bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Urocortin 3 mRNA in the Central Nervous System of the Sea Lamprey Petromyzon marinus
Authors: Sobrido-Cameán Daniel , Anadón Ramón , Barreiro-Iglesias Antón
Published: September 2021

In this study, we analyzed the organization of urocortin 3 (Ucn3)-expressing neuronal populations in the brain of the adult sea lamprey by means of in situ hybridization. We also studied the brain of larval sea lampreys to establish whether this prosocial neuropeptide is expressed differentially in two widely different phases of the sea lamprey life cycle. In adult sea lampreys, Ucn3 transcript expression was observed in neurons of the striatum, prethalamus, nucleus of the medial longitudinal fascicle, torus semicircularis, isthmic reticular formation, interpeduncular nucleus, posterior rhombencephalic reticular formation and nucleus of the solitary tract. Interestingly, in larval sea lampreys, only three regions showed Ucn3 expression, namely the prethalamus, the nucleus of the medial longitudinal fascicle and the posterior rhombencephalic reticular formation. A comparison with distributions of Ucn3 in other vertebrates revealed poor conservation of Ucn3 expression during vertebrate evolution. The large qualitative differences in Ucn3 expression observed between larval and adult phases suggest that the maturation of neuroregulatory circuits in the striatum, torus semicircularis and hindbrain chemosensory systems is closely related to profound life-style changes occurring after the transformation from larval to adult life.
Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions
Authors: Gong Xiping , Zhang Yumeng , Chen Jianhan
Published: September 2021

Intrinsically disordered proteins (IDPs) are highly prevalent and play important roles in biology and human diseases. It is now also recognized that many IDPs remain dynamic even in specific complexes and functional assemblies. Computer simulations are essential for deriving a molecular description of the disordered protein ensembles and dynamic interactions for a mechanistic understanding of IDPs in biology, diseases, and therapeutics. Here, we provide an in-depth review of recent advances in the multi-scale simulation of disordered protein states, with a particular emphasis on the development and application of advanced sampling techniques for studying IDPs. These techniques are critical for adequate sampling of the manifold functionally relevant conformational spaces of IDPs. Together with dramatically improved protein force fields, these advanced simulation approaches have achieved substantial success and demonstrated significant promise towards the quantitative and predictive modeling of IDPs and their dynamic interactions. We will also discuss important challenges remaining in the atomistic simulation of larger systems and how various coarse-grained approaches may help to bridge the remaining gaps in the accessible time- and length-scales of IDP simulations.
NBD2 Is Required for the Rescue of Mutant F508del CFTR by a Thiazole-Based Molecule: A Class II Corrector for the Multi-Drug Therapy of Cystic Fibrosis
Authors: Brandas Chiara , Ludovico Alessandra , Parodi Alice , Moran Oscar , Millo Enrico , Cichero Elena , Baroni Debora
Published: September 2021

Cystic fibrosis (CF) is caused by loss-of-function mutations in the CF transmembrane conductance regulator (CFTR) protein, an anion channel that regulates epithelial surface fluid secretion. The deletion of phenylalanine at position 508 (F508del) is the most common CFTR mutation. F508del CFTR is characterized by folding and trafficking defects, resulting in decreased functional expression of the protein on the plasma membrane. Several classes of small molecules, named correctors, have been developed to rescue defective F508del CFTR. Although individual correctors failed to improve the clinical status of CF patients carrying the F508del mutation, better results were obtained using correctors combinations. These results were obtained according to the premise that the administration of correctors having different sites of action should enhance F508del CFTR rescue. We investigated the putative site of action of an aminoarylthiazole 4-(3-chlorophenyl)-N-(3-(methylthio)phenyl)thiazol-2-amine, named FCG, with proven CFTR corrector activity, and its synergistic effect with the corrector VX809. We found that neither the total expression nor the maturation of WT CFTR transiently expressed in human embryonic kidney 293 cells was influenced by FCG, administrated alone or in combination with VX809. On the contrary, FCG was able to enhance F508del CFTR total expression, and its combination with VX809 provided a further effect, being able to increase not only the total expression but also the maturation of the mutant protein. Analyses on different CFTR domains and groups of domains, heterologously expressed in HEK293 cells, show that NBD2 is necessary for FCG corrector activity. Molecular modelling analyses suggest that FCG interacts with a putative region located into the NBD2, ascribing this molecule to class II correctors. Our study indicates that the continuous development and testing of combinations of correctors targeting different structural and functional defects of mutant CFTR is the best strategy to ensure a valuable therapeutic perspective to a larger cohort of CF patients.
Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution
Authors: Parsons Richard B. , Facey Paul D.
Published: September 2021

Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for NNMT in cancer survival, metastasis, and drug resistance. In this review, we discuss the evidence supporting a role for NNMT in the progression of the cancer phenotype and how it achieves this by driving the activity of pro-oncogenic NAD+-consuming enzymes. We also describe how increased NNMT activity supports the Warburg effect and how it promotes oncogenic changes in gene expression. We discuss the regulation of NNMT activity in cancer cells by both post-translational modification of the enzyme and transcription factor binding to the NNMT gene, and describe for the first time three long non-coding RNAs which may play a role in the regulation of NNMT transcription. We complete the review by discussing the development of novel anti-cancer therapeutics which target NNMT and provide insight into how NNMT-based therapies may be best employed clinically.
Structural and Functional Insights into α-Synuclein Fibril Polymorphism
Authors: Mehra Surabhi , Gadhe Laxmikant , Bera Riya , Sawner Ajay Singh , Maji Samir K.
Published: September 2021

