bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing of Breeding Site Availability Across the North-American Arctic Partly Determines Spring Migration Schedule in a Long-Distance Neotropical Migrant
Authors: Lamarre Jean-François , Gauthier Gilles , Lanctot Richard B. , Saalfeld Sarah T. , Love Oliver P. , Reed Eric , Johnson Oscar W. , Liebezeit Joe , McGuire Rebecca , Russell Mike , Nol Erica , Koloski Laura , Sanders Felicia , McKinnon Laura , Smith Paul A. , Flemming Scott A. , Lecomte Nicolas , Giroux Marie-Andrée , Bauer Silke , Emmenegger Tamara , Bêty Joël
Published: October 2021

Long-distance migrants are under strong selection to arrive on their breeding grounds at a time that maximizes fitness. Many arctic birds start nesting shortly after snow recedes from their breeding sites and timing of snowmelt can vary substantially over the breeding range of widespread species. We tested the hypothesis that migration schedules of individuals co-occurring at the same non-breeding areas are adapted to average local environmental conditions encountered at their specific and distant Arctic breeding locations. We predicted that timing of breeding site availability (measured here as the average snow-free date) should explain individual variation in departure time from shared non-breeding areas. We tested our prediction by tracking American Golden-Plovers (Pluvialis dominica) nesting across the North-American Arctic. These plovers use a non-breeding (wintering) area in South America and share a spring stopover area in the nearctic temperate grasslands, located >1,800 km away from their nesting locations. As plovers co-occur at the same non-breeding areas but use breeding sites segregated by latitude and longitude, we could disentangle the potential confounding effects of migration distance and timing of breeding site availability on individual migration schedule. As predicted, departure date of individuals stopping-over in sympatry was positively related to the average snow-free date at their respective breeding location, which was also related to individual onset of incubation. Departure date from the shared stopover area was not explained by the distance between the stopover and the breeding location, nor by the stopover duration of individuals. This strongly suggests that plover migration schedule is adapted to and driven by the timing of breeding site availability per se. The proximate mechanism underlying the variable migration schedule of individuals is unknown and may result from genetic differences or individual learning. Temperatures are currently changing at different speeds across the Arctic and this likely generates substantial heterogeneity in the strength of selection pressure on migratory schedule of arctic birds migrating sympatrically.
Placental Gene Co-expression Network for Maternal Plasma Lipids Revealed Enrichment of Inflammatory Response Pathways
Authors: Ouidir Marion , Chatterjee Suvo , Mendola Pauline , Zhang Cuilin , Grantz Katherine. L. , Tekola-Ayele Fasil
Published: October 2021

Maternal dyslipidemia during pregnancy has been associated with suboptimal fetal growth and increased cardiometabolic diseasse risk in offspring. Altered placental function driven by placental gene expression is a hypothesized mechanism underlying these associations. We tested the relationship between maternal plasma lipid concentrations and placental gene expression. Among 64 pregnant women from the NICHD Fetal Growth Studies–Singleton cohort with maternal first trimester plasma lipids we extracted RNA-Seq on placental samples obtained at birth. Placental gene co-expression networks were validated by regulatory network analysis that integrated transcription factors and gene expression, and genome-wide transcriptome analysis. Network analysis detected 24 gene co-expression modules in placenta, of which one module was correlated with total cholesterol (r = 0.27, P-value = 0.03) and LDL-C (r = 0.31, P-value = 0.01). Genes in the module (n = 39 genes) were enriched in inflammatory response pathways. Out of the 39 genes in the module, three known lipid-related genes (MPO, PGLYRP1 and LTF) and MAGEC2 were validated by the regulatory network analysis, and one known lipid-related gene (ALX4) and two germ-cell development-related genes (MAGEC2 and LUZP4) were validated by genome-wide transcriptome analysis. Placental gene expression signatures associated with unfavorable maternal lipid concentrations may be potential pathways underlying later life offspring cardiometabolic traits.

Clinical Trial Registration:ClinicalTrials.gov, identifier NCT00912132.
Network Biology Approaches to Achieve Precision Medicine in Inflammatory Bowel Disease
Authors: Thomas John P , Modos Dezso , Korcsmaros Tamas , Brooks-Warburton Johanne
Published: October 2021

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition arising due to complex interactions between multiple genetic and environmental factors. Despite recent advances, the pathogenesis of the condition is not fully understood and patients still experience suboptimal clinical outcomes. Over the past few years, investigators are increasingly capturing multi-omics data from patient cohorts to better characterise the disease. However, reaching clinically translatable endpoints from these complex multi-omics datasets is an arduous task. Network biology, a branch of systems biology that utilises mathematical graph theory to represent, integrate and analyse biological data through networks, will be key to addressing this challenge. In this narrative review, we provide an overview of various types of network biology approaches that have been utilised in IBD including protein-protein interaction networks, metabolic networks, gene regulatory networks and gene co-expression networks. We also include examples of multi-layered networks that have combined various network types to gain deeper insights into IBD pathogenesis. Finally, we discuss the need to incorporate other data sources including metabolomic, histopathological, and high-quality clinical meta-data. Together with more robust network data integration and analysis frameworks, such efforts have the potential to realise the key goal of precision medicine in IBD.
Association Analyses of TP53 Mutation With Prognosis, Tumor Mutational Burden, and Immunological Features in Acute Myeloid Leukemia
Authors: Wen Xiang-mei , Xu Zi-jun , Jin Ye , Xia Pei-hui , Ma Ji-chun , Qian Wei , Lin Jiang , Qian Jun
Published: October 2021

