bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Satellite Sensor Pixel Size and Overpass Time on Undercounting of Cerrado/Savannah Landscape-Scale Fire Radiative Power (FRP): An Assessment Using the MODIS Airborne Simulator
Authors: Sperling Samuel , Wooster Martin J. , Malamud Bruce D.
Published: May 2020

The fire radiative power (FRP) of active fires (AFs) is routinely assessed with spaceborne sensors. MODIS is commonly used, and its 1 km nadir pixel size provides a minimum per-pixel FRP detection limit of ~5–8 MW, leading to undercounting of AF pixels with FRPs of less than around 10 MW. Since most biomes show increasing AF pixel frequencies with decreasing FRP, this results in MODIS failing to detect many fires burning when it overpasses. However, the exact magnitude of the landscape-scale FRP underestimation induced by this type of AF undercounting remains poorly understood, as does its sensitivity to sensor pixel size and overpass time. We investigate these issues using both 1 km spaceborne MODIS data and 50 m MODIS Airborne Simulator (MAS) observations of the Brazilian cerrado, a savannah-like environment covering 2 million km2 (>20%) of Brazil where fires are a frequent occurrence. The MAS data were collected during the 1995 SCAR-B experiment, and are able to be spatially degraded to simulate data from sensors with a wide variety of pixel sizes. We explore multiple versions of these MAS data to deliver recommendations for future satellite sensor design, aiming to discover the most effective sensor characteristics that provide negligible pixel-area related FRP underestimation whilst keeping pixels large enough to deliver relatively wide swath widths. We confirm earlier analyses showing 1 km MODIS-type observations fail to detect a very significant number of active fires, and find the degree of undercounting gets worse away from the early afternoon diurnal fire cycle peak (~ 15:00 local time). However, the effect of these undetected fires on the assessment of total landscape-scale FRP is far less significant, since they are mostly low FRP fires. Using two different approaches we estimate that the MODIS-type 1 km data underestimates landscape scale FRP by around a third, and that whilst the degree of underestimation worsens away from the diurnal fire cycle peak the effect of this maybe less important since there are far fewer fires present. MAS data degraded to a 200 m spatial resolution provides landscape-scale FRP totals almost indistinguishable from those calculated with the original 50 m MAS observations, and still provides a pixel size consistent with a wide swath imaging instrument. Our work provides a potentially useful guide for future mission developers aiming at active fire and FRP applications, and we conclude that such missions need operate at spatial resolutions no higher than 200 m if they rely on cooled, low-noise IR detectors. Further work confirming this for fire-affected biomes beyond the savannah-type environments studied here is recommended.
Potential Activity of Aqueous Fig Leaves Extract, Olive Leaves Extract and Their Mixture as Natural Preservatives to Extend the Shelf Life of Pasteurized Buffalo Milk
Authors: El Dessouky Abdel-Aziz Mohamed , Samir Darwish Mohamed , Mohamed Azza H. , El-Khateeb Ayman Y. , Hamed Sahar E.
Published: May 2020

The aim of this study was to evaluate fig (Ficus carica L.) leaves’ extract (FLE), olive (Olea europaea L.) leaves’ extract (OLE), and their mixture (MLE), to extend the shelf life of pasteurized milk. OLE, FLE, and their mixture MLE (1:1) were added to the pasteurized milk in different concentrations (0.2%, 0.4%, and 0.6%). Several tests were then conducted to determine the activity of these extracts. The antioxidant activity as IC50 was determined by using DPPH radical assay. FLE showed higher IC50 (30.21 µg/mL) compared to the IC50 of OLE (22.43 µg/mL). Phenolic compounds were identified by using high-performance liquid chromatography (HPLC). The highest antimicrobial activity was obtained with 0.6% concentration. Organoleptic properties indicated that the addition of these extracts did not affect the sensory properties of pasteurized milk. Pasteurized milk treated with 0.6% of FLE, OLE, and MLE has significantly decreased (p ≤ 0.05) lipase and protease activity during the storage period, at 5 °C. The results indicated that extending the shelf life of pasteurized milk from 5 to 16 days was successfully achieved through using 0.6% of FLE, OLE, and MLE. The combination of the two extracts (MLE) provides an efficient and safe method to prolong the shelf life of pasteurized milk, without altering the properties of pasteurized buffalo milk.
iMethyl-Deep: N6 Methyladenosine Identification of Yeast Genome with Automatic Feature Extraction Technique by Using Deep Learning Algorithm
Authors: Mahmoudi Omid , Wahab Abdul , Chong Kil To
Published: May 2020

One of the most common and well studied post-transcription modifications in RNAs is N6-methyladenosine (m6A) which has been involved with a wide range of biological processes. Over the past decades, N6-methyladenosine produced some positive consequences through the high-throughput laboratory techniques but still, these lab processes are time consuming and costly. Diverse computational methods have been proposed to identify m6A sites accurately. In this paper, we proposed a computational model named iMethyl-deep to identify m6A Saccharomyces Cerevisiae on two benchmark datasets M6A2614 and M6A6540 by using single nucleotide resolution to convert RNA sequence into a high quality feature representation. The iMethyl-deep obtained 89.19% and 87.44% of accuracy on M6A2614 and M6A6540 respectively which show that our proposed method outperforms the state-of-the-art predictors, at least 8.44%, 8.96%, 8.69% and 0.173 on M6A2614 and 15.47%, 28.52%, 25.54 and 0.5 on M6A6540 higher in terms of four metrics Sp, Sn, ACC and MCC respectively. Meanwhile, M6A6540 dataset never used to train a model.
Investigating Human Mitochondrial Genomes in Single Cells
Authors: Diroma Maria Angela , Varvara Angelo Sante , Attimonelli Marcella , Pesole Graziano , Picardi Ernesto
Published: May 2020

