal models, support a link between EMT and metastasis, with TGFβ, often being a common denominator in this link. This article aims at discussing mechanistic cases where TGFβ signaling and EMT facilitate tumor cell dissemination.
Microduplication of 15q13.3 and Microdeletion of 18q21.32 in a Patient with Moyamoya Syndrome
Authors: Sciacca Francesca Luisa , Rizzo Ambra , Bedini Gloria , Capone Fioravante , Di Lazzaro Vincenzo , Nava Sara , Acerbi Francesco , Sebastiano Davide Rossi , Binelli Simona , Faragò Giuseppe , Gioppo Andrea , Grisoli Marina , Bruzzone Maria Grazia , Ferroli Paolo , Pantaleoni Chiara , Caputi Luigi , Gomez Jesus Vela , Parati Eugenio Agostino , Bersano Anna
Published: November 2018

Moyamoya angiopathy (MA) is a cerebrovascular disease determining a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and their proximal branches and the compensatory development of abnormal “moyamoya” vessels. MA occurs as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes) including several heritable conditions such as Down syndrome, neurofibromatosis type 1 and other genomic defects. Although the mechanism that links MA to these genetic syndromes is still unclear, it is believed that the involved genes may contribute to the disease susceptibility. Herein, we describe the case of a 43 years old woman with bilateral MA and peculiar facial characteristics, having a 484-kb microduplication of the chromosomal region 15q13.3 and a previously unreported 786 kb microdeletion in 18q21.32. This patient may have a newly-recognized genetic syndrome associated with MA. Although the relationship between these genetic variants and MA is unclear, our report would contribute to widening the genetic scenario of MA, in which not only genic mutation, but also genome unbalances are possible candidate susceptibility factors.
Furthest-Pair-Based Decision Trees: Experimental Results on Big Data Classification
Authors: Hassanat Ahmad B. A.
Published: November 2018

Big Data classification has recently received a great deal of attention due to the main properties of Big Data, which are volume, variety, and velocity. The furthest-pair-based binary search tree (FPBST) shows a great potential for Big Data classification. This work attempts to improve the performance the FPBST in terms of computation time, space consumed and accuracy. The major enhancement of the FPBST includes converting the resultant BST to a decision tree, in order to remove the need for the slow K-nearest neighbors (KNN), and to obtain a smaller tree, which is useful for memory usage, speeding both training and testing phases and increasing the classification accuracy. The proposed decision trees are based on calculating the probabilities of each class at each node using various methods; these probabilities are then used by the testing phase to classify an unseen example. The experimental results on some (small, intermediate and big) machine learning datasets show the efficiency of the proposed methods, in terms of space, speed and accuracy compared to the FPBST, which shows a great potential for further enhancements of the proposed methods to be used in practice.
Measuring Bikeshare Access/Egress Transferring Distance and Catchment Area around Metro Stations from Smartcard Data
Authors: Ma Xinwei , Jin Yuchuan , He Mingjia
Published: November 2018

Metro–bikeshare integration is considered a green and efficient travel model. To better develop such integration, it is necessary to monitor and analyze metro–bikeshare transfer characteristics. This paper measures access and egress transferring distances and catchment areas based on smartcard data. A cubic regression model is conducted for the exploration of the 85th access and egress network-based transferring distance around metro stations. Then, the independent samples t-test and one-way analysis of variance (ANOVA) are used to explore access and egress transfer characteristics in demographic groups and spatial and temporal dimension. Additionally, the catchment area is delineated by applying both the network-based distance method and Euclidean distance method. The result reveals that males outcompete females both in access and egress distances and urban dwellers ride a shorter distance than those in suburban areas. Access and egress distances are both shorter in morning peak hours than those in evening peak hours and access distance on weekdays is longer than that on weekends. In addition, network-based catchment area accounts for over 90% of Euclidean catchment area in urban areas, while most of the ratios are less than 85% in suburban. The paper uses data from Nanjing, China as a case study. This study serves as a scientific basis for policy makers and bikeshare companies to improve metro–bikeshare integration.
Annotating a Low-Resource Language with LLOD Technology: Sumerian Morphology and Syntax
Authors: Chiarcos Christian , Khait Ilya , Pagé-Perron Émilie , Schenk Niko , Jayanth  , Fäth Christian , Steuer Julius , Mcgrath William , Wang Jinyan
Published: November 2018

