bluuebunny/crossref_metadata_2025 huggingface dataset:
Wolves, Crows, and Spiders: An eclectic Literature Review inspires a Model explaining Humans’ similar Reactions to ecologically different Wildlife
Authors: Jürgens Uta Maria , Hackett Paul M. W.
Published: February 2021

Coming from the vantage point of managing human relations to potentially problematic wildlife, we bring the following questions: Where do people’s emotionally vigorous and polarized reactions originate? Why do these reactions to different scenarios of human-wildlife conflict appear similar? In this paper we provide the findings from an eclectic review of purposefully sampled literature on human relations to wolves, corvids and spiders. Based on this synthesis, we propose three answers to those questions: 1). The emotional vigor inherent in human-wildlife conflicts is caused by the activation of deep-seated and emotionally loaded factors, specifically worldviews on human-nature relations more broadly, an integral human motivation for seeking control, and symbolic associations to darkness. 2). The opposing attitudes on human-wildlife relations derive from people’s diverging worldviews and different degrees of wanting control in a situation of human-wildlife conflict. 3). Despite ecological specificities, various cases of human-wildlife conflicts may evoke similar mental processes and, accordingly, the same reactions in people. Consequentially, it is possible to develop transferable solutions that may contribute to managing challenges in different instances of human-wildlife encounters.
pH Adaptation Drives Diverse Phenotypes in a Beneficial Bacterium-Host Mutualism
Authors: Nourabadi Neda , Nishiguchi Michele K.
Published: February 2021

Abiotic variation can influence the evolution of specific phenotypes that contribute to the diversity of bacterial strains observed in the natural environment. Environmentally transmitted symbiotic bacteria are particularly vulnerable to abiotic fluctuations, given that they must accommodate the transition between the free-living state and the host's internal environment. This type of life history strategy can strongly influence the success of a symbiont, and whether adapting to changes outside the host will allow a greater capacity to survive in symbiosis with the host partner. One example of how environmental breadth is advantageous to the symbiosis is the beneficial association between Vibrio fischeri and sepiolid squids (Cephalopoda: Sepiolidae). Since Vibrio bacteria are environmentally transmitted, they are subject to a wide variety of abiotic variables prior to infecting juvenile squids and must be poised to survive in the host light organ. In order to better understand how a changing abiotic factor (e.g., pH) influences the diversification of symbionts and their eventual symbiotic competence, we used an experimental evolution approach to ascertain how pH adaptation affects symbiont fitness. Results show that low pH adapted Vibrio strains have more efficient colonization rates compared to their ancestral strains. In addition, growth rates had significant differences compared to ancestral strains (pH 6.5–6.8, and 7.2). Bioluminescence production (a marker for symbiont competence) of pH evolved strains also improved at pH 6.5–7.2. Results imply that the evolution and diversification of Vibrio strains adapted to low pH outside the squid improves fitness inside the squid by allowing a higher success rate for host colonization and symbiotic competence.
Integrated Bioinformatics Analysis Exhibits Pivotal Exercise-Induced Genes and Corresponding Pathways in Malignant Melanoma
Authors: Zhu Jun , Hao Suyu , Zhang Xinyue , Qiu Jingyue , Xuan Qin , Ye Liping
Published: February 2021

Malignant melanoma represents a sort of neoplasm deriving from melanocytes or cells developing from melanocytes. The balance of energy and energy-associated body composition and body mass index could be altered by exercise, thereby directly affecting the microenvironment of neoplasm. However, few studies have examined the mechanism of genes induced by exercise and the pathways involved in melanoma. This study used three separate datasets to perform comprehensive bioinformatics analysis and then screened the probable genes and pathways in the process of exercise-promoted melanoma. In total, 1,627 differentially expressed genes (DEGs) induced by exercise were recognized. All selected genes were largely enriched in NF-kappa B, Chemokine signaling pathways, and the immune response after gene set enrichment analysis. The protein-protein interaction network was applied to excavate DEGs and identified the most relevant and pivotal genes. The top 6 hub genes (Itgb2, Wdfy4, Itgam, Cybb, Mmp2, and Parp14) were identified, and importantly, 5 hub genes (Itgb2, Wdfy4, Itgam, Cybb, and Parp14) were related to weak disease-free survival and overall survival (OS). In conclusion, our findings demonstrate the prognostic value of exercise-induced genes and uncovered the pathways of these genes in melanoma, implying that these genes might act as prognostic biomarkers for melanoma.
IL-23 Inhibition in Ankylosing Spondylitis: Where Did It Go Wrong?
Authors: Baeten Dominique , Adamopoulos Iannis E.
Published: February 2021

Axial spondyloarthritis is a prevalent form of chronic arthritis which is related to psoriatic arthritis and skin psoriasis. TNF and IL-17A as well as IL-17F are key cytokines contributing to the pathobiology of this disease, as evidence by the therapeutic efficacy of inhibition of these factors. Despite the evidence that IL-23 acts as an upstream driver of Th17 cells, the T lymphocytes producing IL-17, and that IL-23 inhibition shows profound efficacy in psoriasis, blocking IL-23 failed to show any evidence of clinical efficacy in axial spondyloarthritis. In this viewpoint article, we revisit the reasons-to-believe in a role of IL-23 in the pathobiology of axial spondyloarthritis, discuss what we have learned on the pathobiology of this disease in general and on the function of the IL-23/IL-17 axis in particular, and share a handful of lessons learned that are of relevance for the translation of emerging biological insights into clinical therapeutics.
The Small GTPase Cdc42 Negatively Regulates the Formation of Neutrophil Extracellular Traps by Engaging Mitochondria
Authors: Tackenberg Heidi , Möller Sonja , Filippi Marie-Dominique , Laskay Tamás
Published: February 2021

