bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibroblast Growth Factor 19 Increases the Excitability of Pre-Motor Glutamatergic Dorsal Vagal Complex Neurons From Hyperglycemic Mice
Authors: Wean Jordan B. , Smith Bret N.
Published: November 2021

Intracerebroventricular administration of the protein hormone fibroblast growth factor 19 (FGF19) to the hindbrain produces potent antidiabetic effects in hyperglycemic mice that are likely mediated through a vagal parasympathetic mechanism. FGF19 increases the synaptic excitability of parasympathetic motor neurons in the dorsal motor nucleus of the vagus (DMV) from hyperglycemic, but not normoglycemic, mice but the source of this synaptic input is unknown. Neurons in the area postrema (AP) and nucleus tractus solitarius (NTS) express high levels of FGF receptors and exert glutamatergic control over the DMV. This study tested the hypothesis that FGF19 increases glutamate release in the DMV by increasing the activity of glutamatergic AP and NTS neurons in hyperglycemic mice. Glutamate photoactivation experiments confirmed that FGF19 increases synaptic glutamate release from AP and NTS neurons that connect to the DMV in hyperglycemic, but not normoglycemic mice. Contrary to expectations, FGF19 produced a mixed effect on intrinsic membrane properties in the NTS with a trend towards inhibition, suggesting that another mechanism was responsible for the observed effects on glutamate release in the DMV. Consistent with the hypothesis, FGF19 increased action potential-dependent glutamate release in the NTS in hyperglycemic mice only. Finally, glutamate photoactivation experiments confirmed that FGF19 increases the activity of glutamatergic AP neurons that project to the NTS in hyperglycemic mice. Together, these results support the hypothesis that FGF19 increases glutamate release from AP and NTS neurons that project to the DMV in hyperglycemic mice. FGF19 therefore modifies the local vago-vagal reflex circuitry at several points. Additionally, since the AP and NTS communicate with several other metabolic regulatory nuclei in the brain, FGF19 in the hindbrain may alter neuroendocrine and behavioral aspects of metabolism, in addition to changes in parasympathetic output.
Strong Interactive Effects of Warming and Insect Herbivory on Soil Carbon and Nitrogen Dynamics at Subarctic Tree Line
Authors: Meyer Nele , Silfver Tarja , Karhu Kristiina , Myller Kristiina , Sietiö Outi-Maaria , Myrsky Eero , Oksanen Elina , Rousi Matti , Mikola Juha
Published: November 2021

Warming will likely stimulate Arctic primary production, but also soil C and N mineralization, and it remains uncertain whether the Arctic will become a sink or a source for CO2. Increasing insect herbivory may also dampen the positive response of plant production and soil C input to warming. We conducted an open-air warming experiment with Subarctic field layer vegetation in North Finland to explore the effects of warming (+3°C) and reduced insect herbivory (67% reduction in leaf damage using an insecticide) on soil C and N dynamics. We found that plant root growth, soil C and N concentrations, microbial biomass C, microbial activity, and soil NH4+availability were increased by both warming and reduced herbivory when applied alone, but not when combined. Soil NO3–availability increased by warming only and in-situ soil respiration by reduced herbivory only. Our results suggest that increasing C input from vegetation under climate warming increases soil C concentration, but also stimulates soil C turnover. On the other hand, it appears that insect herbivores can significantly reduce plant growth. If their abundance increases with warming as predicted, they may curtail the positive effect of warming on soil C concentration. Moreover, our results suggest that temperature and herbivory effects on root growth and soil variables interact strongly, which probably arises from a combination of N demand increasing under lower herbivory and soil mineral N supply increasing under higher temperature. This may further complicate the effects of rising temperatures on Subarctic soil C dynamics.
Is Response to Genotoxic Stress Similar in Populations of African and European Ancestry? A Study of Dose-Response After in vitro Irradiation
Authors: Soumboundou Mamadou , Dossou Julien , Kalaga Yossef , Nkengurutse Innocent , Faye Ibrahima , Guingani Albert , Gadji Macoura , Yameogo Koudbi J. , Zongo Henri , Mbaye Gora , Dem Ahmadou , Diarra Mounibé , Adjibade Rached , Djebou Catherine , Junker Steffen , Oudrhiri Noufissa , Hempel William M. , Dieterlen Alain , Jeandidier Eric , Carde Patrice , El Maalouf Elie , Colicchio Bruno , Bennaceur-Griscelli Annelise , Fenech Michael , Voisin Philippe , Rodriguez-Lafrasse Claire , M’Kacher Radhia
Published: November 2021

Background: Exposure to genotoxic stress such as radiation is an important public health issue affecting a large population. The necessity of analyzing cytogenetic effects of such exposure is related to the need to estimate the associated risk. Cytogenetic biological dosimetry is based on the relationship between the absorbed dose and the frequency of scored chromosomal aberrations. The influence of confounding factors on radiation response is a topical issue. The role of ethnicity is unclear. Here, we compared the dose-response curves obtained after irradiation of circulating lymphocytes from healthy donors of African and European ancestry.

