bluuebunny/crossref_metadata_2025 huggingface dataset:
RGMa Participates in the Blood–Brain Barrier Dysfunction Through BMP/BMPR/YAP Signaling in Multiple Sclerosis
Authors: Zhang Lei , Tang Shi , Ma Yue , Liu Junhang , Monnier Philippe , Li Hang , Zhang Rongrong , Yu Gang , Zhang Mengjie , Li Yongmei , Feng Jinzhou , Qin Xinyue
Published: May 2022

The infiltration of inflammatory cells into the central nervous system (CNS) through the dysfunctional blood–brain barrier (BBB) was critical in the early stages of MS. However, the mechanisms underlying BBB dysfunction remain unknown. Repulsive guidance molecule-a (RGMa) is involved in the pathogenesis of multiple sclerosis (MS), but its role needs to be further explored. This study aimed to evaluate whether RMGa regulates BBB permeability in endothelial cells and MS, and if so, what mechanism may be involved. We created an experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice and a human brain microvascular endothelial cell (HBMEC) culture. The permeability of the BBB is measured in response to various interventions. Our results showed that RGMa is expressed in the endothelial cells in HBMECs and EAE mice. RGMa and its signaling counterpart, bone morphogenetic protein 2 (BMP2)/bone morphogenetic protein receptor type II (BMPRII), were gradually increased as the disease progressed. Moreover, as EAE progressed and the BBB was disrupted, the downstream effector, yes-associated protein (YAP), as well as the tight junctional proteins zonula occludens 1 (ZO-1) and claudin-5, decreased significantly. The permeability assay revealed that lentivirus-induced RGMa overexpression in HBMECs caused a significant breakdown of the BBB, whereas RGMa knockdown significantly strengthens the integrity of the BBB. Furthermore, specifically activating BMPR II or inhibiting YAP based on RGMa knockdown results in a significant decrease of ZO-1 and claudin-5 in vitro. On the contrary, inhibition of BMPR II or activation of YAP after upregulating RGMa prevents the downregulation of ZO-1 and claudin-5 in HBMECs. In addition, serum-soluble RGMa (sRGMa) levels were significantly higher in MS patients, particularly in MS patients with Gd+ lesions, indicating that the BBB has been disrupted. In conclusion, this study shows that RGMa causes BBB dysfunction in endothelial cells via BMP2/BMPR II/YAP, resulting in BBB integrity disruption in MS and that it could be a novel therapeutic target for BBB permeability in MS.
Spatial Resolution of Mycobacterium tuberculosis Bacteria and Their Surrounding Immune Environments Based on Selected Key Transcripts in Mouse Lungs
Authors: Magoulopoulou Anastasia , Qian Xiaoyan , Pediatama Setiabudiawan Todia , Marco Salas Sergio , Yokota Chika , Rottenberg Martin E. , Nilsson Mats , Carow Berit
Published: May 2022

Mycobacterium tuberculosis (Mtb) bacilli are the causative agent of tuberculosis (TB), a major killer of mankind. Although it is widely accepted that local interactions between Mtb and the immune system in the tuberculous granuloma determine whether the outcome of infection is controlled or disseminated, these have been poorly studied due to methodological constraints. We have recently used a spatial transcriptomic technique, in situ sequencing (ISS), to define the spatial distribution of immune transcripts in TB mouse lungs. To further contribute to the understanding of the immune microenvironments of Mtb and their local diversity, we here present two complementary automated bacteria-guided analysis pipelines. These position 33 ISS-identified immune transcripts in relation to single bacteria and bacteria clusters. The analysis was applied on new ISS data from lung sections of Mtb-infected C57BL/6 and C3HeB/FeJ mice. In lungs from C57BL/6 mice early and late post infection, transcripts that define inflammatory macrophages were enriched at subcellular distances to bacteria, indicating the activation of infected macrophages. In contrast, expression patterns associated to antigen presentation were enriched in non-infected cells at 12 weeks post infection. T-cell transcripts were evenly distributed in the tissue. In Mtb-infected C3HeB/FeJ mice, transcripts characterizing activated macrophages localized in apposition to small bacteria clusters, but not in organized granulomas. Despite differences in the susceptibility to Mtb, the transcript patterns found around small bacteria clusters of C3HeB/FeJ and C57BL/6 mice were similar. Altogether, the presented tools allow us to characterize in depth the immune cell populations and their activation that interact with Mtb in the infected lung.
Progress in Xenotransplantation: Immunologic Barriers, Advances in Gene Editing, and Successful Tolerance Induction Strategies in Pig-To-Primate Transplantation
Authors: Eisenson Daniel L. , Hisadome Yu , Yamada Kazuhiko
Published: May 2022

Organ transplantation is the most effective treatment for end stage organ failure, but there are not enough organs to meet burgeoning demand. One potential solution to this organ shortage is xenotransplantation using pig tissues. Decades of progress in xenotransplantation, accelerated by the development of rapid genome editing tools, particularly the advent of CRISPR-Cas9 gene editing technologies, have enabled remarkable advances in kidney and heart xenotransplantation in pig-to-nonhuman primates. These breakthroughs in large animal preclinical models laid the foundation for three recent pig-to-human transplants by three different groups: two kidney xenografts in brain dead recipients deemed ineligible for transplant, and one heart xenograft in the first clinical grade study of pig-to-human transplantation. However, despite tremendous progress, recent data including the first clinical case suggest that gene-modification alone will not overcome all xenogeneic immunologic barriers, and thus an active and innovative immunologic strategy is required for successful xenotransplantation. This review highlights xenogeneic immunologic barriers, advances in gene editing, and tolerance-inducing strategies in pig-to-human xenotransplantation.
Governing Open Ocean and Fish Carbon: Perspectives and Opportunities
Authors: Oostdijk Maartje , Elsler Laura G. , Ramírez-Monsalve Paulina , Orach Kirill , Wisz Mary S.
Published: May 2022