This paper describes work on the morphological and syntactic annotation of Sumerian cuneiform as a model for low resource languages in general. Cuneiform texts are invaluable sources for the study of history, languages, economy, and cultures of Ancient Mesopotamia and its surrounding regions. Assyriology, the discipline dedicated to their study, has vast research potential, but lacks the modern means for computational processing and analysis. Our project, Machine Translation and Automated Analysis of Cuneiform Languages, aims to fill this gap by bringing together corpus data, lexical data, linguistic annotations and object metadata. The project’s main goal is to build a pipeline for machine translation and annotation of Sumerian Ur III administrative texts. The rich and structured data is then to be made accessible in the form of (Linguistic) Linked Open Data (LLOD), which should open them to a larger research community. Our contribution is two-fold: in terms of language technology, our work represents the first attempt to develop an integrative infrastructure for the annotation of morphology and syntax on the basis of RDF technologies and LLOD resources. With respect to Assyriology, we work towards producing the first syntactically annotated corpus of Sumerian.
A Computational Study of AlF3 and ACF Surfaces
Authors: Pandharkar Riddhish , Becker Christian , Budau Johannes Horst , Kaawar Zeinab , Paulus Beate
Published: November 2018

By applying first principles density functional theory (DFT) methods, different metal fluorides and their surfaces have been characterized. One of the most investigated metal fluorides is AlF3 in different polymorphs. Its chloride-doped analogon AlClxF3−x (ACF) has recently attracted much attention due to its application in catalysis. After presenting a summary of different first-principle studies on the bulk and surface properties of different main group fluorides, we will revisit the problem of the stability of different α -AlF3 surfaces and extend the investigation to chloride-doped counterparts to simulate the surface properties of amorphous ACF. For each material, we have considered ten different surface cuts with their respective terminations. We found that terminations of ( 01 1 ¯ 0 ) and ( 11 2 ¯ 0 ) yield the most stable surfaces for α -AlF3 and for the chlorine substituted surfaces. A potential equilibrium shape of the crystal for both α -AlF3 and ACF is visualized by a Wulff construction.
Predictors of Exercise Capacity in Patients with Hypertrophic Obstructive Cardiomyopathy
Authors: Smith Joshua R. , Medina-Inojosa Jose R. , Layrisse Veronica , Ommen Steve R. , Olson Thomas P.
Published: November 2018

Hypertrophic obstructive cardiomyopathy (HOCM) patients exhibit compromised peak exercise capacity (VO2peak). Importantly, severely reduced VO2peak is directly related to increased morbidity and mortality in these patients. Therefore, we sought to determine clinical predictors of VO2peak in HOCM patients. HOCM patients who performed symptom-limited cardiopulmonary exercise testing between 1995 and 2016 were included for analysis. Peak VO2 was reported as absolute peak VO2, indexed to body weight and analyzed as quartiles, with quartile 1 representing the lowest VO2peak. Step-wise regression models using demographic features and clinical and physiologic characteristics were created to determine predictors of HOCM patients with the lowest VO2peak. We included 1177 HOCM patients (age: 53 ± 14 years; BMI: 24 ± 12 kg/m2) with a VO2peak of 18.0 ± 5.6 mL/kg/min. Significant univariate predictors of the lowest VO2peak included age, female sex, New York Health Association (NYHA) class, BMI, left atrial volume index, E/e’, E/A, hemoglobin, N-terminal pro b-type natriuretic peptide (NT-proBNP), and a history of diabetes, hypertension, stroke, atrial fibrillation, or coronary artery disease. Independent predictors of the lowest VO2peak included age (OR, CI: 1.03, 1.02–1.06; p < 0.0001), women (4.66, 2.94–7.47; p = 0.001), a history of diabetes (2.05, 1.17–3.60; p = 0.01), BMI (0.94, 0.92–0.96; p < 0.0001), left atrial volume index (1.07, 1.05–1.21; p = 0.04), E/e’ (1.05, 1.01–1.08; p = 0.004), hemoglobin (0.76, 0.65–0.88; p = 0.0004), and NT-proBNP (1.72, 1.42–2.11; p < 0.0001). These findings demonstrate that demographic factors (i.e., age and sex), comorbidities (e.g., diabetes and obesity), echocardiography indices, and biomarkers (e.g., hemoglobin and NT-proBNP) are predictive of severely compromised VO2peak in HOCM patients.
Valuing Environmental Benefit Streams in the Dryland Ecosystems of Sub-Saharan Africa
Authors: King-Okumu Caroline
Published: November 2018

