bluuebunny/crossref_metadata_2025 huggingface dataset:
Seismic Anisotropy in Subduction Zones: Evaluating the Role of Chloritoid
Authors: Lee Jungjin , Mookherjee Mainak , Kim Taehwan , Jung Haemyeong , Klemd Reiner
Published: March 2021

Subduction zones are often characterized by the presence of strong trench-parallel seismic anisotropy and large delay times. Hydrous minerals, owing to their large elastic anisotropy and strong lattice preferred orientations (LPOs), are often invoked to explain these observations. However, the elasticity and the LPO of chloritoid, which is one of such hydrous phases relevant in subduction zone settings, are poorly understood. In this study, we measured the LPO of polycrystalline chloritoid in natural rock samples, obtained the LPO-induced seismic anisotropy, and evaluated the thermodynamic stability field of chloritoid in subduction zones. The LPO of chloritoid aggregates displayed a strong alignment of the [001] axes subnormal to the rock foliation, with a girdle distribution of the [100] axes and the (010) poles subparallel to the foliation. New elasticity data of single-crystal chloritoid showed a strong elastic anisotropy of chloritoid with 47% for S-waves (VS) and 22% for P-waves (VP), respectively. The combination of the LPO and the elastic anisotropy of the chloritoid aggregates produced a strong S-wave anisotropy with a maximum AVS of 18% and a P-wave anisotropy with an AVP of 10%. The role of chloritoid LPO in seismic anisotropy was evaluated in natural rock samples and a hypothetical blueschist. Our results indicate that the strong LPO of chloritoid along the subduction interface and in subducting slabs can influence the trench-parallel seismic anisotropy in subduction zones with “cold” geotherms.
How Online Teams with Diverse Backgrounds Worked to Excel: Findings from an International eTournament
Authors: Lau Martin , Vuthaluru Rupa , Mui Lawrence , Kerrigan Simon , Kwong Theresa , Law Lisa , Wong Eva Y. W. , Gibson David
Published: March 2021

A tide of changes with technological advances at its center has allowed more efficient and productive synchronous and asynchronous collaborations among dispersed individuals across the globe in recent years. Working effectively in virtual teams of individuals with diverse backgrounds is thus critical for students to succeed in the 21st century. However, relevant training for international collaboration is lacking in the higher education system. The research team examined data from a project aimed to heighten students’ multidisciplinary and multicultural competencies via a team-based, international eTournament organized in 2019 and enhanced and repeated in early 2020 featuring the 17 Sustainable Development Goals (SDGs) of the United Nations. Students were teamed up according to a mechanism, to ensure diversity in each virtual team and mimic the real practice in many workplaces. A two-stage “strategize-play” approach was deployed with activities carried out entirely online. Team members first got to know each other, built up their teams and formulated their strategies for the next stage. In the second stage, the virtual teams competed with one other on a gamified learning platform called PaGamO by answering questions related to the SDGs. About 240 students (2019) and 420 students (2020) participated. Various sets of quantitative and qualitative data were collected, including student chat histories, focus group interviews, data analytics from PaGamO recording how the students progressed in the game, as well as the pre- and post-game surveys. This article focuses on the chat histories of students from the top-5 and bottom-5 teams of the 2019 and 2020 eTournaments. The results provide evidence that the high performing teams took a different gaming approach from the low performing teams in such areas as team building and game strategy deployment.
Seven Novel Genes Related to Cell Proliferation and Migration of VHL-Mutated Pheochromocytoma
Authors: Gao Shuai , Liu Longfei , Li Zhuolin , Pang Yingxian , Shi Jiaqi , Zhu Feizhou
Published: March 2021

Pheochromocytoma, as a neuroendocrine tumor with the highest genetic correlation in all types of tumors, has attracted extensive attention. Von Hipper Lindau (VHL) has the highest mutation frequency among the genes associated with pheochromocytoma. However, the effect of VHL on the proteome of pheochromocytoma remains to be explored. In this study, the VHL knockdown (VHL-KD) PC12 cell model was established by RNA interference (shRNA). We compared the proteomics of VHL-KD and VHL-WT PC12 cell lines. The results showed that the expression of 434 proteins (VHL shRNA/WT > 1.3) changed significantly in VHL-KD-PC12 cells. Among the 434 kinds of proteins, 83 were involved in cell proliferation, cell cycle and cell migration, and so on. More importantly, among these proteins, we found seven novel key genes, including Connective Tissue Growth Factor (CTGF), Syndecan Binding Protein (SDCBP), Cysteine Rich Protein 61 (CYR61/CCN1), Collagen Type III Alpha 1 Chain (COL3A1), Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type V Alpha 2 Chain (COL5A2), and Serpin Family E Member 1 (SERPINE1), were overexpressed and simultaneously regulated cell proliferation and migration in VHL-KD PC12 cells. Furthermore, the abnormal accumulation of HIF2α caused by VHL-KD significantly increased the expression of these seven genes during hypoxia. Moreover, cell-counting, scratch, and transwell assays demonstrated that VHL-KD could promote cell proliferation and migration, and changed cell morphology. These findings indicated that inhibition of VHL expression could promote the development of pheochromocytoma by activating the expression of cell proliferation and migration associated genes.
Mathematical Model of Glucagon Kinetics for the Assessment of Insulin-Mediated Glucagon Inhibition During an Oral Glucose Tolerance Test
Authors: Morettini Micaela , Burattini Laura , Göbl Christian , Pacini Giovanni , Ahrén Bo , Tura Andrea
Published: March 2021

