bluuebunny/crossref_metadata_2025 huggingface dataset:
7q35 Microdeletion and 15q13.3 and Xp22.33 Microduplications in a Patient with Severe Myoclonic Epilepsy, Microcephaly, Dysmorphisms, Severe Psychomotor Delay and Intellectual Disability
Authors: Paduano Francesco , Colao Emma , Loddo Sara , Orlando Valeria , Trapasso Francesco , Novelli Antonio , Perrotti Nicola , Iuliano Rodolfo
Published: May 2020

Copy number variations (CNVs) play a key role in the pathogenesis of several diseases, including a wide range of neurodevelopmental disorders. Here, we describe the detection of three CNVs simultaneously in a female patient with evidence of severe myoclonic epilepsy, microcephaly, hypertelorism, dimorphisms as well as severe psychomotor delay and intellectual disability. Array-CGH analysis revealed a ~240 kb microdeletion at the 7q35 inherited from her father, a ∼538 kb microduplication at the 15q13.3 region and a ∼178 kb microduplication at Xp22.33 region, both transmitted from her mother. The microdeletion in 7q35 was included within an intragenic region of the contactin associated protein-like 2 (CNTNAP2) gene, whereas the microduplications at 15q13.3 and Xp22.33 involved the cholinergic receptor nicotinic α 7 subunit (CHRNA7) and the cytokine receptor-like factor 2 (CRLF2) genes, respectively. Here, we describe a female patient harbouring three CNVs whose additive contribution could be responsible for her clinical phenotypes.
The New Diagnosis-Related Group Reimbursement System and Laboratory Test Quality in Korea: Analysis of External Quality Assessment Results
Authors: Kim Sollip , Yun Yeo-Min , Kim Hyeongsu , Um Tae-Hyun , Chang Jeonghyun , Jeong Hojin , Lee Kun Sei , Chun Sail , Choi Yong-Jun , Heo Jae-Hyeok , Han Tae-Hwa
Published: May 2020

Korea introduced a new diagnosis-related group (NDRG), which is a mixed-bundle reimbursement system. We evaluated the effects of NDRGs on laboratory test quality by analyzing data over three years (2016–2018) from the Korean Association of External Quality Assessment Service (KEQAS). A total of 42 NDRG-participating hospitals (CASE), 84 non-participating similar size-hospitals (CON-1), and 42 tertiary hospitals (CON-2) were included. We assumed the proportion of KEQAS results with a larger than 2 standard deviation index (SDI) to be a bad laboratory quality marker (BLQM). CASE BLQMs were lower than CON-1 BLQMs for more than 2 years in alkaline phosphatase (ALP), alanine aminotransferase (ALT), chloride, glucose, sodium, and total protein, and higher in creatinine. CASE BLQMs were higher than CON-2 BLQMs for more than 2 years in ALP, chloride, creatinine, glucose, lactate dehydrogenase (LDH), phosphorus, potassium, sodium, total calcium, total cholesterol, triglyceride, and uric acid. Mean SDIs for general chemistry tests were not significantly different depending on NDRG participation. However, the NDRG is currently a pilot program that compensates the amount of each institution’s reimbursement based on the fee-for-service system, and most participants were public hospitals. Thus, the effects of NDRGs on laboratory test quality should be re-evaluated after the NDRG program has stabilized and more private hospitals are participating.
Changes in Gait Performance in Stroke Patients after Taping with Scapular Setting Exercise
Authors: Park Shin Jun , Oh Seunghue
Published: May 2020

The purpose of this study was to investigate the effects of combined taping with scapular setting exercise on the gait performance of stroke patients. Twenty stroke patients were randomly allocated to two groups: the taping with scapular setting exercise (TSSE) group (n = 10) and scapular setting exercise (SSE) group (n = 10). Intervention was performed for one week, and pre- and postintervention results for TSSE and SSE were compared. Outcomes were determined using the inertia measurement unit, which can measure spatiotemporal gait parameters, and using the timed up-and-go test. Two-way repeated analysis was used to compare pre- and postintervention results. In the TSSE group, intervention significantly improved cadence, gait speed, stride length, step length, gait cycle, swing phase duration, double support duration, and timed up-and-go test results more than in the SSE group. TSSE was found to improve all spatiotemporal gait parameters examined; thus, we recommend TSSE be considered as an intervention to improve gait parameters in stroke patients.
Is Belonging to a Religious Organization Enough? Differences in Religious Affiliation Versus Self-Ratings of Spirituality on Behavioral and Psychological Variables in Individuals with Heart Failure
Authors: Saiz Jesús , Pung Meredith A. , Wilson Kathleen L. , Pruitt Christopher , Rutledge Thomas , Redwine Laura , Taub Pam R. , Greenberg Barry H. , Mills Paul J.
Published: May 2020

In the United States, heart failure (HF) affects approximately 6.5 million adults. While studies show that individuals with HF often suffer from adverse symptoms such as depression and anxiety, studies also show that these symptoms can be at least partially offset by the presence of spiritual wellbeing. In a sample of 327 men and women with AHA/ACC classification Stage B HF, we found that more spirituality in patients was associated with better clinically-related symptoms such as depressed mood and anxiety, emotional variables (affect, anger), well-being (optimism, satisfaction with life), and physical health-related outcomes (fatigue, sleep quality). These patients also showed better self-efficacy to maintain cardiac function. Simply belonging to a religious organization independent of spiritualty, however, was not a reliable predictor of health-related benefits. In fact, we observed instances of belonging to a religious organization unaccompanied by parallel spiritual ratings, which appeared counterproductive.
The Landscape of Risk Communication Research: A Scientometric Analysis
Authors: Goerlandt Floris , Li Jie , Reniers Genserik
Published: May 2020

