bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceived Knowledge and Attitudes of Faculty Members towards Inclusive Education for Students with Disabilities: Evidence from a Greek University
Authors: Papadakaki Maria , Maraki Anastasia , Bitsakos Nikolaos , Chliaoutakis Joannes
Published: February 2022

The current paper aimed at investigating factors affecting the perceptions and attitudes of faculty members towards inclusive education for students with disabilities in a Greek University. A questionnaire, based on the “Expanding Cultural Awareness of Exceptional Learners-ExCEL” was distributed online to 311 faculty members, during the first semester of 2020. The questionnaire explored participants’ sociodemographic and academic background, prior training and personal experience with disability, perceived knowledge, beliefs and attitudes towards inclusive education practices. A total of 80 questionnaires were completed (males 56.3%; aged 41–50 years 43.7%; working experience > 16 years 52.4%; prior training on disability 77.5%). Factor analysis identified four constructs relevant to: (a) perceived knowledge regarding the legal framework (“Perceived Knowledge”), (b) intention towards the provision of general accommodations in class (“Help in Class”), (c) intention towards resource provision (“Material Offer”), and (d) beliefs about the provision of accommodations to students with disabilities (“Negative Attitude”). Gender, faculty subject and prior training on disability were shown to affect the participants’ “Perceived Knowledge”, while working position was shown to affect “Material Offer”. Age, working experience, and personal experience with disability did not reveal any significant effect. More research is needed to investigate the attitudinal and practical barriers of faculty members towards meeting students’ educational needs.
Assessing the Emergency Response Role of Community-Based Organizations (CBOs) Serving People with Disabilities and Older Adults in Puerto Rico Post-Hurricane María and during the COVID-19 Pandemic
Authors: Engelman Alina , Guzzardo Mariana T. , Antolin Muñiz Marley , Arenas Laura , Gomez Aracely
Published: February 2022

In Puerto Rico, a host of factors makes the role of community-based organizations (CBOs) critically important in emergency preparedness and response (EPR) and disability-inclusive disaster risk reduction (DiDRR) addressing the needs of people with disabilities and older adults. The territory has been the site of recurring hurricanes, earthquakes, medical crises, and human-made disasters. Political, social, and economic problems unique to the archipelago have historically limited the preparedness and response capacity of governmental authorities, especially for its most at-risk populations. In a context of severe constraints on government resources, CBOs are positioned to play an outsized role in providing services for disabled and older adults before, during, and after emergencies. This study assesses the emergency preparedness and response capacity of CBOs (n = 22) for addressing the needs of people with disabilities and the elderly. Semi-structured, largely closed-ended interviews were conducted in Spanish with key informants at Puerto Rican CBOs. The interviews included questions about emergency preparedness and response training, as well as organizational capacity during COVID-19 and post-Hurricane María. This study posits that conditions in Puerto Rico place CBOs at the forefront of critical responsibilities including emergency preparedness and response, warranting assessment of their practices and resources to assist them in fulfilling their mission.
Adolescents’ Perspectives on the Drivers of Obesity Using a Group Model Building Approach: A South African Perspective
Authors: Hendricks Gaironeesa , Savona Natalie , Aguiar Anaely , Alaba Olufunke , Booley Sharmilah , Malczyk Sonia , Nwosu Emmanuel , Knai Cecile , Rutter Harry , Klepp Knut-Inge , Harbron Janetta
Published: February 2022

Overweight and obesity increase the risk of a range of poor physiological and psychosocial health outcomes. Previous work with well-defined cohorts has explored the determinants of obesity and employed various methods and measures; however, less is known on the broader societal drivers, beyond individual-level influences, using a systems framework with adolescents. The aim of this study was to explore the drivers of obesity from adolescents’ perspectives using a systems approach through group model building in four South African schools. Group model building was used to generate 4 causal loop diagrams with 62 adolescents aged 16–18 years. These maps were merged into one final map, and the main themes were identified: (i) physical activity and social media use; (ii) physical activity, health-related morbidity, and socio-economic status; (iii) accessibility of unhealthy food and energy intake/body weight; (iv) psychological distress, body weight, and weight-related bullying; and (v) parental involvement and unhealthy food intake. Our study identified meaningful policy-relevant insights into the drivers of adolescent obesity, as described by the young people themselves in a South African context. This approach, both the process of construction and the final visualization, provides a basis for taking a novel approach to prevention and intervention recommendations for adolescent obesity.
Intriguing Cytotoxicity of the Street Dissociative Anesthetic Methoxphenidine: Unexpected Impurities Spotted
Authors: Jurásek Bronislav , Rimpelová Silvie , Babor Martin , Čejka Jan , Bartůněk Vilém , Kuchař Martin
Published: February 2022

