bluuebunny/crossref_metadata_2025 huggingface dataset:
Vicariously Resilient or Traumatised Social Workers: Exploring Some Risk and Protective Factors
Authors: Méndez-Fernández Ana B , Aguiar-Fernández Francisco J , Lombardero-Posada Xoan , Murcia-Álvarez Evelia , González-Fernández Antonio
Published: April 2021

Due to the indirect exposure to traumatic realities, social workers may experience emotional responses of vicarious traumatisation or vicarious resilience. Previous research indicated that risk factors (workload and trauma caseload) provoke vicarious traumatisation and that protection factors (recovery experiences and organisational support) can buffer this relationship. However, the empirical testing of these associations was scarce amongst social workers. This cross-sectional study aims to answer two main research questions: (i) can workload and trauma caseload predict vicarious resilience and vicarious trauma? (ii) Can recovery experiences and organisational support mediate the influence of risk factors on emotional responses? A sample of 373 Spanish social workers (87 per cent females) completed a questionnaire online. The structural equation modelling analyses showed that workload and trauma caseload make recovery experiences and organisational support less likely, facilitating the emergence of vicarious trauma. Recovery experiences and organisational support protect people from vicarious trauma and promote vicarious resilience, both directly and by limiting the influence of workload and trauma caseload. These results highlight the need for interventions enhancing recovery experiences and organisational support as a means to promote vicarious resilience and to decrease vicarious trauma. The need to reduce other risk factors, enhancing protective factors, is also noted.
Functionally validated SCN5A variants allow interpretation of pathogenicity and prediction of lethal events in Brugada syndrome
Authors: Ishikawa Taisuke , Kimoto Hiroki , Mishima Hiroyuki , Yamagata Kenichiro , Ogata Soshiro , Aizawa Yoshiyasu , Hayashi Kenshi , Morita Hiroshi , Nakajima Tadashi , Nakano Yukiko , Nagase Satoshi , Murakoshi Nobuyuki , Kowase Shinya , Ohkubo Kimie , Aiba Takeshi , Morimoto Shimpei , Ohno Seiko , Kamakura Shiro , Nogami Akihiko , Takagi Masahiko , Karakachoff Matilde , Dina Christian , Schott Jean-Jacques , Yoshiura Koh-Ichiro , Horie Minoru , Shimizu Wataru , Nishimura Kunihiro , Kusano Kengo , Makita Naomasa
Published: April 2021

Aims

The prognostic value of genetic variants for predicting lethal arrhythmic events (LAEs) in Brugada syndrome (BrS) remains controversial. We investigated whether the functional curation of SCN5A variations improves prognostic predictability.

Methods and results

Using a heterologous expression system and whole-cell patch clamping, we functionally characterized 22 variants of unknown significance (VUSs) among 55 SCN5A mutations previously curated using in silico prediction algorithms in the Japanese BrS registry (n = 415). According to the loss-of-function (LOF) properties, SCN5A mutation carriers (n = 60) were divided into two groups: LOF-SCN5A mutations and non-LOF SCN5A variations. Functionally proven LOF-SCN5A mutation carriers (n = 45) showed significantly severer electrocardiographic conduction abnormalities and worse prognosis associated with earlier manifestations of LAEs (7.9%/year) than in silico algorithm-predicted SCN5A carriers (5.1%/year) or all BrS probands (2.5%/year). Notably, non-LOF SCN5A variation carriers (n = 15) exhibited no LAEs during the follow-up period. Multivariate analysis demonstrated that only LOF-SCN5A mutations and a history of aborted cardiac arrest were significant predictors of LAEs. Gene-based association studies using whole-exome sequencing data on another independent SCN5A mutation-negative BrS cohort (n = 288) showed no significant enrichment of rare variants in 16 985 genes including 22 non-SCN5A BrS-associated genes as compared with controls (n = 372). Furthermore, rare variations of non-SCN5A BrS-associated genes did not affect LAE-free survival curves.

Conclusion

In vitro functional validation is key to classifying the pathogenicity of SCN5A VUSs and for risk stratification of genetic predictors of LAEs. Functionally proven LOF-SCN5A mutations are genetic burdens of sudden death in BrS, but evidence for other BrS-associated genes is elusive.
Fungus–bacterium associations are widespread in fungal cultures isolated from a semi-arid natural grassland in Germany
Authors: Muller L A H , Ballhausen M-B , Andrade-Linares D R , Pinek L , Golubeva P , Rillig M C
Published: April 2021

We report on a study that aimed at establishing a large soil–fungal culture collection spanning a wide taxonomic diversity and systematically screening the collection for bacterial associations. Fungal cultures were isolated from soil samples obtained from a natural grassland in eastern Germany and bacterial associations were assessed by PCR-amplification and sequencing of bacterial 16S rRNA. In addition, intraspecies genetic diversities of a subset of the isolated species were estimated by double-digest restriction associated DNA sequencing. A total of 688 fungal cultures, representing at least 106 fungal species from 36 different families, were obtained and even though clonal isolates were identified in almost all fungal species subjected to ddRAD-seq, relatively high genetic diversities could be observed in some of the isolated species. A total of 69% of the fungal isolates in our collection were found to be associated with bacteria and the most commonly identified bacterial genera were Pelomonas, Enterobacter and Burkholderia. Our results indicate that bacterial associations commonly occur in soil fungi, even if antibiotics are being applied during the isolation process, and provide a basis for the use of our culture collection in ecological experiments that want to acknowledge the importance of intraspecies genetic diversity.
Antimicrobial and biofilm-disrupting nanostructured TiO2 coating demonstrating photoactivity and dark activity
Authors: Wasa Alibe , Land Johann G , Gorthy Rukmini , Krumdieck Susan , Bishop Catherine , Godsoe William , Heinemann Jack A
Published: April 2021