Risk communication is a significant research domain with practical importance in supporting societal risk governance and informed private decision making. In this article, a high-level analysis of the risk communication research domain is performed using scientometrics methods and visualization tools. Output trends and geographical patterns are identified, and patterns in scientific categories determined. A journal distribution analysis provides insights into dominant journals and the domain’s intellectual base. Thematic clusters and temporal evolution of focus topics are obtained using a terms analysis, and a co-citation analysis provides insights into the evolution of research fronts and key documents. The results indicate that the research volume grows exponentially, with by far most contributions originating from Western countries. The domain is highly interdisciplinary, rooted in psychology and social sciences, and branching mainly into medicine and environmental sciences. Narrative themes focus on risk communication in medical and societal risk governance contexts. The domain originated from public health and environmental concerns, with subsequent research fronts addressing risk communication concepts and models. Applied research fronts are associated with environmental hazards, public health, medical risks, nuclear power, and emergency response to various natural hazards. Based on the results, various avenues for future research are described.
Effects of Augmented-Reality-Based Exercise on Muscle Parameters, Physical Performance, and Exercise Self-Efficacy for Older Adults
Authors: Jeon Sangwan , Kim Jiyoun
Published: May 2020

This study was intended to determine the applicability of an augmented-reality-based muscle reduction prevention exercise program for elderly Korean women by observing changes in exercise self-efficacy and verifying the effectiveness of the program in the elderly after the application of the program. A total of 27 participants, who were elderly women aged 65+ and had not participated in any exercise programs until this study, were recruited for this study. They were divided into an experimental group (13 people) and a control group (14 people), and then the augmented-reality-based muscle reduction prevention exercise program was applied. This was a 30-min program, which included regular, aerobic, and flexibility exercises, and it was applied 5 times a week for 12 weeks. As a result of observing changes, it was found that the appendicular skeletal muscle mass (ASM) (F = 11.222, p < 0.002) and the skeletal muscle index (SMI) (kg/m2) (F = 10.874, p < 0.003) muscle parameters increased more in the experimental group compared to the control group, and there was a significant increase in gait speed (m/s) (F = 7.221, p < 0.005). For physical performance, as a result of conducting the Senior Fitness Test (SFT), a significant change was observed in the chair stand test (F = 5.110, p < 0.033), 2-min step test (2MST) (F = 6.621, p < 0.020), and the timed up-and-go test (TUG) (F = 5.110, p < 0.032) and a significant increase was also observed for exercise self-efficacy (F = 20.464, p < 0.001). Finally, the augmented-reality-based exercise program in this study was found to be effective in inducing physical activity in the elderly. Therefore, the augmented-reality-based muscle reduction prevention exercise program is considered to be effective in increasing the sustainability of exercise, thus preventing muscle reduction in the elderly.
Time Course of COVID-19 Cases in Austria
Authors: Moshammer Hanns , Poteser Michael , Lemmerer Kathrin , Wallner Peter , Hutter Hans-Peter
Published: May 2020

COVID-19 is an infectious disease caused by a novel coronavirus, which first appeared in China in late 2019, and reached pandemic distribution in early 2020. The first major outbreak in Europe occurred in Northern Italy where it spread to neighboring countries, notably to Austria, where skiing resorts served as a main transmission hub. Soon, the Austrian government introduced strict measures to curb the spread of the virus. Using publicly available data, we assessed the efficiency of the governmental measures. We assumed an average incubation period of one week and an average duration of infectivity of 10 days. One week after the introduction of strict measures, the increase in daily new cases was reversed, and the reproduction number dropped. The crude estimates tended to overestimate the reproduction rate in the early phase. Publicly available data provide a first estimate about the effectiveness of public health measures. However, more data are needed for an unbiased assessment.
The Effects of Urban Containment Policies on Public Health
Authors: Jeon Jeongbae , Kim Solhee , Kwon Sung Moon
Published: May 2020

Public health risks such as obesity are influenced by numerous personal characteristics, but the local spatial structure such as an area’s built environment can also affect the obesity rate. This study analyzes and discusses how a greenbelt plan as a tool of urban containment policy has an effect on obesity. This study conducted spatial econometric regression models with five factors (13 variables) including transportation, socio-economic, public health, region, and policy factors. The relationship was analyzed between two policy effects of a greenbelt (i.e., a green buffer zone) and obesity. The variables for two policy effects of greenbelt zones are the size of the greenbelt and the inside and outside areas of the greenbelt. The results indicate that the two variables have negative effects on obesity. The results of the analyses in this study have several policy implications. Greenbelts play a role as an urban growth management policy, leading to a reduced obesity rate due to the influence of the transportation mode. In addition, greenbelts can also reduce the obesity rate because they provide recreation spaces for people.
Domestic Sewage Treatment Using a One-Stage ANAMMOX Process
Authors: Wei Yuan , Jin Yue , Zhang Wenjie
Published: May 2020

