bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of Two Iodothyronine Deiodinase Genes Inhibits Epinephrine-Induced Larval Metamorphosis of the Hard-Shelled Mussel Mytilus coruscus
Authors: Shi Xue , Wang Yu-Qing , Yang Yue-Ming , Li Yi-Feng
Published: July 2022

The metamorphosis process is a critical life-changing event for marine invertebrate planktonic larvae to transform into benthic adults, which is crucial for the shellfish bed’s ecosystem stability and seed production in aquaculture. The mechanism of neuroendocrine regulation in the larval metamorphosis of bivalves remains ambiguous. In the present study, the expression of two deiodinase genes, McDx and McDy, was analyzed by whole-mount in situ hybridization at four larval stages in the hard-shelled mussel Mytilus coruscus. The McDx and McDy localized in visceral tissues, nervous system, mantle, and velum, indicating that two deiodinase genes are essential for larval development in M. coruscus. Knockdown of the McDx and McDy in the pediveliger larvae of M. coruscus using electroporation of siRNA significantly (p < 0.001) reduced McDx and McDy expression. McDx and McDy knockdown reduced larval metamorphosis in 45% and 49% of the pediveliger larvae induced by epinephrine (EPI). It is hypothesised that the knockdown effects of McDx and McDy repress metamorphic induction rather than larval viability, which does not elicit a lethal effect. The present study corroborates a synergistic action of the adrenergic and thyroid hormones signalling pathway in M. coruscus, and suggests the role of McDx and McDy in larval development and metamorphic transition.
Marine Debris Floating in Arctic and Temperate Northeast Atlantic Waters
Authors: Tekman Mine B. , Gutow Lars , Bergmann Melanie
Published: July 2022

Floating marine debris is ubiquitous in marine environments but knowledge about quantities in remote regions is still limited. Here, we present the results of an extensive survey of floating marine debris by experts, trained scientists from fields other than pollution or non-professional citizen scientists. A total of 276 visual ship-based surveys were conducted between 2015 and 2020 in the Northeast (NE) Atlantic from waters off the Iberian Peninsula to the Central Arctic, however, with a focus on Arctic waters. Spatiotemporal variations among regional seas (Central Arctic, Barents Sea, Greenland Sea, Norwegian Sea, North Sea) and oceanic regions (Arctic waters and the temperate NE Atlantic) were explored. The overall median debris concentration was 11 items km-2, with considerable variability. The median concentration was highest in the North Sea with 19 items km-2. The Nordic seas, except the Central Arctic showed median concentrations ranging from 9 to 13 items km-2. Plastic accounted for 91% of all floating items. Miscellaneous fragments, films, ropes and nets, packaging materials, expanded polystyrene and straps were the most frequently observed plastic types. Although the median debris concentration in the Central Arctic was zero, this region was not entirely free of floating debris. The variations between regional seas and oceanic regions were statistically not significant indicating a continuous supply by a northward transportation of floating debris. The data show a slight annual decrease and clear seasonal differences in debris concentrations with higher levels observed during summer. A correlation between debris concentrations and environmental and spatial variables was found, explaining partly the variability in the observations. Pollution levels were 500 times lower than those recorded on the seafloor indicating the seafloor as a sink for marine debris. The Arctic was characterised by similar pollution levels as regions in temperate latitudes highlighting that Arctic ecosystems face threats from plastic pollution, which add to the effects of rapid climate change.
Fussy Inverse Design of Metamaterial Absorbers Assisted by a Generative Adversarial Network
Authors: Lin Hai , Tian Yuze , Hou Junjie , Xu Weilin , Shi Xinyang , Tang Rongxin
Published: July 2022

The increasing demands for metasurfaces have led researchers to seek effective inverse design methods, which are counting on the developments in the optimization theory and deep learning techniques. Early approaches of the inverse design based on deep learning established a unique mapping between the device’s geometry parameters and its designated EM characteristics. However, the generated solution based on the traditional inverse design method may not be applicable due to practical fabrication conditions. The designers sometimes want to choose the most practical one from multiple schemes which can all meet the requirements of the given EM indicators. A fuzzy inverse design method is quite in demand. In this study, we proposed a fuzzy inverse design method for metamaterial absorbers based on the generative adversarial network (GAN). As a data-driven method, self-built data sets are constructed and trained by the GAN, which contain the absorber’s design parameters and their corresponding spectral response. After the training process is finished, it can generate multiple possible schemes which can satisfy the customized absorptivity and frequency bands for absorbers. The parameters generated by this model include structure sizes and impedance values, which indicates that it has the ability to learn a variety of features. The effectiveness and robustness of the proposed method have been verified by several examples for the design of both narrowband and broadband metamaterial absorbers. Our work proves the feasibility of using deep learning methods to break the limits of one-to-one mapping for the traditional inverse design method. This method may have profound usage for more complex EM device design problems in the future.
Therapeutic potential of the MDM2 inhibitor Nutlin-3 in counteracting SARS-CoV-2 infection of the eye through p53 activation
Authors: Zauli Giorgio , AlHilali Sara , Al-Swailem Samar , Secchiero Paola , Voltan Rebecca
Published: July 2022