Marine life plays a vital role in the ocean’s biological pump by sequestering and mediating fluxes of carbon to the deep sea and sea floor. The roles that fish and other marine vertebrates play in the biological pump are increasingly attracting scientific and policy attention. In this paper, we investigated the interest in and possibilities for the international governance of open ocean and fish carbon ecosystem services. We used semi-structured interviews with representatives from environmental non-governmental organisations (ENGOs), policy makers, and policy experts, along with an exploratory review of grey and peer-reviewed literature to: 1) trace the pathway of important milestones, key actors, and their strategies to influence governance of ocean carbon, and, 2) investigate which frameworks might be used to govern open ocean and fish carbon. Strategies of key actors to direct attention to open ocean and fish carbon included collaborating with scientists, organising side events at climate and biodiversity negotiations and seminars to engage policy makers, as well as educational campaigns directed to the public and policy makers about the co-benefits of open ocean and fish carbon. While we found a strong focus of ENGO activities related to the UN Framework Convention on Climate Change, we also found strong opposition against active governance of open ocean and fish carbon by key Intergovernmental actors in this forum. Opposition stems from a lack of scientific information on how long open ocean and fish carbon is stored, difficulties in attributing carbon flows with individual countries mitigation actions, and fewer perceived co-benefits (e.g. coastal protection in the case of coastal blue carbon) for coastal communities. More viable routes for the future governance of open ocean and fish carbon may lie in international fisheries management and in current negotiations of a treaty for biodiversity conservation in the high seas.
Data Quality Influences the Predicted Distribution and Habitat of Four Southern-Hemisphere Albatross Species
Authors: Goetz Kimberly T. , Stephenson Fabrice , Hoskins Andrew , Bindoff Aidan D. , Orben Rachael A. , Sagar Paul M. , Torres Leigh G. , Kroeger Caitlin E. , Sztukowski Lisa A. , Phillips Richard A. , Votier Stephen C. , Bearhop Stuart , Taylor Graeme A. , Thompson David R.
Published: May 2022

Few studies have assessed the influence of data quality on the predicted probability of occurrence and preferred habitat of marine predators. We compared results from four species distribution models (SDMs) for four southern-hemisphere albatross species, Buller’s (Thalassarche bulleri), Campbell (T. impavida), grey-headed (T. chrysostoma), and white-capped (T. steadi), based on datasets of differing quality, ranging from no location data to twice-daily locations of individual birds collected by geolocation devices. Two relative environmental suitability (RES) models were fit using minimum and maximum preferred and absolute values for each environmental variable based on (1) monthly 50% kernel density contours and background environmental data, and (2) primary literature or expert opinion. Additionally, two boosted regression tree (BRT) models were fit using (1) opportunistic sightings data, and (2) geolocation data from bird-borne electronic tags. Using model-specific threshold values, habitat was quantified for each species and model. Model variables included distance from land, bathymetry, sea surface temperature, and chlorophyll-a concentration. Results from both RES models and the BRT model fit with opportunistic sightings were compared to those from the BRT model fit using geolocation data to assess the influence of data quality on predicted occupancy and habitat. For all species, BRT models outperformed RES models. BRT models offer a predictive advantage over RES models by being able to identify relevant variables, incorporate environmental interactions, and provide spatially explicit estimates of model uncertainty. RES models resulted in larger, less refined areas of predicted habitat for all species. Our study highlights the importance of data quality in predicting the distribution and habitat of albatrosses and emphasises the need to consider the pros and cons associated with different levels of data quality when using SDMs to inform management decisions. Furthermore, we examine the overlap in preferred habitat predicted by each SDM with fishing effort. We discuss the influence of data quality on predicting the wide-scale distributions of pelagic seabirds and how these impacts could result in different protection measures.
Comparative Analysis of Pseudo-nitzschia Chloroplast Genomes Revealed Extensive Inverted Region Variation and Pseudo-nitzschia Speciation
Authors: He Ziyan , Chen Yang , Wang Yichao , Liu Kuiyan , Xu Qing , Li Yang , Chen Nansheng
Published: May 2022