A one-stage anaerobic ammonium oxidation (ANAMMOX) reactor can be quickly started within 40 days by mixing partial nitrifying sludge with ANAMMOX granular sludge with an average temperature of 30 °C. After 70 days of nitrogen load acclimation, Acinetobacter, including Candidatus Kuenenia, became the dominant strain of the system within the reactor, which exhibited high efficiency and a stable nitrogen removal performance. At an influent chemical oxygen demand (COD), NH4+-N content, total nitrogen (TN) content, hydraulic retention time (HRT), temperature, and reactor dissolved oxygen (DO) content of 100, 60, and 70 mg/L, 6 h, 30 ± 1 °C, and below 0.6 mg/L, respectively, the one-stage ANAMMOX reactor could effectively treat domestic sewage on campus. The removal rates of COD, NH4+-N, and TN were approximately 89%, 96.7%, and 70%, respectively.
Assessment and Monitoring of Fish Quality from a Coastal Ecosystem under High Anthropic Pressure: A Case Study in Southern Italy
Authors: La Torre Giovanna Loredana , Cicero Nicola , Bartolomeo Giovanni , Rando Rossana , Vadalà Rossella , Santini Antonello , Durazzo Alessandra , Lucarini Massimo , Dugo Giacomo , Salvo Andrea
Published: May 2020

Fish is a nutrient-rich food but, at the same time, consumption of fish is a possible source of exposure to heavy metals. Since many coastal Mediterranean areas suffer from great anthropomorphic pressure, the aim of this study was to assess the level of potentially toxic inorganic elements in different fish samples from the coastal zone of Southern Italy (Gela) where there is a high mortality rate linked to cancer disease and congenital malformations. The presence of mercury, cadmium, lead, nickel, arsenic, vanadium, and chromium was measured by inductively coupled plasma-mass spectrometry (ICP-MS). The risk assessment was evaluated in terms of estimated daily intake by calculating the amount of potentially toxic elements that an average individual adult weighing 60 kg would ingest. Moreover the non-carcinogenic risk was estimated by target hazard quotient (THQ). The study evidenced significant contamination by inorganic elements, especially cadmium, which can be linked to industrial pollution. The THQ indexes, as indicators of human health, suggest that the consumption of fish from the study area is not free of risk.
Prospective Associations of Serum Adiponectin, Leptin, and Leptin-Adiponectin Ratio with Incidence of Metabolic Syndrome: The Korean Genome and Epidemiology Study
Authors: Lee Kyung Won , Shin Dayeon
Published: May 2020

Although the role of adiponectin and leptin in the etiology of metabolic syndrome (MetS) has been explored in various populations, limited knowledge is available on the prospective association of adiponectin and leptin with the risk of MetS development. The present study aimed to evaluate the associations of adiponectin, leptin, and the leptin-adiponectin (LA) ratio with the future risk of MetS in middle-aged and older Korean adults. Using a prospective, population-based Ansan-Ansung cohort of the Korean Genome and Epidemiology Study (KoGES), 2691 Korean adults (1317 men and 1374 women) were included in the present study. Serum adiponectin and leptin concentrations were measured using commonly available enzyme-linked immunosorbent assay kits. Multivariable Cox proportional hazard models were used to investigate the relationships of the different adiponectin and leptin concentrations and LA ratio with the incident MetS. During a mean follow-up of 6.75 years, a total of 359 (27.26%) men and 385 (28.02%) women were identified as developing new-onset MetS. After controlling for covariates, higher adiponectin levels were associated with lower incidence of MetS (hazard ratio (HR) for third vs. first tertile: 0.53, 95% confidence interval (CI): 0.40–0.70 for men and HR: 0.54, 95% CI: 0.42–0.71 for women), while higher leptin levels (HR for third vs. first tertile: 2.88, 95% CI: 2.01–4.13 for men and HR: 1.55, 95% CI: 1.13–2.13 for women) and LA ratio (HR for third vs. first tertile: 3.07, 95% CI: 2.13–4.44 for men and HR: 1.94, 95% CI: 1.41–2.66 for women) were associated with an increased incidence of MetS. Among men, in the fully adjusted models an increase by one standard deviation (SD) in adiponectin levels was associated with a 10% decrease in MetS risk (HR per SD: 0.90, 95% CI: 0.85–0.95) while leptin and LA ratio was associated with a 5% (HR per SD: 1.05, 95% CI: 1.01–1.08) and 40% (HR per SD: 1.40, 95% CI: 1.22–1.62) increase in MetS risk, respectively. Among women, a significant association with MetS risk was observed only in adiponectin levels (HR per SD: 0.91, 95% CI: 0.88–0.95). We found that higher adiponectin level was associated with a lower risk of MetS, while higher leptin level and LA ratio were associated with elevated MetS incidence, irrespective of body mass index at baseline in both Korean men and women. Adiponectin and leptin levels and LA ratio could play a role as a useful biomarker in the prediction of future MetS development among middle-aged and older Koreans.
Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats
Authors: Cremonese Carla , Schierwagen Robert , Uschner Frank Erhard , Torres Sandra , Tyc Olaf , Ortiz Cristina , Schulz Martin , Queck Alexander , Kristiansen Glen , Bader Michael , Sauerbruch Tilman , Weiskirchen Ralf , Walther Thomas , Trebicka Jonel , Klein Sabine
Published: May 2020

Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially, the development of fibrosis and portal hypertension in NAFLD patients requires treatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. As expected, WD induced obesity and liver fibrosis as confirmed by Sirius Red and Oil Red O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increased during feeding of WD, indicating infiltration of macrophages into the liver, even though this increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin–angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.
Orphan Nuclear Receptor RORα Regulates Enzymatic Metabolism of Cerebral 24S-Hydroxycholesterol through CYP39A1 Intronic Response Element Activation
Authors: Matsuoka Hiroshi , Katayama Miyu , Ohishi Ami , Miya Kaoruko , Tokunaga Riki , Kobayashi Sou , Nishimoto Yuya , Hirooka Kazutake , Shima Akiho , Michihara Akihiro
Published: May 2020

Oxysterols, important regulators of cholesterol homeostasis in the brain, are affected by neurodegenerative diseases. Early-onset Alzheimer’s disease is associated with higher levels of circulating brain-derived 24S-hydroxycholesterol (24S-OHC). Conversion of cholesterol to 24S-OHC is mediated by cholesterol 24S-hydroxylase in the brain, which is the major pathway for oxysterol elimination, followed by oxidation through hepatic first-pass metabolism by CYP39A1. Abnormal CYP39A1 expression results in accumulation of 24S-OHC, influencing neurodegenerative disease-related deterioration; thus, it is important to understand the normal elimination of 24S-OHC and the system regulating CYP39A1, a selective hepatic metabolic enzyme of 24S-OHC. We examined the role of transcriptional regulation by retinoic acid receptor-related orphan receptor α (RORα), a nuclear receptor that responds to oxysterol ligands. In humans, the promoter and first intronic regions of CYP39A1 contain two putative RORα response elements (ROREs). RORα binding and responses of these ROREs were assessed using electrophoretic mobility shift, chromatin immunoprecipitation, and luciferase reporter assays. CYP39A1 was upregulated by RORα overexpression in HEK293 cells, while RORα knockdown by siRNA significantly downregulated CYP39A1 expression in human hepatoma cells. Additionally, CYP39A1 was induced by RORα agonist treatment, suggesting that CYP39A1 expression is activated by RORα nuclear receptors. This may provide a way to increase CYP39A1 activity using RORα agonists, and help halt 24S-OHC accumulation in neurodegenerative illnesses.
Form-Vessel Classification of Cholangioscopy Findings to Diagnose Biliary Tract Carcinoma’s Superficial Spread
Authors: Fukasawa Yoshimitsu , Takano Shinichi , Fukasawa Mitsuharu , Maekawa Shinya , Kadokura Makoto , Shindo Hiroko , Takahashi Ei , Hirose Sumio , Kawakami Satoshi , Hayakawa Hiroshi , Yamaguchi Tatsuya , Nakayama Yasuhiro , Inoue Taisuke , Sato Tadashi , Enomoto Nobuyuki
Published: May 2020

We aimed to evaluate a newly developed peroral cholangioscopy (POCS) classification system by comparing classified lesions with histological and genetic findings. We analyzed 30 biopsied specimens from 11 patients with biliary tract cancer (BTC) who underwent POCS. An original classification of POCS findings was made based on the biliary surface’s form (F factor, 4 grades) and vessel structure (V-factor, 3 grades). Findings were then compared with those of corresponding biopsy specimens analyzed histologically and by next-generation sequencing to identify somatic mutations. In addition, the histology of postoperative surgical stumps and preoperative POCS findings were compared. Histological malignancy rate in biopsied specimens increased with increasing F- and V-factor scores (F1, 0%; F1, 25%; F3, 50%; F4, 62.5%; p = 0.0015; V1, 0%; V2, 20%; V3, 70%; p < 0.001). Furthermore, we observed a statistically significant increase of the mutant allele frequency of mutated genes with increasing F- and V-factor scores (F factor, p = 0.0050; V-factor, p < 0.001). All surgical stumps were accurately diagnosed using POCS findings. The F–V classification of POCS findings is both histologically and genetically valid and will contribute to the methods of diagnosing the superficial spread of BTC tumors.
Coloured Rice Phenolic Extracts Increase Expression of Genes Associated with Insulin Secretion in Rat Pancreatic Insulinoma β-cells
Authors: Kang Gideon Gatluak , Francis Nidhish , Hill Rodney , LE Waters Daniel , Blanchard Christopher L. , Santhakumar Abishek Bommannan
Published: May 2020

Glucose-induced oxidative stress is associated with the overproduction of reactive oxygen species (ROS), which may dysregulate the expression of genes controlling insulin secretion leading to β-cell dysfunction, a hallmark of type 2 diabetes mellitus (T2DM). This study investigated the impact of coloured rice phenolic extracts (CRPEs) on the expression of key genes associated with β-cell function in pancreatic β-cells (INS-1E). These genes included glucose transporter 2 (Glut2), silent mating type information regulation 2 homolog 1 (Sirt1), mitochondrial transcription factor A (Tfam), pancreatic/duodenal homeobox protein 1 (Pdx-1) and insulin 1 (Ins1). INS-1E cells were cultured in high glucose (25 mM) to induce glucotoxic stress conditions (HGSC) and in normal glucose conditions (NGC-11.1 mM) to represent normal β-cell function. Cells were treated with CRPEs derived from two coloured rice cultivars, Purple and Yunlu29-red varieties at concentrations ranged from 50 to 250 µg/mL. CRPEs upregulated the expression of Glut2, Sirt1 and Pdx-1 significantly at 250 µg/mL under HGSC. CRPEs from both cultivars also upregulated Glut2, Sirt1, Tfam, Pdx-1 and Ins1 markedly at 250 µg/mL under NGC with Yunlu29 having the greatest effect. These data suggest that CRPEs may reduce β-cell dysfunction in T2DM by upregulating the expression of genes involved in insulin secretion pathways.
De Novo Synthesized Estradiol: A Role in Modulating the Cerebellar Function
Authors: Dieni Cristina V. , Contemori Samuele , Biscarini Andrea , Panichi Roberto
Published: May 2020