Mitochondria host multiple copies of their own small circular genome that has been extensively studied to trace the evolution of the modern eukaryotic cell and discover important mutations linked to inherited diseases. Whole genome and exome sequencing have enabled the study of mtDNA in a large number of samples and experimental conditions at single nucleotide resolution, allowing the deciphering of the relationship between inherited mutations and phenotypes and the identification of acquired mtDNA mutations in classical mitochondrial diseases as well as in chronic disorders, ageing and cancer. By applying an ad hoc computational pipeline based on our MToolBox software, we reconstructed mtDNA genomes in single cells using whole genome and exome sequencing data obtained by different amplification methodologies (eWGA, DOP-PCR, MALBAC, MDA) as well as data from single cell Assay for Transposase Accessible Chromatin with high-throughput sequencing (scATAC-seq) in which mtDNA sequences are expected as a byproduct of the technology. We show that assembled mtDNAs, with the exception of those reconstructed by MALBAC and DOP-PCR methods, are quite uniform and suitable for genomic investigations, enabling the study of various biological processes related to cellular heterogeneity such as tumor evolution, neural somatic mosaicism and embryonic development.
Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain
Authors: Gonzalez-Quereda Lidia , Rodriguez Maria Jose , Diaz-Manera Jordi , Alonso-Perez Jorge , Gallardo Eduard , Nascimento Andres , Ortez Carlos , Natera-de Benito Daniel , Olive Montse , Gonzalez-Mera Laura , Lopez de Munain Adolfo , Zulaica Miren , Poza Juan Jose , Jerico Ivonne , Torne Laura , Riera Pau , Milisenda Jose , Sanchez Aurora , Garrabou Gloria , Llano Isabel , Madruga-Garrido Marcos , Gallano Pia
Published: May 2020

The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients’ clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.
Cardiovascular Risk Distribution in a Contemporary Polish Collective
Authors: Liput-Sikora Anita , Cybulska Anna , Fabian Wiesława , Fabian-Danielewska Anna , Stanisławska Marzanna , Kamińska Magdalena , Grochans Elżbieta
Published: May 2020

The aim of this study was to assess the prevalence of selected risk factors for cardiovascular disease (hypertension, overweight, obesity, carbohydrate metabolism disorders, a positive family history, a lack of physical activity), and to estimate the risk of a cardiovascular incident according to the Systematic Coronary Risk Evaluation (SCORE) algorithm for patients aged 35, 40, 45, 50, and 55 years, included in a primary-care prevention program, with regard to selected variables (sex and age brackets). The study sample consisted of 2009 subjects, 63% of whom were women. The largest group was the group of 35-year-olds (27%). The research method was the analysis of medical documentation of primary-care patients living in West Pomerania included in the Program of Prevention and Early Detection of Cardiovascular Disease of the National Health Fund. We collected data concerning risk factors for cardiovascular disease, blood pressure, anthropometric measurements (arm circumference, waist circumference, height, weight), body mass index (BMI), and the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and fasting glucose, as well as the SCORE results. Men more often than women were overweight and obese, had hyperglycemia, and had elevated levels of total cholesterol, LDL cholesterol, and triglycerides (p < 0.001). There was also a statistically significant difference in the odds of a cardiovascular incident (p < 0.001)—the SCORE results obtained by men were higher. Men require special preventive measures in order to reduce their risk factors for cardiovascular disease, especially hypertension, dyslipidemia, diabetes, overweight, obesity, smoking, and a positive family history.
Estimating Lifetime Dental Care Expenditure in South Korea: An Abridged Life Table Approach
Authors: Sohn Minsung , Che Xianhua , Lim Sungwon , Park Hee-Jung
Published: May 2020

The aim of this study was to measure the magnitude and distribution of a Korean’s lifetime dental expenses depending on age and sex, by constructing a hypothetical lifetime and life table of survival. Additionally, we estimated the difference in life expectancy between men and women and its impact on dental expenses. We used the 2015 Korea Health Panel Survey to calculate the total dental expenditure, including expenses paid directly by patients and those paid by insurers. We generated survival profiles to simulate dental expenses during a typical lifetime (from birth to age 95) using the abridged life table (five-year intervals for age groups) in 2015 from the South Korean Statistical Information Service. We independently calculated the remaining dental expenses for survivors of all ages. The results showed that an estimate of average lifetime dental expenditure was $31,851 per capita: $31,587 for men and $32,318 for women. Nearly 33% of the average per capita lifetime dental expenditure was attributable to the longer life expectancy of women, with no statistically significant difference in lifetime dental expenditure between men and women. Many survivors incurred 70% of their lifetime dental expenses before age 65. The results highlighted the need for policymakers to address spending on age-specific dental care owing to extended life expectancy, given the disproportionate share of healthcare resources supporting the elderly.
Effects of Long-Term Endurance Exercise and Lithium Treatment on Neuroprotective Factors in Hippocampus of Obese Rats
Authors: Park Jusik , Cheon Wookwang , Kim Kijin
Published: May 2020