Starting from the beginning of the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) global pandemic, most of the published data has concentrated on the respiratory signs and symptoms of Covid-19 infection, underestimating the presence and importance of ocular manifestations, such as conjunctivitis, usually reported in SARS-CoV-2 infected patients. With the present review we intend to resume the ocular involvement in SARS-CoV-2 infection and the recent discoveries about the different cell types and tissues of the eye that can be directly infected by SARS-CoV-2 and propagate the infection. Moreover, reviewing literature data about p53 expression in normal and diseased eye tissues, we hypothesize that the pleiotropic protein p53 present at high levels in cornea, conjunctiva and tear film might play a protective role against SARS-CoV-2 infection. Since p53 can be easily up-regulated by using small molecule non-genotoxic inhibitors of MDM2, we propose that topical use of Nutlin-3, the prototype member of MDM2 inhibitors, might protect the anterior surface of the eye from SARS-CoV-2 infection, reducing the spreading of the virus.
Development of the Interdisciplinary and Interprofessional Course Concept “Advanced Critical Illness Life Support”
Authors: Michael Mark , Biermann Henning , Gröning Ingmar , Pin Martin , Kümpers Philipp , Kumle Bernhard , Bernhard Michael
Published: July 2022

The Advanced Critical Illness Life Support (ACiLS) course was developed on behalf of the German Society for Interdisciplinary Emergency and Acute Medicine (DGINA). The goal of the ACiLS course is to provide a nationally recognized and certified life support course that teaches medical professionals the key principles of initial care of critically ill patients in the emergency department, including the (PR_E-)AUD2IT-algorithm. It is designed for interdisciplinary and multi-professional staff in the resuscitation room to optimize patient safety and outcome. ACiLS includes a new blended learning concept with a theoretical part as comprehensive e-learning and a two-day practical part with strong focus on team training in scenarios and workshops. The course format was conceived to balance best teaching practices within the limited instructional time and resources available. This article describes the development of the ACiLS course and provides an overview of its future implementation.
Whole Genome Multi-Locus Sequence Typing and Genomic Single Nucleotide Polymorphism Analysis for Epidemiological Typing of Pseudomonas aeruginosa From Indonesian Intensive Care Units
Authors: Goyal Manisha , Pelegrin Andreu Coello , Jaillard Magali , Saharman Yulia Rosa , Klaassen Corné H. W. , Verbrugh Henri A. , Severin Juliëtte A. , van Belkum Alex
Published: July 2022

We have previously studied carbapenem non-susceptible Pseudomonas aeruginosa (CNPA) strains from intensive care units (ICUs) in a referral hospital in Jakarta, Indonesia (Pelegrin et al., 2019). We documented that CNPA transmissions and acquisitions among patients were variable over time and that these were not significantly reduced by a set of infection control measures. Three high risk international CNPA clones (sequence type (ST)235, ST823, ST357) dominated, and carbapenem resistance was due to carbapenemase-encoding genes and mutations in the porin OprD. Pelegrin et al. (2019) reported core genome analysis of these strains. We present a more refined and detailed whole genome-based analysis of major clones represented in the same dataset. As per our knowledge, this is the first study reporting Single Nucleotide Polymorphisms (wgSNP) analysis of Pseudomonas strains. With whole genome-based Multi Locus Sequence Typing (wgMLST) of the 3 CNPA clones (ST235, ST357 and ST823), three to eleven subgroups with up to 200 allelic variants were observed for each of the CNPA clones. Furthermore, we analyzed these CNPA clone clusters for the presence of wgSNP to redefine CNPA transmission events during hospitalization. A maximum number 35350 SNPs (including non-informative wgSNPs) and 398 SNPs (ST-specific_informative-wgSNPs) were found in ST235, 34,570 SNPs (including non-informative wgSNPs) and 111 SNPs (ST-specific_informative-wgSNPs) in ST357 and 26,443 SNPs (including non-informative SNPs) and 61 SNPs (ST-specific_informative-wgSNPs) in ST823. ST-specific_Informative-wgSNPs were commonly noticed in sensor-response regulator genes. However, the majority of non-informative wgSNPs was found in conserved hypothetical proteins or in uncharacterized proteins. Of note, antibiotic resistance and virulence genes segregated according to the wgSNP analyses. A total of 8 transmission chains for ST235 strains followed by 9 and 4 possible transmission chains for ST357 and ST823 were traceable on the basis of pairwise distances of informative-wgSNPs (0 to 4 SNPs) among the strains. The present study demonstrates the value of detailed whole genome sequence analysis for highly refined epidemiological analysis of P. aeruginosa.
Genetic Diversity and Low Therapeutic Impact of Variant-Specific Markers in HIV-1 Pol Proteins
Authors: Troyano-Hernáez Paloma , Reinosa Roberto , Holguín Africa
Published: July 2022