The estrogen estradiol is a potent neuroactive steroid that may regulate brain structure and function. Although the effects of estradiol have been historically associated with gonadal secretion, the discovery that this steroid may be synthesized within the brain has expanded this traditional concept. Indeed, it is accepted that de novo synthesized estradiol in the nervous system (nE2) may modulate several aspects of neuronal physiology, including synaptic transmission and plasticity, thereby influencing a variety of behaviors. These modulations may be on a time scale of minutes via non-classical and often membrane-initiated mechanisms or hours and days by classical actions on gene transcription. Besides the high level, recent investigations in the cerebellum indicate that even a low aromatase expression can be related to the fast nE2 effect on brain functioning. These pieces of evidence point to the importance of an on-demand and localized nE2 synthesis to rapidly contribute to regulating the synaptic transmission. This review is geared at exploring a new scenario for the impact of estradiol on brain processes as it emerges from the nE2 action on cerebellar neurotransmission and cerebellum-dependent learning.
Degradation Mechanism of 2,4-Dichlorophenol by Fungi Isolated from Marine Invertebrates
Authors: Nikolaivits Efstratios , Agrafiotis Andreas , Baira Eirini , Le Goff Géraldine , Tsafantakis Nikolaos , Chavanich Suchana A. , Benayahu Yehuda , Ouazzani Jamal , Fokialakis Nikolas , Topakas Evangelos
Published: May 2020

2,4-Dichlorophenol (2,4-DCP) is a ubiquitous environmental pollutant categorized as a priority pollutant by the United States (US) Environmental Protection Agency, posing adverse health effects on humans and wildlife. Bioremediation is proposed as an eco-friendly, cost-effective alternative to traditional physicochemical remediation techniques. In the present study, fungal strains were isolated from marine invertebrates and tested for their ability to biotransform 2,4-DCP at a concentration of 1 mM. The most competent strains were studied further for the expression of catechol dioxygenase activities and the produced metabolites. One strain, identified as Tritirachium sp., expressed high levels of extracellular catechol 1,2-dioxygenase activity. The same strain also produced a dechlorinated cleavage product of the starting compound, indicating the assimilation of the xenobiotic by the fungus. This work also enriches the knowledge about the mechanisms employed by marine-derived fungi in order to defend themselves against chlorinated xenobiotics.
Epigenetic Patterns and Geographical Parthenogenesis in the Alpine Plant Species Ranunculus kuepferi (Ranunculaceae)
Authors: Schinkel Christoph C. F. , Syngelaki Eleni , Kirchheimer Bernhard , Dullinger Stefan , Klatt Simone , Hörandl Elvira
Published: May 2020

Polyploidization and the shift to apomictic reproduction are connected to changes in DNA cytosine-methylation. Cytosine-methylation is further sensitive to environmental conditions. We, therefore, hypothesize that DNA methylation patterns would differentiate within species with geographical parthenogenesis, i.e., when diploid sexual and polyploid apomictic populations exhibit different spatial distributions. On natural populations of the alpine plant Ranunculus kuepferi, we tested differences in methylation patterns across two cytotypes (diploid, tetraploid) and three reproduction modes (sexual, mixed, apomictic), and their correlation to environmental data and geographical distributions. We used methylation-sensitive amplified fragment-length polymorphism (methylation-sensitive AFLPs) and scored three types of epiloci. Methylation patterns differed independently between cytotypes versus modes of reproduction and separated three distinct combined groups (2x sexual + mixed, 4x mixed, and 4x apomictic), with differentiation of 4x apomicts in all epiloci. We found no global spatial autocorrelation, but instead correlations to elevation and temperature gradients in 22 and 36 epiloci, respectively. Results suggest that methylation patterns in R. kuepferi were altered by cold conditions during postglacial recolonization of the Alps, and by the concomitant shift to facultative apomixis, and by polyploidization. Obligate apomictic tetraploids at the highest elevations established a distinct methylation profile. Methylation patterns reflect an ecological gradient rather than the geographical differentiation.
The Potential Functional Roles of NME1 Histidine Kinase Activity in Neuroblastoma Pathogenesis
Authors: Adam Kevin , Lesperance Jacqueline , Hunter Tony , Zage Peter E.
Published: May 2020

