bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole Genome-Based Characterization of Listeria monocytogenes Isolates Recovered From the Food Chain in South Africa
Authors: Mafuna Thendo , Matle Itumeleng , Magwedere Kudakwashe , Pierneef Rian E. , Reva Oleg N.
Published: July 2021

Listeria monocytogenesis an important foodborne pathogen which has the ability to adapt and survive in food and food processing facilities where it can persist for years. In this study, a total of 143L. monocytogenesisolates in South Africa (SA) were characterized for their strain’s genetic relatedness, virulence profiles, stress tolerance and resistance genes associated withL. monocytogenes. The Core Genome Multilocus Sequence Typing (cgMLST) analysis revealed that the most frequent serogroups were IVb and IIa; Sequence Types (ST) were ST204, ST2, and ST1; and Clonal Complexes (CC) were CC204, CC1, and CC2. Examination of genes involved in adaptation and survival ofL. monocytogenesin SA showed that ST1, ST2, ST121, ST204, and ST321 are well adapted in food processing environments due to the significant over-representation of Benzalkonium chloride (BC) resistance genes (bcrABCcassette,ermC, mdrLandIde), stress tolerance genes (SSI-1 and SSI-2), Prophage (φ) profiles (LP_101, vB LmoS 188, vB_LmoS_293, and B054 phage), plasmids profiles (N1-011A, J1776, and pLM5578) and biofilm formation associated genes. Furthermore, theL. monocytogenesstrains that showed hyper-virulent potential were ST1, ST2 and ST204, and hypo-virulent were ST121 and ST321 because of the presence and absence of major virulence factors such as LIPI-1, LIPI-3, LIPI-4 and the internalin gene family members includinginlABCEFJ. The information provided in this study revealed that hyper-virulent strains ST1, ST2, and ST204 could present a major public health risk due to their association with meat products and food processing environments in SA.
Decomposition of Microbial Necromass Is Divergent at the Individual Taxonomic Level in Soil
Authors: Dong Weiling , Song Alin , Yin Huaqun , Liu Xueduan , Li Jianwei , Fan Fenliang
Published: July 2021

The turnover of microbial biomass plays an important part in providing a significant source of carbon (C) to soil organic C. However, whether the decomposition of microbial necromass (non-living microbial biomass) in the soil varies at the individual taxa level remains largely unknown. To fill up these gaps, we compared the necromass decomposition of bacterial and archaeal taxa by separating live microbial biomass with 18O-stable isotope probing from dead microbial biomass in soil. Our results showed that most of the microbial necromass at the operational taxonomic unit level (88.51%), which mainly belong to Acidobacteria, Actinobacteria, Gemmatimonadetes, and Proteobacteria, decomposed significantly after 30 days. In addition, there were great variations in necromass decomposition within each phylum, such as the decomposition of operational taxonomic units in Proteobacteria that ranged from 51% (Beijerinckia) to 92% (Nitrosospira). More importantly, the necromass decomposition was not related to the chemical composition of the cell wall but might positively correlate with the guanine–cytosine content of DNA and negatively correlated with genome size. This study provided a new insight that the decomposition of microbial necromass in soil was divergent at the individual taxonomic level and could not be fully explained by previously proposed mechanisms.
Edging on Mutational Bias, Induced Natural Selection From Host and Natural Reservoirs Predominates Codon Usage Evolution in Hantaan Virus
Authors: Ata Galal , Wang Hao , Bai Haoxiang , Yao Xiaoting , Tao Shiheng
Published: July 2021

The molecular evolutionary dynamics that shape hantaviruses’ evolution are poorly understood even now, besides the contribution of virus-host interaction to their evolution remains an open question. Our study aimed to investigate these two aspects in Hantaan virus (HTNV)—the prototype of hantaviruses and an emerging zoonotic pathogen that infects humans, causing hemorrhagic fever with renal syndrome (HFRS): endemic in Far East Russia, China, and South Korea—via a comprehensive, phylogenetic-dependent codon usage analysis. We found that host- and natural reservoir-induced natural selection is the primary determinant of its biased codon choices, exceeding the mutational bias effect. The phylogenetic analysis of HTNV strains resulted in three distinct clades: South Korean, Russian, and Chinese. An effective number of codon (ENC) analysis showed a slightly biased codon usage in HTNV genomes. Nucleotide composition and RSCU analyses revealed a significant bias toward A/U nucleotides and A/U-ended codons, indicating the potential influence of mutational bias on the codon usage patterns of HTNV. Via ENC-plot, Parity Rule 2 (PR2), and neutrality plot analyses, we would conclude the presence of both mutation pressure and natural selection effect in shaping the codon usage patterns of HTNV; however, natural selection is the dominant factor influencing its codon usage bias. Codon adaptation index (CAI), Relative codon deoptimization index (RCDI), and Similarity Index (SiD) analyses uncovered the intense selection pressure from the host (Human) and natural reservoirs (Striped field mouse and Chinese white-bellied rat) in shaping HTNV biased codon choices. Our study clearly revealed the evolutionary processes in HTNV and the role of virus-host interaction in its evolution. Moreover, it opens the door for a more comprehensive codon usage analysis for all hantaviruses species to determine their molecular evolutionary dynamics and adaptability to several hosts and environments. We believe that our research will help in a better and deep understanding of HTNV evolution that will serve its future basic research and aid live attenuated vaccines design.
Mixotrophic Growth of Chlorella sorokiniana on Acetate and Butyrate: Interplay Between Substrate, C:N Ratio and pH
Authors: Lacroux Julien , Seira Jordan , Trably Eric , Bernet Nicolas , Steyer Jean-Philippe , van Lis Robert
Published: July 2021

