bluuebunny/crossref_metadata_2025 huggingface dataset:
Alzheimer’s disease and COVID-19: Interactions, intrinsic linkages, and the role of immunoinflammatory responses in this process
Authors: Li Wei , Sun Lin , Yue Ling , Xiao Shifu
Published: February 2023

Alzheimer’s disease (AD) and COVID-19 share many common risk factors, such as advanced age, complications, APOE genotype, etc. Epidemiological studies have also confirmed the internal relationship between the two diseases. For example, studies have found that AD patients are more likely to suffer from COVID-19, and after infection with COVID-19, AD also has a much higher risk of death than other chronic diseases, and what’s more interesting is that the risk of developing AD in the future is significantly higher after infection with COVID-19. Therefore, this review gives a detailed introduction to the internal relationship between Alzheimer’s disease and COVID-19 from the perspectives of epidemiology, susceptibility and mortality. At the same time, we focused on the important role of inflammation and immune responses in promoting the onset and death of AD from COVID-19.
Expression of HSPA14 in patients with acute HIV-1 infection and its effect on HIV-1 replication
Authors: Bi Mingyuan , Kang Wen , Sun Yongtao
Published: February 2023

Introduction

Heat shock protein (HSPs) are important intracellular factors, which are often involved in the regulation of viral replication including HIV-1 in infected individuals as molecular chaperone proteins. Heat shock proteins 70 (HSP70/HSPA) family play important roles in HIV replication, but this family contain many subtypes, and it is unclear how these subtypes participate in and affect HIV replication.

Methods

To detect the interaction between HSPA14 and HspBP1 by CO-IP. Simulating HIV infection status in vitro to detect the change of intracellular HSPA14 expression after HIV infection in different cells. Constructing HSPA14 overexpression or knockdown cells to detect intracellular HIV replication levels after in vitro infection. Detecting the difference of HSPA expression levels in CD4+ T cells of untreated acute HIV-infected patients with different viral load.

Results

In this study, we found that HIV infection can lead to changes in the transcriptional level of many HSPA subtypes, among which HSPA14 interacts with HIV transcriptional inhibitor HspBP1. The expression of HSPA14 in Jurkat and primary CD4+T cells infected with HIV were inhibited, overexpression of HSPA14 inhibited HIV replication, while knocking down HSPA14 promoted HIV replication. We also found that the expression level of HSPA14 is higher in peripheral blood CD4+T cells of untreated acute HIV infection patients with low viral load.

Conclusion

HSPA14 is a potential HIV replication inhibitor and may restrict HIV replication by regulating the transcriptional inhibitor HspBP1. Further studies are needed to determine the specific mechanism by which HSPA14 regulates viral replication
Detailed characterization of SARS-CoV-2-specific T and B cells after infection or heterologous vaccination
Authors: Lo Tartaro Domenico , Paolini Annamaria , Mattioli Marco , Swatler Julian , Neroni Anita , Borella Rebecca , Santacroce Elena , Di Nella Alessia , Gozzi Licia , Busani Stefano , Cuccorese Michela , Trenti Tommaso , Meschiari Marianna , Guaraldi Giovanni , Girardis Massimo , Mussini Cristina , Piwocka Katarzyna , Gibellini Lara , Cossarizza Andrea , De Biasi Sara
Published: February 2023

The formation of a robust long-term antigen (Ag)-specific memory, both humoral and cell-mediated, is created following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. Here, by using polychromatic flow cytometry and complex data analyses, we deeply investigated the magnitude, phenotype, and functionality of SARS-CoV-2-specific immune memory in two groups of healthy subjects after heterologous vaccination compared to a group of subjects who recovered from SARS-CoV-2 infection. We find that coronavirus disease 2019 (COVID-19) recovered patients show different long-term immunological profiles compared to those of donors who had been vaccinated with three doses. Vaccinated individuals display a skewed T helper (Th)1 Ag-specific T cell polarization and a higher percentage of Ag-specific and activated memory B cells expressing immunoglobulin (Ig)G compared to those of patients who recovered from severe COVID-19. Different polyfunctional properties characterize the two groups: recovered individuals show higher percentages of CD4+ T cells producing one or two cytokines simultaneously, while the vaccinated are distinguished by highly polyfunctional populations able to release four molecules, namely, CD107a, interferon (IFN)-γ, tumor necrosis factor (TNF), and interleukin (IL)-2. These data suggest that functional and phenotypic properties of SARS-CoV-2 adaptive immunity differ in recovered COVID-19 individuals and vaccinated ones.
Probability-based wind-wave relation
Authors: Gao Yang , Schmitt François G. , Hu Jianyu , Huang Yongxiang
Published: February 2023

In a fully developed sea, the significant wave height (Hs) and wind speed (U10) are conventionally related to a pure quadratic equation. This relation is often violated, since in the field the measured local Hs is often contaminated by the swell, which is propagated from distant places. Therefore, a swell partition is required before the establishment of the wind-wave relation. The Spectra Energy Partition (SEP) is regarded as the best way to isolate the swell and the wind wave relation: it is based on the identification of a separation frequency in the ocean wave spectrum. However, for most field observations, the wave spectra information is unavailable, and thus the SEP is inapplicable. This work proposes a probability-based algorithm to identify the averaged swell without knowing the wave spectrum a priori. The local wind-wave relation is established by either a linear or an energy-conserved decomposition. We also find that the local wind-wave relation is a power-law when the wind speed U10 is above 4 m/s. The proposed method is first validated by applying the SEP method to buoy collected wave spectra data. The global pattern of the swell and the local wind waves is retrieved by applying the proposed method to a 17-year wind and wave database from the JASON satellite. Strong seasonal and spatial variations are obtained. Finally, a prediction model based on the empirical wind-wave relation is shown to successfully retrieve the wave field when the wind field is available.
Acoustic indices respond to specific marine mammal vocalizations and sources of anthropogenic noise
Authors: Ferguson Elizabeth L. , Clayton Hannah M. , Sakai Taiki
Published: February 2023