Antimicrobial materials are tools used to reduce the transmission of infectious microorganisms. Photo-illuminated titania (TiO2) is a known antimicrobial material. Used as a coating on door handles and similar surfaces, it may reduce viability and colonization by pathogens and limit their spread. We tested the survival of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Saccharomyces cerevisiae on a nano-structured TiO2-based thin film, called ‘NsARC’, and on stainless steel under a variety of light wavelengths and intensities. There was significantly less survival (P <0.001) of all the organisms tested on NsARC compared to inert uncoated stainless steel under all conditions. NsARC was active in the dark and possible mechanisms for this are suggested. NsARC inhibited biofilm formation as confirmed by scanning electron microscopy. These results suggest that NsARC can be used as a self-cleaning and self-sterilizing antimicrobial surface coating for the prevention and reduction in the spread of potentially infectious microbes.
Specific PIWI-Interacting RNAs and Related Small Noncoding RNAs Are Associated With Ovarian Aging in Ames Dwarf (df/df) Mice
Authors: Dhahbi Joseph M , Chen Joe W , Bhupathy Supriya , Atamna Hani , Cavalcante Marcelo B , Saccon Tatiana D , Nunes Allancer D C , Mason Jeffrey B , Schneider Augusto , Masternak Michal M
Published: April 2021

The Ames dwarf (df/df) mouse is a well-established model for delayed aging. MicroRNAs (miRNAs), the most studied small noncoding RNAs (sncRNAs), may regulate ovarian aging to maintain a younger ovarian phenotype in df/df mice. In this study, we profile other types of ovarian sncRNAs, PIWI-interacting RNAs (piRNAs) and piRNA-like RNAs (piLRNAs), in young and aged df/df and normal mice. Half of the piRNAs derive from transfer RNA fragments (tRF-piRNAs). Aging and dwarfism alter the ovarian expression of these novel sncRNAs. Specific tRF-piRNAs that increased with age might target and decrease the expression of the breast cancer antiestrogen resistance protein 3 (BCAR3) gene in the ovaries of old df/df mice. A set of piLRNAs that decreased with age and map to D10Wsu102e mRNA may have trans-regulatory functions. Other piLRNAs that decreased with age potentially target and may de-repress transposable elements, leading to a beneficial impact on ovarian aging in df/df mice. These results identify unique responses in ovarian tissues with regard to aging and dwarfism. Overall, our findings highlight the complexity of the aging effects on gene expression and suggest that, in addition to miRNAs, piRNAs, piLRNAs, tRF-piRNAs, and their potential targets can be central players in the maintenance of a younger ovarian phenotype in df/df mice.
Life Course Stressors and Functional Limitations in Later Life Among White, Black, and Hispanic Adults: Deleterious, Hardening, or Benign?
Authors: Sauerteig Madison R , Ferraro Kenneth F , Bauldry Shawn
Published: April 2021

Objectives

Although striking racial and ethnic disparities in health are manifest during later life, they may be rooted in early-life exposures. Drawing from cumulative inequality theory, we investigate whether life course stressors are associated with the risk of later-life functional limitations and whether this relationship differs by race and ethnicity.

Methods

We utilize longitudinal data from the Health and Retirement Study to test whether child and adult stressors predict trajectories of the occurrence and severity of functional limitations among a diverse sample of older adults.

Results

Child and adult stressors are associated with greater occurrence and severity of functional limitations during later life. Mediation analyses reveal the indirect influence of child stressors via adult stressors on occurrence and severity of functional limitations; however, the indirect effects are slightly stronger for Black and Hispanic adults than their White counterparts.

Discussion

Child stressors, in and of themselves, do not increase functional limitations among Black and Hispanic people but are associated with greater adult stress exposure, predisposing them to more functional limitations. Results suggest that childhood stressors are associated with distinct social pathways to functional limitations among White, Black, and Hispanic older adults.
Residual Short-Segment Distal Inflammation Has No Significant Impact on the Major Relapse of Extensive Ulcerative Colitis
Authors: Asonuma Kunio , Kobayashi Taku , Nakano Masaru , Sagami Shintaro , Kiyohara Hiroki , Matsubayashi Mao , Morikubo Hiromu , Miyatani Yusuke , Okabayashi Shinji , Yamazaki Hajime , Kuroki Yuichiro , Hibi Toshifumi
Published: April 2021

Background

Mucosal healing is a treatment target for patients with ulcerative colitis. However, the relevance of proactive treatment for residual inflammation limited to the distal colon is unclear.

Materials and Methods

Patients with ulcerative colitis who had extensive colitis in clinical remission and underwent colonoscopy were retrospectively enrolled and followed up for 2 years. Patients with complete endoscopic remission (CER; Mayo endoscopic subscore [MES] of 0) and those with short-segment distal inflammation (SS; active inflammation only in the sigmoid colon and/or rectum with a proximal MES of 0) were compared for the incidence of minor (only symptomatic) and major (need for induction treatments or hospitalization) relapses.

