bluuebunny/crossref_metadata_2025 huggingface dataset:
Transmembrane serine protease 2 Polymorphisms and Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Type 2 Infection: A German Case-Control Study
Authors: Schönfelder Kristina , Breuckmann Katharina , Elsner Carina , Dittmer Ulf , Fistera David , Herbstreit Frank , Risse Joachim , Schmidt Karsten , Sutharsan Sivagurunathan , Taube Christian , Jöckel Karl-Heinz , Siffert Winfried , Kribben Andreas , Möhlendick Birte
Published: April 2021

The transmembrane serine protease 2 (TMPRSS2) is the major host protease that enables entry of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) into host cells by spike (S) protein priming. Single nucleotide polymorphisms (SNPs) in the gene TMPRSS2 have been associated with susceptibility to and severity of H1N1 or H1N9 influenza A virus infections. Functional variants may influence SARS-CoV-2 infection risk and severity of Coronavirus disease 2019 (COVID-19) as well. Therefore, we analyzed the role of SNPs in the gene TMPRSS2 in a German case-control study. We performed genotyping of the SNPs rs2070788, rs383510, and rs12329760 in the gene TMPRSS2 in 239 SARS-CoV-2-positive and 253 SARS-CoV-2-negative patients. We analyzed the association of the SNPs with susceptibility to SARS-CoV-2 infection and severity of COVID-19. SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding their demographics. The CC genotype of TMPRSS2 rs383510 was associated with a 1.73-fold increased SARS-CoV-2 infection risk, but was not correlated to severity of COVID-19. Neither TMPRSS2 rs2070788 nor rs12329760 polymorphisms were related to SARS-CoV-2 infection risk or severity of COVID-19. In a multivariable analysis (MVA), the rs383510 CC genotype remained an independent predictor for a 2-fold increased SARS-CoV-2 infection risk. In summary, our report appears to be the first showing that the intron variant rs383510 in the gene TMPRSS2 is associated with an increased risk to SARS-CoV-2 infection in a German cohort.
Viral–Host Interactome Analysis Reveals Chicken STAU2 Interacts With Non-structural Protein 1 and Promotes the Replication of H5N1 Avian Influenza Virus
Authors: Wang Qiao , Zhang Qi , Zheng Maiqing , Wen Jie , Li Qinghe , Zhao Guiping
Published: April 2021

As a highly pathogenic influenza virus, H5N1 avian influenza virus (AIV) poses a great threat to poultry production and public health. H5N1 AIV has a small genome and, therefore, relies heavily on its host cellular machinery to replicate. To develop a comprehensive understanding of how H5N1 AIV rewires host cellular machinery during the course of infection, it is crucial to identify which host proteins and complexes come into physical contact with the viral proteins. Here, we utilized affinity purification mass spectrometry (AP-MS) to systematically determine the physical interactions of 11 H5N1 AIV proteins with host proteins in chicken DF1 cells. We identified with high confidence 1,043 H5N1 AIV–chicken interactions involving 621 individual chicken proteins and uncovered a number of host proteins and complexes that were targeted by the viral proteins. Specifically, we revealed that chicken Staufen double-stranded RNA-binding protein 2 interacts with AIV non-structural protein 1 (NS1) and promotes the replication of the virus by enhancing the nuclear export of NS1 mRNA. This dataset facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of H5N1 AIV infection.
Reprogramming Immune Cells for Enhanced Cancer Immunotherapy: Targets and Strategies
Authors: Dong Yan , Wan Zhuo , Gao Xiaotong , Yang Guodong , Liu Li
Published: April 2021

Cancer is one of the leading causes of death and a major public health problem all over the world. Immunotherapy is becoming a revolutionary clinical management for various cancer types. Restoration of aberrant immune surveillance on cancers has achieved markable progress in the past years by eitherin vivoorex vivoengineering of the immune cells. Here, we summarized the central roles of immune cells in tumor progression and regression, and the existing and emerging strategies for different immune cell-based immunotherapies. In addition, the current challenges and the potential solutions in translating the immunotherapies into the clinic are also discussed.
Resource Occurrence and Productivity in Existing and Proposed Wind Energy Lease Areas on the Northeast US Shelf
Authors: Friedland Kevin D. , Methratta Elizabeth T. , Gill Andrew B. , Gaichas Sarah K. , Curtis Tobey H. , Adams Evan M. , Morano Janelle L. , Crear Daniel P. , McManus M. Conor , Brady Damian C.
Published: April 2021

