bluuebunny/crossref_metadata_2025 huggingface dataset:
Coffee Extends Yeast Chronological Lifespan through Antioxidant Properties
Authors: Czachor Jadwiga , Miłek Michał , Galiniak Sabina , Stępień Karolina , Dżugan Małgorzata , Mołoń Mateusz
Published: December 2020

Aging is a multifactorial process accompanied by loss of cell function. Science has been looking for factors responsible for aging for many years. However, despite identifying a number of possible causes, the definite reason for aging has been elusive so far. One of the factors contributing to aging is oxygen free radicals. In this context, beneficial effects of coffee on various organisms, including humans, were investigated, although the results are far from unequivocal. In our research, we used the budding yeast—something of a workhorse in many studies, including the studies of aging. So far, the impact of coffee on the aging of cells in the budding yeast experimental setup has little known about it. Here, we provide strong evidence that coffee compounds, particularly flavonoids, are responsible for scavenging free radicals and longevity in yeast lacking Sod1, Sod2 and Rad52 proteins. In this paper, we compared Arabica and Robusta coffee types. We present an analysis of the concentration of caffeine and flavonoids measured by the High-Performance Liquid Chromatography method. We show that Robusta has a much greater antioxidant capacity than Arabica. We also conclude that coffee infusions significantly extend the chronological lifespan of the Saccharomyces cerevisiae yeast cells by protecting cells against reactive oxygen species, double DNA-strand break and decrease in metabolic activity.
Transcriptional Regulation of Protein Phosphatase 2C Genes to Modulate Abscisic Acid Signaling
Authors: Jung Choonkyun , Nguyen Nguyen Hoai , Cheong Jong-Joo
Published: December 2020

The plant hormone abscisic acid (ABA) triggers cellular tolerance responses to osmotic stress caused by drought and salinity. ABA controls the turgor pressure of guard cells in the plant epidermis, leading to stomatal closure to minimize water loss. However, stomatal apertures open to uptake CO2 for photosynthesis even under stress conditions. ABA modulates its signaling pathway via negative feedback regulation to maintain plant homeostasis. In the nuclei of guard cells, the clade A type 2C protein phosphatases (PP2Cs) counteract SnRK2 kinases by physical interaction, and thereby inhibit activation of the transcription factors that mediate ABA-responsive gene expression. Under osmotic stress conditions, PP2Cs bind to soluble ABA receptors to capture ABA and release active SnRK2s. Thus, PP2Cs function as a switch at the center of the ABA signaling network. ABA induces the expression of genes encoding repressors or activators of PP2C gene transcription. These regulators mediate the conversion of PP2C chromatins from a repressive to an active state for gene transcription. The stress-induced chromatin remodeling states of ABA-responsive genes could be memorized and transmitted to plant progeny; i.e., transgenerational epigenetic inheritance. This review focuses on the mechanism by which PP2C gene transcription modulates ABA signaling.
Investigation on the Interactions between Self-Assembled β-Sheet Peptide Nanofibers and Model Cell Membranes
Authors: Waku Tomonori , Kasai Ayane , Kobori Akio , Tanaka Naoki
Published: December 2020

Self-assembled peptide nanofibers (NFs) obtained from β-sheet peptides conjugated with drugs, including antigenic peptides, have recently attracted significant attention. However, extensive studies on the interactions of β-sheet peptide NFs with model cell membranes have not been reported. In this study, we investigated the interactions between three types of NFs, composed of PEG-peptide conjugates with different ethylene glycol (EG) lengths (6-, 12- and 24-mer), and dipalmitoylphosphatidylcholine (DPPC) Langmuir membranes. When increasing the EG chain length, those interactions significantly decreased considering measurements in the presence of the NFs of: (i) changes in surface pressure of the DPPC Langmuir monolayers and (ii) surface pressure–area (π–A) compression isotherms of DPPC. Because the observed trend was similar to the EG length dependency with regard to cellular association and cytotoxicity of the NFs that was reported previously, the interaction of NFs with phospholipid membranes represented a crucial factor to determine the cellular association and toxicity of the NFs. In contrast to NFs, no changes were observed with varying EG chain length on the interaction of the building block peptide with the DPPC membrane. The results obtained herein can provide a design guideline on the formulation of β-sheet peptide NFs, which may broaden its potential.
Molecular Dysfunctions of Mitochondria-Associated Membranes (MAMs) in Alzheimer’s Disease
Authors: Eysert Fanny , Kinoshita Paula Fernanda , Mary Arnaud , Vaillant-Beuchot Loan , Checler Frédéric , Chami Mounia
Published: December 2020

Alzheimer’s disease (AD) is a multifactorial neurodegenerative pathology characterized by a progressive decline of cognitive functions. Alteration of various signaling cascades affecting distinct subcellular compartment functions and their communication likely contribute to AD progression. Among others, the alteration of the physical association between the endoplasmic reticulum (ER) and mitochondria, also referred as mitochondria-associated membranes (MAMs), impacts various cellular housekeeping functions such as phospholipids-, glucose-, cholesterol-, and fatty-acid-metabolism, as well as calcium signaling, which are all altered in AD. Our review describes the physical and functional proteome crosstalk between the ER and mitochondria and highlights the contribution of distinct molecular components of MAMs to mitochondrial and ER dysfunctions in AD progression. We also discuss potential strategies targeting MAMs to improve mitochondria and ER functions in AD.
Identification of Host Cellular Protein Substrates of SARS-COV-2 Main Protease
Authors: Miczi Márió , Golda Mária , Kunkli Balázs , Nagy Tibor , Tőzsér József , Mótyán János András
Published: December 2020

