bluuebunny/crossref_metadata_2025 huggingface dataset:
An Approach to Changing Competence Assessment for Human Resources in Expert Networks
Authors: Petrov Mikhail
Published: October 2020

An expert network is a community of professionals in a specific field, united by an information system, in which different tasks are solved. One of the main tasks in expert networks is the selection of specialists with specified competencies for joint problem solving. The main characteristic of an expert network member is a set of competencies, which includes both functional aspects and personal qualities. For this reason, the procedure for selecting specialists and ranking them is critical. Such a procedure uses specialists’ competence assessments from the expert network. If these assessments are out of date, the project results can be unsuccessful. This article proposes an approach aimed at automating the assessment of the specialists’ competencies based on the projects results. This approach consists of a reference model and an algorithm of competence assessment change for human resources. The paper also includes an algorithm evaluation on generated data.
Experimental Studies on Thermophysical and Electrical Properties of Graphene–Transformer Oil Nanofluid
Authors: Almeida Charishma , Paul Sohan , Godson Asirvatham Lazarus , Manova Stephen , Nimmagadda Rajesh , Raja Bose Jefferson , Wongwises Somchai
Published: October 2020

The thermophysical and electrical properties of graphene–transformer oil nanofluid at three weight percentage concentrations (0.01%, 0.03%, and 0.05%) were experimentally studied. Experiments conducted to find viscosity, surface tension, density, specific resistance, electrical conductivity, and dielectric dissipation at various temperatures ranging from 20 °C to 90 °C. It was noted that the nanofluid with 0.05% concentration showed an enhancement of 2.5% and 16.6% for density and viscosity, respectively, when compared to transformer oil. In addition, an average reduction in surface tension is noted to be 10.1% for the maximum concentration of nanofluid. Increase in heat load and concentration improves Brownian motion and decreases the cohesive force between these particles, which results in a reduction in surface tension and increases the heat-transfer rate compared to transformer oil. In addition, for the maximum concentration of nanoparticles, the electrical conductivity of nanofluid was observed to be 3.76 times higher than that of the transformer oil at 90 °C. The addition of nanoparticles in the transformer oil decreases the specific resistance and improves the electrical conductivity thereby enhancing the breakdown voltage. Moreover, the thermophysics responsible for the improvement in thermophysical and electrical properties are discussed clearly, which will be highly useful for the design of power transmission/distribution systems.
Comment on Huang, X., et al. “Sourdough Fermentation Degrades Wheat Alpha-Amylase/Trypsin Inhibitor (ATI) and Reduces Pro-Inflammatory Activity”. Foods 2020, 9, 943.
Authors: Laatikainen Reijo
Published: October 2020

I read with great interest the article titled “Sourdough Fermentation Degrades Wheat Alpha-Amylase/Trypsin Inhibitor (ATI) and Reduces Pro-Inflammatory Activity” by Huang et al [...]
Structure and Function of Mung Bean Protein-Derived Iron-Binding Antioxidant Peptides
Authors: Chunkao Siriporn , Youravong Wirote , Yupanqui Chutha T. , Alashi Adeola M. , Aluko Rotimi E.
Published: October 2020

An iron-binding mung bean protein hydrolysate (MBPH) was prepared using a continuous enzymatic membrane reactor followed by peptide separation on anion-exchange (AEC) and reverse-phase HPLC (RP-HPLC) columns. Amino acid sequences of peptides present in the RP-HPLC fraction with the strongest iron-binding capacity were identified using mass spectrometry, and ten peptides of 5–8 amino acids synthesized for antioxidant characterization. Five fractions (AF1– AF5) with higher iron-binding capacity (88.86 ± 6.43 to 153.59 ± 2.18 mg/g peptide) when compared to the MBPH (36.81 ± 0.93 mg/g peptide) were obtained from AEC. PAIDL had the significantly (p < 0.05) highest iron-binding capacity, but LLLLG and LLGIL showed the strongest metal chelating activity. However, PAIDL (46.63%) and LLGIL (81.27%) had significantly (p < 0.05) better DPPH radical scavenging activity than the other peptides. PAIDL and LLGIL were also the most effective (p < 0.05) hydroxyl radical neutralizers with an effective concentration that scavenged 50% (EC50) values of 0.09 and 0.37 mM, respectively. PAIDL and AIVIL showed the lowest EC50 values of 0.07 mM each for superoxide radical scavenging activity. We conclude that short chain length in combination with leucine as the C-terminal amino acid residue contributed to the strong antioxidant properties of peptides in this study.
Protection of Wine from Protein Haze Using Schizosaccharomyces japonicus Polysaccharides
Authors: Millarini Valentina , Ignesti Simone , Cappelli Sara , Ferraro Giovanni , Adessi Alessandra , Zanoni Bruno , Fratini Emiliano , Domizio Paola
Published: October 2020