States in the Northeast United States have the ambitious goal of producing more than 22 GW of offshore wind energy in the coming decades. The infrastructure associated with offshore wind energy development is expected to modify marine habitats and potentially alter the ecosystem services. Species distribution models were constructed for a group of fish and macroinvertebrate taxa resident in the Northeast US Continental Shelf marine ecosystem. These models were analyzed to provide baseline context for impact assessment of lease areas in the Middle Atlantic Bight designated for renewable wind energy installations. Using random forest machine learning, models based on occurrence and biomass were constructed for 93 species providing seasonal depictions of their habitat distributions. We developed a scoring index to characterize lease area habitat use for each species. Subsequently, groups of species were identified that reflect varying levels of lease area habitat use ranging across high, moderate, low, and no reliance on the lease area habitats. Among the species with high to moderate reliance were black sea bass (Centropristis striata), summer flounder (Paralichthys dentatus), and Atlantic menhaden (Brevoortia tyrannus), which are important fisheries species in the region. Potential for impact was characterized by the number of species with habitat dependencies associated with lease areas and these varied with a number of continuous gradients. Habitats that support high biomass were distributed more to the northeast, while high occupancy habitats appeared to be further from the coast. There was no obvious effect of the size of the lease area on the importance of associated habitats. Model results indicated that physical drivers and lower trophic level indicators might strongly control the habitat distribution of ecologically and commercially important species in the wind lease areas. Therefore, physical and biological oceanography on the continental shelf proximate to wind energy infrastructure development should be monitored for changes in water column structure and the productivity of phytoplankton and zooplankton and the effects of these changes on the trophic system.
NeMO-Net – Gamifying 3D Labeling of Multi-Modal Reference Datasets to Support Automated Marine Habitat Mapping
Authors: van den Bergh Jarrett , Chirayath Ved , Li Alan , Torres-Pérez Juan L. , Segal-Rozenhaimer Michal
Published: April 2021

NASA NeMO-Net, The Neural Multimodal Observation and Training Network for global coral reef assessment, is a convolutional neural network (CNN) that generates benthic habitat maps of coral reefs and other shallow marine ecosystems. To segment and classify imagery accurately, CNNs require curated training datasets of considerable volume and accuracy. Here, we present a citizen science approach to create these training datasets through a novel 3D classification game for mobile and desktop devices. Leveraging citizen science, the NeMO-Net video game generates high-resolution 3D benthic habitat labels at the subcentimeter to meter scales. The video game trains users to accurately identify benthic categories and semantically segment 3D scenes captured using NASA airborne fluid lensing, the first remote sensing technology capable of mitigating ocean wave distortions, as well as in situ 3D photogrammetry and 2D satellite remote sensing. An active learning framework is used in the game to allow users to rate and edit other user classifications, dynamically improving segmentation accuracy. Refined and aggregated data labels from the game are used to train NeMO-Net’s supercomputer-based CNN to autonomously map shallow marine systems and augment satellite habitat mapping accuracy in these regions. We share the NeMO-Net game approach to user training and retention, outline the 3D labeling technique developed to accurately label complex coral reef imagery, and present preliminary results from over 70,000 user classifications. To overcome the inherent variability of citizen science, we analyze criteria and metrics for evaluating and filtering user data. Finally, we examine how future citizen science and machine learning approaches might benefit from label training in 3D space using an active learning framework. Within 7 months of launch, NeMO-Net has reached over 300 million people globally and directly engaged communities in coral reef mapping and conservation through ongoing scientific field campaigns, uninhibited by geography, language, or physical ability. As more user data are fed into NeMO-Net’s CNN, it will produce the first shallow-marine habitat mapping products trained on 3D subcm-scale label data and merged with m-scale satellite data that could be applied globally when data sets are available.
DHCR24 Knock-Down Induced Tau Hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, Ser396 Epitopes and Inhibition of Autophagy by Overactivation of GSK3β/mTOR Signaling
Authors: Bai Xiaojing , Wu Junfeng , Zhang Mengqi , Xu Yixuan , Duan Lijie , Yao Kai , Zhang Jianfeng , Bo Jimei , Zhao Yongfei , Xu Guoxiong , Zu Hengbing
Published: April 2021

Accumulating evidences supported that knock-down of DHCR24 is linked to the pathological risk factors of AD, suggesting a potential role of DHCR24 in AD pathogenesis. However, the molecular mechanism link between DHCR24 and tauopathy remains unknown. Here, in order to elucidate the relationship between DHCR24 and tauopathy, we will focus on the effect of DHCR24 on the tau hyperphosphorylation at some toxic sites. In present study, we found that DHCR24 knock-down significantly lead to the hyperphosphorylation of tau sites at Thr181, Ser199, Thr231, Ser262, Ser396. Moreover, DHCR24 knock-down also increase the accumulation of p62 protein, simultaneously decreased the ratio of LC3-II/LC3-I and the number of autophagosome compared to the control groups, suggesting the inhibition of autophagy activity. In contrast, DHCR24 knock-in obviously abolished the effect of DHCR24 knock-down on tau hyperphosphrylation and autophagy. In addition, to elucidate the association between DHCR24 and tauopathy, we further showed that the level of plasma membrane cholesterol, lipid raft-anchored protein caveolin-1, and concomitantly total I class PI3-K (p110α), phospho-Akt (Thr308 and Ser473) were significantly decreased, resulting in the disruption of lipid raft/caveola and inhibition of PI3-K/Akt signaling in silencing DHCR24 SH-SY5Y cells compared to control groups. At the same time, DHCR24 knock-down simultaneously decreased the level of phosphorylated GSK3β at Ser9 (inactive form) and increased the level of phosphorylated mTOR at Ser2448 (active form), leading to overactivation of GSK3β and mTOR signaling. On the contrary, DHCR24 knock-in largely increased the level of membrane cholesterol and caveolin-1, suggesting the enhancement of lipid raft/caveola. And synchronously DHCR24 knock-in also abolished the effect of DHCR24 knock-down on the inhibition of PI3-K/Akt signaling as well as the overactivation of GSK3β and mTOR signaling. Collectively, our data strongly supported DHCR24 knock-down lead to tau hyperphosphorylation and the inhibition of autophagy by a lipid raft-dependent PI3-K/Akt-mediated GSK3β and mTOR signaling. Taking together, our results firstly demonstrated that the decrease of plasma membrane cholesterol mediated by DHCR24 deficiency might contribute to the tauopathy in AD and other tauopathies.
ATP1A1 de novo Mutation-Related Disorders: Clinical and Genetic Features
Authors: Lin Zehong , Li Jinliang , Ji Taoyun , Wu Ye , Gao Kai , Jiang Yuwu
Published: April 2021

