bluuebunny/crossref_metadata_2025 huggingface dataset:
Renewable Energy Sources vs. an Air Quality Improvement in Urbanized Areas - the Metropolitan Area of Kraków Case
Authors: Blazy Rafał , Błachut Jakub , Ciepiela Agnieszka , Łabuz Rita , Papież Renata
Published: October 2021

The premise for the selection of the topic discussed in this article is the lack of research on the level of reduction of air pollutant emissions by the use of photovoltaic micro-installations in single-family buildings, both in Poland and other countries of Central and Eastern Europe. Therefore, the Authors made an attempt to estimate the scale of air pollution reduction (in particular CO2) in the area of the urbanized Metropolitan area of Krakow, which is one of the most polluted regions in Poland. The installation of photovoltaic panels on single-family buildings, co-financed by the government My Electricity Program, is the investment cost in improving the air quality in this region, and thus increasing the well-being of its inhabitants.
Knowledge Mapping in Electricity Demand Forecasting: A Scientometric Insight
Authors: Yang Dongchuan , Guo Ju-e , Li Jie , Wang Shouyang , Sun Shaolong
Published: October 2021

Electricity demand forecasting plays a fundamental role in the operation and planning procedures of power systems, and the publications related to electricity demand forecasting have attracted more and more attention in the past few years. To have a better understanding of the knowledge structure in the field of electricity demand forecasting, we applied scientometric methods to analyze the current state and the emerging trends based on the 831 publications from the Web of Science Core Collection during the past 20 years (1999–2018). Employing statistical description analysis, cooperative network analysis, keyword co-occurrence analysis, co-citation analysis, cluster analysis, and emerging trend analysis techniques, this study gives a comprehensive overview of the most critical countries, institutions, journals, authors, and publications in this field, cooperative networks relationships, research hotspots, and emerging trends. The results can provide meaningful guidance and helpful insights for researchers to enhance the understanding of crucial research, emerging trends, and new developments in electricity demand forecasting.
Nematode Interactions on Beetle Hosts Indicate a Role of Mouth-Form Plasticity in Resource Competition
Authors: Renahan Tess , Sommer Ralf J.
Published: October 2021

Competition is rampant across kingdoms, arising over potential mates, food resources, and space availability. When faced with opponents, phenotypic plasticity proffers organisms indispensable advantageous strategies to outcompete rivals. This tactic is especially crucial on decaying insect hosts as myriad microbes and numerous nematodes struggle to establish thriving populations and ensure resource availability for future generations. Scarab beetles and their associated nematode symbionts on La Réunion Island have provided exceptional systems to study complicated cross-phylum interactions in soil, and recently we have identified a previously unexplored beetle host, Gymnogaster bupthalma, to be reliably co-infested with diplogastrids Pristionchus mayeri and Acrostichus spp. These nematodes maintain the capacity to plastically respond to environmental conditions by developing disparate mouth forms, a strict bacterial-feeding morph or an omnivorous morph that enables predation on other nematodes. In addition, under stressful settings these worms can enter an arrested development stage called dauer, non-feeding dispersal larvae that resume development into reproducing adults when conditions improve. By investigating this beetle-nematode system in a natural context, we uncovered a novel Pristionchus strategy, wherein dauer dispersal from the carcass is gradual and a reproducing population is sustained. Remarkably, usually preferential-bacterial morph P. mayeri develop as predators in populations dense with competitors.
Cryptosporidium hominis Phylogenomic Analysis Reveals Separate Lineages With Continental Segregation
Authors: Cabarcas Felipe , Galvan-Diaz Ana Luz , Arias-Agudelo Laura M. , García-Montoya Gisela María , Daza Juan M. , Alzate Juan F.
Published: October 2021

Cryptosporidium is a leading cause of waterborne outbreaks globally, and Cryptosporidium hominis and C. parvum are the principal cause of human cryptosporidiosis on the planet. Thanks to the advances in Next-Generation Sequencing (NGS) sequencing and bioinformatic software development, more than 100 genomes have been generated in the last decade using a metagenomic-like strategy. This procedure involves the parasite oocyst enrichment from stool samples of infected individuals, NGS sequencing, metagenomic assembly, parasite genome computational filtering, and comparative genomic analysis. Following this approach, genomes of infected individuals of all continents have been generated, although with striking different quality results. In this study, we performed a thorough comparison, in terms of assembly quality and purity, of 100+ de novo assembled genomes of C. hominis. Remarkably, after quality genome filtering, a comprehensive phylogenomic analysis allowed us to discover that C. hominis encompasses two lineages with continental segregation. These lineages were named based on the observed continental distribution bias as C. hominis Euro-American (EA) and the C. hominis Afro-Asian (AA) lineages.
SOD1 Mutation Spectrum and Natural History of ALS Patients in a 15-Year Cohort in Southeastern China
Authors: Chen Lu-Xi , Xu Hai-Feng , Wang Pei-Shan , Yang Xin-Xia , Wu Zhi-Ying , Li Hong-Fu
Published: October 2021

Background: Mutations in superoxide dismutase 1 gene (SOD1) are the most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) in the Chinese population. A detailed natural history of SOD1-mutated ALS patients will provide key information for ongoing genetic clinical trials.

Methods: We screened for SOD1 mutations using whole exome sequencing (WES) in Chinese ALS cases from 2017 to 2021. Functional studies were then performed to confirm the pathogenicity of novel variants. In addition, we enrolled previously reported SOD1 mutations in our centers from 2007 to 2017. The SOD1 mutation spectrum, age at onset (AAO), diagnostic delay, and survival duration were analyzed.