Pseudo-nitzschia is a species-rich genus where many species can induce harmful algae blooms (HABs) associated with the toxin domoic acid (DA) production. Despite the importance of Pseudo-nitzschia species to coastal environments, their genomic information is rather limited, hindering research on biodiversity and evolutionary analysis. In this study, we report full-length chloroplast genomes (cpDNAs) of nine Pseudo‐nitzschia, among which cpDNAs of eight Pseudo-nitzschia species were reported for the first time. The sizes of these Pseudo-nitzschia cpDNAs, which showed typical quadripartite structures, varied substantially, ranging from 116,546 bp to 158,840 bp in size. Comparative analysis revealed the loss of photosynthesis-related gene psaE in cpDNAs of all Pseudo-nitzschia species except that of P. americana, and the selective loss of rpl36 in P. hainanensis. Phylogenetic analysis showed that all Pseudo-nitzschia strains were grouped into two clades, with clade 1 containing cpDNAs of P. multiseries, P. pungens, P. multistriata, and P. americana, and clade 2 containing cpDNAs of P. hainanensis, P. cuspidata, Pseudo-nitzschia sp. CNS00097, P. delicatissima, and P. micropora. The small size of the P. americana cpDNA was primarily due to its shortened inverted repeat (IR) regions. While psaA and psaB were found in the IR regions of cpDNAs of other eight species, these two genes were found outside of the IR regions of P. americana cpDNA. In contrast, P. hainanensis had the largest size because of expansion of IR regions with each IR region containing 15 protein-coding genes (PCGs). Eleven genetic regions of these Pseudo-nitzschia cpDNAs exhibited high nucleotide diversity (Pi) values, suggesting that these regions may be used as molecular markers for distinguishing different Pseudo-nitzschia species with high resolution and high specificity. Phylogenetic analysis of the divergence of nine Pseudo-nitzschia species indicated that these species appeared at approximately 41 Mya. This study provides critical cpDNA resources for future research on the biodiversity and speciation of Pseudo-nitzschia species.
Protistan Communities Within the Galápagos Archipelago With an Emphasis on Micrograzers
Authors: Jang Se Hyeon , Lim Prisca , Torano Olivia , Neave Erika F. , Seim Harvey , Marchetti Adrian
Published: May 2022

The Galápagos Archipelago is a globally significant biodiversity hotspot. However, compared to the relatively well-known megafauna, the distribution and ecological significance of marine protists in this system are poorly understood. To gain an understanding of the protistan assemblages across trophic modes, an intensive oceanographic survey was conducted in the Galápagos Marine Reserve (GMR) in October of 2018. The Equatorial Undercurrent (EUC)-influenced region had higher chlorophyll-a (Chl-a) concentrations than those of the eastern regions of the archipelago, along with higher abundances of protistan grazers. Specifically, proportions of autotrophic and potentially mixotrophic dinoflagellates were higher in the EUC, whereas in the eastern regions, heterotrophic dinoflagellates and chlorophytes dominated. Taxonomic composition and biochemical indicators suggested proportions of micrograzers and their associated heterotrophic biomass was higher in the oligotrophic, low Chl-a regions in the east. We also report observations from a dinoflagellate bloom in the western archipelago, which was heavily influenced by upwelling of the EUC. The red tide-forming dinoflagellate Scrippsiella lachrymosa was highly detected through light microscopy and DNA amplicon sequencing. In addition, the heterotrophic dinoflagellate Polykrikos kofoidii was detected and, based on cell densities observed in this study and grazing rates obtained from the literature, estimated to potentially graze up to 62% of S. lachrymosa bloom population. Our findings thus provide new insights into the composition of micrograzers and their potential roles in structuring protistan communities in the Galápagos Archipelago.
Shear Instability and Turbulent Mixing in the Stratified Shear Flow Behind a Topographic Ridge at High Reynolds Number
Authors: Chen Jia-Lin , Yu Xiao , Chang Ming-Huei , Jan Sen , Yang Yiing Jang , Lien Ren-Chieh
Published: May 2022

Observations on the lee of a topographic ridge show that the turbulence kinetic energy (TKE) dissipation rate due to shear instabilities is three orders of magnitude higher than the typical value in the open ocean. Laboratory-scale studies at low Reynolds number suggest that high turbulent dissipation occurs primarily within the core region of shear instabilities. However, field-scale studies indicate that high turbulence is mainly populated along the braids of shear instabilities. In this study, a high-resolution, resolving the Ozmidov-scale, non-hydrostatic model with Large Eddy Simulation (LES) turbulent closure is applied to investigate dominant mechanisms that control the spatial and temporal scales of shear instabilities and resulting mixing in stratified shear flow at high Reynolds number. The simulated density variance dissipation rate is elevated in the cusp-like bands of shear instabilities with a specific period, consistent with the acoustic backscatter taken by shipboard echo sounder. The vertical length scale of each cusp-like band is nearly half of the vertical length scale of the internal lee wave. However, it is consistent with instabilities originating from a shear layer based on linear stability theory. The model results indicate that the length scale and/or the period of shear instabilities are the key parameters to the mixing enhancement that increases with lateral Froude number FrL, i.e. stronger shear and/or steeper ridge.
How the Skate Embryo Develops: A Fine Developmental Timeline of Kong Skate Okamejei kenojei (Müller & Henle, 1841)
Authors: Guang Gao , Zhizhong Xiao , Yuting Ma , Xiao Chen , Yongshuang Xiao , Jun Li
Published: May 2022

