bluuebunny/crossref_metadata_2025 huggingface dataset:
Frugivore Population Biomass, but Not Density, Affect Seed Dispersal Interactions in a Hyper-Diverse Frugivory Network
Authors: Genes Luísa , Losapio Gianalberto , Donatti Camila I. , Guimarães Paulo R. , Dirzo Rodolfo
Published: May 2022

Mutualistic interactions are regulated by plant and animal traits, including animal body size and population density. In seed dispersal networks, frugivore body size determines the interaction outcome, and species population density determines interaction probability through encounter rates. To date, most studies examining the relative role of body size and population density in seed dispersal networks have examined animal guilds encompassing a narrow range of body sizes (e.g., birds only). Given non-random, body-size dependent defaunation, understanding the relative role of these traits is important to predict and, ideally, mitigate the effects of defaunation. We analyzed a hyper-diverse seed dispersal network composed of birds and mammals that cover a wide range of body sizes and population densities in the Brazilian Pantanal. Animal density per se did not significantly explain interaction patterns. Instead, population biomass, which represents the combination of body size and population density, was the most important predictor for most interaction network metrics. Population biomass was strongly correlated with body size, but not with density. Thus, larger frugivore species dispersed more plant species and were involved in more unique pairwise interactions than smaller species. Moreover, species with larger population biomass had the strongest influence (i.e., as indicated by measures of centrality) on other species in the network and were more generalist, interacting with a broader set of species, compared to species with lower population biomass. We posit that the increased abundance of small-sized frugivores resulting from the pervasive defaunation of large vertebrates would not compensate for the loss-of-function of the latter and the inherent disruption of seed dispersal networks.
Satellitome of the Red Palm Weevil, Rhynchophorus ferrugineus (Coleoptera: Curculionidae), the Most Diverse Among Insects
Authors: Montiel Eugenia E. , Mora Pablo , Rico-Porras José M. , Palomeque Teresa , Lorite Pedro
Published: May 2022

The red palm weevil, Rhynchophorus ferrugineus, is the most harmful species among those pests affecting palm trees. Its impact causes important economic losses around the World. Nevertheless, the genetic information of Rh. ferrugineus is very scarce. Last year, the first genome assembly was published including a rough description of its repeatome. However, no information has been added about one of the main components of repeated DNA, the satellite DNA. Herein, we presented the characterization of the satellitome of this important species that includes 112 satellite DNA families, the largest number in an insect genome. These satellite DNA families made up around 25% of the genome while the most abundant family, RferSat01-169, alone represented 20.4%. Chromosomal location of most abundant satellite DNA families performed by fluorescence in situ hybridization showed that all of them are dispersed in the euchromatin on all chromosomes but some of them are also specifically accumulated either on the pericentromeric heterochromatic regions of all chromosomes or on specific chromosomes. Finally, the transcription of satellitome families was analyzed through Rh. ferrugineus development. It was found that 55 out of 112 satellite DNA families showed transcription, some families seemed to be transcribed across all stages while a few appeared to be stage-specific, indicating a possible role of those satellite DNA sequences in the development of this species.
Allostatic Load in Gambel’s White Crowned Sparrow, Zonotrichia leucophrys gambelii: Relationships With Glucocorticoids
Authors: Word Karen R. , Austin Suzanne H. , Wingfield John C.
Published: May 2022

Regulation of energetic expenditure in a changing environment, considered here as allostatic load, is central to organism-environment interactions. The value of responses that modify behavior or physiology in coping strategies is often measured in terms of energetic benefits. In this study, the total energetic cost incurred by Gambel’s white-crowned sparrows, Zonotrichia leucophrys gambelii, was assessed using heart-rate transmitters. The use of heart rate was validated as a proxy for metabolic rate via flow-through respirometry. Applying heart rate as an indicator of allostatic load, we confirmed that ambient temperature under wintering conditions influences allostatic load. However, baseline corticosterone, proposed to mediate physiological responses to variation in allostatic load, does not appear to vary with heart rate or temperature in captivity, or with temperature under ambient conditions in the field. The relationship between allostatic load and plasma corticosterone levels was also investigated by manipulating feeding effort for captive Gambel’s white-crowned sparrows using a sand-excavation challenge that approximated a type of foraging work that these birds normally perform in the wild. This experiment was designed to test the hypothesis that experimentally increased allostatic load induces elevation in baseline corticosteroids. We did not find support for this hypothesis. We suggest that the adrenocortical response to increased allostatic load may be limited to overload or environmental conditions that meaningfully threaten energy imbalance, indicating new targets for further research.
Impact of Climate Change on Norway Spruce Flowering in the Southern Part of the Western Carpathians
Authors: Škvareninová Jana , Mrekaj Ivan
Published: May 2022