Using passive acoustic methods for biodiversity conservation and effective ecosystem monitoring is hindered by laborious, human-mediated processes of accurately identifying biologic and anthropogenic sounds within large datasets. Soundscape ecology provides a potential means of addressing this need through the use of automated acoustic-based biodiversity indices, which show promise in representing biodiversity in terrestrial environments. However, the direct relationship between specific underwater sounds and acoustic index measurements are largely unexplored. Using passive acoustic data collected from three broadband hydrophones within the Ocean Observatories Initiative’s cabled arrays in the Pacific northwest, we identified periods of vocalizing marine mammals and sources of anthropogenic noise. Automated calculations of seven acoustic indices were compared across biologic and anthropogenic sound type and call parameters. Although several index measurements did not vary significantly, the Acoustic Complexity Index (ACI) measurements increased in response to echolocation clicks from sperm whales (Physeter macrocephalus) and burst pulses originating from unidentified delphinid species. Measurements of the Bioacoustic Index (BI) decreased dramatically in response to sperm whale echolocation clicks, a more obvious trend when loud clicks were parsed from moderate and quiet clicks. Correlations coefficient and confidence interval values between ACI and BI measurements and call characteristics from sperm whales indicate a moderate to strong relationship, which was not found in correlations with delphinid calls. A generalized linear mixed-effect model indicated multiple species and sound types contribute significantly to the variation of several index measurements. Noise generated by passing ships consistently resulted in decreased values for the Normalized Difference Soundscape Index (NDSI) and Total Entropy (H) as compared to quiet periods and periods with vocalizing marine mammals. These findings provide information on the relationship between several acoustic indices and specific underwater sounds produced by marine mammals and anthropogenic sources. This ground-truthing endeavor expands the understanding of acoustic indices and their potential use as a tool for conservation and ecosystem health management purposes.
Industry remotely operated vehicle imagery for assessing marine communities associated with subsea oil and gas infrastructure on the continental shelf of South-East Australia
Authors: Ierodiaconou Daniel , McLean Dianne , Birt Matthew Jon , Bond Todd , Wines Sam , Glade-Wright Ollie , Morris Joe , Higgs Doug , Whitmarsh Sasha K.
Published: February 2023

Introduction

Offshore oil and gas (O & G) infrastructure provides hard substrata of structural complexity in marine environments and has been shown to have ecological value, particularly in oligotrophic environments. As infrastructure approaches end of life, understanding such values is critical to inform decommissioning decisions.

Methods

This study uses a decade of industry remotely operated vehicle (ROV) imagery to describe fish, invertebrate, and benthic communities on gas field infrastructure. Sampling was conducted over 22 km of flowline, three wells and one manifold in the temperate waters of Bass Strait, south east Australia in depths of 155 to 263 m.

Results

A total of 10,343 mobile animals from 69 taxa were observed. A higher diversity of fishes were observed on flowlines (28 taxa) compared to wells (19 taxa). Fish and invertebrate communities observed along flowlines were distinct from those observed on wells/manifold, however, there was also high spatial variability among the different flowlines surveyed and between the three wells and manifold. These differences appear to be driven by habitat and depth preferences of the species observed. Many sand-affiliated species were associated with buried sections of flowlines (Tasmanian giant crab Pseudocarcinus gigas, Balmain bug Ibacus peronii, slender sand burrower Creedia haswelli, red cod Pseudophycis spp., blue grenadier Macruronus novaezelandiae) whilst reef-associated and schooling species were observed on the wells/manifold (jackass morwong Nemadactylus macropterus, redbait Emmelichthys nitidus, splendid perch Callanthias australis). Species of ecological importance were also noted including the Australian fur seal (Arctocephalus pusillus doriferus), long-lived foxfish (Bodianus frenchii), and handfish (Brachionichthyidae spp).

Discussion

This study describes the habitat value of oil and gas infrastructure in a data poor temperate region that is important for understanding how the decommissioning of these structures may affect local marine ecosystems and fisheries. Therefore, it is critical to understand the habitat value of O&G infrastructure to marine life in the Bass Strait and whether decommissioning of these structures affect local marine ecosystems and fisheries. This study shows the complexity of determining temporal change in biodiversity values associated with these O & G structures from historical industry datasets that will be key for informing future decommissioning options. We also provide some guidance on how future quantitative data can be obtained in a systematic way using industry ROV data to better inform ecological investigations and decommissioning options.
Simulation of red tide drift-diffusion process in the Pearl River Estuary and its response to the environment
Authors: Xu Yuanxing , Sun Yan , Xu Guangjun , Liu Dazhao
Published: February 2023