Glucagon is secreted from the pancreatic alpha cells and plays an important role in the maintenance of glucose homeostasis, by interacting with insulin. The plasma glucose levels determine whether glucagon secretion or insulin secretion is activated or inhibited. Despite its relevance, some aspects of glucagon secretion and kinetics remain unclear. To gain insight into this, we aimed to develop a mathematical model of the glucagon kinetics during an oral glucose tolerance test, which is sufficiently simple to be used in the clinical practice. The proposed model included two first-order differential equations -one describing glucagon and the other describing C-peptide in a compartment remote from plasma - and yielded a parameter of possible clinical relevance (i.e., SGLUCA(t), glucagon-inhibition sensitivity to glucose-induced insulin secretion). Model was validated on mean glucagon data derived from the scientific literature, yielding values for SGLUCA(t) ranging from -15.03 to 2.75 (ng of glucagon·nmol of C-peptide-1). A further validation on a total of 100 virtual subjects provided reliable results (mean residuals between -1.5 and 1.5 ng·L-1) and a negative significant linear correlation (r = -0.74, p < 0.0001, 95% CI: -0.82 – -0.64) between SGLUCA(t) and the ratio between the areas under the curve of suprabasal remote C-peptide and glucagon. Model reliability was also proven by the ability to capture different patterns in glucagon kinetics. In conclusion, the proposed model reliably reproduces glucagon kinetics and is characterized by sufficient simplicity to be possibly used in the clinical practice, for the estimation in the single individual of some glucagon-related parameters.
Nutrition and Obesity in the Pathogenesis of Youth-Onset Type 1 Diabetes and Its Complications
Authors: March Christine A. , Becker Dorothy J. , Libman Ingrid M.
Published: March 2021

Since the 1980s, there has been a dramatic rise in the prevalence of overweight and obesity in pediatric populations, in large part driven by sedentary lifestyles and changing dietary patterns with more processed foods. In parallel with the rise in pediatric obesity in the general population, the prevalence of overweight and obesity has increased among children and adolescents with type 1 diabetes. Adiposity has been implicated in a variety of mechanisms both potentiating the risk for type 1 diabetes as well as exacerbating long-term complications, particularly cardiovascular disease. Treatment options targeting the unique needs of obese pediatric patients, both before and after diagnosis of type 1 diabetes, are limited. In this review, we discuss the history of the epidemiology of the obesity epidemic in the context of pediatric type 1 diabetes, highlight the possible role of obesity in type 1 diabetes pathogenesis and review the concept of “double diabetes”. The impact of obesity at and after diagnosis will be discussed, including noted differences in clinical and biochemical markers, lipid abnormalities, and long-term cardiovascular complications. Finally, we will review the existing literature on pharmacologic and nutritional interventions as potential treatment strategies for youth with coexisting type 1 diabetes and obesity.
Case Report: A Case of Pituitary Adenoma Producing Growth Hormone and Thyroid-Stimulating Hormone Simultaneously
Authors: Sanada Junpei , Tatsumi Fuminori , Kamei Shinji , Fushimi Yoshiro , Shimoda Masashi , Kohara Kenji , Nakanishi Shuhei , Kaku Kohei , Mune Tomoatsu , Kaneto Hideaki
Published: March 2021

Background

Pituitary adenoma producing growth hormone (GH) or thyroid-stimulating hormone (TSH) is characterized by various specific symptoms and/or findings. However, the frequency of pituitary adenoma producing both hormones is relatively low. In this report, we show a case of pituitary adenoma producing both GH and TSH simultaneously.

Case presentation

A 27-year-old woman was diagnosed as acromegaly based on various symptoms and clinical findings. For further examination and treatment, she was hospitalized in our institution. It was likely that this subject had pituitary adenoma producing both GH and TSH. In brain magnetic resonance imaging, there was a giant tumor around pituitary fossa. After the diagnosis of GH- and TSH-producing pituitary adenoma, pituitary tumor resection and cyber knife therapy were performed. In addition, we started additional treatment with somatostatin analog and GH receptor antagonist. After then, GH and insulin-like growth factor (IGF-1) levels were suppressed. After the operation, since thyroid function was not sufficiently suppressed, we started anti-thyroid drug thiamazole. After then, thyroid function was normalized and we stopped thiamazole. In GH and TSH staining, many GH-positive and TSH-positive cells were observed. These findings further confirmed our diagnosis that the pituitary adenoma in this subject produced both GH and TSH simultaneously.