This work presents the impact of climate change on full flowering (BBCH 65) in Norway spruce [Picea abies (L.) Karst.] at 54 phenological stations over two 30-year-long periods, from 1961 to 1990 and from 1991 to 2020. The stations were located in 10 protected areas (protected landscape area, national park) at elevations from 390 to 1,400 m a.s.l. We analyzed the changes in average onset of full flowering, trends of the phase, phenological altitudinal gradient, and correlations of flowering to monthly climatological standard normals of air temperature and sum of precipitation. The impact of climate change was observed in the second period, when flowering started 4–8 days earlier. The phenophase was shortened by 4 days in comparison to the first period, and the shift of the significant trend occurred 7 days earlier. The phenological altitudinal gradient did not substantially change. The analysis of the temperature impact on flowering showed an effect of the cold period preceding the onset of the phenological phase on its delayed onset. The change in January temperatures between periods indicated warming by 1.24–1.34°C. The change also occurred in the evaluation of the 3-month period when the spring air temperature increased. The mean 3-month air temperature (January–March) increased by 0.82–1.1°C in the second period. It was more substantial at lower elevations. The most significant changes in precipitation conditions were observed by the increase in precipitation in March and by the decrease in precipitation between the observed periods in April. The results of all indicators for Norway spruce flowering in the second period indicated changes in climatic conditions in the region.
Sedimentation as a Support Ecosystem Service in Different Ecological Types of Mangroves
Authors: Cinco-Castro Siuling , Herrera-Silveira Jorge , Comín Francisco
Published: May 2022

Mangrove vegetation is strongly dependent on the climate, the physicochemical variables of the sediment, and the hydrological dynamics. These drivers regulate the distribution of different mangrove ecotypes and their ecosystem services, so the net sediment accumulation rates in different mangrove ecotypes in Celestun Lagoon, a karstic zone in the NW Yucatan Peninsula, SE Mexico, were estimated. The measurements considering mangrove ecotypes and their spatial variability concerning the lagoon's salinity gradient (inner, middle, and outer lagoon zones) in three climate seasons (dry, rain, and “nortes”) were realized. We registered the structural variables of the forest, interstitial water physicochemical characteristics, and sediment variables that could influence the net sediment deposition. Fringe mangroves are exposed to low hydrodynamism and show the highest sedimentation rate (3.37 ± 0.49 kg m−2 year−1) compared to basin (1.68 ± 0.22 kg m−2 year−1), dwarf (1.27 ± 0.27 kg m−2 year−1), and “peten” (0.52 ± 0.12 kg m−2 year−1) mangroves. The highest sedimentation rate was recorded in the rainy season (0.24 ± 0.08 kg m−2 month−1), while spatially, the highest value was registered in the outer zone (0.44 ± 0.09 kg m−2 month−1). If the extension of each mangrove ecotype is considered, dwarf mangroves have the highest annual sediment accumulation (1,465 t year−1 in 14,706 ha). The structural, physicochemical, and sediment variables of the sites by mangrove ecotype show that dwarf mangroves represent a distinct group from those formed by fringe, basin, and peten mangroves. However, the sedimentation is high in fringe mangroves at the front of the lagoon and diminishes inland where peten mangroves exist. The differences are given by tree density, but salinity, as a proxy variable of the freshwater influence, significantly influences the sedimentation rate. These results indicate that mangroves in karstic environments can have critical roles in confronting climate change, considering water and sediment flows are the basis of sediment accumulation. According to their hydrogeomorphological drivers, conserving, managing, and restoring the mosaic of mangrove ecotypes improves ecosystem services, including mitigation and adaptation to climate change.
Identification of Long Noncoding RNAs Involved in Eyelid Pigmentation of Hereford Cattle
Authors: Jara Eugenio , Peñagaricano Francisco , Armstrong Eileen , Menezes Claudia , Tardiz Lucía , Rodons Gastón , Iriarte Andrés
Published: May 2022

Several ocular pathologies in cattle, such as ocular squamous cell carcinoma and infectious keratoconjunctivitis, have been associated with low pigmentation of the eyelids. The main objective of this study was to analyze the transcriptome of eyelid skin in Hereford cattle using strand-specific RNA sequencing technology to characterize and identify long noncoding RNAs (lncRNAs). We compared the expression of lncRNAs between pigmented and unpigmented eyelids and analyzed the interaction of lncRNAs and putative target genes to reveal the genetic basis underlying eyelid pigmentation in cattle. We predicted 4,937 putative lncRNAs mapped to the bovine reference genome, enriching the catalog of lncRNAs in Bos taurus. We found 27 differentially expressed lncRNAs between pigmented and unpigmented eyelids, suggesting their involvement in eyelid pigmentation. In addition, we revealed potential links between some significant differentially expressed lncRNAs and target mRNAs involved in the immune response and pigmentation. Overall, this study expands the catalog of lncRNAs in cattle and contributes to a better understanding of the biology of eyelid pigmentation.
The Genetic Differentiation of Pyrrhulina (Teleostei, Characiformes) Species is Likely Influenced by Both Geographical Distribution and Chromosomal Rearrangements
Authors: Ferreira Pedro H. N. , Souza Fernando H. S. , de Moraes Renata L. , Perez Manolo F. , Sassi Francisco de M. C. , Viana Patrik F. , Feldberg Eliana , Ezaz Tariq , Liehr Thomas , Bertollo Luiz A. C. , Cioffi Marcelo de B.
Published: May 2022