Neutrophil granulocytes represent the first line of defense against invading pathogens. In addition to the production of Reactive Oxygen Species, degranulation, and phagocytosis, these specialized cells are able to extrude Neutrophil Extracellular Traps. Extensive work was done to elucidate the mechanism of this special form of cell death. However, the exact mechanisms are still not fully uncovered. Here we demonstrate that the small GTPase Cdc42 is a negative regulator of NET formation in primary human and murine neutrophils. We present a functional role for Cdc42 activity in NET formation that differs from the already described NETosis pathways. We show that Cdc42 deficiency induces NETs independent of the NADPH-oxidase but dependent on protein kinase C. Furthermore, we demonstrate that Cdc42 deficiency induces NETosis through activation of SK-channels and that mitochondria play a crucial role in this process. Our data therefore suggests a mechanistic role for Cdc42 activity in primary human neutrophils, and identify Cdc42 activity as a target to modulate the formation of Neutrophil Extracellular Traps.
Immunomodulatory Function of Vitamin D and Its Role in Autoimmune Thyroid Disease
Authors: Zhao Rui , Zhang Wei , Ma Chenghong , Zhao Yaping , Xiong Rong , Wang Hanmin , Chen Weiwen , Zheng Song Guo
Published: February 2021

Vitamin D is one of the most important nutrients required by the human body. It is a steroid hormone that plays an important role in regulating calcium and phosphorus metabolism, and bone health. Epidemiological studies have revealed a close correlation between vitamin D and many common chronic diseases. Additionally, vitamin D has recently been shown to act as an immunomodulatory hormone, and, accordingly, vitamin D deficiency was uncovered as a risk factor for autoimmune thyroid diseases, although the underlying mechanisms are still unknown. It is therefore necessary to disclose the role and mechanism of action of vitamin D in the occurrence and development of autoimmune thyroid diseases. This knowledge will help design intervention and early treatment strategies for patients with autoimmune thyroid diseases who present with low levels of vitamin D.
Eosinophilic Esophagitis and Microbiota: State of the Art
Authors: Mennini Maurizio , Tambucci Renato , Riccardi Carla , Rea Francesca , De Angelis Paola , Fiocchi Alessandro , Assa’ad Amal
Published: February 2021

Eosinophilic esophagitis (EoE) is a chronic, food-triggered, immune-mediated disease of the oesophagus, clinically characterized by symptoms referred to oesophagal dysfunction, and histologically defined by an eosinophil productive inflammation of the oesophagal mucosa, among other cell types. The involvement of an adaptive Th2-type response to food antigens in EoE was known since 2000; several cytokines and chemokines promote food-specific responses, during which local production of IgE, but also IgG4 derived from plasma cells in lamina propria of oesophagal mucosa might play an important role. Evidence pointing towards a possible role for the innate immunity in EoE has arisen recently. Together, this evidence gives rise to a potential role that the innate immune system in general, and also the microbial pattern recognition receptors (PRRs) might play in EoE pathogenesis. Among PRRs, Toll-like receptors (TLRs) are type-I transmembrane receptors expressed both on epithelial and lamina propria cells with the capacity to distinguish between pathogen and commensal microbes. As TLRs in the different intestinal epithelia represent the primary mechanism of epithelial recognition of bacteria, this evidence underlines that oesophagal TLR-dependent signaling pathways in EoE support the potential implication of microbiota and the innate immune system in the pathogenesis of this disease. The oesophagal mucosa hosts a resident microbiota, although in a smaller population as compared with other districts of the gastrointestinal tract. Few studies have focused on the composition of the microbiota of the normal oesophagus alone. Still, additional information has come from studies investigating the oesophagal microbiota in disease and including healthy patients as controls. Our review aims to describe all the evidence on the oesophagal and intestinal microbiota in patients with EoE to identify the specific features of dysbiosis in this condition.
Cyclic-di-GMP Induces STING-Dependent ILC2 to ILC1 Shift During Innate Type 2 Lung Inflammation
Authors: Cavagnero Kellen J. , Badrani Jana H. , Naji Luay H. , Amadeo Michael B. , Leng Anthea S. , Lacasa Lee Diego , Strohm Allyssa N. , Renusch Samantha R. , Gasparian Suzanna S. , Doherty Taylor A.
Published: February 2021

