bluuebunny/crossref_metadata_2025 huggingface dataset:
A Small RNA Is Linking CRISPR–Cas and Zinc Transport
Authors: Märkle Pascal , Maier Lisa-Katharina , Maaß Sandra , Hirschfeld Claudia , Bartel Jürgen , Becher Dörte , Voß Björn , Marchfelder Anita
Published: May 2021

The function and mode of action of small regulatory RNAs is currently still understudied in archaea. In the halophilic archaeon Haloferax volcanii, a plethora of sRNAs have been identified; however, in-depth functional analysis is missing for most of them. We selected a small RNA (s479) from Haloferax volcanii for detailed characterization. The sRNA gene is encoded between a CRISPR RNA locus and the Cas protein gene cluster, and the s479 deletion strain is viable and was characterized in detail. Transcriptome studies of wild-type Haloferax cells and the deletion mutant revealed upregulation of six genes in the deletion strain, showing that this sRNA has a clearly defined function. Three of the six upregulated genes encode potential zinc transporter proteins (ZnuA1, ZnuB1, and ZnuC1) suggesting the involvement of s479 in the regulation of zinc transport. Upregulation of these genes in the deletion strain was confirmed by northern blot and proteome analyses. Furthermore, electrophoretic mobility shift assays demonstrate a direct interaction of s479 with the target znuC1 mRNA. Proteome comparison of wild-type and deletion strains further expanded the regulon of s479 deeply rooting this sRNA within the metabolism of H. volcanii especially the regulation of transporter abundance. Interestingly, s479 is not only encoded next to CRISPR–cas genes, but the mature s479 contains a crRNA-like 5′ handle, and experiments with Cas protein deletion strains indicate maturation by Cas6 and interaction with Cas proteins. Together, this might suggest that the CRISPR–Cas system is involved in s479 function.
Exogenous Hydrogen Sulfide Plays an Important Role Through Regulating Autophagy in Ischemia/Reperfusion Injury
Authors: Lv Shuangyu , Wang Zhu , Wang Jie , Wang Honggang
Published: May 2021

Ischemia/reperfusion (I/R) injury is characterized by limiting blood supply to organs, then restoring blood flow and reoxygenation. It leads to many diseases, including acute kidney injury, myocardial infarction, circulatory arrest, ischemic stroke, trauma, and sickle cell disease. Autophagy is an important and conserved cellular pathway, in which cells transfer the cytoplasmic contents to lysosomes for degradation. It plays an important role in maintaining the balance of cell synthesis, decomposition and reuse, and participates in a variety of physiological and pathological processes. Hydrogen sulfide (H2S), along with carbon monoxide (CO) and nitric oxide (NO), is an important gas signal molecule and regulates various physiological and pathological processes. In recent years, there are many studies on the improvement of I/R injury by H2S through regulating autophagy, but the related mechanisms are not completely clear. Therefore, we summarize the related research in the above aspects to provide theoretical reference for future in-depth research.
Changing the Cortical Conductor’s Tempo: Neuromodulation of the Claustrum
Authors: Wong Kelly L. L. , Nair Aditya , Augustine George J.
Published: May 2021

The claustrum is a thin sheet of neurons that is densely connected to many cortical regions and has been implicated in numerous high-order brain functions. Such brain functions arise from brain states that are influenced by neuromodulatory pathways from the cholinergic basal forebrain, dopaminergic substantia nigra and ventral tegmental area, and serotonergic raphe. Recent revelations that the claustrum receives dense input from these structures have inspired investigation of state-dependent control of the claustrum. Here, we review neuromodulation in the claustrum—from anatomical connectivity to behavioral manipulations—to inform future analyses of claustral function.
Multi-Source Co-adaptation for EEG-Based Emotion Recognition by Mining Correlation Information
Authors: Tao Jianwen , Dan Yufang
Published: May 2021

Since each individual subject may present completely different encephalogram (EEG) patterns with respect to other subjects, existing subject-independent emotion classifiers trained on data sampled from cross-subjects or cross-dataset generally fail to achieve sound accuracy. In this scenario, the domain adaptation technique could be employed to address this problem, which has recently got extensive attention due to its effectiveness on cross-distribution learning. Focusing on cross-subject or cross-dataset automated emotion recognition with EEG features, we propose in this article a robust multi-source co-adaptation framework by mining diverse correlation information (MACI) among domains and features with l2,1−norm as well as correlation metric regularization. Specifically, by minimizing the statistical and semantic distribution differences between source and target domains, multiple subject-invariant classifiers can be learned together in a joint framework, which can make MACI use relevant knowledge from multiple sources by exploiting the developed correlation metric function. Comprehensive experimental evidence on DEAP and SEED datasets verifies the better performance of MACI in EEG-based emotion recognition.
Low Protein Diets and Energy Balance: Mechanisms of Action on Energy Intake and Expenditure
Authors: Pezeshki Adel , Chelikani Prasanth K.
Published: May 2021