The emergence and spread of new HIV-1 variants pose a challenge for the effectiveness of antiretrovirals (ARV) targeting Pol proteins. During viral evolution, non-synonymous mutations have fixed along the viral genome, leading to amino acid (aa) changes that can be variant-specific (V-markers). Those V-markers fixed in positions associated with drug resistance mutations (DRM), or R-markers, can impact drug susceptibility and resistance pathways. All available HIV-1 Pol sequences from ARV-naïve subjects were downloaded from the United States Los Alamos HIV Sequence Database, selecting 59,733 protease (PR), 6,437 retrotranscriptase (RT), and 6,059 integrase (IN) complete sequences ascribed to the four HIV-1 groups and group M subtypes and circulating recombinant forms (CRFs). Using a bioinformatics tool developed in our laboratory (EpiMolBio), we inferred the consensus sequences for each Pol protein and HIV-1 variant to analyze the aa conservation in Pol. We analyzed the Wu–Kabat protein variability coefficient (WK) in PR, RT, and IN group M to study the susceptibility of each site to evolutionary replacements. We identified as V-markers the variant-specific aa changes present in >75% of the sequences in variants with >5 available sequences, considering R-markers those V-markers that corresponded to DRM according to the IAS-USA2019 and Stanford-Database 9.0. The mean aa conservation of HIV-1 and group M consensus was 82.60%/93.11% in PR, 88.81%/94.07% in RT, and 90.98%/96.02% in IN. The median group M WK was 10 in PR, 4 in RT, and 5 in IN. The residues involved in binding or catalytic sites showed a variability <0.5%. We identified 106 V-markers: 31 in PR, 28 in RT, and 47 in IN, present in 11, 12, and 13 variants, respectively. Among them, eight (7.5%) were R-markers, present in five variants, being minor DRM with little potential effect on ARV susceptibility. We present a thorough analysis of Pol variability among all HIV-1 variants circulating to date. The relatively high aa conservation observed in Pol proteins across HIV-1 variants highlights their critical role in the viral cycle. However, further studies are needed to understand the V-markers’ impact on the Pol proteins structure, viral cycle, or treatment strategies, and periodic variability surveillance studies are also required to understand PR, RT, and IN evolution.
Mapping Genetic Events of SARS-CoV-2 Variants
Authors: Qin Luyao , Meng Jing , Ding Xiao , Jiang Taijiao
Published: July 2022

Genetic mutation and recombination are driving the evolution of SARS-CoV-2, leaving many genetic imprints which could be utilized to track the evolutionary pathway of SARS-CoV-2 and explore the relationships among variants. Here, we constructed a complete genetic map, showing the explicit evolutionary relationship among all SARS-CoV-2 variants including 58 groups and 46 recombination types identified from 3,392,553 sequences, which enables us to keep well informed of the evolution of SARS-CoV-2 and quickly determine the parents of novel variants. We found that the 5′ and 3′ of the spike and nucleoprotein genes have high frequencies to form the recombination junctions and that the RBD region in S gene is always exchanged as a whole. Although these recombinants did not show advantages in community transmission, it is necessary to keep a wary eye on the novel genetic events, in particular, the mutants with mutations on spike and recombinants with exchanged moieties on spike gene.
Roles of Alternative Sigma Factors in Invasion and Growth Characteristics of Listeria monocytogenes 10403S Into Human Epithelial Colorectal Adenocarcinoma Caco-2 Cell
Authors: Rukit Junyaluck , Boonmee Atsadang , Kijpornyongpan Teeratas , Tulsook Kan , Baranyi József , Chaturongakul Soraya
Published: July 2022

Listeria monocytogenes is a Gram-positive facultative intracellular bacterium with a broad host range. With its housekeeping sigma factor and four alternative ones (namely SigB, SigC, SigH, and SigL), L. monocytogenes can express genes in response to changing environments. However, the roles of these sigma factors in intracellular survival are still unclear. The objectives of this study were to characterize the role of each alternative σ factor on L. monocytogenes invasion and growth inside human epithelial colorectal adenocarcinoma Caco-2 cells. We used L. monocytogenes 10403S wild type and its 15 alternative sigma factor deletion mutants at a multiplicity of infection of 100 and 1 in invasion and intracellular growth assays in the Caco-2 cells, respectively. At 1.5, 2, 4, 6, 8, 10, and 12 h post-infection, Caco-2 cells were lysed, and intracellular L. monocytogenes were enumerated on brain-heart infusion agar. Colony-forming and growth rates were compared among strains. The results from phenotypic characterization confirmed that (i) SigB is the key factor for L. monocytogenes invasion and (ii) having only SigA (ΔsigBCHL strain) is sufficient to invade and multiply in the host cell at similar levels as the wild type. Our previous study suggested the negative role of SigL in bile stress response. In this study, we have shown that additional deletion of the rpoN (or sigL) gene to ΔsigB, ΔsigC, or ΔsigH could restore the impaired invasion efficiencies of the single mutant, suggesting the absence of SigL could enhance host invasion. Therefore, we further investigated the role of SigL during extracellular and intracellular life cycles. Using RNA sequencing, we identified 118 and 16 SigL-dependent genes during the extracellular and intracellular life cycles, respectively. The sigL gene itself was induced by fivefolds prior to the invasion, and 5.3 folds during Caco-2 infection, further suggesting the role of SigL in intracellular growth.
The Native Microbial Community of Gastropod-Associated Phasmarhabditis Species Across Central and Southern California
Authors: Schurkman Jacob , Liu Rui , Alavi Salma , Tandingan De Ley Irma , Hsiao Ansel , Dillman Adler R.
Published: July 2022