Nowadays commercial preparations of yeast polysaccharides (PSs), in particular mannoproteins, are widely used for wine colloidal and tartrate salt stabilization. In this context, the industry has developed different processes for the isolation and purification of PSs from the cell wall of Saccharomyces cerevisiae. This yeast releases limited amounts of mannoproteins in the growth medium, thus making their direct isolation from the culture broth not economically feasible. On the contrary, Schizosaccharomyces japonicus, a non-Saccharomyces yeast isolated from wine, releases significant amounts of PSs during the alcoholic fermentation. In the present work, PSs released by Sch. japonicus were recovered from the growth medium by ultrafiltration and their impact on the wine colloidal stability was evaluated. Interestingly, these PSs contribute positively to the wine protein stability. The visible haziness of the heat-treated wine decreases as the concentration of added PSs increases. Gel electrophoresis results of the haze and of the supernatant after the heat stability test are consistent with the turbidity measurements. Moreover, particle size distributions of the heat-treated wines, as obtained by Dynamic Light Scattering (DLS), show a reduction in the average dimension of the protein aggregates as the concentration of added PSs increases.
Preoperative Cognitive Impairment and Postoperative Delirium Predict Decline in Activities of Daily Living after Cardiac Surgery—A Prospective, Observational Cohort Study
Authors: Guenther Ulf , Hoffmann Falk , Dewald Oliver , Malek Ramy , Brimmers Kathrin , Theuerkauf Nils , Putensen Christian , Popp Julius
Published: October 2020

Cardiac surgery and subsequent treatment in the intensive care unit (ICU) has been shown to be associated with functional decline, especially in elderly patients. Due to the different assessment tools and assessment periods, it remains yet unclear what parameters determine unfavorable outcomes. This study sought to identify risk factors during the entire perioperative period and focused on the decline in activity of daily living (ADL) half a year after cardiac surgery. Follow-ups of 125 patients were available. It was found that in the majority of patients (60%), the mean ADL declined by 4.9 points (95% CI, −6.4 to −3.5; p < 0.000). In the “No decline” -group, the ADL rose by 3.3 points (2.0 to 4.6; p < 0.001). A multiple regression analysis revealed that preoperative cognitive impairment (MMSE ≤ 26; Exp(B) 2.862 (95%CI, 1.192–6.872); p = 0.019) and duration of postoperative delirium ≥ 2 days (Exp(B) 3.534 (1.094–11.411); p = 0.035) was independently associated with ADL decline half a year after the operation and ICU. Of note, preoperative ADL per se was neither associated with baseline cognitive function nor a risk factor for functional decline. We conclude that the preoperative assessment of cognitive function, rather than functional assessments, should be part of risk stratification when planning complex cardiosurgical procedures.
Antibiotic Treatment Response in Chronic Lyme Disease: Why Do Some Patients Improve While Others Do Not?
Authors: Johnson Lorraine , Shapiro Mira , Stricker Raphael B. , Vendrow Joshua , Haddock Jamie , Needell Deanna
Published: October 2020

There is considerable uncertainty regarding treatment of Lyme disease patients who do not respond fully to initial short-term antibiotic therapy. Choosing the best treatment approach and duration remains challenging because treatment response among these patients varies: some patients improve with treatment while others do not. A previous study examined treatment response variation in a sample of over 3500 patients enrolled in the MyLymeData patient registry developed by LymeDisease.org (San Ramon, CA, USA). That study used a validated Global Rating of Change (GROC) scale to identify three treatment response subgroups among Lyme disease patients who remained ill: nonresponders, low responders, and high responders. The present study first characterizes the health status, symptom severity, and percentage of treatment response across these three patient subgroups together with a fourth subgroup, patients who identify as well. We then employed machine learning techniques across these subgroups to determine features most closely associated with improved patient outcomes, and we used traditional statistical techniques to examine how these features relate to treatment response of the four groups. High treatment response was most closely associated with (1) the use of antibiotics or a combination of antibiotics and alternative treatments, (2) longer duration of treatment, and (3) oversight by a clinician whose practice focused on the treatment of tick-borne diseases.
Performance of Prognostic Scoring Systems in Trauma Patients in the Intensive Care Unit of a Trauma Center
Authors: Wu Shao-Chun , Chou Sheng-En , Liu Hang-Tsung , Hsieh Ting-Min , Su Wei-Ti , Chien Peng-Chen , Hsieh Ching-Hua
Published: October 2020

Background: Prediction of mortality outcomes in trauma patients in the intensive care unit (ICU) is important for patient care and quality improvement. We aimed to measure the performance of 11 prognostic scoring systems for predicting mortality outcomes in trauma patients in the ICU. Methods: Prospectively registered data in the Trauma Registry System from 1 January 2016 to 31 December 2018 were used to extract scores from prognostic scoring systems for 1554 trauma patients in the ICU. The following systems were used: the Trauma and Injury Severity Score (TRISS); the Acute Physiology and Chronic Health Evaluation (APACHE II); the Simplified Acute Physiology Score (SAPS II); mortality prediction models (MPM II) at admission, 24, 48, and 72 h; the Multiple Organ Dysfunction Score (MODS); the Sequential Organ Failure Assessment (SOFA); the Logistic Organ Dysfunction Score (LODS); and the Three Days Recalibrated ICU Outcome Score (TRIOS). Predictive performance was determined according to the area under the receiver operator characteristic curve (AUC). Results: MPM II at 24 h had the highest AUC (0.9213), followed by MPM II at 48 h (AUC: 0.9105). MPM II at 24, 48, and 72 h (0.8956) had a significantly higher AUC than the TRISS (AUC: 0.8814), APACHE II (AUC: 0.8923), SAPS II (AUC: 0.9044), MPM II at admission (AUC: 0.9063), MODS (AUC: 0.8179), SOFA (AUC: 0.7073), LODS (AUC: 0.9013), and TRIOS (AUC: 0.8701). There was no significant difference in the predictive performance of MPM II at 24 and 48 h (p = 0.37) or at 72 h (p = 0.10). Conclusions: We compared 11 prognostic scoring systems and demonstrated that MPM II at 24 h had the best predictive performance for 1554 trauma patients in the ICU.
Changes in Physical Activity Patterns from Childhood to Adolescence: Genobox Longitudinal Study
Authors: Llorente-Cantarero Francisco Jesús , Aguilar-Gómez Francisco Javier , Anguita-Ruiz Augusto , Rupérez Azahara Iris , Vázquez-Cobela Rocío , Flores-Rojas Katherine , Aguilera Concepción M. , Gonzalez-Gil Esther M. , Gil-Campos Mercedes , Bueno-Lozano Gloria , Leis Rosaura
Published: October 2020