Allopatry is generally considered to be one of the main contributors to the remarkable Neotropical biodiversity. However, the role of chromosomal rearrangements including neo-sex chromosomes for genetic diversity is still poorly investigated and understood. Here, we assess the genetic divergence in five Pyrrhulina species using population genomics and combined the results with previously obtained cytogenetic data, highlighting that molecular genetic diversity is consistent with their chromosomal features. The results of a principal coordinate analysis (PCoA) indicated a clear difference among all species while showing a closer relationship of the ones located in the same geographical region. This was also observed in genetic structure analyses that only grouped P. australis and P. marilynae, which were also recovered as sister species in a species tree analysis. We observed a contradictory result for the relationships among the three species from the Amazon basin, as the phylogenetic tree suggested P. obermulleri and P. semifasciata as sister species, while the PCoA showed a high genetic difference between P. semifasciata and all other species. These results suggest a potential role of sex-related chromosomal rearrangements as reproductive barriers between these species.
Modulation of Differentiation and Bone Resorbing Activity of Human (Pre-) Osteoclasts After X-Ray Exposure
Authors: Eckert Denise , Rapp Felicitas , Tsedeke Ayele Taddese , Kraft Daniela , Wente Isabell , Molendowska Jessica , Basheer Sidra , Langhans Markus , Meckel Tobias , Friedrich Thomas , Donaubauer Anna-Jasmina , Becker Ina , Frey Benjamin , Fournier Claudia
Published: May 2022

Low-dose radiotherapy (LD-RT) is a local treatment option for patients with chronic degenerative and inflammatory diseases, in particular musculoskeletal diseases. Despite reported analgesic and anti-inflammatory effects, cellular and molecular mechanisms related to osteoimmunological effects are still elusive. Here we test the hypothesis that X-irradiation inhibits the differentiation of precursor osteoclasts into mature osteoclasts (mOC) and their bone resorbing activity. Circulating monocytes from healthy donors were isolated and irradiated after attachment with single or fractionated X-ray doses, comparable to an LD-RT treatment scheme. Then monocytes underwent ex vivo differentiation into OC during cultivation up to 21 days, under conditions mimicking the physiological microenvironment of OC on bone. After irradiation, apoptotic frequencies were low, but the total number of OC precursors and mOC decreased up to the end of the cultivation period. On top, we observed an impairment of terminal differentiation, i.e. a smaller fraction of mOC, reduced resorbing activity on bone, and release of collagen fragments. We further analyzed the effect of X-irradiation on multinucleation, resulting from the fusion of precursor OC, which occurs late during OC differentiation. At 21 days after exposure, the observation of smaller cellular areas and a reduced number of nuclei per mOC suggest an impaired fusion of OC precursors to form mOC. Before, at 14 days, the nuclear translocation of Nuclear Factor Of Activated T Cells 1 (NFATc1), a master regulator of osteoclast differentiation and fusion, was decreased. In first results, obtained in the frame of a longitudinal LD-RT study, we previously reported a pain-relieving effect in patients. However, in a subgroup of patients suffering from Calcaneodynia or Achillodynia, we did not observe a consistent decrease of established blood markers for resorption and formation of bone, or modified T cell subtypes involved in regulating these processes. To assess the relevance of changes in bone metabolism for other diseases treated with LD-RT will be subject of further studies. Taken together, we observed that in vitro X-irradiation of monocytes results in an inhibition of the differentiation into bone-resorbing OC and a concomitant reduction of resorbing activity. The detected reduced NFATc1 signaling could be one underlying mechanism.
Adaptive Immune Responses and Immunity to SARS-CoV-2
Authors: Primorac Dragan , Vrdoljak Kristijan , Brlek Petar , Pavelić Eduard , Molnar Vilim , Matišić Vid , Erceg Ivkošić Ivana , Parčina Marijo
Published: May 2022

Since the onset of the COVID-19 pandemic, the medical field has been forced to apply the basic knowledge of immunology with the most up-to-date SARS-CoV-2 findings and translate it to the population of the whole world in record time. Following the infection with the viral antigen, adaptive immune responses are activated mainly by viral particle encounters with the antigen-presenting cells or B cell receptors, which induce further biological interactions to defend the host against the virus. After the infection has been warded off, the immunological memory is developed. The SARS-CoV cellular immunity has been shown to persist even 17 years after the infection, despite the undetectable humoral component. Similar has been demonstrated for the SARS-CoV-2 T cell memory in a shorter period by assessing interferon-gamma levels when heparinized blood is stimulated with the virus-specific peptides. T cells also play an irreplaceable part in a humoral immune reaction as the backbone of a cellular immune response. They both provide the signals for B cell activation and the maturation, competence, and memory of the humoral response. B cell production of IgA was shown to be of significant influence in mediating mucosal immunity as the first part of the defense mechanism and in the development of nasal vaccines. Here, we interpret the recent SARS-CoV-2 available research, which encompasses the significance and the current understanding of adaptive immune activity, and compare it among naive, exposed, and vaccinated blood donors. Our recent data showed that those who recovered from COVID-19 and those who are vaccinated with EMA-approved vaccines had a long-lasting cellular immunity. Additionally, we analyze the humoral responses in immunocompromised patients and memory mediated by cellular immunity and the impact of clonality in the SARS-CoV-2 pandemic regarding breakthrough infections and variants of concern, both B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants.
Single Cell Dissection of Epithelial-Immune Cellular Interplay in Acute Kidney Injury Microenvironment
Authors: Zhang Min , Wu Lingling , Deng Yiyao , Peng Fei , Wang Tiantian , Zhao Yinghua , Chen Pu , Liu Jiaona , Cai Guangyan , Wang Liqiang , Wu Jie , Chen Xiangmei
Published: May 2022

Background

Understanding the acute kidney injury (AKI) microenvironment changes and the complex cellular interaction is essential to elucidate the mechanisms and develop new targeted therapies for AKI.