The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate complex. Concerning the unknown and potentially hazardous properties of this sample, we performed an in vitro cytotoxicity screening in cell lines of various origins (e.g., kidney, liver, bladder) which was compared with the toxicity results of the methoxphenidine standard prepared for this purpose. The street methoxphenidine sample exhibited markedly higher toxicity than the standard, which was probably caused by the anion impurity. Since it is not usual to analyze anions in salts of novel psychoactive substances, but such samples may be commonly available at the drug black market, we have developed a method for their identification with X-ray powder diffraction (XRPD), which also enabled us to distinguish between different polymorphs/solvates of methoxphenidine that were crystallized in the laboratory. XRPD offers additional data about samples, which may not be discovered by routine techniques, and in some cases, they may help to find out essential information.
Gremlin-1 and BMP-4 Overexpressed in Osteoarthritis Drive an Osteochondral-Remodeling Program in Osteoblasts and Hypertrophic Chondrocytes
Authors: Pérez-Lozano Maria-Luisa , Sudre Laure , van Eegher Sandy , Citadelle Danièle , Pigenet Audrey , Lafage-Proust Marie-Helène , Pastoureau Philippe , De Ceuninck Frédéric , Berenbaum Francis , Houard Xavier
Published: February 2022

Osteoarthritis (OA) is a whole joint disease characterized by an important remodeling of the osteochondral junction. It includes cartilage mineralization due to chondrocyte hypertrophic differentiation and bone sclerosis. Here, we investigated whether gremlin-1 (Grem-1) and its BMP partners could be involved in the remodeling events of the osteochondral junction in OA. We found that Grem-1, BMP-2, and BMP-4 immunostaining was detected in chondrocytes from the deep layer of cartilage and in subchondral bone of knee OA patients, and was positively correlated with cartilage damage. ELISA assays showed that bone released more Grem-1 and BMP-4 than cartilage, which released more BMP-2. In vitro experiments evidenced that compression stimulated the expression and the release of Grem-1 and BMP-4 by osteoblasts. Grem-1 was also overexpressed during the prehypertrophic to hypertrophic differentiation of murine articular chondrocytes. Recombinant Grem-1 stimulated Mmp-3 and Mmp-13 expression in murine chondrocytes and osteoblasts, whereas recombinant BMP-4 stimulated the expression of genes associated with angiogenesis (Angptl4 and osteoclastogenesis (Rankl and Ccl2). In conclusion, Grem-1 and BMP-4, whose expression at the osteochondral junction increased with OA progression, may favor the pathological remodeling of the osteochondral junction by inducing a catabolic and tissue remodeling program in hypertrophic chondrocytes and osteoblasts.
Network-Assisted Systems Biology Analysis of the Mitochondrial Proteome in a Pre-Clinical Model of Ischemia, Revascularization and Post-Conditioning
Authors: Gallinat Alex , Vilahur Gemma , Padró Teresa , Badimon Lina
Published: February 2022

Infarct size is the major risk predictor for developing heart failure after an acute myocardial infarction (AMI). The discovery of the conditioning phenomena (i.e., repetitive brief cycles of ischemia applied either before or after a prolonged ischemic insult) has highlighted the existence of endogenous protective mechanisms of the heart potentially limiting infarct size after revascularization. However, most cardioprotective strategies, aiming at infarct size reduction, have failed in clinical studies. Thus, cardioprotection is an unmet clinical need. In the present study, we took a network-assisted systems biology approach to explore the mitochondrial proteomic signature of the myocardium after ischemia, ischemia with direct revascularization, and ischemia with re-establishment of blood flow by post-conditioning in a swine model of AMI. Furthermore, network extension with the ENCODE project human regulatory data allowed the prediction of potential transcription factors at play in the response to post-conditioning of the myocardium. Collectively, our results identify cardiac metabolism as a driver of cardioprotection, highlighting a dual role for post-conditioning promoting metabolic reprogramming of the myocardium, and a protective response mediated by VDAC2 and DJ-1 in the mitochondria.
Global N6-Methyladenosine Profiling Revealed the Tissue-Specific Epitranscriptomic Regulation of Rice Responses to Salt Stress
Authors: Wang Yinxiao , Du Fengping , Li Yingbo , Wang Juan , Zhao Xiuqin , Li Zhikang , Xu Jianlong , Wang Wensheng , Fu Binying
Published: February 2022

N6-methyladenosine (m6A) methylation represents a new layer of the epitranscriptomic regulation of plant development and growth. However, the effects of m6A on rice responses to environmental stimuli remain unclear. In this study, we performed a methylated-RNA immunoprecipitation sequencing analysis and compared the changes in m6A methylation and gene expression in rice under salt stress conditions. Salt stress significantly increased the m6A methylation in the shoots (p value < 0.05). Additionally, 2537 and 2304 differential m6A sites within 2134 and 1997 genes were identified in the shoots and roots, respectively, under salt stress and control conditions. These differential m6A sites were largely regulated in a tissue-specific manner. A unique set of genes encoding transcription factors, antioxidants, and auxin-responsive proteins had increased or decreased m6A methylation levels only in the shoots or roots under salt stress, implying m6A may mediate salt tolerance by regulating transcription, ROS homeostasis, and auxin signaling in a tissue-specific manner. Integrating analyses of m6A modifications and gene expression changes revealed that m6A changes regulate the expression of genes controlling plant growth, stress responses, and ion transport under saline conditions. These findings may help clarify the regulatory effects of m6A modifications on rice salt tolerance.
Evolutionary Significance of NHX Family and NHX1 in Salinity Stress Adaptation in the Genus Oryza
Authors: Solis Celymar Angela , Yong Miing-Tiem , Zhou Meixue , Venkataraman Gayatri , Shabala Lana , Holford Paul , Shabala Sergey , Chen Zhong-Hua
Published: February 2022