Microalgae can be cultivated on waste dark fermentation effluents containing volatile fatty acids (VFA) such as acetate or butyrate. These VFA can however inhibit microalgae growth at concentrations above 0.5-1 gC.L–1. This study used the model strain Chlorella sorokiniana to investigate the effects of acetate or butyrate concentration on biomass growth rates and yields alongside C:N:P ratios and pH control. Decreasing undissociated acid levels by raising the initial pH to 8.0 allowed growth without inhibition up to 5 gC.L–1 VFAs. However, VFA concentration strongly affected biomass yields irrespective of pH control or C:N:P ratios. Biomass yields on 1.0 gC.L–1 acetate were around 1.3-1.5 gC.gC–1 but decreased by 26-48% when increasing initial acetate to 2.0 gC.L–1. This was also observed for butyrate with yields decreasing up to 25%. This decrease in yield in suggested to be due to the prevalence of heterotrophic metabolism at high organic acid concentration, which reduced the amount of carbon fixed by autotrophy. Finally, the effects of C:N:P on biomass, lipids and carbohydrates production dynamics were assessed using a mixture of both substrates. In nutrient replete conditions, C. sorokiniana accumulated up to 20.5% carbohydrates and 16.4% lipids while nutrient limitation triggered carbohydrates accumulation up to 45.3%.
The Role of Fatty Acid Metabolites in Vaginal Health and Disease: Application to Candidiasis
Authors: Baldewijns Silke , Sillen Mart , Palmans Ilse , Vandecruys Paul , Van Dijck Patrick , Demuyser Liesbeth
Published: July 2021

Although the vast majority of women encounters at least one vaginal infection during their life, the amount of microbiome-related research performed in this area lags behind compared to alternative niches such as the intestinal tract. As a result, effective means of diagnosis and treatment, especially of recurrent infections, are limited. The role of the metabolome in vaginal health is largely elusive. It has been shown that lactate produced by the numerous lactobacilli present promotes health by limiting the chance of infection. Short chain fatty acids (SCFA) have been mainly linked to dysbiosis, although the causality of this relationship is still under debate. In this review, we aim to bring together information on the role of the vaginal metabolome and microbiome in infections caused byCandida. Vulvovaginal candidiasis affects near to 70% of all women at least once in their life with a significant proportion of women suffering from the recurrent variant. We assess the role of fatty acid metabolites, mainly SCFA and lactate, in onset of infection and virulence of the fungal pathogen. In addition, we pinpoint where lack of research limits our understanding of the molecular processes involved and restricts the possibility of developing novel treatment strategies.
PKC Delta Activation Promotes Endoplasmic Reticulum Stress (ERS) and NLR Family Pyrin Domain-Containing 3 (NLRP3) Inflammasome Activation Subsequent to Asynuclein-Induced Microglial Activation: Involvement of Thioredoxin-Interacting Protein (TXNIP)/Thioredoxin (Trx) Redoxisome Pathway
Authors: Samidurai Manikandan , Palanisamy Bharathi N. , Bargues-Carot Alejandra , Hepker Monica , Kondru Naveen , Manne Sireesha , Zenitsky Gary , Jin Huajun , Anantharam Vellareddy , Kanthasamy Anumantha G. , Kanthasamy Arthi
Published: July 2021

A classical hallmark of Parkinson’s disease (PD) pathogenesis is the accumulation of misfolded alpha-synuclein (αSyn) within Lewy bodies and Lewy neurites, although its role in microglial dysfunction and resultant dopaminergic (DAergic) neurotoxicity is still elusive. Previously, we identified that protein kinase C delta (PKCδ) is activated in post mortem PD brains and experimental Parkinsonism and that it participates in reactive microgliosis; however, the relationship between PKCδ activation, endoplasmic reticulum stress (ERS) and the reactive microglial activation state in the context of α-synucleinopathy is largely unknown. Herein, we show that oxidative stress, mitochondrial dysfunction, NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, and PKCδ activation increased concomitantly with ERS markers, including the activating transcription factor 4 (ATF-4), serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1α (p-IRE1α), p-eukaryotic initiation factor 2 (eIF2α) as well as increased generation of neurotoxic cytokines, including IL-1β in aggregated αSynagg-stimulated primary microglia. Importantly, in mouse primary microglia-treated with αSynagg we observed increased expression of Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of the thioredoxin (Trx) pathway, a major antioxidant protein system. Additionally, αSynagg promoted interaction between NLRP3 and TXNIP in these cells. In vitro knockdown of PKCδ using siRNA reduced ERS and led to reduced expression of TXNIP and the NLRP3 activation response in αSynagg-stimulated mouse microglial cells (MMCs). Additionally, attenuation of mitochondrial reactive oxygen species (mitoROS) via mito-apocynin and amelioration of ERS via the eIF2α inhibitor salubrinal (SAL) reduced the induction of the ERS/TXNIP/NLRP3 signaling axis, suggesting that mitochondrial dysfunction and ERS may act in concert to promote the αSynagg-induced microglial activation response. Likewise, knockdown of TXNIP by siRNA attenuated the αSynagg-induced NLRP3 inflammasome activation response. Finally, unilateral injection of αSyn preformed fibrils (αSynPFF) into the striatum of wild-type mice induced a significant increase in the expression of nigral p-PKCδ, ERS markers, and upregulation of the TXNIP/NLRP3 inflammasome signaling axis prior to delayed loss of TH+ neurons. Together, our results suggest that inhibition of ERS and its downstream signaling mediators TXNIP and NLRP3 might represent novel therapeutic avenues for ameliorating microglia-mediated neuroinflammation in PD and other synucleinopathies.
Neuro4PD: An Initial Neurorobotics Model of Parkinson's Disease
Authors: Pimentel Jhielson M. , Moioli Renan C. , de Araujo Mariana F. P. , Ranieri Caetano M. , Romero Roseli A. F. , Broz Frank , Vargas Patricia A.
Published: July 2021