Results: We found two novel SOD1 variants (p.G17H and p.E134*) that exerted both gain-of-function and loss-of-function effects in vitro. Combined with our previous SOD1-mutated patients, 32 probands with 21 SOD1 mutations were included with the four most frequently occurring mutations of p.V48A, p.H47R, p.C112Y, and p.G148D. SOD1 mutations account for 58.9% of familial ALS (FALS) cases. The mean (SD) AAO was 46 ± 11.4 years with a significant difference between patients carrying mutations in exon 1 [n = 5, 34.6 (12.4) years] and exon 2 [n = 8, 51.4 (8.2) years] (p = 0.038). The mean of the diagnostic delay of FALS patients is significantly earlier than the sporadic ALS (SALS) patients [9.5 (4.8) vs. 20.3 (9.3) years, p = 0.0026]. In addition, male patients survived longer than female patients (40 vs. 16 months, p = 0.05).

Conclusion: Our results expanded the spectrum of SOD1 mutations, highlighted the mutation distribution, and summarized the natural history of SOD1-mutated patients in southeastern China. Male patients were found to have better survival, and FALS patients received an earlier diagnosis. Our findings assist in providing a detailed clinical picture, which is important for ongoing genetic clinical trials.
Signatures Beyond Oncogenic Mutations in Cell-Free DNA Sequencing for Non-Invasive, Early Detection of Cancer
Authors: De Subhajyoti
Published: October 2021

Early detection of cancer saves lives, but an effective detection strategy in public health settings requires a delicate balance - periodic screening should neither miss rapidly progressing disease nor fail to detect rare tumors at unusual locations; on the other hand, even a modest false positive rate carries risks of over-diagnosis and over-treatment of relatively indolent non-malignant disease. Genomic profiling of cell-free DNA from liquid biopsy using massively parallel sequencing is emerging as an attractive, non-invasive screening platform for sensitive detection of multiple types of cancer in a single assay. Genomic data from cell-free DNA can not only identify oncogenic mutation status, but also additional molecular signatures related to potential tissue of origin, the extent of clonal growth, and malignant disease states. Utilization of the full potential of the molecular signatures from cfDNA sequencing data can guide clinical management strategies for targeted follow-ups using imaging or molecular marker-based diagnostic platforms and treatment options.
B Cell Mobilization, Dissemination, Fine Tuning of Local Antigen Specificity and Isotype Selection in Asthma
Authors: Ohm-Laursen Line , Meng Hailong , Hoehn Kenneth B. , Nouri Nima , Jiang Yue , Clouser Chris , Johnstone Timothy G. , Hause Ron , Sandhar Balraj S. , Upton Nadine E. G. , Chevretton Elfy B. , Lakhani Raj , Corrigan Chris J. , Kleinstein Steven H. , Gould Hannah J.
Published: October 2021

In order to better understand how the immune system interacts with environmental triggers to produce organ-specific disease, we here address the hypothesis that B and plasma cells are free to migrate through the mucosal surfaces of the upper and lower respiratory tracts, and that their total antibody repertoire is modified in a common respiratory tract disease, in this case atopic asthma. Using Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) we have catalogued the antibody repertoires of B cell clones retrieved near contemporaneously from multiple sites in the upper and lower respiratory tract mucosa of adult volunteers with atopic asthma and non-atopic controls and traced their migration. We show that the lower and upper respiratory tracts are immunologically connected, with trafficking of B cells directionally biased from the upper to the lower respiratory tract and points of selection when migrating from the nasal mucosa and into the bronchial mucosa. The repertoires are characterized by both IgD-only B cells and others undergoing class switch recombination, with restriction of the antibody repertoire distinct in asthmatics compared with controls. We conclude that B cells and plasma cells migrate freely throughout the respiratory tract and exhibit distinct antibody repertoires in health and disease.
Sustained Drug Treatment Alters the Gut Microbiota in Rheumatoid Arthritis
Authors: Mei Liyan , Yang Zhihua , Zhang Xiaolin , Liu Zehao , Wang Maojie , Wu Xiaodong , Chen Xiumin , Huang Qingchun , Huang Runyue
Published: October 2021

Several studies have investigated the causative role of the microbiome in the development of rheumatoid arthritis (RA), but changes in the gut microbiome in RA patients during drug treatment have been less well studied. Here, we tracked the longitudinal changes in gut bacteria in 22 RA patients who were randomized into two groups and treated with Huayu-Qiangshen-Tongbi formula (HQT) plus methotrexate (MTX) or leflunomide (LEF) plus MTX. There were differences in the gut microbiome between untreated (at baseline) RA patients and healthy controls, with 37 species being more abundant in the RA patients and 21 species (including Clostridium celatum) being less abundant. Regarding the functional analysis, vitamin K2 biosynthesis was associated with RA-enriched bacteria. Additionally, in RA patients, alterations in gut microbial species appeared to be associated with RA-related clinical indicators through changing various gut microbiome functional pathways. The clinical efficacy of the two treatments was further observed to be similar, but the response trends of RA-related clinical indices in the two treatment groups differed. For example, HQT treatment affected the erythrocyte sedimentation rate (ESR), while LEF treatment affected the C-reactive protein (CRP) level. Further, 11 species and 9 metabolic pathways significantly changed over time in the HQT group (including C. celatum, which increased), while only 4 species and 2 metabolic pathways significantly changed over time in the LEF group. In summary, we studied the alterations in the gut microbiome of RA patients being treated with HQT or LEF. The results provide useful information on the role of the gut microbiota in the pathogenesis of RA, and they also provide potentially effective directions for developing new RA treatments.
Epithelial-Macrophage Crosstalk Initiates Sterile Inflammation in Embryonic Skin
Authors: Bhattacharjee Oindrila , Ayyangar Uttkarsh , Kurbet Ambika S. , Lakshmanan Vairavan , Palakodeti Dasaradhi , Ginhoux Florent , Raghavan Srikala
Published: October 2021