Rice (Oryza sativa), a staple crop for a substantial part of the world’s population, is highly sensitive to soil salinity; however, some wild Oryza relatives can survive in highly saline environments. Sodium/hydrogen antiporter (NHX) family members contribute to Na+ homeostasis in plants and play a major role in conferring salinity tolerance. In this study, we analyzed the evolution of NHX family members using phylogeny, conserved domains, tertiary structures, expression patterns, and physiology of cultivated and wild Oryza species to decipher the role of NHXs in salt tolerance in Oryza. Phylogenetic analysis showed that the NHX family can be classified into three subfamilies directly related to their subcellular localization: endomembrane, plasma membrane, and tonoplast (vacuolar subfamily, vNHX1). Phylogenetic and structural analysis showed that vNHX1s have evolved from streptophyte algae (e.g., Klebsormidium nitens) and are abundant and highly conserved in all major land plant lineages, including Oryza. Moreover, we showed that tissue tolerance is a crucial trait conferring tolerance to salinity in wild rice species. Higher Na+ accumulation and reduced Na+ effluxes in leaf mesophyll were observed in the salt-tolerant wild rice species O. alta, O. latifolia, and O. coarctata. Among the key genes affecting tissue tolerance, expression of NHX1 and SOS1/NHX7 exhibited significant correlation with salt tolerance among the rice species and cultivars. This study provides insights into the evolutionary origin of plant NHXs and their role in tissue tolerance of Oryza species and facilitates the inclusion of this trait during the development of salinity-tolerant rice cultivars.
Application of Proteomics in Pancreatic Ductal Adenocarcinoma Biomarker Investigations: A Review
Authors: Vellan Christina Jane , Jayapalan Jaime Jacqueline , Yoong Boon-Koon , Abdul-Aziz Azlina , Mat-Junit Sarni , Subramanian Perumal
Published: February 2022

Pancreatic ductal adenocarcinoma (PDAC), a highly aggressive malignancy with a poor prognosis is usually detected at the advanced stage of the disease. The only US Food and Drug Administration-approved biomarker that is available for PDAC, CA 19-9, is most useful in monitoring treatment response among PDAC patients rather than for early detection. Moreover, when CA 19-9 is solely used for diagnostic purposes, it has only a recorded sensitivity of 79% and specificity of 82% in symptomatic individuals. Therefore, there is an urgent need to identify reliable biomarkers for diagnosis (specifically for the early diagnosis), ascertain prognosis as well as to monitor treatment response and tumour recurrence of PDAC. In recent years, proteomic technologies are growing exponentially at an accelerated rate for a wide range of applications in cancer research. In this review, we discussed the current status of biomarker research for PDAC using various proteomic technologies. This review will explore the potential perspective for understanding and identifying the unique alterations in protein expressions that could prove beneficial in discovering new robust biomarkers to detect PDAC at an early stage, ascertain prognosis of patients with the disease in addition to monitoring treatment response and tumour recurrence of patients.
Conservation and Divergence of SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) Gene Family between Wheat and Rice
Authors: Li Li , Shi Fu , Wang Guoli , Guan Yanbin , Zhang Yufan , Chen Mingjie , Chang Junli , Yang Guangxiao , He Guangyuan , Wang Yuesheng , Li Yin
Published: February 2022

The SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) gene family affects plant architecture, panicle structure, and grain development, representing key genes for crop improvements. The objective of the present study is to utilize the well characterized SPLs’ functions in rice to facilitate the functional genomics of TaSPL genes. To achieve these goals, we combined several approaches, including genome-wide analysis of TaSPLs, comparative genomic analysis, expression profiling, and functional study of TaSPL3 in rice. We established the orthologous relationships of 56 TaSPL genes with the corresponding OsSPLs, laying a foundation for the comparison of known SPL functions between wheat and rice. Some TaSPLs exhibited different spatial–temporal expression patterns when compared to their rice orthologs, thus implicating functional divergence. TaSPL2/6/8/10 were identified to respond to different abiotic stresses through the combination of RNA-seq and qPCR expression analysis. Additionally, ectopic expression of TaSPL3 in rice promotes heading dates, affects leaf and stem development, and leads to smaller panicles and decreased yields per panicle. In conclusion, our work provides useful information toward cataloging of the functions of TaSPLs, emphasized the conservation and divergence between TaSPLs and OsSPLs, and identified the important SPL genes for wheat improvement.
Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta
Authors: Gabanella Francesca , Barbato Christian , Corbi Nicoletta , Fiore Marco , Petrella Carla , de Vincentiis Marco , Greco Antonio , Ferraguti Giampiero , Corsi Alessandro , Ralli Massimo , Pecorella Irene , Di Gioia Cira , Pecorini Francesco , Brunelli Roberto , Passananti Claudio , Minni Antonio , Di Certo Maria Grazia
Published: February 2022

The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic and subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. We observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to the best of our knowledge, this is the first study that provides evidence of colocalization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection can reprogram mitochondrial activity in the highly specialized maternal–fetal interface.
Allosteric Modulation of Adenosine A2A Receptors as a New Therapeutic Avenue
Authors: Korkutata Mustafa , Agrawal Lokesh , Lazarus Michael
Published: February 2022