Acute myeloid leukemia (AML) is a heterogeneous disease related to a broad spectrum of molecular alterations. The successes of immunotherapies treating solid tumors and a deeper understanding of the immune systems of patients with hematologic malignancies have promoted the development of immunotherapies for the treatment of AML. And high tumor mutational burden (TMB) is an emerging predictive biomarker for response to immunotherapy. However, the association of gene mutation in AML with TMB and immunological features still has not been clearly elucidated. In our study, based on The Cancer Genome Atlas (TCGA) and BeatAML cohorts, 20 frequently mutated genes were found to be covered by both datasets in AML. And TP53 mutation was associated with a poor prognosis, and its mutation displayed exclusiveness with other common mutated genes in both datasets. Moreover, TP53 mutation correlated with TMB and the immune microenvironment. Gene Set Enrichment Analysis (GSEA) showed that TP53 mutation upregulated signaling pathways involved in the immune system. In summary, TP53 mutation is frequently mutated in AML, and its mutation is associated with dismal outcome, TMB, and immunological features, which may serve as a biomarker to predict immune response in AML.
Specific Protein Antigen Delivery to Human Langerhans Cells in Intact Skin
Authors: Rentzsch Mareike , Wawrzinek Robert , Zelle-Rieser Claudia , Strandt Helen , Bellmann Lydia , Fuchsberger Felix F. , Schulze Jessica , Busmann Jil , Rademacher Juliane , Sigl Stephan , Del Frari Barbara , Stoitzner Patrizia , Rademacher Christoph
Published: October 2021

Immune modulating therapies and vaccines are in high demand, not least to the recent global spread of SARS-CoV2. To achieve efficient activation of the immune system, professional antigen presenting cells have proven to be key coordinators of such responses. Especially targeted approaches, actively directing antigens to specialized dendritic cells, promise to be more effective and accompanied by reduced payload due to less off-target effects. Although antibody and glycan-based targeting of receptors on dendritic cells have been employed, these are often expensive and time-consuming to manufacture or lack sufficient specificity. Thus, we applied a small-molecule ligand that specifically binds Langerin, a hallmark receptor on Langerhans cells, conjugated to a model protein antigen.Viamicroneedle injection, this construct was intradermally administered into intact human skin explants, selectively loading Langerhans cells in the epidermis. The ligand-mediated cellular uptake outpaces protein degradation resulting in intact antigen delivery. Due to the pivotal role of Langerhans cells in induction of immune responses, this approach of antigen-targeting of tissue-resident immune cells offers a novel way to deliver highly effective vaccines with minimally invasive administration.
The Role of Innate Immune System in the Human Amniotic Membrane and Human Amniotic Fluid in Protection Against Intra-Amniotic Infections and Inflammation
Authors: Šket Tina , Ramuta Taja Železnik , Starčič Erjavec Marjanca , Kreft Mateja Erdani
Published: October 2021

Intra-amniotic infection and inflammation (IAI) affect fetal development and are highly associated with preterm labor and premature rupture of membranes, which often lead to adverse neonatal outcomes. Human amniotic membrane (hAM), the inner part of the amnio-chorionic membrane, protects the embryo/fetus from environmental dangers, including microbial infection. However, weakened amnio-chorionic membrane may be breached or pathogens may enter through a different route, leading to IAI. The hAM and human amniotic fluid (hAF) respond by activation of all components of the innate immune system. This includes changes in 1) hAM structure, 2) presence of immune cells, 3) pattern recognition receptors, 4) cytokines, 5) antimicrobial peptides, 6) lipid derivatives, and 7) complement system. Herein we provide a comprehensive and integrative review of the current understanding of the innate immune response in the hAM and hAF, which will aid in design of novel studies that may lead to breakthroughs in how we perceive the IAI.
Comparative Histological Subtyping of Immune Cell Infiltrates in MPO-ANCA and PR3-ANCA Glomerulonephritis
Authors: Hakroush Samy , Tampe Désirée , Ströbel Philipp , Korsten Peter , Tampe Björn
Published: October 2021

Background

Acute kidney injury (AKI) is a common and severe complication of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), potentially leading to chronic kidney disease (CKD), end-stage renal disease (ESRD), or death. Pathogenic ANCAs, in particular proteinase 3 (PR3) and myeloperoxidase (MPO), trigger a deleterious immune response with intrarenal immune cell infiltration resulting in a pauci-immune necrotizing and crescentic glomerulonephritis (GN). However, a systematic analysis of intrarenal immune cell subtypes concerning neutrophils, eosinophils, plasma cells, and mononuclear cell infiltrates (macrophages, lymphocytes) in ANCA GN remains elusive. Therefore, we aimed to compare distinct immune cell infiltrates in association with clinicopathological findings in ANCA GN.