Low protein diets are associated with increased lifespan and improved cardiometabolic health primarily in rodents, and likely improve human health. There is strong evidence that moderate to severe reduction in dietary protein content markedly influences caloric intake and energy expenditure, which is often followed by a decrease in body weight and adiposity in animal models. While the neuroendocrine signals that trigger hyperphagic responses to protein restriction are better understood, there is accumulating evidence that increased sympathetic flux to brown adipose tissue, fibroblast growth factor-21 and serotonergic signaling are important for the thermogenic effects of low protein diets. This mini-review specifically focuses on the effect of low protein diets with variable carbohydrate and lipid content on energy intake and expenditure, and the underlying mechanisms of actions by these diets. Understanding the mechanisms by which protein restriction influences energy balance may unveil novel approaches for treating metabolic disorders in humans and improve production efficiency in domestic animals.
Serum Folate Status Is Primarily Associated With Neurodevelopment in Children With Autism Spectrum Disorders Aged Three and Under—A Multi-Center Study in China
Authors: Li Qiu , Yang Ting , Chen Li , Dai Ying , Wu Li-Jie , Jia Fei-Yong , Hao Yan , Li Ling , Zhang Jie , Ke Xiao-Yan , Yi Ming-Ji , Hong Qi , Chen Jin-Jin , Fang Shuan-Feng , Wang Yi-Chao , Wang Qi , Jin Chun-Hua , Dong Zhi-Fang , Chen Jie , Li Ting-Yu
Published: May 2021

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Folate has been demonstrated to be associated with ASD. However, current studies on the correlation between folate and symptoms of children with ASD have inconsistent conclusions, use mainly small samples, and lack age-stratified analysis. This study aimed to explore the association between serum folate and symptoms of autistic children at different age groups from a multi-center perspective.

Methods: We enrolled 1,300 children with ASD and 1,246 typically developing (TD) children under 7 years old from 13 cities in China. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS) were used to evaluate the symptoms of children with ASD. China neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) scale was used to evaluate the neurodevelopment of children with ASD. Serum folate was measured by chemiluminescence assay in the two groups.

Results: The serum folate levels of children with ASD were lower than that of TD children. In terms of core symptoms of ASD, we found that the serum folate levels were not associated with ABC, SRS, and CARS scores in ASD children of all ages but negatively associated with communication warning behavior scores of CNBS-R2016 in ASD children aged three and under. Concerning development quotients, it was at the age of three and under that serum folate levels were positively associated with gross motor, fine motor, language, and general quotient of ASD children. These ASD children aged three and under were further divided into two groups according to the median of serum folate (14.33 ng/mL); we found that compared to ASD children with folate ≤ 14.33 ng/mL, those with folate >14.33 ng/mL had lower communication warning behavior score and higher gross motor, fine motor, adaptive behavior, language, person-social, and general development quotients.

Conclusion: We found that serum folate status was primarily associated with the neurodevelopment of children with ASD aged three and under. Furthermore, relatively higher serum folate levels may be more beneficial for children with ASD. Our results suggest that folate level should be paid more attention in ASD children, especially in early life, to better promote the intervention of ASD children.
Combining Multiparametric MRI Radiomics Signature With the Vesical Imaging-Reporting and Data System (VI-RADS) Score to Preoperatively Differentiate Muscle Invasion of Bladder Cancer
Authors: Zheng Zongtai , Xu Feijia , Gu Zhuoran , Yan Yang , Xu Tianyuan , Liu Shenghua , Yao Xudong
Published: May 2021

Background

The treatment and prognosis for muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC) are different. We aimed to construct a nomogram based on the multiparametric MRI (mpMRI) radiomics signature and the Vesical Imaging-Reporting and Data System (VI-RADS) score for the preoperative differentiation of MIBC from NMIBC.

Method

The retrospective study involved 185 pathologically confirmed bladder cancer (BCa) patients (training set: 129 patients, validation set: 56 patients) who received mpMRI before surgery between August 2014 to April 2020. A total of 2,436 radiomics features were quantitatively extracted from the largest lesion located on the axial T2WI and from dynamic contrast-enhancement images. The minimum redundancy maximum relevance (mRMR) algorithm was used for feature screening. The selected features were introduced to construct radiomics signatures using three classifiers, including least absolute shrinkage and selection operator (LASSO), support vector machines (SVM) and random forest (RF) in the training set. The differentiation performances of the three classifiers were evaluated using the area under the curve (AUC) and accuracy. Univariable and multivariable logistic regression were used to develop a nomogram based on the optimal radiomics signature and clinical characteristics. The performance of the radiomics signatures and the nomogram was assessed and validated in the validation set.

Results

Compared to the RF and SVM classifiers, the LASSO classifier had the best capacity for muscle invasive status differentiation in both the training (accuracy: 90.7%, AUC: 0.934) and validation sets (accuracy: 87.5%, AUC: 0.906). Incorporating the radiomics signature and VI-RADS score, the nomogram demonstrated better discrimination and calibration both in the training set (accuracy: 93.0%, AUC: 0.970) and validation set (accuracy: 89.3%, AUC: 0.943). Decision curve analysis showed the clinical usefulness of the nomogram.

