bluuebunny/crossref_metadata_2025 huggingface dataset:
NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female
Authors: Babou Kammoe Romuald Brice , Kauffenstein Gilles , Pelletier Julie , Robaye Bernard , Sévigny Jean
Published: January 2021

Nucleotides released by smooth muscle cells (SMCs) and by innervating nerve terminals activate specific P2 receptors and modulate bladder contraction. We hypothesized that cell surface enzymes regulate SMC contraction in mice bladder by controlling the concentration of nucleotides. We showed by immunohistochemistry, enzymatic histochemistry, and biochemical activities that nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and ecto-5′-nucleotidase were the major ectonucleotidases expressed by SMCs in the bladder. RT-qPCR revealed that, among the nucleotide receptors, there was higher expression of P2X1, P2Y1, and P2Y6 receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (Entpd1−/−) mice compared to wild type controls. The strongest responses were obtained with uridine 5′-triphosphate (UTP) and uridine 5′-diphosphate (UDP), suggesting the involvement of P2Y6 receptors, which was confirmed with P2ry6−/− bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y2 and/or P2Y4, and P2Y12 in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, Entpd1−/−, and P2ry6−/− female bladders showing another difference due to sex. In summary, NTPDase1 modulates the activation of nucleotide receptors in mouse bladder SMCs, and contractions induced by P2Y6 receptor activation were weaker in female bladders.
Structural Insights into Substrate Recognition and Processing by the 20S Proteasome
Authors: Sahu Indrajit , Glickman Michael H.
Published: January 2021

Four decades of proteasome research have yielded extensive information on ubiquitin-dependent proteolysis. The archetype of proteasomes is a 20S barrel-shaped complex that does not rely on ubiquitin as a degradation signal but can degrade substrates with a considerable unstructured stretch. Since roughly half of all proteasomes in most eukaryotic cells are free 20S complexes, ubiquitin-independent protein degradation may coexist with ubiquitin-dependent degradation by the highly regulated 26S proteasome. This article reviews recent advances in our understanding of the biochemical and structural features that underlie the proteolytic mechanism of 20S proteasomes. The two outer α-rings of 20S proteasomes provide a number of potential docking sites for loosely folded polypeptides. The binding of a substrate can induce asymmetric conformational changes, trigger gate opening, and initiate its own degradation through a protease-driven translocation mechanism. Consequently, the substrate translocates through two additional narrow apertures augmented by the β-catalytic active sites. The overall pulling force through the two annuli results in a protease-like unfolding of the substrate and subsequent proteolysis in the catalytic chamber. Although both proteasomes contain identical β-catalytic active sites, the differential translocation mechanisms yield distinct peptide products. Nonoverlapping substrate repertoires and product outcomes rationalize cohabitation of both proteasome complexes in cells.
Lipoxygenase Inhibition by Plant Extracts
Authors: Lončarić Melita , Strelec Ivica , Moslavac Tihomir , Šubarić Drago , Pavić Valentina , Molnar Maja
Published: January 2021

Lipoxygenases are widespread enzymes that catalyze oxidation of polyunsaturated fatty acids (linoleic, linolenic, and arachidonic acid) to produce hydroperoxides. Lipoxygenase reactions can be desirable, but also lipoxygenases can react in undesirable ways. Most of the products of lipoxygenase reactions are aromatic compounds that can affect food properties, especially during long-term storage. Lipoxygenase action on unsaturated fatty acids could result in off-flavor/off-odor development, causing food spoilage. In addition, lipoxygenases are present in the human body and play an important role in stimulation of inflammatory reactions. Inflammation is linked to many diseases, such as cancer, stroke, and cardiovascular and neurodegenerative diseases. This review summarized recent research on plant families and species that can inhibit lipoxygenase activity.
Reconstitution of Human Necrosome Interactions in Saccharomyces cerevisiae
Authors: Ji Y. , Ward L. A. , Hawkins C. J.
Published: January 2021

The necrosome is a large-molecular-weight complex in which the terminal effector of the necroptotic pathway, Mixed Lineage Kinase Domain-Like protein (MLKL), is activated to induce necroptotic cell death. The precise mechanism of MLKL activation by the upstream kinase, Receptor Interacting Serine/Threonine Protein Kinase 3 (RIPK3) and the role of Receptor Interacting Serine/Threonine Protein Kinase 1 (RIPK1) in mediating MLKL activation remain incompletely understood. Here, we reconstituted human necrosome interactions in yeast by inducible expression of these necrosome effectors. Functional interactions were reflected by the detection of phosphorylated MLKL, plasma membrane permeabilization, and reduced proliferative potential. Following overexpression of human necrosome effectors in yeast, MLKL aggregated in the periphery of the cell, permeabilized the plasma membrane and compromised clonogenic potential. RIPK1 had little impact on RIPK3/MLKL-mediated yeast lethality; however, it exacerbated the toxicity provoked by co-expression of MLKL with a RIPK3 variant bearing a mutated RHIM-domain. Small molecule necroptotic inhibitors necrostatin-1 and TC13172, and viral inhibitors M45 (residues 1–90) and BAV_Rmil, abated the yeast toxicity triggered by the reconstituted necrosome. This yeast model provides a convenient tool to study necrosome protein interactions and to screen for and characterize potential necroptotic inhibitors.
The Middle Part of the Plucked Hair Follicle Outer Root Sheath Is Identified as an Area Rich in Lineage-Specific Stem Cell Markers
Authors: Li Hanluo , Masieri Federica Francesca , Schneider Marie , Bartella Alexander , Gaus Sebastian , Hahnel Sebastian , Zimmerer Rüdiger , Sack Ulrich , Maksimovic-Ivanic Danijela , Mijatovic Sanja , Simon Jan-Christoph , Lethaus Bernd , Savkovic Vuk
Published: January 2021

