bluuebunny/crossref_metadata_2025 huggingface dataset:
Balancing Selection of the Intracellular Pathogen Response in Natural Caenorhabditis elegans Populations
Authors: van Sluijs Lisa , Bosman Kobus J. , Pankok Frederik , Blokhina Tatiana , Wilten Jop I. H. A. , te Molder Dennie M. , Riksen Joost A. G. , Snoek Basten L. , Pijlman Gorben P. , Kammenga Jan E. , Sterken Mark G.
Published: January 2022

Genetic variation in host populations may lead to differential viral susceptibilities. Here, we investigate the role of natural genetic variation in the Intracellular Pathogen Response (IPR), an important antiviral pathway in the model organism Caenorhabditis elegans against Orsay virus (OrV). The IPR involves transcriptional activity of 80 genes including the pals-genes. We examine the genetic variation in the pals-family for traces of selection and explore the molecular and phenotypic effects of having distinct pals-gene alleles. Genetic analysis of 330 global C. elegans strains reveals that genetic diversity within the IPR-related pals-genes can be categorized in a few haplotypes worldwide. Importantly, two key IPR regulators, pals-22 and pals-25, are in a genomic region carrying signatures of balancing selection, suggesting that different evolutionary strategies exist in IPR regulation. We infected eleven C. elegans strains that represent three distinct pals-22 pals-25 haplotypes with Orsay virus to determine their susceptibility. For two of these strains, N2 and CB4856, the transcriptional response to infection was also measured. The results indicate that pals-22 pals-25 haplotype shapes the defense against OrV and host genetic variation can result in constitutive activation of IPR genes. Our work presents evidence for balancing genetic selection of immunity genes in C. elegans and provides a novel perspective on the functional diversity that can develop within a main antiviral response in natural host populations.
TNFα Blockade Inhibits Both Initial and Continued Control of Pulmonary Coccidioides
Authors: Powell Daniel A. , Shubitz Lisa F. , Butkiewicz Christine D. , Trinh Hien T. , Donovan Fariba M. , Frelinger Jeffrey A. , Galgiani John N.
Published: January 2022

Tumor necrosis factor alpha (TNFα) is a pluripotent cytokine that is important in many infections, though its role in Coccidioides infection remains poorly understood. The need to understand TNFα in Coccidioides infection has increased recently with the widespread use of TNFα inhibitors for a wide variety of autoimmune conditions. Here, we couple the newly developed Coccidioides infection model using strain Cp1038 and C57BL/6 × DBA/2J F1 (B6D2F1) mice. B6D2F1 mice develop long-lasting control of Cp1038. Treatment of B6D2F1 mice with anti-TNFα antibodies permits significant fungal proliferation and death. Additionally, we show that antibody treatment limited to the first 2 weeks of infection was sufficient to induce this same loss of fungal control. Importantly, anti-TNFα antibody treatment initiated after fungal control leads to a loss of host control. These results highlight the importance of TNFα in both the initial control of murine Coccidioides and ongoing suppression of the fungal disease.
Effects of Antibiotic Use on Saliva Antibody Content and Oral Microbiota in Sprague Dawley Rats
Authors: Cheng Xi , He Fuming , Si Misi , Sun Ping , Chen Qianming
Published: January 2022

Antibiotics are often used to treat systemic diseases not associated with the oral cavity. This application of antibiotics may affect the healthy oral microbiota community, as it destroys the balance between specific bacterial populations throughout the ecosystem and may lead to dysbacteriosis. We hypothesized that the effects on antibiotics on oral microbiota regulation and function would affect antibody content in saliva, depending on the antibiotic type. To address this, a total of 24 Sprague Dawley rats (divided into 4 cages, 6 per pen) were administered amoxicillin (AMX), spiramycin (SP), metronidazole (MTZ), or water (control) daily for 14 days (gavage). After treatment was completed, high-throughput sequencing of 16S rRNA genes was used to determine changes in the composition, metabolic function, and diversity of oral microbiota in the rats. Enzyme-linked immunosorbent assay was used to detect antibodies in saliva, including SIgA, IgG, and IgM. Results showed that AMX, MTZ, and SP significantly affected oral microbiota composition, diversity, and metabolic function in rats. AMX induced substantial changes in the rat salivary antibody concentrations. At the genus level, the relative abundance of Rothia and Haemophilus was higher in the AMX group than in the other groups. In conclusion, antibiotics-induced changes in oral microbiota populations may be associated with changes in salivary antibody concentrations. However, the specific interaction mechanisms remain unknown, and it is still unclear whether significant changes in the oral microbiota cause changes in salivary antibody concentrations or vice versa.
Identification of a Schistosoma japonicum MicroRNA That Suppresses Hepatoma Cell Growth and Migration by Targeting Host FZD4 Gene
Authors: Jiang Pengyue , Wang Jing , Zhu Shanli , Hu Chao , Lin Yu , Pan Weiqing
Published: January 2022

