bluuebunny/crossref_metadata_2025 huggingface dataset:
Wolf Responses to Experimental Human Approaches Using High-Resolution Positioning Data
Authors: Versluijs Erik , Eriksen Ane , Fuchs Boris , Wikenros Camilla , Sand Håkan , Wabakken Petter , Zimmermann Barbara
Published: April 2022

Humans pose a major mortality risk to wolves. Hence, similar to how prey respond to predators, wolves can be expected to show anti-predator responses to humans. When exposed to a threat, animals may show a fight, flight, freeze or hide response. The type of response and the circumstances (e.g., distance and speed) at which the animal flees are useful parameters to describe the responses of wild animals to approaching humans. Increasing knowledge about behavioral responses of wolves toward humans might improve appropriate management and decrease conflicts related to fear of wolves. We did a pilot study by conducting 21 approach trials on seven GPS-collared wolves in four territories to investigate their responses to experimental human approaches. We found that wolves predominantly showed a flight response (N= 18), in a few cases the wolf did not flee (N= 3), but no wolves were seen or heard during trials. When wolves were downwind of the observer the flight initiation distance was significantly larger than when upwind, consistent with the hypothesis that conditions facilitating early detection would result in an earlier flight. Our hypothesis that early detection would result in less intense flights was not supported, as we found no correlation between flight initiation distances and speed, distance or straightness of the flight. Wolves in more concealed habitat had a shorter flight initiation distance or did not flee at all, suggesting that perceived risk might have been affected by horizontal visibility. Contrary to our expectation, resettling positions were less concealed (larger horizontal visibility) than the wolves’ initial site. Although our small number of study animals and trials does not allow for generalizations, this pilot study illustrates how standardized human approach trials with high-resolution GPS-data can be used to describe wolf responses at a local scale. In continuation, this method can be applied at larger spatial scales to compare wolf flight responses within and between populations and across anthropogenic gradients, thus increasing the knowledge of wolf behavior toward humans, and potentially improving coexistence with wolves across their range.
Aboveground Biomass Along an Elevation Gradient in an Evergreen Andean–Amazonian Forest in Ecuador
Authors: Maza Byron , Rodes-Blanco Marina , Rojas Edison
Published: April 2022

The aim of this research was to assess how aboveground biomass (AGB) changes along an altitudinal gradient in evergreen Andean–Amazonian forests [Evergreen Lower Montane Forest, northeastern Cordillera of the Andes; Evergreen Piedmont Forest (EPF), northeastern Cordillera of the Andes; and Evergreen Lowland Forest (ELF), Napo–Curaray] from 373 to 1,826 m above sea level (m.a.s.l.). All trees measured in nine permanent 0.36-ha plots (60 × 60 m) were ≥ 10-cm (diameter at breast height) in the aforementioned ecosystems. We assessed tree density, basal area, species richness, and AGB. In the tree inventory, we measured 2,132 trees (Lower Montane Forest 687, Piedmont Forest 773, and Lowland Forest 672). AGB (Mg ha–1) increases with decreasing elevations: 310.26 ± 81.59 (SD) for the Evergreen Lower Montane Forest, 347.73 ± 90.38 (SD) for the EPF, and 377.39 ± 42.73 (SD) for the ELF.Otoba glycycarpaandAlchornea latifoliawere the species with the highest biomass importance value (BIV) in the Evergreen Lower Montane Forest (1,421–1,826 m.a.s.l.),Spirotheca roseaandPouteria glomeratain the EPF (892–1,195 m.a.s.l.), andOtoba glycycarpaandIriartea deltoideain ELF (373–394 m.a.s.l.). Biomass contribution along the altitudinal gradient in the evergreen Andean–Amazonian forests is concentrated in few species. This has implications in forest management and reforestation programs where the main focus is on carbon sequestration.
GPCR19 Regulates P2X7R-Mediated NLRP3 Inflammasomal Activation of Microglia by Amyloid β in a Mouse Model of Alzheimer’s Disease
Authors: Islam Jahirul , Cho Jung-Ah , Kim Ju-yong , Park Kyung-Sun , Koh Young-Jae , Chung Chu Young , Lee Eun-Jae , Nam Soo Jeong , Lee Kyoungyul , Kim Seoung-Heon , Park Sung-Hye , Lee Dong Young , Kim Byeong C. , Lee Kyung-Hwa , Seong Seung-Yong
Published: April 2022

Amyloid β (Aβ) and/or ATP activate the NLRP3 inflammasome (N3I) via P2X7R in microglia, which is crucial in neuroinflammation in Alzheimer’s disease (AD). Due to polymorphisms, subtypes, and ubiquitous expression of P2X7R, inhibition of P2X7R has not been effective for AD. We first report that taurodeoxycholate (TDCA), a GPCR19 ligand, inhibited the priming phase of N3I activation, suppressed P2X7R expression and P2X7R-mediated Ca++ mobilization and N3I oligomerization, which is essential for production of IL-1β/IL-18 by microglia. Furthermore, TDCA enhanced phagocytosis of Aβ and decreased the number of Aβ plaques in the brains of 5x Familial Alzheimer’s disease (5xFAD) mice. TDCA also reduced microgliosis, prevented neuronal loss, and improved memory function in 5xFAD mice. The pleiotropic roles of GPCR19 in P2X7R-mediated N3I activation suggest that targeting GPCR19 might resolve neuroinflammation in AD patients.
A Genome-Wide Association Study for Tolerance to Paratuberculosis Identifies Candidate Genes Involved in DNA Packaging, DNA Damage Repair, Innate Immunity, and Pathogen Persistence
Authors: Canive María , Badia-Bringué Gerard , Vázquez Patricia , Garrido Joseba M. , Juste Ramón A. , Fernandez Almudena , González-Recio Oscar , Alonso-Hearn Marta
Published: April 2022