Hair follicle outer root sheath (ORS) is a putative source of stem cells with therapeutic capacity. ORS contains several multipotent stem cell populations, primarily in the distal compartment of the bulge region. However, the bulge is routinely obtained using invasive isolation methods, which require human scalp tissue ex vivo. Non-invasive sampling has been standardized by means of the plucking procedure, enabling to reproducibly obtain the mid-ORS part. The mid-ORS shows potential for giving rise to multiple stem cell populations in vitro. To demonstrate the phenotypic features of distal, middle, and proximal ORS parts, gene and protein expression profiles were studied in physically separated portions. The mid-part of the ORS showed a comparable or higher NGFR, nestin/NES, CD34, CD73, CD44, CD133, CK5, PAX3, MITF, and PMEL expression on both protein and gene levels, when compared to the distal ORS part. Distinct subpopulations of cells exhibiting small and round morphology were characterized with flow cytometry as simultaneously expressing CD73/CD271, CD49f/CD105, nestin, and not CK10. Potentially, these distinct subpopulations can give rise to cultured neuroectodermal and mesenchymal stem cell populations in vitro. In conclusion, the mid part of the ORS holds the potential for yielding multiple stem cells, in particular mesenchymal stem cells.
Type III Collagen is Required for Adipogenesis and Actin Stress Fibre Formation in 3T3-L1 Preadipocytes
Authors: Al Hasan Mohammad , Martin Patricia E. , Shu Xinhua , Patterson Steven , Bartholomew Chris
Published: January 2021

GPR56 is required for the adipogenesis of preadipocytes, and the role of one of its ligands, type III collagen (ColIII), was investigated here. ColIII expression was examined by reverse transcription quantitative polymerase chain reaction, immunoblotting and immunostaining, and its function investigated by knockdown and genome editing in 3T3-L1 cells. Adipogenesis was assessed by oil red O staining of neutral cell lipids and production of established marker and regulator proteins. siRNA-mediated knockdown significantly reduced Col3a1 transcripts, ColIII protein and lipid accumulation in 3T3-L1 differentiating cells. Col3a1−/− 3T3-L1 genome-edited cell lines abolished adipogenesis, demonstrated by a dramatic reduction in adipogenic moderators: Pparγ2 (88%) and C/ebpα (96%) as well as markers aP2 (93%) and oil red O staining (80%). Col3a1−/− 3T3-L1 cells displayed reduced cell adhesion, sustained active β-catenin and deregulation of fibronectin (Fn) and collagen (Col4a1, Col6a1) extracellular matrix gene transcripts. Col3a1−/− 3T3-L1 cells also had dramatically reduced actin stress fibres. We conclude that ColIII is required for 3T3-L1 preadipocyte adipogenesis as well as the formation of actin stress fibres. The phenotype of Col3a1−/− 3T3-L1 cells is very similar to that of Gpr56−/− 3T3-L1 cells, suggesting a functional relationship between ColIII and Gpr56 in preadipocytes.
Sex-Dependent End-of-Life Mental and Vascular Scenarios for Compensatory Mechanisms in Mice with Normal and AD-Neurodegenerative Aging
Authors: Muntsant Aida , Jiménez-Altayó Francesc , Puertas-Umbert Lidia , Jiménez-Xarrie Elena , Vila Elisabet , Giménez-Llort Lydia
Published: January 2021

Life expectancy decreases with aging, with cardiovascular, mental health, and neurodegenerative disorders strongly contributing to the total disability-adjusted life years. Interestingly, the morbidity/mortality paradox points to females having a worse healthy life expectancy. Since bidirectional interactions between cardiovascular and Alzheimer’s diseases (AD) have been reported, the study of this emerging field is promising. In the present work, we further explored the cardiovascular–brain interactions in mice survivors of two cohorts of non-transgenic and 3xTg-AD mice, including both sexes, to investigate the frailty/survival through their life span. Survival, monitored from birth, showed exceptionally worse mortality rates in females than males, independently of the genotype. This mortality selection provided a “survivors” cohort that could unveil brain–cardiovascular interaction mechanisms relevant for normal and neurodegenerative aging processes restricted to long-lived animals. The results show sex-dependent distinct physical (worse in 3xTg-AD males), neuropsychiatric-like and cognitive phenotypes (worse in 3xTg-AD females), and hypothalamic–pituitary–adrenal (HPA) axis activation (higher in females), with higher cerebral blood flow and improved cardiovascular phenotype in 3xTg-AD female mice survivors. The present study provides an experimental scenario to study the suggested potential compensatory hemodynamic mechanisms in end-of-life dementia, which is sex-dependent and can be a target for pharmacological and non-pharmacological interventions.
Mesoporous Bioactive Glasses Cytocompatibility Assessment: A Review of In Vitro Studies
Authors: Salètes Margaux , Vartin Marta , Mocquot Caroline , Chevalier Charlène , Grosgogeat Brigitte , Colon Pierre , Attik Nina
Published: January 2021

