bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophils Require Activation to Express Functional Cell-Surface Complement Receptor Immunoglobulin
Authors: Small Annabelle G. , Perveen Khalida , Putty Trishni , Patel Nikita , Quinn Patrick , Wechalekar Mihir D. , Hii Charles S. , Quach Alex , Ferrante Antonio
Published: March 2022

The phagocytosis-promoting complement receptor, Complement Receptor Immunoglobulin (CRIg), is exclusively expressed on macrophages. It has been demonstrated that expression in macrophages could be modulated by inflammatory mediators, including cytokines. This raised the possibility that a major phagocyte, the neutrophil, may also express CRIg following activation with inflammatory mediators. Here we show that resting peripheral blood neutrophil lysates subjected to protein analysis by Western blot revealed a 35 kDa CRIg isoform, consistent with the expression of CRIg mRNA by RT-PCR. By flow cytometry, CRIg was detected intracellularly and in very minor amounts on the cell surface. Interestingly, expression on the cell surface was significantly increased to functional levels after activation with inflammatory mediators/neutrophil activators; N-Formylmethionine-leucyl-phenylalanine, tumor necrosis factor (TNF), Granulocyte-Macrophage Colony stimulating Factor (GM-CSF), bacterial lipopolysaccharide, leukotriene B4 and phorbol myristate acetate. The increase in expression required p38 MAP kinase and protein kinase C activation, as well as intracellular calcium. Neutrophils which were defective in actin microfilament reorganization due to a mutation in ARPC1B or inhibition of its upstream regulator, Rac2 lose their ability to upregulate CRIg expression. Inhibition of another small GTPase, Rab27a, with pharmacological inhibitors prevented the increase in CRIg expression, suggesting a requirement for the actin cytoskeleton and exocytosis. Engagement of CRIg on TNF-primed neutrophils with an anti-CRIg monoclonal antibody increased the release of superoxide and promoted the activation of p38 but not ERK1/ERK2 or JNK MAP kinases. The TNF-induced increase in killing ofStaphylococcus aureuswas blocked by the anti-CRIg antibody. Adding to the anti-microbial role of CRIg, it was found that GM-CSF priming lead to the release of neutrophil extracellular traps. Interestingly in contrast to the above mediators the anti-inflammatory cytokine IL-10 caused a decrease in basal expression and GM-CSF induced increase in CRIg expression. The data demonstrate that neutrophils also express CRIg which is regulated by inflammatory mediators and cytokines. The findings show that the neutrophil antimicrobial function involving CRIg requires priming as a means of arming the cell strategically with microbial invasion of tissues and the bloodstream.
Tick Intrastadial Feeding and Its Role on IgE Production in the Murine Model of Alpha-gal Syndrome: The Tick “Transmission” Hypothesis
Authors: Maldonado-Ruiz L. Paulina , Boorgula Gunavanthi D. , Kim Donghun , Fleming Sherry D. , Park Yoonseong
Published: March 2022

Recent studies have provided strong evidence indicating that lone star tick bites are a cause of AGS (alpha-gal syndrome, also known as red meat allergy RMA) in humans. AGS is characterized by an increase in IgE antibody production against galactose-alpha-1,3-galactose (aGal), which is a common glycan found in mammalian tissue, except in Old World monkeys and humans. The main causative factor of AGS, the lone star tick (Amblyomma americanum), is broadly distributed throughout the east and midwest of the United States and is a vector of a wide range of human and animal pathogens. Our earlier glycomics study of the salivary glands of partially fed male and female ticks revealed relatively high levels of aGal epitopes. In this study, we found that partially fed males ofA. americanumon bovine blood, which engage in multiple intrastadial feedings, carry a large amount of aGal in the salivary glands. In our current work, we aimed to test whether ticks mediate the transmission of the aGal sensitizer acquired from nonhuman blood to humans in the intrastadial host switch (referred to as the “transmission” hypothesis). To test this hypothesis, we used an alpha-galactosyltransferase knockout mutant mouse (aGT-KO) model system infested with ticks that were unfed or partially fed on bovine blood. Based on the levels of total IgE and specific IgG and IgE antibodies against aGal after tick feedings, aGT-KO mice significantly responded to tick feeding and injection of aGal (Galα1-3Galβ1-4GlcNAc) conjugated to human serum albumin or mouse serum albumin (aGal-HSA or aGal-MSA) by increasing total IgE and aGal-specific IgE levels compared to those in C57BL/6 control mice. All of the treatments of aGT-KO mice involving the feeding of partially fed and unfed ticks functioned as sensitizers that increased the levels of specific IgE against aGal, with large individual variations. The data in this study do not support the “transmission” component of AGS, although they confirmed that aGT-KO mice can be used as a model for RMA studies.
Neuroinflammation, Microglia and Implications for Retinal Ganglion Cell Survival and Axon Regeneration in Traumatic Optic Neuropathy
Authors: Au Ngan Pan Bennett , Ma Chi Him Eddie
Published: March 2022