Macrophages are highly responsive to the environmental cues and are the primary responders to tissue stress and damage. While much is known about the role of macrophages during inflammatory disease progression; the initial series of events that set up the inflammation remains less understood. In this study, we use next generation sequencing (NGS) of embryonic skin macrophages and the niche cells - skin epithelia and stroma in the epidermis specific knockout of integrin beta 1 (Itgβ1) model to uncover specific roles of each cell type and identify how these cell types communicate to initiate the sterile inflammatory response. We demonstrate that while the embryonic skin fibroblasts in the Itgβ1 knockout skin are relatively inactive, the keratinocytes and macrophages are the critical responders to the sterile inflammatory cues. The epidermis expresses damage associated molecular patterns (DAMPs), stress response genes, pro-inflammatory cytokines, and chemokines that aid in eliciting the inflammatory response. The macrophages, in-turn, respond by acquiring enhanced M2-like characteristics expressing ECM remodeling and matrisome signatures that exacerbate the basement membrane disruption. Depletion of macrophages by blocking the CSF1 receptor (CSF1R) results in improved basement membrane integrity and reduced ECM remodeling activity in the KO skin. Further, blocking the skin inflammation with celecoxib reveals that the acquired fate of macrophages in the KO skin is dependent on its interaction with the epidermal compartment through COX2 dependent cytokine production. Taken together, our study highlights a critical crosstalk between the epithelia and the dermal macrophages that shapes macrophage fate and initiates sterile inflammation in the skin. The insights gained from our study can be extrapolated to other inflammatory disorders to understand the early events that set up the disease.
Physical Fitness Attenuates the Impact of Higher Body Mass and Adiposity on Inflammation in Women With Systemic Lupus Erythematosus
Authors: Sola-Rodríguez Sergio , Vargas-Hitos José Antonio , Gavilán-Carrera Blanca , Rosales-Castillo Antonio , Ríos-Fernández Raquel , Sabio José Mario , Soriano-Maldonado Alberto
Published: October 2021

Aims

Higher body mass and adiposity represent independent contributors to the systemic low-grade inflammatory state often observed in patients with systemic lupus erythematosus (SLE). This study assessed the role of physical fitness in the association of body mass and adiposity with inflammation in women with SLE.

Methods

A total of 77 women with SLE were included in this cross-sectional study. We obtained body mass index, waist-to-height ratio, and body fat percentage as indicators of body mass and adiposity. Inflammation was assessed through Serum levels of C-reactive protein, interleukin 6, and leptin. Cardiorespiratory fitness was assessed with the 6-minute walk test, range of motion with the back-scratch test, and muscular strength with handgrip dynamometry.

Results

Cardiorespiratory fitness attenuated the association of both body mass index and body fat percentage with interleukin 6 (all, P<0.05). Range of motion attenuated the association of body mass index with interleukin 6 (P<0.05) and the association of body fat percentage with C-reactive protein (P<0.05). These interactions indicated that higher fitness was associated with a lower increase in inflammation per unit increase of body mass or adiposity. Muscular strength showed a non-significant trend to attenuate the association of body fat percentage with interleukin 6 (P=0.057) but potentiated the association of body fat percentage with leptin (P<0.05).

Conclusion

These findings suggest that higher levels of cardiorespiratory fitness and range of motion might attenuate the impact of higher body mass and adiposity on inflammation in women with SLE. The role of muscular strength requires further investigation.
Convenient Auto-Processing Vector Based on Bamboo Mosaic Virus for Presentation of Antigens Through Enzymatic Coupling
Authors: Yang Ming-Hao , Hu Chung-Chi , Wong Chi-Hzeng , Liang Jian-Jong , Ko Hui-Ying , He Meng-Hsun , Lin Yi-Ling , Lin Na-Sheng , Hsu Yau-Heiu
Published: October 2021

We have developed a new binary epitope-presenting CVP platform based on bamboo mosaic virus (BaMV) by using the sortase A (SrtA)-mediated ligation technology. The reconstructed BaMV genome harbors two modifications: 1) a coat protein (CP) with N-terminal extension of the tobacco etch virus (TEV) protease recognition site plus 4 extra glycine (G) residues as the SrtA acceptor; and 2) a TEV protease coding region replacing that of the triple-gene-block proteins. Inoculation of such construct, pKB5G, on Nicotiana benthamiana resulted in the efficient production of filamentous CVPs ready for SrtA-mediated ligation with desired proteins. The second part of the binary platform includes an expression vector for the bacterial production of donor proteins. We demonstrated the applicability of the platform by using the recombinant envelope protein domain III (rEDIII) of Japanese encephalitis virus (JEV) as the antigen. Up to 40% of the BaMV CP subunits in each CVP were loaded with rEDIII proteins in 1 min. The rEDIII-presenting BaMV CVPs (BJLPET5G) could be purified using affinity chromatography. Immunization assays confirmed that BJLPET5G could induce the production of neutralizing antibodies against JEV infections. The binary platform could be adapted as a useful alternative for the development and mass production of vaccine candidates.
Repeated Influenza Vaccination Boosts and Maintains H1N1pdm09 Neuraminidase Antibody Titers
Authors: Hansen Lena , Zhou Fan , Amdam Håkon , Trieu Mai-Chi , Cox Rebecca Jane
Published: October 2021

