bluuebunny/crossref_metadata_2025 huggingface dataset:
Leptin and TGF-β1 Downregulate PREP1 Expression in Human Adipose-Derived Mesenchymal Stem Cells and Mature Adipocytes
Authors: Bruno Andreina , Di Sano Caterina , Simon Hans-Uwe , Chanez Pascal , Patti Angelo Maria , Di Vincenzo Serena , Dino Paola , D’Esposito Vittoria , Formisano Pietro , Beguinot Francesco , Pace Elisabetta
Published: July 2021

Adipose tissue is widely recognized as an extremely active endocrine organ producing adipokines as leptin that bridge metabolism and the immune system. Pre-B-cell leukemia homeobox (Pbx)-regulating protein-1 (PREP1) is a ubiquitous homeodomain transcription factor involved in the adipogenic differentiation and insulin-sensitivity processes. Leptin, as pleiotropic adipokine, and TGF-β, known to be expressed by primary pre-adipocytes [adipose-derived stem cells (ASCs)] and mature differentiated adipocytes, modulate inflammatory responses. We aimed to assess for the first time if leptin and TGF-β interfere with PREP1 expression in both ASCs and mature differentiated adipocytes. Human ASCs were isolated from subcutaneous adipose liposuction and, after expansion, fully differentiated to mature adipocytes. In both ASCs and adipocytes, leptin and TGF-β1 significantly decreased the expression of PREP1, alone and following concurrent Toll-like receptor 4 (TLR4) activation. Moreover, in adipocytes, but not in ASCs, leptin increased TLR4 and IL-33 expression, whereas TGF-β1 enhanced TLR4 and IL-6 expression. Taken together, we provide evidence for a direct regulation of PREP1 by leptin and TGF-β1 in ASCs and mature adipocytes. The effects of leptin and TGF-β1 on immune receptors and cytokines, however, are limited to mature adipocytes, suggesting that modulating immune responses depends on the differentiation of ASCs. Further studies are needed to fully understand the regulation of PREP1 expression and its potential for the development of new therapeutic approaches in obesity-related diseases.
Handling Variables, via Inversion of Partial Least Squares Models for Class-Modelling, to Bring Defective Items to Non-Defective Ones
Authors: Ruiz Santiago , Sarabia Luis Antonio , Sánchez María Sagrario , Ortiz María Cruz
Published: July 2021

In the context of binary class-modelling techniques, the paper presents the computation in the input space of linear boundaries of a class-model constructed with given values of sensitivity and specificity. This is done by inversion of a decision threshold, set with these values of sensitivity and specificity, in the probabilistic class-models computed by means of PLS-CM (Partial Least Squares for Class-Modelling). The characterization of the boundary hyperplanes, in the latent space (space spanned by the selected latent variables of the fitted PLS model) or in the input space, makes it possible to calculate directions that can be followed to move objects toward the class-model of interest. Different points computed along these directions will show how to modify the input variables (provided they can be manipulated) so that, eventually, a computed ‘object’ would be inside the class-model, in terms of the prediction with the PLS model. When the class of interest is that of “adequate” objects, as for example in some process control or product formulation, the proposed procedure helps in answering the question about how to modify the input variables so that a defective object would be inside the class-model of the adequate (non-defective) ones. This is the situation illustrated with some examples, taken from the literature when modelling the class of adequate objects.
Distributed Melt on a Debris-Covered Glacier: Field Observations and Melt Modeling on the Lirung Glacier in the Himalaya
Authors: Steiner Jakob F. , Kraaijenbrink Philip D. A. , Immerzeel Walter W.
Published: July 2021

Debris-covered glaciers, especially in high-mountain Asia, have received increased attention in recent years. So far, few field-based observations of distributed mass loss exist and both the properties of the debris layer as well as the atmospheric drivers of melt below debris remain poorly understood. Using multi-year observations of on-glacier atmospheric data, debris properties and spatial surface elevation changes from repeat flights with an unmanned aerial vehicle (UAV), we quantify the necessary variables to compute melt for the Lirung Glacier in the Himalaya. By applying an energy balance model we reproduce observed mass loss during one monsoon season in 2013. We show that melt is especially sensitive to thermal conductivity and thickness of debris. Our observations show that previously used values in literature for the thermal conductivity through debris are valid but variability in space on a single glacier remains high. We also present a simple melt model, which is calibrated based on the results of energy balance model, that is only dependent on air temperature and debris thickness and is therefore applicable for larger scale studies. This simple melt model reproduces melt under thin debris (<0.5 m) well at an hourly resolution, but fails to represent melt under thicker debris accurately at this high temporal resolution. On the glacier scale and using only off-glacier forcing data we however are able to reproduce the total melt volume of a debris-covered tongue. This is a promising result for catchment scale studies, where quantifying melt from debris covered glaciers remains a challenge.
Feminizing Hormone Therapy Prescription Patterns and Cardiovascular Risk Factors in Aging Transgender Individuals in Australia
Authors: Balcerek Matthew I. , Nolan Brendan J. , Brownhill Adam , Wong Peggy , Locke Peter , Zajac Jeffrey D. , Cheung Ada S.
Published: July 2021

Context

The safety and efficacy of feminizing hormone therapy in aging transgender (trans) individuals is unclear. Current recommendations suggest transdermal estradiol beyond the age of 45 years, especially if cardiometabolic risk factors are present.

Objective

To evaluate feminizing hormone therapy regimens and cardiovascular risk factors in aging trans individuals.