Results

A total of 91 patients with CER and 54 patients with SS were identified and 63 relapses (47 minor and 16 major) were analyzed. Univariate analysis showed that minor relapses were significantly more frequent in the SS group than in the CER group (hazard ratio [HR], 2.22; 95% confidence interval [CI], 1.25-3.97), but major relapses were not more frequent in the SS group than in the CER group (HR, 1.78; 95% CI, 0.65-4.83). Multivariable analysis showed that SS was the only risk factor significantly associated with minor relapse (HR, 2.38; 95% CI, 1.31-4.36). When the SS group was stratified by MES of 1 vs 2/3, minor relapses were significantly more frequent in the subgroup with MES of 2/3 than in the CER group, whereas the incidence of major relapse remained similar.

Conclusions

Residual short-segment distal inflammation is not a risk factor for major relapses as long as endoscopic remission is achieved in the proximal colon. Therefore, reactive but not proactive treatment may be appropriate for such lesions.
Combination of Vedolizumab With Tacrolimus Is More Efficient Than Vedolizumab Alone in the Treatment of Experimental Colitis
Authors: Manzini Roberto , Schwarzfischer Marlene , Atrott Kirstin , Laimbacher Andrea , Lang Silvia , Wawrzyniak Marcin , Rickenbacher Andreas , Turina Matthias , Hruz Petr , Lissner Donata , Siegmund Britta , Rogler Gerhard , Scharl Michael , Spalinger Marianne R
Published: April 2021

Background

Vedolizumab is a widely used and safe therapy in inflammatory bowel disease, particularly in ulcerative colitis (UC), making it a promising candidate for enhanced efficacy by combining it with additional immunomodulatory medications. In this study, we studied the impact of vedolizumab monotreatment vs vedolizumab coadministration with other immunomodulatory drugs on intestinal inflammation and intestinal immune cells in vivo.

Methods

Colon tissue from human patients with UC with active disease or in remission with or without vedolizumab treatment was stained by immunohistochemistry. We reconstituted NOD-SCID-SGM3 mice with human CD34+ cells and treated them with dextran sodium sulfate to induce acute colitis. Mice were treated with vedolizumab alone, or in combination with tacrolimus, ozanimid, or tofacitinib.

Results

Vedolizumab reduced the number of CD3+ T cells and CD68+ monocytes/macrophages in the colon of patients with UC with active disease. Vedolizumab moderately decreased immune cell numbers in acute dextran sodium sulfate–induced colitis. The combination of vedolizumab with tacrolimus further reduced the number of infiltrating CD3+ T cells and CD68+ monocytes/macrophages and was superior in ameliorating intestinal inflammation when compared to vedolizumab monotreatment. In contrast, cotreatment using vedolizumab with ozanimod or tofacitinib had no additive effect.

Conclusions

Our data show that vedolizumab reduces the number of innate and adaptive immune cells in the mucosa of patients with UC. Further, the combination of vedolizumab with tacrolimus was more efficient to reduce immune cell numbers and to increase therapeutic efficacy than vedolizumab monotreatment. This finding indicates that combination treatment using these two drugs may be beneficial for patients who do not respond to vedolizumab monotherapy.
Cytomegalovirus Viral Load Kinetics Predict Cytomegalovirus End-Organ Disease and Mortality After Hematopoietic Cell Transplant
Authors: Stern Anat , Su Yiqi , Dumke Henry , Fang Jiaqi , Tamari Roni , Jakubowski Ann , Cho Christina , Giralt Sergio , Perales Miguel-Angel , Papanicolaou Genovefa A
Published: April 2021

Background

We investigatedthe association between time-averaged area under the curve (AAUC) of cytomegalovirus (CMV) viral load (VL) by day 100 and overall survival (OS) at 1-year after hematopoietic cell transplantation (HCT).

Methods

In a retrospective cohort study, including patients receiving HCT between June 2010 and December 2017 from Memorial Sloan Kettering Cancer Center, AAUC was calculated for patients with detected VL. Patients were categorized into non-controllers (Q4) and controllers (Q1–Q3) using the highest AAUC quartile as cutoff. Cox models were used to estimate the association between AAUC and OS. Patients with non-detected CMV VL were categorized into elite-controllers (recipient+ [R+] or R−/donor+ [D+]) and R−/D−.

Results

The study (N = 952) included 282 controllers, 93 non-controllers, 275 elite-controllers, and 302 R−/D−. OS was 80.1% and 58.1% for controllers and non-controllers, respectively. In multivariable models, non-controllers had worse OS versus controllers (adjusted hazard ratio [HR] = 2.65; 95% confidence interval [CI], 1.71–4.12). In landmark analyses, controllers had similar OS as elite-controllers (HR = 1.26; 95% CI, .83–1.91) or R−/D− (HR = 0.98; 95% CI, .64–1.5).

Conclusions

Non-controllers had worse OS 1-year post-HCT. Controllers had similar OS as elite-controllers or R−/D−. Future studies are needed to validate our AAUC cutoff across different cohorts and CMV management strategies.
Qualitative and Quantitative Analysis of Tryptamines in the Poison of Incilius alvarius (Amphibia: Bufonidae)
Authors: Schwelm Hannes M , Zimmermann Nicole , Scholl Tobias , Penner Johannes , Autret Amy , Auwärter Volker , Neukamm Merja A
Published: April 2021