Antibodies to influenza surface protein neuraminidase (NA) have been found to reduce disease severity and may be an independent correlate of protection. Despite this, current influenza vaccines have no regulatory requirements for the quality or quantity of the NA antigen and are not optimized for induction of NA-specific antibodies. Here we investigate the induction and durability of NA-specific antibody titers after pandemic AS03-adjuvanted monovalent H1N1 vaccination and subsequent annual vaccination in health care workers in a five-year longitudinal study. NA-specific antibodies were measured by endpoint ELISA and functional antibodies measured by enzyme-linked lectin assay (ELLA) and plaque reduction naturalisation assay. We found robust induction of NA inhibition (NAI) titers with a 53% seroconversion rate (>4-fold) after pandemic vaccination in 2009. Furthermore, the endpoint and NAI geometric mean titers persisted above pre-vaccination levels up to five years after vaccination in HCWs that only received the pandemic vaccine, which demonstrates considerable durability. Vaccination with non-adjuvanted trivalent influenza vaccines (TIV) in subsequent influenza seasons 2010/2011 – 2013/2014 further boosted NA-specific antibody responses. We found that each subsequent vaccination increased durable endpoint titers and contributed to maintaining the durability of functional antibody titers. Although the trivalent influenza vaccines boosted NA-specific antibodies, the magnitude of fold-increase at day 21 declined with repeated vaccination, particularly for functional antibody titers. High levels of pre-existing antibodies were associated with lower fold-induction in repeatedly vaccinated HCWs. In summary, our results show that durable NA-specific antibody responses can be induced by an adjuvanted influenza vaccine, which can be maintained and further boosted by TIVs. Although NA-specific antibody responses are boosted by annual influenza vaccines, high pre-existing titers may negatively affect the magnitude of fold-increase in repeatedly vaccinated individuals. Our results support continued development and standardization of the NA antigen to supplement current influenza vaccines and reduce the burden of morbidity and mortality.
A Humanized Mouse Strain That Develops Spontaneously Immune-Mediated Diabetes
Authors: Luce Sandrine , Guinoiseau Sophie , Gadault Alexis , Letourneur Franck , Nitschke Patrick , Bras Marc , Vidaud Michel , Charneau Pierre , Larger Etienne , Colli Maikel L. , Eizirik Decio L. , Lemonnier François , Boitard Christian
Published: October 2021

To circumvent the limitations of available preclinical models for the study of type 1 diabetes (T1D), we developed a new humanized model, the YES-RIP-hB7.1 mouse. This mouse is deficient of murine major histocompatibility complex class I and class II, the murine insulin genes, and expresses as transgenes the HLA-A*02:01 allele, the diabetes high-susceptibility HLA-DQ8A and B alleles, the human insulin gene, and the human co-stimulatory molecule B7.1 in insulin-secreting cells. It develops spontaneous T1D along with CD4+ and CD8+ T-cell responses to human preproinsulin epitopes. Most of the responses identified in these mice were validated in T1D patients. This model is amenable to characterization of hPPI-specific epitopes involved in T1D and to the identification of factors that may trigger autoimmune response to insulin-secreting cells in human T1D. It will allow evaluating peptide-based immunotherapy that may directly apply to T1D in human and complete preclinical model availability to address the issue of clinical heterogeneity of human disease.
Prospective Tracking of Donor-Reactive T-Cell Clones in the Circulation and Rejecting Human Kidney Allografts
Authors: Aschauer Constantin , Jelencsics Kira , Hu Karin , Heinzel Andreas , Gregorich Mariella Gloria , Vetter Julia , Schaller Susanne , Winkler Stephan M. , Weinberger Johannes , Pimenov Lisabeth , Gualdoni Guido A. , Eder Michael , Kainz Alexander , Troescher Anna Regina , Regele Heinz , Reindl-Schwaighofer Roman , Wekerle Thomas , Huppa Johannes Bernhard , Sykes Megan , Oberbauer Rainer
Published: October 2021

Background

Antigen recognition of allo-peptides and HLA molecules leads to the activation of donor-reactive T-cells following transplantation, potentially causing T-cell-mediated rejection (TCMR). Sequencing of the T-cell receptor (TCR) repertoire can be used to track the donor-reactive repertoire in blood and tissue of patients after kidney transplantation.

Methods/Design

In this prospective cohort study, 117 non-sensitized kidney transplant recipients with anti-CD25 induction were included. Peripheral mononuclear cells (PBMCs) were sampled pre-transplant and at the time of protocol or indication biopsies together with graft tissue. Next-generation sequencing (NGS) of the CDR3 region of the TCRbeta chain was performed after donor stimulation in mixed lymphocyte reactions to define the donor-reactive TCR repertoire. Blood and tissue of six patients experiencing a TCMR and six patients without rejection on protocol biopsies were interrogated for these TCRs. To elucidate common features of T-cell clonotypes, a network analysis of the TCR repertoires was performed.

