bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Xcr1 on Dendritic Cells Rapidly Induce Th1-Associated Immune Responses That Contribute to Protection Against Influenza Infection
Authors: Tesfaye Demo Yemane , Bobic Sonja , Lysén Anna , Huszthy Peter Csaba , Gudjonsson Arnar , Braathen Ranveig , Bogen Bjarne , Fossum Even
Published: February 2022

Targeting antigen to conventional dendritic cells (cDCs) can improve antigen-specific immune responses and additionally be used to influence the polarization of the immune responses. However, the mechanisms by which this is achieved are less clear. To improve our understanding, we here evaluate molecular and cellular requirements for CD4+T cell and antibody polarization after immunization with Xcl1-fusion vaccines that specifically target cDC1s. Xcl1-fusion vaccines induced an IgG2a/IgG2b-dominated antibody response and rapid polarization of Th1 cells bothin vitroandin vivo. For comparison, we included fliC-fusion vaccines that almost exclusively induced IgG1, despite inducing a more mixed polarization of T cells. Th1 polarization and IgG2a induction with Xcl1-fusion vaccines required IL-12 secretion but were nevertheless maintained in BATF3-/-mice which lack IL-12-secreting migratory DCs. Interestingly, induction of IgG2a-dominated responses was highly dependent on the early kinetics of Th1 induction and was important for optimal protection in an influenza infection model. Early Th1 induction was dominant, since a combined Xcl1- and fliC-fusion vaccine induced IgG2a/IgG2b polarized antibody responses similar to Xcl1-fusion vaccines alone. In summary, our results demonstrate that targeting antigen to Xcr1+cDC1s is an efficient strategy for enhancing IgG2a antibody responses through rapid Th1 induction, which can be utilized for improved vaccine design.
Altered Fecal Metabolomics and Potential Biomarkers of Psoriatic Arthritis Differing From Rheumatoid Arthritis
Authors: Wang Nan , Yang Linjiao , Shang Lili , Liang Zhaojun , Wang Yanlin , Feng Min , Yu Shuting , Li Xiaoying , Gao Chong , Li Zhenyu , Luo Jing
Published: February 2022

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, and the diagnosis is quite difficult due to the unavailability of reliable clinical markers. This study aimed to investigate the fecal metabolites in PsA by comparison with rheumatoid arthritis (RA), and to identify potential diagnostic biomarkers for PsA. The metabolic profiles of the fecal samples from 27 PsA and 29 RA patients and also 36 healthy controls (HCs) were performed on ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). And differentially altered metabolites were screened and assessed using multivariate analysis for exploring the potential biomarkers of PsA. The results showed that 154 fecal metabolites were significantly altered in PsA patients when compared with HCs, and 45 metabolites were different when compared with RA patients. A total of 14 common differential metabolites could be defined as candidate biomarkers. Furthermore, a support vector machines (SVM) model was performed to distinguish PsA from RA patients and HCs, and 5 fecal metabolites, namely, α/β-turmerone, glycerol 1-hexadecanoate, dihydrosphingosine, pantothenic acid and glutamine, were determined as biomarkers for PsA. Through the metabolic pathways analysis, we found that the abnormality of amino acid metabolism, bile acid metabolism and lipid metabolism might contribute to the occurrence and development of PsA. In summary, our research provided ideas for the early diagnosis and treatment of PsA by identifying fecal biomarkers and analyzing metabolic pathways.
Long-Term Effects of Alemtuzumab on CD4+ Lymphocytes in Multiple Sclerosis Patients: A 72-Month Follow-Up
Authors: Rolla Simona , De Mercanti Stefania Federica , Bardina Valentina , Maglione Alessandro , Taverna Daniela , Novelli Francesco , Cocco Eleonora , Vladic Anton , Habek Mario , Adamec Ivan , Annovazzi Pietro Osvaldo Luigi , Horakova Dana , Clerico Marinella
Published: February 2022

Introduction

Alemtuzumab is highly effective in the treatment of patients with relapsing multiple sclerosis (PwRMS) and selectively targets the CD52 antigen, with a consequent profound lymphopenia, particularly of CD4+ T lymphocytes. However, the immunological basis of its long-term efficacy has not been clearly elucidated.

Methods

We followed up 29 alemtuzumab-treated RMS patients over a period of 72 months and studied the immunological reconstitution of their CD4+ T cell subsets by means of phenotypic and functional analysis and through mRNA-related molecule expression, comparing them to healthy subject (HS) values (rate 2:1).

Results

In patients receiving only two-course alemtuzumab, the percentage of CD4+ lymphocytes decreased and returned to basal levels only at month 48. Immune reconstitution of the CD4+ subsets was characterized by a significant increase (p < 0.001) in Treg cell percentage at month 24, when compared to baseline, and was accompanied by restoration of the Treg suppressor function that increased within a range from 2- to 6.5-fold compared to baseline and that persisted through to the end of the follow-up. Furthermore, a significant decrease in self-reactive myelin basic protein-specific Th17 (p < 0.0001) and Th1 (p < 0.05) cells reaching HS values was observed starting from month 12. There was a change in mRNA of cytokines, chemokines, and transcriptional factors related to Th17, Th1, and Treg cell subset changes, consequently suggesting a shift toward immunoregulation and a reduction of T cell recruitment to the central nervous system.