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19) being associated with severe pneumonia. Like with other viruses, the interaction of SARS-CoV-2 with host cell proteins is necessary for successful replication, and cleavage of cellular targets by the viral protease also may contribute to the pathogenesis, but knowledge about the human proteins that are processed by the main protease (3CLpro) of SARS-CoV-2 is still limited. We tested the prediction potentials of two different in silico methods for the identification of SARS-CoV-2 3CLpro cleavage sites in human proteins. Short stretches of homologous host-pathogen protein sequences (SSHHPS) that are present in SARS-CoV-2 polyprotein and human proteins were identified using BLAST analysis, and the NetCorona 1.0 webserver was used to successfully predict cleavage sites, although this method was primarily developed for SARS-CoV. Human C-terminal-binding protein 1 (CTBP1) was found to be cleaved in vitro by SARS-CoV-2 3CLpro, the existence of the cleavage site was proved experimentally by using a His6-MBP-mEYFP recombinant substrate containing the predicted target sequence. Our results highlight both potentials and limitations of the tested algorithms. The identification of candidate host substrates of 3CLpro may help better develop an understanding of the molecular mechanisms behind the replication and pathogenesis of SARS-CoV-2.
Identification of In Vitro Metabolites of Synthetic Phenolic Antioxidants BHT, BHA, and TBHQ by LC-HRMS/MS
Authors: Ousji Ons , Sleno Lekha
Published: December 2020

Butylated hydroxytoluene (BHT) and its analogs, butylated hydroxyanisole (BHA) and tert-butyl-hydroquinone (TBHQ), are widely used synthetic preservatives to inhibit lipid oxidation in the food, cosmetic and pharmaceutical industries. Despite their widespread use, little is known about their human exposure and related biotransformation products. The metabolism of these compounds was investigated using in vitro incubations with human and rat liver fractions. Liquid chromatography coupled to high-resolution tandem mass spectrometry was employed to detect and characterize stable and reactive species formed via oxidative metabolism, as well as phase II conjugates. Several oxidative metabolites have been detected, as well as glutathione, glucuronide, and sulfate conjugates, many of which were not previously reported. A combination of accurate mass measurements, MS/MS fragmentation behavior, and isotope-labeling studies were used to elucidate metabolite structures.
Identification, Phylogeny, and Comparative Expression of the Lipoxygenase Gene Family of the Aquatic Duckweed, Spirodela polyrhiza, during Growth and in Response to Methyl Jasmonate and Salt
Authors: Upadhyay Rakesh K. , Edelman Marvin , Mattoo Autar K.
Published: December 2020

Lipoxygenases (LOXs) (EC 1.13.11.12) catalyze the oxygenation of fatty acids and produce oxylipins, including the plant hormone jasmonic acid (JA) and its methyl ester, methyl jasmonate (MeJA). Little information is available about the LOX gene family in aquatic plants. We identified a novel LOX gene family comprising nine LOX genes in the aquatic plant Spirodela polyrhiza (greater duckweed). The reduced anatomy of S. polyrhiza did not lead to a reduction in LOX family genes. The 13-LOX subfamily, with seven genes, predominates, while the 9-LOX subfamily is reduced to two genes, an opposite trend from known LOX families of other plant species. As the 13-LOX subfamily is associated with the synthesis of JA/MeJA, its predominance in the Spirodela genome raises the possibility of a higher requirement for the hormone in the aquatic plant. JA-/MeJA-based feedback regulation during culture aging as well as the induction of LOX gene family members within 6 h of salt exposure are demonstrated.
Overexpression of the Auxin Receptor AFB3 in Arabidopsis Results in Salt Stress Resistance and the Modulation of NAC4 and SZF1
Authors: Garrido-Vargas Fernanda , Godoy Tamara , Tejos Ricardo , O’Brien José Antonio
Published: December 2020

Soil salinity is a key problem for crop production worldwide. High salt concentration in soil negatively modulates plant growth and development. In roots, salinity affects the growth and development of both primary and lateral roots. The phytohormone auxin regulates various developmental processes during the plant’s life cycle, including several aspects of root architecture. Auxin signaling involves the perception by specialized receptors which module several regulatory pathways. Despite their redundancy, previous studies have shown that their functions can also be context-specific depending on tissue, developmental or environmental cues. Here we show that the over-expression of Auxin Signaling F-Box 3 receptor results in an increased resistance to salinity in terms of root architecture and germination. We also studied possible downstream signaling components to further characterize the role of auxin in response to salt stress. We identify the transcription factor SZF1 as a key component in auxin-dependent salt stress response through the regulation of NAC4. These results give lights of an auxin-dependent mechanism that leads to the modulation of root system architecture in response to salt identifying a hormonal cascade important for stress response.
A Facile Strategy for Immobilizing GOD and HRP onto Pollen Grain and Its Application to Visual Detection of Glucose
Authors: Jin Shanxia , Liu Liping , Fan Mengying , Jia Yaru , Zhou Ping
Published: December 2020

