bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual Effect of Bleomycin on Histopathological Features of Lungs and Mediastinal Fat-Associated Lymphoid Clusters in an Autoimmune Disease Mouse Model
Authors: Elewa Yaser Hosny Ali , Ichii Osamu , Nakamura Teppei , Kon Yasuhiro
Published: July 2021

Mediastinal fat-associated lymphoid clusters (MFALCs) are novel immune clusters that function in the pathogenesis of bleomycin (BLM)-induced pneumonitis in a C57BL/6 mouse model. However, we lack literature on the effects of BLM in an autoimmune disease mouse model (AIDM). In the present study, BLM sulfate (BLM group) or phosphate-buffered saline (PBS group) were intranasally administered in BXSB/MpJ-Yaa (Yaa) AIDM and its wild-type strains (BXSB/MpJ “BXSB”) and the histopathology of MFALCs and lungs were examined on days 7 and 21 days. Immunohistochemical analysis was performed to detect lymphatic vessels (LVs), high endothelial venules (HEVs), proliferating, and immune cells. Furthermore, the mRNA expression of Yaa locus genes (TLR7,TLR8,Arhgap6,Msl3, andTceanc) was detected in the lung tissues. Here, we show a dual effect of BLM on intra-thoracic immune hemostasis among Yaa AIDM and its corresponding wild-type strain (BXSB mice). The BLM group of BXSB mice displayed significantly higher values of lung injury scores (LIS) and size of MFALCs as compared with the corresponding PBS group. However, an opposite effect was detected in Yaa mice. Furthermore, Yaa mice displayed decreased serum autoantibody titers and downregulated expression ofTLR7,TLR8,Msl3, andTceancin the lungs following BLM administration, especially on day 21. Interestingly, significant positive correlations were detected in both strains between the LIS and the size of MFALCs, LVs, HEVs, and proliferating cells. Conclusively, our findings revealed a crucial function of HEVs on the extent of lung injury and the development of MFALCs in BLM-administered Yaa AIDM and control BXSB mice with dual effects. Moreover, our data suggest that down regulation of Yaa locus genes could contribute as an important attributing factor leading to decrease in the degree of autoimmunity and lung injury in AIDM. Therefore, we suggest that genetic background contributes to BLM diversity among AIDM and the wild-type strain. Targeting some genes or venules could provide novel therapeutic approaches for some autoimmune-associated respiratory diseasesviacontrolling the MFALCs development.
Rapid and Efficient Gene Editing for Direct Transplantation of Naive Murine Cas9+ T Cells
Authors: Majumder Snigdha , Jugovic Isabelle , Saul Domenica , Bell Luisa , Hundhausen Nadine , Seal Rishav , Beilhack Andreas , Rosenwald Andreas , Mougiakakos Dimitrios , Berberich-Siebelt Friederike
Published: July 2021

Gene editing of primary T cells is a difficult task. However, it is important for research and especially for clinical T-cell transfers. CRISPR/Cas9 is the most powerful gene-editing technique. It has to be applied to cells by either retroviral transduction or electroporation of ribonucleoprotein complexes. Only the latter is possible with resting T cells. Here, we make use of Cas9 transgenic mice and demonstrate nucleofection of pre-stimulated and, importantly, of naive CD3+ T cells with guideRNA only. This proved to be rapid and efficient with no need of further selection. In the mixture of Cas9+CD3+ T cells, CD4+ and CD8+ conventional as well as regulatory T cells were targeted concurrently. IL-7 supported survival and naivety in vitro, but T cells were also transplantable immediately after nucleofection and elicited their function like unprocessed T cells. Accordingly, metabolic reprogramming reached normal levels within days. In a major mismatch model of GvHD, not only ablation of NFATc1 and/or NFATc2, but also of the NFAT-target gene IRF4 in naïve primary murine Cas9+CD3+ T cells by gRNA-only nucleofection ameliorated GvHD. However, pre-activated murine T cells could not achieve long-term protection from GvHD upon single NFATc1 or NFATc2 knockout. This emphasizes the necessity of gene-editing and transferring unstimulated human T cells during allogenic hematopoietic stem cell transplantation.
Sex Matters: Physiological Abundance of Immuno-Regulatory CD71+ Erythroid Cells Impair Immunity in Females
Authors: Mashhouri Siavash , Koleva Petya , Huynh Mai , Okoye Isobel , Shahbaz Shima , Elahi Shokrollah
Published: July 2021

Mature erythrocytes are the major metabolic regulators by transporting oxygen throughout the body. However, their precursors and progenitors defined as CD71+ Erythroid Cells (CECs) exhibit a wide range of immunomodulatory properties. Here, we uncover pronounced sexual dimorphism in CECs. We found female but not male mice, both BALB/c and C57BL/6, and human females were enriched with CECs. CECs, mainly their progenitors defined as CD45+CECs expressed higher levels of reactive oxygen species (ROS), PDL-1, VISTA, Arginase II and Arginase I compared to their CD45− counterparts. Consequently, CECs by the depletion of L-arginine suppress T cell activation and proliferation. Expansion of CECs in anemic mice and also post-menstrual cycle in women can result in L-arginine depletion in different microenvironments in vivo (e.g. spleen) resulting in T cell suppression. As proof of concept, we found that anemic female mice and mice adoptively transferred with CECs from anemic mice became more susceptible to Bordetella pertussis infection. These observations highlight the role of sex and anemia-mediated immune suppression in females. Notably, enriched CD45+CECs may explain their higher immunosuppressive properties in female BALB/c mice. Finally, we observed significantly more splenic central macrophages in female mice, which can explain greater extramedullary erythropoiesis and subsequently abundance of CECs in the periphery. Thus, sex-specific differences frequency in the frequency of CECs might be imprinted by differential erythropoiesis niches and hormone-dependent manner.
Monocytes and Macrophages in COVID-19
Authors: Knoll Rainer , Schultze Joachim L. , Schulte-Schrepping Jonas
Published: July 2021