Thanks to their high porosity and surface area, mesoporous bioactive glasses (MBGs) have gained significant interest in the field of medical applications, in particular, with regards to enhanced bioactive properties which facilitate bone regeneration. The aim of this article is to review the state of the art regarding the biocompatibility evaluation of MBGs and provide a discussion of the various approaches taken. The research was performed using PubMed database and covered articles published in the last five years. From a total of 91 articles, 63 were selected after analyzing them according to our inclusion and exclusion criteria. In vitro methodologies and techniques used for biocompatibility assessment were investigated. Among the biocompatibility assessment techniques, scanning electron microscopy (SEM) has been widely used to study cell morphology and adhesion. Viability and proliferation were assessed using different assays including cell counting and/or cell metabolic activity measurement. Finally, cell differentiation tests relied on the alkaline phosphatase assay; however, these were often complemented by specific bimolecular tests according to the exact application of the mesoporous bioactive glass. The standardization and validation of all tests performed for MBG cytocompatibility is a key aspect and crucial point and should be considered in order to avoid inconsistencies, bias between studies, and unnecessary consumption of time. Therefore, introducing standard tests would serve an important role in the future assessment and development of MBG materials.
Detection Technologies for Reactive Oxygen Species: Fluorescence and Electrochemical Methods and Their Applications
Authors: Duanghathaipornsuk Surachet , Farrell Eveline J. , Alba-Rubio Ana C. , Zelenay Piotr , Kim Dong-Shik
Published: January 2021

Reactive oxygen species (ROS) have been found in plants, mammals, and natural environmental processes. The presence of ROS in mammals has been linked to the development of severe diseases, such as diabetes, cancer, tumors, and several neurodegenerative conditions. The most common ROS involved in human health are superoxide (O2•−), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH). Organic and inorganic molecules have been integrated with various methods to detect and monitor ROS for understanding the effect of their presence and concentration on diseases caused by oxidative stress. Among several techniques, fluorescence and electrochemical methods have been recently developed and employed for the detection of ROS. This literature review intends to critically discuss the development of these techniques to date, as well as their application for in vitro and in vivo ROS detection regarding free-radical-related diseases. Moreover, important insights into and further steps for using fluorescence and electrochemical methods in the detection of ROS are presented.
Biosensors for Detection of Biochemical Markers Relevant to Osteoarthritis
Authors: Longo Umile Giuseppe , Candela Vincenzo , Berton Alessandra , De Salvatore Sergio , Fioravanti Sara , Giannone Lucia , Marchetti Anna , De Marinis Maria Grazia , Denaro Vincenzo
Published: January 2021

This systematic review aimed to assess the advantages of biosensors in detecting biomarkers for the early diagnosis of osteoarthritis (OA). OA is the most prevalent musculoskeletal disease and is a leading cause of disability and pain worldwide. The diagnosis of OA could be performed through clinical examinations and imaging only during the late stages of the disease. Biomarkers could be used for the diagnosis of the disease in the very early stages. Biosensors could detect biomarkers with high accuracy and low costs. This paper focuses on the biosensors mainly adopted to detect OA markers (electrochemical, optical, Quartz crystal microbalance, molecular and wearable biosensors). A comprehensive search on PubMed, Cochrane, CINAHL and Embase databases was conducted from the inception to November 2020. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used to improve the reporting of the review. The Methodological Index for Non-Randomized Studies (MINORS) was used for quality assessment. From a total amount of 1086 studies identified, only 19 articles were eligible for this study. The main advantages of the biosensors reported were accuracy, limited cost and ease of use, compared to traditional methods (ELISA). Otherwise, due to the lack of data and the low level of evidence of the papers included, it was impossible to find significant results. Therefore, further high-quality studies are required.
Forward Inverse Relaxation Model Incorporating Movement Duration Optimization
Authors: Takeda Misaki , Nambu Isao , Wada Yasuhiro
Published: January 2021

A computational trajectory formation model based on the optimization principle, which introduces the forward inverse relaxation model (FIRM) as the hardware and algorithm, represents the features of human arm movements well. However, in this model, the movement duration was defined as a given value and not as a planned value. According to considerable empirical facts, movement duration changes depending on task factors, such as required accuracy and movement distance thus, it is considered that there are some criteria that optimize the cost function. Therefore, we propose a FIRM that incorporates a movement duration optimization module. The movement duration optimization module minimizes the weighted sum of the commanded torque change term as the trajectory cost, and the tolerance term as the cost of time. We conducted a behavioral experiment to examine how well the movement duration obtained by the model reproduces the true movement. The results suggested that the model movement duration was close to the true movement. In addition, the trajectory generated by inputting the obtained movement duration to the FIRM reproduced the features of the actual trajectory well. These findings verify the use of this computational model in measuring human arm movements.
Bayesian Network as a Decision Tool for Predicting ALS Disease
Authors: Karaboga Hasan Aykut , Gunel Aslihan , Korkut Senay Vural , Demir Ibrahim , Celik Resit
Published: January 2021