Traumatic optic neuropathy (TON) refers to a pathological condition caused by a direct or indirect insult to the optic nerves, which often leads to a partial or permanent vision deficit due to the massive loss of retinal ganglion cells (RGCs) and their axonal fibers. Retinal microglia are immune-competent cells residing in the retina. In rodent models of optic nerve crush (ONC) injury, resident retinal microglia gradually become activated, form end-to-end alignments in the vicinity of degenerating RGC axons, and actively internalized them. Some activated microglia adopt an amoeboid morphology that engulf dying RGCs after ONC. In the injured optic nerve, the activated microglia contribute to the myelin debris clearance at the lesion site. However, phagocytic capacity of resident retinal microglia is extremely poor and therefore the clearance of cellular and myelin debris is largely ineffective. The presence of growth-inhibitory myelin debris and glial scar formed by reactive astrocytes inhibit the regeneration of RGC axons, which accounts for the poor visual function recovery in patients with TON. In this Review, we summarize the current understanding of resident retinal microglia in RGC survival and axon regeneration after ONC. Resident retinal microglia play a key role in facilitating Wallerian degeneration and the subsequent axon regeneration after ONC. However, they are also responsible for producing pro-inflammatory cytokines, chemokines, and reactive oxygen species that possess neurotoxic effects on RGCs. Intraocular inflammation triggers a massive influx of blood-borne myeloid cells which produce oncomodulin to promote RGC survival and axon regeneration. However, intraocular inflammation induces chronic neuroinflammation which exacerbates secondary tissue damages and limits visual function recovery after ONC. Activated retinal microglia is required for the proliferation of oligodendrocyte precursor cells (OPCs); however, sustained activation of retinal microglia suppress the differentiation of OPCs into mature oligodendrocytes for remyelination after injury. Collectively, controlled activation of retinal microglia and infiltrating myeloid cells facilitate axon regeneration and nerve repair. Recent advance in single-cell RNA-sequencing and identification of microglia-specific markers could improve our understanding on microglial biology and to facilitate the development of novel therapeutic strategies aiming to switch resident retinal microglia’s phenotype to foster neuroprotection.
Abnormal Changes of Monocyte Subsets in Patients With Sjögren’s Syndrome
Authors: He Yan , Chen Rongjuan , Zhang Mengqin , Wang Bin , Liao Zhangdi , Shi Guixiu , Li Yan
Published: March 2022

Background

Recent studies have proven the existence of distinct monocyte subsets, which play a significant role in the development of some rheumatic diseases such as systemic lupus erythematosus (SLE). This study was performed to define the changes of monocyte subsets in patients with Sjögren’s Syndrome (SjS).

Methods

Single cell RNA-sequencing (scRNA-seq) data of monocytes from SjS patients and controls were analyzed. The transcriptomic changes in monocyte subsets between SjS and controls were identified and potential key functional pathways involved in SjS development were also explored.

Results

A total of 11 monocyte subsets were identified in the scRNA-seq analyses of monocytes. A new monocyte subset characterized by higher expression of VNN2 (GPI-80) and S100A12 (Monocyte cluster 3) was identified, and it was increased in SjS patients. Compared with controls, almost all monocyte subsets from SjS patients had increased expression of TNFSF10 (TRAIL). Moreover, interferon (IFN)-related and neutrophil activation-associated pathways were main up-regulated pathways in the monocytes of SjS patients.

Conclusion

This study uncovered the abnormal changes in monocyte subsets and their transcriptomic changes in SjS patients, and identified TNFSF10high/+monocytes as a potential key player in SjS pathogenesis and a promising target for SjS treatment.
Molecular Response of the Brain to Cross-Generational Warming in a Coral Reef Fish
Authors: Bernal Moisés A. , Schmidt Elliott , Donelson Jennifer M. , Munday Philip L. , Ravasi Timothy
Published: March 2022

Ocean warming is a threat to marine biodiversity, as it can push marine species beyond their physiological limits. Detrimental effects can occur when marine poikilotherms are exposed to conditions beyond their thermal optima. However, acclamatory mechanisms, such as plasticity, may enable compensation of detrimental effects if warming is experienced during development or across generations. Studies evaluating the molecular responses of fishes to warming have mostly focused on liver, muscle, and gonads, and little is known about the effects on other vital organs, including the brain. This study evaluated the transcriptional program of the brain in the coral reef fish Acanthochromis polyacanthus, exposed to two different warming scenarios: +1.5°C and +3.0°C, across successive generations. Fish were exposed to these conditions in both developmental (F1 and F2) and transgenerational settings (F2 only), as well as a treatment with step-wise warming between generations. The largest differences in gene expression were between individuals of the first and second generation, a pattern that was corroborated by pairwise comparisons between Control F1 and Control F2 (7,500 DEGs) fish. This large difference could be associated with parental effects, as parents of the F1 generation were collected from the wild, whereas parents of the F2 generation were reared in captivity. A general response to warming was observed at both temperatures and in developmental and transgenerational treatments included protein folding, oxygen transport (i.e., myoglobin), apoptosis and cell death, modification of cellular structure, mitochondrial activity, immunity and changes in circadian regulation. Treatments at the highest temperature showed a reduction in synaptic activity and neurotransmission, which matches previous behavioral observations in coral reef fishes. The Transgenerational +3.0°C treatment showed significant activation of the gene pls3, which is known for the development of neuro-muscular junctions under heat-stress. F2 samples exposed to step-wise warming showed an intermediate response, with few differentially expressed genes compared to developmental and transgenerational groups (except for Transgenerational +1.5°C). In combination with previous studies on liver gene expression, this study indicates that warming produces a molecular signature of stress response in A. polyacanthus that is influenced both by the intensity of warming as well as the duration of exposure.
An Open and Scalable Method for Spatial Measurement of Blue Economies
Authors: Llewellyn Lyndon E.
Published: March 2022