Rising numbers of psychoactive tryptamine derivatives have become available on the drug market over the last decade, making these naturally occurring or synthetically manufactured compounds highly relevant for forensic analyses. One of these compounds is 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a constituent of the dried poison of Incilius alvarius (Colorado River toad), which has a history of ritual and/or recreational use. Still, comprehensive and validated qualitative as well as quantitative analytical data on the psychoactive components of this poison are scarce. In this study, samples of the poison of Incilius alvarius were collected from live toads in the Sonoran Desert, Arizona (USA), and analyzed with a set of complementary methods. Acetone/water (70/30, v/v) proved to be the solvent of choice for the extraction of tryptamine derivatives. Trace compounds were enriched, and overload with 5-MeO-DMT was prevented by chromatographic separation of 5-MeO-DMT prior to qualitative analyses. The method for quantification was validated. Attenuated total reflection–Fourier transform infrared spectroscopy was suitable to identify 5-MeO-DMT as the main tryptamine in samples of the poison. The combined evaluation of analytical data gained from gas chromatography–mass spectrometry (GC–MS), high-performance liquid chromatography–quadrupole time-of-flight high-resolution MS (HPLC–qToF-HRMS) and HPLC–MS-MS confirmed the presence of 5-MeO-DMT, 5-MeO-N-methyltryptamine, 5-MeO-tryptamine, 5-MeO-tryptophol, 2-(5-methoxy-1H-indol-3-yl)-acetic-acid (5-MIAA), 5-HO-N-methyltryptamine, bufotenin, DMT and tryptophan. For the first time, 5-MeO-tryptamine and two positional isomers of hydroxylated MeO-DMT were detected in the poison of Incilius alvarius. The tryptamine present in the highest concentrations was 5-MeO-DMT (mean ± SD: 410,000 ± 30,000 μg/g). Mean concentrations of 5-MeO-tryptamine (490 ± 260 μg/g), 5-HO-N-methyltryptamine (270 ± 120 μg/g), bufotenin (2,800 ± 1,900 μg/g) and DMT (250 ± 80 μg/g) showed a relatively high variability between individual samples. The comprehensive analytical reference data of Incilius alvarius poison presented here might prove useful for forensic chemists.
Atractylodin inhibited the migration and induced autophagy in cholangiocarcinoma cells via PI3K/AKT/mTOR and p38MAPK signalling pathways
Authors: Acharya Bishwanath , Chaijaroenkul Wanna , Na-Bangchang Kesara
Published: April 2021

Objectives

The effects of atractylodin (ATD), the bioactive compound from Atractylodes lancea, on migration and autophagy status of cholangiocarcinoma cell line were investigated.

Methods

Cytotoxic activity and effects on cell migration and invasion were evaluated by MTT and trans-well assay, respectively. Autophagy and underlying molecular mechanisms were investigated using flow cytometry and western blot analysis.

Key findings

ATD regulated the activity of PI3K/AKT/mTOR and p38MAPK signalling pathways which contributed to autophagy induction. HuCCT-1 cell growth was inhibited by ATD in a time- and dose-dependent manner. ATD inhibited the migration and invasion of HuCCT1 cells in a concentration-dependent manner. It also induced autophagy in HuCCT1 cells in a time- and dose-dependent manner. The SB202190 (autophagy inducer) and 3-MA (autophagy inhibitor) significantly increased and decreased the rate of ATD-induced autophagy, respectively. The 24 h exposure of ATD inhibited the phosphorylation of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (p38MAPK) and increased Beclin-1 expression and LC3 conversion. It also reduced p-AKT/AKT, p-mTOR/mTOR and p-p38MAPK/p38MAPK.

Conclusions

ATD inhibits the proliferation and induces CCA cell autophagy via regulating PI3K/AKT/mTOR and p38MAPK signalling pathways.
IgG4-related mastitis requiring differentiation from breast cancer: a case report
Authors: Asano Yuka , Kashiwagi Shinichiro , Kawano Yuko , Tanaka Sayaka , Kuwae Yuko , Takashima Tsutomu , Ohsawa Masahiko , Hirakawa Kosei , Ohira Masaichi
Published: April 2021

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a group of chronic relapsing inflammatory conditions. Although IgG4-RD can occur in various organs, it is rarely observed in mammary glands. Here, we report a case of IgG4-related mastitis (IgG4-RM) that needed to be differentiated from breast cancer. A 54-year-old woman was examined for a tumor in her left breast. Mammary ultrasonography revealed an irregular hypoechoic tumor measuring 45.0 × 43.0 × 32.0 mm in size. A core-needle biopsy of the left breast tissue revealed a high degree of mixed T and B lymphocytic and plasma cell infiltration, as well as interstitial fibrosis. IgG4-RD was diagnosed based on hematological examination that revealed an abnormal IgG4 value of 332 mg/dl. All the clinical diagnostic criteria for IgG4 were met, resulting in a definitive diagnosis of IgG4-RM.
Gestational gigantomastia—a rare entity complicated by life-threatening haemorrhage
Authors: Neblett Carlos , Venugopal Rajeev , Johnson Miguel , Mitchell Derek , Kunc Vojtech
Published: April 2021

Gestational gigantomastia is a psychologically and physically debilitating disease of unknown aetiology. Underlying diseases that present as gigantomastia should be excluded by a thorough workup. Most cases respond to the preferred approach: conservative management, as foetal viability and well-being is of significant importance. However, in those cases where the maternal mortality is at risk, the surgical approach is preferred. Life-threatening haemorrhage may occur and early recognition and treatment is paramount to outcome. A case of gestational gigantomastia complicated by life-threatening haemorrhage is presented and discussed.
Large-Scale Phylogenomic Analyses Reveal the Monophyly of Bryophytes and Neoproterozoic Origin of Land Plants
Authors: Su Danyan , Yang Lingxiao , Shi Xuan , Ma Xiaoya , Zhou Xiaofan , Hedges S Blair , Zhong Bojian
Published: April 2021