The therapeutic potential of targeting adenosine A2A receptors (A2ARs) is immense due to their broad expression in the body and central nervous system. The role of A2ARs in cardiovascular function, inflammation, sleep/wake behaviors, cognition, and other primary nervous system functions has been extensively studied. Numerous A2AR agonist and antagonist molecules are reported, many of which are currently in clinical trials or have already been approved for treatment. Allosteric modulators can selectively elicit a physiologic response only where and when the orthosteric ligand is released, which reduces the risk of an adverse effect resulting from A2AR activation. Thus, these allosteric modulators have a potential therapeutic advantage over classical agonist and antagonist molecules. This review focuses on the recent developments regarding allosteric A2AR modulation, which is a promising area for future pharmaceutical research because the list of existing allosteric A2AR modulators and their physiologic effects is still short.
Distinct Adipogenic and Fibrogenic Differentiation Capacities of Mesenchymal Stromal Cells from Pancreas and White Adipose Tissue
Authors: Aga Heja , Soultoukis George , Stadion Mandy , Garcia-Carrizo Francisco , Jähnert Markus , Gottmann Pascal , Vogel Heike , Schulz Tim J. , Schürmann Annette
Published: February 2022

Pancreatic steatosis associates with β-cell failure and may participate in the development of type-2-diabetes. Our previous studies have shown that diabetes-susceptible mice accumulate more adipocytes in the pancreas than diabetes-resistant mice. In addition, we have demonstrated that the co-culture of pancreatic islets and adipocytes affect insulin secretion. The aim of this current study was to elucidate if and to what extent pancreas-resident mesenchymal stromal cells (MSCs) with adipogenic progenitor potential differ from the corresponding stromal-type cells of the inguinal white adipose tissue (iWAT). miRNA (miRNome) and mRNA expression (transcriptome) analyses of MSCs isolated by flow cytometry of both tissues revealed 121 differentially expressed miRNAs and 1227 differentially expressed genes (DEGs). Target prediction analysis estimated 510 DEGs to be regulated by 58 differentially expressed miRNAs. Pathway analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas (pMSCs) and iWAT MSCs (iwatMSCs), for instance fibrogenic and adipogenic differentiation, respectively. Accordingly, iwatMSCs revealed a higher adipogenic lineage commitment, whereas pMSCs showed an elevated fibrogenesis. As a low degree of adipogenesis was also observed in pMSCs of diabetes-susceptible mice, we conclude that the development of pancreatic steatosis has to be induced by other factors not related to cell-autonomous transcriptomic changes and miRNA-based signals.
Atrial Fibrillation and Aortic Ectasia as Complications of Primary Aldosteronism: Focus on Pathophysiological Aspects
Authors: Bollati Martina , Lopez Chiara , Bioletto Fabio , Ponzetto Federico , Ghigo Ezio , Maccario Mauro , Parasiliti-Caprino Mirko
Published: February 2022

Primary aldosteronism (PA) is the most common cause of secondary hypertension. A growing body of evidence has suggested that, beyond its well-known effects on blood pressure and electrolyte balance, aldosterone excess can exert pro-inflammatory, pro-oxidant and pro-fibrotic effects on the kidney, blood vessels and heart, leading to potentially harmful pathophysiological consequences. In clinical studies, PA has been associated with an increased risk of cardiovascular, cerebrovascular, renal and metabolic complication compared to essential hypertension, including atrial fibrillation (AF) and aortic ectasia. An increased prevalence of AF in patients with PA has been demonstrated in several clinical studies. Aldosterone excess seems to be involved in the pathogenesis of AF by inducing cardiac structural and electrical remodeling that in turn predisposes to arrhythmogenicity. The association between PA and aortic ectasia is less established, but several studies have demonstrated an effect of aldosterone on aortic stiffness, vascular smooth muscle cells and media composition that, in turn, might lead to an increased risk of aortic dilation and dissection. In this review, we focus on the current evidence regarding the potential role of aldosterone excess in the pathogenesis of AF and aortic ectasia.
Selenium-Rich Yeast Peptide Fraction Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis in Mice by Inhibiting Inflammation via MAPK and NF-κB Signaling Pathways
Authors: Guo Hengke , Li Min , Liu Hongmei
Published: February 2022