COVID-19 is a contagious viral disease caused by SARS-CoV-2 that led to an ongoing pandemic with massive global health and socioeconomic consequences. The disease is characterized primarily, but not exclusively, by respiratory clinical manifestations ranging from mild common cold symptoms, including cough and fever, to severe respiratory distress and multi-organ failure. Macrophages, a heterogeneous group of yolk-sac derived, tissue-resident mononuclear phagocytes of complex ontogeny present in all mammalian organs, play critical roles in developmental, homeostatic and host defense processes with tissue-dependent plasticity. In case of infection, they are responsible for early pathogen recognition, initiation and resolution of inflammation, as well as repair of tissue damage. Monocytes, bone-marrow derived blood-resident phagocytes, are recruited under pathological conditions such as viral infections to the affected tissue to defend the organism against invading pathogens and to aid in efficient resolution of inflammation. Given their pivotal function in host defense and the potential danger posed by their dysregulated hyperinflammation, understanding monocyte and macrophage phenotypes in COVID-19 is key for tackling the disease’s pathological mechanisms. Here, we outline current knowledge on monocytes and macrophages in homeostasis and viral infections and summarize concepts and key findings on their role in COVID-19. While monocytes in the blood of patients with moderate COVID-19 present with an inflammatory, interferon-stimulated gene (ISG)-driven phenotype, cellular dysfunction epitomized by loss of HLA-DR expression and induction of S100 alarmin expression is their dominant feature in severe disease. Pulmonary macrophages in COVID-19 derived from infiltrating inflammatory monocytes are in a hyperactivated state resulting in a detrimental loop of pro-inflammatory cytokine release and recruitment of cytotoxic effector cells thereby exacerbating tissue damage at the site of infection.
Development of Sperm Cryopreservation Protocols for Sharks and Rays: New Tools for Elasmobranch Conservation
Authors: García-Salinas Pablo , Gallego Victor , Asturiano Juan F.
Published: July 2021

Elasmobranchs are one of the most endangered vertebrate groups on the planet, but despite this situation the use of reproductive techniques in elasmobranch conservation strategies has been scarce. Among these techniques, sperm preservation is a potential tool forex situconservation and aquaria sustainability. However, there are no widespread preservation protocols for elasmobranch sperm, and shark sperm cryopreservation has never been achieved before. Here we present the establishment of successful cryopreservation protocols for elasmobranch sperm, tested in several species. We have formulated a sperm extender that can be used for different elasmobranch species, capable of maintaining sperm motility for several weeks. Additionally, we achieved the cryopreservation of sperm by previously diluting it in our extender and supplementing it with different combinations of cryoprotectants. The effects of methanol and dimethyl sulfoxide as permeating cryoprotectants were evaluated, as well egg yolk as a non-permeating cryoprotectant. Sperm quality was assessed by studying the motility and membrane integrity post-thawing, demonstrating its effectiveness in the 10 species tested, including two which are considered Critically Endangered. This is the first time that shark sperm cryopreservation has been reported, broadening our knowledge of the reproductive techniques that can be applied to elasmobranchs and laying the foundations for the first cryobanks for shark and ray sperm. Outcomes from this study will be useful forex situconservation efforts developed by public aquaria. A regular supply of frozen sperm will reduce the problems that result from the transport of specimens, inbreeding or lack of synchronized reproductive cycles in captivity.
Distribution of Hydrogen-Producing Bacteria in Tibetan Hot Springs, China
Authors: Ma Li , Wu Geng , Yang Jian , Huang Liuqin , Phurbu Dorji , Li Wen-Jun , Jiang Hongchen
Published: July 2021

Investigating the distribution of hydrogen-producing bacteria (HPB) is of great significance to understanding the source of biological hydrogen production in geothermal environments. Here, we explored the compositions of HPB populations in the sediments of hot springs from the Daggyai, Quzhuomu, Quseyongba, and Moluojiang geothermal zones on the Tibetan Plateau, with the use of Illumina MiSeq high-throughput sequencing of 16S rRNA genes and hydA genes. In the present study, the hydA genes were successfully amplified from the hot springs with a temperature of 46–87°C. The hydA gene phylogenetic analysis showed that the top three phyla of the HPB populations were Bacteroidetes (14.48%), Spirochaetes (14.12%), and Thermotogae (10.45%), while Proteobacteria were absent in the top 10 of the HPB populations, although Proteobacteria were dominant in the 16S rRNA gene sequences. Canonical correspondence analysis results indicate that the HPB community structure in the studied Tibetan hot springs was correlated with various environmental factors, such as temperature, pH, and elevation. The HPB community structure also showed a spatial distribution pattern; samples from the same area showed similar community structures. Furthermore, one HPB isolate affiliated with Firmicutes was obtained and demonstrated the capacity of hydrogen production. These results are important for us to understand the distribution and function of HPB in hot springs.
Hanseniaspora smithiae sp. nov., a Novel Apiculate Yeast Species From Patagonian Forests That Lacks the Typical Genomic Domestication Signatures for Fermentative Environments
Authors: Čadež Neža , Bellora Nicolas , Ulloa Ricardo , Tome Miha , Petković Hrvoje , Groenewald Marizeth , Hittinger Chris Todd , Libkind Diego
Published: July 2021