The relationships among the four major embryophyte lineages (mosses, liverworts, hornworts, vascular plants) and the timing of the origin of land plants are enigmatic problems in plant evolution. Here, we resolve the monophyly of bryophytes by improving taxon sampling of hornworts and eliminating the effect of synonymous substitutions. We then estimate the divergence time of crown embryophytes based on three fossil calibration strategies, and reveal that maximum calibration constraints have a major effect on estimating the time of origin of land plants. Moreover, comparison of priors and posteriors provides a guide for evaluating the optimal calibration strategy. By considering the reliability of fossil calibrations and the influences of molecular data, we estimate that land plants originated in the Precambrian (980–682 Ma), much older than widely recognized. Our study highlights the important contribution of molecular data when faced with contentious fossil evidence, and that fossil calibrations used in estimating the timescale of plant evolution require critical scrutiny.
Genomic Basis of Striking Fin Shapes and Colors in the Fighting Fish
Authors: Wang Le , Sun Fei , Wan Zi Yi , Ye Baoqing , Wen Yanfei , Liu Huiming , Yang Zituo , Pang Hongyan , Meng Zining , Fan Bin , Alfiko Yuzer , Shen Yubang , Bai Bin , Lee May Shu Qing , Piferrer Francesc , Schartl Manfred , Meyer Axel , Yue Gen Hua
Published: April 2021

Resolving the genomic basis underlying phenotypic variations is a question of great importance in evolutionary biology. However, understanding how genotypes determine the phenotypes is still challenging. Centuries of artificial selective breeding for beauty and aggression resulted in a plethora of colors, long-fin varieties, and hyper-aggressive behavior in the air-breathing Siamese fighting fish (Betta splendens), supplying an excellent system for studying the genomic basis of phenotypic variations. Combining whole-genome sequencing, quantitative trait loci mapping, genome-wide association studies, and genome editing, we investigated the genomic basis of huge morphological variation in fins and striking differences in coloration in the fighting fish. Results revealed that the double tail, elephant ear, albino, and fin spot mutants each were determined by single major-effect loci. The elephant ear phenotype was likely related to differential expression of a potassium ion channel gene, kcnh8. The albinotic phenotype was likely linked to a cis-regulatory element acting on the mitfa gene and the double-tail mutant was suggested to be caused by a deletion in a zic1/zic4 coenhancer. Our data highlight that major loci and cis-regulatory elements play important roles in bringing about phenotypic innovations and establish Bettas as new powerful model to study the genomic basis of evolved changes.
PLIP 2021: expanding the scope of the protein–ligand interaction profiler to DNA and RNA
Authors: Adasme Melissa F , Linnemann Katja L , Bolz Sarah Naomi , Kaiser Florian , Salentin Sebastian , Haupt V Joachim , Schroeder Michael
Published: April 2021

With the growth of protein structure data, the analysis of molecular interactions between ligands and their target molecules is gaining importance. PLIP, the protein–ligand interaction profiler, detects and visualises these interactions and provides data in formats suitable for further processing. PLIP has proven very successful in applications ranging from the characterisation of docking experiments to the assessment of novel ligand–protein complexes. Besides ligand–protein interactions, interactions with DNA and RNA play a vital role in many applications, such as drugs targeting DNA or RNA-binding proteins. To date, over 7% of all 3D structures in the Protein Data Bank include DNA or RNA. Therefore, we extended PLIP to encompass these important molecules. We demonstrate the power of this extension with examples of a cancer drug binding to a DNA target, and an RNA–protein complex central to a neurological disease. PLIP is available online at https://plip-tool.biotec.tu-dresden.de and as open source code. So far, the engine has served over a million queries and the source code has been downloaded several thousand times.
Meclofenamate causes loss of cellular tethering and decoupling of functional networks in glioblastoma
Authors: Schneider Matthias , Vollmer Lea , Potthoff Anna-Laura , Ravi Vidhya M , Evert Bernd O , Rahman Mohummad A , Sarowar Shahin , Kueckelhaus Jan , Will Paulina , Zurhorst David , Joseph Kevin , Maier Julian P , Neidert Nicolas , d’Errico Paolo , Meyer-Luehmann Melanie , Hofmann Ulrich G , Dolf Andreas , Salomoni Paolo , Güresir Erdem , Enger Per Ø , Chekenya Martha , Pietsch Torsten , Schuss Patrick , Schnell Oliver , Westhoff Mike-Andrew , Beck Jürgen , Vatter Hartmut , Waha Andreas , Herrlinger Ulrich , Heiland Dieter H
Published: April 2021

Background

Glioblastoma cells assemble to a syncytial communicating network based on tumor microtubes (TMs) as ultra-long membrane protrusions. The relationship between network architecture and transcriptional profile remains poorly investigated. Drugs that interfere with this syncytial connectivity such as meclofenamate (MFA) may be highly attractive for glioblastoma therapy.

Methods

In a human neocortical slice model using glioblastoma cell populations of different transcriptional signatures, three-dimensional tumor networks were reconstructed, and TM-based intercellular connectivity was mapped on the basis of two-photon imaging data. MFA was used to modulate morphological and functional connectivity; downstream effects of MFA treatment were investigated by RNA sequencing and fluorescence-activated cell sorting (FACS) analysis.

Results

TM-based network morphology strongly differed between the transcriptional cellular subtypes of glioblastoma and was dependent on axon guidance molecule expression. MFA revealed both a functional and morphological demolishment of glioblastoma network architectures which was reflected by a reduction of TM-mediated intercellular cytosolic traffic as well as a breakdown of TM length. RNA sequencing confirmed a downregulation of NCAM and axon guidance molecule signaling upon MFA treatment. Loss of glioblastoma communicating networks was accompanied by a failure in the upregulation of genes that are required for DNA repair in response to temozolomide (TMZ) treatment and culminated in profound treatment response to TMZ-mediated toxicity.