To investigate the effects of long-term lithium treatment and low intensity endurance exercise on brain-derived neurotrophic factor (BDNF) expression and glycogen synthase kinase 3 beta (GSK3β) activity in the hippocampus of obese rats. Fifty 10-week-old male Sprague-Dawley rats were selected. There was a control group of 10 rats (chow control group) while the other forty rats were fed on a high-fat diet for eight weeks to induce obesity. Rats were then assigned into four random groups. The rats were given 10 mg/kg lithium chloride (LiCl) dissolved in 1 mL sterile distilled water once a day, 5 times a week. The rats did 20 min of treadmill walking with an exercise intensity of 40% maximal oxygen uptake (VO2 max) (12 m/min, slope 0%). This was performed for 20 min a day, 3 days a week. Twelve weeks of lithium treatment or endurance exercise significantly reduced body weight and body fat mass in obese rats, without showing additive effects when the treatments were given in parallel or significant toxic responses in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in blood and kidney and liver tissues. BDNF expression in the hippocampus was significantly increased both in exercise and lithium groups with synergistic effects found in the group where both exercise and lithium treatments were given in parallel. On the other hand, the decrease in GSK3β activity was shown only in the lithium treatment group, without showing additive effects when the treatments were given in parallel. Lithium and low-intensity endurance exercise for 12 weeks increased the expression of BDNF, a neuroprotective factor in the hippocampus of obese mice. Lithium treatment alone inhibited the activity of GSK3β. This can be interpreted as a positive indication of applicability of the two factors in the prevention of neurodegenerative diseases.
Early Osteoporosis Risks and Associated Factors among Caregivers Working in Disability Institutions: IOF One-Minute Osteoporosis Risk Check
Authors: Lin Lan-Ping , Lai Wei-Ju , Hsu Shang-Wei , Lin Jin-Ding
Published: May 2020

This study employed the International Osteoporosis Foundation’s One-Minute Osteoporosis Risk Test to examine factors related to the osteoporosis risk of institutional caregivers. In this cross-sectional study, a self-developed structured questionnaire comprising the One-Minute Osteoporosis Risk Test was used to obtain data on the caregivers’ demographic data, health habits, working style, and osteoporosis risk. Seven disability welfare institutions were selected as research sites, and 465 copies of questionnaires were distributed to the institutions’ employees, with 455 valid responses collected for a valid return rate of 98%. SPSS for Windows (Version 20.0) was used to analyze questionnaire data; descriptive-statistical frequency, a χ2 test, and logistic regression were used to determine the correlation between demographic data, health habits, working style, and osteoporosis risk. The results revealed that primary risk factors include <30 min of daily exercise (38%), lack of dairy product or calcium tablet intake (28%), and <10 min of daily outdoor activity or not taking vitamin D supplements (29.9%). In total, 395 (86.8%) of the respondents scored less than 5 in the osteoporosis risk test; the remaining 60 (13.2%) scored 5 or higher, revealing a high risk of early osteoporosis. An independent variable analysis revealed that the risk factors of early osteoporosis include age, education level, having undergone bone density tests, prior disease diagnosis, long-term medication use, physical fitness, dietary habits, and average time of exposure to sunlight. In the multivariate analysis, poor physical fitness (odds ratio [OR] = 2.18, 95% confidence interval [CI]: 1.12–4.27, p = 0.023) and average daily time of exposure to sunlight (OR = 0.24, 95% CI: 0.59–2.59, p < 0.001) were significantly correlated with osteoporosis risk. In other words, respondents with poor physical fitness were 2.18 times as likely to have osteoporosis as those with good physical fitness, and those exposed to sunlight for 30 min or longer every day were 0.24 times as likely to have osteoporosis as those exposed to sunlight for less than 30 min every day. Accordingly, institutions must encourage employees to spend more time in the sun every day and improve their physical fitness through exercise.
In-Vitro Growth Inhibition of Bacterial Pathogens by Probiotics and a Synbiotic: Product Composition Matters
Authors: Piatek Jacek , Krauss Hanna , Ciechelska-Rybarczyk Arleta , Bernatek Malgorzata , Wojtyla-Buciora Paulina , Sommermeyer Henning
Published: May 2020

A variety of activities potentially contribute to the beneficial effects of probiotic bacteria observed in humans. Among these is a direct inhibition of the growth of pathogenic bacteria in the gut. The present study characterizes head-to-head the in-vitro pathogen growth inhibition of clinically relevant infectious bacterial strains by different types of probiotics and a synbiotic. In-vitro growth inhibition of Escherichia (E.) coli EPEC, Shigella (Sh.) sonnei, Salmonella (S.) typhimurium, Klebsiella (K.) pneumoniae and Clostridioides (C.) difficile were determined. Investigated products were a yeast mono strain probiotic containing Saccharomyces (Sac.) boulardii, bacterial mono strain probiotics containing either Lactobacillus (L.) rhamnosus GG or L. reuteri DSM 17938, a multi strain probiotic containing three L. rhamnosus strains (E/N, Oxy, Pen), and a multi strain synbiotic containing nine different probiotic bacterial strains and the prebiotic fructooligosaccharides (FOS). Inhibition of pathogens was moderate by Sac. boulardii and L. rhamnosus GG, medium by L. reuteri DSM 17938 and the L. rhamnosus E/N, Oxy, Pen mixture and strong by the multi strain synbiotic. Head-to-head in-vitro pathogen growth inhibition experiments can be used to differentiate products from different categories containing probiotic microorganisms and can support the selection process of products for further clinical evaluation.
A Long-Term Trend Study of Tuberculosis Incidence in China, India and United States 1992–2017: A Joinpoint and Age–Period–Cohort Analysis
Authors: Cui Yiran , Shen Hui , Wang Fang , Wen Haoyu , Zeng Zixin , Wang Yafeng , Yu Chuanhua
Published: May 2020