Longitudinal changes of physical activity (PA) from childhood into adolescence have not been accurately described yet for the Spanish population. The aim of this study is to evaluate the changes of PA, assessed by accelerometry and anthropometric measures in a cohort of 213 children from the prepubertal to pubertal period, focusing on those with valid data from both time points (n = 75). Sedentary time (ST) increased about 50%, while all PA intensities declined from the pre-pubertal to pubertal period. Light PA (LPA) was the major contributor, decreasing by about 30%. Boys were more active than girls in both periods, but they showed a higher decline in PA, especially moderate-to-vigorous PA (MVPA). The proportion who reached the recommendation of 60 min of MVPA decreased by 33.3% in boys and 4.6% in girls. Children with obesity or overweight had lower MVPA than those with normal-weight in the pre-pubertal period, but no differences were found in the pubertal period. This study shows a decrease of PA and an increase of sedentarism in the transition from childhood to adolescence, particularly in boys. Regardless of body weight, adolescents tend to be less active. Therefore, prevention programs should be implemented to achieve optimal PA and reduce sedentarism during infancy considering the differences found by sex.
Well-Being without a Roof: Examining Well-Being among Unhoused Individuals Using Mixed Methods and Propensity Score Matching
Authors: Ahuja Naina J , Nguyen Allison , Winter Sandra J , Freeman Mark , Shi Robert , Rodriguez Espinosa Patricia , Heaney Catherine A
Published: October 2020

The morbidity and mortality experiences of people who are unhoused have been well-described, but much less is known about the overall well-being of these individuals. In this mixed methods study, housed and unhoused participants completed a multi-faceted 10 domain measure of well-being (the Stanford WELL Survey), and a subset of unhoused participants shared their experiences during qualitative interviews. Using propensity score matching, unhoused participants (n = 51) were matched at a ratio of 1:5 with housed participants (n = 255). The mean overall well-being score of the unhoused participants was significantly lower than that of the matched housed participants (B = −5.022, p = 0.013). Additionally, the two groups differed on some of the constituent domains of well-being, with unhoused participants reporting statistically significantly lower mean scores on social connectedness (B = −1.086, p = 0.000), lifestyle and daily practices (B = −1.219, p = 0.000), stress and resilience (B = −0.493, p = 0.023), experience of emotions (B = −0.632, p = 0.009), physical health (B = −0.944, p = 0.0001), and finances (B = −3.099, p = 0.000). The unhoused participants had a statistically significantly higher mean score for spirituality and religiosity (B = 2.401, p = 0.000) than their matched housed counterparts. The qualitative interviews further highlighted spirituality and religion as a coping mechanism for the unhoused. The results of this study highlight both unexpected strengths exhibited by the unhoused individuals and areas of challenge.
The Devil Is in the Detail: Challenging the UK Government’s 2019 Impact Assessment of the Extent of Online Marketing of Unhealthy Foods to Children
Authors: Tatlow-Golden Mimi , Parker Daniel
Published: October 2020

Background: How much unhealthy marketing do children see on digital devices? Marketing of unhealthy food and beverages has long been identified as a factor in children’s preferences, purchase requests and consumption. Rising global obesity mandates States to craft environments that protect children and young people’s health, as recommended by the World Health Organization, among others. However, assessing the impact of marketing restrictions is particularly challenging: the complexity of digital advertising markets means that measurement challenges are profound. In 2019, the UK Department of Health published an Impact Assessment that applied a novel method aiming to calculate costs and benefits of restricting unhealthy food and beverage advertising on digital devices (planned for implementation by 2022). It estimated UK digital unhealthy marketing to children at 0.73 billion advertising impressions annually, compared to television impacts of 3.6 billion. Aim and Method: We assessed this conclusion by reviewing the UK Department of Health/Kantar Consulting’s Online Baseline Methodology (the “Government Model”). We examined the model’s underlying premise and specified the seven analytic steps undertaken. For each step, we reviewed industry and academic evidence to test its assumptions and the validity of data applied. Results: We found that, in each step, the Government Model’s assumptions, and the data sources selected, result in underestimates of the scale of digital advertising of unhealthy foods—at least tenfold, if not substantially more. The model’s underlying premise is also problematic, as digital advertising spend data relate poorly to digital advertising exposure, leading to further underestimation of market scale. Conclusion: We conclude that the Government Model very substantially underestimates the impact of digital unhealthy food advertising restrictions on health. This analysis has relevance for global policy and for the impact of regulation on children’s health and well-being.
Prediction Model for Airborne Microorganisms Using Particle Number Concentration as Surrogate Markers in Hospital Environment
Authors: Seo Ji Hoon , Jeon Hyun Woo , Choi Joung Sook , Sohn Jong-Ryeul
Published: October 2020