A particle tracking model for the Lingdingyang Bay of the Pearl River Estuary (PRE) was established based on the Delft3D model. The model was initialized with remote sensing images to simulate the red tide drift-diffusion process in this sea area in the autumn of 2020 and analyze its response to tides, winds and runoffs. The results show that this red tide occurred in the central sea area of the Lingdingyang Bay. The red tide drifted south with the ebb tide and north with flood tide. The red tide spread northward to the waters near Humen and southward to the western waters of Zhuhai. Through the control variable experiments, it is found that the red tide drift-diffusion process was mainly affected by tide and wind, with minimal influence from runoff. The tide expanded the scope of red tide diffusion, and the wind further changed the distribution of red tide. Under the influence of the northeast wind, the red tide gathered on both sides of Lingdingyang Bay. Comparison with the red tide drift-diffusion process in the sea area near Shenzhen Airport shows that the red tide near Neilingding Island easily diffused toward surrounding waters.
A new species of Caulophacus (Hexactinellida: Lyssacinosida: Rossellidae) from the western Pacific Ocean, with new insights into the mitochondrial genome characteristics of hexactinellid sponges
Authors: Gong Lin , Yang Mei , Janussen Dorte , Dohrmann Martin , Li Xinzheng
Published: February 2023

A new species, belonging to the rossellid subfamily Lanuginellinae Gray, 1872, is described based on two specimens collected from two different seamounts in the western Pacific Ocean. Species characterization was approached by analyzing the morphological and skeletal features as well as the complete mitochondrial genome. Caulophacus (Caulodiscus) iocasicus sp. nov. is distinguishable from its congeners by its branched external shape and a unique combination of microscleres. It only has hemionychohexasters while other C. (Caulodiscus) species additionally have either onychohexasters or discohexasters. Furthermore, the new species has microhexactins, which have not been reported from the other six species of C. (Caulodiscus). Regarding the mitochondrial genome, the occurrence of the atp8 gene, the absence of tRNA E, the translocation of tRNA D between cob and nad6, and the rearrangement of nad6-nad4 distinguish the new species from other rossellids and even other hexactinellids for which mitogenomic information is available. The herein revised morphological and molecular information of the genus Caulophacus also suggests that the monospecific subgenus C. (Caulophacella) should be removed from Caulophacus and reinstated as a separate genus in the subfamily Lanuginellinae.
Investigation of bulk magneto-resistance crossovers in iron doped zinc-oxide using spectroscopic techniques
Authors: Ali Liaqat , Shah Wiqar H. , Ali Akhtar , Eldin Sayed M. , Al-Jaafary Abdullah A. , Sedky A. , Mazher Javed , Imran Naveed , Sohail Muhammad
Published: February 2023

Pellets of Pure and Fe-doped dilute magnetic semiconducting (DMS) samples are studied for bulk magneto-resistance (BMR) at room temperature and at low-temperatures ∼100K. Raman-, photoluminescence- and X-ray photoelectron-spectroscopic techniques are used to determine chemical and electronic structures of the samples. A broadband intense yellow-green-orange luminescence is observed in Fe-doped ZnO samples and emission red-shifts are investigated. Electrical transport is studied with and without applied magnetic field up to 9T and thermal activation and hopping modes of conduction is discussed in light of nature of Fe substitution in the host lattice. Several decremental- to incremental-BMR crossovers are obtained corresponding to experimental variables of Fe concentration 0.025 ≤ x ≤ 0.1, temperature and applied magnetic field. Several possible modes of magneto-transport are discussed to further elucidate the origin of the as-found BMR crossovers in our samples. Positive BMR in pure- and highly doped (x ≥ 0.1) ZnO is found to originate from F-centers and thermal fluctuations, respectively. However, modestly doped (x ≤ 0.05) ZnO exhibit thermally activated conduction and magnetic poloron mediated negative BMR.
Advances in PET and MRI imaging of tumor hypoxia
Authors: Gouel Pierrick , Decazes Pierre , Vera Pierre , Gardin Isabelle , Thureau Sébastien , Bohn Pierre
Published: February 2023

Tumor hypoxia is a complex and evolving phenomenon both in time and space. Molecular imaging allows to approach these variations, but the tracers used have their own limitations. PET imaging has the disadvantage of low resolution and must take into account molecular biodistribution, but has the advantage of high targeting accuracy. The relationship between the signal in MRI imaging and oxygen is complex but hopefully it would lead to the detection of truly oxygen-depleted tissue. Different ways of imaging hypoxia are discussed in this review, with nuclear medicine tracers such as [18F]-FMISO, [18F]-FAZA, or [64Cu]-ATSM but also with MRI techniques such as perfusion imaging, diffusion MRI or oxygen-enhanced MRI. Hypoxia is a pejorative factor regarding aggressiveness, tumor dissemination and resistance to treatments. Therefore, having accurate tools is particularly important.
Myopic tilted disc: Mechanism, clinical significance, and public health implication
Authors: Chan Poemen P. , Zhang Yuqiao , Pang Chi Pui
Published: February 2023