During a survey of Nothofagus trees and their parasitic fungi in Andean Patagonia (Argentina), genetically distinct strains of Hanseniaspora were obtained from the sugar-containing stromata of parasitic Cyttaria spp. Phylogenetic analyses based on the single-gene sequences (encoding rRNA and actin) or on conserved, single-copy, orthologous genes from genome sequence assemblies revealed that these strains represent a new species closely related to Hanseniaspora valbyensis. Additionally, delimitation of this novel species was supported by genetic distance calculations using overall genome relatedness indices (OGRI) between the novel taxon and its closest relatives. To better understand the mode of speciation in Hanseniaspora, we examined genes that were retained or lost in the novel species in comparison to its closest relatives. These analyses show that, during diversification, this novel species and its closest relatives, H. valbyensis and Hanseniaspora jakobsenii, lost mitochondrial and other genes involved in the generation of precursor metabolites and energy, which could explain their slower growth and higher ethanol yields under aerobic conditions. Similarly, Hanseniaspora mollemarum lost the ability to sporulate, along with genes that are involved in meiosis and mating. Based on these findings, a formal description of the novel yeast species Hanseniaspora smithiae sp. nov. is proposed, with CRUB 1602H as the holotype.
Fighting Antibiotic Resistance in Hospital-Acquired Infections: Current State and Emerging Technologies in Disease Prevention, Diagnostics and Therapy
Authors: Avershina Ekaterina , Shapovalova Valeria , Shipulin German
Published: July 2021

Rising antibiotic resistance is a global threat that is projected to cause more deaths than all cancers combined by 2050. In this review, we set to summarize the current state of antibiotic resistance, and to give an overview of the emerging technologies aimed to escape the pre-antibiotic era recurrence. We conducted a comprehensive literature survey of >150 original research and review articles indexed in the Web of Science using “antimicrobial resistance,” “diagnostics,” “therapeutics,” “disinfection,” “nosocomial infections,” “ESKAPE pathogens” as key words. We discuss the impact of nosocomial infections on the spread of multi-drug resistant bacteria, give an overview over existing and developing strategies for faster diagnostics of infectious diseases, review current and novel approaches in therapy of infectious diseases, and finally discuss strategies for hospital disinfection to prevent MDR bacteria spread.
Prevalence, Characteristics and Clonal Distribution of Extended-Spectrum β-Lactamase- and AmpC β-Lactamase-Producing Escherichia coli Following the Swine Production Stages, and Potential Risks to Humans
Authors: Lee Soomin , An Jae-Uk , Guk Jae-Ho , Song Hyokeun , Yi Saehah , Kim Woo-Hyun , Cho Seongbeom
Published: July 2021

The worldwide spread of extended spectrum β-lactamase (ESBL)- and AmpC β-lactamase (AmpC)-producing Escherichia coli poses serious threats to public health. Swine farms have been regarded as important reservoirs of ESBL/AmpC-EC. This study aimed to determine the prevalence, ESBL/AmpC types, and clonal distribution of ESBL/AmpC-EC from swine farms and analyze the difference according to the swine production stages. In addition, we evaluated the potential risks of swine ESBL/AmpC-EC clones to humans. Individual fecal samples (n = 292) were collected from weaning, growing, finishing, and pregnant pigs in nine swine farms of South Korea between July 2017 and March 2020. In total, 161 ESBL/AmpC-EC isolates were identified (55.1%), with the highest prevalence detected in the weaning stage (86.3%). The dominant ESBL and AmpC types were CTX-M-55 (69.6%) and CMY-2 (4.3%), respectively. CTX-M found in all production stages, while CMY was only found in growing and finishing stages. In the conjugation assay, the high transferability of CTX-M gene (55.8%) was identified, while the transfer of CMY gene was not identified. The major clonal complexes (CCs) were CC101-B1 (26.8%), CC10-A (8.7%), and CC648-F (2.9%). There was similarity in clonal distribution between different swine production stages within swine farms, estimated using the k-means analysis, which suggested a clonal transmission between the different swine stages. Among swine ESBL/AmpC-EC sequence types (STs), seven STs (ST101, ST10, ST648, ST457, ST410, ST617, and ST744) were common with the human ESBL/AmpC-EC, which registered in National Center for Biotechnology Information database. The clonal population structure analysis based on the virulence factor (VF) presented that swine ESBL/AmpC-EC clones, especially ST101-B1, harbored a highly virulent profile. In conclusion, ESBL/AmpC-EC was distributed throughout the swine production stages, with the highest prevalence in the weaning stage. The CTX-M was present in all stages, while CMY was mostly found in growing-finishing stages. The swine ESBL/AmpC-EC was identified to harbor shared clone types with human ESBL/AmpC-EC and a virulent profile posing potential risk to humans. Considering the possibility of genetic and clonal distribution of ESBL/AmpC-EC among swine production stages, this study suggests the need for strategies considering the production system to control the prevalence of ESBL/AmpC-EC in swine farms.
Clostridioides difficile Single Cell Swimming Strategy: A Novel Motility Pattern Regulated by Viscoelastic Properties of the Environment
Authors: Schwanbeck Julian , Oehmig Ines , Groß Uwe , Zautner Andreas E. , Bohne Wolfgang
Published: July 2021

