bluuebunny/crossref_metadata_2025 huggingface dataset:
Chrysanthemum indicum and Chrysanthemum morifolium: Chemical Composition of Their Essential Oils and Their Potential Use as Natural Preservatives with Antimicrobial and Antioxidant Activities
Authors: Youssef Fadia S. , Eid Safaa Y. , Alshammari Elham , Ashour Mohamed L. , Wink Michael , El-Readi Mahmoud Z.
Published: October 2020

The composition of essential oils of Chrysanthemum indicum and C. morifolium were comparatively studied using both Gas Chromatography/Flame ionization Detector (GC/FID) and Gas Chromatography/Mass spectrometry (GC/MS) analyses. The antiviral activity was determined using a plaque reduction assay against three common viruses namely, herpes simplex type-1 (HSV-1), hepatitis A (HAV) and vesicular stomatitis virus (VSV). The antimicrobial activity was assessed using agar diffusion and microdilution methods and the minimum inhibitory concentration (MIC) values were determined. In addition, the anti-mycobacterial evaluation was carried out using the Alamar blue assay and the effect against Helicobacter pylori was investigated. The anti-trypanosomal activity was evaluated using the resazurin method. GC investigations revealed that camphor is the major constituent of both oils accounting for 36.69 and 14.56% in the essential oils from C. indicum and C. morifolium, respectively. C. indicum was biologically more active in all experiments; it exhibited a notable antitrypanosomal activity with an IC50 value equals 45.89 μg/mL and a notable antimicrobial activity versus Streptococcus agalactiae with a MIC value of 62.5 μg/mL. It also inhibited the replication of VSV with an IC50 value of 3.14 μg/mL. Both oils revealed antioxidant potential with IC50 values of 2.21 and 2.59 mg/mL for C. indicum and C. morifolium, respectively. This study provides evidence beyond the traditional use of both Chrysanthemum indicum and C. morifolium as anti-infective agents. Thus they could be used as spices in food and can be incorporated in different food products and pharmaceutical preparations as natural preservatives possessing antioxidant potential.
Nutritional Attributes and Sensory Quality during Storage Time of Spiced Lamb Burgers from Manchego Spanish Breed
Authors: Linares María Belén , Cózar Almudena , Garrido María Dolores , Vergara Herminia
Published: October 2020

The aim of this study was to determine the effect of the addition of spices (garlic, rosemary, thyme, sage or clove) on the chemical and sensory characteristics of burgers elaborated with lamb meat from different locations (L: only leg; LNB 2/3 leg + 1/3 neck and breast). Formulation type (L vs. LNB) modified the chemical composition. L burgers showed lower values of fat, saturated fatty acids, monounsaturated fatty acids and higher moisture and polyunsaturated fatty acids content than LNB samples, with both types of burgers maintaining the nutritional indexes (P/S and n6/n3) within the recommended amounts. Nevertheless, the type of formula did not influence the sensory properties of lamb burgers. By contrast, the spice addition affected these characteristics over the period of time considered in this study. At the end of storage their global quality could be listed in the following order, from major to minor rate: Sage > Rosemary > Garlic > Thyme > Clove burgers.
Plant Foods and Underutilized Fruits as Source of Functional Food Ingredients: Chemical Composition, Quality Traits, and Biological Properties
Authors: Donno Dario , Turrini Federica
Published: October 2020

Changes in lifestyle and demographics, rising consumer incomes, and shifting preferences due to advanced knowledge about the relationships between food and health contribute to generate new needs in the food supply. Today, the role of food is not only intended as hunger satisfaction and nutrient supply but also as an opportunity to prevent nutrition-related diseases and improve physical and mental well-being. For this reason, there is a growing interest in the novel or less well-known plant foods that offer an opportunity for health maintenance. Recently, interest in plant foods and underutilized fruits is continuously growing, and agrobiodiversity exploitation offers effective and extraordinary potentialities. Plant foods could be an important source of health-promoting compounds and functional food ingredients with beneficial properties: the description of the quality and physicochemical traits, the identification and quantification of bioactive compounds, and the evaluation of their biological activities are important to assess plant food efficacy as functional foods or source of food supplement ingredients.
Clinical Genetics Can Solve the Pitfalls of Genome-Wide Investigations: Lesson from Mismapping a Loss-of-Function Variant in KANSL1
Authors: Bigoni Stefania , Marangi Giuseppe , Frangella Silvia , Panfili Arianna , Ognibene Davide , Squeo Gabriella Maria , Merla Giuseppe , Zollino Marcella
Published: October 2020

Massive parallel sequencing of 70 genes in a girl with a suspicion of chromatinopathy detected the (NM_015443.4:)c.985_986delTT variant in exon 2 of KANSL1, which led to a diagnostic consideration of Koolen De Vries syndrome. The same variant was present in the healthy mother, consistent with either incomplete penetrance or variant mismapping. A network of second opinion was implemented among clinical geneticists first, and a diagnosis of Koolen De Vries syndrome was considered unlikely. By MLPA, a duplication spanning exons 1-3 of KANSL1 was detected in both the mother and the daughter. On cDNA sequencing, biallelic wild type mRNA was observed. We concluded that the variant affects the noncoding duplicated gene region in our family, and we finally classified it as benign. Parallel wide genomic sequencing is increasingly the first genetic investigation in individuals with intellectual disability. The c.985_986delTT variant in KANSL1 was described both in individuals with typical KdVS and in a limited number of healthy subjects. This report highlights the role of clinical genetics to correctly classify variants and to define proper clinical and diagnostic correlations.
In Silico Model for Chemical-Induced Chromosomal Damages Elucidates Mode of Action and Irrelevant Positives
Authors: Fujita Yurika , Morita Osamu , Honda Hiroshi
Published: October 2020