Myopic tilted disc is a common structural change of myopic eyes. With advancing ocular imaging technology, the associated structural changes of the eye, particularly the optic nerve head, have been extensively studied. These structural changes may increase patients’ susceptibility to axonal damage and the risk of developing serious optic neuropathies including glaucoma. They also lead to diagnostic difficulties of disease suspects and treatment dilemmas of patients, which implicate clinical practice and subsequently the health care system. In the context of the mounting prevalence of myopia worldwide and its implications to irreversible visual impairment and blindness, it is essential to gain a thorough understanding of the structural changes of myopia. Myopic tilted disc has been extensively investigated by different study groups. However, generalizing the knowledge could be difficult because of the variable definitions of myopic tilted disc utilized in these studies and the complexities of the changes. The current review aimed to clarify the concepts and discuss various aspects of myopic tilted disc, including the definitions, association with other myopia-related changes, mechanism of tilted disc development, structural and functional changes, and clinical implications.
Off-season circulation and characterization of enterovirus D68 with respiratory and neurological presentation using whole-genome sequencing
Authors: Cassidy Hayley , Lizarazo-Forero Erley , Schuele Leonard , Van Leer-Buter Coretta , Niesters Hubert G. M.
Published: February 2023

To explore an off-season enterovirus D68 (EV-D68) upsurge in the winter season of 2019/2020, we adapted a whole-genome sequencing approach for Nanopore Sequencing for 20 hospitalized patients with accompanying respiratory or neurological presentation. Applying phylodynamic and evolutionary analysis on Nextstrain and Datamonkey respectively, we report a highly diverse virus with an evolutionary rate of 3.05 × 10−3 substitutions per year (entire EV-D68 genome) and a positive episodic/diversifying selection with persistent yet undetected circulation likely driving evolution. While the predominant B3 subclade was identified in 19 patients, one A2 subclade was identified in an infant presenting with meningitis. Exploring single nucleotide variations using CLC Genomics Server showed high levels of non-synonymous mutations, particularly in the surface proteins, possibly highlighting growing problems with routine Sanger sequencing for typing enteroviruses. Surveillance and molecular approaches to enhance current knowledge of infectious pathogens capable of pandemic potential are paramount to early warning in health care facilities.
Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levels
Authors: Ye Jinhua , Hou Fangpeng , Chen Guanyu , Zhong Tianyu , Xue Junxia , Yu Fangyou , Lai Yi , Yang Yingjie , Liu Dedong , Tian Yuantong , Huang Junyun
Published: February 2023

Objective

The widespread use of antibiotics has inevitably led to the emergence of multidrug-resistant bacterial strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making treatment of this infection a serious challenge. This study aimed to explore new treatment strategies for MRSA infection.

Methods

The structure of Fe3O4 NPs with limited antibacterial activity was optimized, and the Fe2+ ↔ Fe3+ electronic coupling was eliminated by replacing 1/2 Fe2+ with Cu2+. A new type of copper-containing ferrite nanoparticles (hereinafter referred to as Cu@Fe NPs) that fully retained oxidation–reduction activity was synthesized. First, the ultrastructure of Cu@Fe NPs was examined. Then, antibacterial activity was determined by testing the minimum inhibitory concentration (MIC) and safety for use as an antibiotic agent. Next, the mechanisms underlying the antibacterial effects of Cu@Fe NPs were investigated. Finally, mice models of systemic and localized MRSA infections was established for in vivo validation.

Results

It was found that Cu@Fe NPs exhibited excellent antibacterial activity against MRSA with MIC of 1 μg/mL. It effectively inhibited the development of MRSA resistance and disrupted the bacterial biofilms. More importantly, the cell membranes of MRSA exposed to Cu@Fe NPs underwent significant rupture and leakage of the cell contents. Cu@Fe NPs also significantly reduced the iron ions required for bacterial growth and contributed to excessive intracellular accumulation of exogenous reactive oxygen species (ROS). Therefore, these findings may important for its antibacterial effect. Furthermore, Cu@Fe NPs treatment led to a significant reduction in colony forming units within intra-abdominal organs, such as the liver, spleen, kidney, and lung, in mice with systemic MRSA infection, but not for damaged skin in those with localized MRSA infection.

Conclusion

The synthesized nanoparticles has an excellent drug safety profile, confers high resistant to MRSA, and can effectively inhibit the progression of drug resistance. It also has the potential to exert anti-MRSA infection effects systemically in vivo. In addition, our study revealed a unique multifaceted antibacterial mode of Cu@Fe NPs: (1) an increase in cell membrane permeability, (2) depletion of Fe ions in cells, (3) generation of ROS in cells. Overall, Cu@Fe NPs may be potential therapeutic agents for MRSA infections.
Simo decoction curing spleen deficiency constipation was associated with brain-bacteria-gut axis by intestinal mucosal microbiota
Authors: Yi Xin , Zhou Kang , Deng Na , Cai Ying , Peng Xinxin , Tan Zhoujin
Published: February 2023

Background

Simo decoction (SMD) is a traditional prescription for treating gastrointestinal diseases. More and more evidences prove that SMD can treat constipation by regulating intestinal microbiota and related oxidative stress indicators, but the specific mechanism is still unclear.

Methods

A network pharmacological analysis was used to predict the medicinal substances and potential targets of SMD to alleviate constipation. Then, 15 male mice were randomly divided into normal group (MN group), natural recovery group (MR group), and SMD treatment group (MT group). Constipation model mice were constructed by gavage of Folium sennae decoction and control of diet and drinking water, and SMD was used for intervention after successful modeling. The levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), superoxide dismutase (SOD), malondialdehyde (MDA), and fecal microbial activities were measured, and the intestinal mucosal microbiota was sequenced.