Clinical diagnosis of amyotrophic lateral sclerosis (ALS) is difficult in the early period. But blood tests are less time consuming and low cost methods compared to other methods for the diagnosis. The ALS researchers have been used machine learning methods to predict the genetic architecture of disease. In this study we take advantages of Bayesian networks and machine learning methods to predict the ALS patients with blood plasma protein level and independent personal features. According to the comparison results, Bayesian Networks produced best results with accuracy (0.887), area under the curve (AUC) (0.970) and other comparison metrics. We confirmed that sex and age are effective variables on the ALS. In addition, we found that the probability of onset involvement in the ALS patients is very high. Also, a person’s other chronic or neurological diseases are associated with the ALS disease. Finally, we confirmed that the Parkin level may also have an effect on the ALS disease. While this protein is at very low levels in Parkinson’s patients, it is higher in the ALS patients than all control groups.
How Neuronal Noises Influence the Spiking Neural Networks’s Cognitive Learning Process: A Preliminary Study
Authors: Liu Jing , Yang Xu , Zhu Yimeng , Lei Yunlin , Cai Jian , Wang Miao , Huan Ziyi , Lin Xialv
Published: January 2021

In neuroscience, the Default Mode Network (DMN), also known as the default network or the default-state network, is a large-scale brain network known to have highly correlated activities that are distinct from other networks in the brain. Many studies have revealed that DMNs can influence other cognitive functions to some extent. This paper is motivated by this idea and intends to further explore on how DMNs could help Spiking Neural Networks (SNNs) on image classification problems through an experimental study. The approach emphasizes the bionic meaning on model selection and parameters settings. For modeling, we select Leaky Integrate-and-Fire (LIF) as the neuron model, Additive White Gaussian Noise (AWGN) as the input DMN, and design the learning algorithm based on Spike-Timing-Dependent Plasticity (STDP). Then, we experiment on a two-layer SNN to evaluate the influence of DMN on classification accuracy, and on a three-layer SNN to examine the influence of DMN on structure evolution, where the results both appear positive. Finally, we discuss possible directions for future works.
Prenatal Alcohol Exposure and the Facial Phenotype in Adolescents: A Study Based on Meconium Ethyl Glucuronide
Authors: Maschke Janina , Roetner Jakob , Goecke Tamme , Fasching Peter , Beckmann Matthias , Kratz Oliver , Moll Gunther , Lenz Bernd , Kornhuber Johannes , Eichler Anna ,   IMAC-Mind-Consortium
Published: January 2021

Here, we explore the effects of prenatal alcohol exposure (PAE) in adolescence. We investigated associations between meconium ethyl glucoronide (EtG) and facial malformation. For 129 children (66/63 male/female; M = 13.3, SD = 0.32, 12–14 years), PAE was implemented by newborn meconium EtG and maternal self-reports during the third trimester. Cognitive development was operationalized by standardized scores (WISC V). The EtG cut-off values were set at ≥10 ng/g (n = 32, 24.8% EtG10+) and ≥112 ng/g (n = 20, 15.5% EtG112+). The craniofacial shape was measured using FAS Facial Photographic Analysis Software. EtG10+− and EtG112+-affected children exhibited a shorter palpebral fissure length (p = 0.031/p = 0.055). Lip circularity was smaller in EtG112+-affected children (p = 0.026). Maternal self-reports were not associated (p > 0.164). Lip circularity correlated with fluid reasoning (EtG10+ p = 0.031; EtG112+ p = 0.298) and working memory (EtG10+ p = 0.084; EtG112+ p = 0.144). The present study demonstrates visible effects of the facial phenotype in exposed adolescents. Facial malformation was associated with a child’s cognitive performance in the alcohol-exposed group. The EtG biomarker was a better predictor than maternal self-reports.
Neural Evidence of Mirror Self-Recognition in the Secondary Somatosensory Cortex of Macaque: Observations from a Single-Cell Recording Experiment and Implications for Consciousness
Authors: Bretas Rafael , Taoka Miki , Hihara Sayaka , Cleeremans Axel , Iriki Atsushi
Published: January 2021

Despite mirror self-recognition being regarded as a classical indication of self-awareness, little is known about its neural underpinnings. An increasing body of evidence pointing to a role of multimodal somatosensory neurons in self-recognition guided our investigation toward the secondary somatosensory cortex (SII), as we observed single-neuron activity from a macaque monkey sitting in front of a mirror. The monkey was previously habituated to the mirror, successfully acquiring the ability of mirror self-recognition. While the monkey underwent visual and somatosensory stimulation, multimodal visual and somatosensory activity was detected in the SII, with neurons found to respond to stimuli seen through the mirror. Responses were also modulated by self-related or non-self-related stimuli. These observations corroborate that vision is an important aspect of SII activity, with electrophysiological evidence of mirror self-recognition at the neuronal level, even when such an ability is not innate. We also show that the SII may be involved in distinguishing self and non-self. Together, these results point to the involvement of the SII in the establishment of bodily self-consciousness.
Future-Oriented Coping with Weather Stress among Mountain Hikers: Temperamental Personality Predictors and Profiles
Authors: Próchniak Piotr , Próchniak Agnieszka
Published: January 2021