Nematodes in the genus Phasmarhabditis can infect and kill slugs and snails, which are important agricultural pests. This useful trait has been commercialized by the corporation BASF after they mass produced a product labeled Nemaslug®. The product contains Phasmarhabditis hermaphrodita, which has been cultured with Moraxella osloensis, a bacterial strain that was originally thought to be responsible for causing mortality in slugs and snails. The exact mechanism leading to death in a Phasmarhabditis infected host is unknown but may involve contributions from nematode-associated bacteria. The naturally occurring microbial community of Phasmarhabditis is unexplored; the previous Phasmarhabditis microbial community studies have focused on laboratory grown or commercially reared nematodes, and in order to obtain a deeper understanding of the parasite and its host interactions, it is crucial to characterize the natural microbial communities associated with this organism in the wild. We sampled Phasmarhabditis californica, Phasmarhabditis hermaphrodita, and Phasmarhabditis papillosa directly from their habitats in Central and Southern California nurseries and garden centers and identified their native microbial community via 16S amplicon sequencing. We found that the Phasmarhabditis microbial community was influenced by species, location, and possibly gastropod host from which the nematode was collected. The predominant bacteria of the Phasmarhabditis isolates collected included Shewanella, Clostridium perfringens, Aeromonadaceae, Pseudomonadaceae, and Acinetobacter. Phasmarhabditis papillosa isolates exhibited an enrichment with species belonging to Acinetobacter or Pseudomonadaceae. However, further research must be performed to determine if this is due to the location of isolate collection or a species specific microbial community pattern. More work on the natural microbial community of Phasmarhabditis is needed to determine the role of bacteria in nematode virulence.
Efficacy of dietary supplements targeting gut microbiota in the prevention and treatment of gestational diabetes mellitus
Authors: Wan Jiayang , Ma Jingmei
Published: July 2022

Gestational diabetes mellitus (GDM) is a kind of metabolic disease occurring during gestation period, which often leads to adverse pregnancy outcomes and seriously harms the health of mothers and infants. The pathogenesis of GDM may be bound up with the abnormal gut microbiota composition in pregnant women. Previous studies have clarified that dietary supplements can regulate the gut microbiota to play a role. Therefore, using dietary supplements, such as probiotics, prebiotics, and synbiotics to target the gut microbiota to regulate the disordered gut microbiota would become a potential method that benefits for preventing and treating GDM. This paper reviews a series of clinical trials in recent years, expounds on the clinical effects of dietary supplements such as probiotics on GDM, and discusses the intervention effects of dietary supplements on GDM related risk factors, including overweight, obesity, and type 2 diabetes mellitus (T2DM). In addition, the relationship of GDM and gut microbiota is also discussed, and the possible mechanisms of dietary supplements are summarized. This review will help to promote the further development of dietary supplements targeting gut microbiota and provide more knowledge support for clinical application in the prevention and treatment of various diseases.
How do intestinal probiotics restore the intestinal barrier?
Authors: Gou Hong-Zhong , Zhang Yu-Lin , Ren Long-Fei , Li Zhen-Jiao , Zhang Lei
Published: July 2022

The intestinal barrier is a structure that prevents harmful substances, such as bacteria and endotoxins, from penetrating the intestinal wall and entering human tissues, organs, and microcirculation. It can separate colonizing microbes from systemic tissues and prevent the invasion of pathogenic bacteria. Pathological conditions such as shock, trauma, stress, and inflammation damage the intestinal barrier to varying degrees, aggravating the primary disease. Intestinal probiotics are a type of active microorganisms beneficial to the health of the host and an essential element of human health. Reportedly, intestinal probiotics can affect the renewal of intestinal epithelial cells, and also make cell connections closer, increase the production of tight junction proteins and mucins, promote the development of the immune system, regulate the release of intestinal antimicrobial peptides, compete with pathogenic bacteria for nutrients and living space, and interact with the host and intestinal commensal flora to restore the intestinal barrier. In this review, we provide a comprehensive overview of how intestinal probiotics restore the intestinal barrier to provide new ideas for treating intestinal injury-related diseases.
The efficiency of Nextera XT tagmentation depends on G and C bases in the binding motif leading to uneven coverage in bacterial species with low and neutral GC-content
Authors: Segerman Bo , Ástvaldsson Ásgeir , Mustafa Linda , Skarin Joakim , Skarin Hanna
Published: July 2022