In silico tools to predict genotoxicity have become important for high-throughput screening of chemical substances. However, current in silico tools to evaluate chromosomal damage do not discriminate in vitro-specific positives that can be followed by in vivo tests. Herein, we establish an in silico model for chromosomal damages with the following approaches: (1) re-categorizing a previous data set into three groups (positives, negatives, and misleading positives) according to current reports that use weight-of-evidence approaches and expert judgments; (2) utilizing a generalized linear model (Elastic Net) that uses partial structures of chemicals (organic functional groups) as explanatory variables of the statistical model; and (3) interpreting mode of action in terms of chemical structures identified. The accuracy of our model was 85.6%, 80.3%, and 87.9% for positive, negative, and misleading positive predictions, respectively. Selected organic functional groups in the models for positive prediction were reported to induce genotoxicity via various modes of actions (e.g., DNA adduct formation), whereas those for misleading positives were not clearly related to genotoxicity (e.g., low pH, cytotoxicity induction). Therefore, the present model may contribute to high-throughput screening in material design or drug discovery to verify the relevance of estimated positives considering their mechanisms of action.
Precise Genome Editing in Poultry and Its Application to Industries
Authors: Park Jin Se , Lee Kyung Youn , Han Jae Yong
Published: October 2020

Poultry such as chickens are valuable model animals not only in the food industry, but also in developmental biology and biomedicine. Recently, precise genome-editing technologies mediated by the CRISPR/Cas9 system have developed rapidly, enabling the production of genome-edited poultry models with novel traits that are applicable to basic sciences, agriculture, and biomedical industry. In particular, these techniques have been combined with cultured primordial germ cells (PGCs) and viral vector systems to generate a valuable genome-edited avian model for a variety of purposes. Here, we summarize recent progress in CRISPR/Cas9-based genome-editing technology and its applications to avian species. In addition, we describe further applications of genome-edited poultry in various industries.
Localization and RNA Binding of Mitochondrial Aminoacyl tRNA Synthetases
Authors: Garin Shahar , Levi Ofri , Cohen Bar , Golani-Armon Adi , Arava Yoav S.
Published: October 2020

Mitochondria contain a complete translation machinery that is used to translate its internally transcribed mRNAs. This machinery uses a distinct set of tRNAs that are charged with cognate amino acids inside the organelle. Interestingly, charging is executed by aminoacyl tRNA synthetases (aaRS) that are encoded by the nuclear genome, translated in the cytosol, and need to be imported into the mitochondria. Here, we review import mechanisms of these enzymes with emphasis on those that are localized to both mitochondria and cytosol. Furthermore, we describe RNA recognition features of these enzymes and their interaction with tRNA and non-tRNA molecules. The dual localization of mitochondria-destined aaRSs and their association with various RNA types impose diverse impacts on cellular physiology. Yet, the breadth and significance of these functions are not fully resolved. We highlight here possibilities for future explorations.
Genome-Wide Identification, Classification, Characterization, and Expression Analysis of the Wall-Associated Kinase Family during Fruit Development and under Wound Stress in Tomato (Solanum lycopersicum L.)
Authors: Sun Zongyan , Song Yanping , Chen Di , Zang Yudi , Zhang Qiaoli , Yi Yuetong , Qu Guiqin
Published: October 2020

The wall-associated kinase (WAK) and wall-associated kinase like (WAKL) is a subfamily of receptor-like kinases associated with the cell wall, which have been suggested as sensors of the extracellular environment and triggers of intracellular signals. However, these proteins have not yet been comprehensively analyzed in tomato (Solanum lycopersicum L.). In this study, 11 SlWAK and 18 SlWAKL genes were identified in an uneven distribution in 9 of 12 chromosomes. GUB-WAK-bind (wall-associated receptor kinase galacturonan-binding) and epidermal growth factor (EGF) domains appear more often in SlWAK proteins. However, more SlWAKLs (wall-associated kinase like) have a WAK-assoc (wall-associated receptor kinase C-terminal) domain. Based on their phylogenetic relationships, 29 SlWAK-RLKs (wall associated kinase-receptor like kinases) were clustered into three distinct categories analogous to those in Arabidopsis thaliana. High similarities were found in conserved motifs of the genes within each group. Cis-elements in the promoter region of these 29 genes were found mainly in response to methyl jasmonate (MeJA), abscisic acid (ABA), salicylic acid (SA), anaerobic, light, wound, and MYB transcription factors. Public tomato genome RNA-seq data indicates that multiple SlWAK-RLKs showed different expression patterns under developmental and ripening stages of fruits, such as SlWAK4, SlWAKL11, SlWAKL9, SlWAKL15, SlWAKL14, and SlWAKL1, their RPKM (Reads Per Kilo bases per Million reads) value constantly increases during the fruit expansion period, and decreases as the fruit matures. In tomato leaves, our RNA-seq data showed that nine SlWAK-RLKs transcripts (SlWAK3, SlWAK4, SlWAK10,SlWAKL1, SlWAKL2, SlWAKL3, SlWAKL5, SlWAKL14, and SlWAKL18) were significantly induced (p < 0.001), and three transcripts (SlWAK2, SlWAK5, and SlWAKL15) were significantly inhibited (p < 0.001) under mechanical wounding. The qRT-PCR (Quantitative reverse transcription polymerase chain reaction) of SlWAKL1 and SlWAKL6 verify these results.
Exaggerated Autophagy in Stanford Type A Aortic Dissection: A Transcriptome Pilot Analysis of Human Ascending Aortic Tissues
Authors: Zhou Zeyi , Liu Yan , Zhu Xiyu , Tang Xinlong , Wang Yali , Wang Junxia , Xu Can , Wang Dongjin , Du Jie , Zhou Qing
Published: October 2020

