bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysphagia Prevalence, Time Course, and Association with Probable Sarcopenia, Inactivity, Malnutrition, and Disease Status in Older Patients Admitted to an Emergency Department: A Secondary Analysis of Cohort Study Data
Authors: Hansen Tina , Nielsen Rikke Lundsgaard , Houlind Morten Baltzer , Tavenier Juliette , Rasmussen Line Jee Hartmann , Jørgensen Lillian Mørch , Treldal Charlotte , Beck Anne Marie , Pedersen Mette Merete , Andersen Ove , Petersen Janne , Andersen Aino Leegaard
Published: April 2021

There is evolving evidence for an association between dysphagia and sarcopenia in older adults. For optimizing the acute health care initiative across health care settings, this study investigated prevalence and time-course of dysphagia in older patients admitted to an emergency department (ED) as well as its association with parameters for probable sarcopenia, inactivity, malnutrition, disease status, and systemic inflammation. A secondary analysis of data from the FAM-CPH cohort study on acutely admitted older medical patients (n = 125). Data were collected upon ED admission as well as four and 56 weeks after discharge. Using the Eating Assessment Tool cut-off score ≥ 2, signs of dysphagia were present in 34% of the patients at ED admission and persisted in 25% of the patients 56 weeks after discharge. Signs of dysphagia at 56-week follow-up were significantly (p < 0.05) associated with probable sarcopenia (low handgrip strength (OR = 3.79), low leg muscle strength (OR = 8.14), and low physical performance (OR = 5.68)) and with baseline swallowing inactivity (OR = 5.61), malnutrition (OR = 4.35), and systemic inflammation (OR = 1.33). Signs of dysphagia in older patients admitted to an ED was prevalent, persisted 56 weeks after discharge, and was associated with probable sarcopenia and related conditions; all modifiable targets for management of dysphagia in older patients.
Setting Up a Lab-Scale Pilot Plant to Study the New Growing System (NGS®) for Leafy Vegetable and Culinary Herb Growth
Authors: Nicola Silvana , Pignata Giuseppe , Casale Manuela , Hazrati Saeid , Ertani Andrea
Published: April 2021

New cultural techniques have been developed to improve the yield and raw material quality at harvest, and enhance the postharvest shelf life, by standardizing the growing system. Among the different Soilless Cultivation Systems, the New Growing System (NGS®) is a closed-recirculating system that was designed for open fields and protected cultivations. The aim of this work was to investigate the structural setting of the system and its functioning to harness the full potentiality of NGS®. A lab-scale pilot plant (LSPP) was designed with NGS® technology and the technical aspects have been set up to have a standardized and reproducible growing system. The trials were conducted on growing mature-leaf vegetable species; that is, on both head and multi-leaf vegetables, and on culinary herbs at high plant densities. Positive yield results were found for culinary herbs and leafy vegetables. Mints showed high yields for the two re-growths carried out after the first harvest. The LSPP can also be used in a series of reliable experiments and enable researches to test several species, substrates, hydroponic nutrient solutions, and fertigation scheduling.
A Streamflow Bias Correction and Performance Evaluation Web Application for GEOGloWS ECMWF Streamflow Services
Authors: Sanchez Lozano Jorge , Romero Bustamante Giovanni , Hales Riley Chad , Nelson E. James , Williams Gustavious P. , Ames Daniel P. , Jones Norman L.
Published: April 2021

We present the development and testing of a web application called the historical validation tool (HVT) that processes and visualizes observed and simulated historical stream discharge data from the global GEOGloWS ECMWF streamflow services (GESS), performs seasonally adjusted bias correction, computes goodness-of-fit metrics, and performs forward bias correction on subsequent forecasts. The HVT corrects GESS output at a local scale using a technique that identifies and corrects model bias using observed hydrological data that are accessed using web services. HVT evaluates the performance of the GESS historic simulation data and provides more accurate historic simulation and bias-corrected forecast data. The HVT also allows users of the GEOGloWS historical streamflow data to use local observed data to both validate and improve the accuracy of local streamflow predictions. We developed the HVT using Tethys Platform, an open-source web application development framework. HVT presents data visualization using web mapping services and data plotting in the web map interface while functions related to bias correction, metrics reporting, and data generation for statistical analysis are computed by the back end. We present five case studies using the HVT in Australia, Brazil, Colombia, the Dominican Republic, and Peru. In these case studies, in addition to presenting the application, we evaluate the accuracy of the method we implemented in the HVT for bias correction. These case studies show that the HVT bias correction in Brazil, Colombia, and Peru results in significant improvement in historic simulation across the countries, while bias correction only resulted in marginal historic simulation improvements in Australia and the Dominican Republic. The HVT web application allows users to use local data to adjust global historical simulation and forecasts and validate the results, making the GESS modeling results more useful at a local scale.
Structural Equation Modeling of Tongue Function and Tongue Hygiene in Acute Stroke Patients
Authors: Hidaka Rena , Furuya Junichi , Nishiyama Akira , Suzuki Hiroyuki , Aoyagi Michiyo , Matsubara Chiaki , Yoshizumi Yu , Yoshimi Kanako , Nakane Ayako , Tohara Haruka , Sato Yuji , Minakuchi Shunsuke
Published: April 2021