Whole-genome sequencing (WGS) is becoming the new standard for bacterial high-resolution typing and the performance of laboratories is being evaluated in interlaboratory comparisons. The use of the Illumina Nextera XT library preparation kit has been found to be associated with poorer performance due to a GC-content-dependent coverage bias. The bias is especially strong when sequencing low GC-content species. Here, we have made an in-depth analysis of the Nextera XT coverage bias problem using data from a proficiency test of the low GC-content species Campylobacter jejuni. We have compared Nextera XT with Nextera Flex/DNA Prep and examined the consequences on downstream WGS analysis when using different quantities of raw data. We have also analyzed how the coverage bias relates to differential usage of tagmentation cleavage sites. We found that the tagmentation site was characterized by a symmetrical motif with a central AT-rich region surrounded by Gs and Cs. The Gs and Cs appeared to be the main determinant for cleavage efficiency and the genomic regions that were associated with low coverage only contained low-efficiency cleavage sites. This explains why low GC-content genomes and regions are more subjected to coverage bias. We furthermore extended our analysis to other datasets representing other bacterial species. We visualized how the coverage bias was large in low GC-content species such as C. jejuni, C. coli, Staphylococcus aureus, and Listeria monocytogenes, whereas species with neutral GC-content such as Salmonella enterica and Escherichia coli were only affected in certain regions. Species with high GC-content such as Mycobacterium tuberculosis and Pseudomonas aeruginosa were hardly affected at all. The coverage bias associated with Nextera XT was not found when Nextera Flex/DNA Prep had been used.
Daily Reports on Phage-Host Interactions
Authors: Albrycht Kamil , Rynkiewicz Adam A. , Harasymczuk Michal , Barylski Jakub , Zielezinski Andrzej
Published: July 2022

Understanding phage-host relationships is crucial for the study of virus biology and the application of phages in biotechnology and medicine. However, information concerning the range of hosts for bacterial and archaeal viruses is scattered across numerous databases and is difficult to obtain. Therefore, here we present PHD (Phage & Host Daily), a web application that offers a comprehensive, up-to-date catalog of known phage-host associations that allows users to select viruses targeting specific bacterial and archaeal taxa of interest. Our service combines the latest information on virus-host interactions from seven source databases with current taxonomic classification retrieved directly from the groups and institutions responsible for its maintenance. The web application also provides summary statistics on host and virus diversity, their pairwise interactions, and the host range of deposited phages. PHD is updated daily and available at http://phdaily.info or http://combio.pl/phdaily.
A Combination of Novel Microecological Agents and Molasses Role in Digestibility and Fermentation of Rice Straw by Facilitating the Ruminal Microbial Colonization
Authors: Ma Yulin , Chen Xu , Khan Muhammad Zahoor , Xiao Jianxin , Cao Zhijun
Published: July 2022

In this study, we evaluated the effect of microecological agents (MA) combined with molasses (M) on the biodegradation of rice straw in the rumen. Rice straw was pretreated in laboratory polyethylene 25 × 35 cm sterile bags with no additive control (Con), MA, and MA + M for 7, 15, 30, and 45 days, and then the efficacy of MA + M pretreatment was evaluated both in vitro and in vivo. The scanning electron microscopy, X-ray diffraction analysis, and Fourier-transform infrared spectroscopy results showed that the MA or MA + M pretreatment altered the physical and chemical structure of rice straw. Meanwhile, the ruminal microbial attachment on the surface of rice straw was significantly increased after MA+M pretreatment. Furthermore, MA + M not only promoted rice straw fermentation in vitro but also improved digestibility by specifically inducing rumen colonization of Prevotellaceae_UCG-001, Butyrivibrio, and Succinimonas. Altogether, we concluded that microecological agents and molasses could be the best choices as a biological pretreatment for rice straw to enhance its nutritive value as a ruminant's feed.
Application of Fullerenes as Photosensitizers for Antimicrobial Photodynamic Inactivation: A Review
Authors: Hou Wenjia , Shi Guorui , Wu Songze , Mo Jiayi , Shen Lan , Zhang Xiuqiang , Zhu Yabin
Published: July 2022

Antimicrobial photodynamic inactivation (aPDI) is a newly emerged treatment approach that can effectively address the issue of multidrug resistance resulting from the overuse of antibiotics. Fullerenes can be used as promising photosensitizers (PSs) for aPDI due to the advantages of high triplet state yields, good photostability, wide antibacterial spectrum, and permissibility of versatile functionalization. This review introduces the photodynamic activities of fullerenes and the up-to-date understanding of the antibacterial mechanisms of fullerene-based aPDI. The most recent works on the functionalization of fullerenes and the application of fullerene derivatives as PSs for aPDI are also summarized. Finally, certain remaining challenges are emphasized to provide guidance on future research directions for achieving clinical application of fullerene-based aPDI.
An Extended C-Terminus, the Possible Culprit for Differential Regulation of 5-Aminolevulinate Synthase Isoforms
Authors: Hunter Gregory A. , Ferreira Gloria C.
Published: July 2022