Stanford type A aortic dissection (TAAD) is one of the most dangerous diseases of acute aortic syndrome. Molecular pathological studies on TAAD can aid in understanding the disease comprehensively and can provide insights into new diagnostic markers and potential therapeutic targets. In this study, we defined the molecular pathology of TAAD by performing transcriptome sequencing of human ascending aortic tissues. Pathway analysis revealed that activated inflammation, cell death and smooth muscle cell degeneration are the main pathological changes in aortic dissection. However, autophagy is considered to be one of the most important biological processes, regulating inflammatory reactions and degenerative changes. Therefore, we focused on the pathological role of autophagy in aortic dissection and identified 10 autophagy-regulated hub genes, which are all upregulated in TAAD. These results indicate that exaggerated autophagy participates in the pathological process of aortic dissection and may provide new insight for further basic research on TAAD.
Identification of Differentially Methylated Regions Associated with a Knockout of SUV39H1 in Prostate Cancer Cells
Authors: Yan Wenbo , Guo Yuqi , Xu Fangxi , Saxena Deepak , Li Xin
Published: October 2020

Epigenetic alterations, such as histone methylations, affect the pathogenesis of tumors including prostate cancer (PCa). Previously, we reported that metformin reduced SUV39H1, a histone methyltransferase of H3 Lys9, to inhibit the migration of PCa cells. Since histone methylation is functionally linked to DNA methylation, we speculate that the knockout of the SUV39H1 gene will affect the genomic DNA methylation profile to regulate PCa cell migration and invasion. The genome-wide DNA methylation level is lower in SUV39H1 knockout (KO) cells than wild-type (WT) ones. However, the methylation levels in functional regions of CpG Islands (CGI), 5′ untranslated region (UTR5), and exon regions are higher in KO cells than WT cells. Analysis of differentially methylated regions (DMRs) identified 1241 DMR genes that have differential methylation on CG sites when comparing the KO and WT samples. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes Pathways analysis showed that knockout of SUV39H1 affects gene sets and pathways that are heavily involved in cell shapes, cell recognition, adhesion, motility, and migration. Our study suggests that SUV39H1 plays an important role in PCa migration via the epigenetic regulation of methylation on CG sites, and is a novel and legitimate target to inhibit PCa cell migration.
Low RIN Value for RNA-Seq Library Construction from Long-Term Stored Seeds: A Case Study of Barley Seeds
Authors: Puchta Marta , Boczkowska Maja , Groszyk Jolanta
Published: October 2020

Seed aging is a complex biological process and its fundamentals and mechanisms have not yet been fully recognized. This is a key issue faced by research teams involved in the collection and storage of plant genetic resources in gene banks every day. Transcriptomic changes associated with seed aging in the dry state have barely been studied. The aim of the study was to develop an efficient protocol for construction of RNA-Seq libraries from long-term stored seeds with very low viability and low RNA integrity number (RIN). Here, barley seeds that have almost completely lost their viability as a result of long-term storage were used. As a control, fully viable seeds obtained in the course of field regeneration were used. The effectiveness of protocols dedicated to RNA samples with high and low RIN values was compared. The experiment concluded that library construction from low viable or long-term stored seeds with degraded RNA (RIN < 3) should be carried out with extraordinary attention due to the possibility of uneven degradation of different RNA fractions.
Genetic Evaluation in a Cohort of 126 Dutch Pulmonary Arterial Hypertension Patients
Authors: van den Heuvel Lieke M. , Jansen Samara M. A. , Alsters Suzanne I. M. , Post Marco C. , van der Smagt Jasper J. , Handoko-De Man Frances S. , van Tintelen J. Peter , Gille Hans , Christiaans Imke , Vonk Noordegraaf Anton , Bogaard HarmJan , Houweling Arjan C.
Published: October 2020

Pulmonary arterial hypertension (PAH) is a severe, life-threatening disease, and in some cases is caused by genetic defects. This study sought to assess the diagnostic yield of genetic testing in a Dutch cohort of 126 PAH patients. Historically, genetic testing in the Netherlands consisted of the analysis of BMPR2 and SMAD9. These genes were analyzed in 70 of the 126 patients. A (likely) pathogenic (LP/P) variant was detected in 22 (31%) of them. After the identification of additional PAH associated genes, a next generation sequencing (NGS) panel consisting of 19 genes was developed in 2018. Additional genetic testing was offered to the 48 BMPR2 and SMAD9 negative patients, out of which 28 opted for NGS analysis. In addition, this gene panel was analyzed in 56 newly identified idiopathic (IPAH) or pulmonary veno occlusive disease (PVOD) patients. In these 84 patients, NGS panel testing revealed LP/P variants in BMPR2 (N = 4), GDF2 (N = 2), EIF2AK4 (N = 1), and TBX4 (N = 3). Furthermore, 134 relatives of 32 probands with a LP/P variant were tested, yielding 41 carriers. NGS panel screening offered to IPAH/PVOD patients led to the identification of LP/P variants in GDF2, EIF2AK4, and TBX4 in six additional patients. The identification of LP/P variants in patients allows for screening of at-risk relatives, enabling the early identification of PAH.
The Variant rs1784042 of the SIDT2 Gene is Associated with Metabolic Syndrome through Low HDL-c Levels in a Mexican Population
Authors: León-Reyes Guadalupe , Rivera-Paredez Berenice , López Juan Carlos Fernandez , Ramírez-Salazar Eric G. , Aquino-Gálvez Arnoldo , Gallegos-Carrillo Katia , Denova-Gutiérrez Edgar , Salmerón Jorge , Velázquez-Cruz Rafael
Published: October 2020