Methods

A total of 53 kidney biopsies with ANCA GN at the University Medical Center Göttingen were retrospectively analyzed. Histological infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the total area of inflammation.

Results

Neutrophilic infiltrates were associated with glomerular necrosis and severe kidney injury in ANCA GN. Among tubulointerstitial lesions, intrarenal neutrophils correlated with interstitial inflammation, tubulitis, and inflammation in areas of interstitial fibrosis/tubular atrophy (IFTA), representing active inflammatory lesions. Concerning eosinophils, infiltrates were associated with severe kidney injury, interstitial inflammation, and cellular casts independent of glomerular lesions, implicating a distinct role in inflammation and damage in ANCA GN. Plasma cell infiltrates correlated with tubulitis and interstitial fibrosis and were associated with renal replacement therapy during the short-term disease course. Finally, mononuclear cell infiltrates correlated with severe kidney injury and active histopathological lesions (glomerular crescents, interstitial inflammation, tubulitis, inflammation, and tubulitis in areas of IFTA) besides chronic lesions (interstitial fibrosis and tubular atrophy) in ANCA GN. Interestingly, intrarenal subtypes of immune cell infiltrates differed in MPO-ANCA versus PR3-ANCA GN and were associated with distinct glomerular and tubulointerstitial lesions, implicating different pathogenic mechanisms of kidney injury in ANCA subtypes.

Conclusion

Our observations imply distinct pathomechanisms contributing to inflammation and renal injury in MPO vs. PR3-associated ANCA GN and potentially contribute to new therapeutic targets in specific ANCA subtypes.
Microbiome Crosstalk in Immunotherapy and Antiangiogenesis Therapy
Authors: Wan Xueting , Song Mengyao , Wang Aiyun , Zhao Yang , Wei Zhonghong , Lu Yin
Published: October 2021

The human body and its microbiome constitute a highly delicate system. The gut microbiome participates in the absorption of the host’s nutrients and metabolism, maintains the microcirculation, and modulates the immune response. Increasing evidence shows that gut microbiome dysbiosis in the body not only affects the occurrence and development of tumors but also tumor prognosis and treatment. Microbiome have been implicated in tumor control in patients undergoing anti- angiogenesis therapy and immunotherapy. In cases with unsatisfactory responses to chemotherapy, radiotherapy, and targeted therapy, appropriate adjustment of microbes abundance is considered to enhance the treatment response. Here, we review the current research progress in cancer immunotherapy and anti- angiogenesis therapy, as well as the unlimited potential of their combination, especially focusing on how the interaction between intestinal microbiota and the immune system affects cancer pathogenesis and treatment. In addition, we discuss the effects of microbiota on anti-cancer immune response and anti- angiogenesis therapy, and the potential value of these interactions in promoting further research in this field.
Aspartate Metabolism Facilitates IL-1β Production in Inflammatory Macrophages
Authors: Wang Hao , Zheng Xueyue , Liu Bingnan , Xia Yaoyao , Xin Zhongquan , Deng Baichuan , He Liuqin , Deng Jinping , Ren Wenkai
Published: October 2021

Increasing evidence support that cellular amino acid metabolism shapes the fate of immune cells; however, whether aspartate metabolism dictates macrophage function is still enigmatic. Here, we found that the metabolites in aspartate metabolism are depleted in lipopolysaccharide (LPS) plus interferon gamma (IFN-γ)-stimulated macrophages. Aspartate promotes interleukin-1β (IL-1β) secretion in M1 macrophages. Mechanistically, aspartate boosts the activation of hypoxia-inducible factor-1α (HIF-1α) and inflammasome and increases the levels of metabolites in aspartate metabolism, such as asparagine. Interestingly, asparagine also accelerates the activation of cellular signaling pathways and promotes the production of inflammatory cytokines from macrophages. Moreover, aspartate supplementation augments the macrophage-mediated inflammatory responses in mice and piglets. These results uncover a previously uncharacterized role for aspartate metabolism in directing M1 macrophage polarization.
Sequential Analysis of the N/O-Glycosylation of Heavily Glycosylated HIV-1 gp120 Using EThcD-sceHCD-MS/MS
Authors: Zhang Yong , Zheng Shanshan , Zhao Wanjun , Mao Yonghong , Cao Wei , Zeng Wenjuan , Liu Yueqiu , Hu Liqiang , Gong Meng , Cheng Jingqiu , Chen Younan , Yang Hao
Published: October 2021