In acute stroke patients, it is important to maintain tongue hygiene and tongue function for prognosis management. However, the direct relationship between these factors is unclear, since these are often assessed by multiple observables. In this study, we used structural equation modeling (SEM) analysis, a tool to analyze the relationship between concepts that cannot be measured directly, to analyze the relationship between tongue hygiene and tongue function. The subjects were 73 patients with acute stroke admitted to a university hospital who underwent dental intervention. Age, sex, nutritional intake method, clinical severity classification of dysphagia, number of current teeth, number of functional teeth, oral health, tongue movement, tongue coating, number of microorganisms on the tongue surface, tongue surface moisture level, and tongue pressure were measured at the first visit. SEM analysis showed that the relationship between tongue function and tongue hygiene was 0.05 between tongue function and swallowing function was 0.90, and that between tongue hygiene and swallowing function was 0.09. We found no statistical relationship between tongue function and tongue hygiene in acute stroke patients. However, it was reconfirmed that tongue function is strongly related to feeding and swallowing functions.
Mediterranean Dietary Pyramid
Authors: Willett Walter
Published: April 2021

The updated Mediterranean Dietary Pyramid (MDP) described by Serra-Majem et al [...]
Sequestration of Mercury in Soils under Scots Pine and Silver Fir Stands Located in the Proximity to a Roadway
Authors: Gruba Piotr , Kania Mateusz , Kupka Dawid , Pietrzykowski Marcin
Published: April 2021

Forest soils are the main source of mercury (Hg) in stream water. Stocks of Hg in forest soils are related to several factors, including forest species composition. In this study, the potential source of Hg pollution was a relatively new roadway traversing forested areas. We compared Hg accumulation in soils of two coniferous species: Scots pine (Pinus sylvestris L.) and silver fir (Abies alba Mill.). The experimental plots were located near the S7 expressway in Central Poland. The stands differed in the length of time they had been exposed to Hg, because different parts of the roadway were built and opened to traffic at different times. We analyzed 480 soil samples from organic horizons (O) and the top 10 cm of mineral soil (A) sampled from six plots. The overall average Hg concentrations (irrespective of forest stand, n = 240) was 0.225 mg kg−1 in the O horizons and 0.075 mg kg−1 in the mineral horizons. The Hg concentration in the O horizons was more than three times greater in fir stands than that in pine stands. The average Hg:C ratios in the O and A horizons were 1.0 and 2.3 mg Hg kg−1 C, respectively. Our data does not clearly show the effect of road on Hg accumulation near the road. The concentrations of Hg in investigated soils adjacent to the roadway were only slightly higher than ranges reported for unpolluted areas, and no clearly affected by the vicinity of roadway. In contrast to the other reports, our data indicate a significant impact of tree species on Hg concentrations in both the O and A horizons. Moreover, the average Hg:C ratio was strongly dependent on the tree species.
Vitamin D Status and Its Determinants in Mexican Pregnant Women from a Rural and an Urban Area: A Comparative Study
Authors: Chávez-Courtois Mayra , Godínez-Martínez Estela , Muñoz-Manrique Cinthya , Negrete-Martínez Viviana , González-Leyva Carla Patricia , Tolentino-Dolores Maricruz , Suárez-Rico Blanca , Estrada-Gutierrez Guadalupe , Perichart-Perera Otilia
Published: April 2021

Background: During pregnancy, vitamin D requirements are higher due to fetal growth and development. Vitamin D production occurs mainly through sunlight exposure, which is affected by geographic location and lifestyle factors. Methods: This was a case-control study nested within two cohorts of adult pregnant women (n = 298): urban (Mexico City) and rural (Cuetzalan). To reduce confounding, pairs were selected by age, pregestational body mass index, and pregnancy trimester. Generalized linear models were used to assess the two groups according to their vitamin D status. Results: A total of 298 adult women were studied: 149 from a rural area and 149 from an urban area. Vitamin D deficiency and insufficiency were observed in 28% and 38.2% of women, respectively. A trend for higher 25(OH)D concentrations was observed in women from the rural area (27.5 ng/mL vs. 25.8 ng/mL), probably related to the type of job, where women with partial jobs showing less probability of having vitamin D deficiency (OR = 0.26; CI = 0.06–1.16; p = 0.08) and vitamin D insufficiency (OR = 0.24; CI = 0.06–0.99; p = 0.05). Women whose Last Menstrual Period occurred in spring showed lower vitamin D concentration compared to those whose LMP occurred in winter (p < 0.01). Conclusions: A high prevalence of vitamin D deficiency was observed in both rural and urban areas. Women living in rural areas tended to have higher 25(OH)D concentrations, probably related to more sunlight exposure associated with their type of job.
Do Individuals’ Activity Structures Influence Their PM2.5 Exposure Levels? Evidence from Human Trajectory Data in Wuhan City
Authors: Ma Siyu , Yang Lin , Kwan Mei-Po , Zuo Zejun , Qian Haoyue , Li Minghao
Published: April 2021

