bluuebunny/crossref_metadata_2025 huggingface dataset:
Younger age is associated with cardiovascular pathological phenotype of severe COVID-19 at autopsy
Authors: Giugni Fernando R. , Duarte-Neto Amaro N. , da Silva Luiz Fernando F. , Monteiro Renata A. A. , Mauad Thais , Saldiva Paulo H. N. , Dolhnikoff Marisa
Published: January 2024

Introduction

COVID-19 affects patients of all ages. There are few autopsy studies focusing on the younger population. We assessed an autopsy cohort aiming to understand how age influences pathological outcomes in fatal COVID-19.

Methods

This study included autopsied patients, aged 6 months to 83 years, with confirmed COVID-19 in 2020–2021. We collected tissue samples from deceased patients using a minimally invasive autopsy protocol and assessed pathological data following a systematic approach.

Results

Eighty-six patients were included, with a median age of 55 years (IQR 32.3–66.0). We showed that age was significantly lower in patients with acute heart ischemia (p = 0.004), myocarditis (p = 0.03) and lung angiomatosis (p < 0.001), and significantly higher in patients with exudative diffuse alveolar damage (p = 0.02), proliferative diffuse alveolar damage (p < 0.001), lung squamous metaplasia (p = 0.003) and lung viral atypia (p = 0.03), compared to patients without those findings. We stratified patients by their age and showed that cardiovascular findings were more prevalent in children and young adults. We performed principal component analysis and cluster of pathological variables, and showed that cardiovascular variables clustered and covariated together, and separated from pulmonary variables.

Conclusion

We showed that age modulates pathological outcomes in fatal COVID-19. Younger age is associated with cardiovascular abnormalities and older age with pulmonary findings.
First record of Aspergillus nomiae as a broad-spectrum entomopathogenic fungus that provides resistance against phytopathogens and insect pests by colonization of plants
Authors: Zhang Zhengkun , Tian Yifan , Sui Li , Lu Yang , Cheng Ke , Zhao Yu , Li Qiyun , Shi Wangpeng
Published: January 2024

Introduction

Aspergillus nomiae is known as a pathogenic fungus that infects humans and plants but has never been reported as an entomophagous fungus (EPF) that can provide other functions as an endotype.

Methods

A strain of EPF was isolated and identified from diseased larvae of Spodoptera litura in a soybean field and designated AnS1Gzl-1. Pathogenicity of the strain toward various insect pests was evaluated, especially the ability to colonize plants and induce resistance against phytopathogens and insect pests.

Results

The isolated EPF strain AnS1Gzl-1 was identified as A. nomiae; it showed strong pathogenicity toward five insect pests belonging to Lepidoptera and Hemiptera. Furthermore, the strain inhibited the growth of Sclerotinia sclerotiorum in vitro, a causal agent of soil-borne plant disease. It colonized plants as an endophyte via root irrigation with a high colonization rate of 90%, thereby inducing plant resistance against phytopathogen infection, and disrupting the feeding selectivity of S. litura larvae.

Discussion

This is the first record of a natural infection of A. nomiae on insects. A. nomiae has the potential to be used as a dual biocontrol EPF because of its ability to not only kill a broad spectrum of insect pests directly but also induce resistance against phytopathogens via plant colonization.
Study of marine microorganism metabolites: new resources for bioactive natural products
Authors: Barzkar Noora , Sukhikh Stanislav , Babich Olga
Published: January 2024

The marine environment has remained a source of novel biological molecules with diversified applications. The ecological and biological diversity, along with a unique physical environment, have provided the evolutionary advantage to the plant, animals and microbial species thriving in the marine ecosystem. In light of the fact that marine microorganisms frequently interact symbiotically or mutualistically with higher species including corals, fish, sponges, and algae, this paper intends to examine the potential of marine microorganisms as a niche for marine bacteria. This review aims to analyze and summarize modern literature data on the biotechnological potential of marine fungi and bacteria as producers of a wide range of practically valuable products (surfactants, glyco-and lipopeptides, exopolysaccharides, enzymes, and metabolites with different biological activities: antimicrobial, antitumor, and cytotoxic). Hence, the study on bioactive secondary metabolites from marine microorganisms is the need of the hour. The scientific novelty of the study lies in the fact that for the first time, the data on new resources for obtaining biologically active natural products — metabolites of marine bacteria and fungi — were generalized. The review investigates the various kinds of natural products derived from marine microorganisms, specifically focusing on marine bacteria and fungi as a valuable source for new natural products. It provides a summary of the data regarding the antibacterial, antimalarial, anticarcinogenic, antibiofilm, and anti-inflammatory effects demonstrated by marine microorganisms. There is currently a great need for scientific and applied research on bioactive secondary metabolites of marine microorganisms from the standpoint of human and animal health.
The occurrence of clubroot in cruciferous crops correlates with the chemical and microbial characteristics of soils
Authors: Kang Huajun , Lin Zihan , Yuan Xiaowei , Shi Yanxia , Xie Xuewen , Li Lei , Fan Tengfei , Li Baoju , Chai Ali
Published: January 2024