Deciphering the glycosylation of the viral envelope (Env) glycoprotein is critical for evaluating viral escape from the host’s immune response and developing vaccines and antiviral drugs. However, it is still challenging to precisely decode the site-specific glycosylation characteristics of the highly glycosylated Env proteins, although glycoproteomics have made significant advances in mass spectrometry techniques and data analysis tools. Here, we present a hybrid dissociation technique, EThcD-sceHCD, by combining electron transfer/higher-energy collisional dissociation (EThcD) and stepped collision energy/higher-energy collisional dissociation (sceHCD) into a sequential glycoproteomic workflow. Following this scheme, we characterized site-specific N/O-glycosylation of the human immunodeficiency virus type 1 (HIV-1) Env protein gp120. The EThcD-sceHCD method increased the number of identified glycopeptides when compared with EThcD, while producing more comprehensive fragment ions than sceHCD for site-specific glycosylation analysis, especially for accurate O-glycosite assignment. Finally, eighteen N-glycosites and five O-glycosites with attached glycans were assigned unambiguously from heavily glycosylated gp120. These results indicate that our workflow can achieve improved performance for analysis of the N/O-glycosylation of a highly glycosylated protein containing numerous potential glycosites in one process. Knowledge of the glycosylation landscape of the Env glycoprotein will be useful for understanding of HIV-1 infection and development of vaccines and drugs.
Understanding Viral and Immune Interplay During Vertical Transmission of HIV: Implications for Cure
Authors: Amin Omayma , Powers Jenna , Bricker Katherine M. , Chahroudi Ann
Published: October 2021

Despite the significant progress that has been made to eliminate vertical HIV infection, more than 150,000 children were infected with HIV in 2019, emphasizing the continued need for sustainable HIV treatment strategies and ideally a cure for children. Mother-to-child-transmission (MTCT) remains the most important route of pediatric HIV acquisition and, in absence of prevention measures, transmission rates range from 15% to 45%viathree distinct routes:in utero, intrapartum, and in the postnatal period through breastfeeding. The exact mechanisms and biological basis of these different routes of transmission are not yet fully understood. Some infants escape infection despite significant virus exposure, while others do not, suggesting possible maternal or fetal immune protective factors including the presence of HIV-specific antibodies. Here we summarize the unique aspects of HIV MTCT including the immunopathogenesis of the different routes of transmission, and how transmission in the antenatal or postnatal periods may affect early life immune responses and HIV persistence. A more refined understanding of the complex interaction between viral, maternal, and fetal/infant factors may enhance the pursuit of strategies to achieve an HIV cure for pediatric populations.
Crosstalk Between Trophoblast and Macrophage at the Maternal-Fetal Interface: Current Status and Future Perspectives
Authors: Ding Jinli , Zhang Yan , Cai Xiaopeng , Diao Lianghui , Yang Chaogang , Yang Jing
Published: October 2021

The immune tolerance microenvironment is crucial for the establishment and maintenance of pregnancy at the maternal-fetal interface. The maternal-fetal interface is a complex system containing various cells, including lymphocytes, decidual stromal cells, and trophoblasts. Macrophages are the second-largest leukocytes at the maternal-fetal interface, which has been demonstrated to play essential roles in remodeling spiral arteries, maintaining maternal-fetal immune tolerance, and regulating trophoblast’s biological behaviors. Many researchers, including us, have conducted a series of studies on the crosstalk between macrophages and trophoblasts at the maternal-fetal interface: on the one hand, macrophages can affect the invasion and migration of trophoblasts; on the other hand, trophoblasts can regulate macrophage polarization and influence the state of the maternal-fetal immune microenvironment. In this review, we systemically introduce the functions of macrophages and trophoblasts and the cell-cell interaction between them for the establishment and maintenance of pregnancy. Advances in this area will further accelerate the basic research and clinical translation of reproductive medicine.
Semi-Automated Live Tracking of Microglial Activation in CX3CR1GFP Mice During Experimental Autoimmune Encephalomyelitis by Confocal Scanning Laser Ophthalmoscopy
Authors: Frenger Moritz J. , Hecker Christina , Sindi Mustafa , Issberner Andrea , Hartung Hans-Peter , Meuth Sven G. , Dietrich Michael , Albrecht Philipp
Published: October 2021

Confocal scanning laser ophthalmoscopy (cSLO) is a non-invasive technique for real-time imaging of the retina. We developed a step-by-step protocol for the semi-automatic evaluation of myeloid cells in cSLO images from CX3CR1GFP mice, expressing green fluorescent protein (GFP) under control of the endogenous CX3C chemokine receptor 1 locus. We identified cSLO parameters allowing us to distinguish animals with experimental autoimmune encephalomyelitis (EAE) from sham-treated/naïve animals. Especially cell count (CC) and the total microglial area (SuA) turned out to be reliable parameters. Comparing the cSLO results with clinical parameters, we found significant correlations between the clinical EAE score and the SuA and of the inner retinal layer thickness, measured by optical coherence tomography, with the CC as well as the SuA. As a final step, we performed immunohistochemistry to confirm that the GFP-expressing cells visualized by the cSLO are Iba1 positive and validated the step-by-step protocol against manual counting. We present a semi-automatic step-by-step protocol with a balance between fast data evaluation and adequate accuracy, which is optimized by the option to manually adapt the contrast threshold. This protocol may be useful for numerous research questions on the role of microglial polarization in models of inflammatory and degenerating CNS diseases involving the retina.
Dysregulated Immune Responses in COVID-19 Patients Correlating With Disease Severity and Invasive Oxygen Requirements
Authors: García-González Paulina , Tempio Fabián , Fuentes Camila , Merino Consuelo , Vargas Leonardo , Simon Valeska , Ramirez-Pereira Mirliana , Rojas Verónica , Tobar Eduardo , Landskron Glauben , Araya Juan Pablo , Navarrete Mariela , Bastias Carla , Tordecilla Rocío , Varas Macarena A. , Maturana Pablo , Marcoleta Andrés E. , Allende Miguel L. , Naves Rodrigo , Hermoso Marcela A. , Salazar-Onfray Flavio , Lopez Mercedes , Bono María Rosa , Osorio Fabiola
Published: October 2021

The prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery. We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide useful information to better understand the diverse outcomes of severe COVID-19 pathogenesis.
The Ontogeny and Function of Placental Macrophages
Authors: Thomas Jake R. , Naidu Praveena , Appios Anna , McGovern Naomi
Published: October 2021

The placenta is a fetal-derived organ whose function is crucial for both maternal and fetal health. The human placenta contains a population of fetal macrophages termed Hofbauer cells. These macrophages play diverse roles, aiding in placental development, function and defence. The outer layer of the human placenta is formed by syncytiotrophoblast cells, that fuse to form the syncytium. Adhered to the syncytium at sites of damage, on the maternal side of the placenta, is a population of macrophages termed placenta associated maternal macrophages (PAMM1a). Here we discuss recent developments that have led to renewed insight into our understanding of the ontogeny, phenotype and function of placental macrophages. Finally, we discuss how the application of new technologies within placental research are helping us to further understand these cells.
Conventional and Organic Wheat Germ Have Distinct Physiological Effects in the Tobacco Hornworm, Manduca Sexta: Use of Black Mutant Assay to Detect Environmental Juvenoid Activity of Insect Growth Regulators
Authors: Ffrench Jivonsha , Tracewell Jaime , Suzuki Yuichiro
Published: October 2021

Stored grains used in artificial diets are often treated with insecticides to control infestation by pests. In recent years, insect growth regulators (IGRs) have become an increasingly popular form of insect pest control in agricultural settings. Most IGRs specifically target insects by either disrupting their endocrine system or their chitin synthesis. One type of IGRs comprises of chemical analogs of juvenile hormone (JH), a major hormone involved in growth and development of insects. Here we demonstrate that conventional wheat germ contains JH activity and impacts growth and development of the tobacco hornworm,Manduca sexta. Feeding diet containing conventional wheat germ delayed the timing of metamorphosis in wildtype larvae by extending the duration of the final instar. Diet with conventional wheat germ also inhibited melanization of theblackmutant larvae and induced the expression of the JH response gene,Krüppel homolog 1. We demonstrate that theblackmutant bioassay is a sensitive assay that can determine the amount of JH activity in stored grains and suggest that this assay may offer a quick and reliable assay to determine the amount of environmental juvenoids. Researchers are urged to use caution when purchasing stored grains for mass-rearing of research insects.
Integrating Stochastic and Deterministic Process in the Biogeography of N2-Fixing Cyanobacterium Candidatus Atelocyanobacterium Thalassa
Authors: Li Liuyang , Wu Chao , Huang Danyue , Ding Changling , Wei Yuqiu , Sun Jun
Published: October 2021

UCYN-A is one of the most widespread and important marine diazotrophs. Its unusual distribution in both cold/warm and coastal/oceanic waters challenges current understanding about what drives the biogeography of diazotrophs. This study assessed the community assembly processes of the nitrogen-fixing cyanobacterium UCYN-A, developing a framework of assembly processes underpinning the microbial biogeography and diversity. High-throughput sequencing and a qPCR approach targeting the nifH gene were used to investigate three tropical seas: the Bay of Bengal, the Western Pacific Ocean, and the South China Sea. Based on the neutral community model and two types of null models calculating the β-nearest taxon index and the normalized stochasticity ratio, we found that stochastic assembly processes could explain 66–92% of the community assembly; thus, they exert overwhelming influence on UCYN-A biogeography and diversity. Among the deterministic processes, temperature and coastal/oceanic position appeared to be the principal environmental factors driving UCYN-A diversity. In addition, a close linkage between assembly processes and UCYN-A abundance/diversity/drivers can provide clues for the unusual global distribution of UCYN-A.
Listeria monocytogenes 10403S Alternative Sigma-54 Factor σL Has a Negative Role on Survival Ability Under Bile Exposure
Authors: Boonmee Atsadang , Oliver Haley F. , Chaturongakul Soraya
Published: October 2021