Flagellar motility is important for the pathogenesis of many intestinal pathogens, allowing bacteria to move to their preferred ecological niche. Clostridioides difficile is currently the major cause for bacterial health care-associated intestinal infections in the western world. Most clinical strains produce peritrichous flagella and are motile in soft-agar. However, little knowledge exists on the C. difficile swimming behaviour and its regulation at the level of individual cells. We report here on the swimming strategy of C. difficile at the single cell level and its dependency on environmental parameters. A comprehensive analysis of motility parameters from several thousand bacteria was achieved with the aid of a recently developed bacterial tracking programme. C. difficile motility was found to be strongly dependent on the matrix elasticity of the medium. Long run phases of all four motile C. difficile clades were only observed in the presence of high molecular weight molecules such as polyvinylpyrrolidone (PVP) and mucin, which suggests an adaptation of the motility apparatus to the mucin-rich intestinal environment. Increasing mucin or PVP concentrations lead to longer and straighter runs with increased travelled distance per run and fewer turnarounds that result in a higher net displacement of the bacteria. The observed C. difficile swimming pattern under these conditions is characterised by bidirectional, alternating back and forth run phases, interrupted by a short stop without an apparent reorientation or tumbling phase. This motility type was not described before for peritrichous bacteria and is more similar to some previously described polar monotrichous bacteria.
Peptide-Based Inhibitors of ADAM and ADAMTS Metalloproteinases
Authors: Pluda Stefano , Mazzocato Ylenia , Angelini Alessandro
Published: July 2021

ADAM and ADAMTS are two large metalloproteinase families involved in numerous physiological processes, such as shedding of cell-surface protein ectodomains and extra-cellular matrix remodelling. Aberrant expression or dysregulation of ADAMs and ADAMTSs activity has been linked to several pathologies including cancer, inflammatory, neurodegenerative and cardiovascular diseases. Inhibition of ADAM and ADAMTS metalloproteinases have been attempted using various small molecules and protein-based therapeutics, each with their advantages and disadvantages. While most of these molecular formats have already been described in detail elsewhere, this mini review focuses solely on peptide-based inhibitors, an emerging class of therapeutic molecules recently applied against some ADAM and ADAMTS members. We describe both linear and cyclic peptide-based inhibitors which have been developed using different approaches ranging from traditional medicinal chemistry and rational design strategies to novel combinatorial peptide-display technologies.
WS635 Attenuates the Anesthesia/Surgery-Induced Cognitive Impairment in Mice
Authors: Lin Jiefu , Shen Fuyi , Lu Jing , Liang Feng , Zhang Yiying , Xie Zhongcong , Dong Yuanlin
Published: July 2021

Anesthesia/surgery has been reported to be associated with perioperative neurocognitive disorder (PND) in patients and induces cognitive impairment in mice. Previous studies demonstrate cyclosporine A (CsA) attenuates the anesthesia/surgery-induced cognitive impairment in mice. However, CsA has immunosuppressive effects and may not be routinely used to prevent or treat PND in patients. WS635 is a nonimmunosuppressive CsA analog. We, therefore, set out to determine whether WS635 could mitigate the anesthesia/surgery-induced cognitive impairment in mice. We performed abdominal surgery under 1.4% isoflurane anesthesia (anesthesia/surgery) for 2 h in 9 month-old wild-type (WT) mice. We treated the mice with CsA (10 mg/kg) or different doses (13.2 mg/kg, 26.4 mg/kg and 52.8 mg/kg) of WS635 before and after the anesthesia/surgery. Barnes maze and fear conditioning system (FCS) were employed to evaluate the cognitive function in mice. We measured the amounts of postsynaptic density (PSD)-95, synaptophysin, and ATP in the hippocampus and cortex of the mice using western blot and ATP Colorimetric/Fluorometric Assay, respectively. We found that the treatment with 52.8 mg/kg, but not 13.2 mg/kg or 26.4 mg/kg, of WS635 attenuated the anesthesia/surgery-induced cognitive impairment in mice and the reductions in the amounts of PSD-95, synaptophysin, and ATP in the mice brain tissues. These results have established a system to study WS635 further and suggest that we need to perform more experiments to determine whether WS635 can ultimately be used as one of the interventions for PND in patients.
Plasma Proteomic Biomarkers Relating to Alzheimer’s Disease: A Meta-Analysis Based on Our Own Studies
Authors: Shi Liu , Buckley Noel J. , Bos Isabelle , Engelborghs Sebastiaan , Sleegers Kristel , Frisoni Giovanni B. , Wallin Anders , Lléo Alberto , Popp Julius , Martinez-Lage Pablo , Legido-Quigley Cristina , Barkhof Frederik , Zetterberg Henrik , Visser Pieter Jelle , Bertram Lars , Lovestone Simon , Nevado-Holgado Alejo J.
Published: July 2021

Background and Objective: Plasma biomarkers for the diagnosis and stratification of Alzheimer’s disease (AD) are intensively sought. However, no plasma markers are well established so far for AD diagnosis. Our group has identified and validated various blood-based proteomic biomarkers relating to AD pathology in multiple cohorts. The study aims to conduct a meta-analysis based on our own studies to systematically assess the diagnostic performance of our previously identified blood biomarkers.