Although the genetic susceptibility to diseases has been extensively studied, the genetic loci and the primary molecular and cellular mechanisms that control disease tolerance are still largely unknown. Bovine paratuberculosis (PTB) is an enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP). PTB affects cattle worldwide and represents a major issue on animal health. In this study, the associations between host genetic and PTB tolerance were investigated using the genotypes from 277 Spanish Holstein cows with two distinct phenotypes: cases) infected animals with positive PCR and bacteriological culture results but without lesions in gut tissues (N= 24), and controls) animals with negative PCR and culture results but with PTB-associated lesions (N= 253). DNA from peripheral blood of the study population was genotyped with the Bovine EuroG MD Bead Chip, and the corresponding genotypes were imputed to whole-genome sequencing (WGS) data. A genome-wide association study was performed using the WGS data and the defined phenotypes in a case-control approach. A total of 142 single nucleotide polymorphisms (SNPs) were associated (false discovery rate ≤ 0.05, P values between 1.5 × 10-7 and 5.7 × 10-7) with tolerance (heritability= 0.55). The 40 SNPs with P-values < 5 × 10-7 defined 9 QTLs and 98 candidate genes located on BTA4, BTA9, BTA16, BTA25, and BTA26. Some of the QTLs identified in this study overlap with QTLs previously associated with PTB, bovine tuberculosis, mastitis, somatic cell score, bovine diarrhea virus persistent infection, tick resistance, and length of productive life. Two candidate genes with important roles in DNA damage response (ERCC4 and RMI2) were identified on BTA25. Functional analysis using the 98 candidate genes revealed a significant enrichment of the DNA packaging process (TNP2/PRMI1/PRM2/PRM3). In addition, the TNF-signaling (bta04668; TRAF5/CREB5/CASP7/CHUK) and the toxoplasmosis (bta05145; TGFβ2/CHUK/CIITA/SOCS1) pathways were significantly enriched. Interestingly, the nuclear Factor NF-κβ Inhibitor Kinase Alpha (CHUK), a key molecule in the regulation of the NF-κB pathway, was enriched in both pathways. Taken together, our results define a distinct immunogenetic profile in the PTB-tolerant animals designed to control bacterial growth, modulate inflammation, limit tissue damage and increase repair, thus reducing the severity of the disease.
GluR3B Antibody Was a Biomarker for Drug-Resistant Epilepsy in Patients With Focal to Bilateral Tonic-Clonic Seizures
Authors: Lai Qingwei , Li Qingyun , Li Xinyu , Wang Heng , Zhang Wei , Song Xiaotao , Hu Peng , Yao Ruiqin , Fan Hongbin , Xu Xingshun
Published: April 2022

Considering the role of GluR3B antibody-mediated excitotoxicity in the progression of epilepsy, the purpose of this study was to evaluate the clinical significance of GluR3B antibody level as a novel biomarker for the prognosis of unknown etiology drug-resistant epilepsy (DRE) in patients with focal to bilateral tonic-clonic seizures. The study included 193 patients with focal to bilateral tonic-clonic seizures in the modeling cohort. Serum and CSF samples from patients were collected, and GluR3B antibody levels were detected by an ELISA kit. Serum and CSF GluR3B antibody levels in patients with DRE were significantly increased compared with those in patients with drug-responsive epilepsy. Univariate logistic regression analysis underlined that patients with high GluR3B antibody levels had a significantly increased risk of developing DRE. A logistic regression model demonstrated that increased GluR3B antibody levels were an independent factor in predicting DRE. External verification showed that the model constructed for the prediction of DRE had good adaptability. Finally, decision curve analysis highlighted the superior clinical net benefit in DRE prognosis by GluR3B antibody level. In summary, elevated levels of GluR3B antibody are an early biomarker to predict the prognosis of DRE; in addition, targeting GluR3B antibody may be a promising treatment strategy for patients with DRE.
Design and Evaluation of TIM-3-CD28 Checkpoint Fusion Proteins to Improve Anti-CD19 CAR T-Cell Function
Authors: Blaeschke Franziska , Ortner Eva , Stenger Dana , Mahdawi Jasmin , Apfelbeck Antonia , Habjan Nicola , Weißer Tanja , Kaeuferle Theresa , Willier Semjon , Kobold Sebastian , Feuchtinger Tobias
Published: April 2022

Therapeutic targeting of inhibitory checkpoint molecules in combination with chimeric antigen receptor (CAR) T cells is currently investigated in a variety of clinical studies for treatment of hematologic and solid malignancies. However, the impact of co-inhibitory axes and their therapeutic implication remains understudied for the majority of acute leukemias due to their low immunogenicity/mutational load. The inhibitory exhaustion molecule TIM-3 is an important marker for the interaction of T cells with leukemic cells. Moreover, inhibitory signals from malignant cells could be transformed into stimulatory signals by synthetic fusion molecules with extracellular inhibitory receptors fused to an intracellular stimulatory domain. Here, we designed a variety of different TIM-3-CD28 fusion proteins to turn inhibitory signals derived by TIM-3 engagement into T-cell activation through CD28. In the absence of anti-CD19 CAR, two TIM-3-CD28 fusion receptors with large parts of CD28 showed strongest responses in terms of cytokine secretion and proliferation upon stimulation with anti-CD3 antibodies compared to controls. We then combined these two novel TIM-3-CD28 fusion proteins with first- and second-generation anti-CD19 CAR T cells and found that the fusion receptor can increase proliferation, activation, and cytotoxic capacity of conventional anti-CD19 CAR T cells. These additionally armed CAR T cells showed excellent effector function. In terms of safety considerations, the fusion receptors showed exclusively increased cytokine release, when the CAR target CD19 was present. We conclude that combining checkpoint fusion proteins with anti-CD19 CARs has the potential to increase T-cell proliferation capacity with the intention to overcome inhibitory signals during the response against malignant cells.
Characteristics and Outcomes of Paroxysmal Sympathetic Hyperactivity in Anti-NMDAR Encephalitis
Authors: Chen Zhongyun , Zhang Yan , Wu Xiaowen , Huang Huijin , Chen Weibi , Su Yingying
Published: April 2022