Cartilaginous fishes, as an important group of jawed vertebrates, hold great promise for improving our understanding of vertebrate evolution. Previous studies have established a good staging scheme for shark embryos. However, to date, little attention has been paid to the development of skate embryos. In this study, we established a fine developmental timeline for the Kong skate. We hatched eggs of the Kong skate (Okamejei kenojei) at fixed temperatures (16.5°C ± 0.5°C) while observing three samples every day and recorded the complete embryonic development. The embryo weight and development time were found to have a quadratic relationship. The weight-at-day curve was fitted by y = 0.0005x2 - 0.0109x + 0.0882 (R² = 0.9406). In addition, complete embryonic development from gastrula to skate larvae took 92 ± 5 days. Here, we divided the entire development process into 39 stages. This shows that the jaw of O. kenojei is developed from the first pair of pharyngeal arches, and its body disc is formed by the fusion of the pectoral fin and head. The eyespots began to form from stage 36 and then became thicker and bigger until the young skate broke out of the egg. Notably, we found that males and females develop differently from stage 31; the end of the male pelvic fins expands inward, which develop into copulatory organ-claspers, whereas in the females, they do not expand. To the best of our knowledge, this is the first study to record the embryonic development of eyes, body discs, eyespots, and other organs of O. kenojei in detail. We hope that our work will provide valuable information for researchers to identify specific time points for developing skate embryos.
A Scientific Synthesis of Marine Protected Areas in the United States: Status and Recommendations
Authors: Sullivan-Stack Jenna , Aburto-Oropeza Octavio , Brooks Cassandra M. , Cabral Reniel B. , Caselle Jennifer E. , Chan Francis , Duffy J. Emmett , Dunn Daniel C. , Friedlander Alan M. , Fulton-Bennett Heather K. , Gaines Steven D. , Gerber Leah R. , Hines Ellen , Leslie Heather M. , Lester Sarah E. , MacCarthy Jessica M. C. , Maxwell Sara M. , Mayorga Juan , McCauley Douglas J. , Micheli Fiorenza , Moffitt Russell , Nickols Kerry J. , Palumbi Stephen R. , Pearsall Douglas R. , Pike Elizabeth P. , Pikitch Ellen K. , Sancho Gorka , Spalding Ana K. , Suman Daniel O. , Sykora-Bodie Seth T. , Grorud-Colvert Kirsten
Published: May 2022

Marine protected areas (MPAs) are a key tool for achieving goals for biodiversity conservation and human well-being, including improving climate resilience and equitable access to nature. At a national level, they are central components in the U.S. commitment to conserve at least 30% of U.S. waters by 2030. By definition, the primary goal of an MPA is the long-term conservation of nature; however, not all MPAs provide the same ecological and social benefits. A U.S. system of MPAs that is equitable, well-managed, representative and connected, and includes areas at a level of protection that can deliver desired outcomes is best positioned to support national goals. We used a new MPA framework, The MPA Guide, to assess the level of protection and stage of establishment of the 50 largest U.S. MPAs, which make up 99.7% of the total U.S. MPA area (3.19 million km2). Over 96% of this area, including 99% of that which is fully or highly protected against extractive or destructive human activities, is in the central Pacific ocean. Total MPA area in other regions is sparse – only 1.9% of the U.S. ocean excluding the central Pacific is protected in any kind of MPA (120,976 km2). Over three quarters of the non-central Pacific MPA area is lightly or minimally protected against extractive or destructive human activities. These results highlight an urgent need to improve the quality, quantity, and representativeness of MPA protection in U.S. waters to bring benefits to human and marine communities. We identify and review the state of the science, including focal areas for achieving desired MPA outcomes and lessons learned from places where sound ecological and social design principles come together in MPAs that are set up to achieve national goals for equity, climate resilience, and biodiversity conservation. We recommend key opportunities for action specific to the U.S. context, including increasing funding, research, equity, and protection level for new and existing U.S. MPAs.
Effect of Extension Piece Design on Catch Patterns in a Mediterranean Bottom Trawl Fishery
Authors: Petetta Andrea , Herrmann Bent , Virgili Massimo , Li Veli Daniel , Brinkhof Jesse , Lucchetti Alessandro
Published: May 2022

The catch composition of bottom trawls is commonly refined and improved through changes in codend design. Measures like reducing the number of meshes in codend circumference or turning diamond netting by 90 degrees are well known to improve the size selectivity of fish species with rounded cross-sectional shape. Based on this we speculated whether the same measures, if applied in other parts of a bottom trawl, would provide similar benefits as in the codend. Therefore, experiments were carried out by deploying these changes to the trawl extension piece in a Mediterranean bottom trawl fishery. However, for European hake and monkfish, results showed no indication of improved selectivity or catch pattern compared to the standard extension piece in the trawl. Contrary, for red mullet, one of the most important species in this fishery, reducing the number of meshes in the circumference of the extension piece jeopardized the size selection obtained in the trawl with a standard extension piece. The lesson learnt from this study was that the design changes that work for the codend do not necessarily work for other parts of the trawl. In fact, they can even have negative effects.
Experimental Investigation on Isothermal Sections at 1273 and 1473 K in the Co–Ti–W System
Authors: Shi Yu , Guo Cuiping , Li Changrong , Du Zhenmin , Hu Die
Published: May 2022

The microstructures of 25 annealed alloys and XRD patterns of partial critical alloys in the Co–Ti–W system were investigated by using scanning electron microscopy (SEM) with energy dispersive spectrometer (EDS) and X-ray diffraction (XRD) methods. The isothermal sections at 1273 and 1473 K of the Co–Ti–W system were established. Five three-phase regions and five two-phase regions at 1273 K and eight three-phase regions and two two-phase regions at 1473 K were experimentally determined. The maximum solubilities of W in Co3Ti, αCo2Ti, βCo2Ti and CoTi were determined to be ∼7.9 at%, ∼1.5 at.%, ∼5.9 at.% and ∼1.8 at.% at 1273 K, respectively. The maximum solubilities of Ti in Co7W6 and Co3W were determined to be ∼11.9 at.% and ∼15.2 at.% at 1273 K, respectively. The compound Co3Ti with L12 crystal structure was found to be stable at 1473 K in the Co–Ti–W system owing to the addition of W element, which confirmed that W can improve the stability of γ′ with L12 crystal structure in the Co-based superalloys. The composition range of W in Co3Ti was measured to be ∼7.4–10.4 at.% at 1473 K. In addition, the maximum solubilities of Ti in Co7W6 and W in βCo2Ti and CoTi were ∼15.4 at.%, ∼7.6 at.% and ∼3.1 at.% at 1473 K, respectively. No ternary compounds were found in the Co–Ti–W system at 1273 and 1473 K.
How to Adapt Anesthetic Human Resources to Health Emergencies Such as the COVID-19 Outbreak: Replacing a Pre-anesthetic Consultation With a Questionnaire in a University Obstetric Unit
Authors: Boussac Emilie , Gery Charlene , Desseauve David
Published: May 2022