Conclusions

The mpMRI radiomics signature may be useful for the preoperative differentiation of muscle-invasive status in BCa. The proposed nomogram integrating the radiomics signature with the VI-RADS score may further increase the differentiation power and improve clinical decision making.
Identification of a Prognostic Clinical Score for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Treated With Systemic Therapy Including Cetuximab
Authors: Pogorzelski Michael , Hilser Thomas , Ting Saskia C. , Kansy Benjamin , Gauler Thomas C. , Stuschke Martin , Schmid Kurt W. , Lang Stephan , Grünwald Viktor , Schuler Martin , Kasper Stefan
Published: May 2021

Cetuximab-based chemoimmunotherapy has been the standard of care for recurrent or metastatic squamous cell carcinoma of the head and neck (r/m SCCHN) for more than a decade. To date, no predictive or prognostic biomarkers have been established to further guide the systemic treatment with cetuximab-based chemoimmunotherapy in r/m SCCHN. Against this background, we retrospectively analyzed clinical and blood-based parameters from 218 r/m SCCHN patients treated with chemoimmunotherapy including cetuximab. Multivariate Cox-regression models were used to assess their prognostic or predictive value. Eastern Co-operative Oncology Group (ECOG) performance status (≥2), older age (≥61.8 years), anemia (hemoglobin <11.80), and increased neutrophil-to-lymphocyte ratio (NLR ≥5.73) were independently and strongly associated with inferior overall survival (OS). To group patients according to risk profiles we established a prognostic clinical score (PCS) that can easily be used in clinical practice. The PCS stratified the cohort into low, intermediate, poor or very poor risk subgroups with median OS times of 23.4, 12.1, 7.5, and 4.0 months, respectively. Patients with low risk PCS had a prolonged progression-free survival (PFS) and increased overall response rate (ORR) under first-line cetuximab-based therapy. Interestingly, only patients with low and intermediate risk benefitted from the more intensive first-line cisplatin/cetuximab combination compared to carboplatin/cetuximab therapy, whereas the intensity of first-line treatment had no impact in the poor and very poor risk subgroups. Following external validation, particularly in the context of newly established first-line options, the PCS may guide clinical decision making and serve for stratification of patients with r/m SCCHN in future clinical trials.
Role of Cardiac Imaging in the Diagnosis of Immune Checkpoints Inhibitors Related Myocarditis
Authors: Ederhy Stéphane , Salem Joe-Elie , Dercle Laurent , Hasan Abrar Saqif , Chauvet-Droit Marion , Nhan Pascal , Ammari Samy , Pinna Bruno , Redheuil Alban , Boussouar Samia , Champiat Stephane , Soulat-Dufour Laurie , Cohen Ariel
Published: May 2021

Immune checkpoint inhibitors (ICI) have constituted a paradigm shift in the management of patients with cancer. Their administration is associated with a new spectrum of immune-related toxicities that can affect any organ. In patients treated with ICI, cardiovascular toxicities, particularly myocarditis, occur with a low incidence (<1%) but with a high fatality rate (30−50%). ICI-related myocarditis has been attributed to an immune infiltration, comprising of T-cells that are positive for CD3+, CD4+, CD8+, and macrophages that are positive for CD68. The diagnosis remains challenging and is made based on clinical syndrome, an electrocardiogram (ECG), biomarker data, and imaging criteria. In most clinical scenarios, endomyocardial biopsy plays a pivotal role in diagnosis, while cardiac magnetic resonance imaging (cMRI) has limitations that should be acknowledged. In this review, we discuss the role of medical imaging in optimizing the management of ICI related myocarditis, including diagnosis, prognostication, and treatment decisions.
Proteolysis Targeting Chimeras for BTK Efficiently Inhibit B-Cell Receptor Signaling and Can Overcome Ibrutinib Resistance in CLL Cells
Authors: Shorer Arbel Yamit , Katz Ben-Zion , Gabizon Ronen , Shraga Amit , Bronstein Yotam , Kamdjou Talia , Globerson Levin Anat , Perry Chava , Avivi Irit , London Nir , Herishanu Yair
Published: May 2021

Proteolysis targeting chimeras (PROTACs) are small molecules that form ternary complexes between their target and E3 ligase, resulting in ubiquitination and proteasomal degradation of the target protein. Using our own designed Bruton’s tyrosine kinase (BTK) PROTAC compounds, we show herein efficient BTK degradation in chronic lymphocytic leukemia (CLL) cells. The reversible non-covalent compound (NC-1) was the most potent and therefore we focused on this PROTAC to investigate its subsequent effects on the BCR pathway. NC-1 decreased baseline BTK phosphorylation as well as activation of BTK and other signaling molecules downstream of the BCR pathway, following IgM engagement. These effects were also obtained in samples from CLL patients with clinical resistance to ibrutinib and mutations at C481. NC-1 treatment further decreased baseline CD69 surface levels, completely abrogated its upregulation following IgM activation, decreased CLL cells migration toward SDF-1 and overcame stromal anti-apoptotic protection. In conclusion, our results indicate that targeting BTK using the PROTAC strategy could be a potential novel therapeutic approach for CLL.
RETRACTED: Long Noncoding RNA SNHG1 Activates Autophagy and Promotes Cell Invasion in Bladder Cancer
Authors: Guo Changcheng , Li Xin , Xie Jinbo , Liu Dan , Geng Jiang , Ye Lin , Yan Yang , Yao Xudong , Luo Ming
Published: May 2021