Methods: To do this, we included seven studies that our group has conducted during the last decade. These studies used either Luminex xMAP or ELISA to measure proteomic biomarkers. As proteins measured in these studies differed, we selected protein based on the criteria that it must be measured in at least four studies. We then examined biomarker performance using random-effect meta-analyses based on the mean difference between biomarker concentrations in AD and controls (CTL), AD and mild cognitive impairment (MCI), MCI, and CTL as well as MCI converted to dementia (MCIc) and non-converted (MCInc) individuals.

Results: An overall of 2,879 subjects were retrieved for meta-analysis including 1,053 CTL, 895 MCI, 882 AD, and 49 frontotemporal dementia (FTD) patients. Six proteins were measured in at least four studies and were chosen for meta-analyses for AD diagnosis. Of them, three proteins had significant difference between AD and controls, among which alpha-2-macroglobulin (A2M) and ficolin-2 (FCN2) increased in AD while fibrinogen gamma chain (FGG) decreased in AD compared to CTL. Furthermore, FGG significantly increased in FTD compared to AD. None of the proteins passed the significance between AD and MCI, or MCI and CTL, or MCIc and MCInc, although complement component 4 (CC4) tended to increase in MCIc individuals compared to MCInc.

Conclusions: The results suggest that A2M, FCN2, and FGG are promising biomarkers to discriminate AD patients from controls, which are worthy of further validation.
Cerebrovascular Risk Factors in Possible or Probable Cerebral Amyloid Angiopathy, Modifier or Bystander?
Authors: Wagner Andrea , Maderer Jonas , Wilfling Sibylle , Kaiser Johanna , Kilic Mustafa , Linker Ralf A. , Schebesch Karl-Michael , Schlachetzki Felix
Published: July 2021

Goal: Cerebral amyloid angiopathy (CAA) is a frequent cause of atypical intracerebral hemorrhage (ICH) in the elderly. Stroke risk factors such as arterial hypertension (AHT), atrial fibrillation (AFib), diabetes mellitus (DM), and renal dysfunction (RD) are increasingly apparent in these patients. In this retrospective study, we analyzed the presence of these stroke risk factors in different initial CAA presentations comprising cerebral microbleeds (CMB), acute ischemic stroke (AIS), cortical superficial hemosiderosis (cSS), or lobar ICH (LICH) and evaluated their influence on the initial clinical presentation of patients with CAA.

Material and Methods: We identified patients with at least possible CAA defined by the modified Boston criteria admitted to the Department of Neurology or Neurosurgery from 2002 to 2018.

Findings: In the overall cohort of 209 patients, we analyzed the correlation between the number of stroke risk factors and the initial clinical presentation of patients with CAA and could show the high multimorbidity of the collective. There are large differences between the subgroups with different initial clinical presentations, e.g., patients with CMB as initial CAA presentation have the highest number of cerebrovascular risk factors and recurrent AIS, whereas AFib is more frequent in the Neurosurgery Department.

Conclusion: There is a distinct overlap between the subgroups of CAA manifestations and stroke risk factors that need to be verified in larger patient collectives. Since these comorbidities are likely to influence the clinical course of CAA, they represent possible targets for secondary prevention until specific treatment for CAA becomes available.
RBM10 Deficiency Is Associated With Increased Immune Activity in Lung Adenocarcinoma
Authors: Liu Bing , Wang Yaqi , Wang Han , Li Zhongwu , Yang Lujing , Yan Shi , Yang Xin , Ma Yuanyuan , Gao Xuan , Guan Yanfang , Yi Xin , Xia Xuefeng , Li Jingjing , Wu Nan
Published: July 2021

Introduction

RBM10 is one of the frequently mutated genes in lung adenocarcinoma (LUAD). Previous studies have confirmed that RBM10 could suppress the disease progression and cell proliferation in LUAD, but its loss-of-function mutations are more frequent in early-stage disease and decrease with the advancement of the clinical stage. This is contradictory to its role of tumor suppressor. Here, we conducted a systematic analysis to elucidate whether there was other potential biological significance of RBM10 deficiency during the progression of LUAD.

Materials and Methods

The whole exome sequencing data of 39 tumor samples from early-stage LUADs (GGN cohort) and genomic and transcriptome data of the Cancer Genome Atlas (TCGA) LUAD cohort (TCGA_LUAD cohort) and a Chinese LUAD cohort (CHOICE_ADC cohort) were first obtained. Systematic bioinformatic analyses were then conducted to determine gene expression signature, immune infiltration levels and predicted immunotherapy response. Immunohistochemistry (IHC) was also conducted to validate the result of immune infiltration.