Tuberculosis (TB) is one of the major infectious diseases with the largest number of morbidity and mortality. Based on the comparison of high and low burden countries of tuberculosis in China, India and the United States, the influence of age-period-cohort on the incidence of tuberculosis in three countries from 1992 to 2017 was studied based on the Global burden of Disease Study 2017. We studied the trends using Joinpoint regression in the age-standardized incidence rate (ASIR). The regression model showed a significant decreasing behavior in China, India and the United States between 1992 and 2017. Here, we analyzed the tuberculosis incidence trends in China, India, as well as the United States and distinguished age, period and cohort effects by using age-period-cohort (APC) model. We found that the relative risks (RRs) of tuberculosis in China and India have similar trends, but the United States was found different. The period effect showed that the incidence of the three countries as a whole declines with time. The incidence of tuberculosis had increased in most age group. The older the age, the higher the risk of TB incidence. The net age effect in China and India showed a negative trend, while the cohort effect decreased from the earlier birth cohort to the recent birth cohort. Aging may lead to a continuous increase in the incidence of tuberculosis. It is related to the aging of the population and the relative decline of the immune function in the elderly. This should be timely population intervention or vaccine measures, especially for the elderly. The net cohort effect in the United States showed an unfavorable trend, mainly due to rising smoking rates and the emergence of an economic crisis. Reducing tobacco consumption can effectively reduce the incidence.
The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens
Authors: Rodriguez-Barbosa Jose-Ignacio , Schneider Pascal , Graca Luis , Bühler Leo , Perez-Simon Jose-Antonio , del Rio Maria-Luisa
Published: May 2020

Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis factor receptor (TNFR) superfamily members, in particular TNFR2 and DR3, contribute to promote peripheral Tregs expansion and sustain their survival. This property can be leveraged to enhance tolerance to allogeneic transplants by tipping the balance of Tregs over conventional T cells during the course of immune reconstitution. This is of particular interest in peri-transplant tolerance induction protocols in which T cell depletion is applied to reduce the frequency of alloreactive T cells or in conditioning regimens that allow allogeneic bone marrow transplantation. These conditioning regimens are being implemented to limit long-term side effects of continuous immunosuppression and facilitate the establishment of a state of donor-specific tolerance. Lymphopenia-induced homeostatic proliferation in response to cytoreductive conditioning is a window of opportunity to enhance preferential expansion of Tregs during homeostatic proliferation that can be potentiated by agonist stimulation of TNFR.
Endoplasmic Reticulum Calcium Pumps and Tumor Cell Differentiation
Authors: Papp Bela , Launay Sophie , Gélébart Pascal , Arbabian Atousa , Enyedi Agnes , Brouland Jean-Philippe , Carosella Edgardo D. , Adle-Biassette Homa
Published: May 2020

Endoplasmic reticulum (ER) calcium homeostasis plays an essential role in cellular calcium signaling, intra-ER protein chaperoning and maturation, as well as in the interaction of the ER with other organelles. Calcium is accumulated in the ER by sarco/endoplasmic reticulum calcium ATPases (SERCA enzymes) that generate by active, ATP-dependent transport, a several thousand-fold calcium ion concentration gradient between the cytosol (low nanomolar) and the ER lumen (high micromolar). SERCA enzymes are coded by three genes that by alternative splicing give rise to several isoforms, which can display isoform-specific calcium transport characteristics. SERCA expression levels and isoenzyme composition vary according to cell type, and this constitutes a mechanism whereby ER calcium homeostasis is adapted to the signaling and metabolic needs of the cell, depending on its phenotype, its state of activation and differentiation. As reviewed here, in several normal epithelial cell types including bronchial, mammary, gastric, colonic and choroid plexus epithelium, as well as in mature cells of hematopoietic origin such as pumps are simultaneously expressed, whereas in corresponding tumors and leukemias SERCA3 expression is selectively down-regulated. SERCA3 expression is restored during the pharmacologically induced differentiation of various cancer and leukemia cell types. SERCA3 is a useful marker for the study of cell differentiation, and the loss of SERCA3 expression constitutes a previously unrecognized example of the remodeling of calcium homeostasis in tumors.
Synthesis and Therapeutic Applications of Iminosugars in Cystic Fibrosis
Authors: Esposito Anna , D’Alonzo Daniele , De Fenza Maria , De Gregorio Eliana , Tamanini Anna , Lippi Giuseppe , Dechecchi Maria Cristina , Guaragna Annalisa
Published: May 2020