The Mexican population has one of the highest prevalences of metabolic syndrome (MetS) worldwide. The aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) with MetS and its components. First, we performed a pilot Genome-wide association study (GWAS) scan on a sub-sample derived from the Health Workers Cohort Study (HWCS) (n = 411). Based on GWAS results, we selected the rs1784042 and rs17120425 SNPs in the SIDT1 transmembrane family member 2 (SIDT2) gene for replication in the entire cohort (n = 1963), using predesigned TaqMan assays. We observed a prevalence of MetS in the HWCS of 52.6%. The minor allele frequency for the variant rs17120425 was 10% and 29% for the rs1784042. The SNP rs1784042 showed an overall association with MetS (OR = 0.82, p = 0.01) and with low levels of high-density lipoprotein (HDL-c) (odds ratio (OR) = 0.77, p = 0.001). The SNP rs17120425 had a significant association with type 2 diabetes (T2D) risk in the overall population (OR = 1.39, p = 0.033). Our results suggest an association of the rs1784042 and rs17120425 variants with MetS, through different mechanisms in the Mexican population. Further studies in larger samples and other populations are required to validate these findings and the relevance of these SNPs in MetS.
Population Genetic Structure of the Wild Boar (Sus scrofa) in the Carpathian Basin
Authors: Mihalik Bendegúz , Frank Krisztián , Astuti Putri Kusuma , Szemethy Dániel , Szendrei László , Szemethy László , Kusza Szilvia , Stéger Viktor
Published: October 2020

In the Carpathian Basin the wild boar (Sus scrofa) belongs among the most important game species both ecologically and economically, therefore knowing more about the basics of the genetics of the species is a key factor for accurate and sustainable management of its population. The aim of this study was to estimate the genetic diversity and to elucidate the genetic structure and location of wild boar populations in the Carpathian Basin. A total of 486 samples were collected and genotyped using 13 STR markers. The number of alleles varied between 4 and 14, at 9 of the 13 loci the observed heterozygosity was significantly different (p < 0.05) from the expected value, showing remarkable introgression in the population. The population was separated into two groups, with an Fst value of 0.03, suggesting the presence of two subpopulations. The first group included 147 individuals from the north-eastern part of Hungary, whereas the second group included 339 samples collected west and south of the first group. The two subpopulations’ genetic indices are roughly similar. The lack of physical barriers between the two groups indicates that the genetic difference is most likely caused by the high reproduction rate and large home range of the wild boars, or by some genetic traces’ having been preserved from both the last ice age and the period before the Hungarian water regulation.
Trypanosoma Cruzi Genome: Organization, Multi-Gene Families, Transcription, and Biological Implications
Authors: Herreros-Cabello Alfonso , Callejas-Hernández Francisco , Gironès Núria , Fresno Manuel
Published: October 2020

Chagas disease caused by the parasite Trypanosoma cruzi affects millions of people. Although its first genome dates from 2005, its complexity hindered a complete assembly and annotation. However, the new sequencing methods have improved genome annotation of some strains elucidating the broad genetic diversity and complexity of this parasite. Here, we reviewed the genomic structure and regulation, the genetic diversity, and the analysis of the principal multi-gene families of the recent genomes for several strains. The telomeric and sub-telomeric regions are sites with high recombination events, the genome displays two different compartments, the core and the disruptive, and the genome plasticity seems to play a key role in the survival and the infection process. Trypanosoma cruzi (T. cruzi) genome is composed mainly of multi-gene families as the trans-sialidases, mucins, and mucin-associated surface proteins. Trans-sialidases are the most abundant genes in the genome and show an important role in the effectiveness of the infection and the parasite survival. Mucins and MASPs are also important glycosylated proteins of the surface of the parasite that play a major biological role in both insect and mammal-dwelling stages. Altogether, these studies confirm the complexity of T. cruzi genome revealing relevant concepts to better understand Chagas disease.
Characterization of Quantitative Trait Loci for Germination and Coleoptile Length under Low-Temperature Condition Using Introgression Lines Derived from an Interspecific Cross in Rice
Authors: Akhtamov Mirjalol , Adeva Cheryl , Shim Kyu-Chan , Lee Hyun-Sook , Kim Sun Ha , Jeon Yun-A , Luong Ngoc Ha , Kang Ju-Won , Lee Ji-Yoon , Ahn Sang-Nag
Published: October 2020