Pollen grain was explored as a new carrier for enzyme immobilization. After being modified with boric acid-functionalized titania, the pollen grain was able to covalently immobilize glycosylated enzymes by boronate affinity interaction under very mild experimental conditions (e.g., pH 7.0, ambient temperature and free of organic solvent). The glucose oxidase and horse radish peroxidase-immobilized pollen grain became a bienzyme system. The pollen grain also worked as an indicator of the cascade reaction by changing its color. A rapid, simple and cost-effective approach for the visual detection of glucose was then developed. When the glucose concentration exceeded 0.5 mM, the color change was observable by the naked eye. The assay of glucose in body fluid samples exhibited its great potential for practical application.
Role and Regulation of Mechanotransductive HIF-1α Stabilisation in Periodontal Ligament Fibroblasts
Authors: Kirschneck Christian , Thuy Magdalena , Leikam Alexandra , Memmert Svenja , Deschner James , Damanaki Anna , Spanier Gerrit , Proff Peter , Jantsch Jonathan , Schröder Agnes
Published: December 2020

Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1α (HIF-1α) has been shown to be primarily stabilised by compression, but not hypoxia in periodontal ligament fibroblasts (PDLF) during mechanical strain, which are key regulators of OTM. This study aimed to elucidate the role of heparan sulfate integrin interaction and downstream kinase phosphorylation for HIF-1α stabilisation under compressive and tensile strain and to which extent downstream synthesis of VEGF and prostaglandins is HIF-1α-dependent in a model of simulated OTM in PDLF. PDLF were subjected to compressive or tensile strain for 48 h. In various setups HIF-1α was experimentally stabilised (DMOG) or destabilised (YC-1) and mechanotransduction was inhibited by surfen and genistein. We found that HIF-1α was not stabilised by tensile, but rather by compressive strain. HIF-1α stabilisation had an inductive effect on prostaglandin and VEGF synthesis. As expected, HIF-1α destabilisation reduced VEGF expression, whereas prostaglandin synthesis was increased. Inhibition of integrin mechanotransduction via surfen or genistein prevented stabilisation of HIF-1α. A decrease in VEGF expression was observed, but not in prostaglandin synthesis. Stabilisation of HIF-1α via integrin mechanotransduction and downstream phosphorylation of kinases seems to be essential for the induction of VEGF, but not prostaglandin synthesis by PDLF during compressive (but not tensile) orthodontic strain.
CD37 in B Cell Derived Tumors—More than Just a Docking Point for Monoclonal Antibodies
Authors: Bobrowicz Malgorzata , Kubacz Matylda , Slusarczyk Aleksander , Winiarska Magdalena
Published: December 2020

CD37 is a tetraspanin expressed prominently on the surface of B cells. It is an attractive molecular target exploited in the immunotherapy of B cell-derived lymphomas and leukemia. Currently, several monoclonal antibodies targeting CD37 as well as chimeric antigen receptor-based immunotherapies are being developed and investigated in clinical trials. Given the unique role of CD37 in the biology of B cells, it seems that CD37 constitutes more than a docking point for monoclonal antibodies, and targeting this molecule may provide additional benefit to relapsed or refractory patients. In this review, we aimed to provide an extensive overview of the function of CD37 in B cell malignancies, providing a comprehensive view of recent therapeutic advances targeting CD37 and delineating future perspectives.
p53 Is Regulated in a Biphasic Manner in Hypoxic Human Papillomavirus Type 16 (HPV16)-Positive Cervical Cancer Cells
Authors: Zhuang Linhan , Ly Regina , Rösl Frank , Niebler Martina
Published: December 2020

Although the effect of hypoxia on p53 in human papillomavirus (HPV)-positive cancer cells has been studied for decades, the impact of p53 regulation on downstream targets and cellular adaptation processes during different periods under hypoxia remains elusive. Here, we show that, despite continuous repression of HPV16 E6/E7 oncogenes, p53 did not instantly recover but instead showed a biphasic regulation marked by further depletion within 24 h followed by an increase at 72 h. Of note, during E6/E7 oncogene suppression, lysosomal degradation antagonizes p53 reconstitution. Consequently, the transcription of p53 responsive genes associated with senescence (e.g., PML and YPEL3) cannot be upregulated. In contrast, downstream genes involved in autophagy (e.g., DRAM1 and BNIP3) were activated, allowing the evasion of senescence under hypoxic conditions. Hence, dynamic regulation of p53 along with its downstream network of responsive genes favors cellular adaptation and enhances cell survival, although the expression of the viral E6/E7-oncogenes as drivers for proliferation remained inhibited under hypoxia.
Novel Heme Oxygenase-1 (HO-1) Inducers Based on Dimethyl Fumarate Structure
Authors: Sorrenti Valeria , Vanella Luca , Platania Chiara Bianca Maria , Greish Khaled , Bucolo Claudio , Pittalà Valeria , Salerno Loredana
Published: December 2020

Novel heme oxygenase-1 (HO-1) inducers based on dimethyl fumarate (DMF) structure are reported in this paper. These compounds are obtained by modification of the DMF backbone. Particularly, maintaining the α, β-unsaturated dicarbonyl function as the central chain crucial for HO-1 induction, different substituted or unsubstituted phenyl rings are introduced by means of an ester or amide linkage. Symmetric and asymmetric derivatives are synthesized. All compounds are tested on a human hepatic stellate cell line LX-2 to assay their capacity for modifying HO-1 expression. Compounds 1b, 1l and 1m stand out for their potency as HO-1 inducers, being 2–3 fold more active than DMF, and for their ability to reverse reactive oxygen species (ROS) production mediated using palmitic acid (PA). These properties, coupled with a low toxicity toward LX-2 cell lines, make these compounds potentially useful for treatment of diseases in which HO-1 overexpression may counteract inflammation, such as hepatic fibrosis. Docking studies show a correlation between predicted binding free energy and experimental HO-1 expression data. These preliminary results may support the development of new approaches in the management of liver fibrosis.
Solid Lipid Curcumin Particles Protect Medium Spiny Neuronal Morphology, and Reduce Learning and Memory Deficits in the YAC128 Mouse Model of Huntington’s Disease
Authors: Gharaibeh Abeer , Maiti Panchanan , Culver Rebecca , Heileman Shiela , Srinageshwar Bhairavi , Story Darren , Spelde Kristin , Paladugu Leela , Munro Nikolas , Muhn Nathan , Kolli Nivya , Rossignol Julien , Dunbar Gary L.
Published: December 2020