To manage referrals to the pre-anesthetic consultation during the COVID-19 pandemic, a screening questionnaire was created and sent to parturients with anesthetic risk during the pre-anesthetic consultation. This innovative approach enabled the redistribution of medical anesthetic resources in units that were heavily affected by the pandemic.
Theragnostic 64Cu/67Cu Radioisotopes Production With RFT-30 Cyclotron
Authors: Lee Jun Young , Chae Jung Ho , Hur Min Goo , Yang Seung Dae , Kong Young Bae , Lee Jongchul , Ju Jin Sik , Choi Pyeong Seok , Park Jeong Hoon
Published: May 2022

64Cu and 67Cu are theragnostic pair radionuclides with promising application in the nuclear medicine. 64Cu is PET nuclide for the non-invasive diagnosis and 67Cu is beta emitter for therapy of various cancers. This study discusses optimization efforts in the production of these radioactive coppers carried out with 30 MeV cyclotron. Optimized conditions include target preparation, chemical separation, and quality control. The production routes of 64Cu and 67Cu were studied based on the nuclear reactions of 64Ni(p,n)64Cu and 70Zn(p,α)67Cu. The produced 64Cu and 67Cu have >99.9% of the radionuclidic purity. The yield at the end of bombardment (EOB) of 64Cu and 67Cu is 28.5 MBq/μAh and 67Cu is 0.58 MBq/μAh, respectively.
A Competitive Advantage of Middle-Sized Diatoms From Increasing Seawater CO2
Authors: Zhang Qi , Luo Ya-Wei
Published: May 2022

Diatoms, one of the most important phytoplankton groups, fulfill their carbon demand from seawater mainly by obtaining passively diffused carbon dioxide (CO2) and/or actively consuming intracellular energy to acquire bicarbonate (HCO3–). An anthropogenically induced increase in seawater CO2 reduces the HCO3– requirement of diatoms, potentially saving intracellular energy and benefitting their growth. This effect is commonly speculated to be most remarkable in larger diatoms that are subject to a stronger limitation of CO2 supply because of their smaller surface-to-volume ratios. However, we constructed a theoretical model for diatoms and revealed a unimodal relationship between the simulated growth rate response (GRR, the ratio of growth rates under elevated and ambient CO2) and cell size, with the GRR peaking at a cell diameter of ∼7 μm. The simulated GRR of the smallest diatoms was low because the CO2 supply was nearly sufficient at the ambient level, while the decline of GRR from a cell diameter of 7 μm was simulated because the contribution of seawater CO2 to the total carbon demand greatly decreased and diatoms became less sensitive to CO2 increase. A collection of historical data in CO2 enrichment experiments of diatoms also showed a roughly unimodal relationship between maximal GRR and cell size. Our model further revealed that the “optimal” cell size corresponding to peak GRR enlarged with the magnitude of CO2 increase but diminished with elevating cellular carbon demand, leading to projection of the smallest optimal cell size in the equatorial Pacific upwelling zone. Last, we need to emphasize that the size-dependent effects of increasing CO2 on diatoms are multifaceted, while our model only considers the inorganic carbon supply from seawater and optimal allocation of intracellular energy. Our study proposes a competitive advantage of middle-sized diatoms and can be useful in projecting changes in the diatom community in the future acidified high-CO2 ocean.
FRAGTE2: An Enhanced Algorithm to Pre-Select Closely Related Genomes for Bacterial Species Demarcation
Authors: Zeng Jiaqi , Wang Yuxiao , Wu Ziyao , Zhou Yizhuang
Published: May 2022

We previously reported on FRAGTE (hereafter termed FRAGTE1), a promising algorithm for sieving (pre-selecting genome pairs for whole-genome species demarcation). However, the overall amount of pairs sieved by FRAGTE1 is still large, requiring seriously unaffordable computing cost, especially for large datasets. Here, we present FRAGTE2. Tests on simulated genomes, real genomes, and metagenome-assembled genomes revealed that (i) FRAGTE2 outstandingly reduces ~50–60.10% of the overall amount of pairs sieved by FRAGTE1, dramatically decreasing the computing cost required for whole-genome species demarcation afterward; (ii) FRAGTE2 shows superior sensitivity than FRAGTE1; (iii) FRAGTE2 shows higher specificity than FRAGTE1; and (iv) FRAGTE2 is faster than or comparable with FRAGTE1. Besides, FRAGTE2 is independent of genome completeness, the same as FRAGTE1. We therefore recommend FRAGTE2 tailored for sieving to facilitate species demarcation in prokaryotes.
FepR as a Central Genetic Target in the Adaptation to Quaternary Ammonium Compounds and Cross-Resistance to Ciprofloxacin in Listeria monocytogenes
Authors: Douarre Pierre-Emmanuel , Sévellec Yann , Le Grandois Patricia , Soumet Christophe , Bridier Arnaud , Roussel Sophie
Published: May 2022