Previously, five putative quantitative trait loci (QTLs) for low-temperature germination (LTG) have been detected using 96 BC3F8 lines derived from an interspecific cross between the Korean japonica cultivar “Hwaseong” and Oryza rufipogon. In the present study, two introgression lines, CR1517 and CR1518, were used as parents to detect additional QTLs and analyze interactions among QTLs for LTG. The F2 population (154 plants) along with parental lines, Hwaseong and O. rufipogon, were evaluated for LTG and coleoptile length under low-temperature conditions (13 °C). Among five QTLs for LTG, two major QTLs, qLTG1 and qLTG3, were consistently detected at 6 and 7 days after incubation. Three minor QTLs were detected on chromosomes 8 and 10. Two QTLs, qLTG10.1 and qLTG10.2, showing linkage on chromosome 10, exerted opposite effects with the Hwaseong allele at qLTG10.2 and the O. rufipogon allele at qLTG10.1 respectively, in turn, increasing LTG. Interactions among QTLs were not significant, implying that the QTLs act in an additive manner. Near-isogenic line plants with the combination of favorable alleles from O. rufipogon and Hwaseong exhibited higher LTG than two introgression lines. With regard to coleoptile length, three QTLs observed on chromosomes 1, 3, and 8 were colocalized with QTLs for LTG, suggesting the pleiotropy of the single gene at each locus. According to the results, the introgression of favorable O. rufipogon alleles could hasten the development of rice with high LTG and high coleoptile elongation in japonica cultivars.
Two New Cases of Hypertrophic Cardiomyopathy and Skeletal Muscle Features Associated with ALPK3 Homozygous and Compound Heterozygous Variants
Authors: Jorholt John , Formicheva Yulia , Vershinina Tatyana , Kiselev Artem , Muravyev Alexey , Demchenko Elena , Fedotov Petr , Zlotina Anna , Rygkov Anton , Vasichkina Elena , Sejersen Thomas , Kostareva Anna
Published: October 2020

Hypertrophic cardiomyopathy associated with damaging variants in the ALPK3 gene is a fairly recent discovery, and only a small number of patients have been described thus far. Here we present two additional patients with hypertrophic cardiomyopathy caused by biallelic variants in ALPK3. Genetic investigation was performed using a targeted gene panel consisting of known cardiomyopathy-associated genes and whole exome sequencing. The patients showed a large difference in the age of onset, and both presented with extracardiac features that are often seen in ALPK3 patients. The patient with the later onset showed milder extracardiac symptoms, such as decreased muscle tone and distal muscular dystrophy, but had fast progression of cardiac complications leading to the need of heart transplantation. This study further elucidates the variability of both symptoms and age of onset among these patients.
Comparison of the Impact of Pharmacogenetic Variability on the PK of Slow Release and Immediate Release Tacrolimus Formulations
Authors: Gelder Teun van , Etsouli Oumaima , Moes Dirk Jan , Swen Jesse J.
Published: October 2020

Tacrolimus-modified release formulations allow for once-daily dosing, and adherence is better compared to the twice-daily immediate release formulation. When patients are switched from one formulation to another, variable changes in drug concentrations are observed. Current data suggest that the changes in drug exposure are larger in patients who express the CYP3A5 enzyme (CYP3A5 *1/*3 or *1/*1) compared to nonexpressers (CYP3A5*3/*3). Possibly, these differences are due to the fact that in the upper region of the small intestine CYP3A activity is higher, and that this expression of CYP3A decreases towards the more distal parts of the gut. Modified release formulations may therefore be subject to a less presystemic metabolism. However, the full implications of pharmacogenetic variants affecting the expression and function of drug transporters in the gut wall and of enzymes involved in phase I and phase II metabolism on the different formulations are incompletely understood, and additional studies are required. Conclusions: In all patients in whom the formulation of tacrolimus is changed, drug levels need to be checked to avoid clinically relevant under- or overexposure. In patients with the CYP3A5 expresser genotype, this recommendation is even more important, as changes in drug exposure can be expected.
Genetic Risk of Autism Spectrum Disorder in a Pakistani Population
Authors: Khalid Madiha , Raza Hashim , M. Driessen Terri , J. Lee Paul , Tejwani Leon , Sami Abdul , Nawaz Muhammad , Mehmood Baig Shahid , Lim Janghoo , Kaukab Raja Ghazala
Published: October 2020

Autism spectrum disorder (ASD) is a group of complex multifactorial neurodevelopmental and neuropsychiatric disorders in children characterized by impairment of communication and social interaction. Several genes with associated single nucleotide polymorphisms (SNPs) have been identified for ASD in different genetic association studies, meta-analyses, and genome-wide association studies (GWAS). However, associations between different SNPs and ASD vary from population to population. Four SNPs in genes CNTNAP2, EIF4E, ATP2B2, CACNA1C, and SNP rs4307059 (which is found between CDH9 and CDH10 genes) have been identified and reported as candidate risk factors for ASD. The aim of the present study was, for the first time, to assess the association of SNPs in these genes with ASD in the Pakistani population. PCR-based genotyping was performed using allele-specific primers in 93 ASD and 93 control Pakistani individuals. All genetic associations, genotype frequencies, and allele frequencies were computed as odds’ ratios (ORs) using logistic regression with a threshold of p ≤ 0.01 to determine statistical significance. We found that the homozygous genotypes of mutant T alleles of CNTNAP2 and ATP2B2 were significantly associated with Pakistani ASD patients in unadjusted ORs (p < 0.01), but their significance score was lost in the adjusted model. Other SNPs such as rs4307059, rs17850950 of EIF4E, and rs1006737 of CACNA1C were not statistically significant. Based on this, we conclude that SNPs are not associated with, or are not the main cause of, autism in the Pakistani population, indicating the involvement of additional players, which need to be investigated in future studies in a large population size. One of the limitations of present study is its small sample size. However, this study, being the first on Pakistani ASD patients, may lay the foundations for future studies in larger samples.
Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression
Authors: Sherif Iman O. , Al-Mutabagani Laila A. , Sabry Dina , Elsherbiny Nehal M.
Published: October 2020