Results

The mutation rate of RBM10 was significantly higher in the GGN cohort than that in the TCGA_LUAD and CHOICE_ADC cohorts. In both TCGA_LUAD and CHOICE_ADC cohorts, multiple immune related pathways were markedly enriched in RBM10 deficient group. Further analyses showed that tumors with RBM10 mutations displayed higher TMB, and LUADs with RBM10 deficiency also showed higher HLA expression levels, including many HLA class I and II molecules. Additionally, many immune cells, including myeloid dendritic cells, macrophages, neutrophils and CD8+T cells, showed higher infiltration levels in LUADs with RBM10 deficiency. Finally, some immune checkpoint molecules, such as PD-L1 and TIM-3, were highly expressed in RBM10 deficient population and the predicted immunotherapy response was calculated through TIDE algorithm, showing that IFNG expression, MSI score and CD8 expression were higher in RBM10 deficient group, while MDSC and M2 macrophage were lower in RBM10 deficient group.

Conclusion

Our study demonstrates that RBM10 deficient LUADs show higher HLA expression and immune cell infiltration, and some immune checkpoint molecules are also highly expressed. In brief, RBM10 deficiency could enhance anti-tumor immunity in LUAD.
Defining Unmet Need Following Lenalidomide Refractoriness: Real-World Evidence of Outcomes in Patients With Multiple Myeloma
Authors: Lecat Catherine S. Y. , Taube Jessica B. , Wilson William , Carmichael Jonathan , Parrish Christopher , Wallis Gabriel , Kyriakou Charalampia , Lee Lydia , Mahmood Shameem , Papanikolaou Xenofon , Rabin Neil K. , Sive Jonathan , Wechalekar Ashutosh D. , Yong Kwee , Cook Gordon , Popat Rakesh
Published: July 2021

Background

The treatment paradigm for multiple myeloma (MM) continues to evolve with the development of novel therapies and the earlier adoption of continuous treatments into the treatment pathway. Lenalidomide-refractory patients now represent a challenge with inferior progression free survival (PFS) reported to subsequent treatments. We therefore sought to describe the natural history of MM patients following lenalidomide in the real world.

Methods

This was a retrospective cohort review of patients with relapsed MM who received lenalidomide-based treatments in the U.K. Data were collected for demographics, subsequent therapies, treatment responses, survival outcomes and clinical trial enrollment.

Results

198 patients received lenalidomide-based treatments at a median of 2 prior lines of therapy at a median of 41 months (range 0.5-210) from diagnosis. 114 patients (72% of 158 evaluable) became refractory to lenalidomide. The overall survival (OS) after lenalidomide failure was 14.7 months having received between 0-6 subsequent lines of therapy. Few deep responses were observed with subsequent treatments and the PFS to each further line was < 7 months. There was a steep reduction in numbers of patients able to receive further treatment, with an associated increase in number of deaths. The OS of patients progressing on lenalidomide who did not enter a clinical trial incorporating novel agents was very poor (8.8 months versus 30 months, p 0.0002), although the trials group were a biologically fitter group.

Conclusion

These data demonstrate the poor outcomes of patients failing lenalidomide-based treatments in the real world, the highlight need for more effective treatments.
The Impact of lncRNAs and miRNAs on Apoptosis in Lung Cancer
Authors: Ghafouri-Fard Soudeh , Aghabalazade Amin , Shoorei Hamed , Majidpoor Jamal , Taheri Mohammad , Mokhtari Majid
Published: July 2021

Apoptosis is a coordinated cellular process that occurs in several physiological situations. Dysregulation of apoptosis has been documented in numerous pathological situations, particularly cancer. Non-coding RNAs regulate apoptosis via different mechanisms. Lung cancer is among neoplastic conditions in which the role of non-coding RNAs in the regulation of apoptosis has been investigated. Non-coding RNAs that regulate apoptosis in lung cancer have functional interactions with PI3K/Akt, PTEN, GSK-3β, NF-κB, Bcl-2, Bax, p53, mTOR and other important cancer-related pathways. Globally, over-expression of apoptosis-blocking non-coding RNAs has been associated with poor prognosis of patients, while apoptosis-promoting ones have the opposite effect. In the current paper, we describe the impact of lncRNAs and miRNAs on cell apoptosis in lung cancer.
Condensate Formation in Collisionless Plasma
Authors: Treumann R. A. , Baumjohann Wolfgang
Published: July 2021

Particle condensates in general magnetic mirror geometries in high-temperature plasmas may be caused by a discrete resonance with thermal ion-acoustic background noise near mirror points. The resonance breaks the bounce symmetry, temporally locking the particles to the resonant wavelength. The relevant correlation lengths are the Debye length in the parallel direction and the ion gyroradius in the perpendicular direction.
Lipid Body Dynamics in Shoot Meristems: Production, Enlargement, and Putative Organellar Interactions and Plasmodesmal Targeting
Authors: Veerabagu Manikandan , Rinne Päivi L. H. , Skaugen Morten , Paul Laju K. , van der Schoot Christiaan
Published: July 2021