Type 2 inflammation is found in most forms of asthma, which may co-exist with recurrent viral infections, bacterial colonization, and host cell death. These processes drive the accumulation of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group 2 innate lymphoid cells (ILC2s) are critical drivers of type 2 lung inflammation during fungal allergen exposure in mice; however, it is unclear how CDG regulates lung ILC responses during lung inflammation. Here, we show that intranasal CDG induced early airway type 1 interferon (IFN) production and dramatically suppressed CD127+ST2+ ILC2s and type 2 lung inflammation during Alternaria and IL-33 exposure. Further, CD127–ST2–Thy1.2+ lung ILCs, which showed a transcriptomic signature consistent with ILC1s, were expanded and activated by CDG combined with either Alternaria or IL-33. CDG-mediated suppression of type 2 inflammation occurred independent of IL-18R, IL-12, and STAT6 but required the stimulator of interferon genes (STING) and type 1 IFN signaling. Thus, CDG potently suppresses ILC2-driven lung inflammation and promotes ILC1 responses. These results suggest potential therapeutic modulation of STING to suppress type 2 inflammation and/or increase anti-viral responses during respiratory infections.
Street RABV Induces the Cholinergic Anti-inflammatory Pathway in Human Monocyte-Derived Macrophages by Binding to nAChr α7
Authors: Embregts Carmen W. E. , Begeman Lineke , Voesenek Cees J. , Martina Byron E. E. , Koopmans Marion P. G. , Kuiken Thijs , GeurtsvanKessel Corine H.
Published: February 2021

Rabies virus (RABV) is able to reach the central nervous system (CNS) without triggering a strong immune response, using multiple mechanisms to evade and suppress the host immune system. After infectionviaa bite or scratch from a rabid animal, RABV comes into contact with macrophages, which are the first antigen-presenting cells (APCs) that are recruited to the area and play an essential role in the onset of a specific immune response. It is poorly understood how RABV affects macrophages, and if the interaction contributes to the observed immune suppression. This study was undertaken to characterize the interactions between RABV and human monocyte-derived macrophages (MDMs). We showed that street RABV does not replicate in human MDMs. Using a recombinant trimeric RABV glycoprotein (rRABV-tG) we showed binding to the nicotinic acetylcholine receptor alpha 7 (nAChr α7) on MDMs, and confirmed the specificity using the nAChr α7 antagonist alpha-bungarotoxin (α-BTX). We found that this binding induced the cholinergic anti-inflammatory pathway (CAP), characterized by a significant decrease in tumor necrosis factor α (TNF-α) upon LPS challenge. Using confocal microscopy we found that induction of the CAP is associated with significant cytoplasmic retention of nuclear factor κB (NF-κB). Co-cultures of human MDMs exposed to street RABV and autologous T cells further revealed that the observed suppression of MDMs might affect their function as T cell activators as well, as we found a significant decrease in proliferation of CD8+T cells and an increased production of the anti-inflammatory cytokine IL-10. Lastly, using flow cytometric analysis we observed a significant increase in expression of the M2-c surface marker CD163, hinting that street RABV might be able to affect macrophage polarization. Taken together, these results show that street RABV is capable of inducing an anti-inflammatory state in human macrophages, possibly affecting T cell functioning.
From the Genetics of Ankylosing Spondylitis to New Biology and Drug Target Discovery
Authors: Nancy Zaarour , Yan Li , Hui Shi , Paul Bowness , Liye Chen
Published: February 2021

Genome-wide association studies (GWAS) have identified 113 single nucleotide polymorphisms (SNPs) affecting the risk of developing ankylosing spondylitis (AS), and an on-going GWAS study will likely identify 100+ new risk loci. The translation of genetic findings to novel disease biology and treatments has been difficult due to the following challenges: (1) difficulties in determining the causal genes regulated by disease-associated SNPs, (2) difficulties in determining the relevant cell-type(s) that causal genes exhibit their function(s), (3) difficulties in determining appropriate cellular contexts to interrogate the functional role of causal genes in disease biology. This review will discuss recent progress and unanswered questions with a focus on these challenges. Additionally, we will review the investigation of biology and the development of drugs related to the IL-23/IL-17 pathway, which has been partially driven by the AS genetics, and discuss what can be learned from these studies for the future functional and translational study of AS-associated genes.
The Pacific Oyster Mortality Syndrome, a Polymicrobial and Multifactorial Disease: State of Knowledge and Future Directions
Authors: Petton Bruno , Destoumieux-Garzón Delphine , Pernet Fabrice , Toulza Eve , de Lorgeril Julien , Degremont Lionel , Mitta Guillaume
Published: February 2021

The Pacific oyster (Crassostreae gigas) has been introduced from Asia to numerous countries around the world during the 20th century. C. gigas is the main oyster species farmed worldwide and represents more than 98% of oyster production. The severity of disease outbreaks that affect C. gigas, which primarily impact juvenile oysters, has increased dramatically since 2008. The most prevalent disease, Pacific oyster mortality syndrome (POMS), has become panzootic and represents a threat to the oyster industry. Recently, major steps towards understanding POMS have been achieved through integrative molecular approaches. These studies demonstrated that infection by Ostreid herpesvirus type 1 µVar (OsHV-1 µvar) is the first critical step in the infectious process and leads to an immunocompromised state by altering hemocyte physiology. This is followed by dysbiosis of the microbiota, which leads to a secondary colonization by opportunistic bacterial pathogens, which in turn results in oyster death. Host and environmental factors (e.g. oyster genetics and age, temperature, food availability, and microbiota) have been shown to influence POMS permissiveness. However, we still do not understand the mechanisms by which these different factors control disease expression. The present review discusses current knowledge of this polymicrobial and multifactorial disease process and explores the research avenues that must be investigated to fully elucidate the complexity of POMS. These discoveries will help in decision-making and will facilitate the development of tools and applied innovations for the sustainable and integrated management of oyster aquaculture.
Serum Metabolomics Signatures Associated With Ankylosing Spondylitis and TNF Inhibitor Therapy
Authors: Ou Jiayong , Xiao Min , Huang Yefei , Tu Liudan , Chen Zena , Cao Shuangyan , Wei Qiujing , Gu Jieruo
Published: February 2021