Conclusions

These data provide further insight into the mechanism that could contribute to the long-term 6-year persistence of the clinical effect of alemtuzumab on RMS disease activity.
Efficacy of Immune Checkpoint Inhibitors in Patients With EGFR Mutated NSCLC and Potential Risk Factors Associated With Prognosis: A Single Institution Experience
Authors: Bai Menglin , Wang Weiqing , Gao Xuetian , Wu Leilei , Jin Peng , Wu Hui , Yu Jinming , Meng Xue
Published: February 2022

Background

The role of immune checkpoint inhibitors (ICIs) in NSCLC patients with EGFR mutations are controversial. In this study, we aim to investigate the therapeutic efficacy of ICIs alone or in combination in patients with EGFR mutated NSCLC in late-line settings, and explore the factors that may predict the efficacy of ICIs.

Patients and Methods

We retrospectively collected the clinical and pathological information of 75 patients with confirmed EGFR mutations. All patients have developed acquired resistance to EGFR-TKIs, and were treated with ICIs in late line settings from January 2019 to January 2021, at Shandong Caner Hospital and Institute. Therapeutic efficacy was evaluated by tumor response and survival.

Results

The median follow-up period was 7.3months (range 1.8-31.8 months). The overall response rate (ORR) was 8.0%, and the disease control rate (DCR) was 78.7%. The median PFS for all patients was 3.9 months (95% CI, 2.7-5.0), while the median OS was 9.9 months (95% CI, 5.3-14.6). We found that patients with longer response duration to EGFR-TKIs (≥10 months) showed a longer PFS when treated with immunotherapy compared with patients with shorter PFS-TKI (<10 months), the median PFS in two groups were 5.2 months [95%CI 4.2-6.2] and 2.8 months [2.0-3.6]) respectively (HR, 0.53, 95%CI, 0.31-0.91, P=0.005). In exploratory analysis, we found that concurrent extracranial radiotherapy and higher body mass index (BMI) are associated with longer PFS (P values are 0.006 and 0.021 respectively).

Conclusions

We found that combination regimen of immunotherapy plus chemotherapy plus antiangiogenetic agents may yield longer survival in patients with EGFR mutated NSCLC. We also found that patients with longer PFS-TKI, concurrent extracranial radiotherapy and higher BMI may benefit more from immunotherapy.
Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns
Authors: Xu Xiao-Jun , Luo Ze-Bin , Song Hua , Xu Wei-Qun , Henter Jan-Inge , Zhao Ning , Wu Meng-Hui , Tang Yong-Min
Published: February 2022

Background

Hemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune dysregulation. Early initiation of treatment is imperative for saving lives. However, a laboratory approach that could be used to quickly evaluate the HLH subtype and clinical situation is lacking. Our previous studies indicated that cytokines such as interferon (IFN)-γ and interleukin (IL)-10 were helpful for the early diagnosis of HLH and were associated with disease severity. The purpose of this study is to clarify the different cytokine patterns of various subtypes of pediatric HLH and to investigate the role of cytokines in a simple evaluation of disease feature.

Patients and Methods

We enrolled 256 pediatric patients with newly diagnosed HLH. The clinical features and laboratory findings were collected and compared among different subtypes of HLH. A model integrating cytokines was established to stratify HLH patients into different clinical groups.

Results

Twenty-seven patients were diagnosed with primary HLH (pHLH), 179 with EBV-HLH, and 50 with other causes. The IL-6, IL-10, and IFN-γ levels and the ratios of IL-10 to IFN-γ were different among EBV-HLH, other infection-associated HLH, malignancy-associated HLH, familial HLH, and X-linked lymphoproliferative disease. Patients with the ratio of IL-10 to IFN-γ >1.33 and the concentration of IFN-γ ≤225 pg/ml were considered to have pHLH, with a sensitivity of 73% and a specificity of 84%. A four-quadrant model based on the two cutoff values was established to stratify the patients into different clinical situations. The HLH subtypes, cytokine levels, treatment regimens, treatment response, and outcomes were different among the four quadrants, with the 8-week mortality from 2.9 ± 2.9% to 21.4 ± 5.5% and the 5-year overall survival from 93.9 ± 4.2% to 52.6 ± 7.1%.

Conclusions

Different subtypes of HLH present distinct cytokine patterns. IFN-γ and the ratio of IL-10 to IFN-γ are helpful tools to differentiate HLH subtypes. A four-quadrant model based on these two parameters is a useful tool for a simple evaluation of the HLH situation.
The Notorious Harmful Algal Blooms-Forming Dinoflagellate Prorocentrum donghaiense Produces Sexual Resting Cysts, Which Widely Distribute Along the Coastal Marine Sediment of China
Authors: Hu Zhangxi , Liu Yuyang , Deng Yunyan , Tang Ying Zhong
Published: February 2022