Huntington’s disease (HD) is a genetic neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by massive neuronal degeneration in the striatum. In this study, we utilized solid lipid curcumin particles (SLCPs) and solid lipid particles (SLPs) to test their efficacy in reducing deficits in YAC128 HD mice. Eleven-month-old YAC128 male and female mice were treated orally with SLCPs (100 mg/kg) or equivalent volumes of SLPs or vehicle (phosphate-buffered saline) every other day for eight weeks. Learning and memory performance was assessed using an active-avoidance task on week eight. The mice were euthanized, and their brains were processed using Golgi-Cox staining to study the morphology of medium spiny neurons (MSNs) and Western blots to quantify amounts of DARPP-32, brain-derived neurotrophic factor (BDNF), TrkB, synaptophysin, and PSD-95. We found that both SLCPs and SLPs improved learning and memory in HD mice, as measured by the active avoidance task. We also found that SLCP and SLP treatments preserved MSNs arborization and spinal density and modulated synaptic proteins. Our study shows that SLCPs, as well as the lipid particles, can have therapeutic effects in old YAC128 HD mice in terms of recovering from HD brain pathology and cognitive deficits.
Spliceosome Mutations in Uveal Melanoma
Authors: Nguyen Josephine Q.N. , Drabarek Wojtek , Yavuzyigitoglu Serdar , Medico Salsench Eva , Verdijk Robert M. , Naus Nicole C. , de Klein Annelies , Kiliç Emine , Brosens Erwin
Published: December 2020

Uveal melanoma (UM) is the most common primary intraocular malignancy of the eye. It has a high metastatic potential and mainly spreads to the liver. Genetics play a vital role in tumor classification and prognostication of UM metastatic disease. One of the driver genes mutated in metastasized UM is subunit 1 of splicing factor 3b (SF3B1), a component of the spliceosome complex. Recurrent mutations in components of the spliceosome complex are observed in UM and other malignancies, suggesting an important role in tumorigenesis. SF3B1 is the most common mutated spliceosome gene and in UM it is associated with late-onset metastasis. This review summarizes the genetic and epigenetic insights of spliceosome mutations in UM. They form a distinct subgroup of UM and have similarities with other spliceosome mutated malignancies.
Predictive Risk Factors for Retinal Redetachment Following Uncomplicated Pars Plana Vitrectomy for Primary Rhegmatogenous Retinal Detachment
Authors: Guber Josef , Bentivoglio Maico , Valmaggia Christophe , Lang Corina , Guber Ivo
Published: December 2020

Purpose: To investigate clinical and surgical factors influencing the outcome after primary rhegmatogenous retinal detachment surgery. Methods: A retrospective, single-centre, case-control study of 1017 eyes of 1017 consecutive patients with primary rhegmatogenous retinal detachment (RRD) who underwent pars plana vitrectomy (PPV), were included in the study. Analysed surgical factors were: combined procedure with phacoemulsification, type of retinopexy (cryocoagulation, endolaser, combined), type of tamponade (gas, silicone oil), and anatomical factors: primary proliferative vitreoretinopathy (PVR) and macular detachment at the time of surgery. Results: Overall retinal re-detachment rate was 10.1%. The main reason for re-detachment was an insufficient retinopexy in 53.6%, followed by PVR (37.3%), and retinal detachment occurred at a different location caused by another break in 9.1%. No significant difference in the rate of re-detachment was found if a phacoemulsification with simultaneous IOL implantation was performed (p = 0.641). No significant difference between the various retinopexy techniques was found (p = 0.309). Risk factors re-detachment were primary PVR (p = 0.0003), silicone oil as initial tamponade (p = 0.0001) as well as macula off detachments (p = 0.034). Conclusions: The present study showed no significant difference between the types of retinopexy and if additional phacoemulsification was performed or not. Factors associated with a higher risk for re-detachment were detached macula at surgery, primary PVR and primary oil-filling.
Polymorphism of The Regulatory Region of the ITGAM Gene (-323G>A) as a Novel Predictor of a Poor Nutritional Status in Head and Neck Cancer Patients Subjected to Intensity-Modulated Radiation Therapy
Authors: Mazurek Marcin , Mlak Radosław , Homa-Mlak Iwona , Powrózek Tomasz , Brzozowska Anna , Gołębiowski Paweł , Małecka-Massalska Teresa
Published: December 2020

