bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Uncertainty Quantification for an Improved Decision Support Modeling Workflow: A Streamflow Reliability and Water Quality Example
Authors: Hemmings Brioch , Knowling Matthew J. , Moore Catherine R.
Published: November 2020

Effective decision making for resource management is often supported by combining predictive models with uncertainty analyses. This combination allows quantitative assessment of management strategy effectiveness and risk. Typically, history matching is undertaken to increase the reliability of model forecasts. However, the question of whether the potential benefit of history matching will be realized, or outweigh its cost, is seldom asked. History matching adds complexity to the modeling effort, as information from historical system observations must be appropriately blended with the prior characterization of the system. Consequently, the cost of history matching is often significant. When it is not implemented appropriately, history matching can corrupt model forecasts. Additionally, the available data may offer little decision-relevant information, particularly where data and forecasts are of different types, or represent very different stress regimes. In this paper, we present a decision support modeling workflow where early quantification of model uncertainty guides ongoing model design and deployment decisions. This includes providing justification for undertaking (or forgoing) history matching, so that unnecessary modeling costs can be avoided and model performance can be improved. The workflow is demonstrated using a regional-scale modeling case study in the Wairarapa Valley (New Zealand), where assessments of stream depletion and nitrate-nitrogen contamination risks are used to support water-use and land-use management decisions. The probability of management success/failure is assessed by comparing the proximity of model forecast probability distributions to ecologically motivated decision thresholds. This study highlights several important insights that can be gained by undertaking early uncertainty quantification, including: i) validation of the prior numerical characterization of the system, in terms of its consistency with historical observations; ii) validation of model design or indication of areas of model shortcomings; iii) evaluation of the relative proximity of management decision thresholds to forecast probability distributions, providing a justifiable basis for stopping modeling.
Multiparty Conversations With People With Congenital Deafblindness: Operationalization, Significance, and Requirements
Authors: Worm Mijkje , Damen Saskia , Minnaert Alexander , Janssen Marleen J.
Published: November 2020

Typically developing children are exposed to multiparty communication on a daily basis from birth. This facilitates both group belonging and observational learning. However, involvement in multiparty conversations is not self-evident for people with congenital deafblindness due to their dual sensory impairment. This study explored the added value of multiparty conversations for people with congenital deafblindness by analyzing communication partners' narrations of their experiences. Three focus group sessions were conducted with professionals and relatives (n = 24) of people with congenital deafblindness. These sessions were audiotaped, transcribed, and coded using thematic analysis. Participants described the following defining characteristics of multiparty conversations in relation to congenital deafblindness: a minimum of three people involved, with at least one who has congenital deafblindness; awareness of the presence of the other communication partners; attention for the communicative setting; and the use of communication means that are familiar to all communication partners. In their experience, multiparty conversations supported social, emotional, and communication development. Furthermore, focus group participants indicated that spontaneous multiparty conversations with people with congenital deafblindness were scarce and, therefore, needed to be encouraged by communication partners. The participants considered positive beliefs, preparation of the multiparty conversation, repetitions, and a low communication speed as important partner competencies to support the involvement of individuals with congenital deafblindness in multiparty conversations. Accordingly, we recommend the development of an intervention protocol for communication partners to initiate and foster multiparty conversations with people with congenital deafblindness. Another recommendation is to test the effects of MPC on the observational learning of people with congenital deafblindness.
RETRACTED: Overexpression of microRNA-216a-3p Accelerates the Inflammatory Response in Cardiomyocytes in Type 2 Diabetes Mellitus by Targeting IFN-α2
Authors: Liu Xiaomeng , Zhang Yusong , Liang Hongwei , Xu Yanchao
Published: November 2020

Background: Type 2 diabetes mellitus (T2DM) is a chronic, hyperglycemia-associated, metabolic disorder. Heart disease is a major complication of T2DM. The present study aimed to explore the effects of miR-216a-3p on cardiomyocyte proliferation, apoptosis, and inflammation in T2DM through the Toll-like receptor (TLR) pathway involving interferon-α2 (IFN-α2) mediation.

Methods: T2DM was induced in rats by a high-fat diet, in combination with an intraperitoneal injection of low-dose streptozotocin. ELISAs were conducted to measure inflammatory-related factors in serum. Next, isolated cardiomyocytes were used in loss- and gain-of-function experiments, followed by MTT and flow cytometry assays, conducted to evaluate cell proliferation, cell cycle, and apoptosis.

Results: Our results revealed an increase in the inflammatory response in T2DM rat models, accompanied by significantly increased expression of miR-216a-3p and TLR pathway-related genes. However, a decrease in the expression of IFN-α2 was observed. Moreover, the presence of an miR-216a-3p inhibitor and si-IFN-α2 increased the expression of TLR pathway-related genes and cell apoptosis, whereas cell proliferation was significantly decreased in the cardiomyocytes.