The natural flavonoid chrysin possesses antiproliferative activity against various types of cancers, including hepatocellular carcinoma (HCC), which is a common malignancy. However, the exact mechanism of chrysin antiproliferative activity remains unclear. This research was executed to explore the impact of chrysin on glypican-3 (GPC3)/sulfatase-2 (SULF2) axis and lncRNA-AF085935 expression in HCC using HepG2 cells. Cisplatin (20, 50, 100 μg/mL), chrysin (15, 30, and 60 μg/mL) and the combination of 50 μg/mL cisplatin with different concentrations of chrysin were applied for 24/48 h. Cell viability was determined by MTT assay. Protein levels of GPC3 and SULF2 were measured by ELISA at 24/48 h. GPC3 immunoreactivity was detected by immunocytochemistry. Moreover, GPC3 and SULF2 mRNA expressions in addition to lncRNA-AF085935 expression were assessed by qPCR at 48 h. The GPC3 protein, immunostaining and mRNA levels, SULF2 protein and mRNA levels, as well as lncRNA-AF085935 expression, were decreased significantly with cisplatin and chrysin alone when compared with the control untreated HepG2 cells. However, the combination treatment exhibited a better chemopreventive effect in a dose- and time-dependent manner. This study demonstrated, for the first time, the antiproliferative activity of chrysin against HCC through the suppression of the GPC3/SULF2 axis along with the downregulation of lncRNA-AF085935 expression. Synergistic effect of chrysin with cisplatin could potentiate their antiproliferative action in a dose- and time-dependent manner.
DAP Kinase-Related Apoptosis-Inducing Protein Kinase 2 (DRAK2) Is a Key Regulator and Molecular Marker in Chronic Lymphocytic Leukemia
Authors: Szoltysek Katarzyna , Ciardullo Carmela , Zhou Peixun , Walaszczyk Anna , Willmore Elaine , Rand Vikki , Marshall Scott , Hall Andy , J. Harrison Christine , Eswaran Jeyanthy , Soundararajan Meera
Published: October 2020

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western World and it is characterized by a marked degree of clinical heterogeneity. An impaired balance between pro- and anti-apoptotic stimuli determines chemorefractoriness and outcome. The low proliferation rate of CLL cells indicates that one of the primary mechanisms involved in disease development may be an apoptotic failure. Here, we study the clinical and functional significance of DRAK2, a novel stress response kinase that plays a critical role in apoptosis, T-cell biology, and B-cell activation in CLL. We have analyzed CLL patient samples and showed that low expression levels of DRAK2 were significantly associated with unfavorable outcome in our CLL cohort. DRAK2 expression levels showed a positive correlation with the expression of DAPK1, and TGFBR1. Consistent with clinical data, the downregulation of DRAK2 in MEC-1 CLL cells strongly increased cell viability and proliferation. Further, our transcriptome data from MEC-1 cells highlighted MAPK, NF-κB, and Akt and as critical signaling hubs upon DRAK2 knockdown. Taken together, our results indicate DRAK2 as a novel marker of CLL survival that plays key regulatory roles in CLL prognosis.
Effectiveness and Selectiveness of Traps and Baits for Catching the Invasive Hornet Vespa velutina
Authors: Lioy Simone , Laurino Daniela , Capello Michela , Romano Andrea , Manino Aulo , Porporato Marco
Published: October 2020

Vespa velutina is an invasive hornet that is colonising several countries worldwide, with detrimental effects on multiple components but primarily affecting honey bees and native insect species. Traps for wasps and hornets are commonly used for trapping V. velutina, both for monitoring and control purposes. In this study, we compared the performances of two typologies of traps and baits widely used for trapping this invasive hornet, by evaluating their effectiveness and selectiveness in trapping V. velutina in two sites during two different periods of the year, spring and autumn. The performance of the traps changed in relation to (i) the trap’s model, (ii) the bait’s typology and (iii) the period of the year. In spring, traps with common beer as bait were more effective and more selective independently of trap’s model than the commercial bait that has been tested. On the contrary, in autumn, just one combination of trap and attractant (the commercial trap and bait) achieved higher effectiveness and selectiveness. Despite the underlined variations among traps and baits, overall catches of V. velutina were scanty compared to bycatches of non-target insects, since best performing traps either in term of effectiveness and selectiveness caught 3.65% of the target species in spring and 1.35% in autumn upon the total trapped insects. This highlights the urgent necessity of developing more selective trapping methods for monitoring and particularly for controlling purposes.
Identifying the Biological Characteristics Associated with Oviposition Behavior of Tea Leafhopper Empoasca onukii Matsuda Using the Blue Light Detection Method
Authors: Yao Qi , Zhang Huining , Jiao Long , Cai Xiaoming , Wang Manqun , Chen Zongmao
Published: October 2020