Blue economies are measured by mining national statistics or economic modeling, requiring substantial capability and quality data, both of which are not universally available. The lack of harmonized methods hampers international comparisons and results are usually only attributable at the national scale. An alternative method is described here that leverages an open computing environment and data to quantify blue economies using marine night light producing measurements that are intercomparable and scalable from national to regional to global.
Comparison Between Trophic Positions in the Barents Sea Estimated From Stable Isotope Data and a Mass Balance Model
Authors: Pedersen Torstein
Published: March 2022

The trophic position concept is central in system ecology, and in this study, trophic position (TP) estimates from stable-isotopes and an Ecopath mass-balance food web model for the Barents Sea were compared. Two alternative models for estimating TP from stable isotopes, with fixed or scaled trophic fractionation were applied. The mass-balance model was parametrized and balanced for year 2000, was comprised of 108 functional groups (Gs), and was based on biomass and diet data largely based on predator stomach data. Literature search for the Barents Sea Large Marine Ecosystem revealed 93 sources with stable isotope data (δ15N values) for 83 FGs, and 25 of the publications had trophic position estimated from nitrogen stable isotopes. Trophic positions estimated from the mass-balance model ranged to 5.1 TP and were highly correlated with group mean δ15N values, and also highly correlated with the original literature estimates of trophic positions from stable isotopes. On average, TP from the mass-balance model was 0.1 TP higher than the original literature TP estimates (TPSIR) from stable isotopes. A trophic enrichment factor (TEF) was estimated assuming fixed fractionation and minimizing differences between trophic positions from Ecopath and TP predicted from δ15N values assuming a baseline value for δ15N calculated for pelagic particulate organic matter at a baseline TP of 1.0. The estimated TEF of 3.0‰ was lower than the most commonly used TEF of 3.4 and 3.8‰ in the literature. The pelagic whales and pelagic invertebrates functional groups tended to have higher trophic positions from Ecopath than from stable isotopes while benthic invertebrate functional groups tended to show an opposite pattern. Trophic positions calculated using the scaled trophic fractionation approach resulted in lower TP than from Ecopath for intermediate TPs and also a larger TP range in the BS. It is concluded that TPs estimated from δ15N values using a linear model compared better to the Ecopath model than the TPs from scaled fractionation approach.
Habitat and Macrozoobenthic Diversity in Marine Protected Areas of the Southern Romanian Black Sea Coast
Authors: Begun Tatiana , Teacă Adrian , Mureşan Mihaela , Quijón Pedro A. , Menabit Selma , Surugiu Victor
Published: March 2022

Exposure to a variety of anthropogenic stressors has prompted the creation of a growing number of marine protected areas (MPAs). Unfortunately, long-term changes in both the sources of stress and the extent or operation of the MPAs have also occurred, at a pace that is often faster than the research trying to understand the consequences of those changes. This study addresses this challenge by focusing on two MPAs located in the southern Romanian Black Sea, namely the Cape Tuzla and the Mangalia Sulfur springs. Using 95 seafloor samples collected over a 7-year period, we explored distinct benthic habitats and their associated communities in a depth gradient common to both MPAs. We described benthic communities, their density, biomass, and diversity and subsequently used them as indicators of the health of the seafloor. Specifically, we used the M-AMBI*(n) index to assess the ecological status of the benthic habitats found in both MPAs. Our results identified seven distinct habitats across infralittoral and circalittoral areas and described species composition and diversity levels, reaching up to a grand total of 119 benthic taxa. These communities were often dominated by polychaetes and crustaceans in terms of density and by mollusks in terms of biomass. Several mollusks represent key ecosystem engineer species creating or modifying their local habitat conditions. Our results revealed that two thirds of the sampling stations could be characterized as having a good ecological status (GES), and were therefore dominated by species normally considered as either sensitive or indifferent to organic pollution. Meanwhile, the other third of the stations was labeled as non-GES, was dominated by opportunistic species and represent a concern for the coastline system. This study calls for further research to carefully describe the valuable coastal habitats under the frame of MPAs, and to assess the effects of specific pollutants and the response of organisms that seem most affected by these stressors.
The Influence of Long-Term Autoclaving on the Properties of Ultra-High Performance Concrete
Authors: Tian Hongwei , Hirsch Tamino , Stephan Dietmar , Lehmann Christian
Published: March 2022