Conclusion: We found that in T2DM, miR-216a-3p inhibited the proliferation and enhanced the apoptosis of cardiomyocytes and generated an inflammatory response through activation of the TLR pathway and targeting of IFN-α2.
Gestational Diabetes Is Uniquely Associated With Altered Early Seeding of the Infant Gut Microbiota
Authors: Soderborg Taylor K. , Carpenter Charles M. , Janssen Rachel C. , Weir Tiffany L. , Robertson Charles E. , Ir Diana , Young Bridget E. , Krebs Nancy F. , Hernandez Teri L. , Barbour Linda A. , Frank Daniel N. , Kroehl Miranda , Friedman Jacob E.
Published: November 2020

Gestational diabetes mellitus (GDM) is a worldwide public health problem affecting up to 27% of pregnancies with high predictive values for childhood obesity and inflammatory diseases. Compromised seeding of the infant gut microbiota is a risk factor for immunologic and metabolic diseases in the offspring; however, how GDM along with maternal obesity interact to alter colonization remains unknown. We hypothesized that GDM individually and in combination with maternal overweight/obesity would alter gut microbial composition, diversity, and short-chain fatty acid (SCFA) levels in neonates. We investigated 46 full-term neonates born to normal-weight or overweight/obese mothers with and without GDM, accounting for confounders including cesarean delivery, lack of breastfeeding, and exposure to antibiotics. Gut microbiota in 2-week-old neonates born to mothers with GDM exhibited differences in abundance of 26 microbial taxa; 14 of which showed persistent differential abundance after adjusting for pre-pregnancy BMI. Key pioneering gut taxa, including potentially important taxa for establishing neonatal immunity, were reduced. Lactobacillus, Flavonifractor, Erysipelotrichaceae, and unspecified families in Gammaproteobacteria were significantly reduced in neonates from mothers with GDM. GDM was associated with an increase in microbes involved in suppressing early immune cell function (Phascolarctobacterium). No differences in infant stool SCFA levels by maternal phenotype were noted; however, significant correlations were found between microbial abundances and SCFA levels in neonates. Our results suggest that GDM alone and together with maternal overweight/obesity uniquely influences seeding of specific infant microbiota in patterns that set the stage for future risk of inflammatory and metabolic disease.
Applications of Single-Cell Omics to Dissect Tumor Microenvironment
Authors: Guo Tingting , Li Weimin , Cai Xuyu
Published: November 2020

The recent technical and computational advances in single-cell sequencing technologies have significantly broaden our toolkit to study tumor microenvironment (TME) directly from human specimens. The TME is the complex and dynamic ecosystem composed of multiple cell types, including tumor cells, immune cells, stromal cells, endothelial cells, and other non-cellular components such as the extracellular matrix and secreted signaling molecules. The great success on immune checkpoint blockade therapy has highlighted the importance of TME on anti-tumor immunity and has made it a prime target for further immunotherapy strategies. Applications of single-cell transcriptomics on studying TME has yielded unprecedented resolution of the cellular and molecular complexity of the TME, accelerating our understanding of the heterogeneity, plasticity, and complex cross-interaction between different cell types within the TME. In this review, we discuss the recent advances by single-cell sequencing on understanding the diversity of TME and its functional impact on tumor progression and immunotherapy response driven by single-cell sequencing. We primarily focus on the major immune cell types infiltrated in the human TME, including T cells, dendritic cells, and macrophages. We further discuss the limitations of the existing methodologies and the prospects on future studies utilizing single-cell multi-omics technologies. Since immune cells undergo continuous activation and differentiation within the TME in response to various environmental cues, we highlight the importance of integrating multimodal datasets to enable retrospective lineage tracing and epigenetic profiling of the tumor infiltrating immune cells. These novel technologies enable better characterization of the developmental lineages and differentiation states that are critical for the understanding of the underlying mechanisms driving the functional diversity of immune cells within the TME. We envision that with the continued accumulation of single-cell omics datasets, single-cell sequencing will become an indispensable aspect of the immune-oncology experimental toolkit. It will continue to drive the scientific innovations in precision immunotherapy and will be ultimately adopted by routine clinical practice in the foreseeable future.
Feasibility of a Lifestyle Intervention Program for Prevention of Diabetes Among Women With Prior Gestational Diabetes Mellitus (LIVING Study) in South Asia: A Formative Research Study
Authors: Tewari Abha , Praveen Devarsetty , Madhira Pavitra , Josyula Lakshmi K. , Joshi Rohina , Kokku Suresh B. , Garg Vandana , Rawal Ishita , Chopra Kanika , Chakma Nantu , Ahmed Sabrina , Pathmeswaran Arunasalam , Godamunne Pavithra , Lata A. S. , Sahay Rakesh , Patel Tulsi , Gupta Yashdeep , Tandon Nikhil , Naheed Aliya , Patel Anushka , Kapoor Deksha
Published: November 2020

Aim: To refine and contextually adapt a postpartum lifestyle intervention for prevention of type 2 diabetes mellitus (T2DM) in women with prior gestational diabetes mellitus (GDM) in Bangladesh, India, and Sri Lanka.

Materials and Methods: In-depth interviews (IDIs) and focus group discussions (FGDs) were conducted with women with current diagnosis of GDM, and health care professionals involved in their management, to understand relevant local contextual factors for intervention optimization and implementation. This paper describes facilitators and barriers as well as feedback from participants on how to improve the proposed intervention. These factors were grouped and interpreted along the axes of the three main determinants of behavior–capability, opportunity, and motivation. IDIs and FGDs were digitally recorded, transcribed, and translated. Data-driven inductive thematic analysis was undertaken to identify and analyze patterns and themes.