Tea leafhopper (Empoasca onukii Matsuda) is amongst the key pests in tea plantations around the East Asian region. Stereomicroscopy is a conventional method used for detecting tea leafhopper eggs by dissecting the tender tissues. However, there is a need for a faster and more efficient method to directly observe and investigate intact eggs within tea shoots. The absence of a proven method limits research efforts for determining the oviposition behavior of E. onukii. Herein, we applied the blue light detection method (BLDM), a technique recently developed for other species, in order to detect E. onukii eggs directly and non-destructively within the tender shoot. In addition, we compared BLDM against the traditional stereomicroscope detection method (SMDM) for four tea cultivars. Notably, our results revealed that BLDM was precise and effective in measuring the egg laying quantity of E. onukii on intact tea shoots. Neither tea cultivars nor egg density in the tender shoot significantly affected the accuracy of BLDM. Furthermore, biological characteristics that have rarely been reported previously for E. onukii were investigated using the BLDM, including zygote duration, ovipositional rhythm, egg distribution within the tender shoot, and in different leaf positions, numbers of eggs laid by a single female daily, and laid by the entire generation. Therefore, these findings provide insights into the basic and theoretical evidence for the strategy and mechanism associated with the oviposition behavior of E. onukii.
First Account of Phylogeographic Variation, Larval Characters, and Laboratory Rearing of the Endangered Cobblestone Tiger Beetle Cicindelidia marginipennis, Dejean, 1831 with Observations of Their Natural History
Authors: Gwiazdowski Rodger A. , Andersen Jeremy C. , Knisley C. Barry , Griffin Brian P. , Elkinton Joseph S.
Published: October 2020

The cobblestone tiger beetle, Cicindelidia marginipennis (Dejean, 1831) is a North American species specializing in riparian habitats from New Brunswick, Canada, to Alabama in the United States. In the United States, this species is state-listed as threatened or endangered range-wide and periodically receives consideration for federal listing, mostly due to habitat decline. Despite its conservation status, intraspecific genetic diversity for this species has not been explored and little is known about its natural history. To support further inquiry into the biology of C. marginipennis, this study provides the first look at range-wide genetic diversity using mitochondrial DNA (mtDNA), describes all three larval instars, and describes natural history characteristics from captive rearing and field observation. Based on mtDNA analyses, our results suggest that geographically based population structure may exist throughout the range, with individuals from Alabama possessing haplotypes not found elsewhere in our sampling. Further genetic analyses, particularly multi-locus analyses, are needed to determine whether the Alabama population represents a separate cryptic species. Our morphological analysis and descriptions of larval instars reveal a combination of characteristics that can be used to differentiate C. marginipennis from closely related and co-occurring species. Based on our field observations, we find that the larval “throw pile” of soil excavated from burrows is a key search image for locating larvae, and we provide descriptions and detailed photographs to aid surveys. Lastly, we find that this species can be successfully reared in captivity and provide guidelines to aid future recovery efforts.
Deep Learning for Historical Document Analysis and Recognition—A Survey
Authors: Lombardi Francesco , Marinai Simone
Published: October 2020

Nowadays, deep learning methods are employed in a broad range of research fields. The analysis and recognition of historical documents, as we survey in this work, is not an exception. Our study analyzes the papers published in the last few years on this topic from different perspectives: we first provide a pragmatic definition of historical documents from the point of view of the research in the area, then we look at the various sub-tasks addressed in this research. Guided by these tasks, we go through the different input-output relations that are expected from the used deep learning approaches and therefore we accordingly describe the most used models. We also discuss research datasets published in the field and their applications. This analysis shows that the latest research is a leap forward since it is not the simple use of recently proposed algorithms to previous problems, but novel tasks and novel applications of state of the art methods are now considered. Rather than just providing a conclusive picture of the current research in the topic we lastly suggest some potential future trends that can represent a stimulus for innovative research directions.
Prognostic Impact of the Neutrophil-to-Lymphocyte and Lymphocyte-to-Monocyte Ratio, in Patients with Rectal Cancer: A Retrospective Study of 1052 Patients
Authors: Fülöp Zsolt Zoltán , Fülöp Réka Linda , Gurzu Simona , Bara Tivadar , Tímár József , Drágus Emőke , Jung Ioan
Published: October 2020

Despite the description of several new prognostic markers, colorectal cancer still represents the third most frequent cause of cancer-related death. As immunotherapy is considered a therapeutic alternative in such patients, neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte ratio (LMR) are hypothesized to provide reliable prognostic information. A retrospective study was conducted on 1052 patients operated on during 2013–2019 in two clinical hospitals from Hungary and Romania. Inclusion criteria targeted patients over 18 years old, diagnosed with rectal cancer, with preoperatively defined NLR and LMR. The overall survival rate, along with clinical and histopathological data, was evaluated. Overall survival was significantly associated with increased NLR (p = 0.03) and decreased LMR (p = 0.04), with cut-off values of 3.11 and 3.39, respectively. The two parameters were inversely correlated (p < 0.0001). There was no statistically significant association between tumor stage and NLR or LMR (p = 0.30, p = 0.06, respectively). The total mesorectal excision was especially obtained in cases with low NLR (p = 0.0005) and high LMR (p = 0.0009) values. A significant association was also seen between preoperative chemoradiotherapy and high NLR (p = 0.0001) and low LMR (p = 0.0001). In patients with rectal cancer, the preoperative values of NLR and LMR can be used as independent prognostic parameters. An NLR value of ≥3.11 can be used to indicate the response to preoperative chemoradiotherapy, but a low chance of sphincter preservation or obtaining a complete TME. Higher values of NLR and lower values of LMR require a more attentive preoperative evaluation of the mesorectum.
The Unusual Trading Volume and Earnings Surprises in China’s Market
Authors: Chong Terence Tai Leung , Wu Yueer , Su Jue
Published: October 2020