Post-embryonic cells contain minute lipid bodies (LBs) that are transient, mobile, engage in organellar interactions, and target plasmodesmata (PD). While LBs can deliver γ-clade 1,3-β-glucanases to PD, the nature of other cargo is elusive. To gain insight into the poorly understood role of LBs in meristems, we investigated their dynamics by microscopy, gene expression analyzes, and proteomics. In developing buds, meristems accumulated LBs, upregulated several LB-specific OLEOSIN genes and produced OLEOSINs. During bud maturation, the major gene OLE6 was strongly downregulated, OLEOSINs disappeared from bud extracts, whereas lipid biosynthesis genes were upregulated, and LBs were enlarged. Proteomic analyses of the LB fraction of dormant buds confirmed that OLEOSINs were no longer present. Instead, we identified the LB-associated proteins CALEOSIN (CLO1), Oil Body Lipase 1 (OBL1), Lipid Droplet Interacting Protein (LDIP), Lipid Droplet Associated Protein1a/b (LDAP1a/b) and LDAP3a/b, and crucial components of the OLEOSIN-deubiquitinating and degradation machinery, such as PUX10 and CDC48A. All mRFP-tagged LDAPs localized to LBs when transiently expressed in Nicotiana benthamiana. Together with gene expression analyzes, this suggests that during bud maturation, OLEOSINs were replaced by LDIP/LDAPs at enlarging LBs. The LB fraction contained the meristem-related actin7 (ACT7), “myosin XI tail-binding” RAB GTPase C2A, an LB/PD-associated γ-clade 1,3-β-glucanase, and various organelle- and/or PD-localized proteins. The results are congruent with a model in which LBs, motorized by myosin XI-k/1/2, traffic on F-actin, transiently interact with other organelles, and deliver a diverse cargo to PD.
Shifts in the Abundances of Saprotrophic and Ectomycorrhizal Fungi With Altered Leaf Litter Inputs
Authors: Marañón-Jiménez Sara , Radujković Dajana , Verbruggen Erik , Grau Oriol , Cuntz Matthias , Peñuelas Josep , Richter Andreas , Schrumpf Marion , Rebmann Corinna
Published: July 2021

Ectomycorrhizal (EcM) and saprotrophic fungi interact in the breakdown of organic matter, but the mechanisms underlying the EcM role on organic matter decomposition are not totally clear. We hypothesized that the ecological relations between EcM and saprotroph fungi are modulated by resources availability and accessibility, determining decomposition rates. We manipulated the amount of leaf litter inputs (No-Litter, Control Litter, Doubled Litter) on Trenched (root exclusion) and Non-Trenched plots (with roots) in a temperate deciduous forest of EcM-associated trees. Resultant shifts in soil fungal communities were determined by phospholipid fatty acids and DNA sequencing after 3 years, and CO2 fluxes were measured throughout this period. Different levels of leaf litter inputs generated a gradient of organic substrate availability and accessibility, altering the composition and ecological relations between EcM and saprotroph fungal communities. EcM fungi dominated at low levels of fresh organic substrates and lower organic matter quality, where short-distances exploration types seem to be better competitors, whereas saprotrophs and longer exploration types of EcM fungi tended to dominate at high levels of leaf litter inputs, where labile organic substrates were easily accessible. We were, however, not able to detect unequivocal signs of competition between these fungal groups for common resources. These results point to the relevance of substrate quality and availability as key factors determining the role of EcM and saprotroph fungi on litter and soil organic matter decay and represent a path forward on the capacity of organic matter decomposition of different exploration types of EcM fungi.
Initial Validation of the Mindful Presence Scale: The Issue of the Construal Level of Scale Items
Authors: Lengyel Attila , Keczeli Danica , Orosz Róbert , Bács Zoltán , Müller Anetta , Szőke Szilvia , Bába Éva Bácsné
Published: July 2021

Our research has two main aims. It undertakes the validation of a six-item trait mindfulness scale called Mindful Presence Scale (MPS), which measures central aspects of mindfulness. For the first time in mindfulness literature, the construal level of scale items is also examined. Four questionnaire-based online studies were conducted. Study 1 drew three samples (nn= 391,np= 215, andnb= 235) from the students at the University of Debrecen. It examined the factor structure, reliability, and internal consistency of the three differently worded scale versions. The positively worded scale version (MPSp) yielded a stable two-factor structure and demonstrated the best psychometric properties. Study 2 performed a confirmatory factor analysis on a sample drawn from public employees across the country (ncfa= 420). The two-factor solution in Study 1 was confirmed. χ2tests were not significant, and fit indices were excellent. There was no significant difference between the high-level construal subscale (Fhlc) and the low-level construal subscale (Fllc) in terms of factorial stability. Participant of Study 3 were students who did not take part in Study 1. The sample (ninv= 250) was tested for measurement invariance across gender. The scaled results supported strong/threshold invariance. Study 4 tested concurrent validity with 10 concurrent instruments. A sample of secondary school teachers (ncon= 128) was tested by examining Spearman's rank order correlations. There was a significant difference in how the Fhlcand Fllcsubscales predicted scores of some of the concurrent instruments. Further research is warranted into how the construal level of mindfulness scale items affects the recollection of the mindful experience. Overall, MPSpproved to be a valid short mindfulness measure.
Effects of Organizational Support and Organizational Justice on Police Officers’ Work Engagement
Authors: Piotrowski Andrzej , Rawat Samir , Boe Ole
Published: July 2021

The impact of organizational support and organizational justice on work engagement was investigated in a group of police officers. A review of the literature revealed that studies reporting differences between the influence of supervisors and coworker justice and support on work engagement among police officers are grossly insufficient. This study hypothesized that organizational support and organizational justice would positively predict work engagement among police officers. It was also hypothesized that, among police officers, supervisor support is more strongly related to work engagement than coworker support and that supervisor justice is more strongly linked to work engagement than coworker justice. Participants were 170 police officers who worked in police departments in northern Poland. A regression analysis showed that supervisor support and supervisor justice had a positive effect on police officers’ work engagement, whereby organizational support coupled with organizational justice accounted for 26% of the variability of work engagement. Theoretical and practical implications are discussed, and directions for future research are suggested.
Effects of Mindfulness Meditation on Musical Aesthetic Emotion Processing
Authors: Liu Xiaolin , Liu Yong , Shi Huijuan , Zheng Maoping
Published: July 2021