LncRNAs play important roles in bladder cancer. However, only a few studies report on the correlation between lncRNAs expression and autophagy in bladder cancer. This study aimed to explore the effect of lncRNA on autophagy in bladder cancer. The findings showed high expression of SNHG1 in the bladder cancer cells and tumor tissues. The high expression of SNHG1 was positively correlated with bladder cancer cell invasion, proliferation, and autophagy. This finding implies that SNHG1 promotes bladder cancer cell invasion and proliferation via autophagy. Further analysis of the mechanism of action of SNHG1 showed that it functions as a sponge of miRNA-493 in bladder cancer. miRNA-493 binds on the 3’ -UTR of ATG14 mRNA thus affecting ATG14 protein expression, which is implicated in autophagy. These findings are supported by previous preclinical studies using multiple Bca cell lines and TCGA, which demonstrate that SNHG1 plays an oncogenic role by acting as a sponge of miR-493-5p or as its ceRNA. Upregulation of SNHG1 promotes proliferation, invasion, and autophagy of bladder cancer cells through the miR-493-5p/ATG14/autophagy pathway. Therefore, SNHG1 may act as a potential therapeutic target for the treatment of bladder cancer.
Carnosol Is a Novel Inhibitor of p300 Acetyltransferase in Breast Cancer
Authors: Alsamri Halima , Hasasna Hussain El , Baby Bincy , Alneyadi Aysha , Dhaheri Yusra Al , Ayoub Mohammed Akli , Eid Ali H. , Vijayan Ranjit , Iratni Rabah
Published: May 2021

Carnosol, a natural polyphenol abundant in edible plants such as sage, rosemary, and oregano, has shown promising anticancer activity against various types of cancers. Nonetheless, very little is known about its molecular mechanism of action or its downstream target(s). We have previously shown that carnosol inhibits cellular proliferation, migration, invasion, and metastasis as well as triggers autophagy and apoptosis in the highly invasive MDA-MB-231 breast cancer cells. Here, we report that carnosol induces histone hypoacetylation in MDA-MB-231 and Hs578T breast cancer cells. We show that, while carnosol does not affect HDACs, it promotes a ROS-dependent proteasome degradation of p300 and PCAF histone acetyl transferases (HATs) without affecting other HATs such as GCN5 and hMOF. Carnosol-induced histone hypoacetylation remains persistent even when p300 and PCAF protein levels were rescued from degradation by (i) the inhibition of the proteasome activity by the proteasome inhibitors MG-132 and bortezomib, and (ii) the inhibition of ROS accumulation by the ROS scavenger, N-acetylcysteine. In addition, we report that, in a cell-free system, carnosol efficiently inhibits histone acetyltransferase activity of recombinant p300 but not that of PCAF or GCN5. Molecular docking studies reveal that carnosol inhibits p300 HAT activity by blocking the entry of the acetyl-CoA binding pocket of the catalytic domain. The superimposition of the docked conformation of the p300 HAT domain in complex with carnosol shows a similar orientation as the p300 structure with acetyl-CoA. Carnosol occupies the region where the pantetheine arm of the acetyl-CoA is bound. This study further confirms carnosol as a promising anti-breast cancer therapeutic compound and identifies it as a novel natural p300 inhibitor that could be added to the existing panel of inhibitors.
Serum hsa_tsr016141 as a Kind of tRNA-Derived Fragments Is a Novel Biomarker in Gastric Cancer
Authors: Gu Xinliang , Ma Shuo , Liang Bo , Ju Shaoqing
Published: May 2021

Background

Gastric cancer (GC) is one of the most common malignant tumors globally and the third leading cause of cancer-related death. Currently, the sensitivity and specificity of diagnostic markers for GC are low, so it is urgent to find new biomarkers with higher sensitivity and specificity. tRNA-derived small RNAs are a kind of small non-coding RNAs derived from tRNAs. It is abundant in cancer cells and body fluids. Our goal is to find the differentially expressed tRNA-derived small RNAs in GC to explore their potential as a GC biomarker.

Methods

Quantitative real-time PCR was used to detect the expression level of hsa_tsr016141. The molecular characteristics of hsa_tsr016141 were verified by agarose gel electrophoresis, Sanger sequencing, Actinomycin D Assay, and Nuclear and Cytoplasmic RNA Separation Assay. The diagnostic efficiency of hsa_tsr016141 was analyzed through receiver operating characteristic.

Results

The expression level of hsa_tsr016141 in GC tissues and serum was significantly increased. The serum expression level showed a gradient change between GC patients, gastritis patients, and healthy donors and was positively correlated with the degree of lymph node metastasis and tumor grade. ROC analysis showed that the serum expression level of hsa_tsr016141 could significantly distinguish GC patients from healthy donors or gastritis patients. Besides, the expression level of hsa_tsr016141 in GC patients decreased significantly after the operation (P<0.0001).

Conclusions

Serum hsa_tsr016141 has good stability and specificity and can be used for dynamic monitoring of GC patients, suggesting that serum hsa_tsr016141 can be a novel biomarker for GC diagnosis and postoperative monitoring.
Repurposing Infectious Diseases Vaccines Against Cancer
Authors: Vandeborne Liese , Pantziarka Pan , Van Nuffel An M. T. , Bouche Gauthier
Published: May 2021