Abnormal accumulation of aggregated α-synuclein (α-Syn) is seen in a variety of neurodegenerative diseases, including Parkinson’s disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), Parkinson’s disease dementia (PDD), and even subsets of Alzheimer’s disease (AD) showing Lewy-body-like pathology. These synucleinopathies exhibit differences in their clinical and pathological representations, reminiscent of prion disorders. Emerging evidence suggests that α-Syn self-assembles and polymerizes into conformationally diverse polymorphs in vitro and in vivo, similar to prions. These α-Syn polymorphs arising from the same precursor protein may exhibit strain-specific biochemical properties and the ability to induce distinct pathological phenotypes upon their inoculation in animal models. In this review, we discuss clinical and pathological variability in synucleinopathies and several aspects of α-Syn fibril polymorphism, including the existence of high-resolution molecular structures and brain-derived strains. The current review sheds light on the recent advances in delineating the structure–pathogenic relationship of α-Syn and how diverse α-Syn molecular polymorphs contribute to the existing clinical heterogeneity in synucleinopathies.
Publisher’s Note: BioMed—An Open Access Journal
Authors: Zeng Chaya , Vicario Unai , Lin Shu-Kun
Published: September 2021

MDPI is a pioneer of scholarly open access publishing and has supported academic communities since 1996 [...]
The Capacity of APOB-Depleted Plasma in Inducing ATP-Binding Cassette A1/G1-Mediated Macrophage Cholesterol Efflux—But Not Gut Microbial-Derived Metabolites—Is Independently Associated with Mortality in Patients with ST-Segment Elevation Myocardial Infarction
Authors: Canyelles Marina , García-Osuna Álvaro , Junza Alexandra , Yanes Oscar , Puig Núria , Ordóñez-Llanos Jordi , Sionis Alessandro , Sans-Roselló Jordi , Alquézar-Arbé Aitor , Santos David , Rotllan Noemi , Julve Josep , Tondo Mireia , Escolà-Gil Joan Carles , Blanco-Vaca Francisco
Published: September 2021

Impaired HDL-mediated macrophage cholesterol efflux and higher circulating concentrations of trimethylamine N-oxide (TMAO) levels are independent risk factors for cardiovascular mortality. The TMAO precursors, γ-butyrobetaine (γBB) and Trimethyllysine (TML), have also been recently associated with cardiovascular death, but their interactions with HDL-mediated cholesterol efflux remain unclear. We aimed to determine the associations between APOB depleted plasma-mediated macrophage cholesterol efflux and plasma TMAO, γBB, and TML concentrations and explore their association with two-year follow-up mortality in patients with acute ST-elevation myocardial infarction (STEMI) and unstable angina (UA). Baseline and ATP-binding cassette transporter ABCA1 and ABCG1 (ABCA1/G1)-mediated macrophage cholesterol efflux to APOB-depleted plasma was decreased in patients with STEMI, and the latter was further impaired in those who died during follow-up. Moreover, the circulating concentrations of TMAO, γBB, and TML were higher in the deceased STEMI patients when compared with the STEMI survivors or UA patients. However, after statistical adjustment, only ABCA1/G1-mediated macrophage cholesterol efflux remained significantly associated with mortality. Furthermore, neither the TMAO, γBB, nor TML levels altered the HDL-mediated macrophage cholesterol efflux in vitro. We conclude that impaired ABCA1/G1-mediated macrophage cholesterol efflux is independently associated with mortality at follow-up in STEMI patients.
Biomarkers and Utility of the Antioxidant Potential of Probiotic Lactobacilli and Bifidobacteria as Representatives of the Human Gut Microbiota
Authors: Averina Olga V. , Poluektova Elena U. , Marsova Mariya V. , Danilenko Valery N.
Published: September 2021

Lactobacilli and bifidobacteria are an important part of human gut microbiota. Among numerous benefits, their antioxidant properties are attracting more and more attention. Multiple in vivo and in vitro studies have demonstrated that lactobacilli and bifidobacteria, along with their cellular components, possess excellent antioxidant capacity, which provides a certain degree of protection to the human body against diseases associated with oxidative stress. Recently, lactobacilli and bifidobacteria have begun to be considered as a new source of natural antioxidants. This review summarizes the current state of research on various antioxidant properties of lactobacilli and bifidobacteria. Special emphasis is given to the mechanisms of antioxidant activity of these bacteria in the human gut microbiota, which involve bacterial cell components and metabolites. This review is also dedicated to the genes involved in the antioxidant properties of lactobacilli and bifidobacteria strains as indicators of their antioxidant potential in human gut microbiota. Identification of the antioxidant biomarkers of the gut microbiota is of great importance both for creating diagnostic systems for assessing oxidative stress and for choosing strategies aimed at restoring the normal functioning of the microbiota and, through it, restoring human health. In this review, the practical application of probiotic strains with proven antioxidant properties to prevent oxidative stress is also considered.
Miniaturized Electrochemical Sensors to Monitor Fetal Hypoxia and Acidosis in a Pregnant Sheep Model
Authors: Illa Míriam , Pla Laura , Berdún Sergio , Mir Mònica , Rivas Lourdes , Dulay Samuel , Picard-Hagen Nicole , Samitier Josep , Gratacós Eduard , Eixarch Elisenda
Published: September 2021