Mindfulness meditation is a form of self-regulatory training for the mind and the body. The relationship between mindfulness meditation and musical aesthetic emotion processing (MAEP) remains unclear. This study aimed to explore the effect of temporary mindfulness meditation on MAEP while listening to Chinese classical folk instrumental musical works. A 2 [(groups: mindfulness meditation group (MMG); control group (CG)] × 3 (music emotions: calm music, happy music, and sad music) mixed experimental design and a convenience sample of university students were used to verify our hypotheses, which were based on the premise that temporary mindfulness meditation may affect MAEP (MMG vs. CG). Sixty-seven non-musically trained participants (65.7% female, age range: 18–22 years) were randomly assigned to two groups (MMG or CG). Participants in MMG were given a single 10-min recorded mindfulness meditation training before and when listening to music. The instruments for psychological measurement comprised of the Five Facet Mindfulness Questionnaire (FFMQ) and the Positive and Negative Affect Schedule (PANAS). Self-report results showed no significant between-group differences for PANAS and for the scores of four subscales of the FFMQ (p > 0.05 throughout), except for the non-judging of inner experience subscale. Results showed that temporary mindfulness meditation training decreased the negative emotional experiences of happy and sad music and the positive emotional experiences of calm music during recognition and experience and promoted beautiful musical experiences in individuals with no musical training. Maintaining a state of mindfulness while listening to music enhanced body awareness and led to experiencing a faster passage of musical time. In addition, it was found that Chinese classical folk instrumental musical works effectively induced aesthetic emotion and produced multidimensional aesthetic experiences among non-musically trained adults. This study provides new insights into the relationship between mindfulness and music emotion.
Yes! Maximizers Maximize Almost Everything: The Decision-Making Style Is Consistent in Different Decision Domains
Authors: Moyano-Díaz Emilio , Mendoza-Llanos Rodolfo
Published: July 2021

The decision-making literature distinguishes one maximizing style from another satisficing decision-making style, but it is unknown whether these styles remain stable or are variable depending on the occasion. One way to approach it is to verify eventual generalization of these styles in behavior of people in different decision domains. Some incipient results with University students from the United States and Austria suggest that these styles would remain in three different domains. However, it is unknown if this is the case in adults, other cultures, or vital areas of great relevance, such as health and personal finances. The objective here is to identify if Chilean Latin American participants of different sex and age maintain their decision-making style in five different decision domains. The sample was 343 volunteers, 52.6% men, from two regions of central-southern Chile (Maule and Ñuble), aged between 20 and 90 years (M= 45.47;SD= 16.05), who answered the Maximization Tendency Scale, and 45 items corresponding to five different decision domains: health, life decision, finances, services and experiences, and consumer's good. An apparent coherence of decision-making style—maximizing and satisficing—was obtained in the five domains. The health domain stands out for being the one in which it is maximized and with greater internal homogeneity.
Biophilia as Evolutionary Adaptation: An Onto- and Phylogenetic Framework for Biophilic Design
Authors: Barbiero Giuseppe , Berto Rita
Published: July 2021

Biophilia is a human personality trait described initially by Erich Fromm and later by E.O. Wilson, both of whom agree that biophilia has a biological basis and that it is fundamental to develop harmonious relationships between humans and the biosphere. This review aims at establishing a definition of biophilia as an evolutionary process. To this end, the most significant studies of evolutionary psychology were considered, to outline the fundamental characteristics of a hypothetical biophilic temperament/personality and to reconstruct a plausible history of biophilia as an evolutionary process. This process considers different typologies of Nature (wilderness, rural, and urban) and human cultures (Paleolithic, Neolithic, and Burg) and leads us to consider environmental preference and psycho-physiological recovery in relation to the threshold of time spent in contact with Nature. Unfortunately, modern people, especially children, lack direct and frequent contact with Nature and this can have negative consequences on their physical and mental health. Biophilic design, considering the evolutionary roots of this architectural approach, is an effective way of planning/designing interior and urban environments to stimulate the innate biophilia of the individual.
Effectiveness of Mobile Technology in Managing Fatigue: Balert App
Authors: De La Vega Ricardo , Anabalón Héctor , Jara Cristian , Villamil-Cabello Eduardo , Chervellino Miguel , Calvo-Rodríguez Álvaro
Published: July 2021

The performance of professional tasks with a high cognitive, emotional, and even physiological demand, can cause a state of mental fatigue, which implies attentional alterations, greater errors in the tasks performed and a decrease in personal and work productivity caused by a deterioration of the cognitive control processes. The present study presents a mobile phone application named BAlert that allows monitoring and controlling the body's fatigue processes based on the scores obtained in the Stroop effect and the heart rate variability. A pilot study has been carried out with a sample of 63 adults who have used the application a total of 942 times. The results allow us to classify the subjects, by logistic regression analysis, in their fatigue levels in 74% of the occasions. These results highlight the importance of this mobile application to control work fatigue processes in different possible scenarios (military, health, sports, business, etc.).