Thermal energy storage is a key component in harnessing renewable resources, compensating for the energy variations across time scales. A popular strategy for thermal energy storage is storing thermal energy in hot water tanks, which are generally made of copper, stainless steel, and vitreous enamel-lined carbon steel. However, these materials usually suffer a high production cost and short life cycle. UHPC with superior strength and durability holds the potential as a construction material for hot water tanks, which are commercially available and affordable for large-scale applications. During the charging process of hot water tanks, the UHPC structures are thus loaded by a long-term temperature-pressure load (autoclaving condition). However, the influence of long-term autoclaving on UHPC is still unclear. Therefore, the influence of long-term autoclaving at 200°C on the mechanical properties and microstructure of UHPC is studied here. The effect of the long-term autoclaving depends on the UHPC compositions. The compressive strength can stay robust owing to the accelerated formation of hydrates, while the flexural strength is vulnerable to the long-term autoclaving. Katoite, hydroxylellestadite, and scawtite are identified as the new hydrates in the autoclaved UHPC with typical components. The transformation of amorphous C-S-H into more ordered phases results in the low flexural strength and the undensified interface between the matrix and steel fibres. The partial replacement of cement by fly ash mitigates the detrimental effect of the long-term autoclaving. The incorporation of fly ash provides additional silica and increases the ratio of silica to cement, leading to more poorly crystallized C-S-H with a low Ca/Si ratio, which benefits microstructure densification and mechanical strength. The decrease of Ca/Si ratio and the increase of Al by fly ash accelerate the decomposition of katoite and hydroxylellestadite and formation of tobermorite. This study clarifies the influence of the long-term autoclaving on UHPC and provides guidance for developing an applicable and sustainable UHPC as the construction material for hot water tanks.
Preparation and Study on Nitrogen- and Phosphorus- Containing Fire Resistant Coatings for Wood by UV-Cured Methods
Authors: Ma Guoru , Wang Xuan , Cai Wei , Ma Chao , Wang Xin , Zhu Yulu , Kan Yongchun , Xing Weiyi , Hu Yuan
Published: March 2022

Wood has been widely used since ancient times due to its biodegradability, good elasticity, impact resistance, and easy availability. However, the flammability of wood has vastly limited its applications and the fire hazard of wood has cost a great loss of life and property. Thus, it is important to improve the fire resistance of wood. Here, we used a phosphate acrylate monomer (PGMA) which was synthesized with phosphoric acid and glycidyl methacrylate by ring-opening reaction and melamine acrylic ester (MAAR) to make up a series of fireproof coatings with different proportions, and the fire resistance of wood has been investigated using the limiting oxygen index (LOI) test, back temperature test, and cone calorimeter test. When the wood was coated with the composite of 33.3% PGMA and 66.7% MAAR, the total heat release value decreased from 39.0 to 38.2 MJ/m2, and the total smoke release value decreased from 622 to 512 m2/m2, showing a remarkable improvement in fire resistance and smoke suppression. Thus, this easily prepared, cheap, and effective flame retardant coating can promote a wider application of wood.
Human Tissue Kallikreins-Related Peptidases Are Targets for the Treatment of Skin Desquamation Diseases
Authors: Zani Marcelo B. , Sant'Ana Aquiles M. , Tognato Rafael C. , Chagas Jair R. , Puzer Luciano
Published: March 2022

Human tissue Kallikrein-related peptidases (hKLKs) are serine proteases distributed in several tissues that are involved in several biological processes. In skin, many are responsible for skin desquamation in the Stratum Corneum (SC) of the epidermis, specially hKLK5, hKLK7, hKLK6, hKLK8, and hKLK14. In SC, hKLKs cleave proteins of corneodesmosomes, an important structure responsible to maintain corneocytes attached. As part of skin desquamation, hKLKs are also involved in skin diseases with abnormal desquamation and inflammation, such as Atopic Dermatitis (AD), psoriasis, and the rare disease Netherton Syndrome (NS). Many studies point to hKLK overexpression or overactive in skin diseases, and they are also part of the natural skin inflammation process, through the PAR2 cleavage pathway. Therefore, the control of hKLK activity may offer successful treatments for skin diseases, improving the quality of life in patients. Diseases like AD, Psoriasis, and NS have an impact on social life, causing pain, itchy and mental disorders. In this review, we address the molecular mechanisms of skin desquamation, emphasizing the roles of human tissue Kallikrein-related peptidases, and the promising therapies targeting the inhibition of hKLKs.
Favipiravir Effectiveness and Safety in Hospitalized Moderate-Severe COVID-19 Patients: Observational Prospective Multicenter Investigation in Saudi Arabia
Authors: Al-Muhsen Saleh , Al-Numair Nouf S. , Saheb Sharif-Askari Narjes , Basamh Roaa , Alyounes Banan , Jabaan Amjad , Saheb Sharif-Askari Fatemeh , Alosaimi Mohammed F. , Alsohime Fahad , Halwani Rabih , Al-Saud Haya
Published: March 2022

Objectives

There are limited data on the efficacy and safety of favipiravir antiviral in coronavirus disease 2019 (COVID-19), particularly in the more progressed disease phase. This study aims to evaluate the favipiravir effect on reducing the length of hospital stay and in-hospital mortality among moderate and severe hospitalized COVID-19 patients.