Indoor microbiological air quality, including airborne bacteria and fungi, is associated with hospital-acquired infections (HAIs) and emerging as an environmental issue in hospital environment. Many studies have been carried out based on culture-based methods to evaluate bioaerosol level. However, conventional biomonitoring requires laborious process and specialists, and cannot provide data quickly. In order to assess the concentration of bioaerosol in real-time, particles were subdivided according to the aerodynamic diameter for surrogate measurement. Particle number concentration (PNC) and meteorological conditions selected by analyzing the correlation with bioaerosol were included in the prediction model, and the forecast accuracy of each model was evaluated by the mean absolute percentage error (MAPE). The prediction model for airborne bacteria demonstrated highly accurate prediction (R2 = 0.804, MAPE = 8.5%) from PNC1-3, PNC3-5, and PNC5-10 as independent variables. Meanwhile, the fungal prediction model showed reasonable, but weak, prediction results (R2 = 0.489, MAPE = 42.5%) with PNC3-5, PNC5-10, PNC > 10, and relative humidity. As a result of external verification, even when the model was applied in a similar hospital environment, the bioaerosol concentration could be sufficiently predicted. The prediction model constructed in this study can be used as a pre-assessment method for monitoring microbial contamination in indoor environments.
Inhibition of Orbivirus Replication by Aurintricarboxylic Acid
Authors: Alonso Celia , Utrilla-Trigo Sergio , Calvo-Pinilla Eva , Jiménez-Cabello Luis , Ortego Javier , Nogales Aitor
Published: October 2020

Bluetongue virus (BTV) and African horse sickness virus (AHSV) are vector-borne viruses belonging to the Orbivirus genus, which are transmitted between hosts primarily by biting midges of the genus Culicoides. With recent BTV and AHSV outbreaks causing epidemics and important economy losses, there is a pressing need for efficacious drugs to treat and control the spread of these infections. The polyanionic aromatic compound aurintricarboxylic acid (ATA) has been shown to have a broad-spectrum antiviral activity. Here, we evaluated ATA as a potential antiviral compound against Orbivirus infections in both mammalian and insect cells. Notably, ATA was able to prevent the replication of BTV and AHSV in both cell types in a time- and concentration-dependent manner. In addition, we evaluated the effect of ATA in vivo using a mouse model of infection. ATA did not protect mice against a lethal challenge with BTV or AHSV, most probably due to the in vivo effect of ATA on immune system regulation. Overall, these results demonstrate that ATA has inhibitory activity against Orbivirus replication in vitro, but further in vivo analysis will be required before considering it as a potential therapy for future clinical evaluation.
Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients
Authors: Sabbatino Francesco , Liguori Luigi , Polcaro Giovanna , Salvato Ilaria , Caramori Gaetano , Salzano Francesco A. , Casolaro Vincenzo , Stellato Cristiana , Dal Col Jessica , Pepe Stefano
Published: October 2020

Recent advances in cancer immunotherapy have clearly shown that checkpoint-based immunotherapy is effective in a small subgroup of cancer patients. However, no effective predictive biomarker has been identified so far. The major histocompatibility complex, better known in humans as human leukocyte antigen (HLA), is a very polymorphic gene complex consisting of more than 200 genes. It has a crucial role in activating an appropriate host immune response against pathogens and tumor cells by discriminating self and non-self peptides. Several lines of evidence have shown that down-regulation of expression of HLA class I antigen derived peptide complexes by cancer cells is a mechanism of tumor immune escape and is often associated to poor prognosis in cancer patients. In addition, it has also been shown that HLA class I and II antigen expression, as well as defects in the antigen processing machinery complex, may predict tumor responses in cancer immunotherapy. Nevertheless, the role of HLA in predicting tumor responses to checkpoint-based immunotherapy is still debated. In this review, firstly, we will describe the structure and function of the HLA system. Secondly, we will summarize the HLA defects and their clinical significance in cancer patients. Thirdly, we will review the potential role of the HLA as a predictive biomarker for checkpoint-based immunotherapy in cancer patients. Lastly, we will discuss the potential strategies that may restore HLA function to implement novel therapeutic strategies in cancer patients.
Transcriptomic Analysis and Specific Expression of Transcription Factor Genes in the Root and Sporophyll of Dryopteris fragrans (L.) Schott
Authors: Chen Lingling , Zhang Dongrui , Song Chunhua , Wang Hemeng , Tang Xun , Chang Ying
Published: October 2020