5-Aminolevulinate synthase (ALAS; E.C. 2.3.1.37) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyzes the key regulatory step of porphyrin biosynthesis in metazoa, fungi, and α-proteobacteria. ALAS is evolutionarily related to transaminases and is therefore classified as a fold type I PLP-dependent enzyme. As an enzyme controlling the key committed and rate-determining step of a crucial biochemical pathway ALAS is ideally positioned to be subject to allosteric feedback inhibition. Extensive kinetic and mutational studies demonstrated that the overall enzyme reaction is limited by subtle conformational changes of a hairpin loop gating the active site. These findings, coupled with structural information, facilitated early prediction of allosteric regulation of activity via an extended C-terminal tail unique to eukaryotic forms of the enzyme. This prediction was subsequently supported by the discoveries that mutations in the extended C-terminus of the erythroid ALAS isoform (ALAS2) cause a metabolic disorder known as X-linked protoporphyria not by diminishing activity, but by enhancing it. Furthermore, kinetic, structural, and molecular modeling studies demonstrated that the extended C-terminal tail controls the catalytic rate by modulating conformational flexibility of the active site loop. However, the precise identity of any such molecule remains to be defined. Here we discuss the most plausible allosteric regulators of ALAS activity based on divergences in AlphaFold-predicted ALAS structures and suggest how the mystery of the mechanism whereby the extended C-terminus of mammalian ALASs allosterically controls the rate of porphyrin biosynthesis might be unraveled.
Analysis of the Relationship Between Motor Imagery and Age-Related Fatigue for CNN Classification of the EEG Data
Authors: Li Xiangyun , Chen Peng , Yu Xi , Jiang Ning
Published: July 2022

Background

The aging of the world population poses a major health challenge, and brain–computer interface (BCI) technology has the potential to provide assistance and rehabilitation for the elderly.

Objectives

This study aimed to investigate the electroencephalogram (EEG) characteristics during motor imagery by comparing young and elderly, and study Convolutional Neural Networks (CNNs) classification for the elderly population in terms of fatigue analysis in both frontal and parietal regions.

Methods

A total of 20 healthy individuals participated in the study, including 10 young and 10 older adults. All participants completed the left- and right-hand motor imagery experiment. The energy changes in the motor imagery process were analyzed using time–frequency graphs and quantified event-related desynchronization (ERD) values. The fatigue level of the motor imagery was assessed by two indicators: (θ + α)/β and θ/β, and fatigue-sensitive channels were distinguished from the parietal region of the brain. Then, rhythm entropy was introduced to analyze the complexity of the cognitive activity. The phase-lock values related to the parietal and frontal lobes were calculated, and their temporal synchronization was discussed. Finally, the motor imagery EEG data was classified by CNNs, and the accuracy was discussed based on the analysis results.

Result

For the young and elderly, ERD was observed in C3 and C4 channels, and their fatigue-sensitive channels in the parietal region were slightly different. During the experiment, the rhythm entropy of the frontal lobe showed a decreasing trend with time for most of the young subjects, while there was an increasing trend for most of the older ones. Using the CNN classification method, the elderly achieved around 70% of the average classification accuracy, which is almost the same for the young adults.

Conclusion

Compared with the young adults, the elderly are less affected by the level of cognitive fatigue during motor imagery, but the classification accuracy of motor imagery data in the elderly may be slightly lower than that in young persons. At the same time, the deep learning method also provides a potentially feasible option for the application of motor-imagery BCI (MI-BCI) in the elderly by considering the ERD and fatigue phenomenon together.
Potential Value of Serum Uric Acid in the Identification of Postoperative Delirium in Geriatric Patients Undergoing Knee Replacement
Authors: Wang Fei , Tang Xinhui , Wang Jiahan , Liu Siyv , Wu Xiaoyue , Dong Rui , Lin Xu , Wang Bin , Bi Yanlin
Published: July 2022

Objectives

The relationship between preoperative serum uric acid (SUA) and cerebrospinal fluid (CSF) Alzheimer-related biomarkers were investigated to determine whether high SUA is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy.

Methods

The participants were selected from the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study and the Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study. The logistic regression equation was used to analyze the risk factors and protective factors of POD. The interaction term (SUA × Sex) was introduced into the linear model to explore the potential modification effects of sex on the identified correlations. We analyzed the mediating effects of Alzheimer-related biomarkers. Finally, we constructed the receiver operating characteristic (ROC) curve and the nomogram model to evaluate the efficacy of SUA and Alzheimer-related biomarkers in predicting POD.

Results

Patients with POD had elevated SUA level (PNDRFAP: p = 0.002, PNDABLE: p < 0.001). Preoperative SUA level was positively correlated with CSF phosphorylated tau (P-tau) (p = 0.027) and β-amyloid42 (Aβ42)/P-tau (p = 0.023). Interaction analysis did not find any modification effect of sex. The relationship between SUA and POD was partially mediated by CSF P-tau (15.3%). ROC curve showed that the model combining SUA and Alzheimer-related biomarkers had better performance in predicting POD [area under the curve (AUC) = 0.880; p < 0.001], and the predictive model is accurate.