The aim of the study was to explore temperamental personality traits as predictors of fu-ture-oriented coping with weather stress in a group of Polish mountain hikers. The subjects were 209 young mountain hikers (M = 21.20; SD = 3.70) who took three temperament–personality questionnaires, i.e., FCZ-KT Temperament Questionnaire, Sensation Seeking Scale IV and NEO-FFI- Personality Inventory, alongside a recently constructed scale for diagnosing future-oriented coping with weather stress in outdoor context, Preventive and Proactive Coping with Bad Weather Scale in Outdoor Sports. The regression analysis indicated that preventive coping with weather stress in hiking was predicted by activity, emotional reactivity, briskness, sensory sensitivity, experience seeking, agreeableness and conscientiousness. In turn, proactive coping with bad weather in hiking was predicted by endurance, activity, thrill and adventure seeking and extraversion. In turn, the cluster analysis revealed three distinct clusters of hikers characterized by diverse re-sults on the scales of preventive and proactive dealing with adverse weather, namely, prudent hikers (high preventive coping/high proactive coping), reckless hikers (low pre-ventive coping/high proactive coping) and wary hikers (high preventive coping/low proactive coping). The hikers in these clusters differed in terms of temperamental per-sonality traits.
The Influence of Price on Purchase Intentions: Comparative Study between Cognitive, Sensory, and Neurophysiological Experiments
Authors: Levrini Gabriel R. D. , Jeffman dos Santos Mirela
Published: January 2021

Price is considered one of the most important attributes in consumer’s choice. On the other hand, consumer’s knowledge about price tends to be imprecise. This study aims at providing new insights analyzing consumers’ perception of retail store brand (focused on Skin Care Products) comparing with two other skin care products, a premium, and a popular national brand. Second, to analyze the association price versus quality variables in the purchasing decision process. Third, to demonstrate the influence of both, unconscious and cognitive process during the purchase choice intention. Through Neuromarketing tools and protocols (quantitative and qualitative), the study exposes participants to a blind test of the three products and asks participants to talk about their sensory impressions like scent, feelings, and products texture. Using facial electromyography (EMG) and eye-tracker devices we measured consumers’ responses when we introduced price and brand name variables, by this way comparing unconscious and cognitive responses. The findings showed that an unconscious decision could be change when new variables were revealed. The study showed how conscious price variable was the major influence in their purchase intention.
Assessment of Cloud Computing Success Factors for Sustainable Construction Industry: The Case of Nigeria
Authors: Oke Ayodeji , Kineber Ahmed , Albukhari Ibraheem , Othman Idris , Kingsley Chukwuma
Published: January 2021

Cloud Computing has become a valuable platform for sustainability in many countries. This study evaluates the cloud computing implementation and its Critical Success Factors (CSFs) towards ensuring sustainable construction projects in Nigeria. Data were collected from previous literature, supplemented by a quantitative approach via a questionnaire survey. Data were collected from 104 construction professionals while cloud computing CSFs were examined using Relative Importance Ranking (RII) and Exploratory Factor Analysis (EFA). The results show that cloud computing’s awareness level is 96.2%, which means that the respondents are aware of cloud computing concept. Furthermore, the result shows that most of the respondents are adopting the concept. The analysis of the CSFs indicated that reliable data storage, performance as well as cost of accessibility and availability were the four most significant CSFs to cloud computing applications. Analysis of the CSFs through EFA generated four main components which include human satisfaction, organization, client’s acceptance, and industry-based. Consequently, this study contributed to existing body of knowledge by highlighting the cloud computing CSFs for achieving sustainable construction project. As such, the results could be a game-changer in the construction industry—not only in Nigeria but also in developing nations where construction projects are implemented through similar style and procedure. This study would be a benchmark for supporting decision-makers to improve data fragmentation, in which the use of data is paramount to the execution of construction works. Finally, the results of this study would be useful for enhancing sustainability and general management of construction projects through cloud computing implementation.
Spatial Analysis, Interactive Visualisation and GIS-Based Dashboard for Monitoring Spatio-Temporal Changes of Hotspots of Bushfires over 100 Years in New South Wales, Australia
Authors: Visner Michael , Shirowzhan Sara , Pettit Chris
Published: January 2021

The 2019–2020 bushfire season is estimated to be one of the worst fire seasons on record in Australia, especially in New South Wales (NSW). The devastating fire season ignited a heated public debate on whether prescribed burning is an effective tool for preventing bushfires, and how the extent of bushfires has been changing over time. The objective of this study is to answer these questions, and more specifically to identify how bushfire patterns have changed in the last 100 years in NSW. To do so, we conducted a spatio-temporal analysis on prescribed burns and bushfires using a 100-year dataset of bushfires. More specifically, three research questions were developed, with each one of them addressed differently. First, generalised linear modelling was applied to assess the changes in fire patterns. Second, a correlation analysis was conducted to examine whether prescribed burns are an effective tool for reducing bushfire risk. Third, a spatio-temporal analysis was applied to the bushfire location data to explore spatio-temporal clusters of high and low values for bushfires, known as hotspots and coldspots, respectively. The study found that the frequency of bushfires has increased over time; however, it did not identify a significant trend of change in their size. Based on the results of this study for the relationship between prescribed burns and bushfires, it seems impossible to determine whether prescribed burns effectively reduce bushfire risk. Thus, further analysis with a larger amount of data is required in the future. The results of the spatio-temporal analysis showed that cold spots are propagated around metropolitan areas such as Sydney, while hotspots are concentrated in rural areas such as the North Coast and South Coast regions of NSW. The analysis found four statistical areas that have become new bushfire frequency hotspots in the 2019–2020 bushfire season. These areas combined have about 40,000 residents and at least 13,000 built dwellings. We suggest that further analysis is needed in the field to determine if there is a pattern of movement of bushfire towards metropolitan areas. To make the results of this research accessible to the public, an online interactive GIS-based dashboard was developed. The insight gained from the spatial and temporal analyses in this research is crucial to making smarter decisions on allocating resources and developing preventive or mitigating strategies.
Small Molecule-Based Prodrug Targeting Prostate Specific Membrane Antigen for the Treatment of Prostate Cancer
Authors: Wang Xinning , Shirke Aditi , Walker Ethan , Sun Rongcan , Ramamurthy Gopolakrishnan , Wang Jing , Shan Lingpeng , Mangadlao Joey , Dong Zhipeng , Li Jing , Wang Ziying , Schluchter Mark , Luo Dong , Wang Yu , Stauffer Shaun , Brady-Kalnay Susann , Hoimes Christopher , Lee Zhenghong , Basilion James P.
Published: January 2021