Policy-makers and practitioners often struggle or fail to define and quantify the economic impacts that can be achieved through ecologically sustainable investments in dryland ecosystems. This paper reviews the current state of the art in the characterization and valuation of environmental benefits in drought-prone areas of Sub-Saharan Africa. Benefit streams from ecosystem services associated with the production of food, energy and water are characterized, as well as those from supporting and regulating hydrological systems. For each value type, valuation approaches and examples of their application in Sub-Saharan African contexts are presented. The review is drawn from a series of recent methodological discussions, working papers and field research reports focusing on the benefits of locally determined and ecosystem-based adaptations under dryland climate extremes. The focus is on the challenges faced by practitioners and researchers tasked with developing benefit-cost assessments for investments in the adaptive management and conservation of dryland ecosystems, particularly in marginalized dry and drought-prone areas of Sub-Saharan Africa. Recommendations could also interest a wider global community of dryland researchers and development practitioners.
Hollow Fiber Porous Nanocomposite Membranes Produced via Continuous Extrusion: Morphology and Gas Transport Properties
Authors: Razzaz Zahir , Rodrigue Denis
Published: November 2018

In this work, hollow fiber porous nanocomposite membranes were successfully prepared by the incorporation of a porous nanoparticle (zeolite 5A) into a blend of linear low-density polyethylene (LLDPE)/low-density polyethylene (LDPE) combined with azodicarbonamide as a chemical blowing agent (CBA). Processing was performed via continuous extrusion using a twin-screw extruder coupled with a calendaring system. The process was firstly optimized in terms of extrusion and post-extrusion conditions, as well as formulation to obtain a good cellular structure (uniform cell size distribution and high cell density). Scanning electron microscopy (SEM) was used to determine the cellular structure as well as nanoparticle dispersion. Then, the samples were characterized in terms of mechanical and thermal stability via tensile tests and thermogravimetric analysis (TGA), as well as differential scanning calorimetry (DSC). The results showed that the zeolite nanoparticles were able to act as effective nucleating agents during the foaming process. However, the optimum nanoparticle content was strongly related to the foaming conditions. Finally, the membrane separation performances were investigated for different gases (CO2, CH4, N2, O2, and H2) showing that the incorporation of porous zeolite significantly improved the gas transport properties of semi-crystalline polyolefin membranes due to lower cell wall thickness (controlling permeability) and improved separation properties (controlling selectivity). These results show that mixed matrix membranes (MMMs) can be cost-effective, easy to process, and efficient in terms of processing rate, especially for the petroleum industry where H2/CH4 and H2/N2 separation/purification are important for hydrogen recovery.
The Out-of-Plane Compression Behavior of Cross-Ply AS4/PEEK Thermoplastic Composite Laminates at High Strain Rates
Authors: Zou Huiran , Yin Weilong , Cai Chaocan , Wang Bing , Liu Ankang , Yang Zhen , Li Yibin , He Xiaodong
Published: November 2018