Ankylosing spondylitis (AS) is a type of spondyloarthropathies, the diagnosis of which is often delayed. The lack of early diagnosis tools often delays the institution of appropriate therapy. This study aimed to investigate the systemic metabolic shifts associated with AS and TNF inhibitors treatment. Additionally, we aimed to define reliable serum biomarkers for the diagnosis. We employed an untargeted technique, ultra-performance liquid chromatography-mass spectroscopy (LC-MS), to analyze the serum metabolome of 32 AS individuals before and after 24-week TNF inhibitors treatment, as well as 40 health controls (HCs). Multivariate and univariate statistical analyses were used to profile the differential metabolites associated with AS and TNF inhibitors. A diagnostic panel was established with the least absolute shrinkage and selection operator (LASSO). The pathway analysis was also conducted. A total of 55 significantly differential metabolites were detected. We generated a diagnostic panel comprising five metabolites (L-glutamate, arachidonic acid, L-phenylalanine, PC (18:1(9Z)/18:1(9Z)), 1-palmitoylglycerol), capable of distinguishing HCs from AS with a high AUC of 0.998, (95%CI: 0.992–1.000). TNF inhibitors treatment could restore the equilibrium of 21 metabolites. The most involved pathways in AS were amino acid biosynthesis, glycolysis, glutaminolysis, fatty acids biosynthesis and choline metabolism. This study characterized the serum metabolomics signatures of AS and TNF inhibitor therapy. We developed a five-metabolites-based panel serving as a diagnostic tool to separate patients from HCs. This serum metabolomics study yielded new knowledge about the AS pathogenesis and the systemic effects of TNF inhibitors.
Cellular Metabolites Regulate Central Nucleic Acid Sensing Pathways
Authors: Blay-Cadanet Julia , Pedersen Alice , Holm Christian Kanstrup
Published: February 2021

Detection of pathogen-derived DNA or RNA species by cellular nucleic acid sensors prompts release of anti-microbial interferons and cytokines. In contrast to their protective anti-microbial functions, inappropriate or excessive activation of nucleic acid sensors can cause inflammatory diseases. Nucleic acid sensing is therefore tightly controlled by regulatory factors acting through both transcriptional and post-transcriptional mechanisms. Recently, it has become clearer that metabolic pathways—previously thought to be unconnected with immune responses—can influence nucleic acid sensing. This regulation can be observed when immune system cells undergo metabolic reprogramming in response to stimulation with pathogen-associated molecular patterns such as lipopolysaccharide from gram negative bacteria. Metabolic reprogramming leads to accumulation and secretion of metabolites, which have been mostly viewed as end-products of processes providing cellular energy and building blocks. However, metabolites have now been identified as important regulators of nucleic acid sensing. This mini-review aims to outline current knowledge on regulation of central nucleic acid sensing pathways by metabolites during metabolic reprogramming.
Equitable Allocations in Northern Fisheries: Bridging the Divide for Labrador Inuit
Authors: Kourantidou Melina , Hoagland Porter , Dale Aaron , Bailey Megan
Published: February 2021

Canada has undertaken commitments to recognize the rights of Indigenous Peoples in fisheries through policies and agreements, including Integrated Fishery Management Plans, the Reconciliation Strategy, and Land Claim Agreements (LCAs). In addition to recognizing rights, these commitments were intended to respect geographic adjacency principles, to enhance the economic viability of Indigenous communities, and to be reflective of community dependence on marine resources. We examined the determinants of quota allocations in commercial fisheries involving Nunatsiavut, Northern Labrador, the first self-governing region for the Inuit peoples in Canada. It has been argued that current fishery allocations for Nunatsiavut Inuit have not satisfied federal commitments to recognize Indigenous rights. Indicators that measure equity in commercial allocations for the turbot or Greenland halibut (Reinhardtius hippoglossoides) and northern shrimp (Pandalus borealis)fisheries were identified and assessed. In these two cases, historical allocations continue to predominate for allocations based upon equity or other social or economic considerations. We illustrate equity-enhancing changes in the quota distribution under scenarios of different levels of inequality aversion, and we make qualitative assessments of the effects of these allocations to Nunatsiavut for socioeconomic welfare. This approach could benefit fisheries governance in Northern Labrador, where federal commitments to equity objectives continue to be endorsed but have not yet been integrated fully into quota allocations.
Dolphin-Watching Boats Affect Whistle Frequency Modulation in Bottlenose Dolphins
Authors: Perez-Ortega Betzi , Daw Rebecca , Paradee Brennan , Gimbrere Emma , May-Collado Laura J.
Published: February 2021