Background

To explore the clinical characteristics and prognosis of autonomic dysfunction and paroxysmal sympathetic hyperactivity (PSH), and evaluate the efficacy of drugs used to suppress PSH episode in anti-NMDAR encephalitis patients.

Methods

Patients who met the diagnostic criteria of anti-NMDAR encephalitis were enrolled from January 2012 to August 2018 and followed up for 2 years. PSH was diagnosed according to the PSH-Assessment Measure. The demographics data, clinical features, auxiliary tests results, treatments, and outcomes were prospective collected and analyzed.

Results

A total of 132 anti-NMDAR encephalitis patients were enrolled, of which 27.3% and 9.1% experienced autonomic dysfunction and probable PSH respectively. Cardiac autonomic dysfunction was the most common subtype (77.8%). Patients with a higher incidence of ovarian teratoma, mechanical ventilation, neurological intensive care unit admission, and elevated glucose and NMDAR antibody titer in the CSF were more likely to exhibit autonomic dysfunction or PSH. Episodes of PSH can be suppressed by monotherapy in patients without prior sedative drug use with an efficacy of 90%. No significant difference was observed between the prognosis of patients with or without autonomic dysfunction, or between the PSH versus non-PSH groups after 6 months and even during long-term follow-up. However, patients with cardiac autonomic dysfunction had poor prognosis at 6 months.

Conclusion

PSH is a common clinical condition in patients with anti-NMDAR encephalitis, especially in severe cases, and can be effectively managed by several drug monotherapies. Despite necessitating longer hospital stay, autonomic dysfunction or PSH do not seem to compromise the neurological recovery of patients.
Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response
Authors: An Li-Li , Zhao Xiang , Gong Xiu-Ying , Li Yi-Lin , Qu Zi-Ling , Sun Hao-Yu , Guo Wen-Hao , Dan Cheng , Gui Jian-Fang , Zhang Yi-Bing
Published: April 2022

Interferon regulatory factors (IRFs) constitute a family of transcription factors that synchronize interferon (IFN) antiviral response through translocating to nucleus and binding to the promoters of IFN and IFN-stimulated genes (ISGs). Fish contain 11 IRF members; however, whether or how fish IRF family genes function in IFN response remains limited. Herein, we determine the regulatory roles of 11 zebrafish IRF family members in IFN response relevant to their subcellular localization and promoter binding. Zebrafish IRF family members display three patterns of constitutive localization, only in nucleus (IRF1/2/9/11), only in cytoplasm (IRF3/5/7), and largely in nucleus with small amounts in cytoplasm (IRF4b/6/8/10). DNA pull-down assays confirm that all zebrafish IRF proteins are capable to bind fish IFN promoters, albeit to various degrees, thus regulating IFN gene transcription as activators (IRF1/3/5/6/7/8/9/11) or repressors (IRF2/4b/10). Further characterization of distinct IFN gene activation reveals that IRF1/3/5/6/7/8/9/11 efficiently stimulate zebrafish IFNφ1 expression, and IRF1/7/11 are responsible for zebrafish IFNφ3 expression. Two conserved basic residues within the helix α3 of DNA binding domains (DBDs) contribute to constitutive or inducible nuclear import for all zebrafish IRF family members and DNA binding for most members, thereby enabling them to function as transcription factors. Our results reveal a conserved and general mechanism that specifies zebrafish IRF family proteins to nuclear import and DNA binding, thereby regulating fish IFN response.
What Is IL-1 for? The Functions of Interleukin-1 Across Evolution
Authors: Boraschi Diana
Published: April 2022

Interleukin-1 is a cytokine with potent inflammatory and immune-amplifying effects, mainly produced by macrophages during defensive reactions. In mammals, IL-1 is a superfamily of eleven structurally similar proteins, all involved in inflammation or its control, which mainly act through binding to specific receptors on the plasma membrane of target cells. IL-1 receptors are also a family of ten structurally similar transmembrane proteins that assemble in heterocomplexes. In addition to their innate immune/inflammatory effects, the physiological role of IL-1 family cytokines seems to be linked to the development of adaptive immunity in vertebrates. We will discuss why IL-1 developed in vertebrates and what is its physiological role, as a basis for understanding when and how it can be involved in the initiation and establishment of pathologies.
Identification of the Transgene Integration Site and Host Genome Changes in MRP8-Cre/ires-EGFP Transgenic Mice by Targeted Locus Amplification
Authors: Wang Guan , Zhang Cunling , Kambara Hiroto , Dambrot Cheryl , Xie Xuemei , Zhao Li , Xu Rong , Oneglia Andrea , Liu Fei , Luo Hongbo R.
Published: April 2022