This study examines the empirical relationship between unusual trading volume and earnings surprises in China’s A-share market. We provide evidence that an unusually low trading volume can signify negative information about firm fundamentals. Moreover, unusual trading volumes could predict abnormal returns close to the earnings announcement date. The degree of, and changes in, divergence of opinion could explain this result. Our study provides an insight into China’s market, where short sales are strictly forbidden. We report a strong relationship that is quite different from that described in most studies on the United States market.
What Explains the Sovereign Credit Default Swap Spreads Changes in the GCC Region?
Authors: Naifar Nader
Published: October 2020

This paper aimed to investigate the drivers of sovereign credit risk spreads changes in the case of four Gulf Cooperation Council (GCC) countries, namely Kingdom of Saudi Arabia (KSA), the United Arab Emirates (UAE), Qatar, and Bahrain. Specifically, we explained the changes in sovereign credit default swap (hereafter SCDS) spreads at different locations of the spread distributions by three categories of explanatory variables: global uncertainty factors, local financial variables, and global financial market variables. Using weekly data from 5 April 2013, to 17 January 2020, and the quantile regression model, empirical results indicate that the global factors outperform the local factors. The most significant variables for all SCDS spreads are the global financial uncertainty embedded in the Chicago Board Options Exchange (CBOE) volatility index (VIX) and the global conventional bond market uncertainty embedded in the Merrill Lynch Option Volatility Estimate (MOVE) index. Moreover, the MOVE index affects the various SCDS spreads only when the CDS markets are bullish. Interestingly, the SCDS spreads are not affected by the global economic policy and the gold market uncertainties. Additionally, a weak dependence is observed between oil prices and SCDS spreads. For the country-specific factors, stock market returns are the most significant variable and impact the SCDS spreads at different market circumstances.
Assessment Method and Scale of Observation Influence Ecosystem Service Bundles
Authors: Madrigal-Martínez Santiago , Miralles i García José Luis
Published: October 2020

The understanding of relationships between ecosystem services and the appropriate spatial scales for their analysis and characterization represent opportunities for sustainable land management. Bundles have appeared as an integrated method to assess and visualize consistent associations among multiple ecosystem services. Most of the bundle assessments focused on a static framework at a specific spatial scale. Here, we addressed the effects of applying two cluster analyses (static and dynamic) for assessing bundles of ecosystem services across four different scales of observation (two administrative boundaries and two sizes of grids) over 13 years (from 2000 to 2013). We used the ecosystem services matrix to model and map the potential supply of seven ecosystem services in a case study system in the central high-Andean Puna of Peru. We developed a sensitivity analysis to test the robustness of the matrix. The differences between the configuration, spatial patterns, and historical trajectories of bundles were measured and compared. We focused on two hypotheses: first, bundles of ecosystem services are mainly affected by the method applied for assessing them; second, these bundles are influenced by the scale of observation over time. For the first hypothesis, the results suggested that the selection of a method for assessing bundles have inferences on the interactions with land-use change. The diverse implications to management on ecosystem services support that static and dynamic assessments can be complementary to obtain better contributions for decision-making. For the second hypothesis, our study showed that municipality and grid-scales kept similar sensitivity in capturing the aspects of ecosystem service bundles. Then, in favorable research conditions, we recommend the combination of a municipal and a fine-grid scale to assure robustness and successfully land-use planning processes.
Simulation of Adhesive Contact of Soft Microfibrils
Authors: He Xin , Li Qiang , Popov Valentin L.
Published: October 2020

Adhesive contact between a flat brush structure with deformable microfibrils and an elastic half space is numerically simulated. The stiffness of pillars is modeled by linear springs. The fast Fourier transform-assisted boundary element method for the contact of rigid indenters is modified to include the microfibril stiffness so that the deflection of pillars and elastic interaction to elastic foundation are coupled. In the limiting case of rigid pillars (pillar stiffness is much larger than the contact stiffness), the adhesive force is determined by the filling factor of brush, as described earlier. In the case of very soft pillars, the adhesive force is proportional to N1/4, where N is the number of pillars. The influence of relative stiffness, number and distribution of pillars on adhesive force is studied numerically. The results from both regularly and randomly distributed pillars show that the adhesive force is enhanced by splitting a compact punch into microfibrils and this effect becomes larger when the fibrils are softer.
Inertial Neural Networks with Unpredictable Oscillations
Authors: Akhmet Marat , Tleubergenova Madina , Zhamanshin Akylbek
Published: October 2020

In this paper, inertial neural networks are under investigation, that is, the second order differential equations. The recently introduced new type of motions, unpredictable oscillations, are considered for the models. The motions continue a line of periodic and almost periodic oscillations. The research is of very strong importance for neuroscience, since the existence of unpredictable solutions proves Poincaré chaos. Sufficient conditions have been determined for the existence, uniqueness, and exponential stability of unpredictable solutions. The results can significantly extend the role of oscillations for artificial neural networks exploitation, since they provide strong new theoretical and practical opportunities for implementation of methods of chaos extension, synchronization, stabilization, and control of periodic motions in various types of neural networks. Numerical simulations are presented to demonstrate the validity of the theoretical results.