Severe air pollution has become a major risk to human health from a global environmental perspective. It has been recognized that human mobility is an essential component in individual exposure assessment. Activity structure reflects the characteristics of human mobility. Thus, a better understanding of the relationship between human activity structure and individual exposure level is of crucial relevance. This study examines this relationship using a large cell-phone GPS dataset in Wuhan, China. The results indicate that there is a strong linear relationship between people’s activity structures and exposures to PM2.5. Inter-group comparisons based on the four activity structure groups obtained with K-means clustering found that groups with different activity structures do experience different levels of PM2.5 exposure. Furthermore, differences in detailed characteristics of activity structure were also found at different exposure levels at the intra-group level. These results show that people’s activity structures do influence their exposure levels. The paper provides a new perspective for understanding individual exposure through human activity structure, which helps move the perspective of research on individual exposure from the semantic of physical location to the semantic of human activity pattern.
Perceiving Social-Emotional Volatility and Triggered Causes of COVID-19
Authors: Jiang Si , Zhang Hongwei , Qi Jiayin , Fang Binxing , Xu Tingliang
Published: April 2021

Health support has been sought by the public from online social media after the outbreak of novel coronavirus disease 2019 (COVID-19). In addition to the physical symptoms caused by the virus, there are adverse impacts on psychological responses. Therefore, precisely capturing the public emotions becomes crucial to providing adequate support. By constructing a domain-specific COVID-19 public health emergency discrete emotion lexicon, we utilized one million COVID-19 theme texts from the Chinese online social platform Weibo to analyze social-emotional volatility. Based on computed emotional valence, we proposed a public emotional perception model that achieves: (1) targeting of public emotion abrupt time points using an LSTM-based attention encoder-decoder (LAED) mechanism for emotional time-series, and (2) backtracking of specific triggered causes of abnormal volatility in a cognitive emotional arousal path. Experimental results prove that our model provides a solid research basis for enhancing social-emotional security outcomes.
Incorporating Personality Traits to Assess the Risk Level of Aberrant Driving Behaviors for Truck Drivers
Authors: Wei Chien-Hung , Lee Ying , Luo Yu-Wen , Lu Jyun-Jie
Published: April 2021

Economic globalization and the internet economy have resulted in a dramatic increase in freight transportation. Traffic crashes involving trucks usually result in severe losses and casualties. The fatality and injury rates for heavy truck accidents have been 10 times higher than for sedans in Taiwan in recent years. Thus, understanding driving behavior and risk are important for freight carriers. Since personality traits may result in different driving behaviors, the main objective of this study is to apply artificial neural network (ANN) models to predict the frequency of aberrant driving behavior and the risk level of each driver according to drivers’ personality traits. In this case study, relevant information on truck drivers’ personality traits and their tendency to engage in aberrant driving behavior are collected by using respectively a questionnaire and a fleet surveillance system from a truck company. A relative risk level evaluation mechanism is developed considering the frequency and distribution of aberrant driving behavior. The Jenks natural breaks optimization method and the elbow method are adopted to optimally classify 40 truck drivers into 4 aberrant driving behavior levels and 5 driving risk levels. It was found that 5% of drivers were at the highest aberrant driving behavior level, and 7.5% of drivers were at the highest driving risk level. Based on the results, the proposed models show good and stable predictive performance, especially for the class of drivers with excessive rotation speed, hard acceleration, excessive rotation speed, hard deceleration, and driving risk. With the proposed models, the predictive class for aberrant driving behavior and driving risk can be determined by plugging in a driver’s personality traits before or after employment. Based on the prediction results, the manager of a transportation company could plan the training program for each driver to reduce the aberrant driving behavior occurrence.
Effects of Circuit Weight-Interval Training on Physical Fitness, Cardiac Autonomic Control, and Quality of Life in Sedentary Workers
Authors: Oliveira-Junior Silvio A. , Boullosa Daniel , Mendonça Maria L. M. , Vieira Larissa F. C. , Mattos Wania W. , Amaral Bruna O. C. , Lima-Borges Dayanne S. , Reis Filipe A. , Cezar Marcelo D. M. , Vanderlei Luiz C. M. , Martinez Paula F.
Published: April 2021

Sedentary behaviors, those that involve sitting and low levels of energy expenditure, have been associated with several adverse cardiometabolic effects. This study evaluated the chronic effects of a combined circuit weight interval training (CWIT) on physical fitness, quality of life, and heart rate variability (HRV), and compared the effects of CWIT-induced autonomic adaptations on different postures in adult sedentary workers. Twenty-seven sedentary workers (age 36.9 ± 9.2 years old, 13 men and 14 women) were divided into two groups: control, who continued their sedentary behavior, and experimental, who were submitted to a CWIT for 12 weeks, completing two ~40 min sessions per week. Monitoring of 8th, 16th, and 24th sessions revealed a moderate training load during sessions. Participants exhibited an improved aerobic capacity (VO2max, 34.03 ± 5.36 vs. 36.45 ± 6.05 mL/kg/min, p < 0.05) and flexibility (22.6 ± 11.4 vs. 25.3 ± 10.1 cm, p < 0.05) after the training period. In addition, they showed greater quality of life scores. However, the CWIT did not change body composition. Interestingly, more HRV parameters were improved in the seated position. The CWIT used in the current study was associated with improvements in several fitness and quality of life parameters, as well as in cardiac autonomic control of HR in adult sedentary workers. Examination of different body positions when evaluating changes in HRV appears to be a relevant aspect to be considered in further studies. Future randomized controlled trials (RCTs) with larger samples of both sexes should confirm these promising results.
Sleep and Performance during a Preseason in Elite Rugby Union Athletes
Authors: Teece Angus R. , Argus Christos K. , Gill Nicholas , Beaven Martyn , Dunican Ian C. , Driller Matthew W.
Published: April 2021