Clubroot disease, caused by Plasmodiophora brassicae, is a serious soil-borne disease in Brassica crops worldwide. It seriously occurs in conducive soils of southern China, while never happens in some areas of northern China with suppressive soils. To understanding the differences, we measured the soil suppressiveness, chemical properties, and microbial communities in suppressive and conducive soils by bioassay and sequencing of 16S and 18S rRNA amplicons. The biological basis of clubroot suppressiveness was supported by the ability to remove it by pasteurization. The pH value and calcium content in the suppressive soils were higher than those in the conducive soils. Suppressive soils were associated with higher fungal diversity and bacterial abundance. The fungal phyla Chytridiomycota, Olpidiomycota, and Mucoromycota and the bacterial phyla Acidobacteriota and Gemmatimonadota were enriched in suppressive soils. More abundant beneficial microbes, including Chaetomium and Lysobacter, were found in the suppressive soils than in the conducive soils. Molecular ecological network analysis revealed that the fungal network of suppressive soils was more complex than that of conducive soils. Our results indicate that plant health is closely related to soil physicochemical and biological properties. This study is of great significance for developing strategies for clubtroot disease prevention and control.
Mathematical modeling of mechanosensitive reversal control in Myxococcus xanthus
Authors: Chen Yirui , Topo Elias J. , Nan Beiyan , Chen Jing
Published: January 2024

Adjusting motility patterns according to environmental cues is important for bacterial survival. Myxococcus xanthus, a bacterium moving on surfaces by gliding and twitching mechanisms, modulates the reversal frequency of its front-back polarity in response to mechanical cues like substrate stiffness and cell-cell contact. In this study, we propose that M. xanthus’s gliding machinery senses environmental mechanical cues during force generation and modulates cell reversal accordingly. To examine our hypothesis, we expand an existing mathematical model for periodic polarity reversal in M. xanthus, incorporating the experimental data on the intracellular dynamics of the gliding machinery and the interaction between the gliding machinery and a key polarity regulator. The model successfully reproduces the dependence of cell reversal frequency on substrate stiffness observed in M. xanthus gliding. We further propose reversal control networks between the gliding and twitching motility machineries to explain the opposite reversal responses observed in wild type M. xanthus cells that possess both motility mechanisms. These results provide testable predictions for future experimental investigations. In conclusion, our model suggests that the gliding machinery in M. xanthus can function as a mechanosensor, which transduces mechanical cues into a cell reversal signal.
Dietary β-hydroxybutyric acid improves the growth performance of young ruminants based on rumen microbiota and volatile fatty acid biosynthesis
Authors: Chai Jianmin , Liu Zeyue , Wu Jun , Kang Yuan , Abdelsattar Mahmoud M. , Zhao Wei , Wang Shiqin , Yang Shuli , Deng Feilong , Li Ying , Zhuang Yimin , Zhang Naifeng
Published: January 2024

Introduction

The ketone body β-hydroxybutyric acid (BHB) plays critical roles in cellular proliferation and metabolic fuel utilization; however, its effects on the rumen microbiota remain unknown.

Methods

Here, three doses of BHB (low, medium, and high) were supplemented to early-weaned goat kids.

Results

Compared with controls, the beneficial effects of BHB on growth and rumen development were observed in goats at 90 days of age (d). The low dose of dietary BHB increased the concentration of rumen acetate, propionate, and butyrate on d90. The sequencing results of the rumen microbiota revealed marked shifts in rumen microbial community structure after early-weaned goat kids consumed BHB for 2 months. The signature bacterial ASVs for each treatment were identified and were the main drivers contributing to microbial interactions in the rumen. The bacteria associated with rumen weight were also correlated with body weight. Some classified bacterial signatures, includingPrevotella, Olsenella umbonate, andRoseburia faecis, were related to rumen volatile fatty acids and host development.

Conclusion

Overall, dietary BHB altered rumen microbiota and environments in young goats, which contributed to rumen development and growth.
Human lipocalins bind and export fatty acids through the secretory pathway of yeast cells
Authors: Ekim Kocabey Aslihan , Schneiter Roger
Published: January 2024

The activation of fatty acids to their acyl-CoA derivatives is a crucial step for their integration into more complex lipids or their degradation via beta-oxidation. Yeast cells employ five distinct acyl-CoA synthases to facilitate this ATP-dependent activation of acyl chains. Notably, mutant cells that are deficient in two of these fatty acid-activating (FAA) enzymes, namely, Faa1 and Faa4, do not take up free fatty acids but rather export them out of the cell. This unique fatty acid export pathway depends on small, secreted pathogenesis-related yeast proteins (Pry). In this study, we investigate whether the expression of human fatty acid-binding proteins, including Albumin, fatty acid-binding protein 4 (Fabp4), and three distinct lipocalins (ApoD, Lcn1, and Obp2a), could promote fatty acid secretion in yeast. To optimize the expression and secretion of these proteins, we systematically examined various signal sequences in both low-copy and high-copy number plasmids. Our findings reveal that directing these fatty-acid binding proteins into the secretory pathway effectively promotes fatty acid secretion from a sensitized quadruple mutant model strain (faa1∆ faa4∆ pry1∆ pry3∆). Furthermore, the level of fatty acid secretion exhibited a positive correlation with the efficiency of protein secretion. Importantly, the expression of all human lipid-binding proteins rescued Pry-dependent fatty acid secretion, resulting in the secretion of both long-chain saturated and unsaturated fatty acids. These results not only affirm the in vitro binding capabilities of lipocalins to fatty acids but also present a novel avenue for enhancing the secretion of valuable lipidic compounds. Given the growing interest in utilizing yeast as a cellular factory for producing poorly soluble compounds and the potential of lipocalins as platforms for engineering substrate-binding specificity, our model is considered as a powerful tool for promoting the secretion of high-value lipid-based molecules.
Continuous cropping of potato changed the metabolic pathway of root exudates to drive rhizosphere microflora
Authors: Xing Yanhong , Zhang Pingliang , Zhang Wenming , Yu Chenxu , Luo Zhuzhu
Published: January 2024