Methods

We employed unbiased single-cell RNA sequencing to systematically resolve the cellular atlas of kidney tissue samples from mice at 1, 2 and 3 days after ischemia-reperfusion AKI and healthy control. The single-cell transcriptome findings were validated using multiplex immunostaining, western blotting, and functional experiments.

Results

We constructed a systematic single-cell transcriptome atlas covering different AKI timepoints with immune cell infiltration increasing with AKI progression. Three new proximal tubule cells (PTCs) subtypes (PTC-S1-new/PTC-S2-new/PTC-S3-new) were identified, with upregulation of injury and repair-regulated signatures such as Sox9, Vcam1, Egr1, and Klf6 while with downregulation of metabolism. PTC-S1-new exhibited pro-inflammatory and pro-fibrotic signature compared to normal PTC, and trajectory analysis revealed that proliferating PTCs were the precursor cell of PTC-S1-new, and part of PTC-S1-new cells may turn into PTC-injured and then become fibrotic. Cellular interaction analysis revealed that PTC-S1-new and PTC-injured interacted closely with infiltrating immune cells through CXCL and TNF signaling pathways. Immunostaining validated that injured PTCs expressed a high level of TNFRSF1A and Kim-1, and functional experiments revealed that the exogenous addition of TNF-α promoted kidney inflammation, dramatic injury, and specific depletion of TNFRSF1A would abrogate the injury.

Conclusions

The single-cell profiling of AKI microenvironment provides new insight for the deep understanding of molecular changes of AKI, and elucidates the mechanisms and developing new targeted therapies for AKI.
Th1-Like Treg Cells Are Increased But Deficient in Function in Rheumatoid Arthritis
Authors: Zhang Rui , Miao Jinlin , Zhang Kui , Zhang Bei , Luo Xing , Sun Haoyang , Zheng Zhaohui , Zhu Ping
Published: May 2022

Objectives

This study aimed to investigate the changes in quantity and function of T helper (Th)-like T regulatory (Treg) cell subsets in peripheral blood (PB) and synovial fluid (SF) of rheumatoid arthritis (RA) patients and to understand their relationship with disease activity.

Methods

A total of 86 RA patients and 76 gender and age-matched healthy controls (HC) were enrolled in this study. Th-like Treg frequency and function were determined using flow cytometry. The inhibitory function of Th-like Treg cells was detected using an in vitro co-culture suppression assay.

Results

The proportion and absolute number of Th1-like Treg cells from RA PB and RA SF were significantly higher than those of HC PB. In RA SF, the proportions of Treg cells and Th1-like Treg cells were significantly lower in the elevated erythrocyte sedimentation rate or the C-Reactive Protein group, and in the positive groups of anti-CCP antibody and anti-MCV antibody. Additionally, the proportions of Treg cells and Th1-like Treg cells from RA SF were negatively correlated with disease activity. However, the expression levels of CD73 and TGF-β1 in Th1-like Treg cells were decreased, and these Treg cells could not effectively inhibit the proliferation of effector T (Teff) cells.

Conclusion

Our data indicate that Th1-like Treg cells are the predominant Treg cell subset in RA SF, but their suppressive function is defective. Improving the function of Th1-like Treg cells may control inflammation in joints and provide new strategies for Treg-targeted therapies in RA.
Roles of m5C RNA Modification Patterns in Biochemical Recurrence and Tumor Microenvironment Characterization of Prostate Adenocarcinoma
Authors: Xu Zhipeng , Chen Shuqiu , Zhang Yuxi , Liu Ruiji , Chen Ming
Published: May 2022

Background

Prostate cancer is the second most common cancer with a high risk of biochemical recurrence (BCR) among men. Recently, 5-methylcytosine (m5C) modification has attracted more attention as a new layer of RNA post-transcriptional regulation. Hence, we aimed at investigating the potential roles of m5C modification regulators in the BCR of prostate adenocarcinoma (PRAD).

Methods

CNV data, mutation annotation data, mRNA expression profiles, and clinical data were downloaded from TCGA and GEO databases. Kaplan-Meier curves analysis, log-rank test, univariate and multivariate Cox regression, and time-dependent ROC curves analysis were performed to evaluate the prognostic factors. Principal components analysis (PCA) was applied to validate the distinction between subgroups. Gene set variation analysis (GSVA) was used to investigate the underlying pathways associated with m5C modification patterns. Single sample gene set enrichment analysis (ssGSEA) was utilized to assess the infiltration of distinct immune cells. Tumor Immune Dysfunction and Exclusion (TIDE) prediction was carried out to assess the potential response to immune checkpoint blockade (ICB) therapy. The m5C modification signature was constructed via LASSO Cox’s proportional hazards regression method.

Results

After comprehensively analyzing various types of data from TCGA dataset, and exploring the differential expression and prognostic value of each m5C regulator, we identified m5C modification patterns based on 17 m5C regulators. Two patterns presented a significant difference in the risk of BCR, the tumor microenvironment (TME), and immunotherapy response in PRAD. We found that TET2, which was highly expressed in adjacent normal tissues compared to tumor tissues, was closely associated with many infiltrating immune cells. The m5C modification signature was constructed for the clinical application. Risk score calculated by m5C signature was associated with T stage, N stage, Gleason score, and the possibility of BCR (HR, 4.197; 95% CI, 3.016-5.842; p < 0.001). A higher risk score also represented the possibility of immunotherapy response. Finally, the potential roles of m5C modification signature were validated in the testing dataset.