Bottlenose dolphins’ whistles are key in social communication, conveying information about conspecifics and the environment. Therefore, their study can help to infer habitat use and identify areas of concern due to human activities. Here we studied the whistles of bottlenose dolphins (Tursiops truncatus) in two sites of the archipelago of Bocas del Toro, Panama, that contrast in boat traffic. Almirante Bay is a site dominated by taxi-boats and Dolphin Bay is a major location for boat-based dolphin watching. Recordings were made using bottom-mounted hydrophones and from the research boat using an over-the-side hydrophone and a broadband recording system. A total recording effort time of 1,726 h was analyzed. Our results show significant differences in boat detection between sites, and a higher number of whistles detected per minute in the site with tour-boat traffic. Furthermore, whistle modulation accounted for most of the differences between sites, boat presence, and whistle types. Dolphin whistle modulation is thought to be a potential indicator of emotional states including danger, alertness, and stress. In this study, dolphin signature whistle modulation increased significantly with boat presence in both sites but changes in modulation were greater in Dolphin Bay where tour-boats directly and sometimes aggressively interact with the animals. These results support a potential association between whistle modulation and stress (or alertness). These findings indicate that if tour-boat captains behave more like taxi-boat captains by e.g., reducing the distance of approach and contact time during dolphin interactions, dolphin communication, and emotional state would be less disrupted. These measures are implemented in the national guidelines for whale-watching and are known to tour-boat operators. The key to protecting these dolphins is in finding ways to effectively enforce these operator guidelines.
Asymmetric Ocean Response to Atmospheric Forcing in an Island Wake: A 35-Year High-Resolution Study
Authors: Alves José M. R. , Tomé Ricardo , Caldeira Rui M. A. , Miranda Pedro M. A.
Published: February 2021

The present study assesses the thermal variability of the regional ocean around Madeira Island, in intraseasonal and interdecadal time scales, using a 35-year (1983–2017), 3-km horizontal resolution ocean simulation forced by a co-located atmospheric simulation, with SODA and ERA5 boundary and initial conditions, respectively. Atmosphere–ocean interactions in this region are found to be driven by the variability of two quasi-permanent tip-jets, located at the island west and east tips, especially during the summer months. The ocean response is found to be larger in the regions of higher jets speed variability, but its thermal response is highly asymmetrical. On the interdecadal time scale, a significant intensification of both jets during the analyzed period is more prominent in the east tip, but the thermal signature is mostly associated with a much reduced sea surface temperature trend near the west tip.
Bioluminescence in Polynoid Scale Worms (Annelida: Polynoidae)
Authors: Moraes Gabriela V. , Hannon Mary Colleen , Soares Douglas M. M. , Stevani Cassius V. , Schulze Anja , Oliveira Anderson G.
Published: February 2021

Bioluminescence is widespread throughout the phylum Annelida and occurs in terrestrial and marine lineages. Among marine taxa, bioluminescence has been documented in eight families and anecdotally reported in six additional families. Although new bioluminescent systems have been recently described in annelids, there are still many other families whose light emission mechanisms have not been sufficiently studied. Some of these include luminescent species belonging to the Polynoidae family, also known as scale worms, whose iterations of dorsal elytra (scales) have the ability to emit intense light when stimulated. Depending on the degree of stimulation, some polynoids can autotomize these luminous elytra and posterior segments, which could potentially give them an advantage in evading attacks by predators. It is believed that Polynoidae bioluminescence is associated with a membrane enzyme known as “polynoidin,” which was isolated during the early 1980s fromMalmgrenia lunulata. However, the characterization and properties of this enzyme, as well as the chemical nature of its substrate or additional potential cofactors, have never been fully described and remain largely unknown. As such, this paper seeks to revisit previous research involving bioluminescence studies in Polynoidae, as well as the morphological, phylogenetic and ecological aspects related to this emission of light.
Experimental Study on an Innovative Biopolymeric Treatment Against Salt Deterioration of Materials in Cultural Heritage
Authors: Bassi Mattia , Sassoni Enrico , Franzoni Elisa
Published: February 2021

Salt crystallization is one of the harshest deterioration mechanisms affecting heritage materials, causing impressive decay patterns and the loss of a high thickness of original materials. Although salt damage has been widely investigated in the literature from the theoretical and experimental points of view, the solutions to mitigate this problem are still extremely limited. In the present paper, a new biopolymeric treatment based on chitosan was tested on two kinds of porous limestones widely used in historic architecture, aiming at inhibiting the crystallization of sodium sulphate inside the stone and promoting the formation of salt efflorescence over the surface, rather than harmful subflorescence inside the pore network. The treatment was applied to the bare stone and also after an inorganic pre-treatment based on the formation of hydroxyapatite in the stone. Hydroxyapatite was recently proposed for the consolidation and protection of carbonate stones and here it is expected to provide an effective anchoring layer for the chitosan coating on the pores surface, and also to prevent the calcite washout from the stone and hence the removal of chitosan. The effect of hydroxyapatite alone was also tested, for comparison’s sake. Treated and untreated stone specimens were subjected to two different accelerated salt crystallization tests, one based on crystallization cycles (wetting-drying cycles) and the other one based on continuous capillary absorption of a saline solution (“wick effect”), evaluating the results in terms of weight loss, efflorescence formation, and changes in porosity and mechanical properties. The results showed that all the treatments are compatible with the stones, and the combined treatment (hydroxyapatite + chitosan) is extremely promising for the prevention of salt damage.
PCR Array Technology in Biopsy Samples Identifies Up-Regulated mTOR Pathway Genes as Potential Rejection Biomarkers After Kidney Transplantation
Authors: Legaz Isabel , Bernardo María Victoria , Alfaro Rafael , Martínez-Banaclocha Helios , Galián Jose Antonio , Jimenez-Coll Victor , Boix Francisco , Mrowiec Anna , Salmeron Diego , Botella Carmen , Parrado Antonio , Moya-Quiles María Rosa , Minguela Alfredo , Llorente Santiago , Peña-Moral Jesús de la , Muro Manuel
Published: February 2021

Background: Antibody-mediated rejection (AMR) is the major cause of kidney transplant rejection. The donor-specific human leukocyte antigen (HLA) antibody (DSA) response to a renal allograft is not fully understood yet. mTOR complex has been described in the accommodation or rejection of transplants and integrates responses from a wide variety of signals. The aim of this study was to analyze the expression of the mTOR pathway genes in a large cohort of kidney transplant patients to determine its possible influence on the transplant outcome.