For potato production, continuous cropping (CC) could lead to autotoxicity buildup and microflora imbalance in the field soil, which may result in failure of crops and reduction in yield. In this study, non-targeted metabolomics (via liquid chromatography with tandem mass spectrometry (LC–MS/MS)) combined with metagenomic profiling (via high-throughput amplicon sequencing) were used to evaluate correlations between metabolomics of potato root exudates and communities of bacteria and fungi around potato plants to illustrate the impacts of CC. Potato plants were grown in soil collected from fields with various CC years (0, 1, 4, and 7 years). Metabolomic analysis showed that the contents and types of potential autotoxins in potato root exudates increased significantly in CC4 and CC7 plants (i.e., grown in soils with 4 and 7 years of CC). The differentially expressed metabolites were mainly produced via alpha-linolenic acid metabolism in plant groups CC0 and CC1 (i.e., no CC or 1 year CC). The metabolomics of the groups CC4 and CC7 became dominated by styrene degradation, biosynthesis of siderophore group non-ribosomal peptides, phenylpropanoid biosynthesis, and biosynthesis of various plant secondary metabolites. Continuous cropping beyond 4 years significantly changed the bacterial and fungal communities in the soil around the potato crops, with significant reduction of beneficial bacteria and accumulation of harmful fungi. Correlations between DEMs and microflora biomarkers were established with strong significances. These results suggested that continuous cropping of potato crops changed their metabolism as reflected in the plant root exudates and drove rhizosphere microflora to directions less favorable to plant growth, and it needs to be well managed to assure potato yield.
Wetland soil organic carbon balance is reversed by old carbon and iron oxide additions
Authors: Ni Bingbo , Yu Xiaofei , Duan Xun , Zou Yuanchun
Published: January 2024

Iron (Fe) oxides can stabilize organic carbon (OC) through adsorption and co-precipitation, while microbial Fe reduction can disrupt Fe-bound OC (Fe-OC) and further increase OC mineralization. The net effects of OC preservation and mineralization mediated by Fe oxides are still unclear, especially for old carbon (formed from plant litters over millions of years) and crystalline Fe oxides. Accelerating the recovery of wetland carbon sinks is critical for mitigating climate change and achieving carbon neutrality. Quantifying the net effect of Fe-mediated OC mineralization and preservation is vital for understanding the role of crystalline Fe oxides in carbon cycling and promoting the recovery of soil carbon sinks. Here, we explored the OC balances mediated by hematite (Hem) and lignite addition (Lig) to freshwater wetland (FW, rich in C and Fe) and saline-alkaline wetland (SW, poor in C and Fe) soil slurries, incubated under anaerobic conditions. Results showed that Lig caused net OC accumulation (FW: 5.9 ± 3.6 mg g−1; SW: 8.3 ± 3.2 mg g−1), while Hem caused dramatic OC loss, particularly in the FW soils. Hem inhibited microbial Fe(III) reduction by decreasing the relative abundance of Fe respiration reducers, while substantially enhancing OC mineralization through the shift in the microbial community structure of FW soils. Lig resulted in carbon emission, but its contribution to preservation by the formation of Fe-OC was far higher than that which caused OC loss. We concluded that crystalline Fe oxide addition solely favored the increase of OC mineralization by adjusting the microbial community structure, while old carbon enriched with an aromatic and alkyl promoted Fe-OC formation and further increased OC persistence. Our findings could be employed for wetland restoration, particularly for the recovery of soil carbon sinks.
Evaluation of microbiological epidemiology and clinical characteristics of maternal bloodstream infection: a 10 years retrospective study
Authors: Guo Junfei , Wu Yongbing , Li Huan , Deng Wenyu , Lai Weiming , Gu Chunming , Luo Mingyong
Published: January 2024

Objective

Although the incidence of bloodstream infection (BSI) during pregnancy is relatively low, it can lead to unfavorable outcomes. The aim of our study was to analyze the clinical and microbiological characteristics of maternal bacteremia and to assess maternal and fetal outcomes.

Methods

Our study was a retrospective study conducted in a tertiary women and children’s hospital in Guangzhou, China, from 2013 to 2022. Data were extracted from medical records and the laboratory information system. The participants were divided into groups, and the difference between the groups was analyzed.

Results

The incidence of maternal BSI during the 10 years study period was 10.2 cases/10,000 maternities, with a peak found from 2014 to 2016. Escherichia coli (48%) was the predominant causative pathogen, followed by Streptococcus agalactiae (13%). Gestational diabetes mellitus (GDM) (15%) was the most common underlying condition among maternal BSI episodes. Urinary tract (13%) and genital tract (28%) were the predominant source of BSI. About 14% of neonates were infected, and BSI was the most common type of infection. E. coli was the predominant pathogen in mother-neonate pairs with concurrent BSI. Premature rupture of membranes (PROM, OR:4.68) and preterm birth (OR:3.98) were the risk factors predicting neonatal infection. More than 85% of the E. coli were resistant to ampicillin (AMP) and 50% of the E. coli were extended-spectrum β-lactamase (ESBL)-producing bacteria.