Metastatic castration-resistant prostate cancer poses a serious clinical problem with poor outcomes and remains a deadly disease. New targeted treatment options are urgently needed. PSMA is highly expressed in prostate cancer and has been an attractive biomarker for the treatment of prostate cancer. In this study, we explored the feasibility of targeted delivery of an antimitotic drug, monomethyl auristatin E (MMAE), to tumor tissue using a small-molecule based PSMA lig-and. With the aid of Cy5.5, we found that a cleavable linker is vital for the antitumor activity of the ligand–drug conjugate and have developed a new PSMA-targeting prodrug, PSMA-1-VcMMAE. In in vitro studies, PSMA-1-VcMMAE was 48-fold more potent in killing PSMA-positive PC3pip cells than killing PSMA-negative PC3flu cells. In in vivo studies, PSMA-1-VcMMAE significantly inhibited tumor growth leading to prolonged animal survival in different animal models, including metastatic prostate cancer models. Compared to anti-PSMA antibody-MMAE conjugate (PSMA-ADC) and MMAE, PSMA-1-VcMMAE had over a 10-fold improved maximum tolerated dose, resulting in improved therapeutic index. The small molecule–drug conjugates reported here can be easily synthesized and are more cost efficient than anti-body–drug conjugates. The therapeutic profile of the PSMA-1-VcMMAE encourages further clin-ical development for the treatment of advanced prostate cancer.
Prognostic Index for Predicting Prostate Cancer Survival in a Randomized Screening Trial: Development and Validation
Authors: Neupane Subas , Nevalainen Jaakko , Raitanen Jani , Talala Kirsi , Kujala Paula , Taari Kimmo , Tammela Teuvo L. J. , Steyerberg Ewout W. , Auvinen Anssi
Published: January 2021

We developed and validated a prognostic index to predict survival from prostate cancer (PCa) based on the Finnish randomized screening trial (FinRSPC). Men diagnosed with localized PCa (N = 7042) were included. European Association of Urology risk groups were defined. The follow-up was divided into three periods (0–3, 3–9 and 9–20 years) for development and two corresponding validation periods (3–6 and 9–15 years). A multivariable complementary log–log regression model was used to calculate the full prognostic index. Predicted cause-specific survival at 10 years from diagnosis was calculated for the control arm using a simplified risk score at diagnosis. The full prognostic index discriminates well men with PCa with different survival. The area under the curve (AUC) was 0.83 for both the 3–6 year and 9–15 year validation periods. In the simplified risk score, patients with a low risk score at diagnosis had the most favorable survival, while the outcome was poorest for the patients with high risk scores. The prognostic index was able to distinguish well between men with higher and lower survival, and the simplified risk score can be used as a basis for decision making.
The Role and Therapeutic Targeting of JAK/STAT Signaling in Glioblastoma
Authors: Ou Alexander , Ott Martina , Fang Dexing , Heimberger Amy
Published: January 2021

Glioblastoma remains one of the deadliest and treatment-refractory human malignancies in large part due to its diffusely infiltrative nature, molecular heterogeneity, and capacity for immune escape. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes substantively to a wide variety of protumorigenic functions, including proliferation, anti-apoptosis, angiogenesis, stem cell maintenance, and immune suppression. We review the current state of knowledge regarding the biological role of JAK/STAT signaling in glioblastoma, therapeutic strategies, and future directions for the field.
Evolution of the Mesenteric Mass in Small Intestinal Neuroendocrine Tumours
Authors: Blažević Anela , Brabander Tessa , Zandee Wouter T. , Hofland Johannes , Franssen Gaston J. H. , van Velthuysen Marie-Louise F. , Feelders Richard A. , De Herder Wouter W.
Published: January 2021