Perinatal asphyxia is a major cause of severe brain damage and death. For its prenatal identification, Doppler ultrasound has been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. We have evaluated the performance of a miniaturized multiparametric sensor aiming to evaluate tissular oxygen and pH changes continuously in an umbilical cord occlusion (UCO) sheep model. The electrochemical sensors were inserted in fetal hindlimb skeletal muscle and electrochemical signals were recorded. Fetal hemodynamic changes and metabolic status were also monitored during the experiment. Additionally, histological assessment of the tissue surrounding the sensors was performed. Both electrochemical sensors detected the pO2 and pH changes induced by the UCO and these changes were correlated with hemodynamic parameters as well as with pH and oxygen content in the blood. Finally, histological assessment revealed no signs of alteration on the same day of insertion. This study provides the first evidence showing the application of miniaturized multiparametric electrochemical sensors detecting changes in oxygen and pH in skeletal muscular tissue in a fetal sheep model.
Silver Binding to Bacterial Glutaredoxins Observed by NMR
Authors: Bilinovich Stephanie M. , Morris Daniel L. , Prokop Jeremy W. , Caporoso Joel A. , Taraboletti Alexandra , Duangjumpa Nilubol , Panzner Matthew J. , Shriver Leah P. , Leeper Thomas C.
Published: September 2021

Glutaredoxins (GRXs) are a class of enzymes used in the reduction of protein thiols and the removal of reactive oxygen species. The CPYC active site of GRX is a plausible metal binding site, but was previously theorized not to bind metals due to its cis-proline configuration. We have shown that not only do several transition metals bind to the CPYC active site of the Brucella melitensis GRX but also report a model of a dimeric GRX in the presence of silver. This metal complex has also been characterized using enzymology, mass spectrometry, size exclusion chromatography, and molecular modeling. Metalation of GRX unwinds the end of the helix displaying the CPYC active site to accommodate dimerization in a way that is similar to iron sulfur cluster binding in related homologs and may imply that metal binding is a more common occurrence in this class of oxidoreductases than previously appreciated.
Application of the Neonatal Behavioral Assessment Scale to Evaluate the Neurobehavior of Preterm Neonates
Authors: Malak Roksana , Fechner Brittany , Sikorska Dorota , Rosołek Marta , Mojs Ewa , Samborski Włodzimierz , Baum Ewa
Published: September 2021

Background: The neonatal behavioral assessment scale (NBAS) was primarily developed to aid in the assessment of full-term neonates. The aim of this study was to detect if the NBAS was also valuable in the assessment of preterm neonates. Materials and Methods: We assessed 112 infants at a neonatal unit using the NBAS, 4th edition. The inclusion criteria included an oxygen saturation level between 88–95% and a heartrate of 100–205 beats per minute. Infant neurobehavior was assessed using the NBAS. Results: For full-term and preterm neonates, we observed that the NBAS enabled us to assess both groups of infants and gave relevant information pertaining to them. We found a significant correlation between the average week of gestation and response to touch, sensory input, peak of excitement, cost of attention, hand-to-mouth, and quality of alertness. Conclusions: The NBAS is a valuable scale for evaluating the neurobehavior of preterm neonates. The week of gestation at birth affects certain aspects of neurobehavior, such as response to sensory input, putting hand to mouth, peak of excitement, and cost of attention. The NBAS as an individually structured assessment may help in planning for early rehabilitation and intervention for this vulnerable population.
COVID-19 Related Traumatic Distress in Psychotherapy Patients during the Pandemic: The Role of Attachment, Working Alliance, and Therapeutic Agency
Authors: Aafjes-van Doorn Katie , Békés Vera , Luo Xiaochen
Published: September 2021

The early months of the COVID-19 pandemic have been a challenging time for many psychotherapy patients. To understand why certain patients were more resilient, we examined the role of patients’ attachment anxiety and attachment avoidance, as well as collaborative therapy experiences (perceived working alliance and therapeutic agency) in their online sessions on their COVID-related traumatic distress over a three-month period. A total of 466 patients in online psychotherapy completed a survey during the first weeks of the pandemic, and 121 of those completed a follow-up survey three months later. Lower distress at follow-up was predicted by patients’ lower attachment anxiety in their online sessions after controlling for baseline distress and time of survey completion. Higher working alliance predicted less distress at follow-up only for patients with high attachment anxiety. For patients with low attachment avoidance (i.e., more securely attached), higher therapeutic agency predicted less distress. These findings suggest that patients’ attachment anxiety may play a significant role in online therapy during COVID-19 in patient’s experienced traumatic distress, and that working alliance and therapeutic agency may be differentially important for patients with different levels of attachment anxiety and avoidance.
Atomic Layer Deposition of Nanolayered Carbon Films
Authors: Xiao Zhigang , Kisslinger Kim , Monikandan Rebhadevi
Published: September 2021