Background: Preseason training optimises adaptations in the physical qualities required in rugby union athletes. Sleep can be compromised during periods of intensified training. Therefore, we investigated the relationship between sleep quantity and changes in physical performance over a preseason phase in professional rugby union athletes. Methods: Twenty-nine professional rugby union athletes (Mean ± SD, age: 23 ± 3 years) had their sleep duration monitored for 3 weeks using wrist actigraphy. Strength and speed were assessed at baseline and at week 3. Aerobic capacity and body composition were assessed at baseline, at week 3 and at week 5. Participants were stratified into 2 groups for analysis: <7 h 30 min sleep per night (LOW, n = 15) and >7 h 30 min sleep per night (HIGH, n = 14). Results: A significant group x time interaction was determined for aerobic capacity (p = 0.02, d = 1.25) at week 3 and for skinfolds at week 3 (p < 0.01, d = 0.58) and at week 5 (p = 0.02, d = 0.92), in favour of the HIGH sleep group. No differences were evident between groups for strength or speed measures (p ≥ 0.05). Conclusion: This study highlights that longer sleep duration during the preseason may assist in enhancing physical qualities including aerobic capacity and body composition in elite rugby union athletes.
Public Response, Anxiety and Behaviour during the First Wave of COVID-19 Pandemic in Saudi Arabia
Authors: Alqahtani Amani Salem , Alrasheed Meshael Mohammed , Alqunaibet Ada Mohammed
Published: April 2021

This study aims to investigate public response attitude, anxiety, practices and trust in the authorities’ mitigation plan during the first wave of COVID-19 pandemic. A national cross sectional phone survey was conducted among Saudi residents aged 16 years and above. A total of 90,421 (45.2%) individuals participated in the study. Of those, the overall rate of COVID-19 correct knowledge was 82% (mean: 9.84); social media was the most reported source of knowledge. Younger age, low levels of education and foreign residents were associated with poor knowledge. Overall, 49.5% scored 5 or more on the GAD-7 test, indicating anxiety symptoms, 19.2% of them scored 10 and above, suggesting moderate to severe anxiety. Majority of participants (>78%) trusted and supported the interventions implemented by the government to control COVID-19. Social distancing practices among participants was as following, 72.5% stayed at home and avoid going out for nonessential business and 49.5% avoided attending social events and family gatherings. Trust in authorities, being anxious, worry and levels of knowledge about the disease, were the most common factors affecting adoption of the recommended practices. Continuous evaluation of public response about COVID-19, and the effectiveness of protective measures is essential to better inform policy-makers and identify ways of encouraging behaviour change among public during pandemic.
PDLCs and EPCs Co-Cultured on Ta Discs: A Golden Fleece for “Compromised” Osseointegration
Authors: Chopra Hitesh , Han Yuanyuan , Zhang Cheng F. , Pow Edmond H. N.
Published: April 2021

Material research in tissue engineering forms a vital link between basic cell research and animal research. Periodontal ligament cells (PDLCs, P) from the tooth have an osteogenic effect, whereas endothelial progenitor cells (EPCs, E) assist in neovascularization. In the present study, the interaction of PDLCs and EPCs with Tantalum (Ta, I) discs, either alone (IP or IE group) or in 1:1 (IPE) ratio was explored. Additionally, surface analysis of Ta discs with respect to different types and cycles of sterilization and disinfection procedures was evaluated. It was observed that Ta discs could be used for a maximum of three times, after which the changes in properties of Ta discs were detrimental to cell growth, irrespective of the type of the protocol. Cell-Disc’s analysis revealed that cell proliferation in the IE group at day 6 and day 10 was significantly higher (p < 0.05) than other groups. A cell viability assay revealed increased live cells in the IPE group than in the IP or IE group. Similarly, adhesion and penetration of cells in the IPE group were not only higher, but also had an increased thickness of cellular extensions. RT-PCR analysis revealed that on day 8, both osteogenic (ALP, RUNX-2, and BSP) and angiogenic genes (VEGFR-2, CD31) increased significantly in the IPE group as compared to the IP or IE groups (p < 0.05). In conclusion, Ta discs promoted cellular proliferation and increased osteogenic and angiogenic activity by augmenting RUNX-2 and VEGFR-2 activity.
The New Therapeutic Strategies in Pediatric T-Cell Acute Lymphoblastic Leukemia
Authors: Lato Marta Weronika , Przysucha Anna , Grosman Sylwia , Zawitkowska Joanna , Lejman Monika
Published: April 2021

Childhood acute lymphoblastic leukemia is a genetically heterogeneous cancer that accounts for 10–15% of T-cell acute lymphoblastic leukemia (T-ALL) cases. The T-ALL event-free survival rate (EFS) is 85%. The evaluation of structural and numerical chromosomal changes is important for a comprehensive biological characterization of T-ALL, but there are currently no genetic prognostic markers. Despite chemotherapy regimens, steroids, and allogeneic transplantation, relapse is the main problem in children with T-ALL. Due to the development of high-throughput molecular methods, the ability to define subgroups of T-ALL has significantly improved in the last few years. The profiling of the gene expression of T-ALL has led to the identification of T-ALL subgroups, and it is important in determining prognostic factors and choosing an appropriate treatment. Novel therapies targeting molecular aberrations offer promise in achieving better first remission with the hope of preventing relapse. The employment of precisely targeted therapeutic approaches is expected to improve the cure of the disease and quality of life of patients. These include therapies that inhibit Notch1 activation (bortezomib), JAK inhibitors in ETP-ALL (ruxolitinib), BCL inhibitors (venetoclax), and anti-CD38 therapy (daratumumab). Chimeric antigen receptor T-cell therapy (CAR-T) is under investigation, but it requires further development and trials. Nelarabine-based regimens remain the standard for treating the relapse of T-ALL.
In Silico Analysis of the Molecular-Level Impact of SMPD1 Variants on Niemann-Pick Disease Severity
Authors: Ancien François , Pucci Fabrizio , Rooman Marianne
Published: April 2021

Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality.
Combination of Cyclosporine A and Levosimendan Induces Cardioprotection under Acute Hyperglycemia
Authors: Torregroza Carolin , Yueksel Birce , Ruske Raphael , Stroethoff Martin , Raupach Annika , Heinen André , Hollmann Markus W. , Huhn Ragnar , Feige Katharina
Published: April 2021

Prognosis of patients with myocardial infarction is detrimentally affected by comorbidities like diabetes mellitus. In the experimental setting, not only diabetes mellitus but also acute hyperglycemia is shown to hamper cardioprotective properties by multiple pharmacological agents. For Levosimendan-induced postconditioning, a strong infarct size reducing effect is demonstrated in healthy myocardium. However, acute hyperglycemia is suggested to block this protective effect. In the present study, we investigated whether (1) Levosimendan-induced postconditioning exerts a concentration-dependent effect under hyperglycemic conditions and (2) whether a combination with the mitochondrial permeability transition pore (mPTP) blocker cyclosporine A (CsA) restores the cardioprotective properties of Levosimendan under hyperglycemia. For this experimental investigation, hearts of male Wistar rats were randomized and mounted onto a Langendorff system, perfused with Krebs-Henseleit buffer with a constant pressure of 80 mmHg. All isolated hearts were subjected to 33 min of global ischemia and 60 min of reperfusion under hyperglycemic conditions. (1) Hearts were perfused with various concentrations of Levosimendan (Lev) (0.3–10 μM) for 10 min at the onset of reperfusion, in order to investigate a concentration–response relationship. In the second set of experiments (2), 0.3 μM Levosimendan was administered in combination with the mPTP blocker CsA, to elucidate the underlying mechanism of blocked cardioprotection under hyperglycemia. Infarct size was determined by tetrazolium chloride (TTC) staining. (1) Control (Con) hearts showed an infarct size of 52 ± 12%. None of the administered Levosimendan concentrations reduced the infarct size (Lev0.3: 49 ± 9%; Lev1: 57 ± 9%; Lev3: 47 ± 11%; Lev10: 50 ± 7%; all ns vs. Con). (2) Infarct size of Con and Lev0.3 hearts were 53 ± 4% and 56 ± 2%, respectively. CsA alone had no effect on infarct size (CsA: 50 ± 10%; ns vs. Con). The combination of Lev0.3 and CsA (Lev0.3 ± CsA) induced a significant infarct size reduction compared to Lev0.3 (Lev0.3+CsA: 35 ± 4%; p < 0.05 vs. Lev0.3). We demonstrated that (1) hyperglycemia blocks the infarct size reducing effects of Levosimendan-induced postconditioning and cannot be overcome by an increased concentration. (2) Furthermore, cardioprotection under hyperglycemia can be restored by combining Levosimendan and the mPTP blocker CsA.
Structural Fluctuations of the Human Proteasome α7 Homo-Tetradecamer Double Ring Imply the Proteasomal α-Ring Assembly Mechanism
Authors: Song Chihong , Satoh Tadashi , Sekiguchi Taichiro , Kato Koichi , Murata Kazuyoshi
Published: April 2021

The 20S proteasome, which is composed of layered α and β heptameric rings, is the core complex of the eukaryotic proteasome involved in proteolysis. The α7 subunit is a component of the α ring, and it self-assembles into a homo-tetradecamer consisting of two layers of α7 heptameric rings. However, the structure of the α7 double ring in solution has not been fully elucidated. We applied cryo-electron microscopy to delineate the structure of the α7 double ring in solution, revealing a structure different from the previously reported crystallographic model. The D7-symmetrical double ring was stacked with a 15° clockwise twist and a separation of 3 Å between the two rings. Two more conformations, dislocated and fully open, were also identified. Our observations suggest that the α7 double-ring structure fluctuates considerably in solution, allowing for the insertion of homologous α subunits, finally converting to the hetero-heptameric α rings in the 20S proteasome.
In Vivo Silencing of Genes Coding for dTip60 Chromatin Remodeling Complex Subunits Affects Polytene Chromosome Organization and Proper Development in Drosophila melanogaster
Authors: Prozzillo Yuri , Cuticone Stefano , Ferreri Diego , Fattorini Gaia , Messina Giovanni , Dimitri Patrizio
Published: April 2021