Background: Dryopteris fragrans, which is densely covered with glandular trichomes, is considered to be one of the ferns with the most medicinal potential. The transcriptomes from selected tissues of D. fragrans were collected and analyzed for functional and comparative genomic studies. The aim of this study was to determine the transcriptomic characteristics of wild D. fragrans sporangium in tissues from the SR (root), SL (sporophyll), and TRL (sporophyll with glandular trichomes removed). Results: Cluster analysis identified genes that were highly expressed in an organ-specific manner according to read mapping, feature counting, and normalization. The functional map identified gene clusters that can uniquely describe the function of each tissue. We identified a group of three tissue-specific transcription factors targeting the SL, SR, and TRL. In addition, highly expressed transcription factors (TFs) were found in each tissue-specific gene cluster, where ERF and bHLH transcription factors were the two types showing the most distinct expression patterns between the three different tissues. The specific expression of transcription factor genes varied between the different types of tissues. The numbers of transcription factors specifically expressed in the roots and sporophylls were 60 and 30, respectively, while only seven were found for the sporophylls with glandular trichomes removed. The expression of genes known to be associated with the development of glandular trichomes in flowering plants, including MIXTA, ATML1, and MYB106, were also validated and are discussed. In particular, a unigene encoding MIXTA was identified and exhibited the highest expression level in SL in D. fragrans. Conclusions: This study is the first report of global transcriptomic analysis in different tissues of D. fragrans, and the first to discuss these findings in the context of the development of homologous glandular trichomes. These results set the stage for further research on the development, stress resistance, and secondary metabolism of D. fragrans glandular trichomes.
Effects of Fluoride Long-Term Exposure over the Cerebellum: Global Proteomic Profile, Oxidative Biochemistry, Cell Density, and Motor Behavior Evaluation
Authors: Lopes Géssica Oliveira , Martins Ferreira Maria Karolina , Davis Lodinikki , Bittencourt Leonardo Oliveira , Bragança Aragão Walessa Alana , Dionizio Aline , Rabelo Buzalaf Marília Afonso , Crespo-Lopez Maria Elena , Maia Cristiane Socorro Ferraz , Lima Rafael Rodrigues
Published: October 2020

Although the literature does not provide evidence of health risks from exposure to fluoride (F) in therapeutic doses, questions remain about the effects of long-term and high-dose use on the function of the central nervous system. The objective of this study was to investigate the effect of long-term exposure to F at levels similar to those found in areas of artificial water fluoridation and in areas of endemic fluorosis on biochemical, proteomic, cell density, and functional parameters associated with the cerebellum. For this, mice were exposed to water containing 10 mg F/L or 50 mg F/L (as sodium fluoride) for 60 days. After the exposure period, the animals were submitted to motor tests and the cerebellum was evaluated for fluoride levels, antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (MDA), and nitrite levels (NO). The proteomic profile and morphological integrity were also evaluated. The results showed that the 10 mg F/L dose was able to decrease the ACAP levels, and the animals exposed to 50 mg F/L presented lower levels of ACAP and higher levels of MDA and NO. The cerebellar proteomic profile in both groups was modulated, highlighting proteins related to the antioxidant system, energy production, and cell death, however no neuronal density change in cerebellum was observed. Functionally, the horizontal exploratory activity of both exposed groups was impaired, while only the 50 mg F/L group showed significant changes in postural stability. No motor coordination and balance impairments were observed in both groups. Our results suggest that fluoride may impair the cerebellar oxidative biochemistry, which is associated with the proteomic modulation and, although no morphological impairment was observed, only the highest concentration of fluoride was able to impair some cerebellar motor functions.
The Effects of Immune System Modulation on Prion Disease Susceptibility and Pathogenesis
Authors: Mabbott Neil A. , Bradford Barry M. , Pal Reiss , Young Rachel , Donaldson David S.
Published: October 2020

Prion diseases are a unique group of infectious chronic neurodegenerative disorders to which there are no cures. Although prion infections do not stimulate adaptive immune responses in infected individuals, the actions of certain immune cell populations can have a significant impact on disease pathogenesis. After infection, the targeting of peripherally-acquired prions to specific immune cells in the secondary lymphoid organs (SLO), such as the lymph nodes and spleen, is essential for the efficient transmission of disease to the brain. Once the prions reach the brain, interactions with other immune cell populations can provide either host protection or accelerate the neurodegeneration. In this review, we provide a detailed account of how factors such as inflammation, ageing and pathogen co-infection can affect prion disease pathogenesis and susceptibility. For example, we discuss how changes to the abundance, function and activation status of specific immune cell populations can affect the transmission of prion diseases by peripheral routes. We also describe how the effects of systemic inflammation on certain glial cell subsets in the brains of infected individuals can accelerate the neurodegeneration. A detailed understanding of the factors that affect prion disease transmission and pathogenesis is essential for the development of novel intervention strategies.
Adenosine Metabolism in the Cerebral Cortex from Several Mice Models during Aging
Authors: Sánchez-Melgar Alejandro , Albasanz José Luis , Pallàs Mercè , Martín Mairena
Published: October 2020