Results: Two interrelated themes emerged from the IDIs and FGDs: (i) The lifestyle intervention was acceptable and considered to have the potential to improve the existing model of care for women with GDM; and (ii) Certain barriers such as reduced priority of self-care, and adverse societal influences postpartum need to be addressed for the improvement of GDM care. Based on the feedback, the intervention was optimized by including messages for family members in the content of the intervention, providing options for both text and voice messages as reminders, and finalizing the format of the intervention session delivery.

Conclusion: This study highlights the importance of contextual factors in influencing postpartum care and support for women diagnosed with GDM in three South Asian countries. It indicates that although provision of postpartum care is complex, a group lifestyle intervention program is highly acceptable to women with GDM, as well as to health care professionals, at urban hospitals.
Immune Checkpoint Targeted Therapy in Glioma: Status and Hopes
Authors: Qi Yangzhi , Liu Baohui , Sun Qian , Xiong Xiaoxing , Chen Qianxue
Published: November 2020

Glioma is the most malignant primary tumor of the central nervous system and is characterized by an extremely low overall survival. Recent breakthroughs in cancer therapy using immune checkpoint blockade have attracted significant attention. However, despite representing the most promising (immunotherapy) treatment for cancer, the clinical application of immune checkpoint blockade in glioma patients remains challenging due to the “cold phenotype” of glioma and multiple factors inducing resistance, both intrinsic and acquired. Therefore, comprehensive understanding of the tumor microenvironment and the unique immunological status of the brain will be critical for the application of glioma immunotherapy. More sensitive biomarkers to monitor the immune response, as well as combining multiple immunotherapy strategies, may accelerate clinical progress and enable development of effective and safe treatments for glioma patients.
Maturation of Monocyte-Derived DCs Leads to Increased Cellular Stiffness, Higher Membrane Fluidity, and Changed Lipid Composition
Authors: Lühr Jennifer J. , Alex Nils , Amon Lukas , Kräter Martin , Kubánková Markéta , Sezgin Erdinc , Lehmann Christian H. K. , Heger Lukas , Heidkamp Gordon F. , Smith Ana-Sunčana , Zaburdaev Vasily , Böckmann Rainer A. , Levental Ilya , Dustin Michael L. , Eggeling Christian , Guck Jochen , Dudziak Diana
Published: November 2020

Dendritic cells (DCs) are professional antigen-presenting cells of the immune system. Upon sensing pathogenic material in their environment, DCs start to mature, which includes cellular processes, such as antigen uptake, processing and presentation, as well as upregulation of costimulatory molecules and cytokine secretion. During maturation, DCs detach from peripheral tissues, migrate to the nearest lymph node, and find their way into the correct position in the net of the lymph node microenvironment to meet and interact with the respective T cells. We hypothesize that the maturation of DCs is well prepared and optimized leading to processes that alter various cellular characteristics from mechanics and metabolism to membrane properties. Here, we investigated the mechanical properties of monocyte-derived dendritic cells (moDCs) using real-time deformability cytometry to measure cytoskeletal changes and found that mature moDCs were stiffer compared to immature moDCs. These cellular changes likely play an important role in the processes of cell migration and T cell activation. As lipids constitute the building blocks of the plasma membrane, which, during maturation, need to adapt to the environment for migration and DC-T cell interaction, we performed an unbiased high-throughput lipidomics screening to identify the lipidome of moDCs. These analyses revealed that the overall lipid composition was significantly changed during moDC maturation, even implying an increase of storage lipids and differences of the relative abundance of membrane lipids upon maturation. Further, metadata analyses demonstrated that lipid changes were associated with the serum low-density lipoprotein (LDL) and cholesterol levels in the blood of the donors. Finally, using lipid packing imaging we found that the membrane of mature moDCs revealed a higher fluidity compared to immature moDCs. This comprehensive and quantitative characterization of maturation associated changes in moDCs sets the stage for improving their use in clinical application.
Immune Reconstitution After Gene Therapy Approaches in Patients With X-Linked Severe Combined Immunodeficiency Disease
Authors: Blanco Elena , Izotova Natalia , Booth Claire , Thrasher Adrian James
Published: November 2020

X-linked severe immunodeficiency disease (SCID-X1) is an inherited, rare, and life-threating disease. The genetic origin is a defect in the interleukin 2 receptor γ chain (IL2RG) gene and patients are classically characterized by absence of T and NK cells, as well as presence of partially-functional B cells. Without any treatment the disease is usually lethal during the first year of life. The treatment of choice for these patients is hematopoietic stem cell transplantation, with an excellent survival rate (>90%) if an HLA-matched sibling donor is available. However, when alternative donors are used, the success and survival rates are often lower. Gene therapy has been developed as an alternative treatment initially using γ-retroviral vectors to correct the defective γ chain in the absence of pre-conditioning treatment. The results were highly promising in SCID-X1 infants, showing long-term T-cell recovery and clinical benefit, although NK and B cell recovery was less robust. However, some infants developed T-cell acute lymphoblastic leukemia after the gene therapy, due to vector-mediated insertional mutagenesis. Consequently, considerable efforts have been made to develop safer vectors. The most recent clinical trials using lentiviral vectors together with a low-dose pre-conditioning regimen have demonstrated excellent sustained T cell recovery, but also B and NK cells, in both children and adults. This review provides an overview about the different gene therapy approaches used over the last 20 years to treat SCID-X1 patients, particularly focusing on lymphoid immune reconstitution, as well as the developments that have improved the process and outcomes.
Disruption of Host-Symbiont Associations for the Symbiotic Control and Management of Pentatomid Agricultural Pests—A Review
Authors: Gonella Elena , Orrù Bianca , Marasco Ramona , Daffonchio Daniele , Alma Alberto
Published: November 2020