Methods

A prospective, multicenter observational study was conducted that included moderate and severe hospitalized adult COVID-19 patients in four major regions (Riyadh (Riyadh), Eastern (Dammam), Al-Qassem (Buraydah), and Macca (Jeddah) of Saudi Arabia. For the primary outcome of all-cause mortality, a Cox proportional hazard analysis was performed. While the association between favipiravir use and length of hospital stay was determined using adjusted generalized linear model. This study was approved by the Central Institutional Review Board in The Saudi Ministry of Health (MoH) with the approval number IRB # 20-85-M.

Results

This study included 598 moderate and severe COVID-19 patients, of whom 156 (26%) received favipiravir. Favipiravir treatment was associated with more extended hospital stays (14 vs. 10 median days, P = 0.034) and higher mortality rate (aHR 3.63; 95% CI 1.06–12.45) compared to no favipiravir regimen. Despite lack of effectiveness, favipiravir use was only associated with higher diarrhea adverse effects (12 vs. 5%, P = 0.002), but it did not affect the renal and liver profiles of patients.

Conclusion

Favipiravir was ineffective in reducing the length of hospital stay and in-hospital mortality in patients with moderate and severe COVID-19.
Clinical Factors and Perinatal Outcomes Associated With Short Latency Period in Twin Pregnancies With Preterm Premature Rupture of Membranes Before 34 Weeks: A Retrospective Study
Authors: Zhou Shuwei , Mei Lingwei , Zhou Wei , Yang Yajun , Zhang Xiaoyan , Mu Xiaoling , Quan Quan , Wang Lan
Published: March 2022

Background

There is a lack of literature on short latency period (SLP) in twin pregnancies with preterm premature rupture of membranes (PPROM). Thus, the aim of this study was to identify the clinical factors and perinatal outcomes associated with SLP in twin pregnancies with PPROM and to establish a predictive model to identify SLP.

Methods

Twin pregnancies with PPROM between 24 0/7 and 33 6/7 weeks were included and a retrospective analysis was performed. Patients were divided into two groups based on the latency period after PPROM: Group 1 ≤24 h (defined as SLP) and Group 2 >24 h (defined as long latency period, LLP), the clinical factors and perinatal outcomes were compared between the two groups. Binary logistic regression and receiver operating characteristic curve analyses were used to identify the independent clinical factors associated with latency period after PPROM and assess the predictive accuracy for SLP.

Results

98 and 92 pregnant women had short and long latency period, respectively. Prolonged latency significantly increased the occurrence of chorioamnionitis. Neonatal outcomes were not affected by latency duration after PPROM. Binary regression analysis revealed that higher gestational age (GA) at PPROM (P = 0.038), presence of uterine contractions (P < 0.001), Bishop score > 4 (P = 0.030), serum procalcitonin levels ≥0.05 ng/mL upon admission, and absence of use of tocolytic agents (P < 0.001) were significant independent predictors of a SLP. A predictive model developed using these predictors had an area under the curve (AUC) of 0.838, and the presence of uterine contractions alone had an AUC of = 0.711.

Conclusion

Uterine contraction was the most important prognosticator for a SLP. A latency period of >24 h was associated with chorioamnionitis, but adverse neonatal outcomes were not observed.
The Interplay Between Coronavirus and Type I IFN Response
Authors: Xue Wenxiang , Ding Chan , Qian Kun , Liao Ying
Published: March 2022

In the past few decades, newly evolved coronaviruses have posed a global threat to public health and animal breeding. To control and prevent the coronavirus-related diseases, understanding the interaction of the coronavirus and the host immune system is the top priority. Coronaviruses have evolved multiple mechanisms to evade or antagonize the host immune response to ensure their replication. As the first line and main component of innate immune response, type I IFN response is able to restrict virus in the initial infection stage; it is thus not surprising that the primary aim of the virus is to evade or antagonize the IFN response. Gaining a profound understanding of the interaction between coronaviruses and type I IFN response will shed light on vaccine development and therapeutics. In this review, we provide an update on the current knowledge on strategies employed by coronaviruses to evade type I IFN response.
Host Molecules Regulating Neural Invasion of Zika Virus and Drug Repurposing Strategy
Authors: Tan Li Yin , Komarasamy Thamil Vaani , James William , Balasubramaniam Vinod R. M. T.
Published: March 2022