In this paper, carbon thin films were grown using the plasma-enhanced atomic layer deposition (PE-ALD). Methane (CH4) was used as the carbon precursor to grow the carbon thin film. The grown film was analyzed by the high-resolution transmission electron micrograph (TEM), X-ray photoelectron spectroscopy (XPS) analysis, and Raman spectrum analysis. The analyses show that the PE-ALD-grown carbon film has an amorphous structure. It was found that the existence of defective sites (nanoscale holes or cracks) on the substrate of copper foil could facilitate the formation of nanolayered carbon films. The mechanism for the formation of nanolayered carbon film in the nanoscale holes was discussed. This finding could be used for the controlled growth of nanolayered carbon films or other two-dimensional nanomaterials while combining with modern nanopatterning techniques.
CD147 Promotes Tumor Lymphangiogenesis in Melanoma via PROX-1
Authors: Reger de Moura Coralie , Landras Alexandra , Khayati Farah , Maskos Uwe , Maouche Kamel , Battistella Maxime , Menashi Suzanne , Lebbé Céleste , Mourah Samia
Published: September 2021

Malignant melanoma is one of the most aggressive skin cancers and is characterized by early lymph node metastasis and the capacity to develop resistance to therapies. Hence, understanding the regulation of lymphangiogenesis through mechanisms contributing to lymphatic vessel formation represents a treatment strategy for metastatic cancer. We have previously shown that CD147, a transmembrane glycoprotein overexpressed in melanoma, regulates the angiogenic process in endothelial cells. In this study, we show a correlation between high CD147 expression levels and the number of lymphatic vessels expressing LYVE-1, Podoplanin, and VEGFR-3 in human melanoma lymph nodes. CD147 upregulates in vitro lymphangiogenesis and its related mediators through the PROX-1 transcription factor. In vivo studies in a melanoma model confirmed that CD147 is involved in metastasis through a similar mechanism as in vitro. This study, demonstrating the paracrine role of CD147 in the lymphangiogenesis process, suggests that CD147 could be a promising target for the inhibition of melanoma-associated lymphangiogenesis.
Utilization of Clay Materials as Support for Aspergillus japonicus Lipase: An Eco-Friendly Approach
Authors: Remonatto Daniela , Ferrari Bárbara Ribeiro , Bassan Juliana Cristina , Mussagy Cassamo Ussemane , de Carvalho Santos-Ebinuma Valéria , Veloso de Paula Ariela
Published: September 2021

Lipase is an important group of biocatalysts, which combines versatility and specificity, and can catalyze several reactions when applied in a high amount of industrial processes. In this study, the lipase produced by Aspergillus japonicus under submerged cultivation, was immobilized by physical adsorption, using clay supports, namely, diatomite, vermiculite, montmorillonite KSF (MKSF) and kaolinite. Besides, the immobilized and free enzyme was characterized, regarding pH, temperature and kinetic parameters. The most promising clay support was MKSF that presented 69.47% immobilization yield and hydrolytic activity higher than the other conditions studied (270.7 U g−1). The derivative produced with MKSF showed high stability at pH and temperature, keeping 100% of its activity throughout 12 h of incubation in the pH ranges between 4.0 and 9.0 and at a temperature from 30 to 50 °C. In addition, the immobilized lipase on MKSF support showed an improvement in the catalytic performance. The study shows the potential of using clays as support to immobilized lipolytic enzymes by adsorption method, which is a simple and cost-effective process.
Influence of NiO/La2O3 Catalyst Preparation Method on Its Reactivity in the Oxy-Steam Reforming of LNG Process
Authors: Mosinska Magdalena , Maniukiewicz Waldemar , Szynkowska-Jozwik Malgorzata I. , Mierczynski Pawel
Published: September 2021

The oxy-steam reforming of liquefied natural gas reaction (OSR-LNG) is promising process for syngas generation. In this paper, the catalytic properties of NiO/La2O3 systems prepared by wet impregnation and co-precipitation methods were extensively investigated in OSR-LNG reaction. The physicochemical properties of the studied catalytic materials were determined using various techniques including Temperature programmed reduction (TPR-H2), Temperature programmed desorption (TPD-NH3), Brunauer, Emmett and Teller (BET), X-ray diffraction (XRD) and Scanning electron microscopy (SEM) with an energy dispersive X-Ray spectrometer (EDS). Reactivity measurements performed in the OSR-LNG process showed that the catalyst preparation method and the calcination temperature significantly affected the activity of NiO/La2O3 catalysts in the OSR-LNG reaction. The catalytic activity tests showed that NiO/La2O3 system prepared by a wet impregnation method and calcined at 700 °C showed the total conversion of the LNG component at 900 °C and the highest H2 yield at 700 and 900 °C. The phase composition studies confirmed the formation of the LaNiO3 structure in the case of the NiO/La2O3 catalyst prepared by wet impregnation, calcined at the temperature of 700 °C. Catalytic activity measurements showed that the reactivity of the catalysts was related to their phase composition and acidity. SEM images of spent catalysts showed that the smallest amount of carbon deposit was detected on the surface of the most active systems.
Construction of a Novel Chimeric Dextransucrase Fused to the Carbohydrate-Binding Module CBM2a
Authors: Fraga Vidal Reinaldo , Arísticas Ribalta Roberto Carlos , Martínez Valdés Lisandra Teresa , Lafargue Gámez Meinardo , Montes Alvarez Amanda , Rubio Sánchez Arianne , Dubreucq Eric , Moreau Benoît
Published: September 2021