Background:ATP1A1 encodes an α1 isoform of Na+/K+-ATPase, which is expressed abundantly in kidneys and central nervous system. ATP1A1 variants may cause Na+/K+-ATPase loss of function and lead to a wide spectrum of phenotypes. This study aims to summarize the clinical and genetic features of ATP1A1 de novo mutation-related disorders and explore the potential correlations between phenotypes and genotypes.

Methods: We analyzed two new cases harboring novel de novo ATP1A1 variants and reviewed all reported cases.

Results: Both our probands had developmental delay, patient 1 accompanied with sleep disorders, irritability, and patient 2 with refractory seizures. They each had a novel de novo heterozygous missense variant, c.2797G>A[p.Asp933Asn] (NM_000701) and c.2590G>A[p.Gly864Arg] (NM_000701) respectively. Four patients with de novo ATP1A1 variants have been reported in two previous papers. Among them, three patients had refractory seizures and one patient had complex hereditary spastic paraplegia (HSP). Therefore, all six patients had developmental delay, and four of them had epilepsy. All variants located in the transmembrane regions M3, M4, M7, and M8 of ATP1A1 protein. Four patients with mutations in M3 and M7 had more severe phenotypes, including developmental delay and epileptic encephalopathy, three of them with hypomagnesemia, whereas two patients with mutations in M4 and M8 had milder phenotypes, only with mild developmental delay, without seizures or hypomagnesemia. Correcting hypomagnesemia had not controlled those seizures.

Conclusions: Two novel de novo ATP1A1 variants identified in two patients here enriched the genotypic and phenotypic spectrum of ATP1A1 mutation-related disorder. Our findings suggest that hypomagnesemia in this disorder might relate to more severe phenotype and indicate more severe Na+/K+-ATPase dysfunction. Variations in M3 and M7 transmembrane regions were related to more severe phenotype than those in M4 and M8, which suggested that variations in M3 and M7 might cause more severe ATP1A1 functional defect.
Plant Metabolites Drive Different Responses in Caterpillars of Two Closely Related Helicoverpa Species
Authors: Sun Longlong , Hou Wenhua , Zhang Jiajia , Dang Yuli , Yang Qiuyun , Zhao Xincheng , Ma Ying , Tang Qingbo
Published: April 2021

The host acceptances of insects can be determined largely by detecting plant metabolites using insect taste. In the present study, we investigated the gustatory sensitivity and feeding behaviors of two closely related caterpillars, the generalist Helicoverpa armigera (Hübner) and the specialist H. assulta (Guenée), to different plant metabolites by using the single sensillum recording technique and the dual-choice assay, aiming to explore the contribution of plant metabolites to the difference of diet breadth between the two species. The results depicted that the feeding patterns of caterpillars for both plant primary and secondary metabolites were significantly different between the two Helicoverpa species. Fructose, glucose, and proline stimulated feedings of the specialist H. assulta, while glucose and proline had no significant effect on the generalist H. armigera. Gossypol and tomatine, the secondary metabolites of host plants of the generalist H. armigera, elicited appetitive feedings of this insect species but drove aversive feedings of H. assulta. Nicotine and capsaicin elicited appetitive feedings of H. assulta, but drove aversive feedings of H. armigera. For the response of gustatory receptor neurons (GRNs) in the maxillary styloconic sensilla of caterpillars, each of the investigated primary metabolites induced similar responding patterns between the two Helicoverpa species. However, four secondary metabolites elicited different responding patterns of GRNs in the two species, which is consistent with the difference of feeding preferences to these compounds. In summary, our results of caterpillars’ performance to the plant metabolites could reflect the difference of diet breadth between the two Helicoverpa species. To our knowledge, this is the first report showing that plant secondary metabolites could drive appetitive feedings in a generalist insect species, which gives new insights of underscoring the adaptation mechanism of herbivores to host plants.
Change in Evaluation Mode Can Cause a Cheerleader Effect
Authors: Messner Claude , Carnelli Mattia , Höhener Patrick Stefan
Published: April 2021

The cheerleader effect describes the phenomenon whereby faces are perceived as being more attractive when flanked by other faces than when they are perceived in isolation. At least four theories predict the cheerleader effect. Two visual memory processes could cause a cheerleader effect. First, visual information will sometimes be averaged in the visual memory: the averaging of faces could increase the perceived attractiveness of all the faces flanked by other faces. Second, information will often be combined into a higher-order concept. This hierarchical encoding suggests that information processing causes faces to appear more attractive when flanked by highly attractive faces. Two further explanations posit that comparison processes cause the cheerleader effect. While contrast effects predict that a difference between the target face and the flanking faces causes the cheerleader effect due to comparison processes, a change in the evaluation mode, which alters the standard of comparison between joint and separate evaluation of faces, could be sufficient for producing a cheerleader effect. This leads to the prediction that even when there is no contrast between the attractiveness of the target face and the flanking faces, a cheerleader effect could occur. The results of one experiment support this prediction. The findings of this study have practical implications, such as for individuals who post selfies on social media. An individual’s face will appear more attractive in a selfie taken with people of low attractiveness than in a selfie without other people, even when all the faces have equally low levels of attractiveness.
Massive Star Modeling and Nucleosynthesis
Authors: Ekström Sylvia
Published: April 2021