In this work, we present the first steps toward the creation of a new neurorobotics model of Parkinson's Disease (PD) that embeds, for the first time in a real robot, a well-established computational model of PD. PD mostly affects the modulation of movement in humans. The number of people suffering from this neurodegenerative disease is set to double in the next 15 years and there is still no cure. With the new model we were capable to further explore the dynamics of the disease using a humanoid robot. Results show that the embedded model under both conditions, healthy and parkinsonian, was capable of performing a simple behavioural task with different levels of motor disturbance. We believe that this neurorobotics model is a stepping stone to the development of more sophisticated models that could eventually test and inform new PD therapies and help to reduce and replace animals in research.
Superiority of Formalin-Fixed Paraffin-Embedded Brain Tissue for in vitro Assessment of Progressive Supranuclear Palsy Tau Pathology With [18F]PI-2620
Authors: Willroider Marie , Roeber Sigrun , Horn Anja K. E. , Arzberger Thomas , Scheifele Maximilian , Respondek Gesine , Sabri Osama , Barthel Henryk , Patt Marianne , Mishchenko Olena , Schildan Andreas , Mueller André , Koglin Norman , Stephens Andrew , Levin Johannes , Höglinger Günter U. , Bartenstein Peter , Herms Jochen , Brendel Matthias , Beyer Leonie
Published: July 2021

Objectives: Autoradiography on brain tissue is used to validate binding targets of newly discovered radiotracers. The purpose of this study was to correlate quantification of autoradiography signal using the novel next-generation tau positron emission tomography (PET) radiotracer [18F]PI-2620 with immunohistochemically determined tau-protein load in both formalin-fixed paraffin-embedded (FFPE) and frozen tissue samples of patients with Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP).

Methods: We applied [18F]PI-2620 autoradiography to postmortem cortical brain samples of six patients with AD, five patients with PSP and five healthy controls, respectively. Binding intensity was compared between both tissue types and different disease entities. Autoradiography signal quantification (CWMR = cortex to white matter ratio) was correlated with the immunohistochemically assessed tau load (AT8-staining, %-area) for FFPE and frozen tissue samples in the different disease entities.

Results: In AD tissue, relative cortical tracer binding was higher in frozen samples when compared to FFPE samples (CWMRfrozen vs. CWMRFFPE: 2.5-fold, p < 0.001), whereas the opposite was observed in PSP tissue (CWMRfrozen vs. CWMRFFPE: 0.8-fold, p = 0.004). In FFPE samples, [18F]PI-2620 autoradiography tracer binding and immunohistochemical tau load correlated significantly for both PSP (R = 0.641, p < 0.001) and AD tissue (R = 0.435, p = 0.016), indicating a high agreement of relative tracer binding with underlying pathology. In frozen tissue, the correlation between autoradiography and immunohistochemistry was only present in AD (R = 0.417, p = 0.014) but not in PSP tissue (R = −0.115, p = n.s.).

Conclusion: Our head-to-head comparison indicates that FFPE samples show superiority over frozen samples for autoradiography assessment of PSP tau pathology by [18F]PI-2620. The [18F]PI-2620 autoradiography signal in FFPE samples reflects AT8 positive tau in samples of both PSP and AD patients.
Exploring Area-Dependent Pr0.7Ca0.3MnO3-Based Memristive Devices as Synapses in Spiking and Artificial Neural Networks
Authors: Gutsche Alexander , Siegel Sebastian , Zhang Jinchao , Hambsch Sebastian , Dittmann Regina
Published: July 2021

Memristive devices are novel electronic devices, which resistance can be tuned by an external voltage in a non-volatile way. Due to their analog resistive switching behavior, they are considered to emulate the behavior of synapses in neuronal networks. In this work, we investigate memristive devices based on the field-driven redox process between the p-conducting Pr0.7Ca0.3MnO3 (PCMO) and different tunnel barriers, namely, Al2O3, Ta2O5, and WO3. In contrast to the more common filamentary-type switching devices, the resistance range of these area-dependent switching devices can be adapted to the requirements of the surrounding circuit. We investigate the impact of the tunnel barrier layer on the switching performance including area scaling of the current and variability. Best performance with respect to the resistance window and the variability is observed for PCMO with a native Al2O3 tunnel oxide. For all different layer stacks, we demonstrate a spike timing dependent plasticity like behavior of the investigated PCMO cells. Furthermore, we can also tune the resistance in an analog fashion by repeated switching the device with voltage pulses of the same amplitude and polarity. Both measurements resemble the plasticity of biological synapses. We investigate in detail the impact of different pulse heights and pulse lengths on the shape of the stepwise SET and RESET curves. We use these measurements as input for the simulation of training and inference in a multilayer perceptron for pattern recognition, to show the use of PCMO-based ReRAM devices as weights in artificial neural networks which are trained by gradient descent methods. Based on this, we identify certain trends for the impact of the applied voltages and pulse length on the resulting shape of the measured curves and on the learning rate and accuracy of the multilayer perceptron.
Congruency of Information Rather Than Body Ownership Enhances Motor Performance in Highly Embodied Virtual Reality
Authors: Odermatt Ingrid A. , Buetler Karin A. , Wenk Nicolas , Özen Özhan , Penalver-Andres Joaquin , Nef Tobias , Mast Fred W. , Marchal-Crespo Laura
Published: July 2021