Iminosugars are sugar analogues endowed with a high pharmacological potential. The wide range of biological activities exhibited by these glycomimetics associated with their excellent drug profile make them attractive therapeutic candidates for several medical interventions. The ability of iminosugars to act as inhibitors or enhancers of carbohydrate-processing enzymes suggests their potential use as therapeutics for the treatment of cystic fibrosis (CF). Herein we review the most relevant advances in the field, paying attention to both the chemical synthesis of the iminosugars and their biological evaluations, resulting from in vitro and in vivo assays. Starting from the example of the marketed drug NBDNJ (N-butyl deoxynojirimycin), a variety of iminosugars have exhibited the capacity to rescue the trafficking of F508del-CFTR (deletion of F508 residue in the CF transmembrane conductance regulator), either alone or in combination with other correctors. Interesting results have also been obtained when iminosugars were considered as anti-inflammatory agents in CF lung disease. The data herein reported demonstrate that iminosugars hold considerable potential to be applied for both therapeutic purposes.
Therapeutic Targeting of the General RNA Polymerase II Transcription Machinery
Authors: Martin Ryan D. , Hébert Terence E. , Tanny Jason C.
Published: May 2020

Inhibitors targeting the general RNA polymerase II (RNAPII) transcription machinery are candidate therapeutics in cancer and other complex diseases. Here, we review the molecular targets and mechanisms of action of these compounds, framing them within the steps of RNAPII transcription. We discuss the effects of transcription inhibitors in vitro and in cellular models (with an emphasis on cancer), as well as their efficacy in preclinical and clinical studies. We also discuss the rationale for inhibiting broadly acting transcriptional regulators or RNAPII itself in complex diseases.
Free Fatty Acid-Induced Peptide YY Expression Is Dependent on TG Synthesis Rate and Xbp1 Splicing
Authors: Paton Chad M. , Son Yura , Vaughan Roger A. , Cooper Jamie A.
Published: May 2020

Gut-derived satiety hormones provide negative feedback to suppress food intake and maintain metabolic function in peripheral tissues. Despite the wealth of knowledge of the systemic effects of these hormones, very little is known concerning the mechanisms by which nutrients, such as dietary fats, can promote the expression of genes involved in L-cell hormone production. We have tested the role of various dietary fats and found that after hydrolysis into free fatty acids (FFA’s), there is a differential response in the extent to which they induce PYY gene and protein production. The effect of FFA’s also seems to relate to triglyceride (TG) re-esterification rate, with MUFA re-esterifying faster with lower PYY production. We have also found that there are differences in potency of FFA’s based on their desaturation patterns in vitro. The potency effect of FFA’s is influenced by the rate of TG re-esterification, such that the longer FFA’s are in contact with L-cells, the more PYY they produce. We found that chronic consumption of high-fat diets enables the small intestine to re-esterify FFA’s into TG faster and earlier which resulted in a blunted postprandial PYY response. Lastly, we found that FFA’s induce X-box-binding protein-1 activation (Xbp1s) in L-cells and that adenoviral delivery of Xbp1s was sufficient to induce PYY gene expression. Taken together, the present work indicates that dietary fat can induce satiety, in part, prior to re-esterification. Chronic high-fat diet consumption increases the rate of re-esterification which diminishes satiety and may lead to increased food intake. Targeting intestinal TG synthesis may prove beneficial in restoring obesity-associated reductions in postprandial satiety.
Autophagy in Neurodegenerative Diseases: A Hunter for Aggregates
Authors: Park Hyungsun , Kang Ju-Hee , Lee Seongju
Published: May 2020

Cells have developed elaborate quality-control mechanisms for proteins and organelles to maintain cellular homeostasis. Such quality-control mechanisms are maintained by conformational folding via molecular chaperones and by degradation through the ubiquitin-proteasome or autophagy-lysosome system. Accumulating evidence suggests that impaired autophagy contributes to the accumulation of intracellular inclusion bodies consisting of misfolded proteins, which is a hallmark of most neurodegenerative diseases. In addition, genetic mutations in core autophagy-related genes have been reported to be linked to neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Conversely, the pathogenic proteins, such as amyloid β and α-synuclein, are detrimental to the autophagy pathway. Here, we review the recent advances in understanding the relationship between autophagic defects and the pathogenesis of neurodegenerative diseases and suggest autophagy induction as a promising strategy for the treatment of these conditions.
Actin Mutations and Their Role in Disease
Authors: Parker Francine , Baboolal Thomas G. , Peckham Michelle
Published: May 2020

Actin is a widely expressed protein found in almost all eukaryotic cells. In humans, there are six different genes, which encode specific actin isoforms. Disease-causing mutations have been described for each of these, most of which are missense. Analysis of the position of the resulting mutated residues in the protein reveals mutational hotspots. Many of these occur in regions important for actin polymerization. We briefly discuss the challenges in characterizing the effects of these actin mutations, with a focus on cardiac actin mutations.
The Conserved Effector UvHrip1 Interacts with OsHGW and Infection of Ustilaginoidea virens Regulates Defense- and Heading Date-Related Signaling Pathway
Authors: Wei Songhong , Wang Yingling , Zhou Jianming , Xiang Shibo , Sun Wenxian , Peng Xunwen , Li Jing , Hai Yingfan , Wang Yan , Li Shuai
Published: May 2020