Listeria monocytogenes is a Gram-positive bacterium causing listeriosis in animals and humans. To initiate a foodborne infection, L. monocytogenes has to pass through the host gastrointestinal tract (GIT). In this study, we evaluated survival abilities of L. monocytogenes 10403S wild type (WT) and its isogenic mutants in alternative sigma (σ) factor genes (i.e., sigB, sigC, sigH, and sigL) under simulated gastric, duodenal, and bile fluids. Within 10min of exposures, only bile fluid was able to significantly reduce survival ability of L. monocytogenes WT by 2 logs CFU/ml. Loss of sigL showed the greatest bile resistance among 16 strains tested, p<0.0001, (i.e., WT, four single alternative σ factor mutants, six double mutants, four triple mutants, and one quadruple mutant). To further investigate the role of σL in bile response, RNA-seq was conducted to compare the transcriptional profiles among L. monocytogenes 10403S ΔBCH triple mutant (lacking sigB, sigC, and sigH genes; expressing housekeeping σA and σL) and ΔBCHL quadruple mutant (lacking all alternative sigma factor genes; expressing only σA) strains under BHI and 1% bile conditions. A total of 216 and 176 differentially expressed genes (DEGs) were identified in BHI and bile, respectively. We confirmed that mpt operon was shown to be strongly activated by σL. Interestingly, more than 80% of DEGs were found to be negatively regulated in the presence of σL. This includes PrfA regulon and its mediated genes (i.e., hly, hpt, inlB, clpP, clpE, groL, and inlC) which were downregulated in response to bile in the presence of σL. This result suggests the potential negative role of σL on bile survival, and the roles of σL and σB might be in a seesaw model prior to host cell invasion.
Chemodiversity of Soil Dissolved Organic Matter and Its Association With Soil Microbial Communities Along a Chronosequence of Chinese Fir Monoculture Plantations
Authors: Li Ying , Heal Kate , Wang Shuzhen , Cao Sheng , Zhou Chuifan
Published: October 2021

The total dissolved organic matter (DOM) content of soil changes after vegetation transformation, but the diversity of the underlying chemical composition has not been explored in detail. Characterizing the molecular diversity of DOM and its fate enables a better understanding of the soil quality of monoculture forest plantations. This study characterized the chemodiversity of soil DOM, assessed the variation of the soil microbial community composition, and identified specific linkages between DOM molecules and microbial community composition in soil samples from a 100-year chronosequence of Chinese fir monoculture plantations. With increasing plantation age, soil total carbon and dissolved organic carbon first decreased and then increased, while soil nutrients, such as available potassium and phosphorus and total nitrogen, potassium, and phosphorus, increased significantly. Lignin/carboxylic-rich alicyclic molecule (CRAM)-like structures accounted for the largest proportion of DOM, while aliphatic/proteins and carbohydrates showed a decreasing trend along the chronosequence. DOM high in H/C (such as lipids and aliphatic/proteins) degraded preferentially, while low-H/C DOM (such as lignin/CRAM-like structures and tannins) showed recalcitrance during stand development. Soil bacterial richness and diversity increased significantly as stand age increased, while soil fungal diversity tended to increase during early stand development and then decrease. The soil microbial community had a complex connectivity and strong interaction with DOM during stand development. Most bacterial phyla, such as Acidobacteria, Chloroflexi, and Firmicutes, were very significantly and positively correlated with DOM molecules. However, Verrucomicrobia and almost all fungi, such as Basidiomycota and Ascomycota, were significantly negatively correlated with DOM molecules. Overall, the community of soil microorganisms interacted closely with the compositional variability of DOM in the monoculture plantations investigated, both by producing and consuming DOM. This suggests that DOM is not intrinsically recalcitrant but instead persists in soils as a result of simultaneous consumption, transformation, and formation by soil microorganisms with extended stand ages of Chinese fir plantations.
The Nucleolar Localization Signal of Porcine Circovirus Type 4 Capsid Protein Is Essential for Interaction With Serine-48 Residue of Nucleolar Phosphoprotein Nucleophosmin-1
Authors: Zhou Jianwei , Qiu Yonghui , Zhu Ning , Zhou Linyi , Dai Beining , Feng Xufei , Hou Lei , Liu Jue
Published: October 2021

Porcine circovirus type 4 (PCV4) is an emerging etiological agent which was first detected in 2019. The nucleolar localization signal (NoLS) of PCV4 Cap protein and its binding host cellular proteins are still not elucidated. In the present study, we discovered a distinct novel NoLS of PCV4 Cap, which bound to the nucleolar phosphoprotein nucleophosmin-1 (NPM1). The NoLS of PCV4 Cap and serine-48 residue at the N-terminal oligomerization domain of NPM1 were necessary for PCV4 Cap/NPM1 interaction. Furthermore, the charge property of serine residue at position 48 of the NPM1 was crucial for its oligomerization and interaction with PCV4 Cap. In summary, our findings show for the first time that the PCV4 Cap NoLS and the NPM1 oligomerization determine the interaction of Cap/NPM1.
Comparative Study of the Gut Microbiota Among Four Different Marine Mammals in an Aquarium
Authors: Bai Shijie , Zhang Peijun , Zhang Changhao , Du Jiang , Du Xinyi , Zhu Chengwei , Liu Jun , Xie Peiyu , Li Songhai
Published: October 2021