Conclusion

Maternal BSI is a rare event, but continuous monitoring on the aspects of pathogen composition, antimicrobial resistance characteristics, and risk factors for adverse outcomes remains necessary to further reduce poor outcomes and mitigate bacterial resistance.
Membrane properties modulation by SanA: implications for xenobiotic resistance in Salmonella Typhimurium
Authors: Aleksandrowicz Adrianna , Kolenda Rafał , Baraniewicz Karolina , Thurston Teresa L. M. , Suchański Jarosław , Grzymajlo Krzysztof
Published: January 2024

Introduction

Multidrug resistance in bacteria is a pressing concern, particularly among clinical isolates. Gram-negative bacteria like Salmonella employ various strategies, such as altering membrane properties, to resist treatment. Their two-membrane structure affects susceptibility to antibiotics, whereas specific proteins and the peptidoglycan layer maintain envelope integrity. Disruptions can compromise stability and resistance profile toward xenobiotics. In this study, we investigated the unexplored protein SanA’s role in modifying bacterial membranes, impacting antibiotic resistance, and intracellular replication within host cells.

Methods

We generated a sanA deletion mutant and complemented it in trans to assess its biological function. High-throughput phenotypic profiling with Biolog Phenotype microarrays was conducted using 240 xenobiotics. Membrane properties and permeability were analyzed via cytochrome c binding, hexadecane adhesion, nile red, and ethidium bromide uptake assays, respectively. For intracellular replication analysis, primary bone marrow macrophages served as a host cells model.

Results

Our findings demonstrated that the absence of sanA increased membrane permeability, hydrophilicity, and positive charge, resulting in enhanced resistance to certain antibiotics that target peptidoglycan synthesis. Furthermore, the sanA deletion mutant demonstrated enhanced replication rates within primary macrophages, highlighting its ability to evade the bactericidal effects of the immune system. Taking together, we provide valuable insights into a poorly known SanA protein, highlighting the complex interplay among bacterial genetics, membrane physiology, and antibiotic resistance, underscoring its significance in understanding Salmonella pathogenicity.
Construction of Bacillus subtilis for efficient production of fengycin from xylose through CRISPR-Cas9
Authors: Yin Ying , Wang Pan , Wang Xin , Wen Jianping
Published: January 2024

Fengycin is a multifunctional peptide antibiotic produced mainly by Bacillus species and the purpose of this research was to construct a Bacillus subtilis strain that can produce fengycin with the xylose as the substrate with CRSIPR-Cas9. Hence, at the beginning of this study, functional sfp and degQ were expressed in B. subtilis 168 strain to give the strain the ability to produce the fengycin with the titer of 71.21 mg/L. Subsequently, the native promoter PppsA of the cluster responsible for the fengycin synthesis was replaced by the Pveg promoter, resulting in a further 5.22-fold increase in fengycin titer. To confer xylose utilization capacity to B. subtilis, deletion of araR and constitutive overexpression of araE were performed, and the xylose consumption rate of the engineered strain BSUY06 reached 0.29 g/L/h, which is about 6.25-fold higher than that of the parent strain BSUY04-1. In the final phase of this study, the fermentation characteristics were observed and the initial xylose concentration was optimized. In this study, 40 g/L xylose was proved to be the most suitable initial concentration for growth and fengycin fermentation, which leading to a fengycin titer of 430.86 mg/L. This study demonstrated that lignocellulose, the clean and sustainable substrate with xylose as the second largest sugar, is a potential substrate for the production of fengycin.
One year of treatment with elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis homozygous for the F508del mutation causes a significant increase in liver biochemical indexes
Authors: Castaldo Alice , Gelzo Monica , Iacotucci Paola , Longobardi Annalisa , Taccetti Giovanni , Terlizzi Vito , Carnovale Vincenzo
Published: January 2024

Introduction: Modulators of cystic fibrosis transmembrane conductance regulator mutated protein significantly improved the outcome of patients with cystic fibrosis (CF). We describe 63 patients who were independently followed up in two CF regional centers (i.e., Campania and Tuscany regions).

Methods: All patients were homozygous for the F508del mutation and were treated with lumacaftor/ivacaftor (LI) for 3 years, followed by 1 year of treatment with elexacaftor/tezacaftor/ivacaftor (ETI). We studied the biochemical parameters of liver damage and cholesterol metabolism.

Results: Beyond the improvement of BMI and lung function with LI treatment and even more with ETI, we found that the 3 years of LI treatment significantly improved liver function parameters (total and conjugated bilirubin, ALT, AP, and GGT), while the subsequent ETI treatment caused a significant increase of such parameters.