Background: A metastatic mesenteric mass is a hallmark of small intestinal neuroendocrine tumours (SI-NETs). However, little is known on its development over time. Therefore, we conducted a study to assess the evolution of a SI-NET-associated mesenteric mass over time. Methods: Retrospectively, 530 patients with proven SI-NET were included. The presence and growth of a mesenteric mass was assessed using RECIST 1.1 criteria on every consecutive CT-scan until the end of follow-up or resection. Results: At baseline, a mesenteric mass was present in 64% of the patients, of whom 13.5% showed growth of the mesenteric mass with a median time to growth of 40 months. Male gender was the only independent predictor of growth (OR 2.67). Of the patients without a mesenteric mass at the first evaluation, 2.6% developed a pathological mesenteric mass. Treatment with peptide receptor radionuclide therapy (PRRT; N = 132) resulted in an objective size reduction of the mesenteric mass in 3.8%. Conclusion: The metastatic mesenteric mass in SI-NETs has a static behavior over time. Therefore, site-specific growth behavior should be taken into account when selecting target lesions and assessing disease progression and therapeutic response. PRRT appears not to be effective for size reduction of the mesenteric mass.
A Novel Salt Inducible Kinase 2 Inhibitor, ARN-3261, Sensitizes Ovarian Cancer Cell Lines and Xenografts to Carboplatin
Authors: Fan Dengxuan , Yang Hailing , Mao Weiqun , Rask Philip J. , Pang Lan , Xu Congjian , Vankayalapat Hariprasad , Ahmed Ahmed A. , Bast Robert C. , Lu Zhen
Published: January 2021

Salt-induced kinase 2 (SIK2) is a serine-threonine kinase that regulates centrosome splitting, activation of PI3 kinase and phosphorylation of class IIa HDACs, affecting gene expression. Previously, we found that inhibition of SIK2 enhanced sensitivity of ovarian cancer cells to paclitaxel. Carboplatin and paclitaxel constitute first-line therapy for most patients with ovarian carcinoma, producing a 70% clinical response rate, but curing <20% of patients with advanced disease. We have asked whether inhibition of SIK2 with ARN-3261 enhances sensitivity to carboplatin in ovarian cancer cell lines and xenograft models. ARN-3261-induced DNA damage and apoptosis were measured with γ-H2AX accumulation, comet assays, and annexin V. ARN-3261 inhibited growth of eight ovarian cancer cell lines at an IC50 of 0.8 to 3.5 µM. ARN-3261 significantly enhanced sensitivity to carboplatin in seven of eight ovarian cancer cell lines and a carboplatin-resistant cell line tested. Furthermore, ARN-3261 in combination with carboplatin produced greater inhibition of tumor growth than carboplatin alone in SKOv3 and OVCAR8 ovarian cancer xenograft models. ARN-3261 enhanced DNA damage and apoptosis by downregulating expression of survivin. Thus, a SIK2 kinase inhibitor enhanced carboplatin-induced therapy in preclinical models of ovarian cancer and deserves further evaluation in clinical trials.
Diagnosis and Treatment of Primary and Secondary Lung Cancers
Authors: Petrella Francesco
Published: January 2021

Primary and secondary lung cancers are the most common clinical conditions that thoracic surgeons have to deal with: primary lung cancer, in fact, is one of the most frequently diagnosed cancers and is the leading cause of cancer-related death worldwide [...]
Cancer of Unknown Primary: Challenges and Progress in Clinical Management
Authors: Laprovitera Noemi , Riefolo Mattia , Ambrosini Elisa , Klec Christiane , Pichler Martin , Ferracin Manuela
Published: January 2021

Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3–5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. This review article sheds light on this enigmatic disease by summarizing the current knowledge on CUPs focusing on recent discoveries and emerging diagnostic strategies.
Exploitation of Lignocellulose Fiber-Based Biotemplates to Improve the Performance of an Immobilized TiO2 Photocatalyst
Authors: Gonzalez Zoilo , Yus Joaquin , Bravo Yessica , Sanchez-Herencia Antonio Javier , Ferrari Begoña
Published: January 2021

The performance of an immobilized photocatalyst has been successfully improved by colloidal processing of a heterostructure composed by TiO2 nanoparticles and lignocellulose nanofibers (LCNFs) obtained from biomass residues. The incorporation of 4 wt.% of biotemplate to the formulation increased the degradation rate and reduced the operating time to remove the 100% of methyl orange of a liquid solution. The reaction rate constant (k = 0.29–0.45 h−1) of the prepared photocatalytic coatings (using commercial particles and templates obtained from natural-derived resources) are competitive with other pure TiO2 materials (no composites), which were prepared through more complex methodologies. The optimization stages of deposition and sintering processes allowed us to obtain homogeneous and crack-free microstructures with controlled thickness and mass values ranging from 3 to 12 µm and 0.9 to 5.6 mg, respectively. The variation of the microstructures was achieved by varying the amount of LCNF in the formulated suspensions. The versatility of the proposed methodology would allow for implementation over the internal surface of photocatalytic reactors or as a photocatalytic layer of their membranes. In addition, the processing strategy could be applied to immobilize other synthetized semiconductors with higher intrinsic photocatalysis properties.
Recent Catalytic Advances in Hydrotreatment Processes of Pyrolysis Bio-Oil
Authors: Bagnato Giuseppe , Sanna Aimaro , Paone Emilia , Catizzone Enrico
Published: January 2021