Conclusions

High SUA may enhance CSF P-tau level, thus increasing the risk of POD, and the model combining SUA and Alzheimer-related biomarkers can accurately predict the occurrence of POD.
Apolipoprotein E Genotype e2: Neuroprotection and Its Limits
Authors: Kim Hyun , Devanand Davangere P. , Carlson Scott , Goldberg Terry E.
Published: July 2022

In this review, we comprehensively, qualitatively, and critically synthesized several features of APOE-e2, a known APOE protective variant, including its associations with longevity, cognition, and neuroimaging, and neuropathology, all in humans. If e2’s protective effects—and their limits—could be elucidated, it could offer therapeutic windows for Alzheimer’s disease (AD) prevention or amelioration. Literature examining e2 within the years 1994–2021 were considered for this review. Studies on human subjects were selectively reviewed and were excluded if observation of e2 was not specified. Effects of e2 were compared with e3 and e4, separately and as a combined non-e2 group. Our examination of existing literature indicated that the most robust protective role of e2 is in longevity and AD neuropathologies, but e2’s effect on cognition and other AD imaging markers (brain structure, function, and metabolism) were inconsistent, thus inconclusive. Notably, e2 was associated with greater risk of non-AD proteinopathies and a disadvantageous cerebrovascular profile. We identified multiple methodological shortcomings of the literature on brain function and cognition that could have contributed to inconsistent and potentially misleading findings. We make careful interpretations of existing findings and provide directions for research strategies that could effectively examine the independent and unbiased effect of e2 on AD risk.
Ultrasonic Vocalizations in Adult C57BL/6J Mice: The Role of Sex Differences and Repeated Testing
Authors: Premoli Marika , Petroni Valeria , Bulthuis Ronald , Bonini Sara Anna , Pietropaolo Susanna
Published: July 2022

Ultrasonic vocalizations (USVs) are a major tool for assessing social communication in laboratory mice during their entire lifespan. At adulthood, male mice preferentially emit USVs toward a female conspecific, while females mostly produce ultrasonic calls when facing an adult intruder of the same sex. Recent studies have developed several sophisticated tools to analyze adult mouse USVs, especially in males, because of the increasing relevance of adult communication for behavioral phenotyping of mouse models of autism spectrum disorder (ASD). Little attention has been instead devoted to adult female USVs and impact of sex differences on the quantitative and qualitative characteristics of mouse USVs. Most of the studies have also focused on a single testing session, often without concomitant assessment of other social behaviors (e.g., sniffing), so little is still known about the link between USVs and other aspects of social interaction and their stability/variations across multiple encounters. Here, we evaluated the USVs emitted by adult male and female mice during 3 repeated encounters with an unfamiliar female, with equal or different pre-testing isolation periods between sexes. We demonstrated clear sex differences in several USVs' characteristics and other social behaviors, and these were mostly stable across the encounters and independent of pre-testing isolation. The estrous cycle of the tested females exerted quantitative effects on their vocal and non-vocal behaviors, although it did not affect the qualitative composition of ultrasonic calls. Our findings obtained in B6 mice, i.e., the strain most widely used for engineering of transgenic mouse lines, contribute to provide new guidelines for assessing ultrasonic communication in male and female adult mice.
Are Grid-Like Representations a Component of All Perception and Cognition?
Authors: Chen Zhe Sage , Zhang Xiaohan , Long Xiaoyang , Zhang Sheng-Jia
Published: July 2022

Grid cells or grid-like responses have been reported in the rodent, bat and human brains during various spatial and non-spatial tasks. However, the functions of grid-like representations beyond the classical hippocampal formation remain elusive. Based on accumulating evidence from recent rodent recordings and human fMRI data, we make speculative accounts regarding the mechanisms and functional significance of the sensory cortical grid cells and further make theory-driven predictions. We argue and reason the rationale why grid responses may be universal in the brain for a wide range of perceptual and cognitive tasks that involve locomotion and mental navigation. Computational modeling may provide an alternative and complementary means to investigate the grid code or grid-like map. We hope that the new discussion will lead to experimentally testable hypotheses and drive future experimental data collection.
Does Your Loved One With Cognitive Symptoms Need to See a Doctor? Check It Online
Authors: Agüera-Ortiz Luis , Martín-Carrasco Manuel , Arriola-Manchola Enrique , Martínez-Lage Pablo , Pérez-Martínez David Andrés , Ojea Tomás , Soler-López Begoña , García-Ribas Guillermo
Published: July 2022

Widespread access to emerging information and communication technologies (ICT) allows its use for the screening of diseases in the general population. At the initiative of the Spanish Confederation of Associations of Families of People with Alzheimer’s disease and other dementias (CEAFA), a website (http://www.problemasmemoria.com) has been created that provides information about Alzheimer’s disease and includes questionnaires to be completed by family or friends concerned about memory problems of a relative. A cross-sectional, randomized, multicenter study was performed to evaluate feasibility, validity, and user satisfaction with an electronic method of completion vs. the current method of paper-based questionnaires for clinically dementia screening completed by the informants: the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and the Alzheimer’s disease-8 screening test (AD8). A total of 111 pairs were recruited by seven memory clinics. Informants completed IQCODE and AD8 questionnaires both in their paper and electronic versions. The correlation between paper and electronic versions was significantly positive for IQCODE (r = 0.98; p < 0.001) and AD8 (r = 0.96; p < 0.001). The execution time did not differ significantly, and participants considered their use equally easy. This study shows that an electronic version of the IQCODE and AD8 questionnaires is suitable for its online use via the internet and achieves the same results as the traditional paper versions.
Extended Repetitive Transcranial Magnetic Stimulation Therapy for Post-stroke Depression in a Patient With a Pre-frontal Cortical Lesion: A Case Study
Authors: Hordacre Brenton , Chau Anson , Graetz Lynton , Hillier Susan
Published: July 2022