Conclusions

We should bear in mind the possibility of pituitary adenoma producing both GH and TSH at the same time.
Foraging Small White Butterflies, Pieris rapae, Search Flowers Using Color Vision
Authors: Arikawa Kentaro , Nakatani Yoshihiro , Koshitaka Hisaharu , Kinoshita Michiyo
Published: March 2021

We demonstrate that the small white butterfly,Pieris rapae, uses color vision when searching flowers for foraging. We first trained newly emerged butterflies in a series of indoor behavioral experiments to take sucrose solution on paper disks, colored either blue, green, yellow, or red. After confirming that the butterflies were trained to visit a certain colored disk, we presented all disks simultaneously. The butterflies selected the disk of trained color, even among an array of disks with different shades of gray. We performed the training using monochromatic lights and measured the action spectrum of the feeding behavior to determine the targets’Pieris-subjective brightness. We used the subjective brightness information to evaluate the behavioral results and concluded thatPieris rapaebutterflies discriminate visual stimuli based on the chromatic content independent of the intensity: they have true color vision. We also found thatPierisbutterflies innately prefer blue and yellow disks, which appears to match with their flower preference in the field, at least in part.
A Conserved Gcn2-Gcn4 Axis Links Methionine Utilization and the Oxidative Stress Response in Cryptococcus neoformans
Authors: Stovall Anna K. , Knowles Corey M. , Kalem Murat C. , Panepinto John C.
Published: March 2021

The fungal pathogen Cryptococcus neoformans relies on post-transcriptional mechanisms of gene regulation to adapt to stressors it encounters in the human host, such as oxidative stress and nutrient limitation. The kinase Gcn2 regulates translation in response to stress by phosphorylating the initiation factor eIF2, and it is a crucial factor in withstanding oxidative stress in C. neoformans, and amino acid limitation in many fungal species. However, little is known about the role of Gcn2 in nitrogen limitation in C. neoformans. In this study, we demonstrate that Gcn2 is required for C. neoformans to utilize methionine as a source of nitrogen, and that the presence of methionine as a sole nitrogen source induces eIF2 phosphorylation. The stress imposed by methionine leads to an oxidative stress response at both the levels of transcription and translation, as seen through polysome profiling as well as increased abundance of select oxidative stress response transcripts. The transcription factor Gcn4 is also required for methionine utilization and oxidative stress resistance, and RT-qPCR data suggests that it regulates expression of certain transcripts in response to oxidative stress. The results of this study suggest a connection between nitrogen metabolism and oxidative stress in C. neoformans that is mediated by Gcn4, possibly indicating the presence of a compound stress response in this clinically important fungal pathogen.
Epigenetic Lens to Visualize the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection in COVID-19 Pandemic
Authors: Saksena Nitin , Bonam Srinivasa Reddy , Miranda-Saksena Monica
Published: March 2021

In <20 years, we have witnessed three different epidemics with coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2 in human populations, causing widespread mortality. SARS-CoV-2, through its rapid global spread, has led to the pandemic that we call COVID-19. As of February 1, 2021, the global infections linked to SARS-CoV-2 stand at 103,503,340, with 2,236,960 deaths, and 75,108,099 recoveries. This review attempts to highlight host-pathogen interaction with particular emphasis on the role of epigenetic machinery in regulating the disease. Although researchers, since the start of the pandemic, have been intensely engaged in diverse areas to understand the mechanisms involved in SARS-CoV-2 infection to find answers that can bring about innovative ways to swiftly treat and prevent disease progression, this review provides an overview on how the host epigenetics is modulated and subverted by SARS-CoV-2 to enter the host cells and drive immunopathogenesis. Epigenetics is the study that combines genetic and non-genetic factors controlling phenotypic variation, which are primarily a consequence of external and environmental stimuli. These stimuli alter the activity of a gene without impinging on the DNA code. In viral-host interactions, DNA/RNA methylation, non-coding RNAs, chromatin remodeling, and histone modifications are known to regulate and modulate host gene expression patterns. Viruses such as Coronaviruses (an RNA virus) show intrinsic association with these processes. They have evolved the ability to tamper with host epigenetic machinery to interfere with immune sensing pathways to evade host immune response, thereby enhancing its replication and pathogenesis post-entry. These epigenetic alterations allow the virus to weaken the host's immune response to successfully spread infection. How this occurs, and what epigenetic mechanisms are altered is poorly understood both for coronaviruses and other respiratory RNA viruses. The review highlights several cutting-edge aspects of epigenetic work primarily pertinent to SARS-CoV-2, which has been published between 2019 and 2020 to showcase the current knowledge both in terms of success and failures and take lessons that will assist us in understanding the disease to develop better treatments suited to kill SARS-CoV-2.
Evaluating the Reproducibility of Single-Cell Gene Regulatory Network Inference Algorithms
Authors: Kang Yoonjee , Thieffry Denis , Cantini Laura
Published: March 2021

Networks are powerful tools to represent and investigate biological systems. The development of algorithms inferring regulatory interactions from functional genomics data has been an active area of research. With the advent of single-cell RNA-seq data (scRNA-seq), numerous methods specifically designed to take advantage of single-cell datasets have been proposed. However, published benchmarks on single-cell network inference are mostly based on simulated data. Once applied to real data, these benchmarks take into account only a small set of genes and only compare the inferred networks with an imposed ground-truth. Here, we benchmark six single-cell network inference methods based on their reproducibility, i.e., their ability to infer similar networks when applied to two independent datasets for the same biological condition. We tested each of these methods on real data from three biological conditions: human retina, T-cells in colorectal cancer, and human hematopoiesis. Once taking into account networks with up to 100,000 links, GENIE3 results to be the most reproducible algorithm and, together with GRNBoost2, show higher intersection with ground-truth biological interactions. These results are independent from the single-cell sequencing platform, the cell type annotation system and the number of cells constituting the dataset. Finally, GRNBoost2 and CLR show more reproducible performance once a more stringent thresholding is applied to the networks (1,000–100 links). In order to ensure the reproducibility and ease extensions of this benchmark study, we implemented all the analyses in scNET, a Jupyter notebook available at https://github.com/ComputationalSystemsBiology/scNET.
Reduced Animal Models Fitting Only Equations for Phenotyped Animals
Authors: Nilforooshan Mohammad Ali , Garrick Dorian
Published: March 2021