The armored dinoflagellate Prorocentrum donghaiense distributes globally and has been forming large scale and dense ecosystem disruptive algal blooms (EDABs) in the East China Sea (ECS) almost every year since the 1990s and often in other coastal waters of the world. It has long been a mystery, however, about how these blooms were seeded or where the initiating population came from. In this work, we provide a more feasible and universal seeding mechanism, formation of resting cysts. Using light microscopy, we confirmed sexual reproduction according to the observations of mating cells in pairs, planozygotes having two similar flagella, darkened and thick-walled resting cysts with smooth surface, and germination processes of resting cyst. Using morpho-molecular detection, we confirmed P. donghaiense resting cyst in the field, including the positive detections of polymerase chain reaction (PCR) using species-specific primers and then the fluorescence in situ hybridization (FISH) using species-specific probes, and further confirmation via single-cell sequencing for the individual FISH-detected cysts. Furthermore, the distribution and abundance of P. donghaiense cysts along the coast of China Seas were mapped using an approach combining real-time PCR (qPCR) and FISH, with the qPCR quantification taking into account the doubled copy number of LSU rRNA gene in resting cysts. Resting cysts of this species were found to widely distribute in the Yellow Sea (YS), ECS, and South China Sea (SCS), with a relatively low abundance at most sampling sites, but to be absent in the eight samples from the Bohai Sea (BS). Resting cyst production confirmed with evidences from both laboratory cultures and field sediments and the extensive distribution of cysts in the China Seas, as the first case in planktonic species of Prorocentrum, not only filled up a knowledge gap about the life history of P. donghaiense but also provided a possible mechanistic facility to seed the annual blooms in the ECS and the global distribution of the species.
Short-Term Sedimentation Dynamics of Temperate Mangroves in Western Port Bay, Victoria
Authors: Sayers Sabrina , Reef Ruth
Published: February 2022

The promotion of sedimentation by mangrove ecosystems with adequate sediment supply has been well documented. However, predicting the amount of accretion or erosion at a specific point, is difficult due to the inherent stochasticity of sediment movement and deposition. Forcings which have been thought to influence short-term sedimentation rates, such as the amount of suspended matter in the incoming water, the wave regime at the site, elevation above sea level, distance from the low tide mark, and vegetation density, were investigated using large arrays of erosion pins at five sites around Western Port, Victoria over the course of one and a half years. We analyzed large scale/short-term and small-scale/longer-term vertical displacement within and between sites, and quantified small-scale intra-site variability. Results show, that while all study sites within Western Port were accreting sediment, they were not doing so at the same rate, and both intra-site and inter-site variability is high. Short-term large-scale or site wide analysis shows that total suspended matter and significant wave height (SWH) did not significantly affect vertical displacement rates. Surprisingly, neither distance from water nor vegetation density significantly affected vertical displacement or explain the spatial distribution of accretion and erosion within the sites. The coefficient of variation at each pin shows that there is high temporal variability in vertical displacement at each location, with individual pins alternating between erosion and accretion over time. Our study finds that while large scale (1 km2) patterns of sedimentation are temporally consistent, small scale patterns (< 100 m2) are difficult to predict. This small-scale stochasticity therefore compounds management of mangrove ecosystems, especially as it relates to predicting the response to sea level rise. Thus, investment in small scale management of vegetation density, or microtopography, is perhaps not required for overall shoreline stability with sea level rise and blue carbon accumulation, making ecosystem restoration more feasible where resources are limited. However, at larger, forest-wide, spatial scales a higher level of predictability exists such as the overall response of the coastal tract to prevalent wave energy and sediment supply.
First Case of Brevetoxicosis Linked to Rough-Toothed Dolphin (Steno bredanensis) Mass-Mortality Event in Eastern Central Atlantic Ocean: A Climate Change Effect?
Authors: Fernández Antonio , Sierra Eva , Arbelo Manuel , Gago-Martínez Ana , Leao Martins Jose Manuel , García-Álvarez Natalia , Bernaldo de Quiros Yara , Arregui Marina , Vela Ana Isabel , Díaz-Delgado Josue
Published: February 2022

Harmful algal blooms (HABs) have been increasingly recorded over the last decades and much work has linked these events to multiple oceanographic and climate disturbances. HABs can affect ecosystems either as events that affect dissolved oxygen, clog fish gills, or smother corals or through the production of biotoxins which affect living marine resources through food web transfers or aerosols. HAB represent a natural driver of decline and potential extinction of aquatic organisms, from invertebrates to mammals, which may offer little evolutionary adaptation particularly in very high and long-lasting exposures. Despite numerous multispecies mass-mortality events linked to HAB-associated biotoxicosis globally, there are no records in cetaceans off the central eastern Atlantic Ocean. Herein, we report the epidemiology, pathologic, microbiologic and toxicologic investigation results attesting to the first documentation of cetacean mass-mortality in European waters associated with brevetoxins. Twelve rough-toothed dolphins (Steno bredanensis) were found dead adrift or beached along the southwestern coast of Gran Canaria from April 28th to May 7th, 2008. Although pathologic examinations were limited by moderate to advanced autolysis and decomposition of the carcasses, consistent findings included multisystemic hemorrhage and undigested ingesta within the gastric compartments, mainly salema porgy (Sarpa salpa). Toxicologic analysis of gastric contents identified PbTx2 and PbTx3 brevetoxins. Our results provide compelling toxicopathologic evidence of fatal brevetoxicosis in a cohort of rough-toothed dolphins. These data add to the limited knowledge on pathology of HAB in cetaceans and provide the first account of brevetoxicosis in European waters. No other mass-mortality or individual fatality of any cetacean species has been linked to brevetoxicosis in the Canary Islands since this event.
Vaccination for SARS-CoV-2 in Patients With Psoriatic Arthritis: Can Therapy Affect the Immunological Response?
Authors: Benucci Maurizio , Damiani Arianna , Infantino Maria , Manfredi Mariangela , Lari Barbara , Grossi Valentina , Mariotti Elena Biancamaria , Corrà Alberto , Aimo Cristina , Quintarelli Lavinia , Verdelli Alice , Li Gobbi Francesca , Antiga Emiliano , Caproni Marzia
Published: February 2022