Psoriasis, a chronic and immune-mediated inflammatory disease, adversely affects patients’ lives. We previously prepared selenium-rich yeast peptide fraction (SeP) from selenium-rich yeast protein hydrolysate and found that SeP could effectively alleviate ultraviolet radiation-induced skin damage in mice and inhibited H2O2-induced cytotoxicity in cultured human epidermal keratinocyte (HaCaT) cells. This study aimed to investigate whether SeP had a protective effect on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice and the underlying mechanisms. Results showed that SeP significantly ameliorated the severity of skin lesion in IMQ-induced psoriasis-like mouse model. Moreover, SeP treatment significantly attenuated the expression of key inflammatory cytokines, including interleukin (IL)-23, IL-17A, and IL-17F, in the dorsal skin of mice. Mechanistically, SeP application not only inhibited the activation of JNK and p38 MAPK, but also the translocation of NF-κB into the nucleus in the dorsal skin. Furthermore, SeP treatment inhibited the levels of inflammatory cytokines and the activation of MAPK and NF-κB signaling induced by lipopolysaccharide in HaCaT cells and macrophage cell line RAW264.7. Overall, our findings showed that SeP alleviated psoriasis-like skin inflammation by inhibiting MAPK and NF-κB signaling pathways, which suggested that SeP would have a potential therapeutic effect against psoriasis.
Adaptive Synthesis of Functional Amphiphilic Dendrons as a Novel Approach to Artificial Supramolecular Objects
Authors: Edr Antonín , Wrobel Dominika , Krupková Alena , Šťastná Lucie Červenková , Cuřínová Petra , Novák Aleš , Malý Jan , Kalasová Jitka , Malý Jan , Malý Marek , Strašák Tomáš
Published: February 2022

Supramolecular structures, such as micelles, liposomes, polymerosomes or dendrimerosomes, are widely studied and used as drug delivery systems. The behavior of amphiphilic building blocks strongly depends on their spatial distribution and shape of polar and nonpolar component. This report is focused on the development of new versatile synthetic protocols for amphiphilic carbosilane dendrons (amp-CS-DDNs) capable of self-assembly to regular micelles and other supramolecular objects. The presented strategy enables the fine modification of amphiphilic structure in several ways and also enables the facile connection of a desired functionality. DLS experiments demonstrated correlations between structural parameters of amp-CS-DDNs and the size of formed nanoparticles. For detailed information about the organization and spatial distribution of amp-CS-DDNs assemblies, computer simulation models were studied by using molecular dynamics in explicit water.
An Interleukin-4 and Interleukin-13 Induced Atopic Dermatitis Human Skin Equivalent Model by a Skin-On-A-Chip
Authors: Kim Kyunghee , Kim Hyeju , Sung Gun Yong
Published: February 2022

Currently, the mechanism of progression of atopic dermatitis (AD) is not well understood because there is no physiologically appropriate disease model in terms of disease complexity and multifactoriality. Type 2 inflammation, mediated by interleukin (IL)-4 and IL-13, plays an important role in AD. In this study, full-thickness human skin equivalents consisting of human-derived cells were fabricated from pumpless microfluidic chips and stimulated with IL-4 and IL-13. The morphological properties, gene expression, cytokine secretion and protein expression of the stimulated human skin equivalent (HSE) epidermis were investigated. The results showed epidermal and spongy formations similar to those observed in lesions in AD, and decreased expression of barrier-related filaggrin, loricrin and involucrin genes and proteins induced by IL-4Rα signaling. In addition, we induced the expression of carbonic anhydrase II (CAII), a gene specifically expressed in the epidermis of patients with AD. Thus, AD human skin equivalents can be used to mimic the key pathological features of atopic dermatitis, overcoming the limitations of existing studies that rely solely on mouse models and have been unable to translate their effects to humans. Our results will be useful for future research on the development of therapeutic agents for atopic dermatitis.
DNA Methylation Mediates EMT Gene Expression in Human Pancreatic Ductal Adenocarcinoma Cell Lines
Authors: Urbanova Maria , Buocikova Verona , Trnkova Lenka , Strapcova Sabina , Kajabova Viera Horvathova , Melian Emma Barreto , Novisedlakova Maria , Tomas Miroslav , Dubovan Peter , Earl Julie , Bizik Jozef , Svastova Eliska , Ciernikova Sona , Smolkova Bozena
Published: February 2022

Due to abundant stroma and extracellular matrix, accompanied by lack of vascularization, pancreatic ductal adenocarcinoma (PDAC) is characterized by severe hypoxia. Epigenetic regulation is likely one of the mechanisms driving hypoxia-induced epithelial-to-mesenchymal transition (EMT), responsible for PDAC aggressiveness and dismal prognosis. To verify the role of DNA methylation in this process, we assessed gene expression and DNA methylation changes in four PDAC cell lines. BxPC-3, MIA PaCa-2, PANC-1, and SU.86.86 cells were exposed to conditioned media containing cytokines and inflammatory molecules in normoxic and hypoxic (1% O2) conditions for 2 and 6 days. Cancer Inflammation and Immunity Crosstalk and Human Epithelial to Mesenchymal Transition RT² Profiler PCR Arrays were used to identify top deregulated inflammatory and EMT-related genes. Their mRNA expression and DNA methylation were quantified by qRT-PCR and pyrosequencing. BxPC-3 and SU.86.86 cell lines were the most sensitive to hypoxia and inflammation. Although the methylation of gene promoters correlated with gene expression negatively, it was not significantly influenced by experimental conditions. However, DNA methyltransferase inhibitor decitabine efficiently decreased DNA methylation up to 53% and reactivated all silenced genes. These results confirm the role of DNA methylation in EMT-related gene regulation and uncover possible new targets involved in PDAC progression.
Transient Agarose Spot (TAS) Assay: A New Method to Investigate Cell Migration
Authors: Veres-Székely Apor , Pap Domonkos , Szebeni Beáta , Őrfi László , Szász Csenge , Pajtók Csenge , Lévai Eszter , Szabó Attila J. , Vannay Ádám
Published: February 2022