Design

Retrospective cross-sectional analysis.

Setting

Primary care and endocrine specialist clinic in Melbourne, Australia.

Participants

Trans individuals on feminizing therapy for ≥6 months.

Main Outcomes Measures

Feminizing hormone regimens and serum estradiol concentrations by age group: (a) ≥45 years, (b) <45 years, and prevalence of cardiometabolic risk factors in individuals ≥45 years.

Results

296 individuals were stratified by age group: ≥45 years (n=55) and <45 years (n=241). There was no difference in median estradiol concentration between groups (328 nmol/L vs. 300 nmol/L, p=0.22). However, there was a higher proportion of individuals ≥45 years treated with transdermal estradiol (31% vs. 8%, p<0.00001). Of those treated with oral estradiol, the median dose was lower in the ≥45 years group (4mg vs. 6mg, p=0.01). The most prevalent cardiometabolic risk factor in the ≥45 years group was hypertension (29%), followed by current smoking (24%), obesity (20%), dyslipidaemia (16%) and diabetes (9%).

Conclusions

A greater proportion of trans individuals ≥45 years of age were treated with transdermal estradiol. Of those who received oral estradiol, the median dose was lower. This is important given the high prevalence of cardiometabolic risk factors in this age group, however cardiovascular risk management guidelines in this demographic are lacking.
Genomic Responses to Climate Change: Making the Most of the Drosophila Model
Authors: Rodrigues Murillo F. , Cogni Rodrigo
Published: July 2021

It is pressing to understand how animal populations evolve in response to climate change. We argue that new sequencing technologies and the use of historical samples are opening unprecedented opportunities to investigate genome-wide responses to changing environments. However, there are important challenges in interpreting the emerging findings. First, it is essential to differentiate genetic adaptation from phenotypic plasticity. Second, it is extremely difficult to map genotype, phenotype, and fitness. Third, neutral demographic processes and natural selection affect genetic variation in similar ways. We argue that Drosophila melanogaster, a classical model organism with decades of climate adaptation research, is uniquely suited to overcome most of these challenges. In the near future, long-term time series genome-wide datasets of D. melanogaster natural populations will provide exciting opportunities to study adaptation to recent climate change and will lay the groundwork for related research in non-model systems.
Intelligent Mobility in the City: The Influence of System and Context Factors on Drivers’ Takeover Willingness and Trust in Automated Vehicles
Authors: Lanzer Mirjam , Stoll Tanja , Colley Mark , Baumann Martin
Published: July 2021

Automated driving in urban environments not only has the potential to improve traffic flow and heighten driver comfort but also to increase traffic safety, particularly for vulnerable road users such as pedestrians. For these benefits to take effect, drivers need to trust and use automated vehicles. This decision is influenced by both system and context factors. However, it is not yet clear how these factors interact with each other, especially for automated driving in city scenarios with crossing pedestrians. Therefore, we conducted an online experiment in which participants (N= 68) experienced short automated rides from the driver’s perspective through an urban environment. In each of the presented videos, a pedestrian crossed the street in front of the automated vehicle while system and context factors were varied: 1) the crossing pedestrian’s intention was either visualized correctly (as crossing) or incorrectly (visualization missing) by the automated vehicle (system factor), 2) the pedestrian was either distracted by using a smartphone while crossing or not (context factor), and 3) the scenario was either more or less complex depending on the number of other vehicles and pedestrians being present (context factor). In situations with a system malfunction where the crossing pedestrian’s intention was not visualized, participants perceived the situation as more critical, had less trust in the automated system, and a higher willingness to take over control regardless of any context factors. However, when the system worked correctly, the crossing pedestrian’s smartphone usage came into play, especially in the less complex scenario. Participants perceived situations with a distracted pedestrian as more critical, trusted the system less, indicated a higher willingness to take over control, and were more uncertain about their decision. As this study demonstrates the influence of distracted pedestrians, more research is needed on context factors and their inclusion in the design of interfaces to keep drivers informed during automated driving in urban environments.
CXCR5+CD8+ T Cells Shape Antibody Responses In Vivo Following Protein Immunisation and Peripheral Viral Infection
Authors: Tyllis Timona S. , Fenix Kevin A. , Norton Todd S. , Kara Ervin E. , McKenzie Duncan R. , David Shannon C. , Alsharifi Mohammed , Yu Di , McColl Shaun R. , Comerford Iain
Published: July 2021

Crosstalk between T and B cells is crucial for generating high-affinity, class-switched antibody responses. The roles of CD4+T cells in this process have been well-characterised. In contrast, regulation of antibody responses by CD8+T cells is significantly less defined. CD8+T cells are principally recognised for eliciting cytotoxic responses in peripheral tissues and forming protective memory. However, recent findings have identified a novel population of effector CD8+T cells that co-opt a differentiation program characteristic of CD4+T follicular helper (Tfh) cells, upregulate the chemokine receptor CXCR5 and localise to B cell follicles. While it has been shown that CXCR5+CD8+T cells mediate the removal of viral reservoirs in the context of follicular-trophic viral infections and maintain the response to chronic insults by virtue of progenitor/stem-like properties, it is not known if CXCR5+CD8+T cells arise during acute peripheral challenges in the absence of follicular infection and whether they influence B cell responsesin vivoin these settings. Using the ovalbumin-specific T cell receptor transgenic (OT-I) system in an adoptive transfer-immunisation/infection model, this study demonstrates that CXCR5+CD8+T cells arise in response to protein immunisation and peripheral viral infection, displaying a follicular-homing phenotype, expression of cell surface molecules associated with Tfh cells and limited cytotoxic potential. Furthermore, studies assessing the B cell response in the presence of OT-I orCxcr5-/-OT-I cells revealed that CXCR5+CD8+T cells shape the antibody response to protein immunisation and peripheral viral infection, promoting class switching to IgG2c in responding B cells. Overall, the results highlight a novel contribution of CD8+T cells to antibody responses, expanding the functionality of the adaptive immune system.
Inflammatory Bowel Diseases and Sarcopenia: The Role of Inflammation and Gut Microbiota in the Development of Muscle Failure
Authors: Nardone Olga Maria , de Sire Roberto , Petito Valentina , Testa Anna , Villani Guido , Scaldaferri Franco , Castiglione Fabiana
Published: July 2021