Background: The most serious disturbance of the nutritional status is neoplastic cachexia. The main factor contributing to the development of cachexia is the ongoing inflammatory process. The gene associated with the development of the inflammatory response is ITGAM. Therefore, the aim of the study was to assess the relationship between a single nucleotide polymorphism (SNP)-323G>A of the ITGAM gene and the occurrence of nutritional disorders in patients undergoing radiotherapy (RT) due to head and neck cancers (HNC). Methods: The study involved 71 patients with HNC treated with intensity-modulated radiotherapy (IMRT). SNP analysis of the ITGAM gene (-323G>A) was performed using commercial molecular probes and Real-Time PCR. Results: The presence of the A allele of the ITGAM gene significantly (over 14-fold) reduced the risk of severe disturbances in nutritional status assessed according to the subjective global assessment (SGA) scale (odds ratio (OR) = 0.07; p = 0.0213). The GG genotype of this gene was associated with an over three-fold higher risk of shortened overall survival (OR = 3.01; p = 0.0376). Conclusions: Determination of the SNP (-323G>A) of the ITGAM gene may prove to be a useful marker in the assessment of the risk of nutritional disorders in patients with HNC undergoing RT.
Cytokines and Their Genetic Polymorphisms Related to Periodontal Disease
Authors: Kozak Małgorzata , Dabrowska-Zamojcin Ewa , Mazurek-Mochol Małgorzata , Pawlik Andrzej
Published: December 2020

Periodontal disease (PD) is a chronic inflammatory disease caused by the accumulation of bacterial plaque biofilm on the teeth and the host immune responses. PD pathogenesis is complex and includes genetic, environmental, and autoimmune factors. Numerous studies have suggested that the connection of genetic and environmental factors induces the disease process leading to a response by both T cells and B cells and the increased synthesis of pro-inflammatory mediators such as cytokines. Many studies have shown that pro-inflammatory cytokines play a significant role in the pathogenesis of PD. The studies have also indicated that single nucleotide polymorphisms (SNPs) in cytokine genes may be associated with risk and severity of PD. In this narrative review, we discuss the role of selected cytokines and their gene polymorphisms in the pathogenesis of periodontal disease.
Prevalence of Neuropathic Pain and Related Characteristics in Hidradenitis Suppurativa: A Cross-Sectional Study
Authors: Garcovich Simone , Muratori Simona , Moltrasio Chiara , Buscemi Agata Alba , Giovanardi Giulia , Malvaso Dalma , Di Stasio Enrico , Marzano Angelo Valerio , Peris Ketty
Published: December 2020

Background: Pain is a core symptom of hidradenitis suppurativa (HS) and is of complex, multifactorial origin. HS patients frequently report typical neuropathic pain qualities, but its prevalence has been poorly described. Methods: In this cross-sectional study, we examine the prevalence of neuropathic pain (NP) component and related pain-characteristics of a hospital-based cohort of patients with symptomatic HS. We administered the pain-DETECT tool (PDQ), a validated screening tool for NP, collecting clinical and patient-reported data on pain, pruritus and pain-management. We obtained 110 complete datasets from symptomatic HS patients (49.1% females; Hurley I (27.3%])–II (45.5%)–III (27.3%)). According to the PDQ tool, 30% of patients were classified with a high probability (>90%) of neuropathic pain (LNP). LNP status was significantly associated with increased pain severity, disease activity, pruritus intensity and use of pain medication. Regression analysis showed a significant impact of the PDQ score on patient-reported outcomes, including pain severity and the dimensions of activity and affective pain interference. HS patients may present a mixed chronic pain phenotype with a neuropathic component, thus requiring additional pain-assessments. A multi-modal approach to pain management, in combination with disease-specific treatment, should be implemented in future interventional studies.
The Vicious Circle of Hepatic Glucagon Resistance in Non-Alcoholic Fatty Liver Disease
Authors: Galsgaard Katrine D.
Published: December 2020

A key criterion for the most common chronic liver disease—non-alcoholic fatty liver disease (NAFLD)—is an intrahepatic fat content above 5% in individuals who are not using steatogenic agents or having significant alcohol intake. Subjects with NAFLD have increased plasma concentrations of glucagon, and emerging evidence indicates that subjects with NAFLD may show hepatic glucagon resistance. For many years, glucagon has been thought of as the counterregulatory hormone to insulin with a primary function of increasing blood glucose concentrations and protecting against hypoglycemia. However, in recent years, glucagon has re-emerged as an important regulator of other metabolic processes including lipid and amino acid/protein metabolism. This review discusses the evidence that in NAFLD, hepatic glucagon resistance may result in a dysregulated lipid and amino acid/protein metabolism, leading to excess accumulation of fat, hyperglucagonemia, and increased oxidative stress contributing to the worsening/progression of NAFLD.
Efficacy of Combination Chemotherapy Using a Novel Oral Chemotherapeutic Agent, FTD/TPI, with Ramucirumab Murine Version DC101 in a Mouse Syngeneic Cancer Transplantation Model
Authors: Tsunekuni Kenta , Kawakami Hisato , Matsuoka Kazuaki , Nagase Hideki , Mitani Seiichiro , Nakagawa Kazuhiko
Published: December 2020