After a brief introduction to stellar modeling, the main lines of massive star evolution are reviewed, with a focus on the nuclear reactions from which the star gets the needed energy to counterbalance its gravity. The different burning phases are described, as well as the structural impact they have on the star. Some general effects on stellar evolution of uncertainties in the reaction rates are presented, with more precise examples taken from the uncertainties of the 12C(α, γ)16O reaction and the sensitivity of the s-process on many rates. The changes in the evolution of massive stars brought by low or zero metallicity are reviewed. The impact of convection, rotation, mass loss, and binarity on massive star evolution is reviewed, with a focus on the effect they have on the global nucleosynthetic products of the stars.
Psychological Impact of the COVID-19 Pandemic on Athletes
Authors: Uroh Clifford C. , Adewunmi Celina M.
Published: April 2021

This study explored the influence of athletic identity and sports participation on the psychological well-being of athletes during a pandemic. The objective of the study was to understand the psychological impact of the coronavirus lockdown measure on athletes who were not able to carry out their normal daily routine. Athletes from nine different sports completed an online survey during the sixth week of the total lockdown in Nigeria. The online survey consists of an athletic identity scale and the Kessler Psychological Distress Scale (K10). Data collected were analyzed using Multiple regression and the Mann-Whitney test at 0.05 level of significance. The result of the findings revealed that category of sports (individual and team) (M = 0.73, β = −6.116) and athletic identity (M = 59.16, β = −0.166) predicts psychological distress to some degree. Few individual sports athletes and athletes with low athletic identity are prone to higher levels of psychological distress than team sports athletes and athletes with high athletic identity during the coronavirus pandemic lockdown. Individual sports athletes reported elevated levels of psychological distress compared to team sports athletes (z = −2.186, p = 0.03, r = 0.27). In conclusion, the results have confirmed that some athletes competing in individual sports experience elevated levels of psychological distress during the coronavirus pandemic, therefore they need the support of a sports psychologist during such periods to help in maintaining their psychological well-being.
COVID-19 Containment Measures at Childcare and Schools in 19 European Countries: An Observational Study on Local, Federal and National Policies
Authors: Jansen Danielle E. M. C. , Vervoort Johanna P. M. , Illy Károly E. , Hadjipanayis Adamos
Published: April 2021

Objectives: After childcare and schools have been closed in March 2020 to prevent the spread of COVID-19, they were open again in most European countries after the summer holidays till early autumn. Aim of this study is to give an overview and to compare COVID-19 childcare and school containment policies in 19 European countries.

Methods: We collected data on containment measures among delegates of the European Academy of Pediatrics (EAP), through an online, closed questionnaire in the second half of October 2020.

Results: Most policy has been formulated for secondary education. In all three settings policy was most often formulated for individual hygiene, cleaning of surfaces, exclusion of sick children, ventilation, distance between children and between children and teachers. In secondary schools, policy is formulated on face masks in and outside the class. School closure, cancellation of physical education and class size reduction are measures for which the fewest countries have formulated national policies.

Conclusion: We recommend to accompany the opening of children’s facilities and schools by surveillance studies that further clarify questions about control measures implemented to halt COVID-19 pandemic.
Electrochemotherapy in Vulvar Cancer and Cisplatin Combined with Electroporation. Systematic Review and In Vitro Studies
Authors: Perrone Anna Myriam , Ravegnini Gloria , Miglietta Stefano , Argnani Lisa , Ferioli Martina , De Crescenzo Eugenia , Tesei Marco , Di Stanislao Marco , Girolimetti Giulia , Gasparre Giuseppe , Porcelli Anna Maria , De Terlizzi Francesca , Zamagni Claudio , Morganti Alessio Giuseppe , De Iaco Pierandrea
Published: April 2021

Electrochemotherapy (ECT) is an emerging treatment for solid tumors and an attractive research field due to its clinical results. This therapy represents an alternative local treatment to the standard ones and is based on the tumor-directed delivery of non-ablative electrical pulses to maximize the action of specific cytotoxic drugs such as cisplatin (CSP) and bleomycin (BLM) and to promote cancer cell death. Nowadays, ECT is mainly recommended as palliative treatment. However, it can be applied to a wide range of superficial cancers, having an impact in preventing or delaying tumor progression and therefore in improving quality of life. In addition, during the natural history of the tumor, early ECT may improve patient outcomes. Our group has extensive clinical and research experience on ECT in vulvar tumors in the palliative setting, with 70% overall response rate. So far, in most studies, ECT was based on BLM. However, the potential of CSP in this setting seems interesting due to some theoretical advantages. The purpose of this report is to: (i) compare the efficacy of CSP and BLM-based ECT through a systematic literature review; (ii) report the results of our studies on CSP-resistant squamous cell tumors cell lines and the possibility to overcome chemoresistance using ECT; (iii) discuss the future ECT role in gynecological tumors and in particular in vulvar carcinoma.
Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML
Authors: Bertuccio Salvatore Nicola , Anselmi Laura , Masetti Riccardo , Lonetti Annalisa , Cerasi Sara , Polidori Sara , Serravalle Salvatore , Pession Andrea
Published: April 2021