Neuroblastoma is the most common extracranial solid tumor in childhood. Gain of chromosome 17q material is found in >60% of neuroblastoma tumors and is associated with poor patient prognosis. The NME1 gene is located in the 17q21.3 region, and high NME1 expression is correlated with poor neuroblastoma patient outcomes. However, the functional roles and signaling activity of NME1 in neuroblastoma cells and tumors are unknown. NME1 and NME2 have been shown to possess histidine (His) kinase activity. Using anti-1- and 3-pHis specific monoclonal antibodies and polyclonal anti-pH118 NME1/2 antibodies, we demonstrated the presence of pH118-NME1/2 and multiple additional pHis-containing proteins in all tested neuroblastoma cell lines and in xenograft neuroblastoma tumors, supporting the presence of histidine kinase activity in neuroblastoma cells and demonstrating the potential significance of histidine kinase signaling in neuroblastoma pathogenesis. We have also demonstrated associations between NME1 expression and neuroblastoma cell migration and differentiation. Our demonstration of NME1 histidine phosphorylation in neuroblastoma and of the potential role of NME1 in neuroblastoma cell migration and differentiation suggest a functional role for NME1 in neuroblastoma pathogenesis and open the possibility of identifying new therapeutic targets and developing novel approaches to neuroblastoma therapy.
Legumes Protease Inhibitors as Biopesticides and Their Defense Mechanisms against Biotic Factors
Authors: Rodríguez-Sifuentes Lucio , Marszalek Jolanta Elzbieta , Chuck-Hernández Cristina , Serna-Saldívar Sergio O.
Published: May 2020

Legumes are affected by biotic factors such as insects, molds, bacteria, and viruses. These plants can produce many different molecules in response to the attack of phytopathogens. Protease inhibitors (PIs) are proteins produced by legumes that inhibit the protease activity of phytopathogens. PIs are known to reduce nutrient availability, which diminishes pathogen growth and can lead to the death of the pathogen. PIs are classified according to the specificity of the mechanistic activity of the proteolytic enzymes, with serine and cysteine protease inhibitors being studied the most. Previous investigations have reported the efficacy of these highly stable proteins against diverse biotic factors and the concomitant protective effects in crops, representing a possible replacement of toxic agrochemicals that harm the environment.
Identification of Lenalidomide Sensitivity and Resistance Mechanisms in Non-Del(5q) Myelodysplastic Syndromes
Authors: Drusbosky Leylah M. , Cogle Christopher R.
Published: May 2020

Whereas lenalidomide is an effective therapy for del(5q) MDS patients, a minority of non-del(5q) MDS patients achieve hematologic improvement with lenalidomide. We used computational biology modeling and digital drug simulation to examine genomic data from 56 non-del(5q) MDS patients treated with lenalidomide, and then matched treatment response with molecular pathways. The computer inferred genomic abnormalities associating with lenalidomide treatment response in non-del(5q) MDS to include trisomy 8, del(20q), or RUNX1 loss of function mutations. Genomic abnormalities associating with lenalidomide resistance in non-del(5q) MDS patients included mutations in SF3B1, TET2, WNT3A amplification, MCL1 amplification, and/or PSEN2 amplification. These results may inform protocols for determining appropriateness of lenalidomide in non-del(5q) MDS.
Role of Extrinsic Apoptotic Signaling Pathway during Definitive Erythropoiesis in Normal Patients and in Patients with β-Thalassemia
Authors: Raducka-Jaszul Olga , Bogusławska Dżamila M. , Jędruchniewicz Natalia , Sikorski Aleksander F.
Published: May 2020

Apoptosis is a process of programmed cell death which has an important role in tissue homeostasis and in the control of organism development. Here, we focus on information concerning the role of the extrinsic apoptotic pathway in the control of human erythropoiesis. We discuss the role of tumor necrosis factor α (TNFα), tumor necrosis factor ligand superfamily member 6 (FasL), tumor necrosis factor-related apoptosis-inducing (TRAIL) and caspases in normal erythroid maturation. We also attempt to initiate a discussion on the observations that mature erythrocytes contain most components of the receptor-dependent apoptotic pathway. Finally, we point to the role of the extrinsic apoptotic pathway in ineffective erythropoiesis of different types of β-thalassemia.
Role of microRNA-21 and Its Underlying Mechanisms in Inflammatory Responses in Diabetic Wounds
Authors: Liechty Cole , Hu Junyi , Zhang Liping , Liechty Kenneth W. , Xu Junwang
Published: May 2020

A central feature of diabetic wounds is the persistence of chronic inflammation, which is partly due to the prolonged presence of pro-inflammatory (M1) macrophages in diabetic wounds. Persistence of the M1 macrophage phenotype and failure to transition to the regenerative or pro-remodeling (M2) macrophage phenotype plays an indispensable role in diabetic wound impairment; however, the mechanism underlying this relationship remains unclear. Recently, microRNAs have been shown to provide an additional layer of regulation of gene expression. In particular, microRNA-21 (miR-21) is essential for an inflammatory immune response. We hypothesize that miR-21 plays a role in regulating inflammation by promoting M1 macrophage polarization and the production of reactive oxygen species (ROS). To test our hypothesis, we employed an in vivo mouse skin wound model in conjunction with an in vitro mouse model to assess miR-21 expression and macrophage polarization. First, we found that miR-21 exhibits a distinct expression pattern in each phase of healing in diabetic wounds. MiR-21 abundance was higher during early and late phases of wound repair in diabetic wounds, while it was significantly lower in the middle phase of wounding (at days 3 and 7 following wounding). In macrophage cells, M1 polarized macrophages exhibited an upregulation of miR-21, as well as the M1 and pro-inflammatory markers IL-1b, TNFa, iNos, IL-6, and IL-8. Overexpression of miR-21 in macrophage cells resulted in an upregulation of miR-21 and also increased expression of the M1 markers IL-1b, TNFa, iNos, and IL-6. Furthermore, hyperglycemia induced NOX2 expression and ROS production through the HG/miR-21/PI3K/NOX2/ROS signaling cascade. These findings provide evidence that miR-21 is involved in the regulation of inflammation. Dysregulation of miR-21 may explain the abnormal inflammation and persistent M1 macrophage polarization seen in diabetic wounds.
Toll-Like Receptor Signaling and Immune Regulatory Lymphocytes in Periodontal Disease
Authors: Gu Yingzhi , Han Xiaozhe
Published: May 2020