Result

Network pharmacology analysis showed that a total of 24 potential active components were obtained from SMD, and 226 target proteins were obtained after conversion. Meanwhile, we obtained 1,273 and 424 disease-related targets in the GeneCards database and the DisGeNET database, respectively. After combination and deduplication, the disease targets shared 101 targets with the potential active components of SMD. When the mice were intervened with SMD, the 5-HT, VIP, MDA, SOD content, and microbial activity in MT group were close to MN group, and Chao 1 and ACE in MT group were significantly higher than that in MR group. In the Linear discriminant analysis Effect Size (LEfSe) analysis, the abundance of beneficial bacteria such as Bacteroides, Faecalibacterium, Alistipes, Subdoligranulum, Lactiplantibacillus, and Phascolarctobacterium in MT group increased. At the same time, there were some associations between microbiota and brain-gut peptides and oxidative stress indicators.

Conclusion

SMD can promote intestinal health and relieve constipation through brain-bacteria-gut axis associating with intestinal mucosal microbiota and alleviate oxidative stress.
SARS-CoV-2 raw wastewater surveillance from student residences on an urban university campus
Authors: Ash K. T. , Li Y. , Alamilla I. , Joyner D. C. , Williams D. E. , McKay P. J. , Green B. M. , Iler C. , DeBlander S. E. , North C. M. , Kara-Murdoch F. , Swift C. M. , Hazen T. C.
Published: February 2023

The COVID-19 pandemic brought about an urgent need to monitor the community prevalence of infection and detect the presence of SARS-CoV-2. Testing individual people is the most reliable method to measure the spread of the virus in any given community, but it is also the most expensive and time-consuming. Wastewater-based epidemiology (WBE) has been used since the 1960s when scientists implemented monitoring to measure the effectiveness of the Polio vaccine. Since then, WBE has been used to monitor populations for various pathogens, drugs, and pollutants. In August 2020, the University of Tennessee-Knoxville implemented a SARS-CoV-2 surveillance program that began with raw wastewater surveillance of the student residence buildings on campus, the results of which were shared with another lab group on campus that oversaw the pooled saliva testing of students. Sample collection began at 8 am, and the final RT-qPCR results were obtained by midnight. The previous day’s results were presented to the campus administrators and the Student Health Center at 8 am the following morning. The buildings surveyed included all campus dormitories, fraternities, and sororities, 46 buildings in all representing an on-campus community of over 8,000 students. The WBE surveillance relied upon early morning “grab” samples and 24-h composite sampling. Because we only had three Hach AS950 Portable Peristaltic Sampler units, we reserved 24-h composite sampling for the dormitories with the highest population of students. Samples were pasteurized, and heavy sediment was centrifuged and filtered out, followed by a virus concentration step before RNA extraction. Each sample was tested by RT-qPCR for the presence of SARS-CoV-2, using the CDC primers for N Capsid targets N1 and N3. The subsequent pooled saliva tests from sections of each building allowed lower costs and minimized the total number of individual verification tests that needed to be analyzed by the Student Health Center. Our WBE results matched the trend of the on-campus cases reported by the student health center. The highest concentration of genomic copies detected in one sample was 5.06 × 107 copies/L. Raw wastewater-based epidemiology is an efficient, economical, fast, and non-invasive method to monitor a large community for a single pathogen or multiple pathogen targets.
Nanoparticle surface stabilizing agents influence antibacterial action
Authors: Ameh Thelma , Zarzosa Kusy , Dickinson Jake , Braswell W. Evan , Sayes Christie M.
Published: February 2023

The antibacterial properties of nanoparticles are of particular interest because of their potential to serve as an alternative therapy to combat antimicrobial resistance. Metal nanoparticles such as silver and copper nanoparticles have been investigated for their antibacterial properties. Silver and copper nanoparticles were synthesized with the surface stabilizing agents cetyltrimethylammonium bromide (CTAB, to confer a positive surface charge) and polyvinyl pyrrolidone (PVP, to confer a neutral surface charge). Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and viable plate count assays were used to determine effective doses of silver and copper nanoparticles treatment against Escherichia coli, Staphylococcus aureus and Sphingobacterium multivorum. Results show that CTAB stabilized silver and copper nanoparticles were more effective antibacterial agents than PVP stabilized metal nanoparticles, with MIC values in a range of 0.003 μM to 0.25 μM for CTAB stabilized metal nanoparticles and 0.25 μM to 2 μM for PVP stabilized metal nanoparticles. The recorded MIC and MBC values of the surface stabilized metal nanoparticles show that they can serve as effective antibacterial agents at low doses.
Bacillus subtilis vector based oral rabies vaccines induced potent immune response and protective efficacy in mice
Authors: Zhang Ying , Mo Ruo , Sun Sheng , Cui Zhanding , Liang Bo , Li Entao , Wang Tiecheng , Feng Ye , Yang Songtao , Yan Feihu , Zhao Yongkun , Xia Xianzhu
Published: February 2023

Introduction

Rabies is a worldwide epidemic that poses a serious threat to global public health. At present, rabies in domestic dogs, cats, and some pets can be effectively prevented and controlled by intramuscular injection of rabies vaccine. But for some inaccessible animals, especially stray dogs, and wild animals, it is difficult to prevent with intramuscular injection. Therefore, it is necessary to develop a safe and effective oral rabies vaccine.