Materials and Methods: Blood samples from six Africans living in Africa, five Africans living in Europe, and five Caucasians living in Europe were exposed to various doses (0–4 Gy) of X-rays at a dose-rate of 0.1 Gy/min using an X-RAD320 irradiator. A validated cohort composed of 14 healthy Africans living in three African countries was included and blood samples were irradiated using the same protocols. Blood lymphocytes were cultured for 48 h and chromosomal aberrations scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined and the Kruskal-Wallis test was used to compare the dose-response curves of the two populations.

Results: No spontaneous dicentric chromosomes were detected in African donors, thus establishing a very low background of unstable chromosomal aberrations relative to the European population. There was a significant difference in the dose response curves between native African and European donors. At 4 Gy, African donors showed a significantly lower frequency of dicentric chromosomes (p = 8.65 10–17), centric rings (p = 4.0310–14), and resulting double-strand-breaks (DSB) (p = 1.32 10–18) than European donors. In addition, a significant difference was found between African donors living in Europe and Africans living in Africa.

Conclusion: This is the first study to demonstrate the important role of ethnic and environmental factors that may epigenetically influence the response to irradiation. It will be necessary to establish country-of-origen-specific dose response curves to practice precise and adequate biological dosimetry. This work opens new perspective for the comparison of treatments based on genotoxic agents, such as irradiation.
Identification of Intercellular Signaling Changes Across Conditions and Their Influence on Intracellular Signaling Response From Multiple Single-Cell Datasets
Authors: Hao Mengqian , Zou Xiufen , Jin Suoqin
Published: November 2021

Identification of intercellular signaling changes across multiple single-cell RNA-sequencing (scRNA-seq) datasets as well as how intercellular communications affect intracellular transcription factors (TFs) to regulate target genes is crucial in understanding how distinct cell states respond to evolution, perturbations, and diseases. Here, we first generalized our previously developed tool CellChat, enabling flexible comparison analysis of cell–cell communication networks across any number of scRNA-seq datasets from interrelated biological conditions. This greatly facilitates the ready detection of signaling changes of cell–cell communication in response to any biological perturbations. We then investigated how intercellular communications affect intracellular signaling response by inferring a multiscale signaling network which bridges the intercellular communications at the population level and the cell state–specific intracellular signaling network at the molecular level. The latter is constructed by integrating receptor-TF interactions collected from public databases and TF-target gene regulations inferred from a network-regularized regression model. By applying our approaches to three scRNA-seq datasets from skin development, spinal cord injury, and COVID-19, we demonstrated the capability of our approaches in identifying the predominant signaling changes across conditions and the critical signaling mechanisms regulating target gene expression. Together, our work will facilitate the identification of both intercellular and intracellular dysregulated signaling mechanisms responsible for biological perturbations in diverse tissues.
Asymmetric Divergence in Transmitted SNPs of DNA Replication/Transcription and Their Impact on Gene Expression in Polyploid Brassica napus
Authors: Tang Minqiang , Li Juanling , Hu Xu , Sun Lu , Helal MMU , Chen Jianguo , Zhang Yuanyuan
Published: November 2021

The marked increase in plant genomic data has provided valuable resources for investigating the dynamic evolution of duplicate genes in polyploidy. Brassica napus is an ideal model species for investigating polyploid genome evolution. The present study comprehensively analyzed DNA and RNA variation of two representative B. napus inbredlines, Zhongshuang11 and Zhongyou821, and we investigated gene expression levels of An and Cn subgenomes in multiple tissues of the two lines. The distribution of transmitted single nucleotide polymorphisms (SNPs) was significantly different in two subgenomes of B. napus. Gene expression levels were significantly negatively correlated with number of variations in replication and transcription of the corresponding genes, but were positively correlated with the ratios of transmitted SNPs from DNA to RNA. We found a higher density of SNP variation in An than that in Cn during DNA replication and more SNPs were transmitted to RNA during transcription, which may contribute to An expression dominance. These activities resulted in asymmetrical gene expression in polyploid B. napus. The SNPs transmitted from DNA to RNA could be an important complement feature in comparative genomics, and they may play important roles in asymmetrical genome evolution in polyploidy.
HIF-Dependent NFATC1 Activation Upregulates ITGA5 and PLAUR in Intestinal Epithelium in Inflammatory Bowel Disease
Authors: Knyazev Evgeny , Maltseva Diana , Raygorodskaya Maria , Shkurnikov Maxim
Published: November 2021