Ustilaginoidea virens, which causes rice false smut (RFS), is one of the most detrimental rice fungal diseases and poses a severe threat to rice production and quality. Effectors in U. virens often act as a group of essential virulence factors that play crucial roles in the interaction between host and the pathogen. Thus, the functions of individual effectors in U. virens need to be further explored. Here, we demonstrated a small secreted hypersensitive response-inducing protein (hrip), named UvHrip1, which was highly conserved in U. virens isolates. UvHrip1 was also proven to suppress necrosis-like defense symptoms in N. benthamiana induced by the oomycete elicitor INF1. The localization of UvHrip1 was mainly in the nuclei and cytoplasm via monitoring the UvHrip1-GFP fusion protein in rice cells. Furthermore, Y2H and BiFC assay demonstrated that UvHrip1 interacted with OsHGW, which is a critical regulator in heading date and grain weight signaling pathways in rice. Expression patterns of defense- and heading date-related genes, OsPR1#051 and OsMYB21, were down-regulated over U. virens infection in rice. Collectively, our data provide a theory for gaining an insight into the molecular mechanisms underlying the UvHrip1 virulence function.
Probing Nanoelectroporation and Resealing of the Cell Membrane by the Entry of Ca2+ and Ba2+ Ions
Authors: Bo Wenfei , Silkunas Mantas , Mangalanathan Uma , Novickij Vitalij , Casciola Maura , Semenov Iurii , Xiao Shu , Pakhomova Olga N. , Pakhomov Andrei G.
Published: May 2020

The principal bioeffect of the nanosecond pulsed electric field (nsPEF) is a lasting cell membrane permeabilization, which is often attributed to the formation of nanometer-sized pores. Such pores may be too small for detection by the uptake of fluorescent dyes. We tested if Ca2+, Cd2+, Zn2+, and Ba2+ ions can be used as nanoporation markers. Time-lapse imaging was performed in CHO, BPAE, and HEK cells loaded with Fluo-4, Calbryte, or Fluo-8 dyes. Ca2+ and Ba2+ did not change fluorescence in intact cells, whereas their entry after nsPEF increased fluorescence within <1 ms. The threshold for one 300-ns pulse was at 1.5–2 kV/cm, much lower than >7 kV/cm for the formation of larger pores that admitted YO-PRO-1, TO-PRO-3, or propidium dye into the cells. Ba2+ entry caused a gradual emission rise, which reached a stable level in 2 min or, with more intense nsPEF, kept rising steadily for at least 30 min. Ca2+ entry could elicit calcium-induced calcium release (CICR) followed by Ca2+ removal from the cytosol, which markedly affected the time course, polarity, amplitude, and the dose-dependence of fluorescence change. Both Ca2+ and Ba2+ proved as sensitive nanoporation markers, with Ba2+ being more reliable for monitoring membrane damage and resealing.
The Bacterial Toxin CNF1 Protects Human Neuroblastoma SH-SY5Y Cells against 6-Hydroxydopamine-Induced Cell Damage: The Hypothesis of CNF1-Promoted Autophagy as an Antioxidant Strategy
Authors: Travaglione Sara , Loizzo Stefano , Vona Rosa , Ballan Giulia , Rivabene Roberto , Giordani Danila , Guidotti Marco , Dupuis Maria , Maroccia Zaira , Baiula Monica , Rimondini Roberto , Campana Gabriele , Fiorentini Carla
Published: May 2020

Several chronic neuroinflammatory diseases, including Parkinson’s disease (PD), have the so-called ‘redox imbalance’ in common, a dynamic system modulated by various factors. Among them, alteration of the mitochondrial functionality can cause overproduction of reactive oxygen species (ROS) with the consequent induction of oxidative DNA damage and apoptosis. Considering the failure of clinical trials with drugs that eliminate ROS directly, research currently focuses on approaches that counteract redox imbalance, thus restoring normal physiology in a neuroinflammatory condition. Herein, we used SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA), a neurotoxin broadly employed to generate experimental models of PD. Cells were pre-treated with the Rho-modulating Escherichia coli cytotoxic necrotizing factor 1 (CNF1), before the addition of 6-OHDA. Then, cell viability, mitochondrial morphology and dynamics, redox profile as well as autophagic markers expression were assessed. We found that CNF1 preserves cell viability and counteracts oxidative stress induced by 6-OHDA. These effects are accompanied by modulation of the mitochondrial network and an increase in macroautophagic markers. Our results confirm the Rho GTPases as suitable pharmacological targets to counteract neuroinflammatory diseases and evidence the potentiality of CNF1, whose beneficial effects on pathological animal models have been already proven to act against oxidative stress through an autophagic strategy.
Colorectal Cancer Invasion and Atrophy of the Enteric Nervous System: Potential Feedback and Impact on Cancer Progression
Authors: Godlewski Janusz , Kmiec Zbigniew
Published: May 2020