Discussion: We confirm that treatment with LI does not correct hypocholesterolemia, whereas treatment with ETI significantly increases serum cholesterol. Such an increase is likely due to enhanced de novo biosynthesis, as indicated by the significant increase in serum lathosterol, and it is likely that the subsequent liver cholesterol accumulation may contribute to triggering inflammation and worsening liver biochemical indexes. The increase in serum bilirubin and ALT that we observed in approximately 94% and 84% of patients treated with ETI, respectively, suggests further investigation of the impact of ETI therapy on liver function indexes.
Micropopulation mapping of the mouse parafascicular nucleus connections reveals diverse input–output motifs
Authors: Gonzalo-Martín Enrique , Alonso-Martínez Carmen , Sepúlveda Lucía Prensa , Clasca Francisco
Published: January 2024

Introduction

In primates, including humans, the centromedian/parafascicular (CM-Pf) complex is a key thalamic node of the basal ganglia system. Deep brain stimulation in CM-Pf has been applied for the treatment of motor disorders such as Parkinson’s disease or Tourette syndrome. Rodents have become widely used models for the study of the cellular and genetic mechanisms of these and other motor disorders. However, the equivalence between the primate CM-Pf and the nucleus regarded as analogous in rodents (Parafascicular, Pf) remains unclear.

Methods

Here, we analyzed the neurochemical architecture and carried out a brain-wide mapping of the input–output motifs in the mouse Pf at micropopulation level using anterograde and retrograde labeling methods. Specifically, we mapped and quantified the sources of cortical and subcortical input to different Pf subregions, and mapped and compared the distribution and terminal structure of their axons.

Results

We found that projections to Pf arise predominantly (>75%) from the cerebral cortex, with an unusually strong (>45%) Layer 5b component, which is, in part, contralateral. The intermediate layers of the superior colliculus are the main subcortical input source to Pf. On its output side, Pf neuron axons predominantly innervate the striatum. In a sparser fashion, they innervate other basal ganglia nuclei, including the subthalamic nucleus (STN), and the cerebral cortex. Differences are evident between the lateral and medial portions of Pf, both in chemoarchitecture and in connectivity. Lateral Pf axons innervate territories of the striatum, STN and cortex involved in the sensorimotor control of different parts of the contralateral hemibody. In contrast, the mediodorsal portion of Pf innervates oculomotor-limbic territories in the above three structures.

Discussion

Our data thus indicate that the mouse Pf consists of several neurochemically and connectively distinct domains whose global organization bears a marked similarity to that described in the primate CM-Pf complex.
Age-related alterations in the behavioral response to a novel environment in the African turquoise killifish (Nothobranchius furzeri)
Authors: Mariën Valerie , Piskin Ilayda , Zandecki Caroline , Van houcke Jolien , Arckens Lutgarde
Published: January 2024

The African turquoise killifish (Nothobranchius furzeri) has emerged as a popular model organism for neuroscience research in the last decade. One of the reasons for its popularity is its short lifespan for a vertebrate organism. However, little research has been carried out using killifish in behavioral tests, especially looking at changes in their behavior upon aging. Therefore, we used the open field and the novel tank diving test to unravel killifish locomotion, exploration-related behavior, and behavioral changes over their adult lifespan. The characterization of this behavioral baseline is important for future experiments involving pharmacology to improve the aging phenotype. In this study, two cohorts of fish were used, one cohort was tested in the open field test and one cohort was tested in the novel tank diving test. Each cohort was tested from the age of 6 weeks to the age of 24 weeks and measurements were performed every three weeks. In the open field test, we found an increase in the time spent in the center zone from 18 weeks onward, which could indicate altered exploration behavior. However, upon aging, the fish also showed an increased immobility frequency and duration. In addition, after the age of 15 weeks, their locomotion decreased. In the novel tank diving test, we did not observe this aging effect on locomotion or exploration. Killifish spent around 80% of their time in the bottom half of the tank, and we could not observe habituation effects, indicating slow habituation to novel environments. Moreover, we observed that killifish showed homebase behavior in both tests. These homebases are mostly located near the edges of the open field test and at the bottom of the novel tank diving test. Altogether, in the open field test, the largest impact of aging on locomotion and exploration was observed beyond the age of 15 weeks. In the novel tank diving test, no effect of age was found. Therefore, to test the effects of pharmacology on innate behavior, the novel tank diving test is ideally suited because there is no confounding effect of aging.
History of research concerning the ependyma: a view from inside the human brain
Authors: Del Bigio Marc R.
Published: January 2024

The history of research concerning ependymal cells is reviewed. Cilia were identified along the surface of the cerebral ventricles c1835. Numerous anatomical and histopathological studies in the late 1800’s showed irregularities in the ependymal surface that were thought to be indicative of specific pathologies such as syphilis; this was subsequently disproven. The evolution of thoughts about functions of cilia, the possible role of ependyma in the brain-cerebrospinal fluid barrier, and the relationship of ependyma to the subventricular zone germinal cells is discussed. How advances in light and electron microscopy and cell culture contributed to our understanding of the ependyma is described. Discoveries of the supraependymal serotoninergic axon network and supraependymal macrophages are recounted. Finally, the consequences of loss of ependymal cells from different regions of the central nervous system are considered.
Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration
Authors: Lei Shizhen , Hu Mang , Wei Zhongtao
Published: January 2024

Purpose

To investigate the role of senescence-related cytokines (SRCs) in the pathophysiology of age-related macular degeneration (AMD).

Design

The whole study is based on single-cell and bulk tissue transcriptomic analysis of the human neuroretinas with or without AMD. The transcriptomic data of human neuroretinas was obtained from Gene-Expression Omnibus (GEO) database.