Background

A few studies on vaccination in patients with rheumatic diseases, including arthritis, connective tissue diseases, vasculitis, and psoriatic arthropathy (PsA), demonstrated reduced production of neutralizing antibodies to SARS-CoV-2 Spike RBD (receptor-binding domain contained in the N-terminal of the S1 globular head region) when compared to the general population.

Objective

The aim of our study was to observe whether different therapies for PsA [methotrexate, anti-TNF antibodies, soluble TNF receptor (etanercept) or IL-17 inhibitors] have a different impact on SARS-CoV-2 vaccination in a homogeneous population of patients.

Methods

We enrolled 110 PsA patients in remission, assessed with Disease Activity in PSoriatic Arthritis (DAPSA). Of these: 63 were in treatment with anti-TNF-α therapy (26 etanercept, 15 certolizumab, 5 golimumab, 17 adalimumab); 37 with anti-IL17 secukinumab; 10 with methotrexate. All patients underwent vaccination for SARS-CoV-2 with mRNA BNT162b2 vaccine. Assessment of absolute and percentage lymphocyte subsets and anti-SARS-CoV-2 Spike RBD IgG antibody value 3 weeks after the second vaccine dose were performed. In addition, the serum antibody levels of 96 healthy healthcare workers (HCW) were analyzed.

Results

The mean disease activity assessed with DAPSA score was 2.96 (SD = 0.60) with no significant differences between patients under different medications (p = 0.779). Median levels of neutralizing antibodies to SARS-CoV-2 Spike RBD were 928.00 binding antibody unit (BAU)/mL [IQR 329.25, 1632.0]; 1068.00 BAU/ml [IQR 475.00, 1632.00] in patients taking MTX, 846.00 BAU/ml [IQR 125.00, 1632.00] in patients taking etanercept, 908.00 BAU/mL [IQR 396.00, 1632.00] in patients taking anti-IL17 and 1148.00 BAU/ml [IQR 327.00, 1632.00] in patients taking TNF-α inhibitors, without statistically significant differences between these groups. Mean serum antibody level of HCW group was 1562.00 BAU/ml [IQR 975.00, 1632.00], being significantly higher than in the patient group (p = 0.000816). Absolute and percentage count of lymphocyte subsets were not statistically different between the subgroups under different treatments and when compared with HCW.

Conclusions

As for other rheumatic diseases on immunomodulatory treatment, our data showed a reduced humoral response in PsA patients compared to the control group. However, antibody response did not significantly differ between groups treated with different medications.
Higher Wheal Sizes of Dermatophagoides farinae Sensitization Exhibit Worse Nasal Symptoms in Allergic Rhinitis Patients
Authors: Nur Husna Siti Muhamad , Md Shukri Norasnieda , Tan Hern-Tze Tina , Mohd Ashari Noor Suryani , Wong Kah Keng
Published: February 2022

Allergic rhinitis (AR) is a global health burden and it manifests in both nasal and non-nasal symptoms. Skin prick test (SPT) is a routine procedure to diagnose AR sensitized to common allergens including house dust mites (HDMs). The degree of sensitivity of a patient toward allergens is determined by the size of the wheal formed by SPT procedure. SPT wheal sizes are influenced by recent anti-histamine usage, however it remains unclear if SPT wheal sizes are also influenced by other factors. In this study, we set out to investigate the association between SPT wheal sizes with the demographical, clinical and environmental characteristics, as well as nasal and non-nasal symptoms severity scores, of AR patients (n = 30) sensitized to common HDMs (i.e., Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis). We showed that SPT wheal sizes of HDM allergens were not associated with clinical, demographical and environmental characteristics examined. Nonetheless, significant correlations were observed between SPT wheal sizes of D. farinae sensitization with worse severity scores of all five nasal symptoms examined (i.e., sneezing, runny nose, itchy nose, congestion and postnasal drip) and four of the six non-nasal symptoms examined (i.e., throat symptoms, ear symptoms, headache and mental function). Such relationships were not observed in SPT wheal sizes of D. pteronyssinus and B. tropicalis sensitization. We suggest that increased SPT wheal sizes for D. farinae sensitization may predict the likelihood of more severe nasal and, to a lesser extent, non-nasal manifestations in AR patients.
Identification and Application of a Panel of Constitutive Promoters for Gene Overexpression in Staphylococcus aureus
Authors: Liu Qiang , Li Daiyu , Wang Ning , Guo Gang , Shi Yun , Zou Quanming , Zhang Xiaokai
Published: February 2022