Intestinal epithelial cells exist in physiological hypoxia, leading to hypoxia-inducible factor (HIF) activation and supporting barrier function and cell metabolism of the intestinal epithelium. In contrast, pathological hypoxia is a common feature of some chronic disorders, including inflammatory bowel disease (IBD). This work was aimed at studying HIF-associated changes in the intestinal epithelium in IBD. In the first step, a list of genes responding to chemical activation of hypoxia was obtained in an in vitro intestinal cell model with RNA sequencing. Cobalt (II) chloride and oxyquinoline treatment of both undifferentiated and differentiated Caco-2 cells activate the HIF-signaling pathway according to gene set enrichment analysis. The core gene set responding to chemical hypoxia stimulation in the intestinal model included 115 upregulated and 69 downregulated genes. Of this set, protein product was detected for 32 genes, and fold changes in proteome and RNA sequencing significantly correlate. Analysis of publicly available RNA sequencing set of the intestinal epithelial cells of patients with IBD confirmed HIF-1 signaling pathway activation in sigmoid colon of patients with ulcerative colitis and terminal ileum of patients with Crohn’s disease. Of the core gene set from the gut hypoxia model, expression activation of ITGA5 and PLAUR genes encoding integrin α5 and urokinase-type plasminogen activator receptor (uPAR) was detected in IBD specimens. The interaction of these molecules can activate cell migration and regenerative processes in the epithelium. Transcription factor analysis with the previously developed miRGTF tool revealed the possible role of HIF1A and NFATC1 in the regulation of ITGA5 and PLAUR gene expression. Detected genes can serve as markers of IBD progression and intestinal hypoxia.
Glutathione Metabolism Is a Regulator of the Acute Inflammatory Response of Monocytes to (1→3)-β-D-Glucan
Authors: Ramendra Rayoun , Mancini Mathieu , Ayala Jose-Mauricio , Tung Lin Tze , Isnard Stephane , Lin John , Routy Jean-Pierre , Nijnik Anastasia , Langlais David
Published: November 2021

(1→3)-β-D-Glucan (BDG) represents a potent pathogen-associated molecular pattern (PAMP) in triggering the host response to fungal and some bacterial infections. Monocytes play a key role in recognizing BDG and governing the acute host response to infections. However, the mechanisms regulating monocyte’s acute response to BDG are poorly understood. We sought to investigate the response of monocytes to BDG at the epigenetic, transcriptomic, and molecular levels. Response of human monocytes to 1, 4, and 24 hours of BDG exposure was investigated using RNA-seq, ATAC-seq, H3K27ac and H3K4me1 ChIP-seq. We show that pathways including glutathione metabolism, pentose phosphate pathway, and citric acid cycle were upregulated at the epigenetic and transcriptomic levels in response to BDG exposure. Strikingly, unlike bacterial lipopolysaccharides, BDG induced intracellular glutathione synthesis. BDG exposure also induced NADP synthesis, increased NADPH/NADP ratio, and increased expression of genes involved in the pentose phosphate pathway in a GSH-dependent manner. By inhibiting GSH synthesis with L-buthionine sulfoximine (BSO) before BDG exposure we show that the GSH pathway promotes cell survival and regulates monocyte’s effector functions including NO production, phagocytosis, and cytokine production. In summary, our work demonstrates that BDG induces glutathione synthesis and metabolism in monocytes, which is a major promoter of the acute functional response of monocytes to infections.
Solid Tumor Microenvironment Can Harbor and Support Functional Properties of Memory T Cells
Authors: Sullivan Peter M. , Reed Steven James , Kalia Vandana , Sarkar Surojit
Published: November 2021

Robust T cell responses are crucial for effective anti-tumor responses and often dictate patient survival. However, in the context of solid tumors, both endogenous T cell responses and current adoptive T cell therapies are impeded by the immunosuppressive tumor microenvironment (TME). A multitude of inhibitory signals, suppressive immune cells, metabolites, hypoxic conditions and limiting nutrients are believed to render the TME non-conducive to sustaining productive T cell responses. In this study we conducted an in-depth phenotypic and functional comparison of tumor-specific T cells and tumor-nonspecific bystander memory T cells within the same TME. Using two distinct TCR transgenic and solid-tumor models, our data demonstrate that despite exposure to the same cell-extrinsic factors of the TME, the tumor-nonspecific bystander CD8 T cells retain the complete panoply of memory markers, and do not share the same exhaustive phenotype as tumor-reactive T cells. Compared to tumor-specific T cells, bystander memory CD8 T cells in the TME also retain functional effector cytokine production capabilities in response to ex vivo cognate antigenic stimulation. Consistent with these results, bystander memory T cells isolated from tumors showed enhanced recall responses to secondary bacterial challenge in a T cell transplant model. Importantly, the tumor-resident bystander memory cells could also efficiently utilize the available resources within the TME to elaborate in situ recall effector functions following intra-tumoral peptide antigen injection. Additionally, CRISPR-Cas9 gene deletion studies showed that CXCR3 was critical for the trafficking of both tumor antigen-specific and bystander memory T cells to solid tumors. Collectively, these findings that T cells can persist and retain their functionality in distinct solid tumor environments in the absence of cognate antigenic stimulation, support the notion that persistent antigenic signaling is the central driver of T cell exhaustion within the TME. These studies bear implications for programming more efficacious TCR- and CAR-T cells with augmented therapeutic efficacy and longevity through regulation of antigen and chemokine receptors.
MicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells
Authors: Sun Jijun , Liu Ruiling , He Xiaozhen , Bian Jiang , Zhao Wenbo , Shi Weiyun , Ruan Qingguo
Published: November 2021