Methods

We constructed recombinant Bacillus subtilis (B. subtilis) expressing two different strains of rabies virus G protein, named CotG-E-G and CotG-C-G, immunogenicity was studied in mice.

Results

The results showed that CotG-E-G and CotG-C-G could significantly increase the specific SIgA titers in feces, serum IgG titers, and neutralizing antibodies. ELISpot experiments showed that CotG-E-G and CotG-C-G could also induce Th1 and Th2 to mediate the secretion of immune-related IFN-γ and IL-4. Collectively, our results suggested that recombinant B. subtilis CotG-E-G and CotG-C-G have excellent immunogenicity and are expected to be novel oral vaccine candidates for the prevention and control of wild animal rabies.
Genome, transcriptome, and metabolome analyses provide new insights into the resource development in an edible fungus Dictyophora indusiata
Authors: Duan Mingzheng , Long Shengfeng , Wu Xiaojian , Feng Bin , Qin Sunqian , Li Yijie , Li Xiang , Li Changning , Zhao Chenggang , Wang Lingqiang , Yan Yong , Wu Jianming , Zhao Falin , Chen Zhendong , Wang Zeping
Published: February 2023

Dictyophora indusiata(Vent. Ex Pers.) Fisch. (DI) is an edible and medicinal fungus widely used in East Asian countries. However, during DI cultivation, the formation of fruiting bodies cannot be regulated, which leads to yield and quality losses. The present study performed a combined genome, transcriptome, and metabolome analysis of DI. Using Nanopore and Illumina sequencing approaches, we created the DI reference genome, which was 67.32 Mb long with 323 contigs. We identified 19,909 coding genes on this genome, of which 46 gene clusters were related to terpenoid synthesis. Subsequent transcriptome sequencing using five DI tissues (cap, indusia, mycelia, stipe, and volva) showed high expression levels of genes in the cap, indicating the tissue’s importance in regulating the fruiting body formation. Meanwhile, the metabolome analysis identified 728 metabolites from the five tissues. Mycelium was rich in choline, while volva was rich in dendronobilin; stipe had monosaccharides as the primary component, and the cap was the main source of indole acetic acid (IAA) synthesis. We confirmed the importance of tryptophan metabolism for DI fruiting body differentiation based on KEGG pathway analysis. Finally, the combined multiomics analysis identified three new genes related to IAA synthesis of the tryptophan metabolic pathway in the cap, which may regulate DI fruiting body synthesis and improve DI quality. Thus, the study’s findings expand our understanding of resource development and the molecular mechanisms underlying DI development and differentiation. However, the current genome is still a rough draft that needs to be strengthened.
Comparative genomics of Bacillus cereus sensu lato spp. biocontrol strains in correlation to in-vitro phenotypes and plant pathogen antagonistic capacity
Authors: Moshe Maya , Gupta Chhedi Lal , Jain Rakeshkumar Manojkumar , Sela Noa , Minz Dror , Banin Ehud , Frenkel Omer , Cytryn Eddie
Published: February 2023

Bacillus cereus sensu lato (Bcsl) strains are widely explored due to their capacity to antagonize a broad range of plant pathogens. These include B. cereus sp. UW85, whose antagonistic capacity is attributed to the secondary metabolite Zwittermicin A (ZwA). We recently isolated four soil and root-associated Bcsl strains (MO2, S−10, S-25, LSTW-24) that displayed different growth profiles and in-vitro antagonistic effects against three soilborne plant pathogens models: Pythium aphanidermatum (oomycete) Rhizoctonia solani (basidiomycete), and Fusarium oxysporum (ascomycete). To identify genetic mechanisms potentially responsible for the differences in growth and antagonistic phenotypes of these Bcsl strains, we sequenced and compared their genomes, and that of strain UW85 using a hybrid sequencing pipeline. Despite similarities, specific Bcsl strains had unique secondary metabolite and chitinase-encoding genes that could potentially explain observed differences in in-vitro chitinolytic potential and anti-fungal activity. Strains UW85, S-10 and S-25 contained a (~500 Kbp) mega-plasmid that harbored the ZwA biosynthetic gene cluster. The UW85 mega-plasmid contained more ABC transporters than the other two strains, whereas the S-25 mega-plasmid carried a unique cluster containing cellulose and chitin degrading genes. Collectively, comparative genomics revealed several mechanisms that can potentially explain differences in in-vitro antagonism of Bcsl strains toward fungal plant pathogens.
Conserved gene signatures shared among MAPT mutations reveal defects in calcium signaling
Authors: Minaya Miguel A. , Mahali Sidhartha , Iyer Abhirami K. , Eteleeb Abdallah M. , Martinez Rita , Huang Guangming , Budde John , Temple Sally , Nana Alissa L. , Seeley William W. , Spina Salvatore , Grinberg Lea T. , Harari Oscar , Karch Celeste M.
Published: February 2023

Introduction: More than 50 mutations in the MAPT gene result in heterogeneous forms of frontotemporal lobar dementia with tau inclusions (FTLD-Tau). However, early pathogenic events that lead to disease and the degree to which they are common across MAPT mutations remain poorly understood. The goal of this study is to determine whether there is a common molecular signature of FTLD-Tau.