In immersive virtual reality, the own body is often visually represented by an avatar. This may induce a feeling of body ownership over the virtual limbs. Importantly, body ownership and the motor system share neural correlates. Yet, evidence on the functionality of this neuroanatomical coupling is still inconclusive. Findings from previous studies may be confounded by the congruent vs. incongruent multisensory stimulation used to modulate body ownership. This study aimed to investigate the effect of body ownership and congruency of information on motor performance in immersive virtual reality. We aimed to modulate body ownership by providing congruent vs. incongruent visuo-tactile stimulation (i.e., participants felt a brush stroking their real fingers while seeing a virtual brush stroking the same vs. different virtual fingers). To control for congruency effects, unimodal stimulation conditions (i.e., only visual or tactile) with hypothesized low body ownership were included. Fifty healthy participants performed a decision-making (pressing a button as fast as possible) and a motor task (following a defined path). Body ownership was assessed subjectively with established questionnaires and objectively with galvanic skin response (GSR) when exposed to a virtual threat. Our results suggest that congruency of information may decrease reaction times and completion time of motor tasks in immersive virtual reality. Moreover, subjective body ownership is associated with faster reaction times, whereas its benefit on motor task performance needs further investigation. Therefore, it might be beneficial to provide congruent information in immersive virtual environments, especially during the training of motor tasks, e.g., in neurorehabilitation interventions.
Challenges and Opportunities for the Future of Brain-Computer Interface in Neurorehabilitation
Authors: Simon Colin , Bolton David A. E. , Kennedy Niamh C. , Soekadar Surjo R. , Ruddy Kathy L.
Published: July 2021

Brain-computer interfaces (BCIs) provide a unique technological solution to circumvent the damaged motor system. For neurorehabilitation, the BCI can be used to translate neural signals associated with movement intentions into tangible feedback for the patient, when they are unable to generate functional movement themselves. Clinical interest in BCI is growing rapidly, as it would facilitate rehabilitation to commence earlier following brain damage and provides options for patients who are unable to partake in traditional physical therapy. However, substantial challenges with existing BCI implementations have prevented its widespread adoption. Recent advances in knowledge and technology provide opportunities to facilitate a change, provided that researchers and clinicians using BCI agree on standardisation of guidelines for protocols and shared efforts to uncover mechanisms. We propose that addressing the speed and effectiveness of learning BCI control are priorities for the field, which may be improved by multimodal or multi-stage approaches harnessing more sensitive neuroimaging technologies in the early learning stages, before transitioning to more practical, mobile implementations. Clarification of the neural mechanisms that give rise to improvement in motor function is an essential next step towards justifying clinical use of BCI. In particular, quantifying the unknown contribution of non-motor mechanisms to motor recovery calls for more stringent control conditions in experimental work. Here we provide a contemporary viewpoint on the factors impeding the scalability of BCI. Further, we provide a future outlook for optimal design of the technology to best exploit its unique potential, and best practices for research and reporting of findings.
Systems and Circuits Linking Chronic Pain and Circadian Rhythms
Authors: Warfield Andrew E. , Prather Jonathan F. , Todd William D.
Published: July 2021

Research over the last 20 years regarding the link between circadian rhythms and chronic pain pathology has suggested interconnected mechanisms that are not fully understood. Strong evidence for a bidirectional relationship between circadian function and pain has been revealed through inflammatory and immune studies as well as neuropathic ones. However, one limitation of many of these studies is a focus on only a few molecules or cell types, often within only one region of the brain or spinal cord, rather than systems-level interactions. To address this, our review will examine the circadian system as a whole, from the intracellular genetic machinery that controls its timing mechanism to its input and output circuits, and how chronic pain, whether inflammatory or neuropathic, may mediate or be driven by changes in these processes. We will investigate how rhythms of circadian clock gene expression and behavior, immune cells, cytokines, chemokines, intracellular signaling, and glial cells affect and are affected by chronic pain in animal models and human pathologies. We will also discuss key areas in both circadian rhythms and chronic pain that are sexually dimorphic. Understanding the overlapping mechanisms and complex interplay between pain and circadian mediators, the various nuclei they affect, and how they differ between sexes, will be crucial to move forward in developing treatments for chronic pain and for determining how and when they will achieve their maximum efficacy.
Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer
Authors: Bellanger Aurélie , Le Diep T. , Vendrell Julie , Wierinckx Anne , Pongor Lőrinc S. , Solassol Jérôme , Lachuer Joël , Clezardin Philippe , Győrffy Balázs , Cohen Pascale A.
Published: July 2021