The MRP8-Cre-ires/EGFP transgenic mouse (Mrp8creTg, on C57BL/6J genetic background) is popular in immunological and hematological research for specifically expressing Cre recombinase and an EGFP reporter in neutrophils. It is often crossed with other transgenic lines carrying loxP-flanked genes to achieve restricted gene knockout in neutrophils. However, due to the way in which the line was created, basic knowledge about the MRP8-Cre-ires/EGFP transgene in the host genome, such as its integration site(s) and flanking sequences, remains largely unknown, hampering robust experimental design and data interpretation. Here we used a recently developed technique, targeted locus amplification (TLA) sequencing, to fill these knowledge gaps. We found that the MRP8-Cre-ires/EGFP transgene was integrated into chromosome 5 (5qG2) of the host mouse genome. This integration led to a 44 kb deletion of the host genomic sequence, resulting in complete deletion of Serpine1 and partial deletion of Ap1s1. Having determined the flanking sequences of the transgene, we designed a new genotyping protocol that can distinguish homozygous, heterozygous, and wildtype Mrp8creTg mice. To our surprise, crossing heterozygous mice produced no homozygous Mrp8creTg mice, most likely due to prenatal lethality resulting from disrupted Ap1s1 gene expression.
Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy
Authors: Wadden Jack , Ravi Karthik , John Vishal , Babila Clarissa May , Koschmann Carl
Published: April 2022

Gliomas are tumors derived from mutations in glial brain cells. Gliomas cause significant morbidity and mortality and development of precision diagnostics and novel targeted immunotherapies are critically important. Radiographic imaging is the most common technique to diagnose and track response to treatment, but is an imperfect tool. Imaging does not provide molecular information, which is becoming critically important for identifying targeted immunotherapies and monitoring tumor evolution. Furthermore, immunotherapy induced inflammation can masquerade as tumor progression in images (pseudoprogression) and confound clinical decision making. More recently, circulating cell free tumor DNA (cf-tDNA) has been investigated as a promising biomarker for minimally invasive glioma diagnosis and disease monitoring. cf-tDNA is shed by gliomas into surrounding biofluids (e.g. cerebrospinal fluid and plasma) and, if precisely quantified, might provide a quantitative measure of tumor burden to help resolve pseudoprogression. cf-tDNA can also identify tumor genetic mutations to help guide targeted therapies. However, due to low concentrations of cf-tDNA, recovery and analysis remains challenging. Plasma cf-tDNA typically represents <1% of total cf-DNA due to the blood-brain barrier, limiting their usefulness in practice and motivating the development and use of highly sensitive and specific detection methods. This mini review summarizes the current and future trends of various approaches for cf-tDNA detection and analysis, including new methods that promise more rapid, lower-cost, and accessible diagnostics. We also review the most recent clinical case studies for longitudinal disease monitoring and highlight focus areas, such as novel accurate detection methodologies, as critical research priorities to enable translation to clinic.
The Importance of Being Presented: Target Validation by Immunopeptidomics for Epitope-Specific Immunotherapies
Authors: Becker Jonas P. , Riemer Angelika B.
Published: April 2022

Presentation of tumor-specific or tumor-associated peptides by HLA class I molecules to CD8+T cells is the foundation of epitope-centric cancer immunotherapies. While oftenin silicoHLA binding predictions orin vitroimmunogenicity assays are utilized to select candidates, mass spectrometry-based immunopeptidomics is currently the only method providing a direct proof of actual cell surface presentation. Despite much progress in the last decade, identification of such HLA-presented peptides remains challenging. Here we review typical workflows and current developments in the field of immunopeptidomics, highlight the challenges which remain to be solved and emphasize the importance of direct target validation for clinical immunotherapy development.
Mesoscale Advective and Biological Processes Alter Carbon Uptake Capacity in a Shelf Sea
Authors: Macovei Vlad A. , Callies Ulrich , Calil Paulo H. R. , Voynova Yoana G.
Published: April 2022

Marine uptake of carbon dioxide reduces the accumulation of carbon dioxide in the atmosphere. Continental shelf seas are essential for carbon uptake from the atmosphere, but are also highly variable environments, for which uncertainties of carbon budget estimates are large. Recent studies indicate that their carbon sink capacity is weakening. A way to reduce the uncertainty of carbon budgets is to increase our observational capacity, for example through FerryBox installations on Ships-of-Opportunity. Here, we compare FerryBox observations in the North Sea for the fall seasons of 2019 and 2020. We show that short-lived mesoscale events can be characterized when the sampling resolution is adequately high, and that these events cause changes in essential environmental variables on the same magnitude as seasonal cycles. Whether advective or biological in origin, these events rapidly lowered seawater pCO2 by 8–10% and influenced the carbon uptake capacity. We demonstrate the importance of resolving and integrating the variability of these smaller features in regional carbon budget assessments and advocate for the tuning of models in order to capture this small-scale variability.
Interleukin-26 Expression in Inflammatory Bowel Disease and Its Immunoregulatory Effects on Macrophages
Authors: Song Dongjuan , Lai Lijie , Lu Juntao , Tong Jinlu , Ran Zhihua
Published: April 2022

Background and Aim

Interleukin-26 (IL-26) has been implicated in several chronic inflammatory diseases. However, its role in inflammatory bowel disease (IBD) remains to be elucidated. We aimed to investigate IL-26 expression in IBD and its immunoregulatory effects on macrophages.

Methods

We assessed IL-26 expression in the intestinal mucosa and blood samples of IBD patients and healthy controls (HC). The associations between the clinical characteristics of IBD and IL-26 expression levels in serum and peripheral blood mononuclear cells (PBMCs) were investigated. In addition, the transcriptional changes in THP-1 macrophages exposed to IL-26 were determined by RNA sequencing and validated with qRT-PCR, ELISA and western blots.