Methods: We analyzed genes differentially expressed in induced pluripotent stem cell–derived neurons (iPSC-neurons) that represent the three major categories of MAPT mutations: splicing (IVS10 + 16), exon 10 (p.P301L), and C-terminal (p.R406W) compared with isogenic controls. The genes that were commonly differentially expressed in MAPT IVS10 + 16, p.P301L, and p.R406W neurons were enriched in trans-synaptic signaling, neuronal processes, and lysosomal function. Many of these pathways are sensitive to disruptions in calcium homeostasis. One gene, CALB1, was significantly reduced across the three MAPT mutant iPSC-neurons and in a mouse model of tau accumulation. We observed a significant reduction in calcium levels in MAPT mutant neurons compared with isogenic controls, pointing to a functional consequence of this disrupted gene expression. Finally, a subset of genes commonly differentially expressed across MAPT mutations were also dysregulated in brains from MAPT mutation carriers and to a lesser extent in brains from sporadic Alzheimer disease and progressive supranuclear palsy, suggesting that molecular signatures relevant to genetic and sporadic forms of tauopathy are captured in a dish. The results from this study demonstrate that iPSC-neurons capture molecular processes that occur in human brains and can be used to pinpoint common molecular pathways involving synaptic and lysosomal function and neuronal development, which may be regulated by disruptions in calcium homeostasis.
Amyloid oligomers as on-pathway precursors or off-pathway competitors of fibrils
Authors: Muschol Martin , Hoyer Wolfgang
Published: February 2023

Amyloid Diseases involve the growth of disease specific proteins into amyloid fibrils and their deposition in protein plaques. Amyloid fibril formation is typically preceded by oligomeric intermediates. Despite significant efforts, the specific role fibrils or oligomers play in the etiology of any given amyloid disease remains controversial. In neurodegenerative disease, though, amyloid oligomers are widely considered critical contributors to disease symptoms. Aside from oligomers as inevitable on-pathway precursors of fibril formation, there is significant evidence for off-pathway oligomer formation competing with fibril growth. The distinct mechanisms and pathways of oligomer formation directly affect our understanding under which conditions oligomers emerge in vivo, and whether their formation is directly coupled to, or distinct from, amyloid fibril formation. In this review, we will discuss the basic energy landscapes underlying the formation of on-pathway vs. off-pathway oligomers, their relation to the related amyloid aggregation kinetics, and their resulting implications for disease etiology. We will review evidence on how differences in the local environment of amyloid assembly can dramatically shift the relative preponderance of oligomers vs. fibrils. Finally, we will comment on gaps in our knowledge of oligomer assembly, of their structure, and on how to assess their relevance to disease etiology.
Coupled binding and folding of disordered SPIN N-terminal region in myeloperoxidase inhibition
Authors: Zhang Yumeng , Liu Xiaorong , Chen Jianhan
Published: February 2023

Gram-positive pathogenic bacteria Staphylococcus express and secret staphylococcal peroxidase inhibitor (SPIN) proteins to help evade neutrophil-mediated immunity by inhibiting the activity of the main oxidative-defense player myeloperoxidase (MPO) enzyme. SPIN contains a structured 3-helix bundle C-terminal domain, which can specifically bind to MPO with high affinity, and an intrinsically disordered N-terminal domain (NTD), which folds into a structured β-hairpin and inserts itself into the active site of MPO for inhibition. Mechanistic insights of the coupled folding and binding process are needed in order to better understand how residual structures and/or conformational flexibility of NTD contribute to the different strengths of inhibition of SPIN homologs. In this work, we applied atomistic molecular dynamics simulations on two SPIN homologs, from S. aureus and S. delphini, respectively, which share high sequence identity and similarity, to explore the possible mechanistic basis for their different inhibition efficacies on human MPO. Direct simulations of the unfolding and unbinding processes at 450 K reveal that these two SPIN/MPO complexes systems follow surprisingly different mechanisms of coupled binding and folding. While coupled binding and folding of SPIN-aureus NTD is highly cooperative, SPIN-delphini NTD appears to mainly utilize a conformational selection-like mechanism. These observations are in contrast to an overwhelming prevalence of induced folding-like mechanisms for intrinsically disordered proteins that fold into helical structures upon binding. Further simulations of unbound SPIN NTDs at room temperature reveal that SPIN-delphini NTD has a much stronger propensity of forming β-hairpin like structures, consistent with its preference to fold and then bind. These may help explain why the inhibition strength is not well correlated with binding affinity for different SPIN homologs. Altogether, our work establishes the relationship between the residual conformational stability of SPIN-NTD and their inhibitory function, which can help us develop new strategies towards treating Staphylococcal infections.
The impact of iron deposition on the fear circuit of the brain in patients with Parkinson’s disease and anxiety
Authors: Chen Kaidong , Zhang Li , Mao Haixia , Chen Kefei , Shi Yachen , Meng Xiangpan , Wang Feng , Hu Xiaoyun , Fang Xiangming
Published: February 2023

Objective

Anxiety is one of the most common psychiatric symptoms of Parkinson’s disease (PD), and brain iron deposition is considered to be one of the pathological mechanisms of PD. The objective of this study was to explore alterations in brain iron deposition in PD patients with anxiety compared to PD patients without anxiety, especially in the fear circuit.

Methods

Sixteen PD patients with anxiety, 23 PD patients without anxiety, and 26 healthy elderly controls were enrolled prospectively. All subjects underwent neuropsychological assessments and brain magnetic resonance imaging (MRI) examinations. Voxel-based morphometry (VBM) was used to study morphological brain differences between the groups. Quantitative susceptibility mapping (QSM), an MRI technique capable of quantifying susceptibility changes in brain tissue, was used to compare susceptibility changes in the whole brain among the three groups. The correlations between brain susceptibility changes and anxiety scores quantified using the Hamilton Anxiety Rating Scale (HAMA) were compared and analyzed.