Results

After transplantation, the frequency of circulating donor-reactive CD4 T-cells increased significantly from 0.86 ± 0.40% to 2.06 ± 0.40% of all CD4 cells (p < 0.001, mean dif.: -1.197, CI: -1.802, -0.593). The number of circulating donor-reactive CD4 clonotypes increased from 0.72 ± 0.33% to 1.89 ± 0.33% (p < 0.001, mean dif.: -1.168, CI: -1.724, -0.612). No difference in the percentage of donor-reactive T-cells in the circulation at transplant biopsy was found between subjects experiencing a TCMR and the control group [p = 0.64 (CD4+), p = 0.52 (CD8+)]. Graft-infiltrating T-cells showed an up to six-fold increase of donor-reactive T-cell clonotypes compared to the blood at the same time (3.7 vs. 0.6% and 2.4 vs. 1.5%), but the infiltrating TCR repertoire was not reflected by the composition of the circulating TCR repertoire despite some overlap. Network analysis showed a distinct segregation of the donor-reactive repertoire with higher modularity than the overall TCR repertoire in the blood. These findings indicate an unchoreographed process of diverse T-cell clones directed against numerous non-self antigens found in the allograft.

Conclusion

Donor-reactive T-cells are enriched in the kidney allograft during a TCMR episode, and dominant tissue clones are also found in the blood.

Trial Registration

Clinicaltrials.gov: NCT: 03422224 (https://clinicaltrials.gov/ct2/show/NCT03422224).
Dysregulated Microbiota-Driven Gasdermin D Activation Promotes Colitis Development by Mediating IL-18 Release
Authors: Gao Hanchao , Cao Mengtao , Yao Yikun , Hu Wenjun , Sun Huimin , Zhang Yingwei , Zeng Changchun , Tang Jia , Luan Shaodong , Chen Pengfei
Published: October 2021

The balance between gut microbiota and host is critical for maintaining host health. Although dysregulation of the gut microbiota triggers the development of various inflammatory diseases, including colitis, the molecular mechanism of microbiota-driven colitis development is largely unknown. Here, we found that gasdermin D (GSDMD) was activated during acute colitis. In the dextran sulfate sodium (DSS)-induced colitis model, compared to wild-type mice, Gsdmd-deficient mice had less colitis severity. Mechanistically, GSDMD expression in intestinal epithelial cells (IECs), but not infiltrating immune cells, was critical for GSDMD-mediated colitis progression. Moreover, commensal Escherichia coli (E. coli) largely overgrew during colitis, and then the dysregulated commensal E. coli mediated GSDMD activation. Furthermore, the activated GSDMD promoted the release of interleukin-18 (IL-18), but not the transcript or maturation level of IL-18, which in turn mediated goblet cell loss to induce colitis development. Thus, GSDMD promotes colitis development by mediating IL-18 release, and the microbiota can mediate colitis pathogenesis through regulation of GSDMD activation. Our results provide a potential molecular mechanism by which the microbiota-driven GSDMD activation contributes to colitis pathogenesis.
Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond
Authors: Jarmund Anders Hagen , Giskeødegård Guro Fanneløb , Ryssdal Mariell , Steinkjer Bjørg , Stokkeland Live Marie Tobiesen , Madssen Torfinn Støve , Stafne Signe Nilssen , Stridsklev Solhild , Moholdt Trine , Heimstad Runa , Vanky Eszter , Iversen Ann-Charlotte
Published: October 2021

Pregnancy implies delicate immunological balance between two individuals, with constant changes and adaptions in response to maternal capacity and fetal demands. We performed cytokine profiling of 1149 longitudinal serum samples from 707 pregnant women to map immunological changes from first trimester to term and beyond. The serum levels of 22 cytokines and C-reactive protein (CRP) followed diverse but characteristic trajectories throughout pregnancy, consistent with staged immunological adaptions. Eotaxin showed a particularly robust decrease throughout pregnancy. A strong surge in cytokine levels developed when pregnancies progressed beyond term and the increase was amplified as labor approached. Maternal obesity, smoking and pregnancies with large fetuses showed sustained increase in distinct cytokines throughout pregnancy. Multiparous women had increased cytokine levels in the first trimester compared to nulliparous women with higher cytokine levels in the third trimester. Fetal sex affected first trimester cytokine levels with increased levels in pregnancies with a female fetus. These findings unravel important immunological dynamics of pregnancy, demonstrate how both maternal and fetal factors influence maternal systemic cytokines, and serve as a comprehensive reference for cytokine profiles in normal pregnancies.
Graft-Versus-Host Disease Prevention by In Vitro-Generated Myeloid-Derived Suppressor Cells Is Exclusively Mediated by the CD11b+CD11c+ MDSC Subpopulation
Authors: Scheurer Jasmin , Kitt Kerstin , Huber Heinrich J. , Fundel-Clemens Katrin , Pflanz Stefan , Debatin Klaus-Michael , Strauss Gudrun
Published: October 2021