Oncogene alternative splicing events can create distinct functional transcripts that offer new candidate prognostic biomarkers for breast cancer. ZNF217 is a well-established oncogene but its exon 4-skipping isoform (ZNF217-ΔE4) has never been investigated in terms of clinical or biological relevance. Using in silico RNA-seq and RT-qPCR analyses, we demonstrated for the first time the existence of ZNF217-ΔE4 transcripts in primary breast tumors, and a positive correlation between ZNF217-ΔE4 mRNA levels and those of the wild-type oncogene (ZNF217-WT). A pilot retrospective analysis revealed that, in the Luminal subclass, the combination of the two ZNF217 variants (the ZNF217-ΔE4-WT gene-expression signature) provided more information than the mRNA expression levels of each isoform alone. Ectopic overexpression of ZNF217-ΔE4 in breast cancer cells promoted an aggressive phenotype and an increase in ZNF217-WT expression levels that was inversely correlated with DNA methylation of the ZNF217 gene. This study provides new insights into the possible role of the ZNF217-ΔE4 splice variant in breast cancer and suggests a close interplay between the ZNF217-WT and ZNF217-ΔE4 isoforms. Our data suggest that a dual signature combining the expression levels of these two isoforms may serve as a novel prognostic biomarker allowing better stratification of breast cancers with good prognosis and aiding clinicians in therapeutic decisions.
Construction of an Immune-Related Six-lncRNA Signature to Predict the Outcomes, Immune Cell Infiltration, and Immunotherapy Response in Patients With Hepatocellular Carcinoma
Authors: Zhou Pengcheng , Lu Yuhua , Zhang Yewei , Wang Lei
Published: July 2021

Background

Hepatocellular carcinoma (HCC) is one of the world’s most lethal malignant tumors with a poor prognosis. Growing evidence has been demonstrating that immune-related long non-coding RNAs (lncRNAs) are relevant to the tumor microenvironment (TME) and can help assess the effects of immunotherapy and evaluate one’s prognosis. This study aims to identify an immune-related lncRNA signature for the prospective assessment of the immunotherapy and prognosis in HCC.

Method

We downloaded HCC RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) project database. We first used ESTIMATE to evaluate the TME. Then, we conducted a cox regression analysis to construct a prognostic signature and the riskScore. We then applied the univariate Cox regression, multivariate Cox regression, principal components analysis (PCA), receiver operating characteristic (ROC) curve, and stratification analyses to confirm our previous assessments. Afterward, we employed a gene set enrichment analysis (GSEA) to explore the biological processes and pathways. Besides, we used CIBERSORT to estimate the abundance of tumor-infiltrating immune cells (TIICs). Furthermore, we investigated the relationship between the immune-related lncRNA signature and immune checkpoint genes. Finally, we used the quantitative real-time polymerase chain reaction (qRT-PCR) assays to demonstrate the expression of the six lncRNAs.

Results

We identified six immune-related lncRNAs — MSC-AS1, AC145207.5, SNHG3, AL365203.2, AL031985.3, NRAV — which show the ability to stratify patients into high-risk and low-risk groups with significantly different survival rates. The univariate Cox regression, multivariate Cox regression, ROC, and stratification analyses confirmed that the immune-related six-lncRNA signature was a novel independent prognostic factor in HCC patients. The high-risk group and low-risk group illustrated contrasting distributions in PCA. The GSEA suggested that the immune-related six-lncRNA signature was involved in the immune-related biological processes and pathways. Besides, the immune-related six-lncRNA signature was associated with the infiltration of immune cells. Furthermore, it was linked with the expression of critical immune genes and could predict immunotherapy’s clinical response. Finally, the qRT-PCR demonstrated that the six lncRNAs were significantly differentially expressed in HCC cell lines and normal hepatic cell lines.

Conclusion

In summary, we identified an immune-related six-lncRNA signature that can predict the outcomes, immune cell infiltration, and immunotherapy response in patients with hepatocellular carcinoma.
IL-2 Signaling Axis Defects: How Many Faces?
Authors: Consonni Filippo , Favre Claudio , Gambineri Eleonora
Published: July 2021

CD25, Signal transducer and activator of transcription 5B (STAT5B) and Forkhead box P3 (FOXP3) are critical mediators of Interleukin-2 (IL-2) signaling pathway in regulatory T cells (Tregs). CD25 (i.e., IL-2 Receptor α) binds with high affinity to IL-2, activating STAT5B-mediated signaling that eventually results in transcription of FOXP3, a master regulator of Treg function. Consequently, loss-of-function mutations in these proteins give rise to Treg disorders (i.e., Tregopathies) that clinically result in multiorgan autoimmunity. Immunodysregulation, Polyendocrinopathy Enteropathy X-linked (IPEX), due to mutations inFOXP3, has historically been the prototype of Tregopathies. This review describes current knowledge about defects inCD25, STAT5B, andFOXP3, highlighting that these disorders both share a common biological background and display comparable clinical features. However, specific phenotypes are associated with each of these syndromes, while certain laboratory findings could be helpful tools for clinicians, in order to achieve a prompt genetic diagnosis. Current treatment strategies will be outlined, keeping an eye on gene editing, an interesting therapeutic perspective that could definitely change the natural history of these disorders.
Childhood Hypertrophic Cardiomyopathy: A Disease of the Cardiac Sarcomere
Authors: Norrish Gabrielle , Field Ella , Kaski Juan P.
Published: July 2021