Regulatory T cells (Tregs) are considered important for controlling the onset and development of autoimmune disease. Although studies have shown that miR-21 is expressed at higher levels in Treg cells, it remains largely elusive whether miR-21 regulates the immune-suppressive function of Tregs. In the current study, we generated mice lacking miR-21 specifically in their Tregs and investigated the role of miR-21 in regulating Treg function both in vitro and in vivo. Our study revealed that Tregs lacking miR-21 exhibit normal phenotype and unaltered function in suppressing T cell proliferation and dendritic cell activation in vitro. However, compared with miR-21-sufficient Tregs, they produce significant more IL-17 and IL-10 when under pathogenic Th17-priming condition. Adenoviral delivery of miR-21 into Treg cells is able to reduce the expression of both IL-17 and IL-10. Mechanistic study revealed that miR-21 down-regulates IL-10 expression through direct targeting of IL-10, and suppresses reprogramming of Tregs into IL-17-secreting cells through down-regulating Stat3 activity. However, we detected no significant or marginal difference in the development of various autoimmune diseases between wild type mice and mice with Treg-specific deletion of miR-21. In conclusion, our study demonstrated that miR-21 in Tregs regulates diametrically opposed biological Treg functions and is largely dispensable for the development of autoimmune disease.
Exploiting the STAT3 Nexus in Cancer-Associated Fibroblasts to Improve Cancer Therapy
Authors: Allam Amr , Yakou Marina , Pang Lokman , Ernst Matthias , Huynh Jennifer
Published: November 2021

The tumor microenvironment (TME) is composed of a heterogenous population of cells that exist alongside the extracellular matrix and soluble components. These components can shape an environment that is conducive to tumor growth and metastatic spread. It is well-established that stromal cancer-associated fibroblasts (CAFs) in the TME play a pivotal role in creating and maintaining a growth-permissive environment for tumor cells. A growing body of work has uncovered that tumor cells recruit and educate CAFs to remodel the TME, however, the mechanisms by which this occurs remain incompletely understood. Recent studies suggest that the signal transducer and activator of transcription 3 (STAT3) is a key transcription factor that regulates the function of CAFs, and their crosstalk with tumor and immune cells within the TME. CAF-intrinsic STAT3 activity within the TME correlates with tumor progression, immune suppression and eventually the establishment of metastases. In this review, we will focus on the roles of STAT3 in regulating CAF function and their crosstalk with other cells constituting the TME and discuss the utility of targeting STAT3 within the TME for therapeutic benefit.
Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis
Authors: Liu Pei , Bai Miao , Ma Chao , Yan Yaping , Zhang Gejuan , Wu Songdi , Li Zunbo , Zhao Daidi , Ren Kaixi , Li Hongzeng , Guo Jun
Published: November 2021

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.
Observations of Internal Structure Changes in Shoaling Internal Solitary Waves Based on Seismic Oceanography Method
Authors: Song Haibin , Gong Yi , Yang Shengxiong , Guan Yongxian
Published: November 2021

High spatial resolution and deep detection depths of seismic reflection surveying are conducive to studying the fine structure of the internal solitary wave. However, seismic images are instantaneous, which are not conducive to observing kinematic processes of the internal solitary waves. We improved the scheme of seismic data processing and used common-offset gathers to continuously image the same location. In this way, we can observe internal fine structure changes during the movement of the internal solitary waves, especially the part in contact with the seafloor. We observed a first-mode depression internal solitary wave on the continental slope near the Dongsha Atoll of the South China Sea and short-term shoaling processes of the internal solitary wave by using our improved method. We found that the change in shape of waveform varies at different depths. We separately analyzed the evolution of the six waveforms at different depths. The results showed that the waveform in deep water deforms before that in shallow water and the waveform in shallow water deforms to a greater degree. We measured four parameters of the six waveforms during the shoaling including phase velocity, amplitude, wavelength, and slopes of leading and trailing edge. The phase velocity and amplitudes of waveforms in shallow water increase, the wavelengths decrease, and the slopes of trailing edge gradually become larger than that of the leading edge, while the amplitudes of the deep water waveforms do not change significantly and the phase velocities decrease. Our results are consistent with previous studies made by numerical simulations, which suggest the effectiveness of the new processing scheme. This improved scheme cannot only study the internal solitary waves shoaling, but also has great potential in the study of other ocean dynamics.
Presentation and Real-World Management of Giant Cell Arteritis (Artemis Study)
Authors: Mahr Alfred , Hachulla Eric , de Boysson Hubert , Guerroui Nassim , Héron Emmanuel , Vinzio Stéphane , Broner Jonathan , Lapébie François-Xavier , Michaud Martin , Sailler Laurent , Zenone Thierry , Djerad Mohamed , Jouvray Mathieu , Shipley Emilie , Tieulie Nathalie , Armengol Guillaume , Bouldoires Bastien , Viallard Jean-Francois , Idier Isabelle , Paccalin Marc , Devauchelle-Pensec Valérie
Published: November 2021

Background: Few studies of daily practice for patients with giant cell arteritis (GCA) are available. This French study aimed to describe the characteristics and management of GCA in a real-life setting.

Methods: Cross-sectional, non-interventional, multicenter study of patients ≥50 years old who consulted hospital-based specialists for GCA and were under treatment. Patient characteristics and journey, diagnostic methods and treatments were collected. Descriptive analyses were performed.