The family Pentatomidae (Hemiptera: Heteroptera) includes several invasive stink bug species capable to attack a large number of wild and cultivated plants, causing several damages to different crops. Pentatomids rely on obligate symbiotic associations with bacteria of the family Enterobacteriaceae, mainly of the genus Pantoea. A distinctive trait of these associations is the transmission route: during oviposition, females smear egg masses with symbiont-containing secretions, which are ingested by newly hatched nymphs, allowing the symbiont to pass through their digestive tract and establish in the crypts of the posterior midgut. Preventing newborns from orally acquiring symbionts seriously affects their fitness and survival. This symbiont inheritance process can be manipulated to develop innovative pest control measures by sterilization of egg masses prior to nymph hatching. This review summarizes the recent knowledge advances concerning the gut primary symbionts of pentatomids, with a specific focus on the most troubling pest species for agriculture. Current understanding of host colonization dynamics in pentatomids is presented, as well as the phenotypic effects determined in different insect species by the alteration of vertical transmission. Details on the current knowledge on the whole bacterial communities accompanying primary symbionts are analyzed. The recent research exploiting the perturbation of symbiont acquisition by pentatomid nymphs is discussed, by considering published work on laboratory and field trials with several active substances. These translational strategies are presently regarded as promising for limiting the populations of many important pentatomid pests in a sustainable way.
Phenylacetic Acid and Methylphenyl Acetate From the Biocontrol Bacterium Bacillus mycoides BM02 Suppress Spore Germination in Fusarium oxysporum f. sp. lycopersici
Authors: Wu Je-Jia , Huang Jenn-Wen , Deng Wen-Ling
Published: November 2020

Bacillus mycoides strain BM02 originally isolated from the tomato rhizosphere was found to have beneficial functions in tomato by promoting plant growth and reducing the severity of Fusarium wilt caused by Fusarium oxysporum f. sp. lycopersici (Fol). Cytological experiments demonstrated B. mycoides BM02 reduced Fol invasion by reducing spore attachment and increasing hyphal deformation in hydroponics-grown tomato root tissues. Two volatile antifungal compounds, phenylacetic acid (PAA) and methylphenyl acetate (MPA), were identified from the culture filtrates of B. mycoides BM02 by GC-MS analysis. Chemically synthesized PAA, and to a lower extent MPA, suppressed spore germination but have no effects on the hyphal growth of Fol. Our results indicated that the biocontrol agent B. mycoides BM02 produced an array of bioactive compounds including PAA and MPA to suppress plant diseases caused by Fol and other pathogenic microorganisms.
Gut Microbiome Contributes to Liver Fibrosis Impact on T Cell Receptor Immune Repertoire
Authors: Liang Qing , Zhang Meina , Hu Yudi , Zhang Wei , Zhu Ping , Chen Yujie , Xue Pengxin , Li Qiyuan , Wang Kejia
Published: November 2020

Gut microbiota (GM) modifies the intrahepatic immune microenvironment, but the underlying mechanisms remain poorly understood. Liver fibrosis-associated imprinting is predicted to be reflected in GM. This study investigated the link between GM and the intrahepatic T cell receptor (TCR) immune repertoire (IR), and whether GM modulates the intrahepatic immune microenvironment via TCR IR during liver fibrosis. We analyzed the correlation between GM and TCR IR during liver fibrogenesis. Accordingly, 16S rRNA gene sequencing (16S-seq) and bulk immune repertoire sequencing (IR-seq) were performed to characterize GM and intrahepatic TCR IR. Fecal microbial transplant (FMT) and TCRβ knockout (TcrbKO) mouse models were employed to determine the biological link between GM and TCR IR in liver fibrosis. We found that GM and intrahepatic TCR IR are highly correlated, with both showing reduced diversity and centralized distribution during liver fibrosis. The restoration of normal intestinal microbiota may reshape intrahepatic TCR IR and delay liver fibrosis. Interestingly, TCR IR ablation abrogated the impact of GM on liver fibrogenesis. Furthermore, GM modulated hepatic stellate cell (HSC) activation via TCR IR-mediated intrahepatic immune milieu. Our study demonstrates that GM, which exhibits cross-talk with the intrahepatic TCR IR, influences the intrahepatic immune microenvironment and liver fibrosis progression.
Proteome-Wide Analysis of Lysine 2-Hydroxyisobutyrylation in the Phytopathogenic Fungus Botrytis cinerea
Authors: Xu Yang , Li Xiaoxia , Liang Wenxing , Liu Mengjie
Published: November 2020