Methods: A total of 269 kidney transplant patients monitored for DSA were studied. The patients were divided into two groups, one with recipients that had transplant rejection (+DSA/+AMR) and a second group of recipients without rejection (+DSA/–AMR and –DSA/–AMR, controls). Total RNA was extracted from kidney biopsies and reverse transcribed to cDNA. Human mTOR-PCR array technology was used to determine the expression of 84 mTOR pathway genes. STRING and REVIGO software were used to simulate gene to gene interaction and to assign a molecular function.

Results: The studied groups showed a different expression of the mTOR pathway related genes. Recipients that had transplant rejection showed an over-expressed transcript (≥5-fold) of AKT1S1, DDIT4, EIF4E, HRAS, IGF1, INS, IRS1, PIK3CD, PIK3CG, PRKAG3, PRKCB (>12-fold), PRKCG, RPS6KA2, TELO2, ULK1, and VEGFC, compared with patients that did not have rejection. AKT1S1 transcripts were more expressed in +DSA/–AMR biopsies compared with +DSA/+AMR. The main molecular functions of up-regulated gene products were phosphotransferase activity, insulin-like grown factor receptor and ribonucleoside phosphate binding. The group of patients with transplant rejection also showed an under-expressed transcript (≥5-fold) of VEGFA (>15-fold), RPS6, and RHOA compared with the group without rejection. The molecular function of down-regulated gene products such as protein kinase activity and carbohydrate derivative binding proteins was also analyzed.

Conclusions: We have found a higher number of over-expressed mTOR pathway genes than under-expressed ones in biopsies from rejected kidney transplants (+DSA/+AMR) with respect to controls. In addition to this, the molecular function of both types of transcripts (over/under expressed) is different. Therefore, further studies are needed to determine if variations in gene expression profiles can act as predictors of graft loss, and a better understanding of the mechanisms of action of the involved proteins would be necessary.
Involvement of Neuro-Immune Interactions in Pruritus With Special Focus on Receptor Expressions
Authors: Ruppenstein Aylin , Limberg Maren M. , Loser Karin , Kremer Andreas E. , Homey Bernhard , Raap Ulrike
Published: February 2021

Pruritus is a common, but very challenging symptom with a wide diversity of underlying causes like dermatological, systemic, neurological and psychiatric diseases. In dermatology, pruritus is the most frequent symptom both in its acute and chronic form (over 6 weeks in duration). Treatment of chronic pruritus often remains challenging. Affected patients who suffer from moderate to severe pruritus have a significantly reduced quality of life. The underlying physiology of pruritus is very complex, involving a diverse network of components in the skin including resident cells such as keratinocytes and sensory neurons as well as transiently infiltrating cells such as certain immune cells. Previous research has established that there is a significant crosstalk among the stratum corneum, nerve fibers and various immune cells, such as keratinocytes, T cells, basophils, eosinophils and mast cells. In this regard, interactions between receptors on cutaneous and spinal neurons or on different immune cells play an important role in the processing of signals which are important for the transmission of pruritus. In this review, we discuss the role of various receptors involved in pruritus and inflammation, such as TRPV1 and TRPA1, IL-31RA and OSMR, TSLPR, PAR-2, NK1R, H1R and H4R, MRGPRs as well as TrkA, with a focus on interaction between nerve fibers and different immune cells. Emerging evidence shows that neuro-immune interactions play a pivotal role in mediating pruritus-associated inflammatory skin diseases such as atopic dermatitis, psoriasis or chronic spontaneous urticaria. Targeting these bidirectional neuro-immune interactions and the involved pruritus-specific receptors is likely to contribute to novel insights into the underlying pathogenesis and targeted treatment options of pruritus.
Improved Alveolar Dynamics and Structure After Alveolar Epithelial Type II Cell Transplantation in Bleomycin Induced Lung Fibrosis
Authors: Lopez-Rodriguez Elena , Gay-Jordi Gemma , Knudsen Lars , Ochs Matthias , Serrano-Mollar Anna
Published: February 2021