Results: In total, 306 patients (67% females, mean age 74 ± 8 years old) were recruited by 69 physicians (internists: 85%, rheumatologists: 15%); 13% of patients had newly diagnosed GCA (diagnosis-to-visit interval <6 weeks). Overall median disease duration was 13 months (interquartile range 5–26). Most patients were referred by general practitioners (56%), then ophthalmologists (10%) and neurologists (7%). Most common comorbidities were hypertension (46%), psychiatric disorders (10%), dyslipidemia (12%), diabetes (9%), and osteoporosis (6%). Initial GCA presentations included cranial symptoms (89%), constitutional symptoms (74%), polymyalgia rheumatica (48%), and/or other extra-cranial manifestations (35%). Overall, 85, 31, 26, and 30% of patients underwent temporal artery biopsy, high-resolution temporal artery Doppler ultrasonography, 18FDG-PET, and aortic angio-CT, respectively. All patients received glucocorticoids, which were ongoing for 89%; 29% also received adjunct medication(s) (methotrexate: 19%, tocilizumab: 15%). A total of 40% had relapse(s); the median time to the first relapse was 10 months. Also, 37% had comorbidity(ies) related to or aggravated by glucocorticoids therapy.

Conclusion: This large observational study provides insight into current medical practices for GCA. More than one third of patients had comorbidities related to glucocorticoid therapy for a median disease duration of 13 months. Methotrexate and tocilizumab were the most common adjunct medications.
Comparison of Clinical Characteristics for Distinguishing COVID-19 From Influenza During the Early Stages in Guangdong, China
Authors: Li Yongzhi , He Huan , Gao Yuhan , Ou Zejin , He Wenqiao , Chen Caiyun , Fu Jiaqi , Xiong Husheng , Chen Qing
Published: November 2021

Background: To explore the differences in clinical manifestations and infection marker determination for early diagnosis of coronavirus disease-2019 (COVID-19) and influenza (A and B).

Methods: A hospital-based retrospective cohort study was designed. Patients with COVID-19 and inpatients with influenza at a sentinel surveillance hospital were recruited. Demographic data, medical history, laboratory findings, and radiographic characteristics were summarized and compared between the two groups. The chi-square test or Fisher's exact test was used for categorical variables, and Kruskal–Wallis H-test was used for continuous variables in each group. Receiver operating characteristic curve (ROC) was used to differentiate the intergroup characteristics. The Cox proportional hazards model was used to analyze the predisposing factors.

Results: About 23 patients with COVID-19 and 74 patients with influenza were included in this study. Patients with influenza exhibited more symptoms of cough and sputum production than COVID-19 (p < 0.05). CT showed that consolidation and pleural effusion were more common in influenza than COVID-19 (p < 0.05). Subgroup analysis showed that patients with influenza had high values of infection and coagulation function markers, but low values of blood routine and biochemical test markers than patients with COVID-19 (mild or moderate groups) (p < 0.05). In patients with COVID-19, the ROC analysis showed positive predictions of albumin and hematocrit, but negative predictions of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), and erythrocyte sedimentation rate. Multivariate analysis revealed that influenza might associate with risk of elevated CRP, PCT, and LDH, whereas COVID-19 might associated with high HBDH.

Conclusion: Patients with influenza had more obvious clinical symptoms but less common consolidation lesions and pleural effusion than those with COVID-19. These findings suggested that influenza likely presents with stronger inflammatory reactions than COVID-19, which provides some insights into the pathogenesis of these two contagious respiratory illnesses.
COVID-19 Vaccine Uptake, Acceptance, and Hesitancy Among Persons With Mental Disorders During the Second Stage of China's Nationwide Vaccine Rollout
Authors: Huang Hui , Zhu Xiao-Min , Liang Peng-Wei , Fang Zhong-Ming , Luo Wei , Ma Yi-Ming , Zhong Bao-Liang , Chiu Helen Fung-Kum
Published: November 2021