Despite improvements in therapeutic protocols and in risk stratification, acute myeloid leukemia (AML) remains the leading cause of childhood leukemic mortality. Indeed, the overall survival accounts for ~70% but still ~30% of pediatric patients experience relapse, with poor response to conventional chemotherapy. Thus, there is an urgent need to improve diagnosis and treatment efficacy prediction in the context of this disease. Nowadays, in the era of high throughput techniques, AML has emerged as an extremely heterogeneous disease from a genetic point of view. Different subclones characterized by specific molecular profiles display different degrees of susceptibility to conventional treatments. In this review, we describe in detail this genetic heterogeneity of pediatric AML and how it is linked to relapse in terms of clonal evolution. We highlight some innovative tools to characterize minor subclones that could help to enhance diagnosis and a preclinical model suitable for drugs screening. The final ambition of research is represented by targeted therapy, which could improve the prognosis of pediatric AML patients, as well as to limit the side toxicity of current treatments.
Reconciling the Biological and Transcriptional Variability of Hepatoblastoma with Its Mutational Uniformity
Authors: Prochownik Edward V.
Published: April 2021

Hepatoblastoma (HB), the most common childhood liver cancer, is associated with seven distinct histologic subtypes and variable degrees of clinical aggressiveness and presentation. Yet it is among the least genomically altered tumors known, with about half of HBs showing mutation and/or dysregulation of the Wnt/β-catenin and Hippo pathways. This raises the question of how this mutational simplicity can generate such biological and histologic complexity. Recent work shows that the identity of the underlying β-catenin mutation is a major contributor. Mutation or over-expression of the NFE2L2/NRF2 transcription factor, previously thought only to promote anti-oxidant responses, has also recently been shown to accelerate the growth of HBs generated by mutations in the Wnt/β-catenin and Hippo pathways while imparting novel features such as the tumor-associated cysts and necrosis. Moreover, patient-associated NFE2L2 mutations are overtly transforming when co-expressed with either mutant β-catenin or a Hippo pathway effector. The finding that tumorigenesis can be driven by any two arms of the β-catenin/Hippo/NFE2L2 axis has permitted the identification of a small subset of coordinately regulated tumor-specific transcripts, some of whose levels correlate with inferior long-term outcomes in HB and other cancers. Collectively, these findings begin to provide for more refined and molecularly based classification, survival algorithms and design of chemotherapeutic regimens.
Human Endogenous Retrovirus Reactivation: Implications for Cancer Immunotherapy
Authors: Petrizzo Annacarmen , Ragone Concetta , Cavalluzzo Beatrice , Mauriello Angela , Manolio Carmen , Tagliamonte Maria , Buonaguro Luigi
Published: April 2021

Human endogenous retroviruses (HERVs) derive from ancestral exogenous retroviruses whose genetic material has been integrated in our germline DNA. Several lines of evidence indicate that cancer immunotherapy may benefit from HERV reactivation, which can be induced either by drugs or by cellular changes occurring in tumor cells. Indeed, several studies indicate that HERV proviral DNA can be transcribed either to double-stranded RNA (dsRNA) that is sensed as a “danger signal” by pattern recognition receptors (PRRs), leading to a viral mimicry state, or to mRNA that is translated into proteins that may contribute to the landscape of tumor-specific antigens (TSAs). Alternatively, HERV reactivation is associated with the expression of long noncoding RNAs (lncRNAs). In this review, we will highlight recent findings on HERV reactivation in cancer and its implications for cancer immunotherapy.
Quinacrine-Induced Autophagy in Ovarian Cancer Triggers Cathepsin-L Mediated Lysosomal/Mitochondrial Membrane Permeabilization and Cell Death
Authors: Thirusangu Prabhu , Pathoulas Christopher L. , Ray Upasana , Xiao Yinan , Staub Julie , Jin Ling , Khurana Ashwani , Shridhar Viji
Published: April 2021

We previously reported that the antimalarial compound quinacrine (QC) induces autophagy in ovarian cancer cells. In the current study, we uncovered that QC significantly upregulates cathepsin L (CTSL) but not cathepsin B and D levels, implicating the specific role of CTSL in promoting QC-induced autophagic flux and apoptotic cell death in OC cells. Using a Magic Red® cathepsin L activity assay and LysoTracker red, we discerned that QC-induced CTSL activation promotes lysosomal membrane permeability (LMP) resulting in the release of active CTSL into the cytosol to promote apoptotic cell death. We found that QC-induced LMP and CTSL activation promotes Bid cleavage, mitochondrial outer membrane permeabilization (MOMP), and mitochondrial cytochrome-c release. Genetic (shRNA) and pharmacological (Z-FY(tBU)-DMK) inhibition of CTSL markedly reduces QC-induced autophagy, LMP, MOMP, apoptosis, and cell death; whereas induced overexpression of CTSL in ovarian cancer cell lines has an opposite effect. Using recombinant CTSL, we identified p62/SQSTM1 as a novel substrate of CTSL, suggesting that CTSL promotes QC-induced autophagic flux. CTSL activation is specific to QC-induced autophagy since no CTSL activation is seen in ATG5 knockout cells or with the anti-malarial autophagy-inhibiting drug chloroquine. Importantly, we showed that upregulation of CTSL in QC-treated HeyA8MDR xenografts corresponds with attenuation of p62, upregulation of LC3BII, cytochrome-c, tBid, cleaved PARP, and caspase3. Taken together, the data suggest that QC-induced autophagy and CTSL upregulation promote a positive feedback loop leading to excessive autophagic flux, LMP, and MOMP to promote QC-induced cell death in ovarian cancer cells.
Species Delimitation of Southeast Pacific Angel Sharks (Squatina spp.) Reveals Hidden Diversity through DNA Barcoding
Authors: Cañedo-Apolaya Rosa M. , Ortiz-Alvarez Clara , Alfaro-Cordova Eliana , Alfaro-Shigueto Joanna , Velez-Zuazo Ximena , Mangel Jeffrey C. , Siccha-Ramirez Raquel , Yamashiro Carmen , Ramirez Jorge L.
Published: April 2021