Periodontitis is known to be initiated by periodontal microbiota derived from biofilm formation. The microbial dysbiotic changes in the biofilm trigger the host immune and inflammatory responses that can be both beneficial for the protection of the host from infection, and detrimental to the host, causing tissue destruction. During this process, recognition of Pathogen-Associated Molecular Patterns (PAMPs) by the host Pattern Recognition Receptors (PRRs) such as Toll-like receptors (TLRs) play an essential role in the host–microbe interaction and the subsequent innate as well as adaptive responses. If persistent, the adverse interaction triggered by the host immune response to the microorganisms associated with periodontal biofilms is a direct cause of periodontal inflammation and bone loss. A large number of T and B lymphocytes are infiltrated in the diseased gingival tissues, which can secrete inflammatory mediators and activate the osteolytic pathways, promoting periodontal inflammation and bone resorption. On the other hand, there is evidence showing that immune regulatory T and B cells are present in the diseased tissue and can be induced for the enhancement of their anti-inflammatory effects. Changes and distribution of the T/B lymphocytes phenotype seem to be a key determinant of the periodontal disease outcome, as the functional activities of these cells not only shape up the overall immune response pattern, but may directly regulate the osteoimmunological balance. Therefore, interventional strategies targeting TLR signaling and immune regulatory T/B cells may be a promising approach to rebalance the immune response and alleviate bone loss in periodontal disease. In this review, we will examine the etiological role of TLR signaling and immune cell osteoclastogenic activity in the pathogenesis of periodontitis. More importantly, the protective effects of immune regulatory lymphocytes, particularly the activation and functional role of IL-10 expressing regulatory B cells, will be discussed.
MRP1-Collateral Sensitizers as a Novel Therapeutic Approach in Resistant Cancer Therapy: An In Vitro and In Vivo Study in Lung Resistant Tumor
Authors: Riganti Chiara , Giampietro Roberta , Kopecka Joanna , Costamagna Costanzo , Abatematteo Francesca Serena , Contino Marialessandra , Abate Carmen
Published: May 2020

Multidrug resistance (MDR) is the main obstacle to current chemotherapy and it is mainly due to the overexpression of some efflux transporters such as MRP1. One of the most studied strategies to overcome MDR has been the inhibition of MDR pumps through small molecules, but its translation into the clinic unfortunately failed. Recently, a phenomenon called collateral sensitivity (CS) emerged as a new strategy to hamper MDR acting as a synthetic lethality, where the genetic changes developed upon the acquisition of resistance towards a specific agent are followed by the development of hypersensitivity towards a second agent. Among our library of sigma ligands acting as MDR modulators, we identified three compounds, F397, F400, and F421, acting as CS-promoting agents. We deepened their CS mechanisms in the “pure” model of MRP1-expressing cells (MDCK-MRP1) and in MRP1-expressing/drug resistant non-small cell lung cancer cells (A549/DX). The in vitro results demonstrated that (i) the three ligands are highly cytotoxic for MRP1-expressing cells; (ii) their effect is MRP1-mediated; (iii) they increase the cytotoxicity induced by cis-Pt, the therapeutic agent commonly used in the treatment of lung tumors; and (iv) their effect is ROS-mediated. Moreover, a preclinical in vivo study performed in lung tumor xenografts confirms the in vitro findings, making the three CS-promoting agents candidates for a novel therapeutic approach in lung resistant tumors.
14-3-3 Proteins and Other Candidates form Protein-Protein Interactions with the Cytosolic C-terminal End of SOS1 Affecting Its Transport Activity
Authors: Duscha Kerstin , Martins Rodrigues Cristina , Müller Maria , Wartenberg Ruth , Fliegel Larry , Deitmer Joachim W. , Jung Martin , Zimmermann Richard , Neuhaus H. Ekkehard
Published: May 2020