Approximately one-third of stroke survivors experience post-stroke depression. Repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has shown promise as a treatment for depression with few side effects and high tolerability. However, previous post-stroke depression trials have not considered the effect of lesion location, the persistence of clinical improvements, nor the value of ongoing maintenance treatments. These questions are important to determine the therapeutic value of rTMS as a treatment for post-stroke depression. We report a unique case study of a 71-year-old male who had experienced a left hemispheric ischemic stroke 4 years prior. The patient was screened with the Beck Depression Inventory and Patient Health Questionnaire and found to be experiencing moderate levels of depression. Ten daily sessions of left dorsolateral pre-frontal cortex rTMS were applied over a two-week period. A clinically meaningful reduction in depression was achieved. Approximately 10 weeks following rTMS treatment, improvements in depression were attenuating. Weekly maintenance rTMS was delivered to the left dorsolateral pre-frontal cortex for 10 sessions. At the conclusion of maintenance rTMS, clinical assessments indicated depressive symptoms had reduced to a minimal to nil level. Clinically meaningful improvements in depression were maintained at 3 months after rTMS treatment had ceased. These findings provide novel insight to suggest rTMS may reduce depressive symptoms in stroke survivors with a lesion at the site of stimulation. Ongoing maintenance treatments might prove beneficial to enhance persistence of clinical improvements.
Feasibility of FDCT Early Brain Parenchymal Blood Volume Maps in Predicting Short-Term Prognosis in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Wen Lili , Zhou Longjiang , Wu Qi , Zhou Xiaoming , Zhang Xin
Published: July 2022

Purpose

Aneurysmal subarachnoid hemorrhage (SAH) is accompanied by cerebral perfusion changes. We aimed to measure the parenchymal blood volume (PBV) maps acquired by C-arm flat-panel detector CT (FDCT) to assess the cerebral blood volume at an early stage in aneurysmal SAH and to explore the correlation with the outcomes at discharge.

Methods

Data of 66 patients with aneurysmal SAH who underwent FDCT PBV examination were retrospectively analyzed. The PBV of regions of interest, including the cortices of the bilateral frontal lobe, the parietal lobe, the occipital lobe, and the cerebral hemisphere, as well as the basal ganglia, were measured and quantitatively analyzed. The clinical and imaging data of the patients were also collected, and logistic regression analysis was performed to explore the correlation between the perfusion parameters and outcomes at discharge.

Results

The favorable and poor outcomes at discharge were found in 37 (56.06%) and 29 (43.94%) patients, respectively. The whole-brain PBV was significantly correlated with the Hunt-Hess grades (p < 0.005) and the WFNSS grades (p < 0.005). The whole-brain PBV of the poor prognosis was significantly higher than that of the favorable prognosis (35.17 ± 7.66 vs. 29.78 ± 5.54, p < 0.005). The logistic regression analysis showed that the PBV of the parietal lobe at the bleeding side (OR = 1.10, 95%CI: 1.00–1.20, p = 0.04) was an independent risk factor predicting the short-term prognosis.

Conclusions

Parenchymal blood volume (PBV) maps could reflect the cerebral blood volume throughout the brain to characterize its perfusion status at an early stage in aneurysmal SAH. It enables a one-stop imaging evaluation and treatment in the same angio-suite and may serve as a reliable technique in clinical assessment of aneurysmal SAH.
Neuromodulation Strategies to Reduce Inflammation and Improve Lung Complications in COVID-19 Patients
Authors: Czura Christopher J. , Bikson Marom , Charvet Leigh , Chen Jiande D. Z. , Franke Manfred , Fudim Marat , Grigsby Eric , Hamner Sam , Huston Jared M. , Khodaparast Navid , Krames Elliot , Simon Bruce J. , Staats Peter , Vonck Kristl
Published: July 2022

Since the outbreak of the COVID-19 pandemic, races across academia and industry have been initiated to identify and develop disease modifying or preventative therapeutic strategies has been initiated. The primary focus has been on pharmacological treatment of the immune and respiratory system and the development of a vaccine. The hyperinflammatory state (“cytokine storm”) observed in many cases of COVID-19 indicates a prognostically negative disease progression that may lead to respiratory distress, multiple organ failure, shock, and death. Many critically ill patients continue to be at risk for significant, long-lasting morbidity or mortality. The human immune and respiratory systems are heavily regulated by the central nervous system, and intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction. Several technologies, both invasive and non-invasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients. This manuscript provides an overview of the role of the nervous system in inflammation and respiration, the current understanding of neuromodulatory techniques from preclinical and clinical studies and provides a rationale for testing non-invasive neuromodulation to modulate acute systemic inflammation and respiratory dysfunction caused by SARS-CoV-2 and potentially other pathogens. The authors of this manuscript have co-founded the International Consortium on Neuromodulation for COVID-19 to advocate for and support studies of these technologies in the current coronavirus pandemic.