The foodborne pathogen, Listeria monocytogenes, (Lm), frequently undergoes selection pressure associated with the extensive use of disinfectants, such as quaternary ammonium compounds, which are widely used in food processing plants. The repeated exposure to sub-inhibitory biocide concentrations can induce increased tolerance to these compounds, but can also trigger the development of antibiotic resistance, and both increase the risk of food contamination and persistence in food production environments. Although the acquisition of genes can explain biocide tolerance, the genetic mechanisms underlying the adaptive cross-resistance to antibiotics remain unclear. We previously showed that repeated exposure to benzalkonium chloride (BC) and didecyldimethyl ammonium chloride (DDAC) led to reduced susceptibility to ciprofloxacin in Lm strains from diverse sources. Here, we compared the genomes of 16 biocide-adapted and 10 parental strains to identify the molecular mechanisms of fluoroquinolone cross-resistance. A core genome SNP analysis identified various mutations in the transcriptional regulator fepR (lmo2088) for 94% of the adapted strains and mutations in other effectors at a lower frequency. FepR is a local repressor of the MATE fluoroquinolone efflux pump FepA. The impact of the mutations on the structure and function of the protein was assessed by performing in silico prediction and protein homology modeling. Our results show that 75% of the missense mutations observed in fepR are located in the HTH domain of the protein, within the DNA interaction site. These mutations are predicted to reduce the activity of the regulator, leading to the overexpression of the efflux pump responsible for the ciprofloxacin-enhanced resistance.
Exploring the Dynamic of Bacterial Communities in Manila Clam (Ruditapes philippinarum) During Refrigerated Storage
Authors: Yang Yi , Qiu Jingxuan , Wang Xin
Published: May 2022

Microorganism contamination is one of the most important factors affecting the spoilage and food safety of Manila clams. This study aimed to gain insights into bacterial composition and the dynamic change of bacterial communities on retailed Manila clam during refrigerated storage within the edible period. High-throughput sequencing was conducted to monitor the bacterial population with the prolongation of storage time of Day 0, Day 1, and Day 3. Result demonstrated that phyla of Proteobacteria, Actinobacteriota, Acidobacteriota, and Chloroflexi composed the majority of bacterial communities during the whole observation process. Furthermore, the increase of Proteobacteria showed a positive correlation with the storage time, whereas Acidobacteriota and Chloroflexi continued to decline in storage. For genus annotation, none of genus obtained dominant population in storage. From Day 0 to Day 1, the genera of Streptomyces, Bradyrhizobium, and Mycobacterium significantly increased; meanwhile, 12 genera significantly decreased. Compared with samples at Day 0, a total of 15 genera significantly decreased with the reduced proportion ranging from 0.50 to 4.40% at Day 3. At the end of the storage, the genus Crossiella became the most redundant population. Both the richness and diversity decreased at the start of storage at Day 1, and then slightly increased at Day 3 was observed. Based on the result in this study, strategy targeting the increased bacteria could be tested to improve the consumption quality and safety of refrigerated clam.
An Integrated Metabolomic Screening Platform Discovers the Potential Biomarkers of Ischemic Stroke and Reveals the Protective Effect and Mechanism of Folic Acid
Authors: Yang Yan-hui , Lei Lei , Bao Yin-ping , Zhang Lu
Published: May 2022

Folic acid has a protective effect against ischemic stroke. However, the protective pharmacological mechanism remains unclear. The aim of this study is to explore the protective effect of folic acid on ischemic stroke animals by an integrated metabolomic biomarker screening platform. Based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS) coupled with multivariate data analysis, the changes in metabolites and pathways were characterized. We found that the metabolic alteration involved a total of 37 metabolites, of which 26 biomarkers such as γ-aminobutyric acid, lysine, glutamate, ribose, and valine can be regulated by folic acid via metabolic pathways of amino acid metabolism, carbohydrate metabolism, fatty acid metabolism, citrate cycle, and pyruvate metabolism, which may be the potential therapeutic targets of folic acid against ischemic stroke. Folic acid as an emerging potential natural anti-fibrosis agent has significant activity in protecting against middle cerebral artery occlusion-induced rat ischemic stroke model by delaying pathological development, reversing the metabolic biomarkers, and mainly regulating the perturbation in amino acid metabolism, carbohydrate metabolism, fatty acid metabolism, citrate cycle, and pyruvate metabolism. It also showed that the integrated metabolic biomarker screening platform could provide a better understanding of the therapeutic effect and mechanism of drugs.
Mapping of Structure-Function Age-Related Connectivity Changes on Cognition Using Multimodal MRI
Authors: Pur Daiana Roxana , Preti Maria Giulia , de Ribaupierre Anik , Van De Ville Dimitri , Eagleson Roy , Mella Nathalie , de Ribaupierre Sandrine
Published: May 2022

The relationship between age-related changes in brain structural connectivity (SC) and functional connectivity (FC) with cognition is not well understood. Furthermore, it is not clear whether cognition is represented via a similar spatial pattern of FC and SC or instead is mapped by distinct sets of distributed connectivity patterns. To this end, we used a longitudinal, within-subject, multimodal approach aiming to combine brain data from diffusion-weighted MRI (DW-MRI), and functional MRI (fMRI) with behavioral evaluation, to better understand how changes in FC and SC correlate with changes in cognition in a sample of older adults. FC and SC measures were derived from the multimodal scans acquired at two time points. Change in FC and SC was correlated with 13 behavioral measures of cognitive function using Partial Least Squares Correlation (PLSC). Two of the measures indicate an age-related change in cognition and the rest indicate baseline cognitive performance. FC and SC—cognition correlations were expressed across several cognitive measures, and numerous structural and functional cortical connections, mainly cingulo-opercular, dorsolateral prefrontal, somatosensory and motor, and temporo-parieto-occipital, contributed both positively and negatively to the brain-behavior relationship. Whole-brain FC and SC captured distinct and independent connections related to the cognitive measures. Overall, we examined age-related function-structure associations of the brain in a comprehensive and integrated manner, using a multimodal approach. We pointed out the behavioral relevance of age-related changes in FC and SC. Taken together, our results highlight that the heterogeneity in distributed FC and SC connectivity patterns provide unique information about the variable nature of healthy cognitive aging.
Understanding How Physical Exercise Improves Alzheimer’s Disease: Cholinergic and Monoaminergic Systems
Authors: Zong Boyi , Yu Fengzhi , Zhang Xiaoyou , Zhao Wenrui , Sun Peng , Li Shichang , Li Lin
Published: May 2022