Hypertrophic cardiomyopathy is the second most common cause of cardiomyopathy presenting during childhood and whilst its underlying aetiology is variable, the majority of disease is caused by sarcomeric protein gene variants. Sarcomeric disease can present at any age with highly variable disease phenotype, progression and outcomes. The majority have good childhood-outcomes with reported 5-year survival rates above 80%. However, childhood onset disease is associated with considerable life-long morbidity and mortality, including a higher SCD rate during childhood than seen in adults. Management is currently focused on relieving symptoms and preventing disease-related complications, but the possibility of future disease-modifying therapies offers an exciting opportunity to modulate disease expression and outcomes in these young patients.
Systematic Review and Meta-Analysis of Renin–Angiotensin–Aldosterone System Blocker Effects on the Development of Cardiovascular Disease in Patients With Chronic Kidney Disease
Authors: Yanai Katsunori , Ishibashi Kenichi , Morishita Yoshiyuki
Published: July 2021

Background: Cardiovascular events are one of the most serious complications that increase the risk of mortality and morbidity in pre-dialysis and on-dialysis chronic kidney disease (CKD) patients. Activation of the renin–angiotensin–aldosterone system (RAAS) is considered to contribute to the development of cardiovascular events in these populations. Therefore, several kinds of RAAS blockers have been frequently prescribed to prevent cardiovascular events in patients with CKD; however, their effectiveness remains controversial. This systematic review focuses on whether RAAS blockers prevent cardiovascular events in patients with CKD.

Method: PubMed were searched to retrieve reference lists of eligible trials and related reviews. Randomized prospective controlled trials that investigated the effects on cardiovascular events in CKD patients that were published in English from 2010 to 2020 were included.

Results: Among 167 identified studies, 11 eligible studies (n = 8,322 subjects) were included in the meta-analysis. The meta-analysis showed that RAAS blockers significantly reduced cardiovascular events in on-dialysis patients with CKD [three studies; odds ratio (OR), 0.52; 95% confidence interval (CI), 0.36 to 0.74; p = 0.0003], but there was no significant difference in pre-dialysis patients with CKD because of the heterogeneity in each study (eight studies). We also investigated the effects of each kind of RAAS blocker on cardiovascular events in CKD patients. Among the RAAS blockers, mineralocorticoid receptor antagonists significantly decreased cardiovascular events in pre-dialysis or on-dialysis patients with CKD (four studies; OR, 0.60; 95%CI, 0.50 to 0.73, p < 0.0001). However, angiotensin receptor blockers did not show significant effects (four studies; OR, 0.65; 95%CI, 0.42 to 1.01; p = 0.0529). The effects of angiotensin converting enzyme inhibitors and direct renin inhibitors on cardiovascular events in patients with CKD could not be analyzed because there were too few studies.

Conclusion: Mineralocorticoid receptor antagonists may decrease cardiovascular events in pre-dialysis or on-dialysis patients with CKD.
Evidence That Tumor Microenvironment Initiates Epithelial-To-Mesenchymal Transition and Calebin A can Suppress it in Colorectal Cancer Cells
Authors: Buhrmann Constanze , Brockmueller Aranka , Harsha Choudhary , Kunnumakkara Ajaikumar B. , Kubatka Peter , Aggarwal Bharat B. , Shakibaei Mehdi
Published: July 2021

Background: Tumor microenvironment (TME) has a pivotal impact on tumor progression, and epithelial-mesenchymal transition (EMT) is an extremely crucial initial event in the metastatic process in colorectal cancer (CRC) that is not yet fully understood. Calebin A (an ingredient in Curcuma longa) has been shown to repress CRC tumor growth. However, whether Calebin A is able to abrogate TME-induced EMT in CRC was investigated based on the underlying pathways.

Methods: CRC cell lines (HCT116, RKO) were exposed with Calebin A and/or a FAK inhibitor, cytochalasin D (CD) to investigate the action of Calebin A in TME-induced EMT-related tumor progression.

Results: TME induced viability, proliferation, and increased invasiveness in 3D-alginate CRC cultures. In addition, TME stimulated stabilization of the master EMT-related transcription factor (Slug), which was accompanied by changes in the expression patterns of EMT-associated biomarkers. Moreover, TME resulted in stimulation of NF-κB, TGF-β1, and FAK signaling pathways. However, these effects were dramatically reduced by Calebin A, comparable to FAK inhibitor or CD. Finally, TME induced a functional association between NF-κB and Slug, suggesting that a synergistic interaction between the two transcription factors is required for initiation of EMT and tumor cell invasion, whereas Calebin A strongly inhibited this binding and subsequent CRC cell migration.

Conclusion: We propose for the first time that Calebin A modulates TME-induced EMT in CRC cells, at least partially through the NF-κB/Slug axis, TGF-β1, and FAK signaling. Thus, Calebin A appears to be a potential agent for the prevention and management of CRC.
Prolonged Right Ventricular Outflow Tract Endocardial Activation Duration and Presence of Deceleration Zones in Patients With Idiopathic Premature Ventricular Contractions. Association With Low Voltage Areas
Authors: Parreira Leonor , Carmo Pedro , Marinheiro Rita , Mesquita Dinis , Farinha José , Esteves Ana , Amador Pedro , Ferreira António , Fonseca Marta , Caria Rui , Adragao Pedro
Published: July 2021

Background and Aims

The wavefront propagation velocity in the myocardium with fibrosis is characterized by the presence of deceleration zones and late activated zones, that are absent in the normal myocardium. Our aim was to study the right ventricular outflow tract (RVOT) endocardial activation duration in sinus rhythm, and assess the presence of deceleration zones, in patients with premature ventricular contractions (PVCs) and in controls.