Conclusions

Our study revealed the potential roles of m5C modification in the PRAD BCR and TME diversity, which may provide new insight into the field of prostate cancer in future research.
Correlation Between Salivary Microbiome of Parotid Glands and Clinical Features in Primary Sjögren’s Syndrome and Non-Sjögren’s Sicca Subjects
Authors: Kim Donghyun , Jeong Ye Jin , Lee Yerin , Choi Jihoon , Park Young Min , Kwon Oh Chan , Ji Yong Woo , Ahn Sung Jun , Lee Hyung Keun , Park Min-Chan , Lim Jae-Yol
Published: May 2022

Recent studies have demonstrated that the oral microbiome in patients with Sjögren’s syndrome (SS) is significantly different from that in healthy individuals. However, the potential role of the oral microbiome in SS pathogenesis has not been determined. In this study, stimulated intraductal saliva samples were collected from the parotid glands (PGs) of 23 SS and nine non-SS subjects through PG lavage and subjected to 16S ribosomal RNA amplicon sequencing. The correlation between the oral microbiome and clinical features, such as biological markers, clinical manifestations, and functional and radiological characteristics was investigated. The salivary microbial composition was examined using bioinformatic analysis to identify potential diagnostic biomarkers for SS. Oral microbial composition was significantly different between the anti-SSA-positive and SSA-negative groups. The microbial diversity in SS subjects was lower than that in non-SS sicca subjects. Furthermore, SS subjects with sialectasis exhibited decreased microbial diversity and Firmicutes abundance. The abundance of Bacteroidetes was positively correlated with the salivary flow rate. Bioinformatics analysis revealed several potential microbial biomarkers for SS at the genus level, such as decreased Lactobacillus abundance or increased Streptococcus abundance. These results suggest that microbiota composition is correlated with the clinical features of SS, especially the ductal structures and salivary flow, and that the oral microbiome is a potential diagnostic biomarker for SS.
Immunotherapeutic Effects of Different Doses of Mycobacterium tuberculosis ag85a/b DNA Vaccine Delivered by Electroporation
Authors: Liang Yan , Cui Lei , Xiao Li , Liu Xiao , Yang Yourong , Ling Yanbo , Wang Tong , Wang Lan , Wang Jie , Wu Xueqiong
Published: May 2022

Background

Tuberculosis (TB) is a major global public health problem. New treatment methods on TB are urgently demanded.

Methods

Ninety-six female BALB/c mice were challenged with 2×104 colony-forming units (CFUs) of MTB H37Rv through tail vein injection, then was treated with 10μg, 50μg, 100μg, and 200μg of Mycobacterium tuberculosis (MTB) ag85a/b chimeric DNA vaccine delivered by intramuscular injection (IM) and electroporation (EP), respectively. The immunotherapeutic effects were evaluated immunologically, bacteriologically, and pathologically.

Results

Compared with the phosphate-buffered saline (PBS) group, the CD4+IFN-γ+ T cells% in whole blood from 200 µg DNA IM group and four DNA EP groups increased significantly (P<0.05), CD8+IFN-γ+ T cells% (in 200 μg DNA EP group), CD4+IL-4+ T cells% (50 μg DNA IM group) and CD8+IL-4+ T cells% (50 μg and 100 μg DNA IM group, 100 μg and 200 μg DNA EP group) increased significantly only in a few DNA groups (P< 0.05). The CD4+CD25+ Treg cells% decreased significantly in all DNA vaccine groups (P<0.01). Except for the 10 μg DNA IM group, the lung and spleen colony-forming units (CFUs) of the other seven DNA immunization groups decreased significantly (P<0.001, P<0.01), especially the 100 μg DNA IM group and 50 μg DNA EP group significantly reduced the pulmonary bacterial loads and lung lesions than the other DNA groups.

Conclusions

An MTB ag85a/b chimeric DNA vaccine could induce Th1-type cellular immune reactions. DNA immunization by EP could improve the immunogenicity of the low-dose DNA vaccine, reduce DNA dose, and produce good immunotherapeutic effects on the mouse TB model, to provide the basis for the future human clinical trial of MTB ag85a/b chimeric DNA vaccine.
FOXO Dictates Initiation of B Cell Development and Myeloid Restriction in Common Lymphoid Progenitors
Authors: Peña-Pérez Lucía , Kharazi Shabnam , Frengen Nicolai , Krstic Aleksandra , Bouderlique Thibault , Hauenstein Julia , He Minghui , Somuncular Ece , Li Wang Xiaoze , Dahlberg Carin , Gustafsson Charlotte , Johansson Ann-Sofie , Walfridsson Julian , Kadri Nadir , Woll Petter , Kierczak Marcin , Qian Hong , Westerberg Lisa , Luc Sidinh , Månsson Robert
Published: May 2022

The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal switch from predominant Foxo3 to Foxo1 expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.
Identification of CD4+ Conventional T Cells-Related lncRNA Signature to Improve the Prediction of Prognosis and Immunotherapy Response in Breast Cancer
Authors: Ning Shipeng , Wu Jianbin , Pan You , Qiao Kun , Li Lei , Huang Qinghua
Published: May 2022

Background

Breast cancer (BC) is one of the most common malignancies in women, and long non-coding RNAs (lncRNAs) are key regulators of its development. T cells can recognize and kill cancer cells, and CD4+ T conventional (Tconv) cells are the main orchestrators of cancer immune function. However, research on CD4+ Tconv-related lncRNAs (CD4TLAs) prognostic signature in patients with BC is still lacking.