Staphylococcus aureus is a leading pathogen that is currently the most common cause of infection in hospitalized patients. An in-depth genetic analysis of S. aureus virulence genes contributing to pathogenesis is needed to develop novel antimicrobial therapies. However, tools for genetic manipulation in S. aureus are limited, particularly those for gene expression. Here, 38 highly expressed genes were identified in S. aureus USA300_FPR3757 via RNA-seq. Promoter regions from 30 of these genes were successfully cloned, of which 20 promoters exhibited a wide range of activity. By utilizing these active promoters, 20 S. aureus-Escherichia coli shuttle vectors were constructed and evaluated by expressing an egfp reporter gene. Expression of the egfp gene under the control of different promoters was confirmed and quantified by Western blotting and qPCR, which suggested that the activity of these promoters varied from 18 to 650% of the activity of PsarA, a widely used promoter for gene expression. In addition, our constructed vectors were verified to be highly compatible with gene expression in different S. aureus strains. Furthermore, these vectors were evaluated and used to overexpress two endogenous proteins in S. aureus, namely, catalase and the transcriptional repressor of purine biosynthesis (PurR). Meanwhile, the physiological functions and phenotypes of overexpressed PurR and catalase in S. aureus were validated. Altogether, this evidence indicates that our constructed vectors provide a wide range of promoter activity on gene expression in S. aureus. This set of vectors carrying different constitutive promoters developed here will provide a powerful tool for the direct analysis of target gene function in staphylococcal cells.
A New Source of Diterpene Lactones From Andrographis paniculata (Burm. f.) Nees—Two Endophytic Fungi of Colletotrichum sp. With Antibacterial and Antioxidant Activities
Authors: Li Na , Xu Dan , Huang Rui-Hua , Zheng Jian-Yun , Liu You-Yan , Hu Bin-Sheng , Gu Yuan-Qin , Du Qin
Published: February 2022

Endophytic fungi of medicinal plants are abundant, and their metabolites often have antioxidant, antibacterial, and antitumor effects and can produce secondary metabolites identical or similar to those of their hosts, which can mitigate the problem of insufficient supply of medicinal plants. In this study, we screened endophytic fungi for strains that produce the same diterpene lactones as Andrographis paniculata based on their biological activity. Firstly, the dominant group of endophytic fungi of Andrographis paniculata was screened and pathogenicity was studied using Koch’s rule. Secondly, DPPH, ABTS, OH, PTIO radical scavenging, and FRAP assays were used to detect the antioxidant activity of the extracellular extracts of the strains, and total phenol and total flavonoid contents of the strains with high antioxidant capacity were determined. S. aureus, B. subtilis, E. coli, and P. aeruginosa were used to determine the antibacterial activity of the mycelial extracts of the strains. Finally, the secondary metabolites of the mycelial extracts of the strains were examined by high-performance liquid chromatography. The results showed that 32 strains of Andrographis paniculata were relatively isolated > 70% and non-pathogenic. Extracellular extracts of strains AP-1 and AP-4 showed vigorous antioxidant activity, and AP-4, AP-12, AP-47, and AP-48 showed antibacterial activity against four strains of bacteria. The HPLC results indicated that the mycelial extracts of AP-4 and AP-12 contained diterpene lactones. The two endophytic fungi were recognized as Colletotrichum sp. The study successfully obtained diterpene lactones from the endophytic fungus of Andrographis paniculata and confirmed the feasibility of using endophytic fungal strains to produce active substances consistent with the host. It was also useful for exploring endophytic fungi and medicinal plants. The relationship provides theoretical guidance.
Nectin-1 and Non-muscle Myosin Heavy Chain-IIB: Major Mediators of Herpes Simplex Virus-1 Entry Into Corneal Nerves
Authors: Wang Chenchen , Liang Qi , Sun Dong , He Yun , Jiang Jiaxuan , Guo Rongjie , Malla Tejsu , Hamrah Pedram , Liu Xun , Huang Zhenping , Hu Kai
Published: February 2022

Herpes Simplex Virus 1 (HSV-1) invades corneal nerves upon its infection of the cornea and then establishes latency in the trigeminal ganglion (TG). The latent virus in TG is often reactivated and travels back to the cornea, causing recurrent herpes simplex keratitis (HSK). The entry of HSV-1 into the corneal nerve is considered the initial step of infection resulting in HSV-1 latency and HSK recurrence. Several gD and gB receptors have been identified, including nectin-1, herpes virus entry medium (HVEM) and 3-O-sulfated heparan sulfate (3-OS-HS) as gD receptors, and non-muscle myosin heavy chain IIA (NMHC-IIA), NMHC-IIB and myelin-associated glycoprotein (MAG) as gB receptors. However, which receptors contribute to the entry of HSV-1 into corneal nerves are yet to be determined. This study observed that receptors nectin-1, HVEM, 3-OS-HS, NMHC-IIA, and NMHC-IIB, not MAG, were expressed in healthy corneal nerves. Further, we cultured TG neurons extracted from mice in vitro to screen for functional gD/gB receptors. Both in vitro siRNA knockdown and in vivo antibody blocking of either nectin-1 or NMHC-IIB reduced the entry and the replication of HSV-1 as shown by qPCR analysis and immunofluorescence measure, respectively. Also, we observed that the re-localization and the upregulation expression of NMHC-IIB after HSV-1 exposure were inhibited when gD receptor nectin-1 was knocked down. These data suggest that nectin-1 was the main gD receptor and NMHC-IIB was the main gB receptor in mediating HSV-1 entry and hold promise as therapeutic targets for resolving HSV-1 latency and HSK recurrence.
Evolutions and Managements of Soil Microbial Community Structure Drove by Continuous Cropping
Authors: Chen Yudong , Du Jianfeng , Li Yang , Tang Heng , Yin Ziyi , Yang Long , Ding Xinhua
Published: February 2022