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells that dampen overwhelming adaptive immune responses through multiple mechanisms and are recognized as an attractive novel immune intervention therapy for counteracting the destructive effects of graft-versus-host disease (GVHD) developing after allogeneic bone marrow transplantation (BMT). MDSCs can be produced in great numbers for cellular therapy, but they present a mixture of subsets whose functions in GVHD prevention are undefined. Here, we generated MDSCs in vitro from murine BM cells in the presence of GM-CSF and defined the integrin CD11c as a marker to subdivide MDSCs into two functional subgroups: CD11b+CD11c+ and CD11b+CD11c− MDSCs. Isolated CD11b+CD11c+ and CD11b+CD11c− MDSCs both inhibited alloantigen-stimulated T-cell proliferation in vitro, although CD11b+CD11c+ MDSCs were more efficient and expressed higher levels of different immunosuppressive molecules. Likewise, expression of surface markers such as MHC class II, CD80, CD86, or PD-L1 further delineated both subsets. Most importantly, only the adoptive transfer of CD11b+CD11c+ MDSCs into a single MHC class I-disparate allogeneic BMT model prevented GVHD development and strongly decreased disease-induced mortality, while CD11b+CD11c− MDSCs were totally ineffective. Surprisingly, allogeneic T-cell homing and expansion in lymphatic and GVHD target organs were not affected by cotransplanted CD11b+CD11c+ MDSCs indicating a clear contradiction between in vitro and in vivo functions of MDSCs. However, CD11b+CD11c+ MDSCs shifted immune responses towards type 2 immunity reflected by increased Th2-specific cytokine expression of allogeneic T cells. Induction of type 2 immunity was mandatory for GVHD prevention, since CD11b+CD11c+ MDSCs were ineffective if recipients were reconstituted with STAT6-deficient T cells unable to differentiate into Th2 cells. Most importantly, the beneficial graft-versus-tumor (GVT) effect was maintained in the presence of CD11b+CD11c+ MDSCs since syngeneic tumor cells were efficiently eradicated. Strong differences in the transcriptomic landscape of both subpopulations underlined their functional differences. Defining CD11b+CD11c+ MDSCs as the subset of in vitro-generated MDSCs able to inhibit GVHD development might help to increase efficiency of MDSC therapy and to further delineate relevant target molecules and signaling pathways responsible for GVHD prevention.
Lentiviral-Transduced Ectopic Expression of Androgenic Hormone in a Crustacean Hematopoietic Primary Cell Culture
Authors: Rotem-Dai Noa , Weil Simy , Greenshpan Yariv , Abehsera Shai , Manor Rivka , Ofir Rivka , Gazit Roi , Rosental Benyamin , Aflalo Eliahu D. , Sagi Amir
Published: October 2021

Novel monosex biotechnologies in crustacean aquaculture involve the induction of sex reversal through manipulations of the androgenic gland (AG), and its most prominent factor, the insulin-like androgenic gland (IAG) hormone, during early developmental stages. In the giant freshwater prawn Macrobrachium rosenbergii, all-female populations are desirable for aquaculture, since the females can be stocked at higher densities and exhibit more uniform growth than males. Recently, a novel biotechnology for all-female aquaculture was developed based on injection into post-larvae of suspended primary AG cells from mature M. rosenbergii males. However, this biotechnology depends on the availability of appropriate male donors and it requires delicate surgical procedures on the small endocrine AG to produce appropriate quantities of cells for the sex manipulation. We therefore established a new platform for the production of M. rosenbergii IAG (Mr-IAG) in hematopoietic cells. The method rests on the induction of ectopic Mr-IAG expression under the white spot syndrome virus (WSSV) immediate-early 1 (IE1) promoter via a novel lentiviral vector. Our results demonstrate that M. rosenbergii primary cells infected with the Mr-IAG lentiviruses are capable of transcription, translation, and secretion of Mr-IAG in culture. Our new platform, which produces easy-to-harvest cells in abundance, could replace the AG cells used in the first step of the above-mentioned biotechnology for all-female aquaculture and, importantly, pave the way for producing monosex populations in other edible crustacean aquaculture species. In addition, a lentiviral system for crustacean cells provides a useful tool for basic and applied research in crustacean species.
Identifying Pathways for Climate-Resilient Multispecies Fisheries
Authors: Karr Kendra A. , Miller Valerie , Coronado Eva , Olivares-Bañuelos Nadia C. , Rosales Martha , Naretto Javier , Hiriart-Bertrand Luciano , Vargas-Fernández Camila , Alzugaray Romina , Puga Rafael , Valle Servando , Osman L. P. , Solís Julio Chamorro , Mayorga Marco Ide , Rader Doug , Fujita Rod
Published: October 2021

Fish live in communities, and most fisheries catch multiple species, yet fishery management predominately focuses on single species. In many multispecies fisheries, a variety of species are generally caught together at similar rates. Failure to account for this adequately in management has resulted in serial depletion and alterations to the ecosystem. Ideally, multispecies fisheries management should strive to produce good yields from specific valuable stocks and avoid adverse impacts of fishing on marine ecosystems. Moreover, multispecies management should aim to build resilience to changes in stock productivity and distribution driven by climate change. Here, we present tools and pathways that seven fisheries are adopting to achieve these goals. These case studies – from Mexico, Cuba, and Chile – differ in data richness, governance structure, and management resources. The management systems are also in various stages of evolution from unmanaged to complete management of a single species but transitioning to multispecies management. While various analytical tools and decision-making processes are described in the case studies, a common feature is the use of participatory stakeholder processes to build capacity and socialize the importance of multispecies management. We use lessons from these cases to recommend a multispecies management approach to overcome the limitations of current practices (typically single-species catch limits or large spatial restrictions), using the participatory processes and data-limited assessments to create stock complexes that simplify multispecies management (i.e., the “fish baskets” approach). Indicator species for each fish basket are identified to support the development of fishery performance indicators, reference values, harvest control rules, and management measures to create an adaptive management cycle to enhance the fishery’s resilience to impacts induced by climate change and other factors.
Comparison of Standard Caribbean Coral Reef Monitoring Protocols and Underwater Digital Photogrammetry to Characterize Hard Coral Species Composition, Abundance and Cover
Authors: Barrera-Falcon Erick , Rioja-Nieto Rodolfo , Hernández-Landa Roberto C. , Torres-Irineo Edgar
Published: October 2021