Method

A TCGA database and a GEO database were used to collect the BC patients. Through LASSO Cox regression analysis CD4TLAs-related prognostic models were further constructed, and risk scores (RS) were generated and developed a nomogram based on CD4TLAs. The accuracy of this model was validated in randomized cohorts and different clinical subgroups. Gene set enrichment analysis (GSEA) was used to explore potential signature-based functions. The role of RS has been further explored in the tumor microenvironment (TME), immunotherapy, and chemotherapy.

Result

A prognostic model based on 16 CD4TLAs was identified. High-RS was significantly associated with a poorer prognosis. RS was shown to be an independent prognostic indicator in BC patients. The low-RS group had a significant expression of immune infiltrating cells and significantly enriched immune-related functional pathways. In addition, the results of immunotherapy prediction indicated that patients with low-RS were more sensitive to immunotherapy.

Conclusions

Our signature has potential predictive value for BC prognosis and immunotherapy response. The findings of this work have greatly increased our understanding of CD4TLA in BC.
Ethanol Intoxication Impairs Respiratory Function and Bacterial Clearance and Is Associated With Neutrophil Accumulation in the Lung After Streptococcus pneumoniae Infection
Authors: Hulsebus Holly J. , Najarro Kevin M. , McMahan Rachel H. , Boe Devin M. , Orlicky David J. , Kovacs Elizabeth J.
Published: May 2022

Alcohol consumption is commonplace in the United States and its prevalence has increased in recent years. Excessive alcohol use is linked to an increased risk of infections including pneumococcal pneumonia, mostly commonly caused by Streptococcus pneumoniae. In addition, pneumonia patients with prior alcohol use often require more intensive treatment and longer hospital stays due to complications of infection. The initial respiratory tract immune response to S. pneumoniae includes the production of pro-inflammatory cytokines and chemokines by resident cells in the upper and lower airways which activate and recruit leukocytes to the site of infection. However, this inflammation must be tightly regulated to avoid accumulation of toxic by-products and subsequent tissue damage. A majority of previous work on alcohol and pneumonia involve animal models utilizing high concentrations of ethanol or chronic exposure and offer conflicting results about how ethanol alters immunity to pathogens. Further, animal models often employ a high bacterial inoculum which may overwhelm the immune system and obscure results, limiting their applicability to the course of human infection. Here, we sought to determine how a more moderate ethanol exposure paradigm affects respiratory function and innate immunity in mice after intranasal infection with 104 colony forming units of S. pneumoniae. Ethanol-exposed mice displayed respiratory dysfunction and impaired bacterial clearance after infection compared to their vehicle-exposed counterparts. This altered response was associated with increased gene expression of neutrophil chemokines Cxcl1 and Cxcl2 in whole lung homogenates, elevated concentrations of circulating granulocyte-colony stimulating factor (G-CSF), and higher neutrophil numbers in the lung 24 hours after infection. Taken together, these findings suggest that even a more moderate ethanol consumption pattern can dramatically modulate the innate immune response to S. pneumoniae after only 3 days of ethanol exposure and provide insight into possible mechanisms related to the compromised respiratory immunity seen in alcohol consumers with pneumonia.
T Cell Specific BOB.1/OBF.1 Expression Promotes Germinal Center Response and T Helper Cell Differentiation
Authors: Betzler Annika C. , Ezić Jasmin , Abou Kors Tsima , Hoffmann Thomas K. , Wirth Thomas , Brunner Cornelia
Published: May 2022

The transcriptional co-activator BOB.1/OBF.1 is expressed in both B and T cells. The main characteristic of conventional BOB.1/OBF.1 deficient mice is the complete absence of germinal centers (GCs). This defect was mainly attributed to the defective B cell compartment. However, it is unknown whether and how BOB.1/OBF.1 expression in T cells contributes to the GC reaction. To finally clarify this question, we studied the in vivo function of BOB.1/OBF.1 in CD4+ T and follicular T helper (TFH) cell subpopulations by conditional mutagenesis, in the presence of immunocompetent B lymphocytes. BOB.1/OBF.1 deletion in CD4+ T as well as TFH cells resulted in impaired GC formation demonstrating that the impaired GC reaction described for conventional BOB.1/OBF.1-deficient mice cannot exclusively be traced back to the B cell compartment. Furthermore, we show a requirement of BOB.1/OBF.1 for T helper (TH) cell subsets, particularly for TFH cell differentiation.
The Open-Ocean Gulf of Mexico After Deepwater Horizon: Synthesis of a Decade of Research
Authors: Sutton Tracey T. , Milligan Rosanna J. , Daly Kendra , Boswell Kevin M. , Cook April B. , Cornic Maëlle , Frank Tamara , Frasier Kaitlin , Hahn Daniel , Hernandez Frank , Hildebrand John , Hu Chuanmin , Johnston Matthew W. , Joye Samantha B. , Judkins Heather , Moore Jon A. , Murawski Steven A. , Pruzinsky Nina M. , Quinlan John A. , Remsen Andrew , Robinson Kelly L. , Romero Isabel C. , Rooker Jay R. , Vecchione Michael , Wells R. J. David
Published: May 2022