Chromatin organization is developmentally regulated by epigenetic changes mediated by histone-modifying enzymes and chromatin remodeling complexes. In Drosophila melanogaster, the Tip60 chromatin remodeling complex (dTip60) play roles in chromatin regulation, which are shared by evolutionarily-related complexes identified in animal and plants. Recently, it was found that most subunits previously assigned to the dTip60 complex are shared by two related complexes, DOM-A.C and DOM-B.C, defined by DOM-A and DOM-B isoforms, respectively. In this work, we combined classical genetics, cell biology, and reverse genetics approaches to further investigate the biological roles played during Drosophila melanogaster development by a number of subunits originally assigned to the dTip60 complex.
Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia
Authors: Malinská Hana , Hüttl Martina , Miklánková Denisa , Trnovská Jaroslava , Zapletalová Iveta , Poruba Martin , Marková Irena
Published: April 2021

Ovarian hormone deficiency leads to increased body weight, visceral adiposity, fatty liver and disorders associated with menopausal metabolic syndrome. To better understand the underlying mechanisms of these disorders in their early phases of development, we investigated the effect of ovariectomy on lipid and glucose metabolism. Compared to sham-operated controls, ovariectomized Wistar female rats markedly increased whole body and visceral adipose tissue weight (p ˂ 0.05) and exhibited insulin resistance in peripheral tissues. Severe hepatic triglyceride accumulation (p ˂ 0.001) after ovariectomy preceded changes in both serum lipids and glucose intolerance, reflecting alterations in some CYP proteins. Increased CYP2E1 (p ˂ 0.05) and decreased CYP4A (p ˂ 0.001) after ovariectomy reduced fatty acid oxidation and induced hepatic steatosis. Decreased triglyceride metabolism and secretion from the liver contributed to hepatic triglyceride accumulation in response to ovariectomy. In addition, interscapular brown adipose tissue of ovariectomized rats exhibited decreased fatty acid oxidation (p ˂ 0.01), lipogenesis (p ˂ 0.05) and lipolysis (p ˂ 0.05) despite an increase in tissue weight. The results provide evidence that impaired hepatic triglycerides and dysregulation of some CYP450 proteins may have been involved in the development of hepatic steatosis. The low metabolic activity of brown adipose tissue may have contributed to visceral adiposity as well as triglyceride accumulation during the postmenopausal period.
Live Cell FRET Imaging Reveals Amyloid β-Peptide Oligomerization in Hippocampal Neurons
Authors: Gao Yang , Wennmalm Stefan , Winblad Bengt , Schedin-Weiss Sophia , Tjernberg Lars O.
Published: April 2021

Amyloid β-peptide (Aβ) oligomerization is believed to contribute to the neuronal dysfunction in Alzheimer disease (AD). Despite decades of research, many details of Aβ oligomerization in neurons still need to be revealed. Förster resonance energy transfer (FRET) is a simple but effective way to study molecular interactions. Here, we used a confocal microscope with a sensitive Airyscan detector for FRET detection. By live cell FRET imaging, we detected Aβ42 oligomerization in primary neurons. The neurons were incubated with fluorescently labeled Aβ42 in the cell culture medium for 24 h. Aβ42 were internalized and oligomerized in the lysosomes/late endosomes in a concentration-dependent manner. Both the cellular uptake and intracellular oligomerization of Aβ42 were significantly higher than for Aβ40. These findings provide a better understanding of Aβ42 oligomerization in neurons.
Lymphoblastoid Cell Lines as Models to Study Mitochondrial Function in Neurological Disorders
Authors: Annesley Sarah Jane , Fisher Paul Robert
Published: April 2021

Neurological disorders, including neurodegenerative diseases, are collectively a major cause of death and disability worldwide. Whilst the underlying disease mechanisms remain elusive, altered mitochondrial function has been clearly implicated and is a key area of study in these disorders. Studying mitochondrial function in these disorders is difficult due to the inaccessibility of brain tissue, which is the key tissue affected in these diseases. To overcome this issue, numerous cell models have been used, each providing unique benefits and limitations. Here, we focussed on the use of lymphoblastoid cell lines (LCLs) to study mitochondrial function in neurological disorders. LCLs have long been used as tools for genomic analyses, but here we described their use in functional studies specifically in regard to mitochondrial function. These models have enabled characterisation of the underlying mitochondrial defect, identification of altered signalling pathways and proteins, differences in mitochondrial function between subsets of particular disorders and identification of biomarkers of the disease. The examples provided here suggest that these cells will be useful for development of diagnostic tests (which in most cases do not exist), identification of drug targets and testing of pharmacological agents, and are a worthwhile model for studying mitochondrial function in neurological disorders.
Cellular Response to Individual Components of the Platelet Concentrate
Authors: Sovkova Vera , Vocetkova Karolina , Hedvičáková Věra , Hefka Blahnová Veronika , Buzgo Matěj , Amler Evzen , Filová Eva
Published: April 2021

Platelet concentrates and especially their further product platelet lysate, are widely used as a replacement for cell culturing. Platelets contain a broad spectrum of growth factors and bioactive molecules that affect cellular fate. However, the cellular response to individual components of the human platelet concentrate is still unclear. The aim of this study was to observe cellular behavior according to the individual components of platelet concentrates. The bioactive molecule content was determined. The cells were supplemented with a medium containing 8% (v/v) of platelet proteins in plasma, pure platelet proteins in deionized water, and pure plasma. The results showed a higher concentration of fibrinogen, albumin, insulin growth factor I (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF), in the groups containing plasma. On the other hand, chemokine RANTES and platelet-derived growth factor bb (PDGF-bb), were higher in the groups containing platelet proteins. The groups containing both plasma and plasma proteins showed the most pronounced proliferation and viability of mesenchymal stem cells and fibroblasts. The platelet proteins alone were not sufficient to provide optimal cell growth and viability. A synergic effect of platelet proteins and plasma was observed. The data indicated the importance of plasma in platelet lysate for cell growth.
A Germline-Encoded Structural Arginine Trap Underlies the Anti-DNA Reactivity of a Murine V Gene Segment
Authors: dos Santos Araújo Ronny Petterson , França Renato Kaylan Alves , Valadares Napoleão Fonseca , Maranhão Andrea Queiroz , Brigido Marcelo Macedo
Published: April 2021