Zika virus (ZIKV) is a mosquito-borne, single-stranded RNA virus belonging to the genus Flavivirus. Although ZIKV infection is usually known to exhibit mild clinical symptoms, intrauterine ZIKV infections have been associated with severe neurological manifestations, including microcephaly and Guillain Barre syndrome (GBS). Therefore, it is imperative to understand the mechanisms of ZIKV entry into the central nervous system (CNS) and its effect on brain cells. Several routes of neuro-invasion have been identified, among which blood–brain barrier (BBB) disruption is the commonest mode of access. The molecular receptors involved in viral entry remain unknown; with various proposed molecular ZIKV-host interactions including potential non-receptor mediated cellular entry. As ZIKV invade neuronal cells, they trigger neurotoxic mechanisms via cell-autonomous and non-cell autonomous pathways, resulting in neurogenesis dysfunction, viral replication, and cell death, all of which eventually lead to microcephaly. Together, our understanding of the biological mechanisms of ZIKV exposure would aid in the development of anti-ZIKV therapies targeting host cellular and/or viral components to combat ZIKV infection and its neurological manifestations. In this present work, we review the current understanding of ZIKV entry mechanisms into the CNS and its implications on the brain. We also highlight the status of the drug repurposing approach for the development of potential antiviral drugs against ZIKV.
Genome-Wide Transcriptional Response of Mycobacterium smegmatis MC2155 to G-Quadruplex Ligands BRACO-19 and TMPyP4
Authors: Shitikov Egor , Bespiatykh Dmitry , Malakhova Maja , Bespyatykh Julia , Bodoev Ivan , Vedekhina Tatiana , Zaychikova Marina , Veselovsky Vladimir , Klimina Ksenia , Ilina Elena , Varizhuk Anna
Published: March 2022

G-quadruplexes (G4s) are non-canonical DNA structures that could be considered as potential therapeutic targets for antimicrobial compounds, also known as G4-stabilizing ligands. While some of these ligands are shownin vitroto have a stabilizing effect, the precise mechanism of antibacterial action has not been fully investigated. Here, we employed genome-wide RNA-sequencing to analyze the response ofMycobacterium smegmatisto inhibitory concentrations of BRACO-19 and TMPyP4 G4 ligands. The expression profile changed (FDR < 0.05, log2FC > |1|) for 822 (515↑; 307↓) genes inM. smegmatisin response to BRACO-19 and for 680 (339↑; 341↓) genes in response to TMPyP4. However, the analysis revealed no significant ligand-induced changes in the expression levels of G4-harboring genes, genes under G4-harboring promoters, or intergenic regions located on mRNA-like or template strands. Meanwhile, for the BRACO-19 ligand, we found significant changes in the replication and repair system genes, as well as in iron metabolism genes which is, undoubtedly, evidence of the induced stress. For the TMPyP4 compound, substantial changes were found in transcription factors and the arginine biosynthesis system, which may indicate multiple biological targets for this compound.
Comparative Proteomic Analysis of Fucosylated Glycoproteins Produced by Bacteroides thetaiotaomicron Under Different Polysaccharide Nutrition Conditions
Authors: Tian Xiao , Jiang Hao , Cai Binbin , Feng Huxin , Wang Xuan , Yu Guangli
Published: March 2022

Bacteroides thetaiotaomicron, one of the most eminent representative gut commensal Bacteroides species, is able to use the L-fucose in host-derived and dietary polysaccharides to modify its capsular polysaccharides and glycoproteins through a mammalian-like salvage metabolic pathway. This process is essential for the colonization of the bacteria and for symbiosis with the host. However, despite the importance of fucosylated proteins (FGPs) in B. thetaiotaomicron, their types, distribution, and functions remain unclear. In this study, the effects of different polysaccharide (corn starch, mucin, and fucoidan) nutrition conditions on newly synthesized FGPs expressions and fucosylation are investigated using a chemical biological method based on metabolic labeling and bioorthogonal reaction. According to the results of label-free quantification, 559 FGPs (205 downregulated and 354 upregulated) are affected by the dietary conditions. Of these differentially expressed proteins, 65 proteins show extremely sensitive to polysaccharide nutrition conditions (FGPs fold change/global protein fold change ≥2.0 or ≤0.5). Specifically, the fucosylation of the chondroitin sulfate ABC enzyme, Sus proteins, and cationic efflux system proteins varies significantly upon the addition of mucin, corn starch, or fucoidan. Moreover, these polysaccharides can trigger an appreciable increase in the fucosylation level of the two-component system and ammonium transport proteins. These results highlight the efficiency of the combined metabolic glycan labeling and bio-orthogonal reaction in enriching the intestinal Bacteroides glycoproteins. Moreover, it emphasizes the sensitivity of Bacteroides fucosylation to polysaccharide nutrition conditions, which allows for the regulation of bacterial growth.
Heat Shock Protein A6 Is Especially Involved in Enterovirus 71 Infection
Authors: Jia Jiaoyan , Liu Ge , Zhong Jianfeng , Yan Ran , Song Xun , Zheng Kai , Ren Zhe , He Zhendan , Zhu Qinchang
Published: March 2022

Hand foot and mouth disease (HFMD) caused by Enterovirus 71 (EV71) infection is still a major infectious disease threatening children’s life and health in the absence of effective antiviral drugs due to its high prevalence and neurovirulence. A study of EV71-specific host response might shed some light on the reason behind its unique epidemiologic features and help to find means to conquer EV71 infection. We reported that host heat shock protein A6 (HSPA6) was induced by EV71 infection and involved infection in both Rhabdomyosarcoma (RD) cells and neurogliocytes. Most importantly, we found that EV71 did not induce the expression of other heat shock proteins HSPA1, HSPA8, and HSPB1 under the same conditions, and other HFMD-associated viruses including CVA16, CVA6, CVA10, and CVB1-3 did not induce the upregulation of HSPA6. In addition, EV71 infection enhanced the cytoplasmic aggregation of HSPA6 and its colocalization with viral capsid protein VP1. These findings suggest that HSPA6 is a potential EV71-specific host factor worthy of further study.
Integrated Analysis of Transcriptomic and Genomic Data Reveals Blood Biomarkers With Diagnostic and Prognostic Potential in Non-small Cell Lung Cancer
Authors: Kaya Ibrahim H. , Al-Harazi Olfat , Kaya Mustafa T. , Colak Dilek
Published: March 2022

Background: Lung cancer is the second most common cancer and the main leading cause of cancer-associated death worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer diagnoses and more than 50% of all lung cancer cases are diagnosed at an advanced stage; hence have poor prognosis. Therefore, it is important to diagnose NSCLC patients reliably and as early as possible in order to reduce the risk of mortality.