Vaccines used to prevent infections have long been known to stimulate immune responses to cancer as illustrated by the approval of the Bacillus Calmette–Guérin (BCG) vaccine to treat bladder cancer since the 1970s. The recent approval of immunotherapies has rejuvenated this research area with reports of anti-tumor responses with existing infectious diseases vaccines used as such, either alone or in combination with immune checkpoint inhibitors. Here, we have reviewed and summarized research activities using approved vaccines to treat cancer. Data supporting a cancer therapeutic use was found for 16 vaccines. For 10 (BCG, diphtheria, tetanus, human papillomavirus, influenza, measles, pneumococcus, smallpox, typhoid and varicella-zoster), clinical trials have been conducted or are ongoing. Within the remaining 6, preclinical evidence supports further evaluation of the rotavirus, yellow fever and pertussis vaccine in carefully designed clinical trials. The mechanistic evidence for the cholera vaccine, combined with the observational data in colorectal cancer, is also supportive of clinical translation. There is limited data for the hepatitis B and mumps vaccine (without measles vaccine). Four findings are worth highlighting: the superiority of intravesical typhoid vaccine instillations over BCG in a preclinical bladder cancer model, which is now the subject of a phase I trial; the perioperative use of the influenza vaccine to limit and prevent the natural killer cell dysfunction induced by cancer surgery; objective responses following intratumoral injections of measles vaccine in cutaneous T-cell lymphoma; objective responses induced by human papillomavirus vaccine in cutaneous squamous cell carcinoma. All vaccines are intended to induce or improve an anti-tumor (immune) response. In addition to the biological and immunological mechanisms that vary between vaccines, the mode of administration and sequence with other (immuno-)therapies warrant more attention in future research.
Concurrent Empirical Magnetic Reconstruction of Storm and Substorm Spatial Scales Using Data Mining and Virtual Spacecraft
Authors: Stephens Grant K. , Sitnov Mikhail I.
Published: May 2021

Data mining (DM) has ushered in a new era of empirical magnetic reconstructions of the magnetosphere via application of the k-nearest neighbors (kNN) method. In this approach, the combined magnetosphere storm-substorm state is characterized by the Sym-H and AL indices, their time derivatives, and the solar wind electric field vBzIMF. However, using the DM reconstructions to account for the substorm contributions to the ring current as well as describing storm-time substorms remains a problem. The inner region r ≤ 12RE, where the ring current develops, has a much higher density of data than the tail region 12RE ≤ r ≤ 22RE, where substorms operate. This results in two models inconsistent in their scales dictated by the corresponding data densities. The inner model reconstructs storm time dynamics, including the formation of the westward and eastward ring current and pressure distributions. The outer model captures substorm features, including the thinning and rapid dipolarization of the tail sheet during the growth and expansion phases, respectively. However, the substorm model is insufficient to reconstruct the eastward ring current while the storm model cannot fully reproduce substorm effects because it overfits in the tail region. This issue is addressed by constructing a hybrid model which is fit using virtual magnetic field observations generated by sampling the other two models. The resulting merged resolution model concurrently captures the spatial scales associated with both storms in the inner region and substorms in the near-tail region. Hence it is particularly useful for investigation of the storm-substorm relationship, including storm-time substorms and the impact of individual substorm injections to the buildup of the storm-time ring current.
Ligand-Free BaF2: Nd Nanoparticles With Low Cytotoxicity, High Stability and Enhanced Fluorescence Intensity as NIR-II Imaging Probes
Authors: Cui Xiaoxia , Xu Yantao , She Shengfei , Xiao Xusheng , Hou Chaoqi , Guo Haitao
Published: May 2021

Ligand-free BaF2:Nd nanoparticles (NPs) with a size of 10 nm were fabricated by a novel synthetic route in the liquid phase. A transparent dispersion of the BaF2:Nd NPs mixed with propanetriol and DMSO-d6 was done. Highly stable and outstanding near-infrared (NIR) fluorescence centered at 1,058 nm was detected using an excitation wavelength of 808 nm laser. Moreover, the dispersion can be found to be stable for over 1 month, and the cytotoxicity of the BaF2:Nd NP dispersion has also been studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The superior performance of these NPs exhibits their great potential application in high-contrast and high-penetration in vivo imaging.
Effect of F-Actin Organization in Lamellipodium on Viscoelasticity and Migration of Huh-7 Cells Under pH Microenvironments Using AM-FM Atomic Force Microscopy
Authors: Chen Miao , Zhu Wenpeng , Liang Zhihua , Yao Songyou , Zhang Xiaoyue , Zheng Yue
Published: May 2021

Cytoskeleton is responsible for fundamental cellular processes and functions. The filamentous actin (F-actin) is a key constituent of the cytoskeleton system which is intrinsically viscoelastic and greatly determines the mechanical properties of cells. The organization and polymerization of F-actin are relevant to the viscoelasticity distribution and the migration of living cells responding to pH microenvironments. Recently, progression in various diseases such as cancers have been found that cellular migration is related to the alterations in the viscoelasticity of lamellipodium. However, the correlation among F-actin organization, viscoelastic properties and cellular migration of living cancer cells under different pH microenvironments are still poorly understood. Conventional experimental methods of optical microscopy and atomic force microscopy (AFM) can neither break the trade-off between resolution and rate in cytoskeleton imaging, nor achieve the structural characterization and the mechanical measurement simultaneously. Although multifrequency AFM with amplitude modulation-frequency modulation (AM–FM) enables us to probe both the surface topography and the viscoelasticity distribution of cells, it is difficult to image the cytoskeletal filaments with the diameter down to the scale of tens of nanometers. Here, we have improved the AM-FM AFM by employing the high damping of cell culture medium to increase the signal-to-noise ratio and achieve a stable imaging of F-actin with the resolution down to 50 nm underin situmicroenvironment. The approach that can successfully visualize the structures of cytoskeletal filaments and measure the distribution of mechanical properties simultaneously enable us to understand the relationship between the organization of F-actin and the viscoelasticity of living Huh-7 cancer cells under different pH values. Our experimental results have demonstrated that, unlike the randomly distributed F-actin and the homogeneous viscoelasticity at the normal pH level of 7.4, the living Huh-7 cancer cells with the reduced pH level of 6.5 show highly oriented and organized F-actin along the lamellipodium direction associated with the significant gradient increase both in elasticity and viscosity, which are confirmed by immunofluorescence confocal microscopy. The F-actin organization and the gradient viscoelasticity of lamellipodium provide structural and mechanical understanding on the adhesion and migration of living cancer cells that undergo metastasis and malignant transformation.
Autophagy Controls Nrf2-Mediated Dichotomy in Pressure Overloaded Hearts
Authors: Wu Weiwei , Qin Qingyun , Ding Yan , Zang Huimei , Li Dong-Sheng , Nagarkatti Mitzi , Nagarkatti Prakash , Wang Wenjuan , Wang Xuejun , Cui Taixing
Published: May 2021