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, characterized by the accumulation of proteinaceous aggregates and neurofibrillary lesions composed of β-amyloid (Aβ) peptide and hyperphosphorylated microtubule-associated protein tau, respectively. It has long been known that dysregulation of cholinergic and monoaminergic (i.e., dopaminergic, serotoninergic, and noradrenergic) systems is involved in the pathogenesis of AD. Abnormalities in neuronal activity, neurotransmitter signaling input, and receptor function exaggerate Aβ deposition and tau hyperphosphorylation. Maintenance of normal neurotransmission is essential to halt AD progression. Most neurotransmitters and neurotransmitter-related drugs modulate the pathology of AD and improve cognitive function through G protein-coupled receptors (GPCRs). Exercise therapies provide an important alternative or adjunctive intervention for AD. Cumulative evidence indicates that exercise can prevent multiple pathological features found in AD and improve cognitive function through delaying the degeneration of cholinergic and monoaminergic neurons; increasing levels of acetylcholine, norepinephrine, serotonin, and dopamine; and modulating the activity of certain neurotransmitter-related GPCRs. Emerging insights into the mechanistic links among exercise, the neurotransmitter system, and AD highlight the potential of this intervention as a therapeutic approach for AD.
Pathological Role of Natural Killer Cells in Parkinson's Disease: A Systematic Review
Authors: Zhang Le , Zhang Yingshuang , Fan Dongsheng
Published: May 2022

Parkinson's disease (PD) is one of the common neurodegenerative diseases that is characterized by selective degeneration of dopaminergic neurons in the substantia nigra, and misfolding of α-synuclein into aggregates is thought to contribute to its pathology. Studies have shown that immune-inflammatory responses are involved in the development of PD and play an important role in α-synuclein scavenge. Natural killer (NK) cells are first responders in immune cells and can directly promote immune defense mechanisms by cytotoxicity and by secreting cytokines. Recent discoveries suggest that NK cells are increasingly recognized in the pathological features of PD. However, the mechanisms underlying it have not been fully understood. In this review, we systematically retrieved and evaluated published evidence about the functions of NK cells in PD. We find alterations in the number of NK cells and cytotoxicity during the progression of PD, and it seems that NK cells play a neuroprotective role in PD pathogenesis, which may further reveal novel targets for the management and treatment of PD.
Epigenetic and Transcriptional Regulation of Spontaneous and Sensory Activity Dependent Programs During Neuronal Circuit Development
Authors: Pumo Gabriele M. , Kitazawa Taro , Rijli Filippo M.
Published: May 2022

Spontaneous activity generated before the onset of sensory transduction has a key role in wiring developing sensory circuits. From axonal targeting, to synapse formation and elimination, to the balanced integration of neurons into developing circuits, this type of activity is implicated in a variety of cellular processes. However, little is known about its molecular mechanisms of action, especially at the level of genome regulation. Conversely, sensory experience-dependent activity implements well-characterized transcriptional and epigenetic chromatin programs that underlie heterogeneous but specific genomic responses that shape both postnatal circuit development and neuroplasticity in the adult. In this review, we focus on our knowledge of the developmental processes regulated by spontaneous activity and the underlying transcriptional mechanisms. We also review novel findings on how chromatin regulates the specificity and developmental induction of the experience-dependent program, and speculate their relevance for our understanding of how spontaneous activity may act at the genomic level to instruct circuit assembly and prepare developing neurons for sensory-dependent connectivity refinement and processing.
Differentiating Slowly Progressive Subtype of Lower Limb Onset ALS From Typical ALS Depends on the Time of Disease Progression and Phenotype
Authors: Zhang Huagang , Chen Lu , Tian Jinzhou , Fan Dongsheng
Published: May 2022

Background

Flail leg syndrome (FLS) is a regional variant of amyotrophic lateral sclerosis (ALS) with the characteristics of slow progression and the symptoms confined to the lumbosacral region for extended periods. However, FLS may not be easily differentiated from typical ALS.

Objective

The objective of the study was to determine a cutoff time of disease progression that could differentiate FLS from the typical lower limb onset ALS.

Methods

A cutoff point analysis was performed with maximally selected log–rank statistics in patients with lower limb onset ALS registered from 2009 to 2013. Based on the cutoff duration from the lower limb onset to second region significantly involved (SRSI), all patients were divided into the slowly progressive subtype of lower limb onset ALS group and the typical lower limb-onset ALS group. Patients with the slowly progressive subtype of the lower limb onset ALS, who had the flail leg phenotype, were classified as patients with FLS. Differences between groups were analyzed.