Persons with mental disorders (PwMDs) are a priority group for COVID-19 vaccination, but empirical data on PwMDs' vaccine uptake and attitudes toward COVID-19 vaccines are lacking. This study examined the uptake, acceptance, and hesitancy associated with COVID-19 vaccines among Chinese PwMDs during China's nationwide vaccine rollout. In total, 906 adult PwMDs were consecutively recruited from a large psychiatric hospital in Wuhan, China, and administered a self-report questionnaire, which comprised standardized questions regarding sociodemographics, COVID-19 vaccination status, attitudes toward COVID-19 vaccines, and psychopathology. Vaccine-recipients were additionally asked to report adverse events that occurred following vaccination. PwMDs had a much lower rate of vaccination than Wuhan residents (10.8 vs. 40.0%). The rates of vaccine acceptance and hesitancy were 58.1 and 31.1%, respectively. Factors associated with vaccine uptake included having other mental disorders [odds ratio (OR) = 3.63], believing that ≥50% of vaccine-recipients would be immune to COVID-19 (OR = 3.27), being not worried about the side effects (OR = 2.59), and being an outpatient (OR = 2.24). Factors associated with vaccine acceptance included perceiving a good preventive effect of vaccines (OR = 12.92), believing that vaccines are safe (OR = 4.08), believing that ≥50% of vaccine-recipients would be immune to COVID-19 (OR = 2.20), and good insight into the mental illness (OR = 1.71). Adverse events occurred in 21.4% of vaccine-recipients and exacerbated pre-existing psychiatric symptoms in 2.0% of vaccine-recipients. Nevertheless, 95.2% of vaccine-recipients rated adverse events as acceptable. Compared to the 58.1% vaccine acceptance rate and the 40.0% vaccination rate in the general population, the 10.8% vaccine coverage rate suggested a large unmet need for COVID-19 vaccination in Chinese PwMDs. Strategies to increase vaccination coverage among PwMDs may include provision of reliable sources of information on vaccines, health education to foster positive attitudes toward vaccines, a practical guideline to facilitate clinical decision-making for vaccination, and the involvement of psychiatrists in vaccine consultation and post-vaccination follow-up services.
Influenza B Lineages Have More in Common Than Meets the Eye. Trivalent Influenza Vaccines Trigger Heterotypic Antibodies Against Both Influenza B Viruses
Authors: Sánchez-de Prada Laura , Rojo-Rello Silvia , Domínguez-Gil Marta , Tamayo-Gómez Eduardo , Ortiz de Lejarazu-Leonardo Raúl , Eiros José María , Sanz-Muñoz Iván
Published: November 2021

Influenza B is accountable for an important burden during flu epidemics, causing special impact in children and the elderly. Vaccination is the best approach to address influenza infections. However, one of the main problems of this virus is that two different lineages circulate together, Victoria and Yamagata; and trivalent vaccines, that only contain one of these lineages, are still in use. For that reason, if during an epidemic, the lineage not included in the vaccine predominates, a mismatch would occur, and the vaccine effectiveness will be very poor. In this work, we evaluated the cross-protection given by the trivalent Influenza vaccine and compared serological profiles based on age, sex, and the type of vaccine used. We performed a retrospective analysis of serum samples obtained before and after seasonal influenza vaccination during 20 seasons (1998–2018). The results showed that heterotypic reactivity between both influenza B lineages is common, but always lower than the homologous response. Age is a relevant factor for this cross-reactivity between both lineages, while the sex and the type of vaccine not. Vaccination with trivalent influenza vaccines elicits cross-reactive antibodies against both lineages, however, this response might not be enough to provide an appropriate serological protection in case of mismatch.
Transcriptomic Analysis of Listeria monocytogenes in Response to Bile Under Aerobic and Anaerobic Conditions
Authors: Chakravarty Damayanti , Sahukhal Gyan , Arick Mark , Davis Morgan L. , Donaldson Janet R.
Published: November 2021

Listeria monocytogenes is a gram-positive facultative anaerobic bacterium that causes the foodborne illness listeriosis. The pathogenesis of this bacterium depends on its survival in anaerobic, acidic, and bile conditions encountered throughout the gastrointestinal (GI) tract. This transcriptomics study was conducted to analyze the differences in transcript levels produced under conditions mimicking the GI tract. Changes in transcript levels were analyzed using RNA isolated from L. monocytogenes strain F2365 at both aerobic and anaerobic conditions, upon exposure to 0 and 1% bile at acidic and neutral pH. Transcripts corresponding to genes responsible for pathogenesis, cell wall associated proteins, DNA repair, transcription factors, and stress responses had variations in levels under the conditions tested. Upon exposure to anaerobiosis in acidic conditions, there were variations in the transcript levels for the virulence factors internalins, listeriolysin O, etc., as well as many histidine sensory kinases. These data indicate that the response to anaerobiosis differentially influences the transcription of several genes related to the survival of L. monocytogenes under acidic and bile conditions. Though further research is needed to decipher the role of oxygen in pathogenesis of L. monocytogenes, these data provide comprehensive information on how this pathogen responds to the GI tract.
Mutations in the Promoter and Coding Regions of Avr3a Cause Gain of Virulence of Phytophthora sojae to Rps3a in Soybean
Authors: Hu Yanhong , He Zhihua , Kang Yebin , Cui Linkai
Published: November 2021