The dynamic mechanical behavior of thermoplastic composites over a wide range of strain rates has become an important research topic for extreme environmental survivability in the fields of military protection, aircraft safety, and aerospace engineering. However, the dynamic compression response in the out-of-plane direction, which is one of the most important loading conditions resulting in the damage of composite materials, has not been investigated thoroughly when compared to in-plane compression and tensile behavior under high strain rates. Thus, we used split Hopkinson pressure bar (SHPB) tests to conduct the out-of-plane compression test of cross-ply carbon fiber-reinforced polyetheretherketone (AS4/PEEK) composite laminates. Afterward, the damage mechanism under different strain rates was characterized by the macrostructure morphologies and scanning electron microscope micrographs. Two major cases of the incomplete failure condition and complete failure condition were discussed. Dynamic stress-strain curves expound the strain rates dependencies of elastic modulus, failure strength, and failure strain. An obvious spring-back process could be observed under incomplete failure tests. For the complete failure tests, secondary loading could be observed by reconstructing and comparing the dynamic response history. Lastly, various failure modes that occurred in different loading strain rates illustrate that the damage mechanism also shows obvious strain rate sensitivity.
Fibrin-Modified Cellulose as a Promising Dressing for Accelerated Wound Healing
Authors: Bacakova Marketa , Pajorova Julia , Sopuch Tomas , Bacakova Lucie
Published: November 2018

Dermal injuries and chronic wounds usually regenerate with scar formation. Successful treatment without scarring might be achieved by pre-seeding a wound dressing with cells. We aimed to prepare a wound dressing fabricated from sodium carboxymethylcellulose (Hcel® NaT), combined with fibrin and seeded with dermal fibroblasts in vitro. We fabricated the Hcel® NaT in a porous and homogeneous form (P form and H form, respectively) differing in structural morphology and in the degree of substitution of hydroxyl groups. Each form of Hcel® NaT was functionalized with two morphologically different fibrin structures to improve cell adhesion and proliferation, estimated by an MTS assay. Fibrin functionalization of the Hcel® NaT strongly enhanced colonization of the material with human dermal fibroblasts. Moreover, the type of fibrin structures influenced the ability of the cells to adhere to the material and proliferate on it. The fibrin mesh filling the void spaces between cellulose fibers better supported cell attachment and subsequent proliferation than the fibrin coating, which only enwrapped individual cellulose fibers. On the fibrin mesh, the cell proliferation activity on day 3 was higher on the H form than on the P form of Hcel® NaT, while on the fibrin coating, the cell proliferation on day 7 was higher on the P form. The Hcel® NaT wound dressing functionalized with fibrin, especially when in the form of a mesh, can accelerate wound healing by supporting fibroblast adhesion and proliferation.
Industrial Waste Treatment by ETS-10 Ion Exchanger Material
Authors: De Luca Pierantonio , Bernaudo Ivano , Elliani Rosangela , Tagarelli Antonio , Nagy Jànos B. , Macario Anastasia
Published: November 2018

The aim of this project was to study the treatment of industrial waste using ETS-10 zeolite. The pollutants that must be removed were metals sourced from zinc ferrite, a processing waste derived from the use of mineral-containing zinc. The first phase of the work involved the characterization of the industrial waste, zinc ferrite, in order to deepen the knowledge regarding its nature and composition. The second phase involved the removal of the metals released by the zinc ferrite in aqueous systems using the ETS-10 phase as an ion exchanger. Different chemical and physical techniques were used: plasma mass spectrometry, X-ray diffraction, scanning electron microscopy, microanalysis, and thermal analyses. A comparison between ETS-10 and commercial zeolite A performance, in the same aqueous systems, was carried out. The results showed that the metal removal efficiency of ETS-10 phase is higher than that obtained by commercial zeolite A, especially towards dangerous heavy metals such as Pb, Zn and Mn.