Methods

We studied 29 patients with idiopathic PVCs from the outflow tract, subjected to catheter ablation that had an activation and voltage map of the RVOT in sinus rhythm. A control group of 15 patients without PVCs that underwent ablation of supraventricular arrhythmias was also studied. RVOT endocardial activation duration and number of 10 ms isochrones across the RVOT were assessed. Propagation speed was calculated at the zone with the higher number of isochrones per cm radius. Deceleration zones were defined as zones with >3 isochrones within 1 cm radius. Low voltage areas were defined as areas with local electrogram with amplitude <1.5 mV.

Results

The two groups did not differ in relation to age, gender or number of points in the map. RVOT endocardial activation duration and number of 10 ms isochrones were higher in the PVC group; 56 (41–66) ms vs. 39 (35–41) ms, p = 0.001 and 5 (4–8) vs. 4 (4–5), p = 0.001. Presence of deceleration zones and low voltage areas were more frequent in the PVC group; 20 (69%) vs. 0 (0%), p < 0.0001 and 21 (72%) vs. 0 (0%), p < 0.0001. The wavefront propagation speed was significantly lower in patients with PVCs than in the control group, 0.35 (0.27–0.40) vs. 0.63 (0.56–0.66) m/s, p < 0.0001. Patients with low voltage areas had longer activation duration 60 (52–67) vs. 36 (32–40) ms, p < 0.0001, more deceleration zones, 20 (95%) vs. 0 (0%), p < 0.0001, and lower wavefront propagation speed, 0.30 (0.26–0.36) vs. 0.54 (0.36–0.66) m/s, p = 0.002, than patients without low voltage areas.

Conclusion

Right ventricular outflow tract endocardial activation duration was longer, propagation speed was lower and deceleration zones were more frequent in patients with PVCs than in controls and were associated with the presence of low voltage areas.
Solar Radiation as an Isolated Environmental Factor in an Experimental Mesocosm Approach for Studying Photosynthetic Acclimation of Macrocystis pyrifera (Ochrophyta)
Authors: Celis-Plá Paula S. M. , Kappes José Luis , Figueroa Félix L. , Pereda Sandra V. , Villegas Karina , Altamirano Robinson , Hernández-González María Carmen , Buschmann Alejandro H.
Published: July 2021

Solar radiation effects on the ecophysiology and biochemical responses of the brown macroalga Macrocystis pyrifera (L.) C. Agardh were evaluated using a mesocosm approach in Southern Chile. Treatments with different radiation attenuations were simulated with three vertical attenuation coefficients: (1) total (Kd = 0.8 m−1), (2) attenuated (Kd = 1.2 m−1), and (3) low (Kd = 1.6 m−1) radiation levels. Nutrient concentration and temperature did not show differences under the three light conditions. Photosynthetic activity was estimated by in vivo chlorophyll a (Chla) fluorescence under the three light treatments as an isolated physical factor in both in situ solar radiation in the field. This was achieved using a pulse amplitude-modulated (PAM) fluorometera—Diving PAM (in situ). Photosynthetic activity and biochemical composition were measured in winter during two daily cycles (1DC and 2DC) in different parts of the thalli of the plant: (1) canopy zone, (2) middle zone, and (3) down zone, associated with different depths in the mesocosm system. Nevertheless, the in situ electron transport rate (ETRin situ) was higher in the exposed thalli of the canopy zone, independent of the light treatment conditions. The concentration of phenolic compounds (PC) increases in the down zone in the first daily cycle, and it was higher in the middle zone in the second daily cycle. The Chla increased in the morning time under total and attenuated radiation in the first daily cycle. Solar radiation increasing at midday prompted the photoinhibition of photosynthesis in the canopy zone but also an increase in productivity and phenol content. Therefore, light attenuation in the water column drove key differences in the photo-physiological responses of M. pyrifera, with the highest productivity occurring in thalli positioned in the canopy zone when exposed to solar irradiance.
Functional Relationship of Arabidopsis AOXs and PTOX Revealed via Transgenic Analysis
Authors: Wang Danfeng , Wang Chunyu , Li Cai , Song Haifeng , Qin Jing , Chang Han , Fu Weihan , Wang Yuhua , Wang Fei , Li Beibei , Hao Yaqi , Xu Min , Fu Aigen
Published: July 2021