Fibroblasts play a central role in diseases associated with excessive deposition of extracellular matrix (ECM), including idiopathic pulmonary fibrosis. Investigation of different properties of fibroblasts, such as migration, proliferation, and collagen-rich ECM production is unavoidable both in basic research and in the development of antifibrotic drugs. In the present study we developed a cost-effective, 96-well plate-based method to examine the migration of fibroblasts, as an alternative approach to the gold standard scratch assay, which has numerous limitations. This article presents a detailed description of our transient agarose spot (TAS) assay, with instructions for its routine application. Advantages of combined use of different functional assays for fibroblast activation in drug development are also discussed by examining the effect of nintedanib—an FDA approved drug against IPF—on lung fibroblasts.
PACAP-38 Induces Transcriptomic Changes in Rat Trigeminal Ganglion Cells Related to Neuroinflammation and Altered Mitochondrial Function Presumably via PAC1/VPAC2 Receptor-Independent Mechanism
Authors: Takács-Lovász Krisztina , Kun József , Aczél Timea , Urbán Péter , Gyenesei Attila , Bölcskei Kata , Szőke Éva , Helyes Zsuzsanna
Published: February 2022

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a broadly expressed neuropeptide which has diverse effects in both the peripheral and central nervous systems. While its neuroprotective effects have been shown in a variety of disease models, both animal and human data support the role of PACAP in migraine generation. Both PACAP and its truncated derivative PACAP(6-38) increased calcium influx in rat trigeminal ganglia (TG) primary sensory neurons in most experimental settings. PACAP(6-38), however, has been described as an antagonist for PACAP type I (known as PAC1), and Vasoactive Intestinal Polypeptide Receptor 2 (also known as VPAC2) receptors. Here, we aimed to compare the signaling pathways induced by the two peptides using transcriptomic analysis. Rat trigeminal ganglion cell cultures were incubated with 1 µM PACAP-38 or PACAP(6-38). Six hours later RNA was isolated, next-generation RNA sequencing was performed and transcriptomic changes were analyzed to identify differentially expressed genes. Functional analysis was performed for gene annotation using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome databases. We found 200 common differentially expressed (DE) genes for these two neuropeptides. Both PACAP-38 and PACAP(6-38) treatments caused significant downregulation of NADH: ubiquinone oxidoreductase subunit B6 and upregulation of transient receptor potential cation channel, subfamily M, member 8. The common signaling pathways induced by both peptides indicate that they act on the same target, suggesting that PACAP activates trigeminal primary sensory neurons via a mechanism independent of the identified and cloned PAC1/VPAC2 receptor, either via another target structure or a different splice variant of PAC1/VPAC2 receptors. Identification of the target could help to understand key mechanisms of migraine.
Atopic Dermatitis: The Fate of the Fat
Authors: Pavel Petra , Blunder Stefan , Moosbrugger-Martinz Verena , Elias Peter M. , Dubrac Sandrine
Published: February 2022

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease in which dry and itchy skin may develop into skin lesions. AD has a strong genetic component, as children from parents with AD have a two-fold increased chance of developing the disease. Genetic risk loci and epigenetic modifications reported in AD mainly locate to genes involved in the immune response and epidermal barrier function. However, AD pathogenesis cannot be fully explained by (epi)genetic factors since environmental triggers such as stress, pollution, microbiota, climate, and allergens also play a crucial role. Alterations of the epidermal barrier in AD, observed at all stages of the disease and which precede the development of overt skin inflammation, manifest as: dry skin; epidermal ultrastructural abnormalities, notably anomalies of the lamellar body cargo system; and abnormal epidermal lipid composition, including shorter fatty acid moieties in several lipid classes, such as ceramides and free fatty acids. Thus, a compelling question is whether AD is primarily a lipid disorder evolving into a chronic inflammatory disease due to genetic susceptibility loci in immunogenic genes. In this review, we focus on lipid abnormalities observed in the epidermis and blood of AD patients and evaluate their primary role in eliciting an inflammatory response.
Knowledge Distillation: A Method for Making Neural Machine Translation More Efficient
Authors: Jooste Wandri , Haque Rejwanul , Way Andy
Published: February 2022

Neural machine translation (NMT) systems have greatly improved the quality available from machine translation (MT) compared to statistical machine translation (SMT) systems. However, these state-of-the-art NMT models need much more computing power and data than SMT models, a requirement that is unsustainable in the long run and of very limited benefit in low-resource scenarios. To some extent, model compression—more specifically state-of-the-art knowledge distillation techniques—can remedy this. In this work, we investigate knowledge distillation on a simulated low-resource German-to-English translation task. We show that sequence-level knowledge distillation can be used to train small student models on knowledge distilled from large teacher models. Part of this work examines the influence of hyperparameter tuning on model performance when lowering the number of Transformer heads or limiting the vocabulary size. Interestingly, the accuracy of these student models is higher than that of the teachers in some cases even though the student model training times are shorter in some cases. In a novel contribution, we demonstrate for a specific MT service provider that in the post-deployment phase, distilled student models can reduce emissions, as well as cost purely in monetary terms, by almost 50%.
A New Edge Computing Architecture for IoT and Multimedia Data Management
Authors: Debauche Olivier , Mahmoudi Saïd , Guttadauria Adriano
Published: February 2022