Methods

For single-cell transcriptomic analysis, the gene expression matrix goes through quality control (QC) filtering, being normalized, scaled and integrated for downstream analysis. The further analyses were performed using Seurat R package and CellChat R package. After cell type annotation, the expression of phenotype and functional markers of microglia was investigated and cell-cell communication analysis was performed. For bulk tissue transcriptomic analysis, GSE29801 dataset contains the transcriptomic data of human macular neuroretina (n = 118) from control group and AMD patients. The expression of SPP1 in control and AMD subtypes were compared by Student’s t-test. In addition, the AMD macular neuroretina were classified into SPP1-low and SPP1-high groups according to the expression level of SPP1. The differentially expressed genes between these two groups were subsequently identified and the pathway enrichment analysis for these genes was further conducted.

Results

Secreted phosphoprotein 1, as an SRC, was revealed to be highly expressed in microglia of AMD neuroretina and the SPP1-receptor signaling was highly activated in AMD neuroretina. In addition, SPP1 signaling was associated with the pro-inflammatory phenotype and phagocytic state of microglia. SPP1 expression was elevated in macular neuroretina with late dry and wet AMD and the inflammatory pathways were found to be activated in SPP1-high AMD macular neuroretina.

Conclusion

Our findings indicated that SPP1 and microglial activation might play an important role in the pathophysiology of AMD. Therefore, SPP1 might serve as a potential therapeutic target for AMD. More in vitro and in vivo studies are required to confirm the results and the therapeutic effect of SPP1-targeting strategy.
Astrocytes in fragile X syndrome
Authors: Talvio Karo , Castrén Maija L.
Published: January 2024

Astrocytes have an important role in neuronal maturation and synapse function in the brain. The interplay between astrocytes and neurons is found to be altered in many neurodevelopmental disorders, including fragile X syndrome (FXS) that is the most common inherited cause of intellectual disability and autism spectrum disorder. Transcriptional, functional, and metabolic alterations in Fmr1 knockout mouse astrocytes, human FXS stem cell-derived astrocytes as well as in in vivo models suggest autonomous effects of astrocytes in the neurobiology of FXS. Abnormalities associated with FXS astrocytes include differentiation of central nervous system cell populations, maturation and regulation of synapses, and synaptic glutamate balance. Recently, FXS-specific changes were found more widely in astrocyte functioning, such as regulation of inflammatory pathways and maintenance of lipid homeostasis. Changes of FXS astrocytes impact the brain homeostasis and function both during development and in the adult brain and offer opportunities for novel types of approaches for intervention.
Computational components of visual predictive coding circuitry
Authors: Shipp Stewart
Published: January 2024

If a full visual percept can be said to be a ‘hypothesis’, so too can a neural ‘prediction’ – although the latter addresses one particular component of image content (such as 3-dimensional organisation, the interplay between lighting and surface colour, the future trajectory of moving objects, and so on). And, because processing is hierarchical, predictions generated at one level are conveyed in a backward direction to a lower level, seeking to predict, in fact, the neural activity at that prior stage of processing, and learning from errors signalled in the opposite direction. This is the essence of ‘predictive coding’, at once an algorithm for information processing and a theoretical basis for the nature of operations performed by the cerebral cortex. Neural models for the implementation of predictive coding invoke specific functional classes of neuron for generating, transmitting and receiving predictions, and for producing reciprocal error signals. Also a third general class, ‘precision’ neurons, tasked with regulating the magnitude of error signals contingent upon the confidence placed upon the prediction, i.e., the reliability and behavioural utility of the sensory data that it predicts. So, what is the ultimate source of a ‘prediction’? The answer is multifactorial: knowledge of the current environmental context and the immediate past, allied to memory and lifetime experience of the way of the world, doubtless fine-tuned by evolutionary history too. There are, in consequence, numerous potential avenues for experimenters seeking to manipulate subjects’ expectation, and examine the neural signals elicited by surprising, and less surprising visual stimuli. This review focuses upon the predictive physiology of mouse and monkey visual cortex, summarising and commenting on evidence to date, and placing it in the context of the broader field. It is concluded that predictive coding has a firm grounding in basic neuroscience and that, unsurprisingly, there remains much to learn.
Prognostic value of CBV index in patients with acute ischemic stroke treated with endovascular thrombectomy in late therapeutic window
Authors: Sun Aicheng , Cao Yuezhou , Jia Zhenyu , Zhao Linbo , Shi Haibin , Liu Sheng
Published: January 2024

Purpose

To evaluate the prognostic value of the cerebral blood volume (CBV) index for 90-day functional outcomes in patients with acute ischemic stroke (AIS) treated within a late therapeutic window.

Methods

We retrospectively reviewed patients who underwent pre-treatment computed tomography perfusion (CTP) and endovascular thrombectomy (EVT) for large-vessel occlusion (LVO) of the anterior circulation within the late therapeutic window between January 2021 and February 2023. Clinical data, the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) based on unenhanced computed tomography (CT), and perfusion parameters, including ischemic core, hypoperfusion volume, mismatch volume between the core and penumbra, and CBV index, were assessed and compared between patients who achieved favorable outcomes (defined as a modified Rankin Scale score of 0–2).