Results

Compared with HC, in IBD patients, IL-26 expression levels were elevated in the inflamed intestinal mucosa, and reduced in serum and PBMCs. IL-26 mRNA levels in PBMCs, but not serum IL-26 levels, were inversely correlated with disease activity in IBD. Furthermore, IL-26 mRNA levels in PBMCs were significantly lower in patients with complicated Crohn’s disease. A total of 1,303 differentially expressed protein-coding genes were identified between untreated and IL-26-treated macrophages. The up-regulated genes showed enrichment in some inflammatory and immune-related processes and pathways. Additionally, GSEA showed that neutrophil, monocyte, and lymphocyte chemotaxis was significantly enriched in IL-26-treated macrophages. Further validation revealed that IL-26 promotes the secretion of multiple inflammatory cytokines and chemokines and upregulates the expression of adhesion molecules, MMP-8, and MMP-9 while inhibiting MMP-1 in macrophages.

Conclusion

Compared with HC, in IBD patients, IL-26 levels were elevated in the inflamed intestinal mucosa, and reduced in the peripheral blood. The transcriptional changes in macrophages exposed to IL-26 suggest that IL-26 may amplify the aberrant immune response in IBD by activating macrophages.
A Machine Learning-Based Predictive Model for Predicting Lymph Node Metastasis in Patients With Ewing’s Sarcoma
Authors: Li Wenle , Zhou Qian , Liu Wencai , Xu Chan , Tang Zhi-Ri , Dong Shengtao , Wang Haosheng , Li Wanying , Zhang Kai , Li Rong , Zhang Wenshi , Hu Zhaohui , Shibin Su , Liu Qiang , Kuang Sirui , Yin Chengliang
Published: April 2022

Objective

In order to provide reference for clinicians and bring convenience to clinical work, we seeked to develop and validate a risk prediction model for lymph node metastasis (LNM) of Ewing’s sarcoma (ES) based on machine learning (ML) algorithms.

Methods

Clinicopathological data of 923 ES patients from the Surveillance, Epidemiology, and End Results (SEER) database and 51 ES patients from multi-center external validation set were retrospectively collected. We applied ML algorithms to establish a risk prediction model. Model performance was checked using 10-fold cross-validation in the training set and receiver operating characteristic (ROC) curve analysis in external validation set. After determining the best model, a web-based calculator was made to promote the clinical application.

Results

LNM was confirmed or unable to evaluate in 13.86% (135 out of 974) ES patients. In multivariate logistic regression, race, T stage, M stage and lung metastases were independent predictors for LNM in ES. Six prediction models were established using random forest (RF), naive Bayes classifier (NBC), decision tree (DT), xgboost (XGB), gradient boosting machine (GBM), logistic regression (LR). In 10-fold cross-validation, the average area under curve (AUC) ranked from 0.705 to 0.764. In ROC curve analysis, AUC ranged from 0.612 to 0.727. The performance of the RF model ranked best. Accordingly, a web-based calculator was developed (https://share.streamlit.io/liuwencai2/es_lnm/main/es_lnm.py).

Conclusion

With the help of clinicopathological data, clinicians can better identify LNM in ES patients. Risk prediction models established in this study performed well, especially the RF model.
Adherence to European Society of Gastrointestinal Endoscopy Quality Performance Measures for Upper and Lower Gastrointestinal Endoscopy: A Nationwide Survey From the Italian Society of Digestive Endoscopy
Authors: Zagari Rocco Maurizio , Frazzoni Leonardo , Fuccio Lorenzo , Bertani Helga , Crinò Stefano Francesco , Magarotto Andrea , Dajti Elton , Tringali Andrea , Da Massa Carrara Paola , Cengia Gianpaolo , Ciliberto Enrico , Conigliaro Rita , Germanà Bastianello , Lamazza Antonietta , Pisani Antonio , Spinzi Giancarlo , Capelli Maurizio , Bazzoli Franco , Pasquale Luigi
Published: April 2022

Background

The quality of gastrointestinal (GI) endoscopy has been recently identified as a major priority being associated with many outcomes and patient's experience.

Objective

To assess adherence of endoscopists to the European Society of Gastrointestinal Endoscopy (ESGE) quality performance measures for upper and lower GI endoscopy in Italy.

Methods

All endoscopist members of the Italian Society of Digestive Endoscopy (SIED) were invited from October 2018 to December 2018 to participate to a self-administered questionnaire-based survey. The questionnaire included questions on demographics and professional characteristics, and the recent ESGE quality performance measures for upper and lower GI endoscopy.

Results

A total of 392 endoscopists participated in the study. Only a minority (18.2%) of participants recorded the duration of esophagogastroduodenoscopy (EGD) and 51% provided accurate photo documentation in the minimum standard of 90% of cases. Almost all endoscopists correctly used Prague and Los Angeles classifications (87.8% and 98.2%, respectively), as well as Seattle and Management of precancerous conditions and lesions in the stomach (MAPS) biopsy protocols (86.5% and 91.4%, respectively). However, only 52.8% of participants monitored complications after therapeutic EGD, and 40.8% recorded patients with a diagnosis of Barrett's esophagus (BE). With regard to colonoscopy, almost all endoscopists (93.9%) used the Boston Bowel Preparation Scale for measuring bowel preparation quality and reported a cecal intubation rate ≥90%. However, about a quarter (26.2%) of participants reported an adenoma detection rate of <25%, only 52.8% applied an appropriate polypectomy technique, 48% monitored complications after the procedure, and 12.4% measured patient's experience.