Burgeoning evidence has indicated that normal autophagy is required for nuclear factor erythroid 2-related factor (Nrf2)-mediated cardiac protection whereas autophagy inhibition turns on Nrf2-mediated myocardial damage and dysfunction in a setting of pressure overload (PO). However, such a concept remains to be fully established by a careful genetic interrogation in vivo. This study was designed to validate the hypothesis using a mouse model of PO-induced cardiomyopathy and heart failure, in which cardiac autophagy and/or Nrf2 activity are genetically inhibited. Myocardial autophagy inhibition was induced by cardiomyocyte-restricted (CR) knockout (KO) of autophagy related (Atg) 5 (CR-Atg5KO) in adult mice. CR-Atg5KO impaired cardiac adaptations while exacerbating cardiac maladaptive responses in the setting of PO. Notably, it also turned off Nrf2-mediated defense while switching on Nrf2-operated tissue damage in PO hearts. In addition, cardiac autophagy inhibition selectively inactivated extracellular signal regulated kinase (ERK), which coincided with increased nuclear accumulation of Nrf2 and decreased nuclear translocation of activated ERK in cardiomyocytes in PO hearts. Mechanistic investigation revealed that autophagy is required for the activation of ERK, which suppresses Nrf2-driven expression of angiotensinogen in cardiomyocytes. Taken together, these results provide direct evidence consolidating the notion that normal autophagy enables Nrf2-operated adaptation while switching off Nrf2-mediated maladaptive responses in PO hearts partly through suppressing Nrf2-driven angiotensinogen expression in cardiomyocytes.
“Psyosphere”: A GPS Data-Analysing Tool for the Behavioural Sciences
Authors: Ziepert Benjamin , de Vries Peter W. , Ufkes Elze
Published: May 2021

Positioning technologies, such as GPS are widespread in society but are used only sparingly in behavioural science research, e.g., because processing positioning technology data can be cumbersome. The current work attempts to unlock positioning technology potential for behavioural science studies by developing and testing a research tool to analyse GPS tracks. This tool—psyosphere—is published as open-source software, and aims to extract behaviours from GPSs data that are more germane to behavioural research. Two field experiments were conducted to test application of the research tool. During these experiments, participants played a smuggling game, thereby either smuggling tokens representing illicit material past border guards or not. Results suggested that participants varied widely in variables, such as course and speed variability and distance from team members in response to the presence of border guards. Subsequent analyses showed that some of these GPS-derived behavioural variables could be linked to self-reported mental states, such as fear. Although more work needs to be done, the current study demonstrates that psyosphere may enable researchers to conduct behavioural experiments with positioning technology, outside of a laboratory setting.
Can Optic Flow Further Stimulate Treadmill-Elicited Stepping in Newborns?
Authors: Barbu-Roth Marianne , Siekerman Kim , Anderson David I. , Donnelly Alan , Huet Viviane , Goffinet François , Teulier Caroline
Published: May 2021

Typically developing 3-day-old newborns take significantly more forward steps on a moving treadmill belt than on a static belt. The current experiment examined whether projecting optic flows that specified forward motion onto the moving treadmill surface (black dots moving on the white treadmill surface) would further enhance forward stepping. Twenty newborns were supported on a moving treadmill without optic flow (No OF), with optic flow matching the treadmill’s direction and speed (Congruent), with optic flow in the same direction but at a faster speed (Faster), and in a control condition with an incoherent optic flow moving at the same speed as in the Congruent condition but in random directions (Random). The results revealed no significant differences in the number or coordination of forward treadmill steps taken in each condition. However, the Faster condition generated significantly fewer leg pumping movements than the Random control condition. When highly aroused, newborns made significantly fewer single steps and significantly more parallel steps and pumping movements. We speculate the null findings may be a function of the high friction material that covered the treadmill surface.
Network-Based Online Survey Exploring Self-Reported Depression Among University and College Students During the Early Days of the COVID-19 Outbreak
Authors: Jing Yurong , Han Wantong , Wang Yali , Zhang Jiao , Qin Wenzhe , Jing Xiang , Niu Aimin , Xu Lingzhong
Published: May 2021

Background: The psychology of university and college students is immature, they are thus more likely to suffer from depression due to the COVID-19 pandemic. The present study aims to investigate the self-reported depression status of Chinese university and college students and explore its influencing factors.