Adenosine is a neuromodulator that has been involved in aging and neurodegenerative diseases as Alzheimer’s disease (AD). In the present work, we analyzed the possible modulation of purine metabolites, 5’nucleotidase (5′NT) and adenosine deaminase (ADA) activities, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) and its phosphorylated form during aging in the cerebral cortex. Three murine models were used: senescence-accelerated mouse-resistant 1 (SAMR1, normal senescence), senescence-accelerated mouse-prone 8 (SAMP8, a model of AD), and the wild-type C57BL/6J (model of aging) mice strains. Glutamate and excitatory amino acid transporter 2 (EAAT2) levels were also measured in these animals. HPLC, Western blotting, and enzymatic activity evaluation were performed to this aim. 5′-Nucleotidase (5′NT) activity was decreased at six months and recovered at 12 months in SAMP8 while opposite effects were observed in SAMR1 at the same age, and no changes in C57BL/6J mice. ADA activity significantly decreased from 3 to 12 months in the SAMR1 mice strain, while a significant decrease from 6 to 12 months was observed in the SAMP8 mice strain. Regarding purine metabolites, xanthine and guanosine levels were increased at six months in SAMR1 without significant differences in SAMP8 mice. In C57BL/6J mice, inosine and xanthine were increased, while adenosine decreased, from 4 to 24 months. The AMPK level was decreased at six months in SAMP8 without significant changes nor in SAMR1 or C57BL/6J strains. Glutamate and EAAT2 levels were also modulated during aging. Our data show a different modulation of adenosine metabolism participants in the cerebral cortex of these animal models. Interestingly, the main differences between SAMR1 and SAMP8 mice were found at six months of age, SAMP8 being the most affected strain. As SAMP8 is an AD model, results suggest that adenosinergic metabolism is involved in the neurodegeneration of AD.
Preconditioned and Genetically Modified Stem Cells for Myocardial Infarction Treatment
Authors: Raziyeva Kamila , Smagulova Aiganym , Kim Yevgeniy , Smagul Saltanat , Nurkesh Ayan , Saparov Arman
Published: October 2020

Ischemic heart disease and myocardial infarction remain leading causes of mortality worldwide. Existing myocardial infarction treatments are incapable of fully repairing and regenerating the infarcted myocardium. Stem cell transplantation therapy has demonstrated promising results in improving heart function following myocardial infarction. However, poor cell survival and low engraftment at the harsh and hostile environment at the site of infarction limit the regeneration potential of stem cells. Preconditioning with various physical and chemical factors, as well as genetic modification and cellular reprogramming, are strategies that could potentially optimize stem cell transplantation therapy for clinical application. In this review, we discuss the most up-to-date findings related to utilizing preconditioned stem cells for myocardial infarction treatment, focusing mainly on preconditioning with hypoxia, growth factors, drugs, and biological agents. Furthermore, genetic manipulations on stem cells, such as the overexpression of specific proteins, regulation of microRNAs, and cellular reprogramming to improve their efficiency in myocardial infarction treatment, are discussed as well.
A Perspective on Therapeutic Pan-Resistance in Metastatic Cancer
Authors: Korentzelos Dimitrios , Clark Amanda M. , Wells Alan
Published: October 2020

Metastatic spread represents the leading cause of disease-related mortality among cancer patients. Many cancer patients suffer from metastatic relapse years or even decades after radical surgery for the primary tumor. This clinical phenomenon is explained by the early dissemination of cancer cells followed by a long period of dormancy. Although dormancy could be viewed as a window of opportunity for therapeutic interventions, dormant disseminated cancer cells and micrometastases, as well as emergent outgrowing macrometastases, exhibit a generalized, innate resistance to chemotherapy and even immunotherapy. This therapeutic pan-resistance, on top of other adaptive responses to targeted agents such as acquired mutations and lineage plasticity, underpins the current difficulties in eradicating cancer. In the present review, we attempt to provide a framework to understand the underlying biology of this major issue.
Lupinus albus γ-Conglutin, a Protein Structurally Related to GH12 Xyloglucan-Specific Endo-Glucanase Inhibitor Proteins (XEGIPs), Shows Inhibitory Activity against GH2 β-Mannosidase
Authors: Benedetti Stefano De , Galanti Elisabetta , Capraro Jessica , Magni Chiara , Scarafoni Alessio
Published: October 2020

γ-conglutin (γC) is a major protein of Lupinus albus seeds, but its function is still unknown. It shares high structural similarity with xyloglucan-specific endo-glucanase inhibitor proteins (XEGIPs) and, to a lesser extent, with Triticum aestivum endoxylanase inhibitors (TAXI-I), active against fungal glycoside hydrolases GH12 and GH11, respectively. However, γC lacks both these inhibitory activities. Since β-galactomannans are major components of the cell walls of endosperm in several legume plants, we tested the inhibitory activity of γC against a GH2 β-mannosidase (EC 3.2.1.25). γC was actually able to inhibit the enzyme, and this effect was enhanced by the presence of zinc ions. The stoichiometry of the γC/enzyme interaction was 1:1, and the calculated Ki was 1.55 μM. To obtain further insights into the interaction between γC and β-mannosidase, an in silico structural bioinformatic approach was followed, including some docking analyses. By and large, this work describes experimental findings that highlight new scenarios for understanding the natural role of γC. Although structural predictions can leave space for speculative interpretations, the full complexity of the data reported in this work allows one to hypothesize mechanisms of action for the basis of inhibition. At least two mechanisms seem plausible, both involving lupin-γC-peculiar structures.
The Immune Microenvironment in Pancreatic Cancer
Authors: Huber Magdalena , Brehm Corinna U. , Gress Thomas M. , Buchholz Malte , Alashkar Alhamwe Bilal , von Strandmann Elke , Slater Emily P. , Bartsch Jörg W. , Bauer Christian , Lauth Matthias
Published: October 2020