Trifluridine/tipiracil (FTD/TPI) (a.k.a. TAS-102) is a combination drug for metastatic colorectal cancer (CRC) and severely pretreated metastatic gastric/gastroesophageal junction (GEJ) cancers, comprising FTD, a thymidine-based antineoplastic nucleoside analog, and TPI, which enhances FTD bioavailability. Herein, in KRAS mutant murine colorectal cancer CT26 syngeneic models, we investigate whether combination therapy with DC101 (a surrogate ramucirumab antibody, rat antimouse vascular endothelial growth factor receptor (VEGFR)-2 monoclonal antibody (mAb)) improves FTD/TPI efficacy. Tumor growth inhibition (TGI) on day 15 was 38.0% and 30.6% upon DC101 monotherapy and FTD/TPI monotherapy respectively, and 60.3% upon combination therapy. Tumor volume was significantly lower (p < 0.001) upon combination treatment than upon FTD/TPI or DC101 monotherapy, indicating the additive effects of FTD/TPI and DC101. DNA-incorporated FTD levels on Day 8 were significantly higher in combination therapy with FTD/TPI (for 5 consecutive days) and DC101 (on alternate days for 7days) than in FTD/TPI monotherapy. Furthermore, vascular endothelial cell-specific marker CD31 was downregulated in DC101-treated tumors on day 8. These results indicate that combination therapy with FTD/TPI and DC101 is a promising treatment alternative regardless of KRAS mutations.
Revealing the Role of Divergent Thinking and Fluid Intelligence in Children’s Semantic Memory Organization
Authors: Rastelli Clara , Greco Antonino , Finocchiaro Chiara
Published: December 2020

The current theories suggest the fundamental role of semantic memory in creativity, mediating bottom-up (divergent thinking) and top-down (fluid intelligence) cognitive processes. However, the relationship between creativity, intelligence, and the organization of the semantic memory remains poorly-characterized in children. We investigated the ways in which individual differences in children’s semantic memory structures are influenced by their divergent thinking and fluid intelligence abilities. The participants (mean age 10) were grouped by their levels (high/low) of divergent thinking and fluid intelligence. We applied a recently-developed Network Science approach in order to examine group-based semantic memory graphs. Networks were constructed from a semantic fluency task. The results revealed that divergent thinking abilities are related to a more flexible structure of the semantic network, while fluid intelligence corresponds to a more structured semantic network, in line with the previous findings from the adult sample. Our findings confirm the crucial role of semantic memory organization in creative performance, and demonstrate that this phenomenon can be traced back to childhood. Finally, we also corroborate the network science methodology as a valid approach to the study of creative cognition in the developmental population.
One-Stage Soft Tissue Reconstruction Following Sarcoma Excision: A Personalized Multidisciplinary Approach Called “Orthoplasty”
Authors: Angelini Andrea , Tiengo Cesare , Sonda Regina , Berizzi Antonio , Bassetto Franco , Ruggieri Pietro
Published: December 2020

Background and Objectives. Wide surgical resection is a relevant factor for local control in sarcomas. Plastic surgery is mandatory in demanding reconstructions. We analyzed patients treated by a multidisciplinary team to evaluate indications and surgical approaches, complications and therapeutic/functional outcomes. Methods. We analyzed 161 patients (86 males (53%), mean age 56 years) from 2006 to 2017. Patients were treated for their primary tumor (120, 75.5%) or after unplanned excision/recurrence (41, 25.5%). Sites included lower limbs (36.6%), upper limbs (19.2%), head/neck (21.1%), trunk (14.9%) and pelvis (8.1%). Orthoplasty has been considered for flaps (54), skin grafts (42), wide excisions (40) and other procedures (25). Results. At a mean follow-up of 5.3 years (range 2–10.5), patients continuously showed no evidence of disease (NED) in 130 cases (80.7%), were alive with disease (AWD) in 10 cases (6.2%) and were dead with disease (DWD) in 21 cases (13.0%). Overall, 62 patients (38.5%) developed a complication (56 minor (90.3%) and 6 major (9.7%)). Flap loss occurred in 5/48 patients (10.4%). The mean Musculoskeletal Tumor Society (MSTS) and Toronto Extremity Salvage Score (TESS) was 74.8 ± 14 and 79.1 ± 13, respectively. Conclusions. Orthoplasty is a combined approach effective in management of sarcoma patients, maximizing adequate surgical resection, limb salvaging and functional recovery. One-stage reconstructions are technically feasible and are not associated with increased risk of complications.
A Wide Spectrum of Genetic Disorders Causing Severe Childhood Epilepsy in Taiwan: A Case Series of Ultrarare Genetic Cause and Novel Mutation Analysis in a Pilot Study
Authors: Hong Syuan-Yu , Yang Jiann-Jou , Li Shuan-Yow , Lee Inn-Chi
Published: December 2020

Background: Pediatric epileptic encephalopathy and severe neurological disorders comprise a group of heterogenous diseases. We used whole-exome sequencing (WES) to identify genetic defects in pediatric patients. Methods: Patients with refractory seizures using ≥2 antiepileptic drugs (AEDs) receiving one AED and having neurodevelopmental regression or having severe neurological or neuromuscular disorders with unidentified causes were enrolled, of which 54 patients fulfilled the inclusion criteria, were enrolled, and underwent WES. Results: Genetic diagnoses were confirmed in 24 patients. In the seizure group, KCNQ2, SCN1A, TBCID 24, GRIN1, IRF2BPL, MECP2, OSGEP, PACS1, PIGA, PPP1CB, SMARCA4, SUOX, SZT2, UBE3A, 16p13.11 microdeletion, [4p16.3p16.1(68,345–7,739,782)X1, 17q25.1q25.3(73,608,322–81,041,938)X3], and LAMA2 were identified. In the nonseizure group, SCN2A, SPTBN2, DMD, and FBN1 were identified. Ten novel mutations were identified. The recurrent genes included SCN1A, KCNQ2, and TBCID24. Male pediatric patients had a significantly higher (57% vs. 29%; p < 0.05, odds ratio = 3.18) yield than their female counterparts. Seventeen genes were identified from the seizure groups, of which 82% were rare genetic etiologies for childhood seizure and did not appear recurrently in the case series. Conclusions: Wide genetic variation was identified for severe childhood seizures by WES. WES had a high yield, particularly in male infantile patients.
Digital Phenotyping and Patient-Generated Health Data for Outcome Measurement in Surgical Care: A Scoping Review
Authors: Jayakumar Prakash , Lin Eugenia , Galea Vincent , Mathew Abraham J. , Panda Nikhil , Vetter Imelda , Haynes Alex B.
Published: December 2020