Reduced models are equivalent models to the full model that enable reduction in the computational demand for solving the problem, here, mixed model equations for estimating breeding values of selection candidates. Since phenotyped animals provide data to the model, the aim of this study was to reduce animal models to those equations corresponding to phenotyped animals. Non-phenotyped ancestral animals have normally been included in analyses as they facilitate formation of the inverse numerator relationship matrix. However, a reduced model can exclude those animals and obtain identical solutions for the breeding values of the animals of interest. Solutions corresponding to non-phenotyped animals can be back-solved from the solutions of phenotyped animals and specific blocks of the inverted relationship matrix. This idea was extended to other forms of animal model and the results from each reduced model (and back-solving) were identical to the results from the corresponding full model. Previous studies have been mainly focused on reduced animal models that absorb equations corresponding to non-parents and solve equations only for parents of phenotyped animals. These two types of reduced animal model can be combined to formulate only equations corresponding to phenotyped parents of phenotyped progeny.
Neural Differentiation of Mouse Embryonic Stem Cells—An in vitro Approach to Profile DNA Methylation of Reprogramming Factor Sox2-SRR2
Authors: Batool Sajida , Kayani Mahmood Akhtar , Valis Martin , Kuca Kamil
Published: March 2021

Sox2 is one of the core transcription factors maintaining the embryonic stem cells (ES) pluripotency and, also indispensable for cellular reprogramming. However, limited data is available about the DNA methylation of pluripotency genes during lineage-specific differentiations. This study investigated the DNA methylation of Sox2 regulatory region 2 (SRR2) during directed differentiation of mouse ES into neural lineage. ES cells were first grown to form embryoid bodies in suspension which were then dissociated, and cultured in defined medium to promote neural differentiation. Typical neuronal morphology together with the up-regulation of Pax6, neuroepithelial stem cell intermediate filament and β-tubulin III and, down-regulation of pluripotency genes Oct4, Nanog and Sox2 showed the existence of neural phenotype in cells undergoing differentiation. Three CpGs in the core enhancer region of neural-specific SRR2 were individually investigated by direct DNA sequencing post-bisulfite treatment and, found to be unmethylated in differentiated cells at time-points chosen for analysis. This analysis does not limit the possibility of methylation at other CpG sites than those profiled here and/or transient methylation. Hence, similar analyses exploring the DNA methylation at other regions of the Sox2 gene could unravel the onset and transitions of epigenetic signatures influencing the outcome of differentiation pathways and neural development. The data presented here shows thatin vitroneural differentiation of embryonic stem cells can be employed to study and characterize molecular regulatory mechanisms governing neurogenesis by applying diverse pharmacological and toxicological agents.
NOX2 Deficiency Permits Sustained Survival of S. aureus in Macrophages and Contributes to Severity of Infection
Authors: Tosetti Bettina , Ward Beate , Grumme Daniela , Herb Marc , Schramm Michael , Utermöhlen Olaf , Heukamp Lukas C. , Krönke Martin , Krut Oleg
Published: March 2021

Although the crucial role of professional phagocytes for the clearance of S. aureus infections is well-established, several studies indicate an adverse role of leukocytes in the dissemination of S. aureus during infection. Since only little is known about macrophages in this context, we analyzed the role of macrophages, and in particular reactive oxygen species deficiency, for the seeding of S. aureus metastases. Infection of bone marrow-derived macrophages (BMDM) with S. aureus revealed that NADPH oxidase 2 (NOX2-) deficient, but not NOX1- or NOX4-deficient, BMDM failed to clear intracellular S. aureus. Despite of larger intracellular bacterial burden, NOX2-deficient BMDM showed significantly improved survival. Intravenous injection of mice with in vitro-infected BMDMs carrying intracellular viable S. aureus led to higher bacterial loads in kidney and liver of mice compared to injection with plain S. aureus. An even higher frequency of liver abscesses was observed in mice infected with S. aureus-loaded nox2−/− BMDM. Thus, the improved intracellular survival of S. aureus and improved viability of NOX2-deficient BMDM is associated with an aggravated metastatic dissemination of S. aureus infection. A combination of vancomycin and the intracellularly active antibiotic rifampicin led to complete elimination of S. aureus from liver within 48 h, which was not achieved with vancomycin treatment alone, underscoring the impact of intracellular S. aureus on the course of disease. The results of our study indicate that intracellular S. aureus carried by macrophages are sufficient to establish a systemic infection. This suggests the inclusion of intracellularly active antibiotics in the therapeutic regimen of invasive S. aureus infections, especially in patients with NADPH oxidase deficiencies such as chronic granulomatous disease.
Longitudinal CSF Findings in Autoimmune Encephalitis—A Monocentric Cohort Study
Authors: Zrzavy Tobias , Höftberger Romana , Wimmer Isabella , Berger Thomas , Rommer Paulus , Macher Stefan
Published: March 2021