The Internet of Things and multimedia devices generate a tremendous amount of data. The transfer of this data to the cloud is a challenging problem because of the congestion at the network level, and therefore processing time could be too long when we use a pure cloud computing strategy. On the other hand, new applications requiring the processing of large amounts of data in real time have gradually emerged, such as virtual reality and augmented reality. These new applications have gradually won over users and developed a demand for near real-time interaction of their applications, which has completely called into question the way we process and store data. To address these two problems of congestion and computing time, edge architecture has emerged with the goal of processing data as close as possible to users, and to ensure privacy protection and responsiveness in real-time. With the continuous increase in computing power, amounts of memory and data storage at the level of smartphone and connected objects, it is now possible to process data as close as possible to sensors or directly on users devices. The coupling of these two types of processing as close as possible to the data and to the user opens up new perspectives in terms of services. In this paper, we present a new distributed edge architecture aiming to process and store Internet of Things and multimedia data close to the data producer, offering fast response time (closer to real time) in order to meet the demands of modern applications. To do this, the processing at the level of the producers of data collaborate with the processing ready for the users, establishing a new paradigm of short supply circuit for data transmission inspired of short supply chains in agriculture. The removing of unnecessary intermediaries between the producer and the consumer of the data improves efficiency. We named this new paradigm the Short Supply Circuit Internet of Things (SSCIoT).
Phlebotomine Sand Flies in Southern Thailand: Entomological Survey, Identification of Blood Meals and Molecular Detection of Trypanosoma spp.
Authors: Buatong Jirayu , Dvorak Vit , Thepparat Arunrat , Thongkhao Kanaphot , Koyadun Surachart , Siriyasatien Padet , Pengsakul Theerakamol
Published: February 2022

An entomological survey at rural and cavernicolous localities in four provinces in southern Thailand provided 155 blood-fed females of sand flies (Diptera: Psychodidae) that were identified based on morphological characters as Idiophlebotomus asperulus (n = 19), Phlebotomus stantoni (n = 4), P. argentipes (n = 3), Sergentomyia anodontis (n = 20), S. barraudi (n = 9), S. hamidi (n = 23), S. hodgsoni (n = 4), S. hodgsoni hodgsoni (n = 32), S. indica (n = 5), S. iyengari (n = 2), S. khawi (n = 17), S. silvatica (n = 11) and Sergentomyia sp. (n = 6). The dominant species in this study was S. hodgsoni hodgsoni, which was collected specifically in a Buddha cave. Screening for DNA of parasitic protozoans revealed eight specimens (5.16%) of four species (S. barraudi, S. indica, S. khawi and Id. asperulus) positive for Trypanosoma sp., while no Leishmania spp. DNA was detected. Blood meals of engorged females were identified by PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) assay on a fragment of cytochrome b (cyt b) gene with a success rate 36%, humans, dogs, and rats being determined as sources of blood. Bloodmeal analysis of two Trypanopsoma-positive females (S. barraudi and Sergentomyia sp.) identified blood from dogs and humans, respectively. Our findings indicate that S. barraudi, S. indica, S. khawi and Id. asperulus may be incriminated in circulation of detected Trypanosoma spp.
Hard Ticks (Ixodidae) from Wildlife in Liguria, Northwest Italy: Tick Species Diversity and Tick-Host Associations
Authors: Accorsi Annalisa , Schiavetti Irene , Listorti Valeria , Dellepiane Monica , Masotti Chiara , Ercolini Carlo , Guardone Lisa , Razzuoli Elisabetta
Published: February 2022

Hard ticks’ geographical distribution and abundance are influenced by wildlife population. This work presents the results of the identification of ticks retrieved from wild animals in the framework of a Regional Plan of Monitoring and Surveillance of Wildlife health. The frequency of distribution of ticks in different hosts and their geographical patterns were also investigated. Ticks were collected from game animals (Sus scrofa, Capreolus capreolus, Dama dama, and Rupicapra rupicapra) during two hunting seasons (2018–2019 and 2019–2020) in the four provinces of the Liguria region in northwest Italy. In the same period, ticks were also collected from carcasses of Vulpes vulpes, Canis lupus, Meles meles, and Asio otus received for necropsy. Tick species were identified according to taxonomic keys. A total of 819 ticks, removed from 259 animals, were found and identified. Overall, Ixodes ricinus was the dominant species (62.6%), followed by Dermacentor marginatus (24.5%), Rhipicephalus sanguineus s.l. (12.5%), Haemaphysalis punctata (0.2%), and Ixodes hexagonus (0.1%). I. ricinus was also the prevalent species in roe deer and in fallow deer and the only species collected from the three wolf carcasses examined. In contrast, D. marginatus was the dominant species in S. scrofa. This last tick species was also more frequent in one province (Imperia), whereas Ixodes spp. were more common in another one (Savona). Wild animals proved to be useful for characterizing and monitoring tick population.
Numerical and Experimental Analysis of Transient Flow Field and Pressure Pulsations of an Axial-Flow Pump Considering the Pump–Pipeline Interaction
Authors: Yang Fan , Li Zhongbin , Fu Jianguo , Lv Yuting , Ji Qingwei , Jian Hongfu
Published: February 2022