Lactic acid bacteria (LAB) have the potential to produce homoexopolysaccharides (HoPS). Their health benefits and physicochemical properties have been the subject of extensive research. The HoPS functional properties are determined by molecular weight, the type of glycosidic linkages, degrees of branching and chemical composition. The dextransucrases (DSases) produce a kind of HoPS (dextrans), which are among the first biopolymers produced at industrial scale with applications in medicine and biotechnology. The glycodiversification opens additional applications for DSases. Therefore, the design and characterization of new DSases is of prime importance. Previously, we described the isolation and characterization of a novel extracellular dextransucrase (DSR-F) encoding gene. In this study, from DSR-F, we design a novel chimeric dextransucrase DSR-F-∆SP-∆GBD-CBM2a, where DSR-F-∆SP-∆GBD (APY repeats and a CW repeat deleted) was fused to the carbohydrate-binding module (CBM2a) of the β-1-4 exoglucanase/xylanase Cex (Xyn10A) of Cellulomonas fimi ATCC 484. This dextransucrase variant is active and the specificity is not altered. The DSR-F-∆SP-∆GBD-CBM2a was purified by cellulose affinity chromatography for the first time. This research showed that hybrids and chimeric biocatalyst DSases with novel binding capacity to cellulose can be designed to purify and immobilize using renewable lignocellulosic materials as supports.
A Facile Synthesis of Bi2O3/CoFe2O4 Nanocomposite with Improved Synergistic Photocatalytic Potential for Dye Degradation
Authors: Naveed Abdul Basit , Riaz Fakhira , Mahmood Azhar , Shahid Ammara , Aqeel Saman
Published: September 2021

Semiconductor-based photocatalysis is a probable approach to overcoming many pollution problems and eradicating toxic organic materials from wastewater. This research endeavor aimed to explore the synergistic potential of different semiconductor nanocomposites for photocatalytic degradation of organic pollutants in contaminated water. A facile hydrothermal approach was employed to synthesize bismuth oxide and cobalt ferrite nanoparticles from their precursors—bismuth nitrate pentahydrate, ferric chloride hexahydrate and cobalt chloride hexahydrate—with various concentrations and conditions to optimize the product. Subsequently, nanocomposites of bismuth oxide and cobalt ferrite were prepared by solid-state mixing in varying concentrations followed by calcination. UV/visible diffuse reflectance spectroscopy, X-ray diffraction, scanning electron microscopy and elemental dispersive X-ray spectroscopic techniques have corroborated the successful synthesis of nanocomposites. The energy gaps of bismuth oxide and cobalt ferrite nanocomposites were computed in the range of 1.58–1.62 eV by Tauc plots. These nanocomposite materials were ascertained for photocatalytic potential to degrade methyl orange organic dye in water. A nanocomposite with equiquantic proportions has shown the best photocatalytic degradation activity, which may be attributed to the type-II band configuration and a synergistic effect, because Bi2O3 acts as an electron sink. This synergism has reduced the cogent band gap, hindered electron hole recombination and increased electron hole availabilities for photodegradation reactions, thus ensuing an efficient photodegradation co-work of Bi2O3/CoFe2O4 nanocomposites.
Inflammaging, an Imbalanced Immune Response That Needs to Be Restored for Cancer Prevention and Treatment in the Elderly
Authors: Serrano-López Juana , Martín-Antonio Beatriz
Published: September 2021

Nowadays, new advances in society and health have brought an increased life expectancy. However, at the same time, aging comes with complications that impact the development of autoimmunity, neurodegenerative diseases and cancer. These complications affect the quality of life and impact the public health system. Specifically, with aging, a low-grade chronic sterile systemic inflammation with self-reactivity in the absence of acute infection occurs termed inflammaging. Inflammaging is related to an imbalanced immune response that can be either naturally acquired with aging or accelerated due to external triggers. Different molecules, metabolites and inflammatory forms of cell death are highly involved in these processes. Importantly, adoptive cellular immunotherapy is a modality of treatment for cancer patients that administers ex vivo expanded immune cells in the patient. The manipulation of these cells confers them enhanced proinflammatory properties. A general consequence of proinflammatory events is the development of autoimmune diseases and cancer. Herein, we review subsets of immune cells with a pertinent role in inflammaging, relevant proteins involved in these inflammatory events and external triggers that enhance and accelerate these processes. Moreover, we mention relevant preclinical studies that demonstrate associations of chronic inflammation with cancer development.
Unraveling the Multifaceted Nature of CD8 T Cell Exhaustion Provides the Molecular Basis for Therapeutic T Cell Reconstitution in Chronic Hepatitis B and C
Authors: Barili Valeria , Vecchi Andrea , Rossi Marzia , Montali Ilaria , Tiezzi Camilla , Penna Amalia , Laccabue Diletta , Missale Gabriele , Fisicaro Paola , Boni Carolina
Published: September 2021

In chronic hepatitis B and C virus infections persistently elevated antigen levels drive CD8+ T cells toward a peculiar differentiation state known as T cell exhaustion, which poses crucial constraints to antiviral immunity. Available evidence indicates that T cell exhaustion is associated with a series of metabolic and signaling deregulations and with a very peculiar epigenetic status which all together lead to reduced effector functions. A clear mechanistic network explaining how intracellular metabolic derangements, transcriptional and signaling alterations so far described are interconnected in a comprehensive and unified view of the T cell exhaustion differentiation profile is still lacking. Addressing this issue is of key importance for the development of innovative strategies to boost host immunity in order to achieve viral clearance. This review will discuss the current knowledge in HBV and HCV infections, addressing how innate immunity, metabolic derangements, extensive stress responses and altered epigenetic programs may be targeted to restore functionality and responsiveness of virus-specific CD8 T cells in the context of chronic virus infections.
Lamin B1 Accumulation’s Effects on Autosomal Dominant Leukodystrophy (ADLD): Induction of Reactivity in the Astrocytes
Authors: Ratti Stefano , Rusciano Isabella , Mongiorgi Sara , Neri Irene , Cappellini Alessandra , Cortelli Pietro , Suh Pann-Ghill , McCubrey James A. , Manzoli Lucia , Cocco Lucio , Ramazzotti Giulia
Published: September 2021