Sarcopenia represents a major health burden in industrialized country by reducing substantially the quality of life. Indeed, it is characterized by a progressive and generalized loss of muscle mass and function, leading to an increased risk of adverse outcomes and hospitalizations. Several factors are involved in the pathogenesis of sarcopenia, such as aging, inflammation, mitochondrial dysfunction, and insulin resistance. Recently, it has been reported that more than one third of inflammatory bowel disease (IBD) patients suffered from sarcopenia. Notably, the role of gut microbiota (GM) in developing muscle failure in IBD patient is a matter of increasing interest. It has been hypothesized that gut dysbiosis, that typically characterizes IBD, might alter the immune response and host metabolism, promoting a low-grade inflammation status able to up-regulate several molecular pathways related to sarcopenia. Therefore, we aim to describe the basis of IBD-related sarcopenia and provide the rationale for new potential therapeutic targets that may regulate the gut-muscle axis in IBD patients.
Allo-Specific Humoral Responses: New Methods for Screening Donor-Specific Antibody and Characterization of HLA-Specific Memory B Cells
Authors: Song Shengli , Manook Miriam , Kwun Jean , Jackson Annette M. , Knechtle Stuart J. , Kelsoe Garnett
Published: July 2021

Antibody-mediated allograft rejection (AMR) causes more kidney transplant failure than any other single cause. AMR is mediated by antibodies recognizing antigens expressed by the graft, and antibodies generated against major histocompatibility complex (MHC) mismatches are especially problematic. Most research directed towards the management of clinical AMR has focused on identifying and characterizing circulating donor-specific HLA antibody (DSA) and optimizing therapies that reduce B-cell activation and/or block antibody secretion by inhibiting plasmacyte survival. Here we describe a novel set of reagents and techniques to allow more specific measurements of MHC sensitization across different animal transplant models. Additionally, we have used these approaches to isolate and clone individual HLA-specific B cells from patients sensitized by pregnancy or transplantation. We have identified and characterized the phenotypes of individual HLA-specific B cells, determined the V(D)J rearrangements of their paired H and L chains, and generated recombinant antibodies to determine affinity and specificity. Knowledge of the BCR genes of individual HLA-specific B cells will allow identification of clonally related B cells by high-throughput sequence analysis of peripheral blood mononuclear cells and permit us to re-construct the origins of HLA-specific B cells and follow their somatic evolution by mutation and selection.
The Missing Layers: Integrating Sociocultural Values Into Marine Spatial Planning
Authors: Pennino Maria Grazia , Brodie Stephanie , Frainer André , Lopes Priscila F. M. , Lopez Jon , Ortega-Cisneros Kelly , Selim Samiya , Vaidianu Natasa
Published: July 2021

Graphical Abstract
Exploring Ocean Biogeochemistry Using a Lab-on-Chip Phosphate Analyser on an Underwater Glider
Authors: Birchill Antony J. , Beaton A. D. , Hull Tom , Kaiser Jan , Mowlem Matt , Pascal R. , Schaap A. , Voynova Yoana G. , Williams C. , Palmer M.
Published: July 2021

The ability to make measurements of phosphate (PO43–) concentrations at temporal and spatial scales beyond those offered by shipboard observations offers new opportunities for investigations of the marine phosphorus cycle. We here report the first in situ PO43– dataset from an underwater glider (Kongsberg Seaglider) equipped with a PO43– Lab-on-Chip (LoC) analyser. Over 44 days, a 120 km transect was conducted in the northern North Sea during late summer (August and September). Surface depletion of PO43– (<0.2 μM) was observed above a seasonal thermocline, with elevated, but variable concentrations within the bottom layer (0.30–0.65 μM). Part of the variability in the bottom layer is attributed to the regional circulation and across shelf exchange, with the highest PO43– concentrations being associated with elevated salinities in northernmost regions, consistent with nutrient rich North Atlantic water intruding onto the shelf. Our study represents a significant step forward in autonomous underwater vehicle sensor capabilities and presents new capability to extend research into the marine phosphorous cycle and, when combined with other recent LoC developments, nutrient stoichiometry.
De novo Sequencing and Comparative Transcriptome Analyses Provide First Insights Into Polysaccharide Biosynthesis During Fruiting Body Development of Lentinula edodes
Authors: Li Qiaozhen , Chen Jing , Liu Jianyu , Yu Hailong , Zhang Lujun , Song Chunyan , Li Yu , Jiang Ning , Tan Qi , Shang Xiaodong , Gu Yunfu
Published: July 2021