The internal flow in a vertical axial-flow pump is a complex unsteady three-dimensional viscous flow. An unstable flow often produces complex flow phenomena such as flow separation, vortices, and secondary reflux, which reduces the operating efficiency of the pump and can endanger safety and stability. In this paper, computational fluid dynamics is used to calculate the flow characteristics in an axial-flow pump using the shear stress transport and curvature correction (SST-CC) model for turbulence modified to account for the rotational curvature. Furthermore, the dependability of the numerical results was confirmed by a test with an actual model of a pump. The transient deviation angle at the impeller inlet of the pump, the stream field attributes in various spanwise parts of the impeller and guide vane, and the velocity distributions at the impeller inlet and outlet were analyzed. The omega method was utilized to recognize the vortex structure inside the guide vane. Moreover, the development of the transient vortex structure inside the guide vane was studied. As the flow rate increased, the scale and turbulent kinetic energy of the vortex structure gradually decreased. The time-domain graph for the impeller inlet is clearly periodic, with three peaks and three troughs in an impeller rotational period. The dominant frequency in the spectrum at each monitoring point was basically the blade frequency, and the secondary dominant frequency was twice the blade frequency.
Establishment of an Efficient Polyethylene Glycol (PEG)-Mediated Transformation System in Pleurotus eryngii var. ferulae Using Comprehensive Optimization and Multiple Endogenous Promoters
Authors: Zhang Qi , Zhao Liting , Shen Mengye , Liu Jingyun , Li Youran , Xu Sha , Chen Lei , Shi Guiyang , Ding Zhongyang
Published: February 2022

Pleurotus eryngii var. ferulae, a fungus of the genus Pleurotus, efficiently degrades lignin, especially during co-cultivation with other fungi. However, low transformation efficiency and heterologous gene expression restrict systematic studies of the molecular mechanisms and metabolic control of natural products in this mushroom. In this study, the homologous resistance marker carboxin (cbx) was used to establish a polyethylene glycol-mediated transformation (PMT) system in P. eryngii var. ferulae. Optimization of the transformation process greatly improved the number of positive transformants. In particular, we optimized: (i) protoplast preparation and regeneration; (ii) screening methods; and (iii) transformation-promoting factors. The optimized transformation efficiency reached 72.7 CFU/μg, which is higher than the average level of Pleurotus sp. (10–40 CFU/μg). Moreover, three endogenous promoters (Ppfgpd1, Ppfgpd2, and Ppfsar1) were screened and evaluated for different transcription initiation characteristics. A controllable overexpression system was established using these three promoters that satisfied various heterologous gene expression requirements, such as strong or weak, varied, or stable expression levels. This study lays the foundation for recombinant protein expression in P. eryngii var. ferulae and provides a method to investigate the underlying molecular mechanisms and secondary metabolic pathway modifications.
Sputum Galactomannan Has Utility in the Diagnosis of Chronic Pulmonary Aspergillosis
Authors: Nuh Ali , Ramadan Newara , Shah Anand , Armstrong-James Darius
Published: February 2022

Diagnosis of pulmonary aspergillosis (PA), a fungal disease caused by Aspergillus species, is challenging since symptoms are unspecific. The galactomannan (antigen secreted by Aspergillus species) test in bronchoalveolar lavage (BAL) fluid is a valuable diagnostic adjunct test in the diagnosis of PA. However, BAL collection is invasive and may not be suitable to severely ill patients. Sputum is non-invasive, easily collected, and lung specific and may be an alternative to BAL. The aim of this research was to retrospectively evaluate the utility of sputum galactomannan in the diagnosis of pulmonary aspergillosis in patients with chronic respiratory diseases and to estimate the sputum galactomannan cut-off value. We collected data from patients with clinical suspicion of pulmonary aspergillosis who had sputum galactomannan, culture, and Aspergillus IgG tests performed within four weeks. Sputum galactomannan was validated against the clinical diagnosis of aspergillosis, Aspergillus culture, and Aspergillus IgG tests. In total, 218 patients met inclusion criteria. Overall, sputum GM showed satisfactory agreement with clinical diagnosis of aspergillosis, Aspergillus culture, and Aspergillus IgG. When a receiver operating characteristic curve was constructed using Aspergillus culture/IgG and clinical diagnosis, the same cut-off (CO) of 0.71 (AUC: 0.83; CI: 0.69–0.86, p < 0.001) was determined. Against clinical diagnosis, sputum GM gave sensitivity and specificity of 70% and 71%, respectively. Sensitivity of 77% and specificity of 78% were found when sputum GM was evaluated against Aspergillus culture/IgG. In conclusion, this study showed that sputum galactomannan antigen testing has utility in the diagnosis of chronic forms of pulmonary aspergillosis and further prospective validation is indicated.
When Is Arteriovenous Fistula Dangerous for Hemodialysis Patients?
Authors: Malík Jan
Published: February 2022

Hemodialysis arteriovenous fistula is a shortcut of the systemic circulation and sometimes fistula flow exceeds 2 L/min. Possible hemodynamic and clinical consequences are discussed.