Autoimmunity may have its origins of early repertoire selection in developmental B cells. Such a primary repertoire is probably shaped by selecting B cells that can efficiently perform productive signaling, stimulated by self-antigens in the bone marrow, such as DNA. In support of that idea, we previously found a V segment from VH10 family that can form antibodies that bind to DNA independent of CDR3 usage. In this paper we designed four antibody fragments in a novel single-chain pre-BCR (scpre-BCR) format containing germinal V gene segments from families known to bind DNA (VH10) or not (VH4) connected to a murine surrogate light chain (SLC), lacking the highly charged unique region (UR), by a hydrophilic peptide linker. We also tested the influence of CDR2 on DNA reactivity by shuffling the CDR2 loop. The scpre-BCRs were expressed in bacteria. VH10 bearing scpre-BCR could bind DNA, while scpre-BCR carrying the VH4 segment did not. The CDR2 loop shuffling hampered VH10 reactivity while displaying a gain-of-function in the nonbinding VH4 germline. We modeled the binding sites demonstrating the conservation of a positivity charged pocket in the VH10 CDR2 as the possible cross-reactive structural element. We presented evidence of DNA reactivity hardwired in a V gene, suggesting a structural mechanism for innate autoreactivity. Therefore, while autoreactivity to DNA can lead to autoimmunity, efficiently signaling for B cell development is likely a trade-off mechanism leading to the selection of potentially autoreactive repertoires.
Metal Nano/Microparticles for Bioapplications
Authors: Pham Xuan-Hung , Park Seung-min , Jun Bong-Hyun
Published: April 2021

Nano/micro particles are considered to be the most valuable and important functional materials in the field of materials science and engineering [...]
Molecular Characterization of Xyloglucanase cel74a from Trichoderma reesei
Authors: Lopes Douglas Christian Borges , Carraro Cláudia Batista , Silva Roberto Nascimento , de Paula Renato Graciano
Published: April 2021

Background: The filamentous fungus Trichoderma reesei is used on an industrial scale to produce enzymes of biotechnological interest. This fungus has a complex cellulolytic system involved in the degradation of lignocellulosic biomass. However, several aspects related to the regulation of the expression of holocellulolytic genes and the production of cellulases by this fungus are still understood. Methods: Here, we constructed a null mutant strain for the xyloglucanase cel74a gene and performed the characterization of the Δcel74a strain to evaluate the genetic regulation of the holocellulases during sugarcane bagasse (SCB) cultivation. Results: Our results demonstrate that the deletion of xyloglucanase cel74a may impact the regulation of holocellulase expression during SCB cultivation. The expression of cellulases cel7a, cel7b, and cel6a was reduced in Δcel74a strain, while the hemicellulases xyn1 and xyn2 were increased in the presence of SCB. The cel74a mutation also affected the xyloglucan hydrolysis patterns. In addition, CEL74A activity was modulated in the presence of calcium, suggesting that this ion may be required for efficient degradation of xyloglucan. Conclusions: CEL74A affects the regulation of holocellulolytic genes and the efficient degradation of SCB in T. reesei. This data makes a significant contribution to our understanding of the carbon utilization of fungal strains as a whole.
Acylated Anthocyanins from Red Cabbage and Purple Sweet Potato Can Bind Metal Ions and Produce Stable Blue Colors
Authors: Fenger Julie-Anne , Sigurdson Gregory T. , Robbins Rebecca J. , Collins Thomas M. , Giusti M. Mónica , Dangles Olivier
Published: April 2021

Red cabbage (RC) and purple sweet potato (PSP) are naturally rich in acylated cyanidin glycosides that can bind metal ions and develop intramolecular π-stacking interactions between the cyanidin chromophore and the phenolic acyl residues. In this work, a large set of RC and PSP anthocyanins was investigated for its coloring properties in the presence of iron and aluminum ions. Although relatively modest, the structural differences between RC and PSP anthocyanins, i.e., the acylation site at the external glucose of the sophorosyl moiety (C2-OH for RC vs. C6-OH for PSP) and the presence of coordinating acyl groups (caffeoyl) in PSP anthocyanins only, made a large difference in the color expressed by their metal complexes. For instance, the Al3+-induced bathochromic shifts for RC anthocyanins reached ca. 50 nm at pH 6 and pH 7, vs. at best ca. 20 nm for PSP anthocyanins. With Fe2+ (quickly oxidized to Fe3+ in the complexes), the bathochromic shifts for RC anthocyanins were higher, i.e., up to ca. 90 nm at pH 7 and 110 nm at pH 5.7. A kinetic analysis at different metal/ligand molar ratios combined with an investigation by high-resolution mass spectrometry suggested the formation of metal–anthocyanin complexes of 1:1, 1:2, and 1:3 stoichiometries. Contrary to predictions based on steric hindrance, acylation by noncoordinating acyl residues favored metal binding and resulted in complexes having much higher molar absorption coefficients. Moreover, the competition between metal binding and water addition to the free ligands (leading to colorless forms) was less severe, although very dependent on the acylation site(s). Overall, anthocyanins from purple sweet potato, and even more from red cabbage, have a strong potential for development as food colorants expressing red to blue hues depending on pH and metal ion.
Genome-Wide Analysis of the Late Embryogenesis Abundant (LEA) and Abscisic Acid-, Stress-, and Ripening-Induced (ASR) Gene Superfamily from Canavalia rosea and Their Roles in Salinity/Alkaline and Drought Tolerance
Authors: Lin Ruoyi , Zou Tao , Mei Qiming , Wang Zhengfeng , Zhang Mei , Jian Shuguang
Published: April 2021