Methods: We conducted a network-based online survey, and a total of 17,876 participants completed the questionnaire. Depression was measured by the Self-Rating Depression Scale (SDS). Univariate analysis and multivariate logistic analysis were performed to explore the influencing factors of self-reported depression symptoms.

Results: The proportion of self-reported depression symptoms, mild self-reported depression symptoms, and moderate to severe (M/S) self-reported depression symptoms was 65.2, 53.7, and 11.5%, respectively. The mean score of self-reported depression was 54.8 ± 9.0. Female, personality type of partial introversion, junior college educational level, “moderate” or “high” self-perceived risk of infection, “moderately” or “highly” impacted by the outbreak, and being eager to go back to school were risk factors for M/S self-reported depression symptoms (p < 0.05). While, “moderate” or “high” concern about the outbreak, “moderate” or “high” satisfaction with pandemic prevention and control measures, and having health literacy on communicable diseases were protective factors for M/S self-reported depression symptoms (p < 0.05).

Conclusion: The status of self-reported depression symptoms among university and college students was severer than expected, and the influencing factors were multifaceted. Government and school administrators should strengthen the dissemination of knowledge on disease prevention and control. Moreover, much attention should be paid to female and junior college students.
Applying Genomic Epidemiology to Characterize a COVID-19 Outbreak in a Developmentally Disabled Adult Group Home Setting, Arizona
Authors: Yaglom Hayley D. , Gebhardt Marette , Pfeiffer Ashlyn , Ormsby Mary Ellen , Jasso-Selles Daniel E. , Lemmer Darrin , Folkerts Megan L. , French Chris , Maurer Matthew , Bowers Jolene R. , Engelthaler David M.
Published: May 2021

Individuals living in congregate settings, including those in group homes, have been disproportionately impacted by COVID-19 and may be at increased risk of exposure or infection due to underlying illness. In mid-May 2020, local public health officials responded to an outbreak of COVID-19 among staff and residents associated with a multi-residential group home that provides care for adults with intellectual and developmental disabilities. Samples were collected at 16 of the homes. In four of the homes all the residents tested positive, and in the remaining 12 houses where samples were collected, all residents tested negative. Of the 152 individuals tested, 15/58 (25.9%) residents and 27/94 (28.7%) staff were positive for SARS-CoV-2, including eight hospitalizations and four deaths. Phylogenetic analysis of genomes from this outbreak in the context of genomes from Northern Arizona shows that very few mutations separate the samples from this outbreak. A potential transmission network was developed to illustrate person-place epidemiologic linkages and further demonstrates the dynamic connections between staff and residents with respect to each group home location. Epidemiologic and genomic evidence correlate, and suggest that asymptomatic infected staff likely introduced and spread COVID-19 in this setting. Implementation of public health prevention measures alongside rapid genomic analysis can help guide policy development and guide management efforts to prevent and mitigate future outbreaks.
Chatbots as a Tool to Scale Mentoring Processes: Individually Supporting Self-Study in Higher Education
Authors: Neumann Alexander Tobias , Arndt Tamar , Köbis Laura , Meissner Roy , Martin Anne , de Lange Peter , Pengel Norbert , Klamma Ralf , Wollersheim Heinz-Werner
Published: May 2021

Like most curricula in the humanities and social sciences, the curriculum of pre-service teacher training in educational sciences often includes time-consuming reading and writing tasks, which require high quality support and feedback in a timely manner. A well-known way to provide this support to students is one-to-one mentoring. However, limited time and resources in the German university context require to effectively scale the benefits of individual feedback. The use of scalable technologies to support learning processes seems to be promising, but its development usually requires a deep technical understanding. With an interdisciplinary approach, this contribution investigates how personal mentoring can be made available to as many students as possible, taking into account the didactic, organizational and technical frameworks at universities. We describe the development and implementation process of two chatbots that both aim to support students of educational sciences in their self-study of the seminar topics and literature. The chatbots were used by over 700 students during the course of 1 year and our evaluations show promising results that bear the potential to improve the availability of digital mentoring support for all students.
Similarities and Differences in Gene Expression Networks Between the Breast Cancer Cell Line Michigan Cancer Foundation-7 and Invasive Human Breast Cancer Tissues
Authors: Tran Vy , Kim Robert , Maertens Mikhail , Hartung Thomas , Maertens Alexandra
Published: May 2021