Digital phenotyping—the moment-by-moment quantification of human phenotypes in situ using data related to activity, behavior, and communications, from personal digital devices, such as smart phones and wearables—has been gaining interest. Personalized health information captured within free-living settings using such technologies may better enable the application of patient-generated health data (PGHD) to provide patient-centered care. The primary objective of this scoping review is to characterize the application of digital phenotyping and digitally captured active and passive PGHD for outcome measurement in surgical care. Secondarily, we synthesize the body of evidence to define specific areas for further work. We performed a systematic search of four bibliographic databases using terms related to “digital phenotyping and PGHD,” “outcome measurement,” and “surgical care” with no date limits. We registered the study (Open Science Framework), followed strict inclusion/exclusion criteria, performed screening, extraction, and synthesis of results in line with the PRISMA Extension for Scoping Reviews. A total of 224 studies were included. Published studies have accelerated in the last 5 years, originating in 29 countries (mostly from the USA, n = 74, 33%), featuring original prospective work (n = 149, 66%). Studies spanned 14 specialties, most commonly orthopedic surgery (n = 129, 58%), and had a postoperative focus (n = 210, 94%). Most of the work involved research-grade wearables (n = 130, 58%), prioritizing the capture of activity (n = 165, 74%) and biometric data (n = 100, 45%), with a view to providing a tracking/monitoring function (n = 115, 51%) for the management of surgical patients. Opportunities exist for further work across surgical specialties involving smartphones, communications data, comparison with patient-reported outcome measures (PROMs), applications focusing on prediction of outcomes, monitoring, risk profiling, shared decision making, and surgical optimization. The rapidly evolving state of the art in digital phenotyping and capture of PGHD offers exciting prospects for outcome measurement in surgical care pending further work and consideration related to clinical care, technology, and implementation.
Environmental Regulations, the Industrial Structure, and High-Quality Regional Economic Development: Evidence from China
Authors: Chen Lingming , Ye Wenzhong , Huo Congjia , James Kieran
Published: December 2020

Environmental regulation is an important means of restraining enterprises and protecting the environment. Rationalization of environmental regulatory policies can promote high-quality regional economic development. The optimization and upgrading of the industrial structure has an intermediary effect on the impact of environmental regulations on the high-quality development of the regional economy. After collating and analyzing previous research, this article proposes to classify 30 Chinese provinces into regions with higher than the national average HDI (human development index) and lower than the national average HDI based on the average HDI of Chinese provinces. We explore the mediating effect of industrial structure on environmental regulation and high-quality regional economic development. The model passed the full-sample robustness test and the robustness test with GDP as the replacement variable. The empirical results show that environmental regulations of different intensities have different effects on the quality of regional economic development. The effect of environmental regulations on development quality is mainly mediated through the transformation and upgrading of the industrial structure. Enterprises need reasonable incentives from environmental regulations to transform and upgrade. The mediating effect of the industrial structure on environmental regulations is greater in regions with below-average HDI values than in regions with above-average HDI values, which shows that the industrial structure is the mechanism underlying the effect of environmental regulations on the quality of regional economic development. This result proves that adjusting environmental regulatory policies can effectively promote the upgrading of industrial structure, thereby promoting high-quality regional economic development. Based on this, the article puts forward several policy recommendations.
Agent-Based Modeling for Integrating Human Behavior into the Food–Energy–Water Nexus
Authors: Magliocca Nicholas R.
Published: December 2020

The nexus of food, energy, and water systems (FEWS) has become a salient research topic, as well as a pressing societal and policy challenge. Computational modeling is a key tool in addressing these challenges, and FEWS modeling as a subfield is now established. However, social dimensions of FEWS nexus issues, such as individual or social learning, technology adoption decisions, and adaptive behaviors, remain relatively underdeveloped in FEWS modeling and research. Agent-based models (ABMs) have received increasing usage recently in efforts to better represent and integrate human behavior into FEWS research. A systematic review identified 29 articles in which at least two food, energy, or water sectors were explicitly considered with an ABM and/or ABM-coupled modeling approach. Agent decision-making and behavior ranged from reactive to active, motivated by primarily economic objectives to multi-criteria in nature, and implemented with individual-based to highly aggregated entities. However, a significant proportion of models did not contain agent interactions, or did not base agent decision-making on existing behavioral theories. Model design choices imposed by data limitations, structural requirements for coupling with other simulation models, or spatial and/or temporal scales of application resulted in agent representations lacking explicit decision-making processes or social interactions. In contrast, several methodological innovations were also noted, which were catalyzed by the challenges associated with developing multi-scale, cross-sector models. Several avenues for future research with ABMs in FEWS research are suggested based on these findings. The reviewed ABM applications represent progress, yet many opportunities for more behaviorally rich agent-based modeling in the FEWS context remain.
Infiltration Capacity of Rain Gardens Using Full-Scale Test Method: Effect of Infiltration System on Groundwater Levels in Bergen, Norway
Authors: Venvik Guri , Boogaard Floris
Published: December 2020