Despite an increasing appreciation in the importance of host–microbe interactions in ecological and evolutionary processes, information on the gut microbial communities of some marine mammals is still lacking. Moreover, whether diet, environment, or host phylogeny has the greatest impact on microbial community structure is still unknown. To fill part of this knowledge gap, we exploited a natural experiment provided by an aquarium with belugas (Delphinapterus leucas) affiliated with family Monodontidae, Pacific white-sided dolphins (Lagenorhynchus obliquidens) and common bottlenose dolphin (Tursiops truncatus) affiliated with family Delphinidae, and Cape fur seals (Arctocephalus pusillus pusillus) affiliated with family Otariidae. Results show significant differences in microbial community composition of whales, dolphins, and fur seals and indicate that host phylogeny (family level) plays the most important role in shaping the microbial communities, rather than food and environment. In general, the gut microbial communities of dolphins had significantly lower diversity compared to that of whales and fur seals. Overall, the gut microbial communities were mainly composed of Firmicutes and Gammaproteobacteria, together with some from Bacteroidetes, Fusobacteria, and Epsilonbacteraeota. However, specific bacterial lineages were differentially distributed among the marine mammal groups. For instance,Lachnospiraceae,Ruminococcaceae, andPeptostreptococcaceaewere the dominant bacterial lineages in the gut of belugas, while for Cape fur seals,MoraxellaceaeandBacteroidaceaewere the main bacterial lineages. Moreover, gut microbial communities in both Pacific white-sided dolphins and common bottlenose dolphins were dominated by a number of pathogenic bacteria, includingClostridium perfringens,Vibrio fluvialis, andMorganella morganii, reflecting the poor health condition of these animals. Although there is a growing recognition of the role microorganisms play in the gut of marine mammals, current knowledge about these microbial communities is still severely lacking. Large-scale research studies should be undertaken to reveal the roles played by the gut microbiota of different marine mammal species.
Cooperation of Conical and Polyunsaturated Lipids to Regulate Initiation and Processing of Membrane Fusion
Authors: François-Martin Claire , Bacle Amélie , Rothman James E. , Fuchs Patrick F. J. , Pincet Frédéric
Published: October 2021

The shape of lipids has long been suspected to be a critical determinant for the control of membrane fusion. To experimentally test this assertion, we used conical and malleable lipids and measured their influence on the fusion kinetics. We found that, as previously suspected, both types of lipids accelerate fusion. However, the implicated molecular mechanisms are strikingly different. Malleable lipids, with their ability to change shape with low energy cost, favor fusion by decreasing the overall activation energy. On the other hand, conical lipids, with their small polar head relative to the area occupied by the hydrophobic chains, tend to make fusion less energetically advantageous because they tend to migrate towards the most favorable lipid leaflet, hindering fusion pore opening. They could however facilitate fusion by generating hydrophobic defects on the membranes; this is suggested by the similar trend observed between the experimental rate of fusion nucleation and the surface occupied by hydrophobic defects obtained by molecular simulations. The synergy of dual-process, activation energy and nucleation kinetics, could facilitate membrane fusion regulation in vivo.
Alcohol Seeking Under Risk of Punishment Is Associated With Activation of Cortical and Subcortical Brain Regions
Authors: McDonald Allison J. , Alonso-Lozares Isis , Rauh Vasco , van Mourik Yvar , Schetters Dustin , De Vries Taco J. , Marchant Nathan J.
Published: October 2021

In humans, stimuli associated with alcohol availability can provoke relapse during abstinence. In this study, we investigated the role of discriminative stimuli (DS) in the control of alcohol seeking in two types of behavioral tests. The first test examined the ability of an alcohol-associated DS to promote alcohol seeking (relapse) after punishment-imposed abstinence in the presence of a different DS. Following this, we tested whether the differentially associated DS can promote and suppress alcohol self-administration in a within-session discrimination task. During the within-session discrimination task, we also tested the rate of alcohol self-administration when two DS are presented in a compound. We first trained Long-Evans male rats (n = 24) to self-administer alcohol in the presence of one DS (reward-associated discriminative stimulus, rewDS) and then punished that behavior in the presence of a different DS (punishment-associated discriminative stimulus, punDS). On the test, we found that rats tested with the rewDS showed higher alcohol seeking than rats tested with the punDS. This result shows that a single Cue DS can promote alcohol seeking in a manner comparable to contexts. Subsequently, we trained 16 of these rats in a within-session trial-based discrimination task, comprised of intervening 2-min trials of rewDS, punDS, or conflict with rewDS and punDS in compound and a reduced probability of punishment. We found that alcohol self-administration is bi-directionally regulated by the rewDS and punDS. In conflict trials, alcohol self-administration was at a rate that was intermediate between the rewDS and punDS trials. In a final test, rats were presented with one of the three trial conditions and perfused for Fos immunohistochemistry. We found Fos expression was higher in the rats tested in the conflict condition in three interconnected sub-cortical brain regions. This study demonstrated the important role that alcohol-associated DS plays an important role in promoting relapse to alcohol seeking after punishment-imposed abstinence. We also implemented a within-session discrimination task that allows for the study of alcohol seeking under motivational conflict, which may be relevant for alcohol use despite negative consequences. The results from the Fos data suggest that higher alcohol seeking in approach-avoidance motivational conflict is associated with activation of sub-cortical regions but not cortical regions.
Inactivation of Zona Incerta Blocks Social Conditioned Place Aversion and Modulates Post-traumatic Stress Disorder-Like Behaviors in Mice
Authors: Zhou Hong , Xiang Wei , Huang Mengbing
Published: October 2021