Polysaccharides separated from Lentinula edodes are well known for their medicinal properties. However, the precise molecular mechanisms of polysaccharide biosynthesis in L. edodes remain unclear. In this study, the fruiting bodies of L. edodes in four developmental stages with significant differences in polysaccharide yield were collected, and the characteristics of polysaccharides were studied. De novo sequencing and comparative transcriptomic analysis were performed by using high-throughput Illumina RNA-sequencing. KS1P30, KS2P30, KS3P30, and KS4P30 were obtained from the four developmental stages, respectively, by hot water extraction and 30% ethanol precipitation. These four polysaccharides had good immune activity in vitro; all of them were β-glucopyranose with a high molecular weight. Glucose was the main monosaccharide component of these polysaccharides. High-quality clean reads (57.88, 53.17, 53.28, and 47.56 million for different growth stages) and mapping ratios ranging from 84.75 to 90.11% were obtained. In total, 11,493 (96.56%) unigenes and 18,924 (97.46%) transcripts were successfully annotated in five public databases. The biosynthetic pathway and related genes of LEFP30 were mined. The molecular mechanism of LEFP30 yield change in the different developmental stages was predicted. The results provide some insights into the possible mechanisms involved in the biosynthetic pathway of this kind of polysaccharide in L. edodes fruiting bodies. They also indicate that candidate genes can be used as important resources for biotechnology and molecular breeding to regulate L. edodes fruiting body polysaccharide biosynthesis.
Genomic Characterization of Strains From a Cluster of Infant Botulism Type A in a Small Town in Colorado, United States
Authors: Gladney Lori , Halpin Jessica L. , Lúquez Carolina
Published: July 2021

Three cases of infant botulism were reported in a small Colorado town between 1981 and 1984. The first two cases occurred in 1981, 6 months apart, and the third case occurred in 1984. Clostridium botulinum type A was isolated from stool of all three case patients and from environmental samples of the patient’s homes. An epidemiological investigation and follow-up study were conducted from 1981 to 1986 and concluded the cases were likely related. In this study, we sought to determine whether the C. botulinum type A clinical isolates were related to each other and to isolates obtained from environmental samples. We performed whole genome sequencing (WGS) for 17 isolates associated with this potential cluster of infant botulism. Fifteen isolates were confirmed to be C. botulinum type A(B) and contained botulinum toxin gene subtypes A1 and B5 by WGS; these strains formed a monophyletic cluster in a phylogeny and were considered closely related to each other (0–18 high-quality single-nucleotide polymorphisms), but distinct from other C. botulinum type A(B) in Colorado and elsewhere in the United States. Results of our study suggest that the three infant botulism cases could have represented a cluster due to a C. botulinum type A(B) strain present in the environment.
Comparison of Two Aspergillus oryzae Genomes From Different Clades Reveals Independent Evolution of Alpha-Amylase Duplication, Variation in Secondary Metabolism Genes, and Differences in Primary Metabolism
Authors: Chacón-Vargas Katherine , McCarthy Colin O. , Choi Dasol , Wang Long , Yu Jae-Hyuk , Gibbons John G.
Published: July 2021

Microbes (bacteria, yeasts, molds), in addition to plants and animals, were domesticated for their roles in food preservation, nutrition and flavor. Aspergillus oryzae is a domesticated filamentous fungal species traditionally used during fermentation of Asian foods and beverage, such as sake, soy sauce, and miso. To date, little is known about the extent of genome and phenotypic variation of A. oryzae isolates from different clades. Here, we used long-read Oxford Nanopore and short-read Illumina sequencing to produce a highly accurate and contiguous genome assemble of A. oryzae 14160, an industrial strain from China. To understand the relationship of this isolate, we performed phylogenetic analysis with 90 A. oryzae isolates and 1 isolate of the A. oryzae progenitor, Aspergillus flavus. This analysis showed that A. oryzae 14160 is a member of clade A, in comparison to the RIB 40 type strain, which is a member of clade F. To explore genome variation between isolates from distinct A. oryzae clades, we compared the A. oryzae 14160 genome with the complete RIB 40 genome. Our results provide evidence of independent evolution of the alpha-amylase gene duplication, which is one of the major adaptive mutations resulting from domestication. Synteny analysis revealed that both genomes have three copies of the alpha-amylase gene, but only one copy on chromosome 2 was conserved. While the RIB 40 genome had additional copies of the alpha-amylase gene on chromosomes III, and V, 14160 had a second copy on chromosome II and an third copy on chromosome VI. Additionally, we identified hundreds of lineage specific genes, and putative high impact mutations in genes involved in secondary metabolism, including several of the core biosynthetic genes. Finally, to examine the functional effects of genome variation between strains, we measured amylase activity, proteolytic activity, and growth rate on several different substrates. RIB 40 produced significantly higher levels of amylase compared to 14160 when grown on rice and starch. Accordingly, RIB 40 grew faster on rice, while 14160 grew faster on soy. Taken together, our analyses reveal substantial genome and phenotypic variation within A. oryzae.
Antibiofilm Effects of Nanoparticles and Visible Light Illumination Against Listeria monocytogenes
Authors: Puranen Sanna , Riekkinen Kati , Korhonen Jenni
Published: July 2021