Idiopathic pulmonary fibrosis (IPF) is a progressively and ultimately fatal lung disease. Previously it has been shown that intratracheal administration of alveolar epithelial type II cells (AE2C) in the animal model of bleomycin-induced pulmonary fibrosis is able to reverse fibrosis and restore surfactant protein levels. However, to date, it has not been evaluated whether these changes involve any improvement in alveolar dynamics. Consequently, the aim of the present work was to study lung physiology after AE2C transplantation at different time points during the development of injury and fibrosis. Lung fibrosis was induced by intratracheal instillation of bleomycin (4U/kg) in rat lungs. The animals were transplanted with AE2C (2.5 × 106 cells/animal) 3 or 7 days after bleomycin instillation. Assessments were done at day 7 and 14 after the induction of fibrosis to plot time dependent changes in lung physiology and mechanics. To assess the pressures and rates at which closed alveoli reopens invasive pulmonary tests using a small-animal mechanical ventilator (Flexivent®, Scireq, Canada) including de-recruitability tests and forced oscillation technique as well as quasi-static pressure volume loops were performed. Afterwards lungs were fixed by vascular perfusion and subjected to design-based stereological evaluation at light and electron microscopy level. AE2C delivered during the lung injury phase (3 days) of the disease are only able to slightly recover the volume of AE2C and volume fraction of LB in AE2C. However, it did not show either positive effects regarding ventilated alveolar surface nor any increase of lung compliance. On the other hand, when AE2C are delivered at the beginning of the fibrotic phase (7 days after bleomycin instillation), an increased ventilated alveolar surface to control levels and reduced septal wall thickness can be observed. Moreover, transplanted animals showed better lung performance, with increased inspiratory capacity and compliance. In addition, a detailed analysis of surfactant active forms [mainly tubular myelin, lamellar body (LB)-like structures and multilamellar vesicles (MLV)], showed an effective recovery during the pro-fibrotic phase due to the healthy AE2C transplantation. In conclusion, AE2C transplantation during fibrogenic phases of the disease improves lung performance, structure and surfactant ultrastructure in bleomycin-induced lung fibrosis.
COVID-19 and Risk of Acute Ischemic Stroke and Acute Lung Injury in Patients With Type II Diabetes Mellitus: The Anti-inflammatory Role of Metformin
Authors: Al-kuraishy Hayder M. , Al-Gareeb Ali I. , Alblihed M. , Cruz-Martins Natália , Batiha Gaber El-Saber
Published: February 2021

Background: Coronavirus disease 19 (COVID-19) is regarded as an independent risk factor for acute ischemic stroke (AIS) due to the induction of endothelial dysfunction, coagulopathy, cytokine storm, and plaque instability.

Method: In this retrospective cohort study, a total of 42 COVID-19 patients with type 2 diabetes mellitus (T2DM) who presented with AIS within 1 week of displaying COVID-19 symptoms were recruited. According to the current anti-DM pharmacotherapy, patients were divided into two groups: a Metformin group of T2DM patients with COVID-19 and AIS on metformin therapy (850 mg, 3 times daily (n = 22), and a Non-metformin group of T2DM patients with COVID-19 and AIS under another anti-DM pharmacotherapy like glibenclamide and pioglitazone (n = 20). Anthropometric, biochemical, and radiological data were evaluated.

Results: Ferritin serum level was lower in metformin-treated patients compared to non-metformin treated patients (365.93 ± 17.41 vs. 475.92 ± 22.78 ng/mL, p = 0.0001). CRP, LDH, and D-dimer serum levels were also lowered in metformin-treated patients compared to non-metformin treated patients (p = 0.0001). In addition, lung CT scan scores of COVID-19 patients was 30.62 ± 10.64 for metformin and 36.31 ± 5.03 for non-metformin treated patients.

Conclusion: Metformin therapy in T2DM patients was linked to a lower risk of AIS during COVID-19. Further studies are needed to observe the link between AIS in COVID-19 diabetic patients and metformin therapy.
Identification of a Novel Brevibacillus laterosporus Strain With Insecticidal Activity Against Aedes albopictus Larvae
Authors: Barbieri Giulia , Ferrari Carolina , Mamberti Stefania , Gabrieli Paolo , Castelli Michele , Sassera Davide , Ursino Emanuela , Scoffone Viola Camilla , Radaelli Giacomo , Clementi Emanuela , Sacchi Luciano , Ferrari Eugenio , Gasperi Giuliano , Albertini Alessandra M.
Published: February 2021

Bacterial species able to produce proteins that are toxic against insects have been discovered at the beginning of the last century. However, up to date only two of them have been used as pesticides in mosquito control strategies targeting larval breeding sites: Bacillus thuringensis var. israelensis and Lysinibacillus sphaericus. Aiming to expand the arsenal of biopesticides, bacterial cultures from 44 soil samples were assayed for their ability to kill larvae of Aedes albopictus. A method to select, grow and test the larvicidal capability of spore-forming bacteria from each soil sample was developed. This allowed identifying 13 soil samples containing strains capable of killing Ae. albopictus larvae. Among the active isolates, one strain with high toxicity was identified as Brevibacillus laterosporus by 16S rRNA gene sequencing and by morphological characterization using transmission electron microscopy. The new isolate showed a larvicidal activity significantly higher than the B. laterosporus LMG 15441 reference strain. Its genome was phylogenomically characterized and compared to the available Brevibacillus genomes. Thus, the new isolate can be considered as a candidate adjuvant to biopesticides formulations that would help preventing the insurgence of resistance.
Vibrio natriegens as a pET-Compatible Expression Host Complementary to Escherichia coli
Authors: Xu Jiaqi , Dong Feng , Wu Meixian , Tao Rongsheng , Yang Junjie , Wu Mianbin , Jiang Yu , Yang Sheng , Yang Lirong
Published: February 2021