Posttranslational modifications (PTMs) of the whole proteome have become a hot topic in the research field of epigenetics, and an increasing number of PTM types have been identified and shown to play significant roles in different cellular processes. Protein lysine 2-hydroxyisobutyrylation (Khib) is a newly detected PTM, and the 2-hydroxyisobutyrylome has been identified in several species. Botrytis cinerea is recognized as one of the most destructive pathogens due to its broad host distribution and very large economic losses; thus the many aspects of its pathogenesis have been continuously studied. However, distribution and function of Khib in this phytopathogenic fungus are not clear. In this study, a proteome-wide analysis of Khib in B. cinerea was performed, and 5,398 Khib sites on 1,181 proteins were identified. Bioinformatics analysis showed that the 2-hydroxyisobutyrylome in B. cinerea contains both conserved proteins and novel proteins when compared with Khib proteins in other species. Functional classification, functional enrichment and protein interaction network analyses showed that Khib proteins are widely distributed in cellular compartments and involved in diverse cellular processes. Significantly, 37 proteins involved in different aspects of regulating the pathogenicity of B. cinerea were detected as Khib proteins. Our results provide a comprehensive view of the 2-hydroxyisobutyrylome and lay a foundation for further studying the regulatory mechanism of Khib in both B. cinerea and other plant pathogens.
Plant Species-Dependent Increased Abundance and Diversity of IncP-1 Plasmids in the Rhizosphere: New Insights Into Their Role and Ecology
Authors: Shintani Masaki , Nour Eman , Elsayed Tarek , Blau Khald , Wall Inessa , Jechalke Sven , Spröer Cathrin , Bunk Boyke , Overmann Jörg , Smalla Kornelia
Published: November 2020

IncP-1 plasmids, first isolated from clinical specimens (R751, RP4), are recognized as important vectors spreading antibiotic resistance genes. The abundance of IncP-1 plasmids in the environment, previously reported, suggested a correlation with anthropogenic pollution. Unexpectedly, qPCR-based detection of IncP-1 plasmids revealed also an increased relative abundance of IncP-1 plasmids in total community DNA from the rhizosphere of lettuce and tomato plants grown in non-polluted soil along with plant age. Here we report the successful isolation of IncP-1 plasmids by exploiting their ability to mobilize plasmid pSM1890. IncP-1 plasmids were captured from the rhizosphere but not from bulk soil, and a high diversity was revealed by sequencing 14 different plasmids that were assigned to IncP-1β, δ, and ε subgroups. Although backbone genes were highly conserved and mobile elements or remnants as Tn501, IS1071, Tn402, or class 1 integron were carried by 13 of the sequenced IncP-1 plasmids, no antibiotic resistance genes were found. Instead, seven plasmids had a mer operon with Tn501-like transposon and five plasmids contained putative metabolic gene clusters linked to these mobile elements. In-depth sequence comparisons with previously known plasmids indicate that the IncP-1 plasmids captured from the rhizosphere are archetypes of those found in clinical isolates. Our findings that IncP-1 plasmids do not always carry accessory genes in unpolluted rhizospheres are important to understand the ecology and role of the IncP-1 plasmids in the natural environment.
Application of Wickerhamomyces anomalus in Simulated Solid-State Fermentation for Baijiu Production: Changes of Microbial Community Structure and Flavor Metabolism
Authors: Wang Wenhua , Fan Guangsen , Li Xiuting , Fu Zhilei , Liang Xin , Sun Baoguo
Published: November 2020

Wickerhamomyces anomalus is conducive to the synthesis of ester compounds in brewing the Chinese liquor Baijiu; esters are crucial for the quality of Baijiu. In this study, simulated solid-state fermentation for Baijiu production was used to explore whether artificial addition of W. anomalus could improve the flavor substance in Baijiu, and the underlying mechanisms. Two experimental groups were studied, in which W. anomalus Y3604 (Group A) and YF1503 (Group B) were added, respectively; in the control group (Group C), no W. anomalus was added. Adding strain Y3604 increased the content of esters in fermentation samples, especially ethyl acetate and ethyl caproate, and reduced the content of higher alcohols. Adding strain YF1503 had little effect on the ester content but decreased the content of higher alcohols. The diversity and abundance of prokaryotic genera in Group A and B samples were similar, but there were some differences compared with Group C. The correlations of genera in Group A or B samples were simple compared with group C. Although the predominant eukaryotic genera in the three groups were consistent, the abundance of each gene varied among groups. Based on our findings, bioaugmentation of Baijiu fermentation with W. anomalus will change the ethyl acetate content and cause changes in the levels of other flavor substances. We suggest that the changes in flavor substances caused by the addition of W. anomalus are mainly due to changes in the microbial community structure that result from the addition of W. anomalus.
Chemotropism Assays for Plant Symbiosis and Mycoparasitism Related Compound Screening in Trichoderma atroviride
Authors: Moreno-Ruiz Dubraska , Lichius Alexander , Turrà David , Di Pietro Antonio , Zeilinger Susanne
Published: November 2020