Autoimmune encephalitis (AIE) poses a diagnostic challenge due to its heterogeneous clinical presentation, which overlaps with various neurological and psychiatric diseases. During the diagnostic work-up, cerebrospinal fluid (CSF) is routinely obtained, allowing for differential diagnostics as well as for the determination of antibody subclasses and specificities. In this monocentric cohort study, we describe initial and serial CSF findings of 33 patients diagnosed with antibody-associated AIE (LGI1 (n=8), NMDA (n=7), CASPR2 (n=3), IgLON5 (n=3), AMPAR (n=1), GAD65/67 (n=4), Yo (n=3), Ma-1/2 (n=2), CV2 (n=2)). Routine CSF parameters of 12.1% of AIE patients were in normal ranges, while 60.6% showed elevated protein levels and 45.4% had intrathecal oligoclonal bands (OCBs). Repeated CSF analyses showed a trend towards normalization of initial pathological CSF findings, while relapses were more likely to be associated with increased cell counts and total protein levels. OCB status conversion in anti-NMDARE patients coincided with clinical improvement. In summary, we show that in routine CSF analysis at diagnosis, a considerable number of patients with AIE did not exhibit alteration in the CSF and therefore, diagnosis may be delayed if antibody testing is not performed. Moreover, OCB status in anti-NMDAR AIE patients could represent a potential prognostic biomarker, however further studies are necessary to validate these exploratory findings.
Three-Dimensional Movements and Habitat Selection of Young White Sharks (Carcharodon carcharias) Across a Temperate Continental Shelf Ecosystem
Authors: Shaw Rachel L. , Curtis Tobey H. , Metzger Gregory , McCallister Michael P. , Newton Alisa , Fischer G. Christopher , Ajemian Matthew J.
Published: March 2021

As highly mobile predators with extensive home ranges, some shark species often utilize a continuum of habitats across the continental shelf ranging from the surf zone to the open ocean. For many species, these cross-shelf distributions can change depending on ontogeny or seasonal conditions. Recent research has confirmed a white shark (Carcharodon carcharias) summer nursery off Long Island, New York; however, habitat characterization of this nursery has not yet been conducted nor has fine-scale analysis of vertical behavior. Between 2016 and 2019, 21 young-of-the-year and juvenile white sharks were fitted with satellite and acoustic tags to examine distribution and selection for a suite of oceanographic variables during their late summertime (i.e., August to October) residence in the New York Bight. Horizontal position estimates were used to extract a suite of environmental measurements via remote sensing platforms and were linked with vertical profiles to produce three-dimensional movements for a subset of individuals also fitted with pop-up satellite archival tags (n = 7). Sharks exhibited horizontal movements parallel to Long Island’s southern shoreline and coastal New Jersey, with distances from 0.1 to 131.5 km from shore. Log-likelihood chi-square analyses determined selection for waters with underlying bathymetry of 20–30 m, sea surface temperatures between 20.0 and 22.0°C, sea surface salinities between 31.0 and 32.0 ppt, and chlorophyll-a concentrations between 2.0 and 8.0 mg⋅m–3. Multiple individuals also traversed the mid- to outer shelf region after leaving the Montauk tagging area. Vertical depth profiles illustrated oscillations between the surface and 199 m of water, with an average swimming depth of 9.2 ± 8.9 m. Water column temperatures during these oscillations ranged between 7.9 and 26.2°C (mean = 19.5 ± 2.0°C) with several individuals traversing highly stratified regions presumably associated with a mid-shelf cold pool adjacent to the Hudson Shelf Valley. These results suggest young white sharks exhibit connectivity between the immediate shoreline and mid-continental shelf region, where they play important ecological roles as predators on a variety of species. Our study improves characterization of essential fish habitat for young white sharks and provides new insights into their reliance on this productive continental shelf ecosystem.
Preparation and Absorption Carbon Monoxide Properties of a Novel Flame Retardants Based Fire-Fighting Foam
Authors: Li Xiujuan , Guo Ruisong , Qian Xiaodong
Published: March 2021

The toxicity of CO threatens the life of people in the fire site. In this study, flame retardants of nano magnesium hydroxide particles and water-soluble flame retardant 8124 are used to be mixed into the aqueous film forming fire extinguishing agent (AFFF). Smoke-suppressed fire extinguishing agent was prepared in Waring-Blender mixing cup and then stirred at 3,000 r/min for 5 min. The new extinguishing agent shows a good performance of absorption of CO and reducing the flue gas temperature. The concentration of CO was decreased below 131 ppm and flue gas temperature was basically kept below 40°C, which was 367 ppm and 83.1°C less than that in free-fire. Using new extinguishing agent can effectively reduce the harm to the trapped personnel and firemen in the fire site. It was of great significance. The harm of CO concentration below 131 ppm and flue gas temperature below 40°C was low. The time to reach the maximum CO concentration and the maximum flue gas temperature was delayed, which ensures that people have more time to escape. Even if there was not enough time to escape, people will not be seriously threatened.
Effects of Diet Induced Weight Reduction on Cartilage Pathology and Inflammatory Mediators in the Joint Tissues
Authors: Sun Antonia RuJia , Wu Xiaoxin , Crawford Ross , Li Hongxing , Mei Lin , Luo Yong , Xiao Yin , Mao Xinzhan , Prasadam Indira
Published: March 2021