Alternative oxidase (AOX) and plastid terminal oxidase (PTOX) are terminal oxidases of electron transfer in mitochondria and chloroplasts, respectively. Here, taking advantage of the variegation phenotype of the Arabidopsis PTOX deficient mutant (im), we examined the functional relationship between PTOX and its five distantly related homologs (AOX1a, 1b, 1c, 1d, and AOX2). When engineered into chloroplasts, AOX1b, 1c, 1d, and AOX2 rescued the im defect, while AOX1a partially suppressed the mutant phenotype, indicating that AOXs could function as PQH2 oxidases. When the full length AOXs were overexpressed in im, only AOX1b and AOX2 rescued its variegation phenotype. In vivo fluorescence analysis of GFP-tagged AOXs and subcellular fractionation assays showed that AOX1b and AOX2 could partially enter chloroplasts while AOX1c and AOX1d were exclusively present in mitochondria. Surprisingly, the subcellular fractionation, but not the fluorescence analysis of GFP-tagged AOX1a, revealed that a small portion of AOX1a could sort into chloroplasts. We further fused and expressed the targeting peptides of AOXs with the mature form of PTOX in im individually; and found that targeting peptides of AOX1a, AOX1b, and AOX2, but not that of AOX1c or AOX1d, could direct PTOX into chloroplasts. It demonstrated that chloroplast-localized AOXs, but not mitochondria-localized AOXs, can functionally compensate for the PTOX deficiency in chloroplasts, providing a direct evidence for the functional relevance of AOX and PTOX, shedding light on the interaction between mitochondria and chloroplasts and the complex mechanisms of protein dual targeting in plant cells.
Alterations in Source-Sink Relations Affect Rice Yield Response to Elevated CO2: A Free-Air CO2 Enrichment Study
Authors: Gao Bo , Hu Shaowu , Jing Liquan , Niu Xichao , Wang Yunxia , Zhu Jianguo , Wang Yulong , Yang Lianxin
Published: July 2021

To understand the effects of source-sink relationships on rice yield response to elevated CO2 levels (eCO2), we conducted a field study using a popular japonica cultivar grown in a free-air CO2 enrichment environment in 2017–2018. The source-sink ratio of rice was set artificially via source-sink treatments (SSTs) at the heading stage. Five SSTs were performed in 2017 (EXP1): cutting off the flag leaf (LC1) and the top three functional leaves (LC3), removing one branch in every three branches of a panicle (SR1/3) and one branch in every two branches of a panicle (SR1/2), and the control (CK) without any leaf cutting or spikelet removal. The eCO2 significantly increased grain yield by 15.7% on average over all treatments; it significantly increased grain yield of CK, LC1, LC3, SR1/3, and SR1/2 crops by 13.9, 18.1, 25.3, 12.0, and 10.9%, respectively. The yield response to eCO2 was associated with a significant increase of panicle number and fully-filled grain percentage (FGP), and the response of crops under different SSTs was significantly positively correlated with FGP and the average grain weight of the seeds. Two SSTs (CK and LC3) were performed in 2018 (EXP2), which confirmed that the yield response of LC3 crops (25.1%) to eCO2 was significantly higher than that of CK (15.9%). Among the different grain positions, yield response to eCO2 of grains attached to the lower secondary rachis was greater than that of grains attached to the upper primary rachis. Reducing the source-sink ratio via leaf-cutting enhanced the net photosynthetic rate response of the remaining leaves to eCO2 and increased the grain filling ability. Conversely, spikelet removal increased the non-structural carbohydrate (NSC) content of the stem, causing feedback inhibition and photosynthetic down-regulation. This study suggests that reducing the source-sink ratio by adopting appropriate management measures can increase the response of rice to eCO2.
The Contribution of Personality and Intelligence Toward Cognitive Competences in Higher Education
Authors: Cerni Tania , Di Benedetto Annalisa , Rumiati Raffaella I.
Published: July 2021

Personality and cognition are found to be two interrelated concepts and to both have a predictive power on educational and life outcomes. With this study we aimed at evaluating the extent to which personality traits interact with cognition in acquiring cognitive competences during higher education. In a sample of university students at different stages of their career and from different fields of study, we collected Big Five traits, as a measure of personality, and Intelligent Quotient (IQ), as a proxy of cognition. A set of multiple regressions served to explore the relative contribution of IQ and personality traits on the performance on two cognitive competences tests: literacy and numeracy. Results showed that IQ highly modulated numeracy but had a moderate or no impact on literacy while, compared with IQ, personality affects literacy more. In a further explorative analysis, we observed that both the effects of personality and IQ on cognitive competences were modulated by the level of the students' career (freshmen, undergraduates, and bachelor graduates). Different traits, and particularly conscientiousness, increased or decreased their impact on achieved scores depending on the educational level, while IQ lost its effect in undergraduates suggesting that personal dispositions become more influential in advancing the academic carrier. Finally, the field of study resulted to be a predictor of numeracy, but also an important covariate altering the pattern of personality impact.
Automation Use and Dis-Use in Golf: The Impact of Distance Measuring Devices on Trust in Technology and Confidence in Determining Distance
Authors: Dithurbide Lori , Neyedli Heather F. , Swinimer Jamie , MacFarlane Jamie
Published: July 2021

An athlete’s decision to use technology depends on trust in the automation, and confidence in their abilities. Distance measuring devices (DMD) are used in golf to estimate yardage. The purpose of these studies was to examine how DMD usage affects trust in the DMD, confidence in determining yardage manually, and golf performance over time. In study 1, DMD non-users played four rounds of golf, two with the DMD and two without. In study 2, DMD users played five rounds, three with the device, and two without. Participants’ trust in automation, confidence, and performance were recorded by online survey at baseline and following each round. Giving a DMD to non-users influenced trust in automation and confidence. When DMD users relinquished the device, confidence decreased briefly but rebounded quickly, trust in automation was unaffected. Performance was unchanged in both groups. These studies provide information about how confidence in abilities and trust in automation interact.