Results

Among the 196 patients recruited, 157 patients with a duration <14 months from lower limb onset to SRSI were classified as having typical lower limb onset ALS. Twenty-nine patients with a duration more than or equal to 14 months and the flail leg phenotype were classified as having FLS. Patients with FLS exhibited a median diagnostic delay of 25 months, a median duration of 24 months from lower limb onset to SRSI, a forced vital capacity abnormity rate of 12.5% at the first visit to our department, and a median survival time of 80 months, which were significantly different from those of patients with typical lower limb onset ALS (p < 0.001, p < 0.001, p = 0.024, p < 0.001). The 5-year survival rate of the FLS group (79.3%) was much higher than that of the other group (1.9%).

Conclusions

A crucial feature in differentiating FLS from typical lower limb onset ALS in Chinese patients may be symptoms confined to the lumbosacral region for at least 14 months, which may be better than 12 or 24 months used in the previous studies. The FLS was characterized by slower progression, less and later respiratory dysfunction, and a more benign prognosis than the typical lower limb onset ALS.
Intestinal Barrier Dysfunction in the Absence of Systemic Inflammation Fails to Exacerbate Motor Dysfunction and Brain Pathology in a Mouse Model of Parkinson's Disease
Authors: Jackson Aeja , Engen Phillip A. , Forsyth Christopher B. , Shaikh Maliha , Naqib Ankur , Wilber Sherry , Frausto Dulce M. , Raeisi Shohreh , Green Stefan J. , Bradaric Brinda Desai , Persons Amanda L. , Voigt Robin M. , Keshavarzian Ali
Published: May 2022

Introduction

Parkinson's disease (PD) is the second most common neurodegenerative disease associated with aging. PD patients have systemic and neuroinflammation which is hypothesized to contribute to neurodegeneration. Recent studies highlight the importance of the gut-brain axis in PD pathogenesis and suggest that gut-derived inflammation can trigger and/or promote neuroinflammation and neurodegeneration in PD. However, it is not clear whether microbiota dysbiosis, intestinal barrier dysfunction, or intestinal inflammation (common features in PD patients) are primary drivers of disrupted gut-brain axis in PD that promote neuroinflammation and neurodegeneration.

Objective

To determine the role of microbiota dysbiosis, intestinal barrier dysfunction, and colonic inflammation in neuroinflammation and neurodegeneration in a genetic rodent model of PD [α-synuclein overexpressing (ASO) mice].

Methods

To distinguish the role of intestinal barrier dysfunction separate from inflammation, low dose (1%) dextran sodium sulfate (DSS) was administered in cycles for 52 days to ASO and control mice. The outcomes assessed included intestinal barrier integrity, intestinal inflammation, stool microbiome community, systemic inflammation, motor function, microglial activation, and dopaminergic neurons.

Results

Low dose DSS treatment caused intestinal barrier dysfunction (sugar test, histological analysis), intestinal microbiota dysbiosis, mild intestinal inflammation (colon shortening, elevated MPO), but it did not increase systemic inflammation (serum cytokines). However, DSS did not exacerbate motor dysfunction, neuroinflammation (microglial activation), or dopaminergic neuron loss in ASO mice.

Conclusion

Disruption of the intestinal barrier without overt intestinal inflammation is not associated with worsening of PD-like behavior and pathology in ASO mice.
Synthetic Oxytocin and Vasopressin Act Within the Central Amygdala to Exacerbate Aggression in Female Wistar Rats
Authors: Oliveira Vinícius E. de M. , de Jong Trynke R. , Neumann Inga D.
Published: May 2022

Exacerbated aggression is a high-impact, but poorly understood core symptom of several psychiatric disorders, which can also affect women. Animal models have successfully been employed to unravel the neurobiology of aggression. However, despite increasing evidence for sex-specificity, little is known about aggression in females. Here, we studied the role of the oxytocin (OXT) and arginine vasopressin (AVP) systems within the central amygdala (CeA) on aggressive behavior displayed by virgin female Wistar rats using immunohistochemistry, receptor autoradiography, and neuropharmacology. Our data show that CeA GABAergic neurons are activated after an aggressive encounter in the female intruder test. Additionally, neuronal activity (pERK) negatively correlated with the display of aggression in low-aggressive group-housed females. Binding of OXT receptors, but not AVP-V1a receptors, was increased in the CeA of high-aggressive isolated and trained (IST) females. Finally, local infusion of either synthetic OXT or AVP enhanced aggression in IST females, whereas blockade of either of these receptors did not affect aggressive behavior. Altogether, our data support a moderate role of the CeA in female aggression. Regarding neuropeptide signaling, our findings suggest that synthetic, but not endogenous OXT and AVP modulate aggressive behavior in female Wistar rats.
Effect of Anesthesia on Oligodendrocyte Development in the Brain
Authors: Fu Ningning , Zhu Ruilou , Zeng Shuang , Li Ningning , Zhang Jiaqiang
Published: May 2022

Oligodendrocytes (OLs) participate in the formation of myelin, promoting the propagation of action potentials, and disruption of their proliferation and differentiation leads to central nervous system (CNS) damage. As surgical techniques have advanced, there is an increasing number of children who undergo multiple procedures early in life, and recent experiments have demonstrated effects on brain development after a single or multiple anesthetics. An increasing number of clinical studies showing the effects of anesthetic drugs on the development of the nervous system may mainly reside in the connections between neurons, where myelin development will receive more research attention. In this article, we review the relationship between anesthesia exposure and the brain and OLs, provide new insights into the development of the relationship between anesthesia exposure and OLs, and provide a theoretical basis for clinical prevention of neurodevelopmental risks of general anesthesia drugs.