Listeria monocytogenes bacteria pose a particular risk to the food industry as the species is known to form biofilm and to survive in a wide range of challenging environmental conditions. L. monocytogenes can cause listeriosis, a serious food-borne disease, and effective and safe antibiofilm materials and sanitary methods for food processing environments are intensively sought. A variety of nanoparticle materials have been recognized as safe to use in food environments, which allows the application of nanomaterials also for food safety purposes. Nanoparticles together with light illumination generate reactive oxygen species which inactivate bacteria by breaking down cell membranes, proteins, and DNA. The main objective of this study was to evaluate the efficacy of nanomaterials and blue light illumination for L. monocytogenes ATCC 7644 biofilm inactivation. Biofilm was allowed to form for 72 h on nanocoated stainless steel and aluminum plates, after which the plates were illuminated. Non-coated control plates were used to evaluate the antibiofilm efficacy of nanocoating. Plate count method was used to evaluate bacteria counts after illumination. Nanocoating did not affect initial biofilm formation compared to the control plates. Biofilm was significantly (p < 0.05) reduced on stainless steel, aluminum, and TiO2-coated aluminum plates after 72-h illumination by 1.9, 3.2, and 5.9 log, respectively. Nanocoating with visible light illumination could be an effective and safe method for enhancing food safety in food processing facilities to control biofilm formation. Evidence of antibiofilm properties of nanomaterials together with visible light illumination is limited; hence, future studies with variable light intensities and nanomaterials are needed.
Negative Feedback Role of Astrocytes in Shaping Excitation in Brain Cell Co-cultures
Authors: Khezerlou Elnaz , Prajapati Neela , DeCoster Mark A.
Published: July 2021

Glial cells play an important role in maintaining neuronal homeostasis and may thus influence excitability in epileptogenesis. These cells in the brain have glutamate (Glu) transporters, which remove this neurotransmitter from the extracellular space. Lack of negative (−) feedback makes local neuronal circuits more excitable and potentially contributing to epileptogenic phenomena. In this study, the role of glial cells in providing (−) feedback is shown through different models of brain cells in culture imaged for intracellular calcium concentration [(Ca2+)i]. Moreover, here we study the individual cells by putting them in categories. Neuronal networks with high and low (−) feedback were established by using anti-mitotics to deplete glial cells. Separate stimuli with very low subthreshold concentrations of Glu (250–750 nM) were added to cultures to test if the order of stimulations matter in regard to calcium dynamics outcomes. Additionally, KCl and ATP were used to stimulate glial cells. We found that for cultures high in (−) feedback, order of the stimulus was not important in predicting cellular responses and because of the complexity of networks in low (−) feedback cultures the order of stimulus matters. As an additional method for analysis, comparison of high (−) feedback cultures, and pure astrocytes was also considered. Glial cells in pure astrocyte cultures tend to be larger in size than glial cells in high (−) feedback cultures. The potential effect of (−) feedback at the blood brain barrier (BBB) was also considered for the inflammatory responses of nitric oxide (NO) production and [Ca2+]i regulation using brain microvascular endothelial cells (BMVECs). The inflammatory and calcium signaling pathways both indicate the negative feedback role of astrocytes, poised between the BBB and structures deeper within the brain, where neuronal synapses are homeostatically maintained by glial uptake of neurotransmitters.
Spatiotemporal Dynamics of Affective and Semantic Valence Among Women
Authors: Wang Luchun , Li Xiying , Pi Zhongling , Xiang Shuoqi , Yao Xuemei , Qi Senqing
Published: July 2021

As an important dimension of emotional assessment, valence can refer to affective valence reflecting an emotional response, or semantic valence reflecting knowledge about the nature of a stimulus. A previous study has used repeated exposure to separate these two similar cognitive processes. Here, for the first time, we compared the spatiotemporal dynamics of the affective and semantic modes of valence by combining event-related potentials with repeated exposure. Forty-seven female participants were assigned to the feeling-focused and semantic-focused groups and thereafter repeatedly viewed the pictures selected for the study. Self-report behavioral results showed that post-test scores were significantly lower than pre-test scores in the feeling-focused group, while the differences between the two tests were not significant in the semantic-focused group. At the neural level, N2 amplitudes decreased and early late positive potential amplitudes increased in both groups, suggesting that the participants perceived the repeated pictures more fluently and retrieved the traces of the stimulus spontaneously regardless of the valence they judged. However, the late positive potential amplitudes in anterior areas and the activity of the middle frontal gyrus were attenuated in the feeling-focused group; however, this component in posterior areas and the activity of the precentral gyrus were increased in the semantic-focused group. Therefore, the processes of affective and semantic valence are similar in the early stages of image perception and retrieval, while in the later stage of valence judgment, these processes show different brain activation patterns. The results provide electrophysiological evidence for the differences in psychological processes when judging the two modes of valence.
Recording Strategies for High Channel Count, Densely Spaced Microelectrode Arrays
Authors: Pérez-Prieto Norberto , Delgado-Restituto Manuel
Published: July 2021