The biology of solid tumors is strongly determined by the interactions of cancer cells with their surrounding microenvironment. In this regard, pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) represents a paradigmatic example for the multitude of possible tumor–stroma interactions. PDAC has proven particularly refractory to novel immunotherapies, which is a fact that is mediated by a unique assemblage of various immune cells creating a strongly immunosuppressive environment in which this cancer type thrives. In this review, we outline currently available knowledge on the cross-talk between tumor cells and the cellular immune microenvironment, highlighting the physiological and pathological cellular interactions, as well as the resulting therapeutic approaches derived thereof. Hopefully a better understanding of the complex tumor–stroma interactions will one day lead to a significant advancement in patient care.
Seminal Plasma Transcriptome and Proteome: Towards a Molecular Approach in the Diagnosis of Idiopathic Male Infertility
Authors: Cannarella Rossella , Barbagallo Federica , Crafa Andrea , La Vignera Sandro , Condorelli Rosita A. , Calogero Aldo E.
Published: October 2020

As the “-omic” technology has largely developed, its application in the field of medical science seems a highly promising tool to clarify the etiology, at least in part, of the so-called idiopathic male infertility. The seminal plasma (SP) is made-up of secretions coming from the male accessory glands, namely epididymis, seminal vesicles, and prostate. It is not only a medium for sperm transport since it is able to modulate the female reproductive environment and immunity, to allow the acquisition of sperm competence, to influence the sperm RNA content, and even embryo development. The aim of this systematic review was to provide an updated and comprehensive description of the main transcripts and proteins reported by transcriptome and proteome studies performed in the human SP of patients with idiopathic infertility, in the attempt of identifying possible candidate molecular targets. We recurrently found that micro RNA (miR)-34, miR-122, and miR-509 are down-regulated in patients with non-obstructive azoospermia (NOA) and oligozoospermia compared with fertile controls. These molecules may represent interesting targets whose predictive role in testicular sperm extraction (TESE) or assisted reproductive techniques (ART) outcome deserves further investigation. Furthermore, according to the available proteomic studies, ECM1, TEX101, lectingalactoside-binding andsoluble 3 binding protein (LGALS3BP) have been reported as accurate predictors of TESE outcome. Interestingly, ECM1 is differently expressed in patients with different ART outcomes. Further prospective, ample-sized studies are needed to validate these molecular targets that will help in the counseling of patients with NOA or undergoing ART.
Neural Stem Cells and Cannabinoids in the Spotlight as Potential Therapy for Epilepsy
Authors: Lourenço Diogo M. , Ribeiro-Rodrigues Leonor , Sebastião Ana M. , Diógenes Maria J. , Xapelli Sara
Published: October 2020

Epilepsy is one of the most common brain diseases worldwide, having a huge burden in society. The main hallmark of epilepsy is the occurrence of spontaneous recurrent seizures, having a tremendous impact on the lives of the patients and of their relatives. Currently, the therapeutic strategies are mostly based on the use of antiepileptic drugs, and because several types of epilepsies are of unknown origin, a high percentage of patients are resistant to the available pharmacotherapy, continuing to experience seizures overtime. Therefore, the search for new drugs and therapeutic targets is highly important. One key aspect to be targeted is the aberrant adult hippocampal neurogenesis (AHN) derived from Neural Stem Cells (NSCs). Indeed, targeting seizure-induced AHN may reduce recurrent seizures and shed some light on the mechanisms of disease. The endocannabinoid system is a known modulator of AHN, and due to the known endogenous antiepileptic properties, it is an interesting candidate for the generation of new antiepileptic drugs. However, further studies and clinical trials are required to investigate the putative mechanisms by which cannabinoids can be used to treat epilepsy. In this manuscript, we will review how cannabinoid-induced modulation of NSCs may promote neural plasticity and whether these drugs can be used as putative antiepileptic treatment.
Poly(3-Hydroxybutyrate)-Based Nanoparticles for Sorafenib and Doxorubicin Anticancer Drug Delivery
Authors: Babos György , Rydz Joanna , Kawalec Michal , Klim Magdalena , Fodor-Kardos Andrea , Trif László , Feczkó Tivadar
Published: October 2020

Dual drug-loaded nanotherapeutics can play an important role against the drug resistance and side effects of the single drugs. Doxorubicin and sorafenib were efficiently co-encapsulated by tailor-made poly([R,S]-3-hydroxybutyrate) (PHB) using an emulsion–solvent evaporation method. Subsequent poly(ethylene glycol) (PEG) conjugation onto nanoparticles was applied to make the nanocarriers stealth and to improve their drug release characteristics. Monodisperse PHB–sorafenib–doxorubicin nanoparticles had an average size of 199.3 nm, which was increased to 250.5 nm after PEGylation. The nanoparticle yield and encapsulation efficiencies of drugs decreased slightly in consequence of PEG conjugation. The drug release of the doxorubicin was beneficial, since it was liberated faster in a tumor-specific acidic environment than in blood plasma. The PEG attachment decelerated the release of both the doxorubicin and the sorafenib, however, the release of the latter drug remained still significantly faster with increased initial burst compared to doxorubicin. Nevertheless, the PEG–PHB copolymer showed more beneficial drug release kinetics in vitro in comparison with our recently developed PEGylated poly(lactic-co-glycolic acid) nanoparticles loaded with the same drugs.
Reproductive Potential of Yeast Cells Depends on Overall Action of Interconnected Changes in Central Carbon Metabolism, Cellular Biosynthetic Capacity, and Proteostasis
Authors: Maslanka Roman , Zadrag-Tecza Renata
Published: October 2020