Conclusion

The capacity of TM formation reflects transcriptional cellular heterogeneity. MFA effectively demolishes functional and morphological TM-based syncytial network architectures. These findings might pave the way to a clinical implementation of MFA as a TM-targeted therapeutic approach.
Tobacco transcription factor bHLH123 improves salt tolerance by activating NADPH oxidase NtRbohE expression
Authors: Liu Dan , Li Yang-Yang , Zhou Zhi-Cheng , Xiang Xiaohua , Liu Xin , Wang Jie , Hu Zheng-Rong , Xiang Shi-Peng , Li Wei , Xiao Qin-Zhi , Wang Yuanying , Hu Ri-Sheng , Zhao Qiang
Published: April 2021

In plants, reactive oxygen species (ROS) produced following the expression of the respiratory burst oxidase homolog (Rboh) gene are important regulators of stress responses. However, little is known about how plants acclimate to salt stress through the Rboh-derived ROS signaling pathway. Here, we showed that a 400-bp fragment of the tobacco (Nicotiana tabacum) NtRbohE promoter played a critical role in the salt response. Using yeast one-hybrid (Y1H) screens, NtbHLH123, a bHLH transcription factor, was identified as an upstream partner of the NtRbohE promoter. These interactions were confirmed by Y1H, electrophoretic mobility assay, and chromatin immunoprecipitation assays. Overexpression of NtbHLH123 resulted in greater resistance to salt stress, while NtbHLH123-silenced plants had reduced resistance to salt stress. We also found that NtbHLH123 positively regulates the expression of NtRbohE and ROS production soon after salt stress treatment. Moreover, knockout of NtRbohE in the 35S::NtbHLH123 background resulted in reduced expression of ROS-scavenging and salt stress-related genes and salt tolerance, suggesting that NtbHLH123-regulated salt tolerance is dependent on the NtbHLH123-NtRbohE signaling pathway. Our data show that NtbHLH123 is a positive regulator and acts as a molecular switch to control a Rboh-dependent mechanism in response to salt stress in plants.
Business sectors’ initiatives on health and safety protocols and vaccination program among employees during the COVID-19 pandemic
Authors: Yutuc Alma V , Olazo Danzen B , Sarmiento Philip Joseph D
Published: April 2021

In a recent correspondence, the author discussed the issues of ‘no-jab, no job’ policy, which is planned to be implemented by governments and companies in many countries. This paper highlights the business sectors’ initiatives in ensuring the implementation of health and safety protocols and vaccination program among employees during the COVID-19 pandemic.
Anti-Semitism in the United States: An Overview and Strategies to Create a More Socially Just Society
Authors: Hodge David R , Boddie Stephanie Clintonia
Published: April 2021

Hate crimes against members of the Jewish community have increased dramatically over the past few years. According to federal data, the number of hate crimes directed at Jews now appears to exceed those directed at many, if not most, minority groups. Yet, despite the number of hate crimes aimed at Jews, little recent scholarship has considered the issue of anti-Semitism. To address this gap in the profession’s literature, this article examines the issue of anti-Semitism in the United States. Toward that end, the Jewish population is described and data on anti-Semitism are reviewed along with factors that contribute to this prejudice. The article concludes by discussing strategies that social work educators, practitioners, and researchers might pursue to help create a more socially just society for the Jewish community in the United States and elsewhere. For instance, social workers might seek to address spiritual microaggressions aimed at members of the Jewish community. As part of this process, social workers might help create a culture that respects religious freedom, a fundamental human right, and advocate for equitable portrayals of Jewish people and perspectives in diverse media. Particular attention should be paid to Orthodox Jews, who are often targets of anti-Semitism.
Phoma medicaginis Isolate Differences Determine Disease Severity and Phytoestrogen Production in Annual Medicago spp.
Authors: Omidvari Mahtab , Flematti Gavin R. , You Ming Pei , Abbaszadeh-Dahaji Payman , Barbetti Martin J.
Published: April 2021

Phoma black stem and leaf spot disease of annual Medicago spp., caused by Phoma medicaginis, not only can devastate forage and seed yield but can reduce herbage quality by inducing production of phytoestrogens (particularly coumestrol and 4′-O-methylcoumestrol), which can also reduce the ovulation rates of animals grazing infected forage. We determined the consequent phytoestrogen levels on three different annual Medicago species/cultivars (Medicago truncatula cultivar Cyprus, Medicago polymorpha var. brevispina cultivar Serena, and Medicago murex cultivar Zodiac) after inoculation with 35 isolates of P. medicaginis. Across the isolate × cultivar combinations, leaf disease incidence, petiole/stem disease incidence, leaf disease severity, petiole disease severity, and leaf yellowing severity ranged up to 100, 89.4, 100, 58.1, and 61.2%, respectively. Cultivars Cyprus and Serena were the most susceptible and cultivar Zodiac was the most resistant to P. medicaginis. Isolates WAC3653, WAC3658, and WAC4252 produced the most severe disease. Levels of phytoestrogens in stems ranged from 25 to 1,995 mg/kg for coumestrol and from 0 to 418 mg/kg for 4′-O-methylcoumestrol. There was a significant positive relationship of disease incidence and severity parameters with both coumestrol and 4′-O-methylcoumestrol contents, as noted across individual cultivars and across the three cultivars overall, where r = 0.39 and 0.37 for coumestrol and 4′-O-methylcoumestrol, respectively (P < 0.05). Although cultivar Serena was most susceptible to P. medicaginis and produced the highest levels of phytoestrogens in the presence of P. medicaginis, cultivar Zodiac contained the highest levels of phytoestrogens in comparison with other cultivars in the absence of P. medicaginis. There was a 15-fold increase in coumestrol in cultivar Serena but only a 7-fold increase in cultivar Zodiac from infection of P. medicaginis. The study highlights that the intrinsic ability of a particular cultivar to produce phytoestrogens in the absence of the pathogen, and its comparative ability to produce phytoestrogens in the presence of the P. medicaginis, are both important and highly relevant to developing new annual Medicago spp. cultivars that offer improved disease resistance and better animal reproductive outcomes.
Functional plasticity in lateral hypothalamus and its prediction of cognitive impairment in patients with diffuse axonal injury: evidence from a resting-state functional connectivity study
Authors: Wang Yao , Zhou Fuqing , Li Yan , Li Jian , Kuang Hongmei , Chen Qi , Hong Tao , Gong Honghan
Published: April 2021