The precise assessing and monitoring of coral reefs are necessary to address and understand the threats and changes in coral communities. With the development of new technologies and algorithms for image processing, new protocols like underwater photogrammetry are implemented to study these ecosystems. This study compares the main ecological metrics for reef condition assessment, obtained with an underwater digital photogrammetry protocol (UWP) and traditional sampling design simulations in coral reefs of the Cozumel Reefs National Park. Three orthomosaics (380 m2) per reef on six fringing reefs were constructed, and the hard coral community characterized using a Geographic Information System (GIS). The orthomosaics were also used as a basis to simulate transect lines and obtain data on the hard coral community according to the video transect (VT) protocol, point intercept (PIT) protocol, and the Atlantic and Gulf Rapid Reef Assessment (AGRRA) protocol. Higher colony abundance, species richness, and lower coral cover estimates (p < 0.05) were obtained with the UWP. This protocol was also sensitive to small sized species. All the sampling designs showed similar capability to identify dominant species in terms of colony abundance and coral cover. The VT, PIT, and AGGRA showed similar coral cover values (p > 0.05), which seems to indicate that these sampling designs overestimate this important metric. Our results will help to understand and integrate the observations obtained with UWP with long-term data obtained with commonly used monitoring protocols in the Caribbean region.
The Gulf of St. Lawrence Biogeochemical Model: A Modelling Tool for Fisheries and Ocean Management
Authors: Lavoie Diane , Lambert Nicolas , Starr Michel , Chassé Joël , Riche Olivier , Le Clainche Yvonnick , Azetsu-Scott Kumiko , Béjaoui Béchir , Christian James R. , Gilbert Denis
Published: October 2021

The goal of this paper is to give a detailed description of the coupled physical-biogeochemical model of the Gulf of St. Lawrence that includes dissolved oxygen and carbonate system components, as well as a detailed analysis of the riverine contribution for different nitrogen and carbonate system components. A particular attention was paid to the representation of the microbial loop in order to maintain the appropriate level of the different biogeochemical components within the system over long term simulations. The skill of the model is demonstrated using in situ data, satellite data and estimated fluxes from different studies based on observational data. The model reproduces the main features of the system such as the phytoplankton bloom, hypoxic areas, pH and calcium carbonate saturation states. The model also reproduces well the estimated transport of nitrate from one region to the other. We revisited previous estimates of the riverine nutrient contribution to surface nitrate in the Lower St. Lawrence Estuary using the model. We also explain the mechanisms that lead to high ammonium concentrations, low dissolved oxygen, and undersaturated calcium carbonate conditions on the Magdalen Shallows.
DNA Metabarcoding Revealed Interspecific Dietary Difference and Prey Selectivity in Juvenile Horseshoe Crabs Carcinoscorpius rotundicauda and Tachypleus tridentatus From Hong Kong
Authors: Lee Bo Yee , Wakabayashi Kaori , Sin Simon Yung Wa , Ohtsuka Susumu , Tsang Ling Ming
Published: October 2021

Horseshoe crabs provide important ecological services including bioturbation and linking of food web in the shallow waters, but their populations are declining globally, leading to major concerns on conservation of these iconic animals. Baseline information of horseshoe crab ecology, such as their trophic role and food source, is pre-requisite for habitat protection plan and captive restocking program. Trophic ecology of Asian horseshoe crabs is relatively poorly understood and previous studies on their juveniles have suggested that they are selective feeders rather than opportunistic generalists. This study demonstrates a non-invasive approach, using DNA metabarcoding analyses of the nuclear 18S rRNA gene on fecal samples to assess the dietary compositions of Carcinoscorpius rotundicauda and Tachypleus tridentatus juveniles to (1) determine their dietary compositions and trophic roles in their ecosystem, (2) determine any prey selectivity, and (3) distinguish the interspecific dietary differences with potential implications on the habitat requirement and ecological partitioning between these two horseshoe crab species. The results based on relative read abundance (RRA) suggested that oligochaetes were the major prey items for both C. rotundicauda (41.6%) and T. tridentatus (32.4%). Bivalves and crustaceans were second major prey groups for C. rotundicauda (8.6 and 8.4%, respectively). Surprisingly, anthozoans contributed a considerable portion of T. tridentatus’s diet (22.8%), which has never been reported. Furthermore, the major prey groups identified in the fecal samples were not the dominant benthic organisms in the studied area as revealed by environmental DNA (eDNA) analyses on the sediment samples, implying that both species are selective feeders rather than dietary generalists. Significant differences observed in the dietary compositions of the two species might be partially due to the difference in habitat preference between the two species. This study provides new insights into the trophic ecology of the two Asian horseshoe crab species in the estuarine habitat and establishes a new framework for future detailed molecular dietary analyses on all developmental stages of horseshoe crabs around the world, which will allow us to evaluate the food sources needed for the survival of horseshoe crabs and facilitate future conservation strategies without killing the animals.
Microvasculature Features of Vogt-Koyanagi-Harada Disease Revealed by Widefield Swept-Source Optical Coherence Tomography Angiography
Authors: Ye Xiaoyuan , Zhang Haiping , Xiao Peng , Wang Gengyuan , Hu Xiaoqing , Yan Chun , Li Fan , Hu Yixin , Su Lishi , Luo Jiawen , Yuan Jin , Wen Feng , Chi Wei
Published: October 2021

Background: Vogt-Koyanagi-Harada (VKH) disease is a multisystem autoimmune disorder which could induce bilateral panuveitis involving the posterior pole and peripheral fundus. Optical coherence tomography angiography (OCTA) provides several advantages over traditional fluorescence angiography for revealing pathological abnormalities of the retinal vasculature. Until recently, however, the OCTA field of view (FOV) was limited to 6 × 6 mm2 scans.