Conclusion

The adherence of endoscopists to ESGE performance measures for GI endoscopy is sub-optimal in Italy. There is a need to disseminate and implement performance measures and endorse educational and scientific interventions on the quality of endoscopy.
A Relevant Wound-Like in vitro Media to Study Bacterial Cooperation and Biofilm in Chronic Wounds
Authors: Pouget Cassandra , Dunyach-Remy Catherine , Bernardi Thierry , Provot Christian , Tasse Jason , Sotto Albert , Lavigne Jean-Philippe
Published: April 2022

Biofilm on the skin surface of chronic wounds is an important factor in the pathology, inhibiting wound healing. The polymicrobial nature of these infected wounds and bacterial interactions inside this pathogenic biofilm are the keys for understanding chronic infection. The aim of our work was to develop an innovative in vitro medium that closely mimics the chronic wound emphasizing the microbiological, cellular, and inflammatory environment of chronic wounds but also focusing on the pH found at the wound level. This new medium, called chronic wound medium (CWM), will thus facilitate the study of pathogenic biofilm organization. Clinical Staphylococcus aureus and Pseudomonas aeruginosa strains coisolated from diabetic foot infection were collected and cultivated in this new medium for 24 h in monoculture and coculture. Bacterial growth (growth curves), presence of small colony variant (SCV), biofilm formation (BioFilm Ring Test® assay, biofilm biomass quantification), and virulence (survival curve in a Caenorhabditis elegans model) were evaluated. After 24 h in the in vitro conditions, we observed that P. aeruginosa growth was not affected, compared with a control bacterial medium, whereas for S. aureus, the stationary phase was reduced by two logs. Interestingly, S. aureus growth increased when cocultured with P. aeruginosa in CWM. In coculture with P. aeruginosa, SCV forms of S. aureus were detected. Biofilm studies showed that bacteria, alone and in combination, formed biofilm faster (as soon as 3 h) than the bacteria exposed in a control medium (as soon as 5 h). The virulence of all strains decreased in the nematode model when cultivated in our new in vitro medium. Taken together, our data confirmed the impact of the chronic wound environment on biofilm formation and bacteria virulence. They indicated that P. aeruginosa and S. aureus cooperated in coinfected wounds. Therefore, this in vitro model provides a new tool for bacterial cooperation investigation and polymicrobial biofilm formation.
Optimization of Protoplast Preparation and Establishment of Genetic Transformation System of an Arctic-Derived Fungus Eutypella sp.
Authors: Ning Yaodong , Hu Bo , Yu Haobing , Liu Xiaoyu , Jiao Binghua , Lu Xiaoling
Published: April 2022

Arctic-derived fungus Eutypella sp. D-1 has attracted wide attention due to its huge ability to synthesize secondary metabolites. However, current studies only focus on stimulating its production of new secondary metabolites by OSMAC strategies, and the relationship between secondary metabolites and biosynthetic gene clusters (BGCs) has not been explored. In this study, the preparation and regeneration conditions of Eutypella sp. D-1 protoplasts were explored to lay a foundation for the study of genetic transformation of this fungus. Orthogonal experiment showed that the optimal preparation conditions were 0.75 M NaCl, 20 g/L of lysing enzyme, and 20 g/L of driselase, 28°C for 6 h. The maximum yield of Eutypella sp. D-1 protoplasts could reach 6.15 × 106 cells·ml−1, and the concentration of osmotic stabilizer NaCl was the most important factor for Eutypella sp. D-1 protoplasts. The results of FDA staining showed that the prepared protoplasts had good activity. Besides, the best protoplasts regeneration medium was YEPS, whose maximum regeneration rate is 36%. The mediums with nitrogen sources, such as SR and RM, also had good effects on the Eutypella sp. D-1 protoplast regeneration, indicating that nitrogen sources played an important role on the Eutypella sp. D-1 protoplast regeneration. Subsequent transformation experiments showed that hygromycin resistance genes (hrg) could be successfully transferred into the genome of Eutypella sp. D-1, indicating that the prepared protoplasts could meet the needs of subsequent gene manipulation and research. This study lays a foundation for the genetic transformation of Eutypella sp. D-1.
Deletion of the Response Regulator PhoP Accelerates the Formation of Aerial Mycelium and Spores in Actinosynnema pretiosum
Authors: Zhang Peipei , Zhang Kunyu , Liu Yayu , Fu Jiafang , Zong Gongli , Ma Xin , Cao Guangxiang
Published: April 2022

PhoPR is an important two-component signal transduction system (TCS) for microorganisms to sense and respond to phosphate limitation. Although the response regulator PhoP controls morphological development and secondary metabolism in various Streptomyces species, the function of PhoP in Actinosynnema pretiosum remains unclear. In this study, we showed that PhoP significantly represses the morphological development of the A. pretiosum X47 strain. Production of aerial mycelium and spore formation occurred much earlier in the ΔphoP strain than in X47 during growth on ISP2 medium. Transcription analysis indicated that 222 genes were differentially expressed in ∆phoP compared to strain X47. Chemotaxis genes (cheA, cheW, cheX, and cheY); flagellum biosynthesis and motility genes (flgBCDGKLN, flaD, fliD-R, motA, and swrD); and differentiation genes (whiB and ssgB) were significantly upregulated in ∆phoP. Gel-shift analysis indicated that PhoP binds to the promoters of flgB, flaD, and ssgB genes, and PHO box-like motif with the 8-bp conserved sequence GTTCACGC was identified. The transcription of phoP/phoR of X47 strain was induced at low phosphate concentration. Our results demonstrate that PhoP is a negative regulator that controls the morphological development of A. pretiosum X47 by repressing the transcription of differentiation genes.
Species Diversity, Molecular Phylogeny, and Ecological Habits of Fomitopsis (Polyporales, Basidiomycota)
Authors: Liu Shun , Song Chang-Ge , Xu Tai-Min , Ji Xing , Wu Dong-Mei , Cui Bao-Kai
Published: April 2022