Results

PD patients with anxiety had a longer duration of PD and higher HAMA scores than PD patients without anxiety. No morphological brain differences were observed between the groups. In contrast, voxel-based and ROI-based QSM analyses showed that PD patients with anxiety had significantly increased QSM values in the medial prefrontal cortex, anterior cingulate cortex, hippocampus, precuneus, and angular cortex. Furthermore, the QSM values of some of these brain regions were positively correlated with the HAMA scores (medial prefrontal cortex: r = 0.255, p = 0.04; anterior cingulate cortex: r = 0.381, p < 0.01; hippocampus: r = 0.496, p < 0.01).

Conclusion

Our findings support the idea that anxiety in PD is associated with iron burden in the brain fear circuit, providing a possible new approach to explaining the potential neural mechanism of anxiety in PD.
The knowledge domain of cognitive neuroscience of aging: A Scientometric and bibliometric analysis
Authors: Jiang Jiaxing , Fan Lin , Liu Jia
Published: February 2023

Cognitive neuroscience of aging (CNA) is a relatively young field compared with other branches of cognitive aging (CA). From the beginning of this century, scholars in CNA have contributed many valuable research to explain the cognitive ability decline in aging brains in terms of functional changes, neuromechanism, and neurodegenerative diseases. However, very few studies have systematically reviewed the research in the domain of CAN, with regard to its primary research topics, theories, findings, and future development. Therefore, this study used CiteSpace to conduct a bibliometric analysis of 1,462 published articles in CNA from Web of Science (WOS) and investigated the highly influential and potential research topics and theories of CNA, as well as important brain areas involved in CAN during 2000–2021. The results revealed that: (1) the research topics of “memory” and “attention” have been the focus of most studies, progressing into a fMRI-oriented stage; (2) the scaffolding theory and hemispheric asymmetry reduction in older adults model hold a key status in CNA, characterizing aging as a dynamic process and presenting compensatory relationships between different brain areas; and (3) age-related changes always occur in temporal (especially the hippocampus), parietal, and frontal lobes and the cognitive declines establish the compensation relationship between the anterior and posterior regions.
Label-free, fast, 2-photon volume imaging of the organization of neurons and glia in the enteric nervous system
Authors: Hazart Doriane , Delhomme Brigitte , Oheim Martin , Ricard Clément
Published: February 2023

The enteric nervous system (ENS), sometimes referred to as a “second brain” is a quasi-autonomous nervous system, made up of interconnected plexuses organized in a mesh-like network lining the gastrointestinal tract. Originally described as an actor in the regulation of digestion, bowel contraction, and intestinal secretion, the implications of the ENS in various central neuropathologies has recently been demonstrated. However, with a few exceptions, the morphology and pathologic alterations of the ENS have mostly been studied on thin sections of the intestinal wall or, alternatively, in dissected explants. Precious information on the three-dimensional (3-D) architecture and connectivity is hence lost. Here, we propose the fast, label-free 3-D imaging of the ENS, based on intrinsic signals. We used a custom, fast tissue-clearing protocol based on a high refractive-index aqueous solution to increase the imaging depth and allow us the detection of faint signals and we characterized the autofluorescence (AF) from the various cellular and sub-cellular components of the ENS. Validation by immunofluorescence and spectral recordings complete this groundwork. Then, we demonstrate the rapid acquisition of detailed 3-D image stacks from unlabeled mouse ileum and colon, across the whole intestinal wall and including both the myenteric and submucosal enteric nervous plexuses using a new spinning-disk two-photon (2P) microscope. The combination of fast clearing (less than 15 min for 73% transparency), AF detection and rapid volume imaging [less than 1 min for the acquisition of a z-stack of 100 planes (150*150 μm) at sub-300-nm spatial resolution] opens up the possibility for new applications in fundamental and clinical research.
Neurofeedback-dependent influence of the ventral striatum using a working memory paradigm targeting the dorsolateral prefrontal cortex
Authors: Pereira Daniela Jardim , Sayal Alexandre , Pereira João , Morais Sofia , Macedo António , Direito Bruno , Castelo-Branco Miguel
Published: February 2023

Executive functions and motivation have been established as key aspects for neurofeedback success. However, task-specific influence of cognitive strategies is scarcely explored. In this study, we test the ability to modulate the dorsolateral prefrontal cortex, a strong candidate for clinical application of neurofeedback in several disorders with dysexecutive syndrome, and investigate how feedback contributes to better performance in a single session. Participants of both neurofeedback (n = 17) and sham-control (n = 10) groups were able to modulate DLPFC in most runs (with or without feedback) while performing a working memory imagery task. However, activity in the target area was higher and more sustained in the active group when receiving feedback. Furthermore, we found increased activity in the nucleus accumbens in the active group, compared with a predominantly negative response along the block in participants receiving sham feedback. Moreover, they acknowledged the non-contingency between imagery and feedback, reflecting the impact on motivation. This study reinforces DLPFC as a robust target for neurofeedback clinical implementations and enhances the critical influence of the ventral striatum, both poised to achieve success in the self-regulation of brain activity.