Neuroscience research into how complex brain functions are implemented at an extra-cellular level requires in vivo neural recording interfaces, including microelectrodes and read-out circuitry, with increased observability and spatial resolution. The trend in neural recording interfaces toward employing high-channel-count probes or 2D microelectrodes arrays with densely spaced recording sites for recording large neuronal populations makes it harder to save on resources. The low-noise, low-power requirement specifications of the analog front-end usually requires large silicon occupation, making the problem even more challenging. One common approach to alleviating this consumption area burden relies on time-division multiplexing techniques in which read-out electronics are shared, either partially or totally, between channels while preserving the spatial and temporal resolution of the recordings. In this approach, shared elements have to operate over a shorter time slot per channel and active area is thus traded off against larger operating frequencies and signal bandwidths. As a result, power consumption is only mildly affected, although other performance metrics such as in-band noise or crosstalk may be degraded, particularly if the whole read-out circuit is multiplexed at the analog front-end input. In this article, we review the different implementation alternatives reported for time-division multiplexing neural recording systems, analyze their advantages and drawbacks, and suggest strategies for improving performance.
A β-Wrapin Targeting the N-Terminus of α-Synuclein Monomers Reduces Fibril-Induced Aggregation in Neurons
Authors: Szegő Éva M. , Boß Fabian , Komnig Daniel , Gärtner Charlott , Höfs Lennart , Shaykhalishahi Hamed , Wördehoff Michael M. , Saridaki Theodora , Schulz Jörg B. , Hoyer Wolfgang , Falkenburger Björn H.
Published: July 2021

Reducing α-synuclein pathology constitutes a plausible strategy against Parkinson’s disease. As we recently demonstrated, the β-wrapin protein AS69 binds an N-terminal region in monomeric α-synuclein, interferes with fibril nucleation, and reduces α-synuclein aggregation in vitro and in a fruit fly model of α-synuclein toxicity. The aim of this study was to investigate whether AS69 also reduces α-synuclein pathology in mammalian neurons. To induce α-synuclein pathology, primary mouse neurons were exposed to pre-formed fibrils (PFF) of human α-synuclein. PFF were also injected into the striatum of A30P-α-synuclein transgenic mice. The extent of α-synuclein pathology was determined by phospho-α-synuclein staining and by Triton X-100 solubility. The degeneration of neuronal somata, dendrites, and axon terminals was determined by immunohistochemistry. AS69 and PFF were taken up by primary neurons. AS69 did not alter PFF uptake, but AS69 did reduce PFF-induced α-synuclein pathology. PFF injection into mouse striatum led to α-synuclein pathology and dystrophic neurites. Co-injection of AS69 abrogated PFF-induced pathology. AS69 also reduced the PFF-induced degeneration of dopaminergic axon terminals in the striatum and the degeneration of dopaminergic dendrites in the substantia nigra pars reticulata. AS69 reduced the activation of astroglia but not microglia in response to PFF injection. Collectively, AS69 reduced PFF-induced α-synuclein pathology and the associated neurodegeneration in primary neurons and in mouse brain. Our data therefore suggest that small proteins binding the N-terminus of α-synuclein monomers are promising strategies to modify disease progression in Parkinson’s disease.
Identification and Confirmation of the miR-30 Family as a Potential Central Player in Tobacco-Related Head and Neck Squamous Cell Carcinoma
Authors: Zhang Tingting , Zhu Xueqin , Sun Qiang , Qin Xing , Zhang Zhen , Feng Yuanyong , Yan Ming , Chen Wantao
Published: July 2021

Constituents of tobacco that can cause DNA adduct formation and oxidative stress are implicated in the development of head and neck squamous cell carcinoma (HNSCC). However, there are few studies on the mechanism(s) that underlie tobacco-associated HNSCC. Here, we used a model in which tumors were induced in rats using 4-nitroquinoline 1-oxide (4NQO), which mimicked tobacco-related HNSCC, and analyzed the expression profiles of microRNAs and mRNAs. Our results indicated that 57 miRNAs and 474 mRNA/EST transcripts exhibited differential expression profiles between tumor and normal tongue tissues. In tumor tissue, the expression levels of rno-miR-30 family members (rno-miR-30a, rno-miR-30a-3p, rno-miR-30b-5p, rno-miR-30c, rno-miR-30d, rno-miR-30e and rno-miR-30e-3p) were only 8% to 37% of those in the control group. The GO terms enrichment analysis of the differentially expressed miRNAs indicated that oxidation reduction was the most enriched process. Low expression of miR-30 family members in human HNSCC cell lines and tissues was validated by qPCR. The results revealed that the expression of miR-30b-5p and miR-30e-5p was significantly decreased in the TCGA HNSCC dataset and validation datasets, and this decrease in expression further distinguishes HNSCC associated with tobacco use from other subtypes of HNSCC. CCK8, colony formation, transwell migration and HNSCC xenograft tumor assays indicated that miR-30b-5p or miR-30e-5p inhibited proliferation, migration and invasion in vitro, and miR-30b-5p suppressed tumor growth in vivo. Moreover, we uncovered that KRAS might be the potential target gene of miR-30e-5p or miR-30b-5p. Thus, our data clearly showed that decreased expression of miR-30e-5p or miR-30b-5p may play a crucial role in cancer development, especially that of tobacco-induced HNSCC, and may be a novel candidate biomarker and target for this HNSCC subtype.
Development of a Machine Learning Classifier Based on Radiomic Features Extracted From Post-Contrast 3D T1-Weighted MR Images to Distinguish Glioblastoma From Solitary Brain Metastasis
Authors: de Causans Alix , Carré Alexandre , Roux Alexandre , Tauziède-Espariat Arnault , Ammari Samy , Dezamis Edouard , Dhermain Frederic , Reuzé Sylvain , Deutsch Eric , Oppenheim Catherine , Varlet Pascale , Pallud Johan , Edjlali Myriam , Robert Charlotte
Published: July 2021

Objectives

To differentiate Glioblastomas (GBM) and Brain Metastases (BM) using a radiomic features-based Machine Learning (ML) classifier trained from post-contrast three-dimensional T1-weighted (post-contrast 3DT1) MR imaging, and compare its performance in medical diagnosis versus human experts, on a testing cohort.