Results

Of the 118 patients, 56 (47.5%) had favorable outcomes. In the univariate analysis, age, National Institutes of Health Stroke Scale (NIHSS) score at admission, ASPECTS score, CBV index, and ischemic core volume were significantly associated with functional outcomes (P < 0.05). In multivariate analyses, age (odds ratio [OR], 1.060; 95% confidence interval [CI] 1.013–1.110, P = 0.012), NIHSS score at admission (OR, 1.126; 95% CI 1.031–1.229, P = 0.009), and CBV index (OR, 0.001; 95% CI 0.000–0.240, P = 0.014) were independent predictors of a 90-day favorable outcome.

Conclusion

A high CBV index was independently associated with favorable outcomes in patients who underwent mechanical thrombectomy within the late therapeutic window. In addition, a higher CBV index reflects improved blood flow and favorable digital subtraction angiography collateral status.
Associations between NIHSS sub-item scores and prognosis and intracranial hemorrhage after endovascular therapy for acute anterior circulation ischemic stroke
Authors: Qi Shuang , Shi Mingchao , Li Chao , Song Kangjia , Zhou Jie , Yue Feixue , Zhang Wenbin , Wang Shouchun
Published: January 2024

Purpose

The relationship between sub-item scores on the National Institutes of Health Stroke Scale (NIHSS) scores and prognosis and intracranial hemorrhage in patients with acute ischemic stroke undergoing endovascular treatment (EVT) has been insufficiently studied. The aim of this study was to investigate the correlation between NIHSS sub-item scores, prognosis, and intracranial hemorrhage.

Methods

This study included patients with acute anterior circulation ischemic stroke undergoing EVT between February 2019 and April 2022. The outcomes included functional independence, defined as a modified Rankin Scale (mRS) score ≤ 2 at 3 months after EVT, intracranial hemorrhage within 24 h after EVT, and mortality within 3 months. A multivariate regression analysis was performed, including NIHSS sub-item scores and other adjusted variables.

Results

A total of 568 patients were enrolled. Of the 568 patients, 239 (45%) achieved functional independence at 3 months after EVT. The median age in this group was 63 years (IQR 52–69) and 176 (73.6%) were male patients. Intracranial hemorrhage within 24 h after EVT occurred in 170 (30%) patients. The median age in this group was 65 years (IQR 56–71) and 105 (61.8%) were male patients. In a multivariate analysis adjusted for age, gender, and factors with a value of p of <0.05, the NIHSS limb movement sub-item score was strongly associated with prognosis at 3 months (OR 0.833, 95% CI 0.758–0.915) and intracranial hemorrhage within 24 h after EVT (OR 1.161, 95% CI 1.037–1.300).

Conclusion

Higher limb movement sub-item scores on the NIHSS were independently associated with a poorer prognosis at 3 months and a higher rate of intracranial hemorrhage within 24 h after EVT among patients with acute anterior circulation ischemic stroke.
Remote assessment of cognition in Parkinson’s disease and Cerebellar Ataxia: the MoCA test in English and Hebrew
Authors: Binoy Sharon , Montaser-Kouhsari Leila , Ponger Penina , Saban William
Published: January 2024

There is a critical need for accessible neuropsychological testing for basic research and translational studies worldwide. Traditional in-person neuropsychological studies are inherently difficult to conduct because testing requires the recruitment and participation of individuals with neurological conditions. Consequently, studies are often based on small sample sizes, are highly time-consuming, and lack diversity. To address these challenges, in the last decade, the utilization of remote testing platforms has demonstrated promising results regarding the feasibility and efficiency of collecting patient data online. Herein, we tested the validity and generalizability of remote administration of the Montreal Cognitive Assessment (MoCA) test. We administered the MoCA to English and Hebrew speakers from three different populations: Parkinson’s disease, Cerebellar Ataxia, and healthy controls via video conferencing. First, we found that the online MoCA scores do not differ from traditional in-person studies, demonstrating convergent validity. Second, the MoCA scores of both our online patient groups were lower than controls, demonstrating construct validity. Third, we did not find differences between the two language versions of the remote MoCA, supporting its generalizability to different languages and the efficiency of collecting binational data (USA and Israel). Given these results, future studies can utilize the remote MoCA, and potentially other remote neuropsychological tests to collect data more efficiently across multiple different patient populations, language versions, and nations.
The determinants of COVID-induced brain dysfunctions after SARS-CoV-2 infection in hospitalized patients
Authors: Yasir Shahwar , Jin Yu , Razzaq Fuleah A. , Caballero-Moreno Antonio , Galán-García Lidice , Ren Peng , Valdes-Sosa Mitchell , Rodriguez-Labrada Roberto , Bringas-Vega Maria L. , Valdes-Sosa Pedro A.
Published: January 2024