Fomitopsis is a worldwide brown-rot fungal genus of Polyporales, which grows on different gymnosperm and angiosperm trees and has important ecological functions and economic values. In this study, species diversity, phylogenetic relationships, and ecological habits of Fomitopsis were investigated. A total of 195 specimens from 24 countries representing 29 species of Fomitopsis were studied. Based on the morphological characters and phylogenetic evidence of DNA sequences including the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), the small subunit of nuclear ribosomal RNA gene (nSSU), the small subunit of mitochondrial rRNA gene (mtSSU), the translation elongation factor 1-α gene (TEF), and the second subunit of RNA polymerase II (RPB2), 30 species are accepted in Fomitopsis, including four new species: F. resupinata, F. srilankensis, F. submeliae and F. yimengensis. Illustrated descriptions of the novel species and the geographical locations of the Fomitopsis species are provided.
A U-Box Type E3 Ubiquitin Ligase Prp19-Like Protein Negatively Regulates Lipid Accumulation and Cell Size in Chlamydomonas reinhardtii
Authors: Luo Qiulan , Zhu Hui , Wang Chaogang , Li Yajun , Zou Xianghui , Hu Zhangli
Published: April 2022

Microalgae lipid triacylglycerol is considered as a promising feedstock for national production of biofuels. A hotspot issue in the biodiesel study is to increase TAG content and productivity of microalgae. Precursor RNA processing protein (Prp19), which is the core component of eukaryotic RNA splice NTC (nineteen associated complex), plays important roles in the mRNA maturation process in eukaryotic cells, has a variety of functions in cell development, and is even directly involved in the biosynthesis of oil bodies in mouse. Nevertheless, its function in Chlamydomonas reinhardtii remains unknown. Here, transcriptional level of CrPrp19 under nutrition deprivation was analyzed, and both its RNA interference and overexpressed transformants were constructed. The expression level of CrPrp19 was suppressed by nitrogen or sulfur deficiency. Cell densities of CrPrp19 RNAi lines decreased, and their neutral lipid contents increased 1.33 and 1.34 times over those of controls. The cells of CrPrp19 RNAi lines were larger and more resistant to sodium acetate than control. Considerably none of the alterations in growth or neutral lipid contents was found in the CrPrp19 overexpression transformants than wild type. Fatty acids were also significantly increased in CrPrp19 RNAi transformants. Subcellular localization and yeast two-hybrid analysis showed that CrPrp19 was a nuclear protein, which might be involved in cell cycle regulation. In conclusion, CrPrp19 protein was necessary for negatively regulating lipid enrichment and cell size, but not stimulatory for lipid storage.
Two Type VI Secretion DNase Effectors are Utilized for Interbacterial Competition in the Fish Pathogen Pseudomonas plecoglossicida
Authors: Li Yanyan , Yan Xiaojun , Tao Zhen
Published: April 2022

Pseudomonas plecoglossicida is a facultative fish pathogen that possesses three distinct type VI secretion systems (named T6SS-1, T6SS-2, and T6SS-3). Our previous work indicated that only T6SS-2 of P. plecoglossicida mediates interbacterial competition. However, the antibacterial T6SS effectors and their functions are unclear. Here, we reported two T6SS effectors that mediate antibacterial activity. We first identified four putative antibacterial effectors (denoted as Txe1, Txe2, Txe3, and Txe4) and their cognate immunity proteins encoded in P. plecoglossicida strain XSDHY-P by analyzing the regions downstream of three vgrG genes. We showed that the growth of Escherichia coli cells expressing Txe1, Txe2, and Txe4 was inhibited, and these three effectors exhibited nuclease activity in vivo. The interbacterial competition assays with single- or multi-effector deletion mutants as attackers revealed that Txe1 was the predominant T6SS toxin of P. plecoglossicida strain XSDHY-P mediating the interbacterial killing. This work contributes to our understanding of bacterial effectors involved in the interbacterial competition.
A Potential Mechanism for Targeting Aggregates With Proteasomes and Disaggregases in Liquid Droplets
Authors: Mee Hayes Emma , Sirvio Liina , Ye Yu
Published: April 2022

Insoluble protein deposits are hallmarks of neurodegenerative disorders and common forms of dementia. The aberrant aggregation of misfolded proteins involves a complex cascade of events that occur over time, from the cellular to the clinical phase of neurodegeneration. Declining neuronal health through increased cell stress and loss of protein homeostasis (proteostasis) functions correlate with the accumulation of aggregates. On the cellular level, increasing evidence supports that misfolded proteins may undergo liquid-liquid phase separation (LLPS), which is emerging as an important process to drive protein aggregation. Studying the reverse process of aggregate disassembly and degradation has only recently gained momentum, following reports of enzymes with distinct aggregate-disassembly activities. In this review, we will discuss how the ubiquitin-proteasome system and disaggregation machineries such as VCP/p97 and HSP70 system may disassemble and/or degrade protein aggregates. In addition to their canonically associated functions, these enzymes appear to share a common feature: reversibly assembling into liquid droplets in an LLPS-driven manner. We review the role of LLPS in enhancing the disassembly of aggregates through locally increasing the concentration of these enzymes and their co-proteins together within droplet structures. We propose that such activity may be achieved through the concerted actions of disaggregase machineries, the ubiquitin-proteasome system and their co-proteins, all of which are condensed within transient aggregate-associated droplets (TAADs), ultimately resulting in aggregate clearance. We further speculate that sustained engagement of these enzymatic activities within TAADs will be detrimental to normal cellular functions, where these activities are required. The possibility of facilitating endogenous disaggregation and degradation activities within TAADs potentially represents a novel target for therapeutic intervention to restore protein homeostasis at the early stages of neurodegeneration.
Bottlenecks, Modularity, and the Neural Control of Behavior
Authors: Nande Anjalika , Dubinkina Veronika , Ravasio Riccardo , Zhang Grace H. , Berman Gordon J.
Published: April 2022