Obesogenic diets contribute to the pathology of osteoarthritis (OA) by altering systemic and local metabolic inflammation. Yet, it remains unclear how quickly and reproducibly the body responds to weight loss strategies and improve OA. In this study we tested whether switching obese diet to a normal chow diet can mitigate the detrimental effects of inflammatory pathways that contribute to OA pathology. Male C57BL/6 mice were first fed with obesogenic diet (high fat diet) and switched to normal chow diet (obese diet → normal diet) or continued obese diet or normal diet throughout the experiment. A mouse model of OA was induced by surgical destabilization of the medial meniscus (DMM) model into the knee joint. Outcome measures included changes in metabolic factors such as glucose, insulin, lipid, and serum cytokines levels. Inflammation in synovial biopsies was scored and inflammation was determined using FACs sorted macrophages. Cartilage degeneration was monitored using histopathology. Our results indicate, dietary switching (obese diet → normal diet) reduced body weight and restored metabolic parameters and showed less synovial tissue inflammation. Systemic blood concentrations of pro-inflammatory cytokines IL-1α, IL-6, IL-12p40, and IL-17 were decreased, and anti-inflammatory cytokines IL-4 and IL-13 were increased in dietary switch group compared to mice that were fed with obesogenic diet continuously. Although obese diet worsens the cartilage degeneration in DMM OA model, weight loss induced by dietary switch does not promote the histopathological changes of OA during this study period. Collectively, these data demonstrate that switching obesogenic diet to normal improved metabolic syndrome symptoms and can modulate both systemic and synovium inflammation levels.
Gut-Derived Metabolite Indole-3-Propionic Acid Modulates Mitochondrial Function in Cardiomyocytes and Alters Cardiac Function
Authors: Gesper Maren , Nonnast Alena B. H. , Kumowski Nina , Stoehr Robert , Schuett Katharina , Marx Nikolaus , Kappel Ben A.
Published: March 2021

Background: The gut microbiome has been linked to the onset of cardiometabolic diseases, in part facilitated through gut microbiota-dependent metabolites such as trimethylamine-N-oxide. However, molecular pathways associated to heart failure mediated by microbial metabolites remain largely elusive. Mitochondria play a pivotal role in cellular energy metabolism and mitochondrial dysfunction has been associated to heart failure pathogenesis. Aim of the current study was to evaluate the impact of gut-derived metabolites on mitochondrial function in cardiomyocytes via an in vitro screening approach.

Methods: Based on a systematic Medline research, 25 microbial metabolites were identified and screened for their metabolic impact with a focus on mitochondrial respiration in HL-1 cardiomyocytes. Oxygen consumption rate in response to different modulators of the respiratory chain were measured by a live-cell metabolic assay platform. For one of the identified metabolites, indole-3-propionic acid, studies on specific mitochondrial complexes, cytochrome c, fatty acid oxidation, mitochondrial membrane potential, and reactive oxygen species production were performed. Mitochondrial function in response to this metabolite was further tested in human hepatic and endothelial cells. Additionally, the effect of indole-3-propionic acid on cardiac function was studied in isolated perfused hearts of C57BL/6J mice.

Results: Among the metabolites examined, microbial tryptophan derivative indole-3-propionic acid could be identified as a modulator of mitochondrial function in cardiomyocytes. While acute treatment induced enhancement of maximal mitochondrial respiration (+21.5 ± 7.8%, p < 0.05), chronic exposure led to mitochondrial dysfunction (−18.9 ± 9.1%; p < 0.001) in cardiomyocytes. The latter effect of indole-3-propionic acids could also be observed in human hepatic and endothelial cells. In isolated perfused mouse hearts, indole-3-propionic acid was dose-dependently able to improve cardiac contractility from +26.8 ± 11.6% (p < 0.05) at 1 μM up to +93.6 ± 14.4% (p < 0.001) at 100 μM. Our mechanistic studies on indole-3-propionic acids suggest potential involvement of fatty acid oxidation in HL-1 cardiomyocytes.

Conclusion: Our data indicate a direct impact of microbial metabolites on cardiac physiology. Gut-derived metabolite indole-3-propionic acid was identified as mitochondrial modulator in cardiomyocytes and altered cardiac function in an ex vivo mouse model.
Comparative Metagenomics Reveals Microbial Signatures of Sugarcane Phyllosphere in Organic Management
Authors: Khoiri Ahmad Nuruddin , Cheevadhanarak Supapon , Jirakkakul Jiraporn , Dulsawat Sudarat , Prommeenate Peerada , Tachaleat Anuwat , Kusonmano Kanthida , Wattanachaisaereekul Songsak , Sutheeworapong Sawannee
Published: March 2021

Converting conventional farms to organic systems to improve ecosystem health is an emerging trend in recent decades, yet little is explored to what extent and how this process drives the taxonomic diversity and functional capacity of above-ground microbes. This study was, therefore, conducted to investigate the effects of agricultural management, i.e., organic, transition, and conventional, on the structure and function of sugarcane phyllosphere microbial community using the shotgun metagenomics approach. Comparative metagenome analysis exhibited that farming practices strongly influenced taxonomic and functional diversities, as well as co-occurrence interactions of phyllosphere microbes. A complex microbial network with the highest connectivity was observed in organic farming, indicating strong resilient capabilities of its microbial community to cope with the dynamic environmental stressors. Organic farming also harbored genus Streptomyces as the potential keystone species and plant growth-promoting bacteria as microbial signatures, including Mesorhizobium loti, Bradyrhizobium sp. SG09, Lactobacillus plantarum, and Bacillus cellulosilyticus. Interestingly, numerous toxic compound-degrading species were specifically enriched in transition farming, which might suggest their essential roles in the transformation of conventional to organic farming. Moreover, conventional practice diminished the abundance of genes related to cell motility and energy metabolism of phyllosphere microbes, which could negatively contribute to lower microbial diversity in this habitat. Altogether, our results demonstrated the response of sugarcane-associated phyllosphere microbiota to specific agricultural managements that played vital roles in sustainable sugarcane production.
An Integrative Approach for the Characterization of Plant-Pathogenic Streptomyces spp. Strains Based on Metabolomic, Bioactivity, and Phylogenetic Analysis
Authors: Croce Valentina , López-Radcenco Andrés , Lapaz María Inés , Pianzzola María Julia , Moyna Guillermo , Siri María Inés
Published: March 2021