The severity of the pandemic and its consequences on health and social care systems were quite diverse and devastating. COVID-19 was associated with an increased risk of neurological and neuropsychiatric disorders after SARS-CoV-2 infection. We did a cross-sectional study of 3 months post-COVID consequences of 178 Cuban subjects. Our study has a unique CUBAN COVID-19 cohort of hospitalized COVID-19 patients and healthy subjects. We constructed a latent variable for pre-health conditions (PHC) through Item Response Theory (IRT) and for post-COVID neuropsychiatric symptoms (Post-COVID-NPS) through Factor Analysis (FA). There seems to be a potential causal relationship between determinants of CIBD and post-COVID-NPS in hospitalized COVID-19 patients. The causal relationships accessed by Structural Equation Modeling (SEM) revealed that PHC (p < 0.001) and pre-COVID cognitive impairments (p < 0.001) affect the severity of COVID-19 patients. The severity of COVID-19 eventually results in enhanced post-COVID-NPS (p < 0.001), even after adjusting for confounders (age, sex, and pre-COVID-NPS). The highest loadings in PHC were for cardiovascular diseases, immunological disorders, high blood pressure, and diabetes. On the other hand, sex (p < 0.001) and pre-COVID-NPS including neuroticism (p < 0.001), psychosis (p = 0.005), cognition (p = 0.036), and addiction (p < 0.001) were significantly associated with post-COVID-NPS. The most common neuropsychiatric symptom with the highest loadings includes pain, fatigue syndrome, autonomic dysfunctionalities, cardiovascular disorders, and neurological symptoms. Compared to healthy people, COVID-19 patients with pre-health comorbidities or pre-neuropsychiatric conditions will have a high risk of getting severe COVID-19 and long-term post-COVID neuropsychiatric consequences. Our study provides substantial evidence to highlight the need for a complete neuropsychiatric follow-up on COVID-19 patients (with severe illness) and survivors (asymptomatic patients who recovered).
Response to photic stimulation as a measure of cortical excitability in epilepsy patients
Authors: Vranic-Peters Michaela , O'Brien Patrick , Seneviratne Udaya , Reynolds Ashley , Lai Alan , Grayden David B. , Cook Mark J. , Peterson Andre D. H.
Published: January 2024

Studying states and state transitions in the brain is challenging due to nonlinear, complex dynamics. In this research, we analyze the brain's response to non-invasive perturbations. Perturbation techniques offer a powerful method for studying complex dynamics, though their translation to human brain data is under-explored. This method involves applying small inputs, in this case via photic stimulation, to a system and measuring its response. Sensitivity to perturbations can forewarn a state transition. Therefore, biomarkers of the brain's perturbation response or “cortical excitability” could be used to indicate seizure transitions. However, perturbing the brain often involves invasive intracranial surgeries or expensive equipment such as transcranial magnetic stimulation (TMS) which is only accessible to a minority of patient groups, or animal model studies. Photic stimulation is a widely used diagnostic technique in epilepsy that can be used as a non-invasive perturbation paradigm to probe brain dynamics during routine electroencephalography (EEG) studies in humans. This involves changing the frequency of strobing light, sometimes triggering a photo-paroxysmal response (PPR), which is an electrographic event that can be studied as a state transition to a seizure state. We investigate alterations in the response to these perturbations in patients with genetic generalized epilepsy (GGE), with (n = 10) and without (n = 10) PPR, and patients with psychogenic non-epileptic seizures (PNES; n = 10), compared to resting controls (n = 10). Metrics of EEG time-series data were evaluated as biomarkers of the perturbation response including variance, autocorrelation, and phase-based synchrony measures. We observed considerable differences in all group biomarker distributions during stimulation compared to controls. In particular, variance and autocorrelation demonstrated greater changes in epochs close to PPR transitions compared to earlier stimulation epochs. Comparison of PPR and spontaneous seizure morphology found them indistinguishable, suggesting PPR is a valid proxy for seizure dynamics. Also, as expected, posterior channels demonstrated the greatest change in synchrony measures, possibly reflecting underlying PPR pathophysiologic mechanisms. We clearly demonstrate observable changes at a group level in cortical excitability in epilepsy patients as a response to perturbation in EEG data. Our work re-frames photic stimulation as a non-invasive perturbation paradigm capable of inducing measurable changes to brain dynamics.
Neural correlates of thermal stimulation during active touch
Authors: Park Wanjoo , Korres Georgios , Jamil Muhammad Hassan , Eid Mohamad
Published: January 2024

Introduction

Thermal feedback technologies have been explored in human-computer interaction to provide secondary information and enhance the overall user experience. Unlike fast-response haptic modalities such as vibration and force feedback, the human brain's processes associated with thermal feedback are not fully understood.

Methods

In this study, we utilize electroencephalography (EEG) brain imaging to systematically examine the neural correlates associated with a wide range of thermal stimuli, including 9, 15, 32, and 42°C, during active touch at the fingertip. A custom experimental setup is developed to provide thermal stimulation at the desirable temperature levels. A total of 30 participants are recruited to experience the four levels of thermal stimulation by actively touching a thermal stimulation unit with the index finger while recording brain activities via EEG. Time-frequency analysis and power spectral density (PSD) of the EEG data are utilized to analyze the delta, theta, alpha, beta, and gamma frequency bands.

Results

The results show that the delta, theta, and alpha PSDs of 9 and 15°C stimuli are significantly higher than the PSDs of 32 and 42°C in the right frontal area during the early stage of the stimulation, from 282 ms up to 1,108 ms (One-way ANOVA test, Holm-Bonferroni correction, p < 0.05). No significant differences in PSDs are found between 9 and 15°C thermal stimuli or between 32 and 42°C thermal stimuli.

Discussion

The findings of this study inform the development of thermal feedback system in human-computer interaction.