Methods

We enrolled 143 patients (71 GBM and 72 BM) in a retrospective bicentric study from January 2010 to May 2019 to train the classifier. Post-contrast 3DT1 MR images were performed on a 3-Tesla MR unit and 100 radiomic features were extracted. Selection and optimization of the Machine Learning (ML) classifier was performed using a nested cross-validation. Sensitivity, specificity, balanced accuracy, and area under the receiver operating characteristic curve (AUC) were calculated as performance metrics. The model final performance was cross-validated, then evaluated on a test set of 37 patients, and compared to human blind reading using a McNemar’s test.

Results

The ML classifier had a mean [95% confidence interval] sensitivity of 85% [77; 94], a specificity of 87% [78; 97], a balanced accuracy of 86% [80; 92], and an AUC of 92% [87; 97] with cross-validation. Sensitivity, specificity, balanced accuracy and AUC were equal to 75, 86, 80 and 85% on the test set. Sphericity 3D radiomic index highlighted the highest coefficient in the logistic regression model. There were no statistical significant differences observed between the performance of the classifier and the experts’ blinded examination.

Conclusions

The proposed diagnostic support system based on radiomic features extracted from post-contrast 3DT1 MR images helps in differentiating solitary BM from GBM with high diagnosis performance and generalizability.
CD4+ Memory Stem T Cell in Peripheral Blood: A Promising Immune Index for Early Screening and Auxiliary Diagnosis of Colorectal Cancer
Authors: Lu Yan , Zhang Qiaohong , Zhang Longyi
Published: July 2021

Background and Aims

Colorectal cancer (CRC) lacks obvious symptoms in the early stage of the disease, making it is easy to be misdiagnosed and remain undetected. Here, we explored the role of CD4+ memory stem T cells (TSCM) in peripheral blood in the early screening and auxiliary diagnosis of CRC.

Materials and Methods

Patients diagnosed with a “colorectal mass” by colonoscopy, at the Dongyang People’s Hospital (Zhejiang, China), between November 2020 and June 2021, were included in this prospective study. Using histopathological results as the gold standard for diagnosis, patients were divided into “CRC group” and “benign tumor group”. Healthy volunteers were recruited as “healthy controls.” Ten-color flow cytometry was used to detect CD4+ T cell subsets, and the results were analyzed using the Kaluza software. Carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) were detected by the Roche Cobas e 602 electrochemiluminescence immunoassay analyzer.

Results

This study involved 33 patients with CRC, 41 patients with colorectal benign tumors, and 49 healthy volunteers. The absolute value and frequency of CD4+ TSCM can clearly distinguish colorectal cancer, benign tumors, and healthy controls. According to the area under the receiver operating characteristic curve (AUC), the absolute value of CD4+ TSCM used to assist in the diagnosis of CRC was 0.758 (sensitivity: 0.612; specificity: 0.788), which is higher than the values for CEA (AUC: 0.707) and CA199 (AUC: 0.552). In early screening, the sensitivity of the absolute value of CD4+ TSCM (sensitivity: 0.612) was significantly higher than that of CEA (sensitivity: 0.333) and CA199 (sensitivity: 0.259).

Conclusion

CD4+ TSCM in peripheral blood may be a promising immune index for the early screening and auxiliary diagnosis of CRC.
Differential Contributions of MYCs to Insect Defense Reveals Flavonoids Alleviating Growth Inhibition Caused by Wounding in Arabidopsis
Authors: Wang Dan-Dan , Li Pai , Chen Qiu-Yi , Chen Xue-Ying , Yan Zi-Wei , Wang Mu-Yang , Mao Ying-Bo
Published: July 2021

In Arabidopsis, basic helix–loop–helix transcription factors (TFs) MYC2, MYC3, and MYC4 are involved in many biological processes, such as defense against insects. We found that despite functional redundancy, MYC-related mutants displayed different resistance to cotton bollworm (Helicoverpa armigera). To screen out the most likely genes involved in defense against insects, we analyzed the correlation of gene expression with cotton bollworm resistance in wild-type (WT) and MYC-related mutants. In total, the expression of 94 genes in untreated plants and 545 genes in wounded plants were strongly correlated with insect resistance, and these genes were defined as MGAIs (MYC-related genes against insects). MYC3 had the greatest impact on the total expression of MGAIs. Gene ontology (GO) analysis revealed that besides the biosynthesis pathway of glucosinolates (GLSs), MGAIs, which are well-known defense compounds, were also enriched in flavonoid biosynthesis. Moreover, MYC3 dominantly affected the gene expression of flavonoid biosynthesis. Weighted gene co-expression network analysis (WGCNA) revealed that AAE18, which is involved in activating auxin precursor 2,4-dichlorophenoxybutyric acid (2,4-DB) and two other auxin response genes, was highly co-expressed with flavonoid biosynthesis genes. With wounding treatment, the WT plants exhibited better growth performance than chalcone synthase (CHS), which was defective in flavonoid biosynthesis. The data demonstrated dominant contributions of MYC3 to cotton bollworm resistance and imply that flavonoids might alleviate the growth inhibition caused by wounding in Arabidopsis.
Perceived Motion and Operational Momentum: How Speed, Distance, and Time Influence Two-Digit Arithmetic
Authors: Haman Maciej , Młodzianowski Hubert , Gołȩbiowski Michał
Published: July 2021