Continuous cropping obstacles have increasingly become an important phenomenon affecting crop yield and quality. Its harm includes the deterioration of soil basic physical and chemical properties, changes of soil microbial community structure, accumulation of autotoxins, weakness of plant growth, and aggravation of diseases and pests. In this review, the evolutionary trend of soil microbial structure driven by continuous cropping was generalized, while drivers of these changes summed up as destruction of soil microbial living environment and competition within the community. We introduced a microorganism proliferation and working model with three basics and a vector, and four corresponding effective measures to reshape the structure were comprehensively expounded. According to the model, we also put forward three optimization strategies of the existing measures. In which, synthetic microbiology provides a new solution for improving soil community structure. Meanwhile, to ensure the survival and reproduction of soil microorganisms, it is necessary to consider their living space and carbon sources in soil fully. This review provided a comprehensive perspective for understanding the evolutionary trend of the soil microbial community under continuous cropping conditions and a summary of reshaping measures and their optimization direction.
An Overview of the Electron-Transfer Proteins That Activate Alkane Monooxygenase (AlkB)
Authors: Williams Shoshana C. , Austin Rachel Narehood
Published: February 2022

Alkane-oxidizing enzymes play an important role in the global carbon cycle. Alkane monooxygenase (AlkB) oxidizes most of the medium-chain length alkanes in the environment. The first AlkB identified was from P. putida GPo1 (initially known as P. oleovorans) in the early 1970s, and it continues to be the family member about which the most is known. This AlkB is found as part of the OCT operon, in which all of the key proteins required for growth on alkanes are present. The AlkB catalytic cycle requires that the diiron active site be reduced. In P. putida GPo1, electrons originate from NADH and arrive at AlkB via the intermediacy of a flavin reductase and an iron–sulfur protein (a rubredoxin). In this Mini Review, we will review what is known about the canonical arrangement of electron-transfer proteins that activate AlkB and, more importantly, point to several other arrangements that are possible. These other arrangements include the presence of a simpler rubredoxin than what is found in the canonical arrangement, as well as two other classes of AlkBs with fused electron-transfer partners. In one class, a rubredoxin is fused to the hydroxylase and in another less well-explored class, a ferredoxin reductase and a ferredoxin are fused to the hydroxylase. We review what is known about the biochemistry of these electron-transfer proteins, speculate on the biological significance of this diversity, and point to key questions for future research.
Community Structure and Functional Annotations of the Skin Microbiome in Healthy and Diseased Catfish, Heteropneustes fossilis
Authors: Sultana Shirin , Khan Md. Nasir , Hossain Muhammad Shahdat , Dai Jingcheng , Rahman Mohammad Shamsur , Salimullah Md.
Published: February 2022

The skin mucosa of fish serves as a primary barrier against pathogens. In lesion sites in diseased fish, the mucosal barrier is expected to be compromised, with a substantial presence of potential pathogens. An understanding of the skin microbiome and its functional repertoire would provide important insights into host-microbe interactions, which has important implications for prophylactic measures in aquaculture. This study revealed the skin microbiomes and their functional annotations from healthy and diseased stinging catfish (Heteropneustes fossilis) based on 16S rRNA metagenomics. The OTUs consisted of four major phyla, Proteobacteria, Bacteroidota, Actinobacteriota and Firmicutes. Among members of the predominant phyla, Proteobacteria were rich in healthy fishes, but Bacteroidota and Firmicutes were significantly differentiated in healthy and diseased fish. The diversified microbiome was high in the skin of healthy fishes and did not significantly differ from that of the diseased groups. At the genus level,Pseudomonasshowed the highest abundance in healthy fish but was nearly absent in diseased fish, whereasFlavobacteriumshowed the highest abundance in diseased fish. Linear discriminant analysis identified two phyla (Bacteroidota, Firmicutes) and two genera (Flavobacterium,Allorhizobium) that were consistently identified in diseased fishes. Functional prediction analysis specified that the genes related to physiological functions such as metabolism, immune and digestive systems and environmental adaptations could be highly expressed in diseased fishes. The present study indicates that the compositions, richness and functions of the bacterial community could influence the health status of cultured stinging catfish. Aquaculture-associated pathogenic bacteria may be identified, and preventive measures can be taken for the surveillance of fish health.
Oncolytic Virotherapy in Peritoneal Metastasis Gastric Cancer: The Challenges and Achievements
Authors: Shao Su , Yang Xue , Zhang You-Ni , Wang Xue-Jun , Li Ke , Zhao Ya-Long , Mou Xiao-Zhou , Hu Pei-Yang
Published: February 2022