Efficient and novel recombinant protein expression systems can further reduce the production cost of enzymes. Vibrio natriegens is the fastest growing free-living bacterium with a doubling time of less than 10 min, which makes it highly attractive as a protein expression host. Here, 196 pET plasmids with different genes of interest (GOIs) were electroporated into the V. natriegens strain VnDX, which carries an integrated T7 RNA polymerase expression cassette. As a result, 65 and 75% of the tested GOIs obtained soluble expression in V. natriegens and Escherichia coli, respectively, 20 GOIs of which showed better expression in the former. Furthermore, we have adapted a consensus “what to try first” protocol for V. natriegens based on Terrific Broth medium. Six sampled GOIs encoding biocatalysts enzymes thus achieved 50–128% higher catalytic efficiency under the optimized expression conditions. Our study demonstrated V. natriegens as a pET-compatible expression host with a spectrum of highly expressed GOIs distinct from E. coli and an easy-to-use consensus protocol, solving the problem that some GOIs cannot be expressed well in E. coli.
Adaptive Gene Content and Allele Distribution Variations in the Wild and Domesticated Populations of Saccharomyces cerevisiae
Authors: Han Da-Yong , Han Pei-Jie , Rumbold Karl , Koricha Anbessa Dabassa , Duan Shou-Fu , Song Liang , Shi Jun-Yan , Li Kuan , Wang Qi-Ming , Bai Feng-Yan
Published: February 2021

Recent studies on population genomics of Saccharomyces cerevisiae have substantially improved our understanding of the genetic diversity and domestication history of the yeast. However, the origin of the domesticated population of S. cerevisiae and the genomic changes responsible for ecological adaption of different populations and lineages remain to be fully revealed. Here we sequenced 64 African strains from various indigenous fermented foods and forests in different African countries and performed a population genomic analysis on them combined with a set of previously sequenced worldwide S. cerevisiae strains representing the maximum genetic diversity of the species documented so far. The result supports the previous observations that the wild and domesticated populations of S. cerevisiae are clearly separated and that the domesticated population diverges into two distinct groups associated with solid- and liquid-state fermentations from a single ancestor. African strains are mostly located in basal lineages of the two domesticated groups, implying a long domestication history of yeast in Africa. We identified genes that mainly or exclusively occur in specific groups or lineages and genes that exhibit evident group or lineage specific allele distribution patterns. Notably, we show that the homing endonuclease VDE is generally absent in the wild but commonly present in the domesticated lineages of S. cerevisiae. The genes with group specific allele distribution patterns are mostly enriched in functionally similar or related fundamental metabolism processes, including the evolutionary conserved TOR signaling pathway.
The Emergence of Invasive Streptococcus pneumoniae Serotype 24F in Lebanon: Complete Genome Sequencing Reveals High Virulence and Antimicrobial Resistance Characteristics
Authors: Reslan Lina , Finianos Marc , Bitar Ibrahim , Moumneh Mohamad Bahij , Araj George F. , Zaghlout Alissar , Boutros Celina , Jisr Tamima , Nabulsi Malak , Kara yaccoub Gilbert , Hamze Monzer , Osman Marwan , Bou Raad Elie , Hrabak Jaroslav , Matar Ghassan M. , Dbaibo Ghassan
Published: February 2021

Background

Invasive pneumococcal disease (IPD) remains a global health problem. IPD incidence has significantly decreased by the use of pneumococcal conjugate vaccines (PCV). Nevertheless, non-PCV serotypes remain a matter of concern. Eight Streptococcus pneumoniae serotype 24F isolates, belonging to a non-PCV serotype, were detected through the Lebanese Inter-Hospital Pneumococcal Surveillance Program. The aim of the study is to characterize phenotypic and genomic features of the 24F isolates in Lebanon.

Methods

WGS using long reads sequencing (PacBio) was performed to produce complete circular genomes and to determine clonality, antimicrobial resistance and virulence determinants.

Results

The sequencing results yielded eight closed circular genomes. Three multilocus sequence typing (MLST) types were identified (ST11618, ST14184, ST15253). Both MLST and WGS analyses revealed that these isolates from Lebanon were genetically homogenous belonging to clonal complex CC230 and clustered closely with isolates originating from Canada, United States of America, United Kingdom and Iceland. Their penicillin binding protein profiles correlated with both β-lactam susceptibility patterns and MLST types. Moreover, the isolates harbored the macrolide and tetracycline resistance genes and showed a similar virulence gene profile. To our knowledge, this study represents the first report of complete phenotypic and genomic characterization of the emerging Streptococcus pneumoniae, serotype 24F, in the Middle East and North Africa region.
The Prognostic Value and Mechanisms of TMEM16A in Human Cancer
Authors: Chen Wenjian , Gu Meng , Gao Chaobing , Chen Bangjie , Yang Junfa , Xie Xiaoli , Wang Xinyi , Sun Jun , Wang Jinian
Published: February 2021

As a calcium ion-dependent chloride channel transmembrane protein 16A (TMEM16A) locates on the cell membrane. Numerous research results have shown that TMEM16A is abnormally expressed in many cancers. Mechanically, TMEM16A participates in cancer proliferation and migration by affecting the MAPK and CAMK signaling pathways. Additionally, it is well documented that TMEM16A exerts a regulative impact on the hyperplasia of cancer cells by interacting with EGFR in head and neck squamous cell carcinoma (HNSCC), an epithelial growth factor receptor in head and neck squamous cell carcinoma respectively. Meanwhile, as an EGFR activator, TMEM16A is considered as an oncogene or a tumor-promoting factor. More and more experimental data showed that down-regulation of TMEM16A or gene targeted therapy may be an effective treatment for cancer. This review summarized its role in various cancers and research advances related to its clinical application included treatment and diagnosis.