Trichoderma atroviride is a mycoparasitic fungus used as biological control agent to protect plants against fungal pathogens. Successful biocontrol is based on the perception of signals derived from both the plant symbiont and the fungal prey. Here, we applied three different chemotropic assays to study the chemosensing capacity of T. atroviride toward compounds known or suspected to play a role in the mycoparasite/plant or host/prey fungal interactions and to cover the complete spectrum of T. atroviride developmental stages. Purified compounds, including nutrients, the fungal secondary metabolite 6-amyl-α-pyrone (6-pentyl-α-pyrone, 6-PP) and the plant oxylipin 13-(s)-HODE, as well as culture supernatants derived from fungal preys, including Rhizoctonia solani, Botrytis cinerea and Fusarium oxysporum, were used to evaluate chemotropic responses of conidial germlings, microcolonies and fully differentiated mycelia. Our results show that germlings respond preferentially to compounds secreted by plant roots and T. atroviride itself than to compounds secreted by prey fungi. With the progression of colony development, host plant cues and self-generated signaling compounds remained the strongest chemoattractants. Nevertheless, mature hyphae responded differentially to certain prey-derived signals. Depending on the fungal prey species, chemotropic responses resulted in either increased or decreased directional colony extension and hyphal density at the colony periphery closest to the test compound source. Together these findings suggest that chemotropic sensing during germling development is focused on plant association and colony network formation, while fungal prey recognition develops later in mature hyphae of fully differentiated mycelium. Furthermore, the morphological alterations of T. atroviride in response to plant host and fungal prey compounds suggest the presence of both positive and negative chemotropism. The presented assays will be useful for screening of candidate compounds, and for evaluating their impact on the developmental spectrum of T. atroviride and other related species alike. Conidial germlings proved particularly useful for simple and rapid compound screening, whereas more elaborate microscopic analysis of microcolonies and fully differentiated mycelia was essential to understand process-specific responses, such as plant symbiosis and biocontrol.
The Puzzle of Metabolite Exchange and Identification of Putative Octotrico Peptide Repeat Expression Regulators in the Nascent Photosynthetic Organelles of Paulinella chromatophora
Authors: Oberleitner Linda , Poschmann Gereon , Macorano Luis , Schott-Verdugo Stephan , Gohlke Holger , Stühler Kai , Nowack Eva C. M.
Published: November 2020

The endosymbiotic acquisition of mitochondria and plastids more than one billion years ago was central for the evolution of eukaryotic life. However, owing to their ancient origin, these organelles provide only limited insights into the initial stages of organellogenesis. The cercozoan amoeba Paulinella chromatophora contains photosynthetic organelles—termed chromatophores—that evolved from a cyanobacterium ∼100 million years ago, independently from plastids in plants and algae. Despite the more recent origin of the chromatophore, it shows tight integration into the host cell. It imports hundreds of nucleus-encoded proteins, and diverse metabolites are continuously exchanged across the two chromatophore envelope membranes. However, the limited set of chromatophore-encoded solute transporters appears insufficient for supporting metabolic connectivity or protein import. Furthermore, chromatophore-localized biosynthetic pathways as well as multiprotein complexes include proteins of dual genetic origin, suggesting that mechanisms evolved that coordinate gene expression levels between chromatophore and nucleus. These findings imply that similar to the situation in mitochondria and plastids, also in P. chromatophora nuclear factors evolved that control metabolite exchange and gene expression in the chromatophore. Here we show by mass spectrometric analyses of enriched insoluble protein fractions that, unexpectedly, nucleus-encoded transporters are not inserted into the chromatophore inner envelope membrane. Thus, despite the apparent maintenance of its barrier function, canonical metabolite transporters are missing in this membrane. Instead we identified several expanded groups of short chromatophore-targeted orphan proteins. Members of one of these groups are characterized by a single transmembrane helix, and others contain amphipathic helices. We hypothesize that these proteins are involved in modulating membrane permeability. Thus, the mechanism generating metabolic connectivity of the chromatophore fundamentally differs from the one for mitochondria and plastids, but likely rather resembles the poorly understood mechanism in various bacterial endosymbionts in plants and insects. Furthermore, our mass spectrometric analysis revealed an expanded family of chromatophore-targeted helical repeat proteins. These proteins show similar domain architectures as known organelle-targeted expression regulators of the octotrico peptide repeat type in algae and plants. Apparently these chromatophore-targeted proteins evolved convergently to plastid-targeted expression regulators and are likely involved in gene expression control in the chromatophore.
Inactivation Efficacy of 405 nm LED Against Cronobacter sakazakii Biofilm
Authors: Huang Yixiao , Pei Quanwei , Deng Ruisha , Zheng Xiaoying , Guo Jialu , Guo Du , Yang Yanpeng , Liang Sen , Shi Chao
Published: November 2020

The objectives of this study were to evaluate the inactivation efficacy of a 405-nm light-emitting diode (LED) against Cronobacter sakazakii biofilm formed on stainless steel and to determine the sensitivity change of illuminated biofilm to food industrial disinfectants. The results showed that LED illumination significantly reduced the population of viable biofilm cells, showing reduction of 2.0 log (25°C), 2.5 log (10°C), and 2.0 log (4°C) between the non-illuminated and LED-illuminated groups at 4 h. Images of confocal laser scanning microscopy and scanning electron microscopy revealed the architectural damage to the biofilm caused by LED illumination, which involved destruction of the stereoscopic conformation of the biofilm. Moreover, the loss of biofilm components (mainly polysaccharide and protein) was revealed by attenuated total reflection Fourier-transformed infrared spectroscopy, and the downregulation of genes involved in C. sakazakii biofilm formation was confirmed by real time quantitative PCR analysis, with greatest difference observed in fliD. In addition, the sensitivity of illuminated-biofilm cells to disinfectant treatment was found to significantly increased, showing the greatest sensitivity change with 1.5 log reduction between non-LED and LED treatment biofilms in the CHX-treated group. These results indicated that 405 nm LED illumination was effective at inactivating C. sakazakii biofilm adhering to stainless steel. Therefore, the present study suggests the potential of 405 nm LED technology in controlling C. sakazakii biofilms in food processing and storage, minimizing the risk of contamination.
Propofol Requirement and EEG Alpha Band Power During General Anesthesia Provide Complementary Views on Preoperative Cognitive Decline
Authors: Touchard Cyril , Cartailler Jérôme , Levé Charlotte , Serrano José , Sabbagh David , Manquat Elsa , Joachim Jona , Mateo Joaquim , Gayat Etienne , Engemann Denis , Vallée Fabrice
Published: November 2020