Phytophthora sojaethreatens soybean production worldwide, and the cultivation of soybean cultivars carryingRpsgenes is the most effective way to control this pathogen. However, DNA mutations in theAvrgenes ofP. sojaecan escape recognization of the correspondingRpsgenes, leading to the loss of soybean resistance. In this study, we investigated sequence polymorphism and transcript level of theAvr3agene in Chinese isolates ofP. sojae. Twenty-four mutations resulting in five uniqueAvr3aalleles were discovered in theAvr3acoding region from 32P. sojaeisolates. TheAvr3atranscripts were detectable in the isolates containingAvr3a(I),Avr3a(II),Avr3a(III), andAvr3a(IV) but not in the isolates containingAvr3a(V). Promoter and 5'-UTR sequence analysis revealed eight unique mutations in the promoter region ofAvr3a(V), suggesting that the mutations could result in the loss ofAvr3a(V) transcription. Virulence tests indicated the isolates containingAvr3a(II) andAvr3a(IV) were virulent, suggesting that the mutations in the coding regions ofAvr3a(II) andAvr3a(IV) caused the gain of virulence toRps3a. Based on DNA mutations ofAvr3ain virulent alleles, two SNP markers and one PCR-based marker were developed successfully for detecting the virulence ofP. sojaeisolates toRps3a. These findings provide new insights into escape mechanisms ofAvr3aand effective support for accurate pathotype identification ofP. sojaeusing molecular methods.
Accelerating Complete Phytoplasma Genome Assembly by Immunoprecipitation-Based Enrichment and MinION-Based DNA Sequencing for Comparative Analyses
Authors: Tan Choon Meng , Lin Yu-Chen , Li Jian-Rong , Chien Yuan-Yu , Wang Chien-Jui , Chou Lin , Wang Cheng-Wei , Chiu Yi-Ching , Kuo Chih-Horng , Yang Jun-Yi
Published: November 2021

Phytoplasmas are uncultivated plant-pathogenic bacteria with agricultural importance. Those belonging to the 16SrII group, represented by ‘Candidatus P. aurantifolia’, have a wide range of plant hosts and cause significant yield losses in valuable crops, such as pear, sweet potato, peanut, and soybean. In this study, a method that combines immunoprecipitation-based enrichment and MinION long-read DNA sequencing was developed to solve the challenge of phytoplasma genome studies. This approach produced long reads with high mapping rates and high genomic coverage that can be combined with Illumina reads to produce complete genome assemblies with high accuracy. We applied this method to strain NCHU2014 and determined its complete genome sequence, which consists of one circular chromosome with 635,584 bp and one plasmid with 4,224 bp. Although ‘Ca. P. aurantifolia’ NCHU2014 has a small chromosome with only 471 protein-coding genes, it contains 33 transporter genes and 27 putative effector genes, which may contribute to obtaining nutrients from hosts and manipulating host developments for their survival and multiplication. Two effectors, the homologs of SAP11 and SAP54/PHYL1 identified in ‘Ca. P. aurantifolia’ NCHU2014, have the biochemical activities in destabilizing host transcription factors, which can explain the disease symptoms observed in infected plants. Taken together, this study provides the first complete genome available for the 16SrII phytoplasmas and contributes to the understanding of phytoplasma pathogenicity.
DNA Engineering and Hepatitis B Virus Replication
Authors: Gan Chun-yang , Cui Jing , Zhang Wen-lu , Wang Yu-wei , Huang Ai-long , Hu Jie-li
Published: November 2021

Recombinant DNA technology is a vital method in human hepatitis B virus (HBV), producing reporter viruses or vectors for gene transferring. Researchers have engineered several genes into the HBV genome for different purposes; however, a systematic analysis of recombinant strategy is lacking. Here, using a 500-bp deletion strategy, we scanned the HBV genome and identified two regions, region I (from nt 2,118 to 2,814) and region II (from nt 99 to 1,198), suitable for engineering. Ten exogenous genes, including puromycin N-acetyl transferase gene (Pac), blasticidin S deaminase gene (BSD), Neomycin-resistance gene (Neo), Gaussia luciferase (Gluc), NanoLuc (Nluc), copGFP, mCherry, UnaG, eGFP, and tTA1, were inserted into these two regions and fused into the open reading frames of hepatitis B core protein (HBC) and hepatitis B surface protein (HBS) via T2A peptide. Recombination of 9 of the 10 genes at region 99–1198 and 5 of the 10 genes at region 2118–2814 supported the formation of relaxed circular (RC) DNA. HBV DNA and HBV RNA assays implied that exogenous genes potentially abrogate RC DNA by inducing the formation of adverse secondary structures. This hypothesis was supported because sequence optimization of the UnaG gene based on HBC sequence rescued RC DNA formation. Findings from this study provide an informative basis and a valuable method for further constructing and optimizing recombinant HBV and imply that DNA sequence might be intrinsically a potential source of selective pressure in the evolution of HBV.
Hybrid de novo Genome Assembly of Erwinia sp. E602 and Bioinformatic Analysis Characterized a New Plasmid-Borne lac Operon Under Positive Selection
Authors: Xia Yu , Wei Zhi-Yuan , He Rui , Li Jia-Huan , Wang Zhi-Xin , Huo Jun-Da , Chen Jian-Huan
Published: November 2021

Our previous study identified a new β-galactosidase in Erwinia sp. E602. To further understand the lactose metabolism in this strain, de novo genome assembly was conducted by using a strategy combining Illumina and PacBio sequencing technology. The whole genome of Erwinia sp. E602 includes a 4.8 Mb chromosome and a 326 kb large plasmid. A total of 4,739 genes, including 4,543 protein-coding genes, 25 rRNAs, 82 tRNAs and 7 other ncRNAs genes were annotated. The plasmid was the largest one characterized in genus Erwinia by far, and it contained a number of genes and pathways responsible for lactose metabolism and regulation. Moreover, a new plasmid-borne lac operon that lacked a typical β-galactoside transacetylase (lacA) gene was identified in the strain. Phylogenetic analysis showed that the genes lacY and lacZ in the operon were under positive selection, indicating the adaptation of lactose metabolism to the environment in Erwinia sp. E602. Our current study demonstrated that the hybrid de novo genome assembly using Illumina and PacBio sequencing technologies, as well as the metabolic pathway analysis, provided a useful strategy for better understanding of the evolution of undiscovered microbial species or strains.
Multiplexed Single-Cell in situ RNA Profiling
Authors: Wang Yu-Sheng , Guo Jia
Published: November 2021