Autosomal dominant leukodystrophy (ADLD) is an extremely rare and fatal neurodegenerative disease due to the overexpression of the nuclear lamina component Lamin B1. Many aspects of the pathology still remain unrevealed. This work highlights the effect of Lamin B1 accumulation on different cellular functions in an ADLD astrocytic in vitro model. Lamin B1 overexpression induces alterations in cell survival signaling pathways with GSK3β inactivation, but not the upregulation of β-catenin targets, therefore resulting in a reduction in astrocyte survival. Moreover, Lamin B1 build up affects proliferation and cell cycle progression with an increase of PPARγ and p27 and a decrease of Cyclin D1. These events are also associated to a reduction in cell viability and an induction of apoptosis. Interestingly, ADLD astrocytes trigger a tentative activation of survival pathways that are ineffective. Finally, astrocytes overexpressing Lamin B1 show increased immunoreactivity for both GFAP and vimentin together with NF-kB phosphorylation and c-Fos increase, suggesting astrocytes reactivity and substantial cellular activation. These data demonstrate that Lamin B1 accumulation is correlated to biochemical, metabolic, and morphologic remodeling, probably related to the induction of a reactive astrocytes phenotype that could be strictly associated to ADLD pathological mechanisms.
Evaluation of an RNAseq-Based Immunogenomic Liquid Biopsy Approach in Early-Stage Prostate Cancer
Authors: Van Neste Leander , Wojno Kirk J. , Henao Ricardo , Mane Shrikant , Korman Howard , Hafron Jason , Kernen Kenneth , Tinawi-Aljundi Rima , Putzi Mathew , Kassis Amin I. , Kantoff Philip W.
Published: September 2021

The primary objective of this study is to detect biomarkers and develop models that enable the identification of clinically significant prostate cancer and to understand the biologic implications of the genes involved. Peripheral blood samples (1018 patients) were split chronologically into independent training (n = 713) and validation (n = 305) sets. Whole transcriptome RNA sequencing was performed on isolated phagocytic CD14+ and non-phagocytic CD2+ cells and their gene expression levels were used to develop predictive models that correlate to adverse pathologic features. The immune-transcriptomic model with the highest performance for predicting adverse pathology, based on a subtraction of the log-transformed expression signals of the two cell types, displayed an area under the curve (AUC) of the receiver operating characteristic of 0.70. The addition of biomarkers in combination with traditional clinical risk factors (age, serum prostate-specific antigen (PSA), PSA density, race, digital rectal examination (DRE), and family history) enhanced the AUC to 0.91 and 0.83 for the training and validation sets, respectively. The markers identified by this approach uncovered specific pathway associations relevant to (prostate) cancer biology. Increased phagocytic activity in conjunction with cancer-associated (mis-)regulation is also represented by these markers. Differential gene expression of circulating immune cells gives insight into the cellular immune response to early tumor development and immune surveillance.
Classification of Cell-in-Cell Structures: Different Phenomena with Similar Appearance
Authors: Borensztejn Karol , Tyrna Paweł , Gaweł Agata M. , Dziuba Ireneusz , Wojcik Cezary , Bialy Lukasz P. , Mlynarczuk-Bialy Izabela
Published: September 2021

A phenomenon known for over 100 years named “cell-in-cell” (CIC) is now undergoing its renaissance, mostly due to modern cell visualization techniques. It is no longer an esoteric process studied by a few cell biologists, as there is increasing evidence that CICs may have prognostic and diagnostic value for cancer patients. There are many unresolved questions stemming from the difficulties in studying CICs and the limitations of current molecular techniques. CIC formation involves a dynamic interaction between an outer or engulfing cell and an inner or engulfed cell, which can be of the same (homotypic) or different kind (heterotypic). Either one of those cells appears to be able to initiate this process, which involves signaling through cell–cell adhesion, followed by cytoskeleton activation, leading to the deformation of the cellular membrane and movements of both cells that subsequently result in CICs. This review focuses on the distinction of five known forms of CIC (cell cannibalism, phagoptosis, enclysis, entosis, and emperipolesis), their unique features, characteristics, and underlying molecular mechanisms.
Current State of Laser-Induced Fluorescence Spectroscopy for Designing Biochemical Sensors
Authors: Taylor Adam Thomas , Lai Edward P. C.
Published: September 2021