Background: Although cognitive decline (CD) is associated with increased post-operative morbidity and mortality, routinely screening patients remains difficult. The main objective of this prospective study is to use the EEG response to a Propofol-based general anesthesia (GA) to reveal CD.

Methods: 42 patients with collected EEG and Propofol target concentration infusion (TCI) during GA had a preoperative cognitive assessment using MoCA. We evaluated the performance of three variables to detect CD (MoCA < 25 points): age, Propofol requirement to induce unconsciousness (TCI at SEF95: 8–13 Hz) and the frontal alpha band power (AP at SEF95: 8–13 Hz).

Results: The 17 patients (40%) with CD were significantly older (p < 0.001), had lower TCI (p < 0.001), and AP (p < 0.001). We found using logistic models that TCI and AP were the best set of variables associated with CD (AUC: 0.89) and performed better than age (p < 0.05). Propofol TCI had a greater impact on CD probability compared to AP, although both were complementary in detecting CD.

Conclusion: TCI and AP contribute additively to reveal patient with preoperative cognitive decline. Further research on post-operative cognitive trajectory are necessary to confirm the interest of intra operative variables in addition or as a substitute to cognitive evaluation.
HPG-Dependent Peri-Pubertal Regulation of Adult Neurogenesis in Mice
Authors: Trova Sara , Bovetti Serena , Pellegrino Giuliana , Bonzano Sara , Giacobini Paolo , Peretto Paolo
Published: November 2020

Adult neurogenesis, a striking form of neural plasticity, is involved in the modulation of social stimuli driving reproduction. Previous studies on adult neurogenesis have shown that this process is significantly modulated around puberty in female mice. Puberty is a critical developmental period triggered by increased secretion of the gonadotropin releasing hormone (GnRH), which controls the activity of the hypothalamic-pituitary-gonadal axis (HPG). Secretion of HPG-axis factors at puberty participates to the refinement of neural circuits that govern reproduction. Here, by exploiting a transgenic GnRH deficient mouse model, that progressively loses GnRH expression during postnatal development (GnRH::Cre;DicerloxP/loxPmice), we found that a postnatally-acquired dysfunction in the GnRH system affects adult neurogenesis selectively in the subventricular-zone neurogenic niche in a sexually dimorphic way. Moreover, by examining adult females ovariectomized before the onset of puberty, we provide important evidence that, among the HPG-axis secreting factors, the circulating levels of gonadal hormones during pre-/peri-pubertal life contribute to set-up the proper adult subventricular zone-olfactory bulb neurogenic system.
Endogenous Stimuli-Responsive DNA Nanostructures Toward Cancer Theranostics
Authors: Hu Xiaoxue , Xu Ziqi , Min Qianhao , Teng Chao , Tian Ye
Published: November 2020

Nanostructures specifically responsive to endogenous biomolecules hold great potential in accurate diagnosis and precision therapy of cancers. In the pool of nanostructures with responsiveness to unique triggers, nanomaterials derived from DNA self-assembly have drawn particular attention due to their intrinsic biocompatibility and structural programmability, enabling the selective bioimaging, and site-specific drug delivery in cancer cells and tumor tissues. In this mini review, we summarize the most recent advances in the development of endogenous stimuli-responsive DNA nanostructures featured with precise self-assembly, targeted delivery, and controlled drug release for cancer theranostics. This mini review briefly discusses the diverse dynamic DNA nanostructures aiming at bioimaging and biomedicine, including DNA self-assembling materials, DNA origami structures, DNA hydrogels, etc. We then elaborate the working principles of DNA nanostructures activated by biomarkers (e.g., miRNA, mRNA, and proteins) in tumor cells and microenvironments of tumor tissue (e.g., pH, ATP, and redox gradient). Subsequently, applications of the endogenous stimuli-responsive DNA nanostructures in biological imaging probes for detecting cancer hallmarks as well as intelligent carriers for drug release in vivo are discussed. In the end, we highlight the current challenges of DNA nanotechnology and the further development of this promising research direction.
Analysis of Feasibility, Adherence, and Appreciation of a Newly Developed Tele-Rehabilitation Program for People With MCI and VCI
Authors: Mosca Irene Eleonora , Salvadori Emilia , Gerli Filippo , Fabbri Laura , Pancani Silvia , Lucidi Giulia , Lombardi Gemma , Bocchi Leonardo , Pazzi Stefania , Baglio Francesca , Vannetti Federica , Sorbi Sandro , Macchi Claudio
Published: November 2020

Background:Patients with Mild Cognitive Impairment (MCI) and Vascular Cognitive Impairment (VCI) are at a high risk of progressing to dementia. Recent guidelines indicate the importance of promoting multidimensional and multi-domain interventions to prevent further decline. Due to its growing effectiveness, comparable to conventional face-to-face interventions, the use of technology is gaining relevance. Tele-rehabilitation systems have the potential to engage patients in multi-dimensional activity programs and to guarantee a low-cost continuum of care through remote control. A possible limitation of such programs is represented by the lack of familiarization with technology and computers in elderly people. The purpose of this study is to describe the feasibility, adherence, and appreciation of the GOAL Tele-R system, administered by a web-application through remote control in patients with MCI/VCI.