Objective

Diffuse axonal injury (DAI) is a common pathological process after traumatic brain injury, which may cause survivors severe functional disorders, including cognitive impairment and physical disability. Recent literature indicated lateral hypothalamus and medial hypothalamus damage during DAI. Thus, we aim to investigate whether there is imaging evidence of hypothalamic injury in patients with DAI and its clinical association.

Methods

Twenty-four patients with diagnosed DAI and 26 age and sex-matched healthy controls underwent resting-state functional MRI. We assessed the lateral hypothalamus and medial hypothalamus functional connectivity with seed-based analysis in DAI. Furthermore, a partial correlation was used to measure its clinical association. The prediction of the severity of DAI from the altered lateral hypothalamus and medial hypothalamus connectivity was conducted using a general linear model.

Results

Compared with healthy control, the DAI group showed significantly decreased lateral hypothalamus functional connectivity with the basal ganglia and cingulate gyrus, which was positively correlated with mini-mental state examination scores (Bonferroni correction at P < 0.0125). Importantly, this disrupted functional connectivity can be used to predict the patients’ cognitive state reliably (P = 0.006; P = 0.009, respectively) in DAI. Moreover, we also observed increased connectivity of medial hypothalamus with the superior temporal gyrus and the regions around the operculum. Furthermore, there was a trend of negative correlation between the medial hypothalamus functional connectivity changes to the right superior temporal gyrus and the disability rating scale scores in the DAI group.

Conclusion

Our results suggest that there are alterations of medial hypothalamus and lateral hypothalamus connectivity in DAI and further understand its clinical symptoms, including related cognitive impairment.
Identification of Rpd3 as a novel epigenetic regulator of Drosophila FIG 4, a Charcot-Marie-Tooth disease-causing gene
Authors: Muraoka Yuuka , Nikaido Atsushi , Kowada Ryosuke , Kimura Hiroshi , Yamaguchi Masamitsu , Yoshida Hideki
Published: April 2021

Mutations in the factor-induced-gene 4 (FIG 4) gene are associated with multiple disorders, including Charcot-Marie-Tooth disease (CMT), epilepsy with polymicrogyria, Yunis–Varón syndrome and amyotrophic lateral sclerosis. The wide spectrum of disorders associated with FIG 4 may be related to the dysregulated epigenetics. Using Gene Expression Omnibus, we found that HDAC1 binds to the FIG 4 gene locus in the genome of human CD4+ T cells. Rpd3 is a well-known Drosophila homolog of human HDAC1. We previously established Drosophila models targeting Drosophila FIG 4 (dFIG 4) that exhibited defective locomotive ability, abnormal synapse morphology at neuromuscular junctions, enlarged vacuoles in the fat body and aberrant compound eye morphology. Genetic crossing experiments followed by physiological and immunocytochemical analyses revealed that Rpd3 mutations suppressed these defects induced by dFIG 4 knockdown. This demonstrated Rpd3 to be an important epigenetic regulator of dFIG 4, suggesting that the inhibition of HDAC1 represses the pathogenesis of FIG 4-associated disorders, including CMT. Defects in epigenetic regulators, such as HDAC1, may also explain the diverse symptoms of FIG 4-associated disorders.
Atrophy of lacunosum moleculare layer is important for learning and memory in APP/PS1 transgenic mice
Authors: Zhang Yi , Chao Feng-lei , Zhou Chun-ni , Jiang Lin , Zhang Lei , Liang Xin , Tang Jing , Tang Yong
Published: April 2021

Changes in the hippocampus are closely associated with learning and memory in Alzheimer’s disease; however, it is not clear which morphological and cellular and subcellular changes are essential for learning and memory. Here, we accurately quantitatively studied the hippocampal microstructure changes in Alzheimer’s disease model mice and analyzed the relationship between the hippocampal microstructure changes and learning and memory. Ten-month-old male APP/PS1 transgenic mice and age-matched nontransgenic littermate mice were randomly selected. The spatial learning and memory abilities were assessed using the Morris water maze. The volumes of each layer and numbers of neurons, dendritic spines and oligodendrocytes in the hippocampal subregions were investigated using unbiased stereological techniques. The APP/PS1 transgenic mice showed a decline in hippocampus-dependent spatial learning and memory abilities, smaller volumes of each layer (other than stratum radiatum) and fewer numbers of neurons, dendritic spine synapses and mature oligodendrocytes in the hippocampal subregions than nontransgenic mice. In particular, the decline of spatial learning ability was significantly correlated with the atrophy of lacunosum moleculare layer (LMol) and the decrease of hippocampal neurons and mature oligodendrocytes rather than dendritic spines. The CA1-3 fields (including LMol) atrophy was significantly correlated with the decrease both of neurons, dendritic spines and mature oligodendrocytes. However, the dentate gyrus atrophy was significantly correlated with the decrease of neurons and mature oligodendrocytes rather than dendritic spines. The loss of neurons, dendritic spines synapses and mature oligodendrocytes together caused the LMol atrophy and then led to a decline in hippocampus-dependent spatial learning ability in mice with Alzheimer’s disease.
Balancing selection and drift in a polymorphic salamander metapopulation
Authors: Giery Sean T. , Zimova Marketa , Drake Dana L. , Urban Mark C.
Published: April 2021