The rain gardens at Bryggen in Bergen, Western Norway, is designed to collect, retain, and infiltrate surface rainfall runoff water, recharge the groundwater, and replenish soil moisture. The hydraulic infiltration capacity of the Sustainable Drainage System (SuDS), here rain gardens, has been tested with small-scale and full-scale infiltration tests. Results show that infiltration capacity meets the requirement and is more than sufficient for infiltration in a cold climate. The results from small-scale test, 245–404 mm/h, shows lower infiltration rates than the full-scale infiltration test, with 510–1600 mm/h. As predicted, an immediate response of the full-scale infiltration test is shown on the groundwater monitoring in the wells located closest to the infiltration point (<30 m), with a ca. 2 days delayed response in the wells further away (75–100 m). Results show that there is sufficient capacity for a larger drainage area to be connected to the infiltration systems. This study contributes to the understanding of the dynamics of infiltration systems such as how a rain garden interacts with local, urban water cycle, both in the hydrological and hydrogeological aspects. The results from this study show that infiltration systems help to protect and preserve the organic rich cultural layers below, as well as help with testing and evaluating of the efficiency, i.e., SuDS may have multiple functions, not only storm water retention. The functionality is tested with water volumes of 40 m3 (600 L/min for 2 h and 10 min), comparable to a flash flood, which give an evaluation of the infiltration capacity of the system.
Rural Landscapes—Challenges and Solutions to Landscape Governance
Authors: Primdahl Jørgen , Van Eetvelde Veerle , Pinto-Correia Teresa
Published: December 2020

Rural landscape dynamics are challenging existing policy regimes for a number of reasons and new approaches to landscape governance are needed [...]
Bird Eye View of Protein Subcellular Localization Prediction
Authors: Kumar Ravindra , Dhanda Sandeep Kumar
Published: December 2020

Proteins are made up of long chain of amino acids that perform a variety of functions in different organisms. The activity of the proteins is determined by the nucleotide sequence of their genes and by its 3D structure. In addition, it is essential for proteins to be destined to their specific locations or compartments to perform their structure and functions. The challenge of computational prediction of subcellular localization of proteins is addressed in various in silico methods. In this review, we reviewed the progress in this field and offered a bird eye view consisting of a comprehensive listing of tools, types of input features explored, machine learning approaches employed, and evaluation matrices applied. We hope the review will be useful for the researchers working in the field of protein localization predictions.
Influence of Humidity on the Elastic Modulus and Axis Compressive Strength of Concrete in a Water Environment
Authors: Zhang Guohui , Li Changbing , Wei Hai , Wang Mingming , Yang Zhendong , Gu Yanshuang
Published: December 2020

Concrete structures are often in different humidity conditions that have a significant impact on the elastic modulus of concrete, therefore, systematic research on the evolution of the law of concrete elastic modulus under different humidity conditions is needed. In this study, the variation laws of the water saturation of concrete specimens with strength grades C15, C20, and C30 were obtained, and then the influence laws of the water saturation on the concrete axial compressive strength were carried out, and the prediction model of elastic modulus of concrete with respect to water saturation was constructed. The results showed that the water saturation of concrete with strength grades C15, C20, and C30 increased with an extension of immersion time, and the water saturation showed an approximately linear rapid growth within three soaking hours, reaching 47.56%, 71.63%, and 47.29%, respectively. Note, the concrete reached saturation state when the soaking time was 240 h. The axial compressive strength with strength grades C15, C20, and C30 decreased with increased water saturation, and the axial compressive strength of saturated concrete decreased by 27.25%, 21.14%, and 20.76%, respectively, as compared with the dry state concrete. The elastic modulus of concrete with strength grades C15, C20, and C30 increased with increased water saturation, and the elastic modulus of saturated concrete was 1.18, 1.19, and 1.24 times higher than those of dry concrete, respectively.
Influence of Redispersible Powder on Properties of Self-Leveling Mortar of Ternary Cementitious System
Authors: Dong Wenyan , Fang Congqi , Hu Ran
Published: December 2020

The self-leveling mortar (SLM) of a ternary cementitious system with different dosages of redispersible powder (RP) with ordinary Portland cement (OPC), sulfoaluminate cement (SAC), and calcium sulfate (CS) as cementitious materials was investigated with regard to fluidity, bond strength, shrinkage rate, abrasion resistance, flexural strength, and compressive strength. The performance parameters obtained from the experimental test for SLM were weighted values calculated with an analytic hierarchy process (AHP). The comprehensive index of performance was evaluated on the basis of a weighted-sum method, and the optimal dosage of RP was determined according to the comprehensive index. The experimental results demonstrated that the fluidity of SLM decreased with the increase in RP dosage at the beginning but then increased thereafter and decreased rapidly as the dosage went beyond 3.0%. The addition of RP resulted in a significant improvement in bond strength (of SLM), reduction in the shrinkage rate, abrasion loss, early flexural strength and compressive strength, and resistance to cracking. The properties of SLM with 3.0% RP can meet the requirements of the industrial standard for cementitious self-leveling floor mortar. Compared with the SLM without RP, the bond strength of SLM with 3.0% RP was increased by 46.7%, while the shrinkage rate and abrasion loss were reduced by 50% and 71.9% respectively. The weighted values of fluidity, compressive strength, flexural strength, stability, cohesiveness, and abrasion resistance were 0.422, 0.196, 0.196, 0.089, 0.058, and 0.039, respectively. A higher value of the comprehensive index generally denotes a better performance. The comprehensive index of SLM with 3.0% RP was the highest.