In almost all animals, the transfer of information from the brain to the motor circuitry is facilitated by a relatively small number of neurons, leading to a constraint on the amount of information that can be transmitted. Our knowledge of how animals encode information through this pathway, and the consequences of this encoding, however, is limited. In this study, we use a simple feed-forward neural network to investigate the consequences of having such a bottleneck and identify aspects of the network architecture that enable robust information transfer. We are able to explain some recently observed properties of descending neurons—that they exhibit a modular pattern of connectivity and that their excitation leads to consistent alterations in behavior that are often dependent upon the desired behavioral state of the animal. Our model predicts that in the presence of an information bottleneck, such a modular structure is needed to increase the efficiency of the network and to make it more robust to perturbations. However, it does so at the cost of an increase in state-dependent effects. Despite its simplicity, our model is able to provide intuition for the trade-offs faced by the nervous system in the presence of an information processing constraint and makes predictions for future experiments.
Clinical Profile and Treatment Outcome in MOGAD: A Single-Center Case-Series Study in Guiyang, China
Authors: Lei Xiaoyang , Guo Shipeng , Cui Shengnan , Pu Yin , Zhang Anni , He Dian
Published: April 2022

Background

The clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is expanding over time. However, the long-term management and prognosis of this disorder are still controversial. Therefore, this study aimed to report the clinical profiles and treatment outcomes of MOGAD in our center.

Methods

This was a single-center case-series study. Clinical and para-clinical data, along with treatment outcomes of patients with MOGAD were analyzed.

Results

A total of 27 patients were identified, of which 19 (70%) patients were women, and the median age at disease onset was 40 years (range 20–67). A total of 47 episodes were observed, with optic neuritis (53%) being the most frequent presentation and 60% of them were unilateral. Other presentations included rhombencephalitis (RE) (17%), limbic encephalitis (9%), simultaneous optic neuritis and myelitis (9%), acute disseminated encephalomyelitis (ADEM)-like presentation (6%), myelitis (4%), and ADEM (2%). One patient presenting with RE also met the diagnostic criteria of area postrema syndrome (APS). Another patient with RE presented with imaging characteristics of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). A total of 29 lumbar punctures were recorded, among which an elevated protein level was found in 34% of the samples, pleocytosis was found in 14% of the samples, and positive intrathecal oligoclonal bands were found in 19% of the patients. One patient was found to have anti-N-methyl-D-aspartate receptor antibodies both in his serum and cerebrospinal fluid. Intravenous methylprednisolone (IVMP) was administrated for 85% of the attacks while both IVMP and intravenous immunoglobulin were for 6% of the attacks. Moreover, nine patients received maintenance therapy. Among them, six patients were treated with mycophenolate mofetil, three patients were treated with prednisone, rituximab, and teriflunomide, respectively. The median follow-up period was 20 months (range 6–127). At follow-up, twelve (44%) patients experienced a relapsing course, and the median time to the first relapse was 9.5 months (range 2–120). The median Expanded Disability Status Scale score at nadir was 3.5 (range 2–8) and was 0 (range 0–3) at the last follow-up.

Conclusion

The clinical spectrum of MOGAD is heterogenous, wherein APS and CLIPPERS-form can occur. The long-term outcome of MOGAD seems benign. Further studies are warranted to determine the risk factors of relapse and identify the optimal steroid-sparing agents.
Case Report: Accessible Digital Musical Instrument Can Be Used for Active Music Therapy in a Person With Severe Dementia and Worsening Behavioral and Psychological Symptoms: A Case Study Over a Year and a Half
Authors: Kondo Eisuke , Tabei Ken-ichi , Okuno Ryuhei , Akazawa Kenzo
Published: April 2022

Despite the fact that accessible digital musical instruments can take into account the level of cognitive demands, previous studies have been conducted with patients with mild cognitive impairment (MCI), and it is not known whether they can be used by people with moderate to severe dementia or dementia with worsening behavioral and psychological symptoms of dementia (BPSD). The participant was an 88-year-old woman with vascular dementia (VaD) (Mini-Mental State Examination [MMSE] and Neuropsychiatric Inventory [NPI] scores: 8 and 20, respectively). Music therapy (MT) was provided twice a week for 15 min, and MT sessions spanned over 18 months. For the MT, we used the cyber musical instrument with score (Cymis), an accessible digital musical instrument; it could be played using a touch panel and switches. The cognitive function of the participant declined further, with MMSE scores of 4 after 1 year and 0 after 1.5 years. BPSD peaked with the NPI score of 54 at 1 year and declined thereafter, although only apathy remained. Despite these changes, during MT, she was able to play the accessible digital musical instrument and focus on the performance. These results suggest that even patients with severe VaD can play an accessible digital instrument and continue active music therapy even if their BPSD progress with cognitive decline.