Colorectal cancer (CRC) invasion within the large intestine wall results in the replacement of normal tissue architecture by tumour mass. Cancer cells digest the extracellular matrix (ECM) by the release of proteolytic enzymes. The disintegration of matrix ground substance activates several deposited growth factors which stimulate cell proliferation. Stromal (mainly fibroblasts), immune and cancer cells dominate in this area and become involved in a network of multimodal interactions which significantly induce proliferation of colon cancer cells, inhibit their apoptosis and promote their spreading within the local tumour microenvironment. Cancer invasion destroys nerve fibres and neurons of the local enteric nervous system (ENS) and induces subsequent atrophy of the submucosal and myenteric plexuses in areas adjacent to the cancer boundary. Interestingly, the reduction of plexuses’ size is accompanied by the increased number of galanin-immunoreactive neurons and increased galanin content in parts of the colon located close to the tumour. Galanin, a neuroprotective peptide, may inhibit the extrinsic pathway of apoptosis and in this way promote cancer cell survival. The possible role of acetylcholine and some ENS neuropeptides was also discussed. Invasion of cancer cells spreads along nerve fibres with the involvement of locally-released neutrophins which promote, via their specific receptors, cancer cell proliferation and pro-survival signalling pathways. Thus, during CRC development cancer cells and neurons of the ENS release many neurotransmitters/neuropeptides which affect key cellular signalling pathways promoting cancer cell proliferation and pro-survival phenotype. The multiple interactions between ENS neurons, cancer cells and other cell types present in the colon wall increase cancer cell invasiveness and have a negative impact on the course of CRC.
Disease-Specific Derangement of Circulating Endocannabinoids and N-Acylethanolamines in Myeloproliferative Neoplasms
Authors: Forte Dorian , Fanelli Flaminia , Mezzullo Marco , Barone Martina , Corradi Giulia , Auteri Giuseppe , Bartoletti Daniela , Martello Marina , Ottaviani Emanuela , Terragna Carolina , Curti Antonio , Pagotto Uberto , Palandri Francesca , Cavo Michele , Catani Lucia
Published: May 2020

Growing evidence highlights the endocannabinoid (EC) system involvement in cancer progression. Lipid mediators of this system are secreted by hematopoietic cells, including the ECs 2-arachidonoyl-glycerol (2AG) and arachidonoyl-ethanolamide (AEA), the 2AG metabolite 1AG, and members of N-acylethanolamine (NAE) family—palmitoyl-ethanolamide (PEA) and oleoyl-ethanolamide (OEA). However, the relevance of the EC system in myeloproliferative neoplasms (MPN) was never investigated. We explored the EC plasma profile in 55 MPN patients, including myelofibrosis (MF; n = 41), polycythemia vera (PV; n = 9), and essential thrombocythemia (ET; n = 5) subclasses and in 10 healthy controls (HC). AEA, PEA, OEA, 2AG, and 1AG plasma levels were measured by LC–MS/MS. Overall considered, MPN patients displayed similar EC and NAE levels compared to HC. Nonetheless, AEA levels in MPN were directly associated with the platelet count. MF patients showed higher levels of the sum of 2AG and 1AG compared to ET and PV patients, higher OEA/AEA ratios compared to HC and ET patients, and higher OEA/PEA ratios compared to HC. Furthermore, the sum of 2AG and 1AG positively correlated with JAK2V617F variant allele frequency and splenomegaly in MF and was elevated in high-risk PV patients compared to in low-risk PV patients. In conclusion, our work revealed specific alterations of ECs and NAE plasma profile in MPN subclasses and potentially relevant associations with disease severity.
NMR Investigations of Crystalline and Glassy Solid Electrolytes for Lithium Batteries: A Brief Review
Authors: Morales Daniel J , Greenbaum Steven
Published: May 2020

The widespread use of energy storage for commercial products and services have led to great advancements in the field of lithium-based battery research. In particular, solid state lithium batteries show great promise for future commercial use, as solid electrolytes safely allow for the use of lithium-metal anodes, which can significantly increase the total energy density. Of the solid electrolytes, inorganic glass-ceramics and Li-based garnet electrolytes have received much attention in the past few years due to the high ionic conductivity achieved compared to polymer-based electrolytes. This review covers recent work on novel glassy and crystalline electrolyte materials, with a particular focus on the use of solid-state nuclear magnetic resonance spectroscopy for structural characterization and transport measurements.
Selecting a Secure Cloud Provider—An Empirical Study and Multi Criteria Approach
Authors: Pape Sebastian , Paci Federica , Jürjens Jan , Massacci Fabio
Published: May 2020

Security has become one of the primary factors that cloud customers consider when they select a cloud provider for migrating their data and applications into the Cloud. To this end, the Cloud Security Alliance (CSA) has provided the Consensus Assessment Questionnaire (CAIQ), which consists of a set of questions that providers should answer to document which security controls their cloud offerings support. In this paper, we adopted an empirical approach to investigate whether the CAIQ facilitates the comparison and ranking of the security offered by competitive cloud providers. We conducted an empirical study to investigate if comparing and ranking the security posture of a cloud provider based on CAIQ’s answers is feasible in practice. Since the study revealed that manually comparing and ranking cloud providers based on the CAIQ is too time-consuming, we designed an approach that semi-automates the selection of cloud providers based on CAIQ. The approach uses the providers’ answers to the CAIQ to assign a value to the different security capabilities of cloud providers. Tenants have to prioritize their security requirements. With that input, our approach uses an Analytical Hierarchy Process (AHP) to rank the providers’ security based on their capabilities and the tenants’ requirements. Our implementation shows that this approach is computationally feasible and once the providers’ answers to the CAIQ are assessed, they can be used for multiple CSP selections. To the best of our knowledge this is the first approach for cloud provider selection that provides a way to assess the security posture of a cloud provider in practice.
Morphological and Molecular Characterization of Lema bilineata (Germar), a New Alien Invasive Leaf Beetle for Europe, with Notes on the Related Species Lema daturaphila Kogan & Goeden
Authors: Monti Maurilia M. , Ruocco Michelina , Grobbelaar Elizabeth , Pedata Paolo A.
Published: May 2020