The scale of the Deepwater Horizon disaster was and is unprecedented: geographic extent, pollutant amount, countermeasure scope, and of most relevance to this Research Topic issue, range of ecotypes affected. These ecotypes include coastal/nearshore, continental shelf, deep benthic, and open-ocean domains, the last of which is the subject of this synthesis. The open-ocean ecotype comprises ~90% of the volume of the Gulf of Mexico. The exact percentage of this ecotype contaminated with toxins is unknown due to its three-dimensional nature and dynamics, but estimates suggest that the footprint encompassed most of its eastern half. Further, interactions between the water column and the deep benthos may be persistent, making this synthesis one of time (a decade) rather than event conclusion. Here we examine key elements of the open-ocean ecosystem, with emphasis on vulnerability and resilience. Of paramount importance relative to the Gulf nearshore and shelf ecotypes, pre-disaster baseline data were lacking for most of the fauna. In such cases, inferences were drawn from post-disaster assessments. Both phytoplankton and mesozooplankton vulnerabilities were quite high, but resilience appeared equally so. The phytoplankton situation was a bit more complex in that toxin-imposed reductions may have been offset by nutrient injection via high freshwater discharge in 2010. Intermediate trophic levels exhibited population-level depressions, ostensibly due to high vulnerability and low resilience. Apex predator impacts were variable. Certain large epipelagic fishes may have avoided the highest concentrations of hydrocarbons/dispersant, and thus larval abundances returned to pre-disaster levels of variability and abundance within a few years after a steep initial decline. Oceanic cetaceans, particularly shallow-diving stenellid dolphins, did not appear to avoid oiled waters and exhibited strong declines in the northern Gulf. Given that population declines of many open-ocean taxa appear to be ongoing a decade later, we conclude that this largest of Gulf ecosystem components, like its deep-benthic counterpart, is as fragile as it is voluminous. This is particularly concerning given the rapid, and likely irreversible, shift to deeper waters by the US and Mexican oil industries in concert with the higher likelihood of accidents with increasing platform depth.
Abundant and Rare Microbial Communities Respectively Contribute to an Aquaculture Pond Ecosystem
Authors: Hou Dongwei , Zhou Renjun , Wei Dongdong , Zeng Shenzheng , Weng Shaoping , Yan Qingyun , He Jianguo , Huang Zhijian
Published: May 2022

Unraveling the assembly mechanism is a core research topic of microbial ecology. Abundant and rare microbial communities are crucial for diversity, function and host health in a given ecosystem, but few studies focused on their assembly strategies. Here, we explored the microbial diversity of abundant and rare communities of water, shrimp intestine and sediment habitats in the shrimp cultural ponds. Our results found that the numbers of rare operational taxonomic units (OTUs) (6,003, 4,566 and 8,237 OTUs of water, intestine and sediment) was dozens of times more than abundant ones (only 199, 157 and 122 OTUs of water, intestine and sediment). The community diversity of abundant and rare microbial taxa was markedly different, as well as their taxonomic composition. Despite different diversity, similar abundance-occupancy relationship and biogeographic patterns between the abundant and rare microbial communities were observed, with much stronger obvious distance-decay relationships for rare community than abundant community. Furthermore, stochastic processes dominated the community assemblies of both abundant and rare microbial taxa, and deterministic process contributed more microbial community variation to rare taxa than abundant taxa. All the findings advance our understanding on the community assembly strategies of abundant and rare microbial taxa and prompt the contributions of abundant and rare microbial community to the aquatic ecosystems, which will improve aquaculture management strategy.
Distribution and Differentiation Patterns of Sympatric Squids Alloteuthis media and Alloteuthis subulata (Cephalopoda: Loliginidae) Using Morphological and Molecular Approaches
Authors: Alujević Karla , Šegvić-Bubić Tanja , Isajlović Igor , Trumbić Željka , Petrić Mirela
Published: May 2022

Identification of the two sympatric species,Alloteuthis mediaandAlloteuthis subulata, has long relied on a set of identifying morphometric parameters and descriptive guidelines. To resolve taxonomic status ofAlloteuthisin the Eastern Adriatic, we used morphological and molecular approach on a dataset collected during MEDITS expeditions sampling the entire Eastern Adriatic over consecutive summers. Phylogenetic analyses inferred from mitochondrial DNA cytochrome oxidase I (COI) gene sequences confirmed presence of both species in the Eastern Adriatic, withA. subulataoccurring only in its central and southern parts. Analyses of genetic diversity showed thatA. subulatasamples in the Eastern Adriatic shared a single haplotype whileA. mediashowed high haplotype diversity. Comparison of Eastern AdriaticA. mediasamples and populations from other regions showed statistically significant genetic differentiation between the Atlantic haplotypes and each of the Adriatic, Aegean, and Ionian populations. Conversely,A. subulatahad low genetic diversity with only two haplotypes present across samples collected globally. There was no single morphometric character with strong enough power to discriminate between species, however, when morphological traits were looked as a composite metric rather than in isolation, the majority of individuals were correctly classified into one of three groups (A. mediamales or females andA. subulata).
A Shuttling Protein Kank1 Plays Important Role in the Sex Determination in Yellow Drum
Authors: Sun Sha , Liu Jieping , Zhang Sen , He Qiwei , Han Wei , Ye Kun , Han Fang , Li Wanbo , Wang Zhiyong
Published: May 2022