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death globally. Although the mortality rate in some parts of the world, such as East Asia, is still high, new treatments and lifestyle changes have effectively reduced deaths from this type of cancer. One of the main challenges of this type of cancer is its late diagnosis and poor prognosis. GC patients are usually diagnosed in the advanced stages of the disease, which is often associated with peritoneal metastasis (PM) and significantly reduces survival. This type of metastasis in patients with GC poses a serious challenge due to limitations in common therapies such as surgery and tumor resection, as well as failure to respond to systemic chemotherapy. To solve this problem, researchers have used virotherapy such as reovirus-based anticancer therapy in patients with GC along with PM who are resistant to current chemotherapies because this therapeutic approach is able to overcome immune suppression by activating dendritic cells (DCs) and eventually lead to the intrinsic activity of antitumor effector T cells. This review summarizes the immunopathogenesis of peritoneal metastasis of gastric cancer (PMGC) and the details for using virotherapy as an effective anticancer treatment approach, as well as its challenges and opportunities.
Hearing Loss and Cognition: What We Know and Where We Need to Go
Authors: Powell Danielle S. , Oh Esther S. , Reed Nicholas S. , Lin Frank R. , Deal Jennifer A.
Published: February 2022

Although a causal association remains to be determined, epidemiologic evidence suggests an association between hearing loss and increased risk of dementia. If we determine the association is causal, opportunity for targeted intervention for hearing loss may play a fundamental role in dementia prevention. In this discussion, we summarize current research on the association between hearing loss and dementia and review potential casual mechanisms behind the association (e.g., sensory-deprivation hypothesis, information-degradation hypothesis, common cause). We emphasize key areas of research which might best inform our investigation of this potential casual association. These selected research priorities include examination of the causal mechanism, measurement of co-existing hearing loss and cognitive impairment and determination of any bias in testing, potential for managing hearing loss for prevention of dementia and cognitive decline, or the potential to reduce dementia-related symptoms through the management of hearing loss. Addressing these research gaps and how results are then translated for clinical use may prove paramount for dementia prevention, management, and overall health of older adults.
Adaptive Fusion Based Method for Imbalanced Data Classification
Authors: Liang Zefeng , Wang Huan , Yang Kaixiang , Shi Yifan
Published: February 2022

The imbalance problem is widespread in real-world applications. When training a classifier on the imbalance datasets, the classifier is hard to learn an appropriate decision boundary, which causes unsatisfying classification performance. To deal with the imbalance problem, various ensemble algorithms are proposed. However, conventional ensemble algorithms do not consider exploring an effective feature space to further improve the performance. In addition, they treat the base classifiers equally and ignore the different contributions of each base classifier to the ensemble result. In order to address these problems, we propose a novel ensemble algorithm that combines effective data transformation and an adaptive weighted voting scheme. First, we utilize modified metric learning to obtain an effective feature space based on imbalanced data. Next, the base classifiers are assigned different weights adaptively. The experiments on multiple imbalanced datasets, including images and biomedical datasets verify the superiority of our proposed ensemble algorithm.
Post-transcriptional and Post-translational Modifications of Primary Cilia: How to Fine Tune Your Neuronal Antenna
Authors: Rocha Cecilia , Prinos Panagiotis
Published: February 2022

Primary cilia direct cellular signaling events during brain development and neuronal differentiation. The primary cilium is a dynamic organelle formed in a multistep process termed ciliogenesis that is tightly coordinated with the cell cycle. Genetic alterations, such as ciliary gene mutations, and epigenetic alterations, such as post-translational modifications and RNA processing of cilia related factors, give rise to human neuronal disorders and brain tumors such as glioblastoma and medulloblastoma. This review discusses the important role of genetics/epigenetics, as well as RNA processing and post-translational modifications in primary cilia function during brain development and cancer formation. We summarize mouse and human studies of ciliogenesis and primary cilia activity in the brain, and detail how cilia maintain neuronal progenitor populations and coordinate neuronal differentiation during development, as well as how cilia control different signaling pathways such as WNT, Sonic Hedgehog (SHH) and PDGF that are critical for neurogenesis. Moreover, we describe how post-translational modifications alter cilia formation and activity during development and carcinogenesis, and the impact of missplicing of ciliary genes leading to ciliopathies and cell cycle alterations. Finally, cilia genetic and epigenetic studies bring to light cellular and molecular mechanisms that underlie neurodevelopmental disorders and brain tumors.
Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion
Authors: Ramos Raul , Wu Chi-Hong , Turrigiano Gina G.
Published: February 2022

Generalization is an adaptive mnemonic process in which an animal can leverage past learning experiences to navigate future scenarios, but overgeneralization is a hallmark feature of anxiety disorders. Therefore, understanding the synaptic plasticity mechanisms that govern memory generalization and its persistence is an important goal. Here, we demonstrate that strong CTA conditioning results in a long-lasting generalized aversion that persists for at least 2 weeks. Using brain slice electrophysiology and activity-dependent labeling of the conditioning-active neuronal ensemble within the gustatory cortex, we find that strong CTA conditioning induces a long-lasting increase in synaptic strengths that occurs uniformly across superficial and deep layers of GC. Repeated exposure to salt, the generalized tastant, causes a rapid attenuation of the generalized aversion that correlates with a reversal of the CTA-induced increases in synaptic strength. Unlike the uniform strengthening that happens across layers, reversal of the generalized aversion results in a more pronounced depression of synaptic strengths in superficial layers. Finally, the generalized aversion and its reversal do not impact the acquisition and maintenance of the aversion to the conditioned tastant (saccharin). The strong correlation between the generalized aversion and synaptic strengthening, and the reversal of both in superficial layers by repeated salt exposure, strongly suggests that the synaptic changes in superficial layers contribute to the formation and reversal of the generalized aversion. In contrast, the persistence of synaptic strengthening in deep layers correlates with the persistence of CTA. Taken together, our data suggest that layer-specific synaptic plasticity mechanisms separately govern the persistence and generalization of CTA memory.
Case Report: Sequential Transarterial and Trans-Cortical Venous Embolization of a Mixed Pial-Dural AVM
Authors: Yeboah Kevin , Fares Mary-Ann , Hansen Paul , Yoo Albert J.
Published: February 2022