The ability to quantify a large number of varied transcripts in single cells in their native spatial context is crucial to accelerate our understanding of health and disease. Bulk cell RNA analysis masks the heterogeneity in the cell population, while the conventional RNA imaging approaches suffer from low multiplexing capacity. Recent advances in multiplexed fluorescence in situ hybridization (FISH) methods enable comprehensive RNA profiling in individual cells in situ. These technologies will have wide applications in many biological and biomedical fields, including cell type classification, signaling network analysis, tissue architecture, disease diagnosis and patient stratification, etc. In this minireview, we will present the recent technological advances of multiplexed single-cell in situ RNA profiling assays, discuss their advantages and limitations, describe their biological applications, highlight the current challenges, and propose potential solutions.
Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort
Authors: Liu Yi , Xiang Juan , Peng Gang , Shen Chenfu
Published: November 2021

PDZ-binding kinase (PBK) is known to regulate tumor progression in some cancer types. However, its relationship to immune cell infiltration and prognosis in different cancers is unclear. This was investigated in the present study by analyzing data from TCGA, GEO, GETx, TIMER, CPTAC, GEPIA2, cBioPortal, GSCALite, PROGNOSCAN, PharmacoDB, STRING, and ENCORI databases. PBK was overexpressed in most tumors including adenocortical carcinoma (hazard ratio [HR] = 2.178, p < 0.001), kidney renal clear cell carcinoma (KIRC; HR = 1.907, p < 0.001), kidney renal papillary cell carcinoma (HR = 3.024, p < 0.001), and lung adenocarcinoma (HR = 1.255, p < 0.001), in which it was associated with poor overall survival and advanced pathologic stage. PBK methylation level was a prognostic marker in thyroid carcinoma (THCA). PBK expression was positively correlated with the levels of BIRC5, CCNB1, CDC20, CDK1, DLGAP5, MAD2L1, MELK, PLK1, TOP2A, and TTK in 32 tumor types; and with the levels of the transcription factors E2F1 and MYC, which regulate apoptosis, the cell cycle, cell proliferation and invasion, tumorigenesis, and metastasis. It was also negatively regulated by the microRNAs hsa-miR-101-5p, hsa-miR-145-5p, and hsa-miR-5694. PBK expression in KIRC, liver hepatocellular carcinoma, THCA, and thymoma was positively correlated with the infiltration of immune cells including B cells, CD4+T cells, CD8+ T cells, macrophages, monocytes, and neutrophils. The results of the functional enrichment analysis suggested that PBK and related genes contribute to tumor development via cell cycle regulation. We also identified 20 drugs that potentially inhibit PBK expression. Thus, PBK is associated with survival outcome in a variety of cancers and may promote tumor development and progression by increasing immune cell infiltration into the tumor microenvironment. These findings indicate that PBK is a potential therapeutic target and has prognostic value in cancer treatment.
Finger Gesture Recognition Using Sensing and Classification of Surface Electromyography Signals With High-Precision Wireless Surface Electromyography Sensors
Authors: Fu Jianting , Cao Shizhou , Cai Linqin , Yang Lechan
Published: November 2021

Finger gesture recognition (FGR) plays a crucial role in achieving, for example, artificial limb control and human-computer interaction. Currently, the most common methods of FGR are visual-based, voice-based, and surface electromyography (EMG)-based ones. Among them, surface EMG-based FGR is very popular and successful because surface EMG is a cumulative bioelectric signal from the surface of the skin that can accurately and intuitively represent the force of the fingers. However, existing surface EMG-based methods still cannot fully satisfy the required recognition accuracy for artificial limb control as the lack of high-precision sensor and high-accurate recognition model. To address this issue, this study proposes a novel FGR model that consists of sensing and classification of surface EMG signals (SC-FGR). In the proposed SC-FGR model, wireless sensors with high-precision surface EMG are first developed for acquiring multichannel surface EMG signals from the forearm. Its resolution is 16 Bits, the sampling rate is 2 kHz, the common-mode rejection ratio (CMRR) is less than 70 dB, and the short-circuit noise (SCN) is less than 1.5 μV. In addition, a convolution neural network (CNN)-based classification algorithm is proposed to achieve FGR based on acquired surface EMG signals. The CNN is trained on a spectrum map transformed from the time-domain surface EMG by continuous wavelet transform (CWT). To evaluate the proposed SC-FGR model, we compared it with seven state-of-the-art models. The experimental results demonstrate that SC-FGR achieves 97.5% recognition accuracy on eight kinds of finger gestures with five subjects, which is much higher than that of comparable models.