Actinomycetes are generally recognized as a diverse group of gram-positive, mycelium-forming, soil bacteria that play an important role in mineralization processes and plant health, being Streptomyces the most well-known genus from this group. Although plant pathogenicity is a rare attribute in this genus, some species have significant impact worldwide due to their ability to cause important crop diseases such as potato common scab (CS). In this work, an integrative approach was applied to investigate the pathogenic potential of Streptomyces spp. isolates obtained from a local collection of actinomycetes isolated from potato fields. Secretion of phytotoxic compounds was verified in most pathogenic strains from our collection (27 out of 29), and we followed metabolomic analysis to investigate those phytotoxins. We first evaluated the production of the known phytotoxins thaxtomin A (TXT) and desmethylmensacarcin (DMSN) in phytotoxic Streptomyces spp. by HPLC analysis, resulting in 17 TXT and 6 DMSN producers. In addition, NMR-based metabolomic models were able to classify strains according to their phytotoxicity, and metabolomic data was also used to infer chemotaxonomy within pathogenic species. A correlation between phylogeny and the production of distinct phytotoxins was found, supporting the idea that there are “species specific” metabolites produced by this genus. The recently discovered polyketide DMSN was associated unequivocally with S. niveiscabiei strains and was not produced by other species in the growth conditions employed. Two S. niveiscabiei and two S. puniciscabiei phytotoxic strains that did not produce TXT nor DMSN suggest the production of other kind of metabolites involved in phytotoxicity, and allowed the prioritization of these strains for further chemical studies. Indeed, we found two S. niveiscabiei strains whose supernatants were not phytotoxic in the radish assay, suggesting other pathogenic mechanisms involved. We believe our work will be useful to help understand relations between metabolites and phylogenetic clades within actinomycetes.
Dual-Viral Transduction Utilizing Highly Efficient Retrograde Lentivirus Improves Labeling of Long Propriospinal Neurons
Authors: Brown Brandon L. , Zalla Rachel M. , Shepard Courtney T. , Howard Russell M. , Kopechek Jonathan A. , Magnuson David S. K. , Whittemore Scott R.
Published: March 2021

The nervous system coordinates pathways and circuits to process sensory information and govern motor behaviors. Mapping these pathways is important to further understand the connectivity throughout the nervous system and is vital for developing treatments for neuronal diseases and disorders. We targeted long ascending propriospinal neurons (LAPNs) in the rat spinal cord utilizing Fluoro-Ruby (FR) [10kD rhodamine dextran amine (RDA)], and two dual-viral systems. Dual-viral tracing utilizing a retrograde adeno-associated virus (retroAAV), which confers robust labeling in the brain, resulted in a small number of LAPNs being labeled, but dual-viral tracing using a highly efficient retrograde (HiRet) lentivirus provided robust labeling similar to FR. Additionally, dual-viral tracing with HiRet lentivirus and tracing with FR may preferentially label different subpopulations of LAPNs. These data demonstrate that dual-viral tracing in the spinal cord employing a HiRet lentivirus provides robust and specific labeling of LAPNs and emphasizes the need to empirically optimize viral systems to target specific neuronal population(s).
Subcellular Dissection of a Simple Neural Circuit: Functional Domains of the Mauthner-Cell During Habituation
Authors: Bátora Dániel , Zsigmond Áron , Lőrincz István Z. , Szegvári Gábor , Varga Máté , Málnási-Csizmadia András
Published: March 2021

Sensorimotor integration is a pivotal feature of the nervous system for ensuring a coordinated motor response to external stimuli. In essence, such neural circuits can optimize behavioral performance based on the saliency of environmental cues. In zebrafish, habituation of the acoustic startle response (ASR) is a simple behavior integrated into the startle command neurons, called the Mauthner cells. Whereas the essential neuronal components that regulate the startle response have been identified, the principles of how this regulation is integrated at the subcellular regions of the Mauthner cell, which in turn modulate the performance of the behavior, is still not well understood. Here, we reveal mechanistically distinct dynamics of excitatory inputs converging onto the lateral dendrite (LD) and axon initial segment (AIS) of the Mauthner cell byin vivoimaging glutamate release using iGluSnFR, an ultrafast glutamate sensing fluorescent reporter. We find that modulation of glutamate release is dependent on NMDA receptor activity exclusively at the AIS, which is responsible for setting the sensitivity of the startle reflex and inducing a depression of synaptic activity during habituation. In contrast, glutamate-release at the LD is not regulated by NMDA receptors and serves as a baseline component of Mauthner cell activation. Finally, usingin vivocalcium imaging at the feed-forward interneuron population component of the startle circuit, we reveal that these cells indeed play pivotal roles in both setting the startle threshold and habituation by modulating the AIS of the Mauthner cell. These results indicate that a command neuron may have several functionally distinct regions to regulate complex aspects of behavior.
Can Machines Find the Bilingual Advantage? Machine Learning Algorithms Find No Evidence to Differentiate Between Lifelong Bilingual and Monolingual Cognitive Profiles
Authors: Jones Samuel Kyle , Davies-Thompson Jodie , Tree Jeremy
Published: March 2021