Endovascular therapy is the primary treatment modality for dural arteriovenous fistulas. Pre-treatment angiographic evaluation of dural fistulas must rule out the presence of a mixed pial component or supply from pial-dural collaterals, as the pial supply must be closed before definitive occlusion of the draining vein to prevent iatrogenic rupture. In this report, we described a case of a mixed pial-dural arterial venous malformation (AVM), which was effectively treated with a sequential transarterial and trans-cortical venous embolization.
The Affective Neuroscience of Sexuality: Development of a LUST Scale
Authors: Fuchshuber Jürgen , Jauk Emanuel , Hiebler-Ragger Michaela , Unterrainer Human Friedrich
Published: February 2022

Background

In recent years, there have been many studies using the Affective Neuroscience Personality Scales (ANPS) to investigate individual differences in primary emotion traits. However, in contrast to other primary emotion traits proposed by Jaak Panksepp and colleagues, there is a considerable lack of research on the LUST (L) dimension – defined as an individual’s capacity to attain sexual desire and satisfaction – a circumstance mainly caused by its exclusion from the ANPS. Therefore, this study aims to take a first step toward the development of a standardized self-rate measurement for the L-disposition. For this purpose, two versions of the L-scales (L-12 and L-5) were developed and evaluated regarding reliability and aspects of validity.

Materials and Methods

After a pilot study (N= 204; female: 81%) with an initial 20-item pool item reductions were conducted. This led to the construction of a 12-item (L-12) version and a 5-item version (L-5), which were assessed in a second sample consisting of 371 German-speaking healthy adults (58.50% female) aged 18–69 years (M= 28;SD= 9.75). Aspects of external validity were assessed by investigation of correlations with the ANPS, psychiatric symptoms (Brief Symptom Inventory-18), attachment security (Adult Attachment Scales) and personality functioning (Operationalized Psychodynamic Diagnostics Structure Questionnaire). To evaluate structural validity, both L-scales were investigated via confirmatory factor analysis (CFA).

Results

Cronbach’s α indicated excellent internal consistency regarding L-12 (α = 0.90), while L-5 showed acceptable reliability (α = 0.82). CFA of a bifactor model of the L-12 indicated excellent model fit. Moreover, an excellent model fit was observed regarding a single factor model of L-5. For both scales small to moderate positive correlations were observed with SEEKING, PLAY, and secure attachment, while they exhibited small to moderate negative correlations with SADNESS, insecure attachment, lower personality functioning, and increased psychiatric symptom load.

Conclusion

Both newly developed scales exhibit satisfying psychometric properties, indicating high reliability, good structural validity and plausible correlations with external criteria. Hence, this study poses an important step toward the operationalization of the LUST concept. However, more research is needed in particular with respect to the scale’s external validity and its applicability in clinical populations.
The Mental Maxwell Relations: A Thermodynamic Allegory for Higher Brain Functions
Authors: O’Neill Joseph , Schoth Andreas
Published: February 2022

The theoretical framework of classical thermodynamics unifies vastly diverse natural phenomena and captures once-elusive effects in concrete terms. Neuroscience confronts equally varied, equally ineffable phenomena in the mental realm, but has yet to unite or to apprehend them rigorously, perhaps due to an insufficient theoretical framework. The terms for mental phenomena, the mental variables, typically used in neuroscience are overly numerous and imprecise. Unlike in thermodynamics or other branches of physics, in neuroscience, there are no core mental variables from which all others formally derive and it is unclear which variables are distinct and which overlap. This may be due to the nature of mental variables themselves. Unlike the variables of physics, perhaps they cannot be interpreted as composites of a small number of axioms. However, it is well worth exploring if they can, as that would allow more parsimonious theories of higher brain function. Here we offer a theoretical exercise in the spirit of the National Institutes of Health Research Domain Criteria (NIH RDoC) Initiative and the Cognitive Atlas Project, which aim to remedy this state of affairs. Imitating classical thermodynamics, we construct a formal framework for mental variables, an extended analogy – an allegory – between mental and thermodynamic quantities. Starting with mental correlates of the physical indefinables length, time, mass or force, and charge, we pursue the allegory up to mental versions of the thermodynamic Maxwell Relations. The Maxwell Relations interrelate the thermodynamic quantitiesvolume,pressure,temperature, andentropyand were chosen since they are easy to derive, yet capable of generating nontrivial, nonobvious predictions. Our “Mental Maxwell Relations” interlink the mental variables consciousness, salience, arousal, and distraction and make nontrivial, nonobvious statements about mental phenomena. The mental system thus constructed is internally consistent, in harmony with introspection, and respects the RDoC criteria of employing only psychologically valid constructs with some evidence of a brain basis. We briefly apply these concepts to the problem of decision-making and sketch how some of them might be tested empirically.