Angel sharks are distributed worldwide in tropical to subtropical waters. Across the Eastern Pacific Ocean (EPO), two valid species are reported: The Pacific angelshark Squatina californica and the Chilean angelshark Squatina armata; however, there is still uncertainty about their geographic distribution, mainly along the northern Peru coast where the species have been reported to be sympatric. The aim of this study is to describe the genetic differences between the genus Squatina from the EPO, including samples from northern Peru, and using DNA barcoding and three species delimitation models: Poisson tree processes (PTP) model, Bayesian implementation of the PTP (bPTP) model and the general mixed Yule coalescent (GMYC) model. The three approaches summarized 19 nominal Squatina species in 23 consensus Molecular Taxonomic Units (MOTU). Only 16 of them were in accordance with taxonomic identifications. From the EPO, four Squatina MOTUs were identified, one from North America (S. californica USA/Mexico) and three sampled in northern Peru, S. californica Peru, S. armata and Squatina sp. (a potential new species). This study contributes to the management and conservation policies of angel sharks in Peru, suggesting the presence of an undescribed species inhabiting the northern Peruvian coast. The use of molecular approaches, such as DNA barcoding, has the potential to quickly flag undescribed species in poorly studied regions, including the Southeast Pacific, within groups of ecologically and economically important groups like angel sharks.
Enhanced Emission of Monoterpene 3-Carene in Pinus densiflora Infected by Pine Wood Nematode and Characterization of 3-Carene Synthase
Authors: Hwang Hwan-Su , Han Jung-Yeon , Choi Yong-Eui
Published: April 2021

Pinus densiflora is an important pine species in Northeast Asia due to its historical, cultural, and economic values. Pine wood nematode (PWN) seriously damages P. densiflora, causing the pine wilt disease (PWD). Changes of phyto-compounds in resin and monoterpenes in P. densiflora after infection of PWN were studied. The changes were identified by GC-MS in control and infected P. densiflora. Among the resin phytochemicals (in P. densiflora), 3-carene was distinctly enhanced after PWN inoculation. The emitted plant volatile monoterpenes were analyzed by HS-SPME/GC-MS. It was observed that the amount of 3-carene enhanced conspicuously after infection of PWNs in both P. densiflora and P. koraiensis at 9.7 and 54.7 times, respectively. 3-Carene synthase gene (Pd3-cars) of P. densiflora was isolated and functionally characterized by transgenic tobacco overexpressing Pd3-cars. Integration and expression of transgenic tobacco were confirmed by genomic and RT-PCR analysis. The Pd3-cars gene was expressed in transgenic tobacco plants. Furthermore, the production of 3-carene was identified by HS-SPME/GC-MS analysis as the volatile compounds emitted from leaves of transgenic tobacco. Treatment of 3-carene to PWNs showed a mild nematicidal activity with 45.98% mortality at the concentration of 10 mg/mL. The current findings may apply to the early diagnosis of pine wilt disease infected by PWNs through enhanced emission of 3-carene.
Host-Diet Effect on the Metabolism of Bifidobacterium
Authors: Satti Maria , Modesto Monica , Endo Akihito , Kawashima Takeshi , Mattarelli Paola , Arita Masanori
Published: April 2021

Bifidobacterium has a diverse host range and shows several beneficial properties to the hosts. Many species should have co-evolved with their hosts, but the phylogeny of Bifidobacterium is dissimilar to that of host animals. The discrepancy could be linked to the niche-specific evolution due to hosts’ dietary carbohydrates. We investigated the relationship between bifidobacteria and their host diet using a comparative genomics approach. Since carbohydrates are the main class of nutrients for bifidobacterial growth, we examined the distribution of carbohydrate-active enzymes, in particular glycoside hydrolases (GHs) that metabolize unique oligosaccharides. When bifidobacterial species are classified by their distribution of GH genes, five groups arose according to their hosts’ feeding behavior. The distribution of GH genes was only weakly associated with the phylogeny of the host animals or with genomic features such as genome size. Thus, the hosts’ dietary pattern is the key determinant of the distribution and evolution of GH genes.
Comparative Distribution of Repetitive Sequences in the Karyotypes of Xenopus tropicalis and Xenopus laevis (Anura, Pipidae)
Authors: Roco Álvaro S. , Liehr Thomas , Ruiz-García Adrián , Guzmán Kateryna , Bullejos Mónica
Published: April 2021