Laser-induced fluorescence (LIF) has been a valuable analytical technique since the 1970s that has only been made more useful through advances in other scientific fields such as biochemistry. Moreover, advances in laser and detector technology have seen a decrease in LIF detector costs and an increase in their ease of use. These changes have allowed for LIF technology to be widely adopted for various sensor designs in combination with advanced instruments. With advances in biochemistry necessitating the detection of complex metabolites, labelling with fluorescent chemical reagents may be necessary to improve detection sensitivity. Furthermore, advances made in fluorescent labeling technologies have allowed for the use of LIF in the detection of nanoparticles as well as for imaging techniques using nanoparticles as signal amplifiers. This technology has become invaluable in the detection of environmental pollutants, monitoring of biological metabolites, biological imaging, and cancer diagnosis, making it one of the most valuable analytical science techniques currently available.
Introduction of 24 h Resident Consultant Cover in a Tertiary Neonatal Unit—Impact on Mortality and Clinical Outcomes
Authors: Zorro Carolina , Dassios Theodore , Hickey Ann , Arasu Anusha , Bhat Ravindra , Greenough Anne
Published: September 2021

Background: We aimed to determine whether the introduction of 24 h cover by resident consultants in a tertiary neonatal unit affected mortality and other clinical outcomes. Methods: Retrospective cohort study in a tertiary medical and surgical neonatal unit between 2010–2020 of all liveborn infants admitted to the neonatal unit. Out of hours cover was rearranged in 2014 to ensure 24 h presence of a senior trained neonatologist (resident consultant). Results: In the study period, 4778 infants were included: 2613 in the pre-resident period and 2165 in the resident period. The median (IQR) time to first consultation by a senior member of staff was significantly longer in the pre-resident period [1.5 (0.6–4.3) h] compared to the resident period [0.5 (0.3–1.5) h, p < 0.001]. Overall, mortality was similar in the pre-resident and the resident periods (3.2% versus 2.3%, p = 0.077), but the mortality of infants born at night was significantly higher in the pre-resident (4.5%) compared to the resident period (2.5%, p = 0.016). The resident period was independently associated with an increased survival to discharge (adjusted p < 0.001, odds ratio: 2.0) after adjusting for gestational age, admission temperature and duration of ventilation. Conclusions: Following introduction of a resident consultant model the mortality and time to consultation after admission decreased.
Renadirsen, a Novel 2′OMeRNA/ENA® Chimera Antisense Oligonucleotide, Induces Robust Exon 45 Skipping for Dystrophin In Vivo
Authors: Ito Kentaro , Takakusa Hideo , Kakuta Masayo , Kanda Akira , Takagi Nana , Nagase Hiroyuki , Watanabe Nobuaki , Asano Daigo , Goda Ryoya , Masuda Takeshi , Nakamura Akifumi , Onishi Yoshiyuki , Onoda Toshio , Koizumi Makoto , Takeshima Yasuhiro , Matsuo Masafumi , Takaishi Kiyosumi
Published: September 2021

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by out-of-frame or nonsense mutation in the dystrophin gene. It begins with a loss of ambulation between 9 and 14 years of age, followed by various other symptoms including cardiac dysfunction. Exon skipping of patients’ DMD pre-mRNA induced by antisense oligonucleotides (AOs) is expected to produce shorter but partly functional dystrophin proteins, such as those possessed by patients with the less severe Becker muscular dystrophy. We are working on developing modified nucleotides, such as 2′-O,4′-C-ethylene-bridged nucleic acids (ENAs), possessing high nuclease resistance and high affinity for complementary RNA strands. Here, we demonstrate the preclinical characteristics (exon-skipping activity in vivo, stability in blood, pharmacokinetics, and tissue distribution) of renadirsen, a novel AO modified with 2′-O-methyl RNA/ENA chimera phosphorothioate designed for dystrophin exon 45 skipping and currently under clinical trials. Notably, systemic delivery of renadirsen sodium promoted dystrophin exon skipping in cardiac muscle, skeletal muscle, and diaphragm, compared with AOs with the same sequence as renadirsen but conventionally modified by PMO and 2′OMePS. These findings suggest the promise of renadirsen sodium as a therapeutic agent that improves not only skeletal muscle symptoms but also other symptoms in DMD patients, such as cardiac dysfunction.
Antidiabetic Effect of Taxifolin in Cultured L6 Myotubes and Type 2 Diabetic Model KK-Ay/Ta Mice with Hyperglycemia and Hyperuricemia
Authors: Kondo Shinji , Adachi Shin-ichi , Yoshizawa Fumiaki , Yagasaki Kazumi
Published: September 2021

Muscle is the largest tissue in our body and plays an important role in glucose homeostasis and hence diabetes. In the present study, we examined the effects of taxifolin (TXF) on glucose metabolism in cultured L6 muscle cells (myotubes) and in type 2 diabetic (T2D) model KK-Ay/Ta mice. TXF dose-dependently increased glucose uptake (GU) in L6 myotubes under the condition of insulin absence. This increase in GU was partially, but significantly canceled by TXF treatment in combination with either LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), which phosphorylates protein kinase B (Akt) or Compound C, an inhibitor of 5’-adenosine monophosphate-activated protein kinase (AMPK). Furthermore, TXF was demonstrated to activate (=phosphorylate) both Akt and AMPK, and promote glucose transporter 4 (GLUT4) translocation to the plasma membrane from cytosol of L6 myotubes via both PI3K/Akt and AMPK signaling pathways. Based on these in vitro findings, we conducted an in vivo experiment in KK-Ay/Ta mice with hyperglycemia and hyperuricemia. Fasting plasma glucose, insulin, uric acid levels and an index of insulin resistance (HOMA-IR) increased significantly in the T2D model mice compared with normal ones. Such rises in the T2D state were significantly suppressed by oral administration of TXF for four weeks. These results suggest that TXF is a potent antihyperglycemic and antihyperuricemic phytochemical in the T2D state.
What Drives Climate Action in Canada’s Provincial North? Exploring the Role of Connectedness to Nature, Climate Worry, and Talking with Friends and Family
Authors: Galway Lindsay P. , Beery Thomas , Buse Chris , Gislason Maya K.
Published: September 2021