Zona incerta (ZI), a largely inhibitory subthalamic region connected with many brain areas, has been suggested to serve as an integrative node for modulation of behaviors and physiological states, such as fear memory conditioning and aversion responses. It is, however, unclear whether ZI regulated the repeated social defeat stress (RSDS)-induced social conditioned place aversion (CPA) and post-traumatic stress disorder (PTSD)-like behaviors. In this study, the function of ZI was silenced via bilateral injection of tetanus toxin light chain (Tet-tox), a neurotoxin that completely blocks the evoked synaptic transmissions, expressing adeno-associated viruses (AAVs). We found ZI silencing: (1) significantly blocked the expression of RSDS-induced social CPA with no effect on the innate preference; (2) significantly enhanced the anxiety level in mice experienced RSDS with no effect on the locomotion activity; (3) altered the PTSD-associated behaviors, including the promotion of spatial cognitive impairment and the preventions of PPI deficit and social avoidance behavior. These effects were not observed on non-stressed mice. In summary, our results suggest the important role of ZI in modulating RSDS-induced social CPA and PTSD-like behaviors.
Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions
Authors: Tan Xiaoying , Vrana Kent , Ding Zheng-Ming
Published: October 2021

Tobacco use disorder continues to be a leading public health issue and cause of premature death in the United States. Nicotine is considered as the major tobacco alkaloid causing addiction through its actions on nicotinic acetylcholine receptors (nAChRs). Current pharmacotherapies targeting nicotine’s effects produce only modest effectiveness in promoting cessation, highlighting the critical need for a better understanding of mechanisms of nicotine addiction to inform future treatments. There is growing interest in identifying potential contributions of non-nicotine components to tobacco reinforcement. Cotinine is a minor alkaloid, but the major metabolite of nicotine that can act as a weak agonist of nAChRs. Accumulating evidence indicates that cotinine produces diverse effects and may contribute to effects of nicotine. In this review, we summarize findings implicating cotinine as a neuroactive metabolite of nicotine and discuss available evidence regarding potential mechanisms underlying its effects. Preclinical findings reveal that cotinine crosses the blood brain barrier and interacts with both nAChRs and non-nAChRs in the nervous system, and produces neuropharmacological and behavioral effects. Clinical studies suggest that cotinine is psychoactive in humans. However, reviewing evidence regarding mechanisms underlying effects of cotinine provides a mixed picture with a lack of consensus. Therefore, more research is warranted in order to provide better insight into the actions of cotinine and its contribution to tobacco addiction.
Meta-Analysis Reveals Transcription Factor Upregulation in Cells of Injured Mouse Sciatic Nerve
Authors: Li Mingchao , Banton Matthew C. , Min Qing , Parkinson David B. , Dun Xinpeng
Published: October 2021

Following peripheral nerve injury, transcription factors upregulated in the distal nerve play essential roles in Schwann cell reprogramming, fibroblast activation and immune cell function to create a permissive distal nerve environment for axonal regrowth. In this report, we first analysed four microarray data sets to identify transcription factors that have at least twofold upregulation in the mouse distal nerve stump at day 3 and day 7 post-injury. Next, we compared their relative mRNA levels through the analysis of an available bulk mRNA sequencing data set at day 5 post-injury. We then investigated the expression of identified TFs in analysed single-cell RNA sequencing data sets for the distal nerve at day 3 and day 9 post-injury. These analyses identified 55 transcription factors that have at least twofold upregulation in the distal nerve following mouse sciatic nerve injury. Expression profile for the identified 55 transcription factors in cells of the distal nerve stump was further analysed on the scRNA-seq data. Transcription factor network and functional analysis were performed in Schwann cells. We also validated the expression pattern of Jun, Junb, Runx1, Runx2, and Sox2 in the mouse distal nerve stump by immunostaining. The findings from our study not only could be used to understand the function of key transcription factors in peripheral nerve regeneration but also could be used to facilitate experimental design for future studies to investigate the function of individual TFs in peripheral nerve regeneration.
Modeling C9orf72-Related Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in Drosophila
Authors: Sharpe Joanne L. , Harper Nikki S. , Garner Duncan R. , West Ryan J. H.
Published: October 2021

An intronic hexanucleotide (GGGGCC) expansion in theC9orf72gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In the decade following its discovery, much progress has been made in enhancing our understanding of how it precipitates disease. Both loss of function caused by reducedC9orf72transcript levels, and gain of function mechanisms, triggered by the production of repetitive sense and antisense RNA and dipeptide repeat proteins, are thought to contribute to the toxicity.Drosophilamodels, with their unrivaled genetic tractability and short lifespan, have played a key role in developing our understanding ofC9orf72-related FTD/ALS. There is noC9orf72homolog in fly, and although this precludes investigations into loss of function toxicity, it is useful for elucidating mechanisms underpinning gain of function toxicity. To date there are a range ofDrosophila C9orf72models, encompassing different aspects of gain of function toxicity. In addition to pure repeat transgenes, which produce both repeat RNA and dipeptide repeat proteins (DPRs), RNA only models and DPR models have been generated to unpick the individual contributions of RNA and each dipeptide repeat protein toC9orf72toxicity. In this review, we discuss howDrosophilamodels have shaped our understanding ofC9orf72gain of function toxicity, and address opportunities to utilize these models for further research.