Operational momentum was originally defined as a bias toward underestimating outcomes of subtraction and overestimating outcomes of addition. It was suggested that these estimation biases are due to leftward attentional shift along the mental number-line (spatially organized internal representation of number) in subtraction and rightward shift in addition. This assumes the use of “recycled” mechanisms of spatial attention, including “representational momentum” – a tendency to overestimate future position of a moving object, which compensates for the moving object’s shift during preparation of a reaction. We tested a strong version of this assumption directly, priming two-digit addition and subtraction problems with leftward and rightward motion of varied velocity, as velocity of the tracked object was found to be a factor in determining representational momentum effect size. Operands were subsequently moving across the computer screen, and the participants’ task was to validate an outcome proposed at the end of the event, which was either too low, correct, or too high. We found improved accuracy in detecting too-high outcomes of addition, as well as complex patterns of interactions involving arithmetic operation, outcome option, speed, and direction of motion, in the analysis of reaction times. These results significantly extend previous evidence for the involvement of spatial attention in mental arithmetic, showing movement of the external attention focus as a factor directing internal attention in processing numerical information. As a whole, however, the results are incompatible with expectations derived from the strong analogy between operational and representational momenta. We suggest that the full model may be more complex than simply “moving attention along the mental number-line” as a direct counterpart of attention directed at a moving object.
Mental Health Self-Stigma of Syrian Refugees With Posttraumatic Stress Symptoms: Investigating Sociodemographic and Psychopathological Correlates
Authors: Bär Jonathan , Pabst Alexander , Röhr Susanne , Luppa Melanie , Renner Anna , Nagl Michaela , Dams Judith , Grochtdreis Thomas , Kersting Anette , König Hans-Helmut , Riedel-Heller Steffi G.
Published: July 2021

Background: The high prevalence of mental disorders related to posttraumatic stress among Syrian refugees is often in contrast with their low utilization of mental health care in the host countries. Mental health self-stigma, i.e., internalized stigma of having a mental disorder, could prevent individuals from seeking mental health care. Therefore, we aimed to provide evidence on different aspects of mental health self-stigmatization among adult Syrian refugees with posttraumatic stress symptoms residing in Germany. Moreover, we investigated associations with sociodemographic and psychopathological variables in order to identify those at higher risk of self-stigmatization.

Material and Methods: Overall, 133 participants with mild to moderate posttraumatic stress symptoms were recruited in the metropolitan areas of Leipzig, Dresden and Halle, Germany, using a multimodal approach. Mental health self-stigma was assessed using the Self-Stigma of Mental Illness Scale – Short Form (SSMIS-SF), consisting of four subscales (Stereotype awareness, Stereotype agreement, Application to self , Harm to self-esteem), each scoring from 5 (low) to 45 (high) points. Linear regression analysis was used to test associations of sociodemographic and psychopathological variables with self-stigma subscales.

Results: On average, self-stigma ratings ranged from 16.5 (SD = 6.6) points on Application to self to 28.3 (SD = 7.5) points on Stereotype awareness. Results showed higher scores on Application to self for individuals who were younger (t = 2.65, p = 0.009) and single (F = 5.70, p = 0.004). Regression analyses yielded statistically significant associations between having multiple comorbidities and a higher Application to self stigma (β = 0.18, p = 0.044), controlling for sociodemographic covariates.

Discussion: Mental health self-stigma was increased among Syrian refugees in Germany. Correlates of increased self-stigma could inform efforts to improve access to mental health care among Syrian refugees with mental ill-health. Longitudinal studies following an intersectional approach by concurrently examining multiple forms of public and internalized stigma could provide helpful insights for developing tailored stigma reduction efforts in this context.
Oxygen and Mortality in COVID-19 Pneumonia: A Comparative Analysis of Supplemental Oxygen Policies and Health Outcomes Across 26 Countries
Authors: Mansab Fatma , Donnelly Harry , Kussner Albrecht , Neil James , Bhatti Sohail , Goyal Daniel K.
Published: July 2021

Introduction: Hypoxia is the main cause of morbidity and mortality in COVID-19. During the COVID-19 pandemic, some countries have reduced access to supplemental oxygen, whereas other nations have maintained and even improved access to supplemental oxygen. We examined whether variation in the nationally determined oxygen guidelines had any association with national mortality rates in COVID-19.

Methods: Three independent investigators searched for, identified, and extracted the nationally recommended target oxygen levels for the commencement of oxygen in COVID-19 pneumonia from the 29 worst affected countries. Mortality estimates were calculated from three independent sources. We then applied both parametric (Pearson's R) and non-parametric (Kendall's Tau B) tests of bivariate association to determine the relationship between case fatality rate (CFR) and target SpO2, and also between potential confounders and CFR.

Results: Of the 26 nations included, 15 had employed conservative oxygen strategies to manage COVID-19 pneumonia. Of them, Belgium, France, USA, Canada, China, Germany, Mexico, Spain, Sweden, and the UK guidelines advised commencing oxygen when oxygen saturations (SpO2) fell to 91% or less. A statistically significant correlation was found between SpO2 and CFR both parametrically (R = −0.53, P < 0.01) and non-parametrically (−0.474, P < 0.01).

Conclusion: Our study highlights the disparity in oxygen provision for COVID-19 patients between the nations analysed. In those nations that pursued a conservative oxygen strategy, there was an association with higher national mortality rates. We discuss the potential reasons for such an association.