Xenopus laevis and its diploid relative, Xenopus tropicalis, are the most used amphibian models. Their genomes have been sequenced, and they are emerging as model organisms for research into disease mechanisms. Despite the growing knowledge on their genomes based on data obtained from massive genome sequencing, basic research on repetitive sequences in these species is lacking. This study conducted a comparative analysis of repetitive sequences in X. laevis and X. tropicalis. Genomic in situ hybridization (GISH) and fluorescence in situ hybridization (FISH) with Cot DNA of both species revealed a conserved enrichment of repetitive sequences at the ends of the chromosomes in these Xenopus species. The repeated sequences located on the short arm of chromosome 3 from X. tropicalis were not related to the sequences on the short arm of chromosomes 3L and 3S from X. laevis, although these chromosomes were homoeologous, indicating that these regions evolved independently in these species. Furthermore, all the other repetitive sequences in X. tropicalis and X. laevis may be species-specific, as they were not revealed in cross-species hybridizations. Painting experiments in X. laevis with chromosome 7 from X. tropicalis revealed shared sequences with the short arm of chromosome 3L. These regions could be related by the presence of the nucleolus organizer region (NOR) in both chromosomes, although the region revealed by chromosome painting in the short arm of chromosome 3L in X. laevis did not correspond to 18S + 28S rDNA sequences, as they did not colocalize. The identification of these repeated sequences is of interest as they provide an explanation to some problems already described in the genome assemblies of these species. Furthermore, the distribution of repetitive DNA in the genomes of X. laevis and X. tropicalis might be a valuable marker to assist us in understanding the genome evolution in a group characterized by numerous polyploidization events coupled with hybridizations.
The Effectiveness of an Acceptance and Commitment Therapy and Mindfulness Group Intervention for Enhancing the Psychological and Physical Well-Being of Adults with Overweight or Obesity Seeking Treatment: The Mind&Life Randomized Control Trial Study Protocol
Authors: Iturbe Idoia , Pereda-Pereda Eva , Echeburúa Enrique , Maiz Edurne
Published: April 2021

Although several interventions that target obesity have been examined, the success of these interventions in generating and maintaining positive results has yet to be confirmed. This study protocol therefore presents a trial aimed at analyzing the effectiveness of a well-being-centered acceptance and commitment therapy (ACT)- and mindfulness-based group intervention following the valued-based healthy living (VHL) approach (Mind&Life intervention) for individuals experiencing overweight-related distress. A randomized controlled trial with two parallel groups will be conducted in 110 adults attending primary care units with overweight or obesity. Participants will be randomly allocated to one of the two study conditions. Interventions will either be the treatment as usual (TAU) or the Mind&Life intervention—an ACT- and mindfulness-based intervention—plus the TAU intervention. Quality of life, weight self-stigma, general health status, eating habits, physical activity, eating behavior, anthropometric, body composition, cardiovascular, and physiological variables, as well as process variables, will be examined at baseline, posttreatment, 6-month follow-up, and 1-year follow-up. This trial aims to offer a novel psychological approach for addressing the psychological and physical impairments suffered by people with overweight or obesity in the current environment. ClinicalTrials.gov identifier: NCT03718728.
Effects of Internet-Based Support Program on Parenting Outcomes for Primiparous Women: A Pilot Study
Authors: Huang Lingling , Shen Qu , Fang Qiyu , Zheng Xujuan
Published: April 2021

(1) Background: Some primiparous women are usually confronted with many parenting problems after childbirth, which can negatively influence the wellbeing of some mothers and infants. Evidence identified that internet interventions can include more tailored information, reach a larger research group, and supply more anonymity than face-to-face traditional interventions. Therefore, the internet-based support program (ISP) was designed to improve the parenting outcomes for Chinese first-time mothers. (2) Methods: A multicenter, single-blinded, pilot randomized controlled trial was conducted. From May to October 2020, a total of 44 participants were recruited in the obstetrical wards of two tertiary hospitals in China. Eighteen women in the control group received routine postnatal care; while eighteen women in the intervention group accessed to the ISP and routine postnatal care. The duration of intervention was not less than three months. Intervention outcomes were assessed through questionnaires before randomization (T0), immediately after intervention (T1), and three months after intervention (T2). The Self-efficacy in Infant Care Scale (SICS), Edinburgh Postnatal Depression Scale (EPDS), and Postpartum Social Support Scale (PSSS) were included to measure MSE, postpartum depression (PPD), and social support, respectively. (3) Results: No significant difference between the two groups were found in terms of the baseline social-demographic characteristics; and the scores of SICS, EPDS and PSSS at T0 (p > 0.05). Repeated measures multivariate analysis of covariance found that women in the intervention group had a higher MSE score at T1 (6.63, p = 0.007), and T2 (5.75, p = 0.020); a lower EPDS score at T1 (3.11, p = 0.003), and T2 (2.50, p = 0.005); and a higher PSSS score at T1 (4.30, p = 0.001); and no significant difference at T2 (0.35, p = 0.743), compared with women in the control group. (4) Conclusion: The effect of ISP was evaluated to significantly increase primiparous women’s MSE, social support, and to alleviate their PPD symptoms. However, the small sample in pilot study restricted the research results. Therefore, the ISP should be further investigated with a larger, diverse sample to confirm whether it should be adopted as routine postnatal care to support primiparous women on parenting outcomes and mental wellbeing in the early stage of motherhood.
Indigenous Community Perspectives of Food Security, Sustainable Food Systems and Strategies to Enhance Access to Local and Traditional Healthy Food for Partnering Williams Treaties First Nations (Ontario, Canada)
Authors: Domingo Ashleigh , Charles Kerry-Ann , Jacobs Michael , Brooker Deborah , Hanning Rhona M.
Published: April 2021