Purpose: This study examined retinal vasculature and choriocapillaris abnormalities across multiple regions of the retina (15 × 9 mm2 wide field, macular, peripapillary regions) among acute and convalescent VKH patients using a novel widefield swept-source OCTA (WSS-OCTA) device and assessed correlations between imaging features and best-corrected visual acuity (BCVA).

Methods: Twenty eyes of 13 VHK disease patients in the acute phase, 30 eyes of 17 patients in the convalescent phase, and 30 eyes of 15 healthy controls (HCs) were included in this study. Vascular length density (VLD) in superficial and deep vascular plexuses (SVP, DVP), vascular perfusion density (VPD) in SVP, DVP, and choriocapillaris (CC), and flow voids (FV) in CC were measured across multiple retinal regions via WSS-OCTA (PLEX Elite 9000, Carl Zeiss Meditec Inc., USA) using the 15 × 9 mm2 scan pattern centered on the fovea and quantified by ImageJ.

Results: Compared to HCs, acute phase VKH patients exhibited significantly reduced SVP-VLD, SVP-VPD, and CC-VPD across multiple retinal regions (all p < 0.01). Notably, the FV area was more extensive in VKH patients, especially those in the acute phase (p < 0.01). These changes were reversed in the convalescent phase. Stepwise multiple linear regression analysis demonstrated that macular DVP-VLD and macular CC-VPD were the best predictive factors for BCVA in the acute and convalescent VKH groups.

Conclusion: The wider field of SS-OCAT provides more comprehensive and detailed images of the microvasculature abnormalities characterizing VKH disease. The quantifiable and layer-specific information from OCTA allows for the identification of sensitive and specific imaging markers for prognosis and treatment guidance, highlighting WSS-OCTA as a promising modality for the clinical management of VKH disease.
Genomic Characterisation of Campylobacter jejuni Isolates Recovered During Commercial Broiler Production
Authors: Truccollo Brendha , Whyte Paul , Burgess Catherine M. , Bolton Declan J.
Published: October 2021

Background:Campylobacter is commonly transmitted to humans from chickens. Campylobacter jejuni is the species most frequently associated with human illness, and the most prevalent species recovered from poultry.

Objective: The objective of this study was to analyse a sub-population of C. jejuni from two broiler flocks on the farm and at slaughter using whole-genome sequencing to gain insights into the changes in the Campylobacter population during broiler production, including changes in virulence and antimicrobial resistance profiles.

Methods: In this study, ten composite faecal samples (n=10), obtained by pooling ten fresh faecal samples (n=10), were collected in the broiler house on two farms on days 14, 21, 28, and 34 (n=80) and ten composite (n=10) caecal samples were collected at the time of slaughter for each flock (n=20). These were tested for C. jejuni using the ISO 10272-2:2016 method. Seven isolates were randomly selected from each of the nine Campylobacter-positive sampling points (n=63) and were subjected to antimicrobial susceptibility tests. Their genomes were sequenced and the data obtained was used to characterise the population structure, virulence, antimicrobial resistance determinants and inter-strain variation.

Results: The Farm 1 isolates had three MLST types (ST257-257, ST814-661 and ST48-48) while those on Farm 2 were ST6209-464 and ST9401. Interestingly, only the MLST types positive for most of the virulence genes tested in this study persisted throughout the production cycle, and the detection of antimicrobial resistance determinants (gyrA T86I and tetO) increased after thinning and at slaughter, with the detection of new strains.

Conclusion: The persistence of the most virulent strains detected in this study throughout the production cycle has important implications for the risk to consumers and requires further investigation. The detection of new strains within the population corresponding with the time of thinning and transportation reflects previous reports and provides further evidence that these activities pose a risk of introducing new Campylobacter strains to broiler batches.
Characterization of Basal Transcriptomes Identifies Potential Metabolic and Virulence-Associated Adaptations Among Diverse Nontyphoidal Salmonella enterica Serovars
Authors: Cohn Alexa R. , Orsi Renato H. , Carroll Laura M. , Chen Ruixi , Wiedmann Martin , Cheng Rachel A.
Published: October 2021

The zoonotic pathogenSalmonella entericaincludes >2,600 serovars, which differ in the range of hosts they infect and the severity of disease they cause. To further elucidate the mechanisms behind these differences, we performed transcriptomic comparisons of nontyphoidalSalmonella(NTS) serovars with the model for NTS pathogenesis,S. Typhimurium. Specifically, we used RNA-seq to characterize the understudied NTS serovarsS. Javiana andS. Cerro, representing a serovar frequently attributed to human infectionviacontact with amphibians and reptiles, and a serovar primarily associated with cattle, respectively. Whole-genome sequence (WGS) data were utilized to ensure that strains characterized with RNA-seq were representative of their respective serovars. RNA extracted from representative strains of each serovar grown to late exponential phase in Luria-Bertani (LB) broth showed that transcript abundances of core genes were significantly higher (p<0.001) than those of accessory genes for all three serovars. Inter-serovar comparisons identified that transcript abundances of genes inSalmonellaPathogenicity Island (SPI) 1 were significantly higher in bothS. Javiana andS. Typhimurium compared toS. Cerro. Together, our data highlight potential transcriptional mechanisms that may facilitateS. Cerro andS. Javiana survival in and adaptation to their respective hosts and impact their ability to cause disease in others. Furthermore, our analyses demonstrate the utility of omics approaches in advancing our understanding of the diversity of metabolic and virulence mechanisms of different NTS serovars.