Despite widespread calls to action from the scientific community and beyond, a concerning climate action gap exists. This paper aims to enhance our understanding of the role of connectedness to nature in promoting individual-level climate action in a unique setting where climate research and action are lacking: Canada’s Provincial North. To begin to understand possible pathways, we also examined whether climate worry and talking about climate change with family and friends mediate the relationship between connectedness to nature and climate action. We used data collected via postal surveys in two Provincial North communities, Thunder Bay (Ontario), and Prince George (British Columbia) (n = 628). Results show that connectedness to nature has a direct positive association with individual-level climate action, controlling for gender and education. Results of parallel mediation analyses further show that connectedness to nature is indirectly associated with individual-level climate action, mediated by both climate worry and talking about climate change with family and friends. Finally, results suggest that climate worry and talking about climate change with family and friends serially mediate the relationship between connectedness to nature and with individual-level climate action. These findings are relevant for climate change engagement and action, especially across Canada’s Provincial North, but also in similar settings characterized by marginalization, heightened vulnerability to climate change, urban islands within vast rural and remote landscapes, and economies and social identities tied to resource extraction. Drawing on these findings, we argue that cultivating stronger connections with nature in the places where people live, learn, work, and play is an important and currently underutilized leverage point for promoting individual-level climate action. This study therefore adds to the current and increasingly relevant calls for (re-)connecting with nature that have been made by others across a range of disciplinary and sectoral divides.
Potential for More Sustainable Energy Usage in the Postharvest Handling of Horticultural Produce through Management of Ethylene
Authors: Wills Ron Baden Howe
Published: September 2021

The perishable nature of fruit and vegetables requires some technological intervention to maintain quality during handling and marketing. The technology of choice for many years has been use of low temperatures as it is effective in reducing metabolism and hence extend postharvest life. However, refrigerated storage is energy intensive and the growing urgency to reduce international greenhouse gas emissions has created a need for technologies that are more environmentally sustainable but still acceptable to consumers. Ethylene is well known to promote ripening and senescence of fruit and vegetables. This presentation will review the existing data that support the potential for managing the concentration of ethylene in the atmosphere around produce in postharvest situations to allow a reduced reliance on refrigeration and thus reduce energy consumption. Methods for managing ethylene levels around produce, and barriers that need to be overcome in order to move from a temperature-based mindset are discussed.
RETRACTED: The Effect of Structural Phase Transitions on Electronic and Optical Properties of CsPbI3 Pure Inorganic Perovskites
Authors: Syah Rahmad , Davarpanah Afshin , Nasution Mahyuddin , Wali Qamar , Ramdan Dadan , Albaqami Munirah , Ouladsmane Mohamed , Noori Saja
Published: September 2021

Hybrid inorganic perovskites (HIPs) have been developed in recent years as new high-efficiency semiconductors with a wide range of uses in various optoelectronic applications such as solar cells and light-emitting diodes (LEDs). In this work, we used a first-principles theoretical study to investigate the effects of phase transition on the electronic and optical properties of CsPbI3 pure inorganic perovskites. The results showed that at temperatures over 300 °C, the structure of CsPbI3 exhibits a cube phase (pm3m) with no tilt of PbI6 octahedra (distortion index = 0 and bond angle variance = 0). As the temperature decreases (approximately to room temperature), the PbI6 octahedra is tilted, and the distortion index and bond angle variance increase. Around room temperature, the CsPbI3 structure enters an orthorhombic phase with two tilts PbI6 octahedra. It was found that changing the halogens in all structures reduces the volume of PbI6 octahedra. The tilted PbI6 octahedra causes the distribution of interactions to vary drastically, which leads to a change in band gap energy. This is the main reason for the red and blue shifts in the absorption spectrum of CsPbI3. In general, it can be said that the origin of all changes in the structural, electronic, and optical properties of HIPs is the changes in the volume, orientation, and distortion index of PbI6 octahedra.
Flexural Performance of Small-Scale Textile-Reinforced Concrete Beams
Authors: Alrshoudi Fahed
Published: September 2021

Textile-reinforced concrete (TRC) as a novel high-performance composite material can be used as a strengthening material and component bearing load alone. The flexural performance of TRC beams strengthened with textile reinforcement such as carbon tows was experimentally examined and associated with those of steel-reinforced concrete (SRC) beams. Through four-point bending tests, this research explores the effects of textile layers and dosages of short textile fibre on the flexural strength of concrete beams. A total of 64 prism samples of size 100 mm × 100 mm × 500 mm were made, flexure-strengthened, and tested to evaluate various characteristics and the efficiency of TRC versus SRC beams. TRC beams performed exceptionally well as supporting material in enhancing concrete’s flexural capacity; in addition, TRC’s average ultimate load effectiveness was up to 56% than that of SRC specimens. Furthermore, the maximum deflection was about 37% lesser than SRC beams. The results showed that by increasing the number of layers, the TRC’s effectiveness was significantly increased, and the failure mode became more ductile.