Sex is one of the most important scientific topics, and the existence of sex dimorphism is a conserved feature in vertebrate taxa. The research on sex-determining genes and sex chromosome evolution is a hot topic in biology. The majority of sex-determining genes expressed in somatic cells, and reciprocal interactions between germ cells and somatic cells, are important for gonadal differentiation. However, the knowledge of how signals are transmitted between somatic cells and germ cells remains unclear. In this study, we confirmed the 36 dph was a sex determination critical stage in yellow drum through transcriptome analysis at the early development stages. We further found that Kank1 participated in the germ cells’ motility process in yellow drum through KEGG pathway analysis together with protein-protein interaction network. With the dual-luciferase reporter assay, we detected that Kank1 increased the transcription of dmrt1_Luc gene in CHO cells and 293T cells. Additionally, we observed that Kank1 was not only expressed in the cytoplasm but also in the nucleus in CHO cells through a fluorescence microscope. These results suggest that Kank1 acts as a shuttling protein as in humans and may play a difunctional role at the early gonad development stage in yellow drum, and it not only participated in the germ cells’ motility but also increased the expression of dmrt1 in yellow drum.
Influence of Wear Profile Geometry on Critical Plane Fatigue Crack Initiation Criteria in Plane and Axisymmetric Elastic Fretting Contacts
Authors: Willert Emanuel
Published: May 2022

The subsurface elastic stress fields in plane and axisymmetric contacts with friction under oscillating tangential loading are calculated via a very robust, high-precision method, which operates with appropriate superpositions of analytic solutions for the respective Hertzian contact problems. Based on the stress fields, two critical plane fatigue crack initiation criteria—the Smith-Watson-Topper (SWT) parameter and the Findley parameter—are evaluated for three types of contact profile geometries: (unworn) parabolic contact, the partial slip limiting wear profile of an initially parabolic contact, and truncated parabolic contact. Appropriate scaling laws are introduced to formulate a general solution in terms of non-dimensional variables. The crack initiation criteria are determined in the full subsurface loading plane. It is found that the truncated profile—which may originate from sliding wear—has practically the same local distribution of crack initiation criteria as the unworn profile, despite the (weak) stress singularity at the edge of the flat face. The partial slip limiting wear profile, on the other hand, exhibits a strong edge stress singularity at the boundary of the permanent stick zone, the crack initiation criteria are drastically increased (and theoretically infinite). Also, while for the unworn and truncated profiles high values of the crack initiation criteria are extremely localized around “hotspots” at the surface, for the partial slip limiting wear profile they reach much deeper into the subsurface material. This offers a new explanation for the dominance of fatigue failure in the partial slip regime of fretting. The differences between plane and axisymmetric cases are generally small. The SWT parameter is generally more localized than the Findley parameter.
Factors Facilitating and Hindering the Use of Newly Acquired Positioning Skills in Clinical Practice: A Longitudinal Survey
Authors: Ludwig Vera U. , Pickenbrock Heidrun , Döppner Daniel A.
Published: May 2022

Background

After learning new skills, healthcare professionals do not always apply them in practice, despite being motivated. This may be referred to as an intention-behavior gap. One example is the positioning of immobilized and disabled patients in hospitals, nursing homes, or neurorehabilitation clinics. Positioning is crucial to prevent complications such as pressure sores, pneumonia, and deep vein thrombosis. However, it is often not carried out optimally even when professionals have completed education programs. The LiN-method is a positioning procedure involving a special focus on aligning and stabilizing body parts, which has been shown to have advantages over conventional positioning. We assess which factors may facilitate or hinder the use of LiN in clinical practice after participants complete training.

Methods

A longitudinal survey with 101 LiN-course participants was conducted in Germany. Each participant completed a questionnaire directly after the course and 12 weeks later, including a report of the frequency of use in practice. They also completed a questionnaire which surveyed 23 aspects that might facilitate or hinder use of the new skills, covering the workplace, socio-collegial factors, motivation, self-confidence, and mindset.

Results

Most assessed aspects were associated with LiN-use, with the highest correlations found for confidence with the method, perceived ease of application, sufficient time, assessing one's skills as sufficient, remembering the relevant steps, and a work environment open to advanced therapeutic concepts. To reduce data complexity, the questionnaire was subjected to a factor analysis, revealing six factors. A regression analysis showed that four factors predicted use 12 weeks after course completion, in the following order of importance: (1) subjective aspects/confidence, (2) access to materials, (3) work context, and (4) competent support in the workplace.

Conclusion

Numerous aspects are associated with the use of recently acquired clinical or nursing skills, such as LiN. Many of these can be improved by appropriately setting up the workplace. The aspects most associated with use, however, are confidence with the method and self-perceived competence of healthcare professionals. While causality still needs to be demonstrated, this suggests that education programs should support participants in developing confidence and foster a mindset of continuous learning.