Failure to adequately characterize cell lines, and understand the differences between in vitro and in vivo biology, can have serious consequences on the translatability of in vitro scientific studies to human clinical trials. This project focuses on the Michigan Cancer Foundation-7 (MCF-7) cells, a human breast adenocarcinoma cell line that is commonly used for in vitro cancer research, with over 42,000 publications in PubMed. In this study, we explore the key similarities and differences in gene expression networks of MCF-7 cell lines compared to human breast cancer tissues. We used two MCF-7 data sets, one data set collected by ARCHS4 including 1032 samples and one data set from Gene Expression Omnibus GSE50705 with 88 estradiol-treated MCF-7 samples. The human breast invasive ductal carcinoma (BRCA) data set came from The Cancer Genome Atlas, including 1212 breast tissue samples. Weighted Gene Correlation Network Analysis (WGCNA) and functional annotations of the data showed that MCF-7 cells and human breast tissues have only minimal similarity in biological processes, although some fundamental functions, such as cell cycle, are conserved. Scaled connectivity—a network topology metric—also showed drastic differences in the behavior of genes between MCF-7 and BRCA data sets. Finally, we used canSAR to compute ligand-based druggability scores of genes in the data sets, and our results suggested that using MCF-7 to study breast cancer may lead to missing important gene targets. Our comparison of the networks of MCF-7 and human breast cancer highlights the nuances of using MCF-7 to study human breast cancer and can contribute to better experimental design and result interpretation of study involving this cell line.
Comparing CxBladder to Urine Cytology as Adjunct to Cystoscopy in Surveillance of Non-muscle Invasive Bladder Cancer—A Pilot Study
Authors: Chai C. A. , Yeoh W. S. , Rajandram R. , Aung K. P. , Ong T. A. , Kuppusamy S. , Nazran A. , Kumaran K. , Razack A. H. A. , Teoh J. Y.
Published: May 2021

Purpose: Guidelines advocate cystoscopy surveillance (CS) for non-muscle invasive bladder cancer (NMIBC) post-resection. However, cystoscopy is operator dependent and may miss upper tract lesions or carcinoma in-situ (CIS). Urine cytology is a common adjunct but lacks sensitivity and specificity in detecting recurrence. A new mRNA biomarker (CxBladder) was compared with urine cytology as an adjunct to cystoscopy in detecting a positive cystoscopy findings during surveillance cystoscopy in our center.

Materials and Methods: Consented patients older than 18, undergoing CS for NMIBC, provide paired urine samples for cytology and CxBladder test. Patients with positive cystoscopy findings would undergo re-Trans Urethral Resection of Bladder Tumor (TURBT).

Results: Thirty-five patients were enrolled from April to June 2019. Seven contaminated urine samples were excluded. The remaining cohort of 23 (82%) and 5 (18%) females had a mean age of 66.69 (36–89). Eight (29%) patients with positive cystoscopy finding underwent TURBT. All 8 patients also had positive CxBladder result. This shows that CxBladder has a sensitivity and negative predictive value (NPV) of 100%, specificity of 75% and positive predictive value (PPV) of 62% in predicting a positive cystoscopy finding. TURBT Histo-pathological findings showed Low-grade Ta NMIBC in one patient (4%), and 7 (25%) patients had inflammatory changes. Urine cytology was only positive in one patient with a positive cystoscopy finding. This led to a sensitivity of merely 13% and NPV of 74%, while specificity and PPV was 100% in predicting a positive cystoscopy finding.

Conclusion: CxBladder had high NPV and sensitivity which accurately predicted suspicious cystoscopy findings leading to further investigation. It has great potential for use as adjunct to cystoscopy for surveillance of NMIBC.
Crosstalk between Peroxisomal Activities and Nrf2 Signaling in Porcine Embryos
Authors: Kim Eui-Hyun , Ridlo Muhammad-Rosyid , Lee Byeong-Chun , Kim Geon A.
Published: May 2021

Melatonin and phytanic acid (PA) are known to be involved in lipid metabolism and β-oxidation, in which peroxisomal activities also significantly participate. In addition, other studies have reported that the nuclear factor-erythroid-derived 2-like 2 (Nrf2 or NFE2L2) signaling pathway mediates lipid metabolism and its subsequent cascades. As these mechanisms are partially involved in porcine oocytes or embryonic development, we hypothesized that the factors governing these mechanisms could be interconnected. Therefore, we aimed to investigate possible crosstalk between peroxisomal activities and Nrf2 signaling in porcine embryos following melatonin and PA treatment. Porcine embryos were cultured for seven days after parthenogenetic activation, and subsequently treated with melatonin and PA, or injected with Pex19-targeted siRNAs. Real-time PCR, immunocytochemistry, and BODIPY staining were used to evaluate peroxisomal activities, Nrf2 signaling, and subsequent lipid metabolism. We found that melatonin/PA treatment enhanced embryonic development, whereas injection with Pex19-targeted siRNAs had the opposite effect. Moreover, melatonin/PA treatment upregulated peroxisomal activities, Nrf2 signaling, lipid metabolism, and mitochondrial membrane potentials, whereas most of these mechanisms were downregulated by Pex19-targeted siRNAs. Therefore, we suggest that there is a connection between the action of melatonin and PA and the Nrf2 signaling pathway and peroxisomal activities, which positively influences porcine embryonic development.
Plant Extracts as Alternative Additives for Sperm Preservation
Authors: Ros-Santaella José Luis , Pintus Eliana
Published: May 2021

Sperm preservation is a crucial factor for the success of assisted reproductive technology (ART) in humans, livestock, and wildlife. Irrespective of the extender and the storage conditions used, semen handling and preservation negatively affect sperm quality. Moreover, oxidative stress, which often arises during semen storage, significantly reduces sperm function and compromises the sperm fertilizing ability by inducing oxidative damage to proteins, lipids, and nucleic acids. Plant extracts have recently emerged as a cheap and natural source of additives to preserve and enhance sperm function during semen storage. The present work provides an update on the use of these natural compounds as alternative additives for sperm preservation in 13 animal species, including humans. A detailed description of the effects of 45 plant species, belonging to 28 families, on sperm function during semen storage is presented. The plant material and extraction method employed, dosage, possible toxic effects, and antimicrobial properties are provided.