Methods: We identified blood-based gene markers for early NSCLC by performing a multi-omics approach utilizing integrated analysis of global gene expression and copy number alterations of NSCLC patients using array-based techniques. We also validated the diagnostic and the prognostic potential of the gene signature using independent datasets with detailed clinical information.

Results: We identified 12 genes that are significantly expressed in NSCLC patients’ blood, at the earliest stages of the disease, and associated with a poor disease outcome. We then validated 12-gene signature’s diagnostic and prognostic value using independent datasets of gene expression profiling of over 1000 NSCLC patients. Indeed, 12-gene signature predicted disease outcome independently of other clinical factors in multivariate regression analysis (HR = 2.64, 95% CI = 1.72–4.07; p = 1.3 × 10−8). Significantly altered functions, pathways, and gene networks revealed alterations in several key genes and cancer-related pathways that may have importance for NSCLC transformation, including FAM83A, ZNF696, UBE2C, RECK, TIMM50, GEMIN7, and XPO5.

Conclusion: Our findings suggest that integrated genomic and network analyses may provide a reliable approach to identify genes that are associated with NSCLC, and lead to improved diagnosis detecting the disease in early stages in patients’ blood instead of using invasive techniques and also have prognostic potential for discriminating high-risk patients from the low-risk ones.
Transformer-Based High-Frequency Oscillation Signal Detection on Magnetoencephalography From Epileptic Patients
Authors: Guo Jiayang , Xiao Naian , Li Hailong , He Lili , Li Qiyuan , Wu Ting , He Xiaonan , Chen Peizhi , Chen Duo , Xiang Jing , Peng Xueping
Published: March 2022

High-frequency oscillations (HFOs), observed within 80–500 Hz of magnetoencephalography (MEG) data, are putative biomarkers to localize epileptogenic zones that are critical for the success of surgical epilepsy treatment. It is crucial to accurately detect HFOs for improving the surgical outcome of patients with epilepsy. However, in clinical practices, detecting HFOs in MEG signals mainly depends on visual inspection by clinicians, which is very time-consuming, labor-intensive, subjective, and error-prone. To accurately and automatically detect HFOs, machine learning approaches have been developed and have demonstrated the promising results of automated HFO detection. More recently, the transformer-based model has attracted wide attention and achieved state-of-the-art performance on many machine learning tasks. In this paper, we are investigating the suitability of transformer-based models on the detection of HFOs. Specifically, we propose a transformer-based HFO detection framework for biomedical MEG one-dimensional signal data. For signal classification, we develop a transformer-based HFO (TransHFO) classification model. Then, we investigate the relationship between depth of deep learning models and classification performance. The experimental results show that the proposed framework outperforms the state-of-the-art HFO classifiers, increasing classification accuracy by 7%. Furthermore, we find that shallow TransHFO (<10 layers) outperforms deep TransHFO models (≥10 layers) on most data augmented factors.
Untargeted Metabolomics Study of Three Matrices: Seminal Fluid, Urine, and Serum to Search the Potential Indicators of Prostate Cancer
Authors: Buszewska-Forajta Magdalena , Raczak-Gutknecht Joanna , Struck-Lewicka Wiktoria , Nizioł Magdalena , Artymowicz Małgorzata , Markuszewski Marcin , Kordalewska Marta , Matuszewski Marcin , Markuszewski Michał J.
Published: March 2022