Canavalia rosea (bay bean), distributing in coastal areas or islands in tropical and subtropical regions, is an extremophile halophyte with good adaptability to seawater and drought. Late embryogenesis abundant (LEA) proteins typically accumulate in response to various abiotic stresses, including dehydration, salinity, high temperature, and cold, or during the late stage of seed development. Abscisic acid-, stress-, and ripening-induced (ASR) genes are stress and developmentally regulated plant-specific genes. In this study, we reported the first comprehensive survey of the LEA and ASR gene superfamily in C. rosea. A total of 84 CrLEAs and three CrASRs were identified in C. rosea and classified into nine groups. All CrLEAs and CrASRs harbored the conserved motif for their family proteins. Our results revealed that the CrLEA genes were widely distributed in different chromosomes, and all of the CrLEA/CrASR genes showed wide expression features in different tissues in C. rosea plants. Additionally, we introduced 10 genes from different groups into yeast to assess the functions of the CrLEAs/CrASRs. These results contribute to our understanding of LEA/ASR genes from halophytes and provide robust candidate genes for functional investigations in plant species adapted to extreme environments.
Microglia and Inhibitory Circuitry in the Medullary Dorsal Horn: Laminar and Time-Dependent Changes in a Trigeminal Model of Neuropathic Pain
Authors: García-Magro Nuria , Martin Yasmina B. , Negredo Pilar , Zafra Francisco , Avendaño Carlos
Published: April 2021

Craniofacial neuropathic pain affects millions of people worldwide and is often difficult to treat. Two key mechanisms underlying this condition are a loss of the negative control exerted by inhibitory interneurons and an early microglial reaction. Basic features of these mechanisms, however, are still poorly understood. Using the chronic constriction injury of the infraorbital nerve (CCI-IoN) model of neuropathic pain in mice, we have examined the changes in the expression of GAD, the synthetic enzyme of GABA, and GlyT2, the membrane transporter of glycine, as well as the microgliosis that occur at early (5 days) and late (21 days) stages post-CCI in the medullary and upper spinal dorsal horn. Our results show that CCI-IoN induces a down-regulation of GAD at both postinjury survival times, uniformly across the superficial laminae. The expression of GlyT2 showed a more discrete and heterogeneous reduction due to the basal presence in lamina III of ‘patches’ of higher expression, interspersed within a less immunoreactive ‘matrix’, which showed a more substantial reduction in the expression of GlyT2. These patches coincided with foci lacking any perceptible microglial reaction, which stood out against a more diffuse area of strong microgliosis. These findings may provide clues to better understand the neural mechanisms underlying allodynia in neuropathic pain syndromes.
Arrhythmogenic Cardiomyopathy Is a Multicellular Disease Affecting Cardiac and Bone Marrow Mesenchymal Stromal Cells
Authors: Scalco Arianna , Liboni Cristina , Angioni Roberta , Di Bona Anna , Albiero Mattia , Bertoldi Nicole , Fadini Gian Paolo , Thiene Gaetano , Chelko Stephen P. , Basso Cristina , Viola Antonella , Mongillo Marco , Zaglia Tania
Published: April 2021

Arrhythmogenic cardiomyopathy (AC) is a familial cardiac disorder at high risk of arrhythmic sudden death in the young and athletes. AC is hallmarked by myocardial replacement with fibro-fatty tissue, favoring life-threatening cardiac arrhythmias and contractile dysfunction. The AC pathogenesis is unclear, and the disease urgently needs mechanism-driven therapies. Current AC research is mainly focused on ‘desmosome-carrying’ cardiomyocytes, but desmosomal proteins are also expressed by non-myocyte cells, which also harbor AC variants, including mesenchymal stromal cells (MSCs). Consistently, cardiac-MSCs contribute to adipose tissue in human AC hearts. We thus approached AC as a multicellular disorder, hypothesizing that it also affects extra-cardiac bone marrow (BM)-MSCs. Our results show changes in the desmosomal protein profile of both cardiac- and BM- MSCs, from desmoglein-2 (Dsg2)-mutant mice, accompanied with profound alterations in cytoskeletal organization, which are directly caused by AC-linked DSG2 downregulation. In addition, AC BM-MSCs display increased proliferation rate, both in vitro and in vivo, and, by using the principle of the competition homing assay, we demonstrated that mutant circulating BM-MSCs have increased propensity to migrate to the AC heart. Taken altogether, our results indicate that cardiac- and BM- MSCs are additional cell types affected in Dsg2-linked AC, warranting the novel classification of AC as a multicellular and multiorgan disease.