In partnership with communities of the Williams Treaties First Nations in southern Ontario (Canada), we describe an approach to work with communities, and highlight perspectives of food security and sustainability, including priorities and opportunities to revitalize local food systems as a pathway to food security and food sovereignty. The objectives of our project were: (1) to build a shared understanding of food security and sustainability; and (2) to document community priorities, challenges and opportunities to enhance local food access. Utilizing an Indigenous methodology, the conversational method, within the framework of community-based participatory research, formative work undertaken helped to conceptualize food security and sustainability from a community perspective and solidify interests within the four participating communities to inform community-led action planning. Knowledge generated from our project will inform development of initiatives, programs or projects that promote sustainable food systems. The community-based actions identified support a path towards holistic wellbeing and, ultimately, Indigenous peoples’ right to food security and food sovereignty.
Acute Effects of Kinesiology Taping Stretch Tensions on Soleus and Gastrocnemius H-Reflex Modulations
Authors: Chen Yung-Sheng , Zhou Shi , Crowley-McHattan Zachary J. , Bezerra Pedro , Tseng Wei-Chin , Chen Che-Hsiu , Ye Xin
Published: April 2021

This study examined the acute effects of stretch tensions of kinesiology taping (KT) on the soleus (SOL), medial (MG), and lateral (LG) gastrocnemius Hoffmann-reflex (H-reflex) modulation in physically active healthy adults. A cross-over within-subject design was used in this study. Twelve physically active collegiate students voluntarily participated in the study (age = 21.3 ± 1.2 years; height = 175.6 ± 7.1 cm; body weight = 69.9 ± 7.1 kg). A standard Y-shape of KT technique was applied to the calf muscles. The KT was controlled in three tension intensities in a randomised order: paper-off, 50%, and 100% of maximal stretch tension of the tape. The peak-to-peak amplitude of maximal M-wave (Mmax) and H-reflex (Hmax) responses in the SOL, MG, and LG muscles were assessed before taping (pre-taping), taping, and after taping (post-taping) phases in the lying prone position. The results demonstrated significantly larger LG Hmax responses in the pre-taping condition than those in the post-taping condition during paper-off KT (p = 0.002). Moreover, the ΔHmax/Mmax of pre- and post-taping in the SOL muscle was significantly larger during 50%KT tension than that of paper-off (p = 0.046). In conclusion, the stretch tension of KT contributes minor influence on the spinal motoneuron excitability in the triceps surae during rest.
“Hang the Flesh off the Bones”: Cultivating an “Ideal Body” in Taijiquan and Neigong
Authors: Ma Xiujie , Jennings George
Published: April 2021

In a globalized, media-driven society, people are being exposed to different cultural and philosophical ideas. In Europe, the School of Internal Arts (pseudonym) follows key principles of the ancient Chinese text The Yijinjing (The Muscle-Tendon Change Classic) “Skeleton up, flesh down”, in its online and offline pedagogy. This article draws on an ongoing ethnographic, netnographic and cross-cultural investigation of the transmission of knowledge in this atypical association that combines Taijiquan with a range of practices such as Qigong, body loosening exercises and meditation. Exploring the ideal body cultivated by the students, we describe and illustrate key (and often overlooked) body areas—namely the spine, scapula, Kua and feet, which are continually worked on in the School of Internal Arts’ exercise-based pedagogy. We argue that Neigong and Taijiquan, rather than being forms of physical education, are vehicles for adult physical re-education. This re-education offers space in which mind-body tension built over the life course are systematically released through specific forms of attentive, meditative exercise to lay the foundations for a strong, powerful body for martial artistry and health.
Trauma and Mental Health Awareness in Emergency Service Workers: A Qualitative Evaluation of the Behind the Seen Education Workshops
Authors: Fogarty Andrea , Steel Zachary , Ward Philip B. , Boydell Katherine M. , McKeon Grace , Rosenbaum Simon
Published: April 2021

Emergency service workers (ESWs) are at high risk of experiencing poor mental health, including posttraumatic stress disorder (PTSD). Programs led by ex-service organizations may play an unrecognized but critical role in mental health prevention and promotion. Behind the Seen (BTS) is an Australian ex-service organization that runs workshops to raise awareness and facilitate conversations around the mental health of ESWs. The purpose of the study is to conduct a qualitative evaluation of workshop participants’ experiences, to understand the acceptability and perceived usefulness over the immediate- (within 1 month), intermediate- (6 months) and longer-terms (12 months). Participants (n = 59 ESWs) were recruited using purposive sampling across five fire and rescue services in metropolitan, regional, and rural locations. Focus groups methodology was used for data collection and data were analyzed using iterative categorization techniques. Participants reported (i) a high perceived need for education about PTSD, (ii) highly salient aspects of the presentation that made for a positive learning experience, including the importance of the lived experiences of the facilitators in the learning process, (iii) key features of changes to intentions, attitudes, and behavior, and (iv) major aspects of the organizational context that affected the understanding and uptake of the program’s key messages. BTS was perceived as an acceptable means of delivering mental health, PTSD, and help-seeking information to ESWs. The program is a promising candidate for scaling-up and further translation.