Lema bilineata (Germar) is an alien invasive leaf beetle (Coleoptera: Chrysomelidae) first recorded in Europe in the summer of 2017 in the province of Naples (Campania, Italy). It occurs on both cultivated plants (Nicotiana tabacum) and weeds (Salpichroa origanifolia and Datura spp.). Information on morphological characters, color variation and molecular data are deficient for L. bilineata, as is the case for most Lema species. These data could be useful to discriminate between this species and the closely related Lema daturaphila Kogan & Goeden, which has the same potential to become an alien invasive species. In this paper, color variation in adults and the morphology of the aedeagi and spermathecae of the two species are documented and compared, including micrographic images. Additional data on the current distribution of L. bilineata in Campania is also provided. The cytochrome c oxidase I (COI) barcoding region of both Italian and South African specimens of L. bilineata, as well as South African specimens of L. daturaphila, was sequenced. A preliminary phylogenetic tree is provided, based on the sequences available for Lema species.
A Randomized Comparison of Plasma Levobupivacaine Concentrations Following Thoracic Epidural Analgesia and Subpleural Paravertebral Analgesia in Open Thoracic Surgery
Authors: Matek Jan , Cernohorsky Stanislav , Trca Stanislav , Krska Zdenek , Hoskovec David , Bruthans Jan , Sima Martin , Michalek Pavel
Published: May 2020

Background: The aim of this study was to compare plasma levobupivacaine concentrations in thoracic epidural and subpleural paravertebral analgesia. Methods: Forty-four patients indicated for open lung resection had an epidural catheter inserted preoperatively or a subpleural catheter surgically. A bolus of 0.25% levobupivacaine at a dosage of 0.5 mg × kg−1 was given after the thoracotomy closure. Plasma levobupivacaine level at 30 min was the primary outcome. Pharmacokinetic modeling was performed subsequently. Secondary outcomes included the quality of analgesia, complications, and patients’mobility. Results: Plasma concentrations were similar 30 min after application—0.389 mg × L−1 in the epidural and 0.318 mg × L−1 in the subpleural group (p = 0.33) and lower in the subpleural group at 120 min (p = 0.03). The areas under the curve but not maximum concentrations were lower in the subpleural group. The time to reach maximum plasma level was similar in both groups—27.6 vs. 24.2 min. No clinical symptoms of local anesthetic toxicity were recorded. Conclusions: Levobupivacaine systemic concentrations were low in both groups without the symptoms of toxicity. This dosage should be safe for postoperative analgesia after thoracotomy.
Impact of Glomerular Filtration Rate on the Incidence and Prognosis of New-Onset Atrial Fibrillation in Acute Myocardial Infarction
Authors: Cosentino Nicola , Ballarotto Marco , Campodonico Jeness , Milazzo Valentina , Bonomi Alice , Genovesi Simonetta , Moltrasio Marco , De Metrio Monica , Rubino Mara , Veglia Fabrizio , Assanelli Emilio , Marana Ivana , Grazi Marco , Lauri Gianfranco , Bartorelli Antonio L. , Marenzi Giancarlo
Published: May 2020

Background: Atrial fibrillation (AF) is a frequent complication of acute myocardial infarction (AMI) and is associated with a worse prognosis. Patients with chronic kidney disease are more likely to develop AF. Whether the association between AF and glomerular filtration rate (GFR) is also true in AMI has never been investigated. Methods: We prospectively enrolled 2445 AMI patients. New-onset AF was recorded during hospitalization. Estimated GFR was estimated at admission, and patients were grouped according to their GFR (group 1 (n = 1887): GFR >60; group 2 (n = 492): GFR 60–30; group 3 (n = 66): GFR <30 mL/min/1.73 m2). The primary endpoint was AF incidence. In-hospital and long-term (median 5 years) mortality were secondary endpoints. Results: The AF incidence in the population was 10%, and it was 8%, 16%, 24% in groups 1, 2, 3, respectively (p < 0.0001). In the overall population, AF was associated with a higher in-hospital (5% vs. 1%; p < 0.0001) and long-term (34% vs. 13%; p < 0.0001) mortality. In each study group, in-hospital mortality was higher in AF patients (3.5% vs. 0.5%, 6.5% vs. 3.0%, 19% vs. 8%, respectively; p < 0.0001). A similar trend was observed for long-term mortality in three groups (20% vs. 9%, 51% vs. 24%, 81% vs. 50%; p < 0.0001). The higher risk of in-hospital and long-term mortality associated with AF in each group was confirmed after adjustment for major confounders. Conclusions: This study demonstrates that new-onset AF incidence during AMI, as well as the associated in-hospital and long-term mortality, increases in parallel with GFR reduction assessed at admission.