Carbon metabolism is a crucial aspect of cell life. Glucose, as the primary source of energy and carbon skeleton, determines the type of cell metabolism and biosynthetic capabilities, which, through the regulation of cell size, may affect the reproductive capacity of the yeast cell. Calorie restriction is considered as the most effective way to improve cellular physiological capacity, and its molecular mechanisms are complex and include several nutrient signaling pathways. It is widely assumed that the metabolic shift from fermentation to respiration is treated as a substantial driving force for the mechanism of calorie restriction and its influence on reproductive capabilities of cells. In this paper, we propose another approach to this issue based on analysis the connection between energy-producing and biomass formation pathways which are closed in the metabolic triangle, i.e., the respiration-glycolysis-pentose phosphate pathway. The analyses were based on the use of cells lacking hexokinase 2 (∆hxk2) and conditions of different glucose concentration corresponding to the calorie restriction and the calorie excess. Hexokinase 2 is the key enzyme involved in central carbon metabolism and is also treated as a calorie restriction mimetic. The experimental model used allows us to explain both the role of increased respiration as an effect of calorie restriction but also other aspects of carbon metabolism and the related metabolic flux in regulation of reproductive potential of the cells. The obtained results reveal that increased respiration is not a prerequisite for reproductive potential extension but rather an accompanying effect of the positive role of calorie restriction. More important seems to be the changes connected with fluxes in central carbon metabolic pathways resulting in low biosynthetic capabilities and improved proteostasis.
Roles of ASYMMETRIC LEAVES2 (AS2) and Nucleolar Proteins in the Adaxial–Abaxial Polarity Specification at the Perinucleolar Region in Arabidopsis
Authors: Iwakawa Hidekazu , Takahashi Hiro , Machida Yasunori , Machida Chiyoko
Published: October 2020

Leaves of Arabidopsis develop from a shoot apical meristem grow along three (proximal–distal, adaxial–abaxial, and medial–lateral) axes and form a flat symmetric architecture. ASYMMETRIC LEAVES2 (AS2), a key regulator for leaf adaxial–abaxial partitioning, encodes a plant-specific nuclear protein and directly represses the abaxial-determining gene ETTIN/AUXIN RESPONSE FACTOR3 (ETT/ARF3). How AS2 could act as a critical regulator, however, has yet to be demonstrated, although it might play an epigenetic role. Here, we summarize the current understandings of the genetic, molecular, and cellular functions of AS2. A characteristic genetic feature of AS2 is the presence of a number of (about 60) modifier genes, mutations of which enhance the leaf abnormalities of as2. Although genes for proteins that are involved in diverse cellular processes are known as modifiers, it has recently become clear that many modifier proteins, such as NUCLEOLIN1 (NUC1) and RNA HELICASE10 (RH10), are localized in the nucleolus. Some modifiers including ribosomal proteins are also members of the small subunit processome (SSUP). In addition, AS2 forms perinucleolar bodies partially colocalizing with chromocenters that include the condensed inactive 45S ribosomal RNA genes. AS2 participates in maintaining CpG methylation in specific exons of ETT/ARF3. NUC1 and RH10 genes are also involved in maintaining the CpG methylation levels and repressing ETT/ARF3 transcript levels. AS2 and nucleolus-localizing modifiers might cooperatively repress ETT/ARF3 to develop symmetric flat leaves. These results raise the possibility of a nucleolus-related epigenetic repression system operating for developmental genes unique to plants and predict that AS2 could be a molecule with novel functions that cannot be explained by the conventional concept of transcription factors.
Interactions between Two Parasitoids of Tephritidae: Diachasmimorpha longicaudata (Ashmead) and Psyttalia cosyrae (Wilkinson) (Hymenoptera: Braconidae), under Laboratory Conditions
Authors: Ndlela Shepard , Mohamed Samira Abuelgasim , Azrag Abdelmutalab G.A. , Ndegwa Paul Nduati , Ong’amo George Otieno , Ekesi Sunday
Published: October 2020

The braconid wasp, Diachasmimorpha longicaudata (Ashmead), was introduced in Kenya from Hawaii for classical biological control of the invasive tephritid, Bactrocera dorsalis Hendel. Following reports that D. longicaudata had formed new associations with Ceratitis cosyra, laboratory experiments were conducted to assess the interaction between the introduced and the native parasitoid of C. cosyra; Psyttalia cosyrae (Wilkinson) under three scenarios: B. dorsalis only, C. cosyra only and mixed populations of the two species. Parasitoids were introduced to the host as sole, sequential and simultaneous releases. Host searching and probing events were five times higher for D. longicaudata than P. cosyrae with both hosts. Total parasitism was highest (78%) when D. longicaudata was released alone on C. cosyra, compared to 20% for P. cosyrae released on the same host. Releases of P. cosyrae on B. dorsalis resulted in 0% parasitism, compared to 64% parasitism by D. longicaudata. Specific parasitism for P. cosyrae was three times higher when P. cosyrae was released first in sequential releases on C. cosyra compared to when it was released after D. longicaudata. These findings suggest that the two parasitoids can both suppress C. cosyra but B. dorsalis acts as a reproductive sink for P. cosyrae. Our findings should form the basis of field investigations where options are much wider for both parasitoids.