Methods:Feasibility of the Tele-R system was evaluated by means of distribution of patients' attrition along the study phases, controlling for potential systematic bias in drop-out rates due to the technological device. Adherence was evaluated analyzing drop-out rates and indexes of carried out activities. Patients' appreciation was analyzed throughad hocsatisfaction questionnaire items.

Results:Out of 86 approached patients, 25 (29%) were not enrolled, 30 (35%) dropped-out after randomization, and 31 (36%) completed the study (standard care groupn= 12, the tele-R groupn= 19). Compared to the tele-R group, rates of drop-outs resulted significantly higher for the standard care group (34 vs. 62%, respectively,p= 0.029). Taking into account baseline characteristics, females resulted in a statistically significant higher rate of drop-outs compared to males (66 vs. 27%, respectively,p= 0.003). Overall adherence to the proposed activities was 84% (85% for cognitive module and 83% for physical activity module). Concerning satisfaction, participants provided a good mean level of appreciation (3.7 ± 0.8, range 1–5), a positive feedback for usability, and a subjective perception of cognitive, emotional, and physical benefits due to the training.

Conclusion:The GOAL Tele-R system seems a feasible technological rehabilitation program, reaching an acceptable level of adherence and appreciation in patients with an MCI/VCI condition.

Clinical Trial Registration:www.ClinicalTrials.gov, ID: NCT03383549 (registration date: 26/dec/2017).
Difficulties and Countermeasures in Hospital Emergency Management for Fast-Lane Treatment of Acute Stroke During the COVID-19 Epidemic Prevention and Control
Authors: Yang Haojun , Chen Zhuohui , Fan Yishu , Xiang Lan , Hu Xinhang , Wu Tong , Xiao Bo , Feng Li , Zhao Zhihong , Chi Yunfang , Zhang Mengqi
Published: November 2020

Background: Coronavirus disease 2019 (COVID-19) has a long incubation period and a high degree of infectivity. Patients may not show specific signs or symptoms of upper respiratory tract infection, and the age of onset is similar to that of stroke. Furthermore, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. Providing emergency treatment for acute stroke in accordance with the strict epidemic control measures is currently one of the main challenges, as acute stroke is rapid onset and a major cause of death and disability globally. We aimed to evaluate the emergency treatment system for acute stroke during the epidemic control period to provide a reference and basis for informing government and medical institutions on improving patient treatment rates during this period.

Methods: Difficulties faced in providing emergency treatment for stroke during an epidemic were investigated and combined with medical educational resources and clinical management experiences to construct an emergency treatment framework for acute stroke during the epidemic.

Findings: Currently, emergency treatment measures for acute stroke during the epidemic control period are limited because the main focus is on identifying COVID-19 comorbidities during the critical period. Establishing standards for patients in the neurological outpatient consultation rooms and emergency observation and resuscitation zones; implementing a fast-lane system for the emergency treatment of patients with acute stroke, and strengthening ward management and medicine popularization, can improve the treatment efficiency for stroke patients during the epidemic and provide a reference for peers in clinical practice.

Interpretation: Emergency treatment for acute stroke during COVID-19 epidemic control period requires a joint promotion of clinical, popularization, and teaching resources.
Egocentric Navigation Abilities Predict Episodic Memory Performance
Authors: Committeri Giorgia , Fragueiro Agustina , Campanile Maria Maddalena , Lagatta Marco , Burles Ford , Iaria Giuseppe , Sestieri Carlo , Tosoni Annalisa
Published: November 2020

The medial temporal lobe supports both navigation and declarative memory. On this basis, a theory of phylogenetic continuity has been proposed according to which episodic and semantic memories have evolved from egocentric (e.g., path integration) and allocentric (e.g., map-based) navigation in the physical world, respectively. Here, we explored the behavioral significance of this neurophysiological model by investigating the relationship between the performance of healthy individuals on a path integration and an episodic memory task. We investigated the path integration performance through a proprioceptive Triangle Completion Task and assessed episodic memory through a picture recognition task. We evaluated the specificity of the association between performance in these two tasks by including in the study design a verbal semantic memory task. We also controlled for the effect of attention and working memory and tested the robustness of the results by including alternative versions of the path integration and semantic memory tasks. We found a significant positive correlation between the performance on the path integration the episodic, but not semantic, memory tasks. This pattern of correlation was not explained by general cognitive abilities and persisted also when considering a visual path integration task and a non-verbal semantic memory task. Importantly, a cross-validation analysis showed that participants' egocentric navigation abilities reliably predicted episodic memory performance. Altogether, our findings support the hypothesis of a phylogenetic continuity between egocentric navigation and episodic memory and pave the way for future research on the potential causal role of egocentric navigation on multiple forms of episodic memory.