Catalytic hydrotreatment (HT) is one of the most important refining steps in the actual petroleum-based refineries for the production of fuels and chemicals, and it will play also a crucial role for the development of biomass-based refineries. In fact, the utilization of HT processes for the upgrading of biomass and/or lignocellulosic residues aimed to the production of synthetic fuels and chemical intermediates represents a reliable strategy to reduce both carbon dioxide emissions and fossil fuels dependence. At this regard, the catalytic hydrotreatment of oils obtained from either thermochemical (e.g., pyrolysis) or physical (e.g., vegetable seeds pressing) processes allows to convert biomass-derived oils into a biofuel with properties very similar to conventional ones (so-called drop-in biofuels). Similarly, catalytic hydro-processing also may have a key role in the valorization of other biorefinery streams, such as lignocellulose, for the production of high-added value chemicals. This review is focused on recent hydrotreatment developments aimed to stabilizing the pyrolytic oil from biomasses. A particular emphasis is devoted on the catalyst formulation, reaction pathways, and technologies.
Recent Developments in the Use of Heterogeneous Semiconductor Photocatalyst Based Materials for a Visible-Light-Induced Water-Splitting System—A Brief Review
Authors: Arunachalam Prabhakarn , Nagai Keiji , Amer Mabrook S. , Ghanem Mohamed A. , Ramalingam Rajabathar Jothi , Al-Mayouf Abdullah M.
Published: January 2021

Visible-light-driven photoelectrochemical (PEC) and photocatalytic water splitting systems featuring heterogeneous semiconductor photocatalysts (oxynitrides, oxysulfides, organophotocatalysts) signify an environmentally friendly and promising approach for the manufacturing of renewable hydrogen fuel. Semiconducting electrode materials as the main constituents in the PEC water splitting system have substantial effects on the device’s solar-to-hydrogen (STH) conversion efficiency. Given the complication of the photocatalysis and photoelectrolysis methods, it is indispensable to include the different electrocatalytic materials for advancing visible-light-driven water splitting, considered a difficult challenge. Heterogeneous semiconductor-based materials with narrower bandgaps (2.5 to 1.9 eV), equivalent to the theoretical STH efficiencies ranging from 9.3% to 20.9%, are recognized as new types of photoabsorbents to engage as photoelectrodes for PEC water oxidation and have fascinated much consideration. Herein, we spotlight mainly on heterogenous semiconductor-based photoanode materials for PEC water splitting. Different heterogeneous photocatalysts based materials are emphasized in different groups, such as oxynitrides, oxysulfides, and organic solids. Lastly, the design approach and future developments regarding heterogeneous photocatalysts oxide electrodes for PEC applications and photocatalytic applications are also discussed.
Surface Modifications of 2D-Ti3C2O2 by Nonmetal Doping for Obtaining High Hydrogen Evolution Reaction Activity: A Computational Approach
Authors: Li Fangtao , Wang Xiaoxu , Wang Rongming
Published: January 2021

As a typical two-dimensional (2D) MXene, Ti3C2O2 has been considered as a potential material for high-performance hydrogen evolution reaction (HER) catalyst, due to its anticorrosion and hydrophilic surface. However, it is still a challenge to improve the Ti3C2O2 surficial HER catalytic activity. In this work, we investigated the HER activity of Ti3C2O2 after the surface was doped with S, Se, and Te by the first principles method. The results indicated that the HER activity of Ti3C2O2 is improved after being doped with S, Se, Te because the Gibbs free energy of hydrogen adsorption (ΔGH) is increased from −2.19 eV to 0.08 eV. Furthermore, we also found that the ΔGH of Ti3C2O2 increased from 0.182 eV to 0.08 eV with the doping concentration varied from 5.5% to 16.7%. The HER catalytic activity improvement of Ti3C2O2 is attributed to the local crystal structure distortion in catalytic active sites and Fermi level shift leads to the p-d orbital hybridization. Our results pave a new avenue for preparing a low-cost and high performance HER catalyst.
Design of a New Gemini Lipoaminoacid with Immobilized Lipases Based on an Eco-Friendly Biosynthetic Process
Authors: Carvalho Patrícia M. , Guedes Rita C. , Bronze Maria R. , Faustino Célia M. C. , Ribeiro Maria H. L.
Published: January 2021

Lipoaminoacids (LAA) are an important group of biosurfactants, formed by a polar hydrophilic part (amino acid) and a hydrophobic tail (lipid). The gemini LAA structures allow the formation of a supramolecular complex with bioactive molecules, like DNA, which provides them with good transfection efficiency. Since lipases are naturally involved in lipid and protein metabolism, they are an alternative to the chemical production of LAA, offering an eco-friendly biosynthetic process option. This work aimed to design the production of novel cystine derived gemini through a bioconversion system using immobilized lipases. Three lipases were used: porcine pancreatic lipase (PPL); lipase from Thermomyces lanuginosus (TLL); and lipase from Rizhomucor miehei (RML). PPL was immobilized in sol-gel lenses. L-cystine dihydrochloride and dodecylamine were used as substrates for the bioreaction. The production of LAA was evaluated by thin layer chromatography (TLC), and colorimetric reaction with eosin. The identification and quantification was carried out by High Performance Liquid Chromatographer-Mass Spectrometry (HPLC-MS/MS). The optimization of media design included co-solvent (methanol, dimethylsulfoxide), biphasic (n-hexane and 2-propanol) or solvent-free media, in order to improve the biocatalytic reaction rates and yields. Moreover, a new medium was tested where dodecylamine was melted and added to the cystine and to the biocatalyst, building a system of mainly undissolved substrates, leading to 5 mg/mL of LAA. Most of the volume turned into foam, which indicated the production of the biosurfactant. For the first time, the gemini derived cystine lipoaminoacid was produced, identified, and quantified in both co-solvent and solvent-free media, with the lipases PPL, RML, and TLL.