The simultaneous determination of metabolites from biological fluids may provide more accurate information about the current body condition. So far, the metabolomics approach has been successfully applied to study the mechanism of several disorders and to search for novel biomarkers. Urine and plasma are widely accepted matrices for the evaluation of several pathologies, while prostate cancer (CaP) development is still unknown. For this reason, an alternative matrix, the seminal fluid, was proposed to expand the knowledge about the CaP pathomechanism. The main aim of this study was to develop and optimize the sample preparation protocol to ensure the highest coverage of the metabolome of ejaculate samples. Parameters like the type and composition of the solvent mixture, time of extraction, and applied volume of the solvent were tested. The optimized method was applied for the untargeted metabolomics profiling of seminal fluid samples obtained from CaP patients. Moreover, urine and serum samples were also prepared for untargeted metabolomics analysis. Analyses were carried out with the use of two complementary analytical techniques: GC-EI-QqQ/MS and LC-ESI-TOF/MS. Finally, the metabolic signature of seminal fluid (n = 7), urine (n = 7), and plasma (n = 7) samples was compared. Furthermore, the hypothesis of the increased level of metabolites in ejaculate samples related to the CaP development was evaluated. The results indicated that the developed and optimized sample preparation protocol for seminal fluid may be successfully applied for metabolomics study. Untargeted analysis of ejaculate enabled to determine the following classes of compounds: fatty acids, sphingolipids, phospholipids, sugars, and their derivatives, as well as amino acids. Finally, a comparison of the three tested matrices was carried out. To our best knowledge, it is the first time when the metabolic profile of the three matrices, namely, urine, plasma, and seminal fluid, was compared. Based on the results, it can be pointed out that ejaculate comprises the metabolic signature of both matrices (polar compounds characteristic for urine, and non-polar ones present in plasma samples). Compared to plasma, semen samples revealed to have a similar profile; however, determined levels of metabolites were lower in case of ejaculate. In case of urine samples, compared to semen metabolic profiles, the levels of detected metabolites were decreased in the latter ones.
Proximity-Dependent Biotinylation Approaches to Explore the Dynamic Compartmentalized Proteome
Authors: Dionne Ugo , Gingras Anne-Claude
Published: March 2022

In recent years, proximity-dependent biotinylation approaches, including BioID, APEX, and their derivatives, have been widely used to define the compositions of organelles and other structures in cultured cells and model organisms. The associations between specific proteins and given compartments are regulated by several post-translational modifications (PTMs); however, these effects have not been systematically investigated using proximity proteomics. Here, we discuss the progress made in this field and how proximity-dependent biotinylation strategies could elucidate the contributions of PTMs, such as phosphorylation, to the compartmentalization of proteins.
Performance of Impedance Control-Based Strategies in Power-Assisted Wheelchairs: A Predictive Simulation Study
Authors: Cuerva Vinicius Ishimoto , Ackermann Marko , Leonardi Fabrizio
Published: March 2022

Manual wheelchair propulsion is known to be inefficient and causes upper extremity pain, fatigue, and injury. Power-assisted wheelchairs can mitigate these effects through motors that reduce users' effort and load during propulsion. Among the different control strategies proposed to govern the user-wheelchair interaction, impedance control-based ones appear to be the most natural and effective. It can change the apparent dynamical properties of the wheelchair, particularly mass and friction, and automatically compensate for external disturbances such as terrain conditions. This study investigates the advantages and disadvantages of this control strategy employing predictive simulations of locomotion with power-assisted wheelchairs in different scenarios. The simulations are generated using a biomechanically realistic model of the upper extremities and their interaction with the power-assisted wheelchair by solving an optimal control problem. Investigated scenarios include steady-state locomotion vs. a transient maneuver starting from rest, movement on a ramp vs. a level surface, and different choices of reference model parameters. The results reveal that the investigated impedance control-based strategy can effectively reproduce the reference model and reduce the user's effort, with a more significant effect of inertia in the transient maneuver and of friction in steady-state locomotion. However, the simulations also show that imposing a first-order, linear reference model with constant parameters can produce disadvantageous locomotion patterns, particularly in the recovery phase, leading to unnecessary energy dissipation and consequent increase in energy consumption from the batteries. These observations indicate there is room for improvement, for instance, by exploring energy regeneration in the recovery phase or by switching reference model nature or parameters along the cycle. To the best of our knowledge, this is the first investigation of impedance control-based strategies for power-assisted wheelchairs using predictive simulations and a realistic, nonlinear model of the user-wheelchair system.
Evidence That Substantia Nigra Pars Compacta Dopaminergic Neurons Are Selectively Vulnerable to Oxidative Stress Because They Are Highly Metabolically Active
Authors: Ni Anjie , Ernst Carl
Published: March 2022

There are 400–500 thousand dopaminergic cells within each side of the human substantia nigra pars compacta (SNpc) making them a minuscule portion of total brain mass. These tiny clusters of cells have an outsized impact on motor output and behavior as seen in disorders such as Parkinson’s disease (PD). SNpc dopaminergic neurons are more vulnerable to oxidative stress compared to other brain cell types, but the reasons for this are not precisely known. Here we provide evidence to support the hypothesis that this selective vulnerability is because SNpc neurons sustain high metabolic rates compared to other neurons. A higher baseline requirement for ATP production may lead to a selective vulnerability to impairments in oxidative phosphorylation (OXPHOS) or genetic insults that impair Complex I of the electron transport chain. We suggest that the energy demands of the unique morphological and electrophysiological properties of SNpc neurons may be one reason these cells produce more ATP than other cells. We further provide evidence to support the hypothesis that transcription factors (TFs) required to drive induction, differentiation, and maintenance of midbrain dopaminergic neural progenitor cells which give rise to terminally differentiated SNpc neurons are uniquely involved in both developmental patterning and metabolism, a dual function unlike other TFs that program neurons in other brain regions. The use of these TFs during induction and differentiation may program ventral midbrain progenitor cells metabolically to higher ATP levels, allowing for the development of those specialized cell processes seen in terminally differentiated cells. This paper provides a cellular and developmental framework for understanding the selective vulnerability of SNpc dopaminergic cells to oxidative stress.