Understanding how genetic variation is maintained in a metapopulation is a longstanding problem in evolutionary biology. Historical resurveys of polymorphisms have offered efficient insights about evolutionary mechanisms, but are often conducted on single, large populations, neglecting the more comprehensive view afforded by considering all populations in a metapopulation. Here, we resurveyed a metapopulation of spotted salamanders (Ambystoma maculatum) to understand the evolutionary drivers of frequency variation in an egg mass colour polymorphism. We found that this metapopulation was demographically, phenotypically and environmentally stable over the last three decades. However, further analysis revealed evidence for two modes of evolution in this metapopulation—genetic drift and balancing selection. Although we cannot identify the balancing mechanism from these data, our findings present a clear view of contemporary evolution in colour morph frequency and demonstrate the importance of metapopulation-scale studies for capturing a broad range of evolutionary dynamics.
Age and social experience induced plasticity across brain regions of the paper waspPolistes fuscatus
Authors: Jernigan Christopher M. , Zaba Natalie C. , Sheehan Michael J.
Published: April 2021

Developmental studies of brain volumes can reveal which portions of neural circuits are sensitive to environmental inputs. In social insects, differences in relative investment across brain regions emerge as behavioural repertoires change during ontogeny or as a result of experience. Here, we test the effects of maturation and social experience on morphological brain development inPolistes fuscatuspaper wasps,focusing on brain regions involved in visual and olfactory processing. We find that mature wasps regardless of social experience have relatively larger brains than newly emerged wasps and this difference is driven by changes to mushroom body calyx and visual regions but not olfactory processing neuropils. Notably, social wasps invest more in the anterior optic tubercle (AOT), a visual glomerulus involved in colour and object processing in other taxa, relative to other visual integration centres the mushroom body calyces compared with aged socially naive wasps. Differences in developmental plasticity between visual and olfactory neuropil volumes are discussed in light of behavioural maturation in paper wasps, especially as it relates to social recognition. Previous research has shown thatP. fuscatusneed social experience to develop specialized visual processing of faces, which is used to individually recognize conspecifics. The present study suggests that the AOT is a candidate brain region that could mediate facial processing in this species.
Constraints and variation in food web link-species space
Authors: Gibert Jean P. , Wieczynski Daniel J.
Published: April 2021

Predicting food web structure in future climates is a pressing goal of ecology. These predictions may be impossible without a solid understanding of the factors that structure current food webs. The most fundamental aspect of food web structure—the relationship between the number of links and species—is still poorly understood. Some species interactions may be physically or physiologically ‘forbidden'—like consumption by non-consumer species—with possible consequences for food web structure. We show that accounting for these ‘forbidden interactions' constrains the feasible link-species space, in tight agreement with empirical data. Rather than following one particular scaling relationship, food webs are distributed throughout this space according to shared biotic and abiotic features. Our study provides new insights into the long-standing question of which factors determine this fundamental aspect of food web structure.
School closures reduced social mixing of children during COVID-19 with implications for transmission risk and school reopening policies
Authors: Head Jennifer R. , Andrejko Kristin L. , Cheng Qu , Collender Philip A. , Phillips Sophie , Boser Anna , Heaney Alexandra K. , Hoover Christopher M. , Wu Sean L. , Northrup Graham R. , Click Karen , Bardach Naomi S. , Lewnard Joseph A. , Remais Justin V.
Published: April 2021

School closures may reduce the size of social networks among children, potentially limiting infectious disease transmission. To estimate the impact of K–12 closures and reopening policies on children's social interactions and COVID-19 incidence in California's Bay Area, we collected data on children's social contacts and assessed implications for transmission using an individual-based model. Elementary and Hispanic children had more contacts during closures than high school and non-Hispanic children, respectively. We estimated that spring 2020 closures of elementary schools averted 2167 cases in the Bay Area (95% CI: −985, 5572), fewer than middle (5884; 95% CI: 1478, 11.550), high school (8650; 95% CI: 3054, 15 940) and workplace (15 813; 95% CI: 9963, 22 617) closures. Under assumptions of moderate community transmission, we estimated that reopening for a four-month semester without any precautions will increase symptomatic illness among high school teachers (an additional 40.7% expected to experience symptomatic infection, 95% CI: 1.9, 61.1), middle school teachers (37.2%, 95% CI: 4.6, 58.1) and elementary school teachers (4.1%, 95% CI: −1.7, 12.0). However, we found that reopening policies for elementary schools that combine universal masking with classroom cohorts could result in few within-school transmissions, while high schools may require masking plus a staggered hybrid schedule. Stronger community interventions (e.g. remote work, social distancing) decreased the risk of within-school transmission across all measures studied, with the influence of community transmission minimized as the effectiveness of the within-school measures increased.