The plasma membrane transporter SOS1 (SALT-OVERLY SENSITIVE1) is vital for plant survival under salt stress. SOS1 activity is tightly regulated, but little is known about the underlying mechanism. SOS1 contains a cytosolic, autoinhibitory C-terminal tail (abbreviated as SOS1 C-term), which is targeted by the protein kinase SOS2 to trigger its transport activity. Here, to identify additional binding proteins that regulate SOS1 activity, we synthesized the SOS1 C-term domain and used it as bait to probe Arabidopsis thaliana cell extracts. Several 14-3-3 proteins, which function in plant salt tolerance, specifically bound to and interacted with the SOS1 C-term. Compared to wild-type plants, when exposed to salt stress, Arabidopsis plants overexpressing SOS1 C-term showed improved salt tolerance, significantly reduced Na+ accumulation in leaves, reduced induction of the salt-responsive gene WRKY25, decreased soluble sugar, starch, and proline levels, less impaired inflorescence formation and increased biomass. It appears that overexpressing SOS1 C-term leads to the sequestration of inhibitory 14-3-3 proteins, allowing SOS1 to be more readily activated and leading to increased salt tolerance. We propose that the SOS1 C-term binds to previously unknown proteins such as 14-3-3 isoforms, thereby regulating salt tolerance. This finding uncovers another regulatory layer of the plant salt tolerance program.
The p53–53BP1-Related Survival of A549 and H1299 Human Lung Cancer Cells after Multifractionated Radiotherapy Demonstrated Different Response to Additional Acute X-ray Exposure
Authors: Pustovalova Margarita , Alhaddad Lina , Smetanina Nadezhda , Chigasova Anna , Blokhina Taisia , Chuprov-Netochin Roman , Osipov Andreyan N. , Leonov Sergey
Published: May 2020

Radiation therapy is one of the main methods of treating patients with non-small cell lung cancer (NSCLC). However, the resistance of tumor cells to exposure remains the main factor that limits successful therapeutic outcome. To study the molecular/cellular mechanisms of increased resistance of NSCLC to ionizing radiation (IR) exposure, we compared A549 (p53 wild-type) and H1299 (p53-deficient) cells, the two NSCLC cell lines. Using fractionated X-ray irradiation of these cells at a total dose of 60 Gy, we obtained the survived populations and named them A549IR and H1299IR, respectively. Further characterization of these cells showed multiple alterations compared to parental NSCLC cells. The additional 2 Gy exposure led to significant changes in the kinetics of γH2AX and phosphorylated ataxia telangiectasia mutated (pATM) foci numbers in A549IR and H1299IR compared to parental NSCLC cells. Whereas A549, A549IR, and H1299 cells demonstrated clear two-component kinetics of DNA double-strand break (DSB) repair, H1299IR showed slower kinetics of γH2AX foci disappearance with the presence of around 50% of the foci 8 h post-IR. The character of H2AX phosphorylation in these cells was pATM-independent. A decrease of residual γH2AX/53BP1 foci number was observed in both A549IR and H1299IR compared to parental cells post-IR at extra doses of 2, 4, and 6 Gy. This process was accompanied with the changes in the proliferation, cell cycle, apoptosis, and the expression of ATP-binding cassette sub-family G member 2 (ABCG2, also designated as CDw338 and the breast cancer resistance protein (BCRP)) protein. Our study provides strong evidence that different DNA repair mechanisms are activated by multifraction radiotherapy (MFR), as well as single-dose IR, and that the enhanced cellular survival after MFR is reliant on both p53 and 53BP1 signaling along with non-homologous end-joining (NHEJ). Our results are of clinical significance as they can guide the choice of the most effective IR regimen by analyzing the expression status of the p53–53BP1 pathway in tumors and thereby maximize therapeutic benefits for the patients while minimizing collateral damage to normal tissue.
Software Support for Discourse-Based Textual Information Analysis: A Systematic Literature Review and Software Guidelines in Practice
Authors: Martin-Rodilla Patricia , Sánchez Miguel
Published: May 2020

The intrinsic characteristics of humanities research require technological support and software assistance that also necessarily goes through the analysis of textual narratives. When these narratives become increasingly complex, pragmatics analysis (i.e., at discourse or argumentation levels) assisted by software is a great ally in the digital humanities. In recent years, solutions have been developed from the information visualization domain to support discourse analysis or argumentation analysis of textual sources via software, with applications in political speeches, debates, online forums, but also in written narratives, literature or historical sources. This paper presents a wide and interdisciplinary systematic literature review (SLR), both in software-related areas and humanities areas, on the information visualization and the software solutions adopted to support pragmatics textual analysis. As a result of this review, this paper detects weaknesses in existing works on the field, especially related to solutions’ availability, pragmatic framework dependence and lack of information sharing and reuse software mechanisms. The paper also provides some software guidelines for improving the detected weaknesses, exemplifying some guidelines in practice through their implementation in a new web tool, Viscourse. Viscourse is conceived as a complementary tool to assist textual analysis and to facilitate the reuse of informational pieces from discourse and argumentation text analysis tasks.
A Novel Solution to Find the Dynamic Response of an Euler–Bernoulli Beam Fitted with Intraspan TMDs under Poisson Type Loading
Authors: Di Matteo Alberto , Dunn Iain Peter , Failla Giuseppe , Pirrotta Antonina
Published: May 2020

This contribution considers a virtual experiment on the vibrational response of rail and road bridges equipped with smart devices in the form of damping elements to mitigate vibrations. The internal damping of the bridge is considered a discontinuity that contain a dashpot. Exact complex eigenvalues and eigenfunctions are derived from a characteristic equation built as the determinant of a 4 × 4 matrix; this is accomplished through the use of the theory of generalized functions to find the response variables at the positions of the damping elements. To relate this to real world applications, the response of a bridge under Poisson type white noise is evaluated; this is similar to traffic loading that would be seen in a bridge’s service life. The contribution also discusses the importance of smart damping and dampers to sustainability efforts through the reduction of required materials, and it discusses the role played by robust mathematical modelling in the design phase.