Bilingualism has been identified as a potential cognitive factor linked to delayed onset of dementia as well as boosting executive functions in healthy individuals. However, more recently, this claim has been called into question following several failed replications. It remains unclear whether these contradictory findings reflect how bilingualism is defined between studies, or methodological limitations when measuring the bilingual effect. One key issue is that despite the claims that bilingualism yields general protection to cognitive processes (i.e., the cognitive reserve hypothesis), studies reporting putative bilingual differences are often focused on domain specific experimental paradigms. This study chose a broader approach, by considering the consequences of bilingualism on a wide range of cognitive functions within individuals. We utilised 19 measures of different cognitive functions commonly associated with bilingual effects, to form a “cognitive profile” for 215 non-clinical participants. We recruited Welsh speakers, who as a group of bilinguals were highly homogeneous, as means of isolating the bilingualism criterion. We sought to determine if such analyses would independently classify bilingual/monolingual participant groups based on emergent patterns driven by collected cognitive profiles, such that population differences would emerge. Multiple predictive models were trained to independently recognise the cognitive profiles of bilinguals, older adults (60-90 years of age) and higher education attainment. Despite managing to successfully classify cognitive profiles based on age and education, the model failed to differentiate between bilingual and monolingual cognitive ability at a rate greater than that of chance. Repeated modelling using alternative definitions of bilingualism, and just the older adults, yielded similar results. In all cases then, using our “bottom–up” analytical approach, there was no evidence that bilingualism as a variable indicated differential cognitive performance – as a consequence, we conclude that bilinguals are not cognitively different from their monolingual counterparts, even in older demographics. We suggest that studies that have reported a bilingual advantage (typically recruiting immigrant populations) could well have confounded other key variables that may be driving reported advantages. We recommend that future research refine the machine learning methods used in this study to further investigate the complex relationship between bilingualism and cognition.
Brain Entropy During Aging Through a Free Energy Principle Approach
Authors: Cieri Filippo , Zhuang Xiaowei , Caldwell Jessica Z. K. , Cordes Dietmar
Published: March 2021

Neural complexity and brain entropy (BEN) have gained greater interest in recent years. The dynamics of neural signals and their relations with information processing continue to be investigated through different measures in a variety of noteworthy studies. The BEN of spontaneous neural activity decreases during states of reduced consciousness. This evidence has been showed in primary consciousness states, such as psychedelic states, under the name of “the entropic brain hypothesis.” In this manuscript we propose an extension of this hypothesis to physiological and pathological aging. We review this particular facet of the complexity of the brain, mentioning studies that have investigated BEN in primary consciousness states, and extending this view to the field of neuroaging with a focus on resting-state functional Magnetic Resonance Imaging. We first introduce historic and conceptual ideas about entropy and neural complexity, treating the mindbrain as a complex nonlinear dynamic adaptive system, in light of the free energy principle. Then, we review the studies in this field, analyzing the idea that the aim of the neurocognitive system is to maintain a dynamic state of balance between order and chaos, both in terms of dynamics of neural signals and functional connectivity. In our exploration we will review studies both on acute psychedelic states and more chronic psychotic states and traits, such as those in schizophrenia, in order to show the increase of entropy in those states. Then we extend our exploration to physiological and pathological aging, where BEN is reduced. Finally, we propose an interpretation of these results, defining a general trend of BEN in primary states and cognitive aging.
Mapping Solute Clearance From the Mouse Hippocampus Using a 3D Imaging Cryomicrotome
Authors: Naessens Daphne M. P. , Dobbe Johannes G. G. , de Vos Judith , VanBavel Ed , Bakker Erik N. T. P.
Published: March 2021

The hippocampus is susceptible to protein aggregation in neurodegenerative diseases such as Alzheimer’s disease. This protein accumulation is partially attributed to an impaired clearance; however, the removal pathways for fluids and waste products are not fully understood. The aim of this study was therefore to map the clearance pathways from the mouse brain. A mixture of two fluorescently labeled tracers with different molecular weights was infused into the hippocampus. A small subset of mice (n = 3) was sacrificed directly after an infusion period of 10 min to determine dispersion of the tracer due to the infusion, while another group was sacrificed after spreading of the tracers for an additional 80 min (n = 7). Upon sacrifice, mice were frozen and sectioned as a whole by the use of a custom-built automated imaging cryomicrotome. Detailed 3D reconstructions were created to map the tracer spreading. We observed that tracers distributed over the hippocampus and entered adjacent brain structures, such as the cortex and cerebroventricular system. An important clearance pathway was found along the ventral part of the hippocampus and its bordering interpeduncular cistern. From there, tracers left the brain via the subarachnoid spaces in the directions of both the nose and the spinal cord. Although both tracers followed the same route, the small tracer distributed further, implying a major role for diffusion in addition to convection. Taken together, these results reveal an important clearance pathway of solutes from the hippocampus.