Previous studies have demonstrated miRNAs derived from plants and parasites can modulate mammalian gene expression and cell phenotype in a cross-kingdom manner, leading to occurrence of diseases or strengthening resistance of host to diseases such as cancer. In this study, we identified a schistosome miRNA (named Sja-miR-71a) through screening of 57 Schistosoma japonicum miRNAs that exerts antitumor activity in vitro and in vivo models. We demonstrated presence of this parasite miRNA in liver cells during infection. We showed that Sja-miR-71a arrested cell cycle at G0/G1 phase of hepatoma cell lines and inhibited cell proliferation in vitro. The HepG2 transfected with Sja-miR-71a mimics displayed significant reduction of migration and colony formation. Further, growth of the tumor cells transfected with the Sja-miR-71a mimics was obviously suppressed in a xenograft mouse model. Mechanically, we found the antitumor activity of Sja-miR-71a was through targeting a host gene encoding Frizzled Class Receptor 4 (FZD4), as FZD4 small interfering RNAs (siRNAs) generated a similar inhibitory effect on the tumor. These data indicated that Sja-miR-71a is a tumor suppressor miRNA and suggested this parasite-derived miRNA as a potential therapeutic target for cancer.
Optimal Dispatch and Control Strategy of Integrated Energy System Considering Multiple P2H to Provide Integrated Demand Response
Authors: Huang Xin , Wang Kai , Zhao Mintong , Huan Jiajia , Yu Yundong , Jiang Kai , Yan Xiaohe , Liu Nian
Published: January 2022

With the increase in multi-energy loads and renewable energy (RE) penetration, the valley-to-peak value of the electric-heat system is gradually increasing. Although the integrated energy system (IES) and power-to-hydrogen (P2H) technology are widely used to improve energy efficiency and promote the consumption of REs, the dispatch strategies for the IES with P2H to provide integrated demand response (IDR) are not investigated clearly. Thus, this paper presents an optimal dispatch strategy for the IES to provide IDR with multiple P2H technologies. Firstly, a unified mathematical model is built for describing multiple P2H technologies with joint consideration of start/shutdown and ramping constraints. Then, a bi-level P2H-coupled IDR dispatch model is built where the upper level is the IES model including P2H and hydrogen storages with consideration of electric/gas/thermal multi-energy coupling, and the lower level is a flexible user model including transferrable and reduced loads. The Karush–Kuhn–Tucker (KKT) condition and big M methods are used to reformulate the lower-level user model into several complementary relaxation constraints. Then, the whole model is transferred into a solvable single level and linearized model. Finally, the case study shows that the proposed method can improve system flexibility and effectively reduce load peak-to-valley difference. Besides, the addition of P2H and HS into the IES can further optimize the whole economic profits, energy efficiency, and ability to consume REs.
The Influence of CO2 Saturated Brine on Microstructure of Coal: Implications for Carbon Geo-Sequestration
Authors: Li Xiaolong , Yu Hongyan , Lebedev Maxim , Lu Minghui , Yuan Yujie , Yang Zhen , Cheng Wei , Chen Sisi , Zhan Jie , Ding Shuaiwei , Johnson Lukman
Published: January 2022

Carbon dioxide geological storage in deep underground oil and gas reservoirs or coal seam is considered a key technology to effectively mitigate carbon emissions. Deep coal seams are the potential host rock for CO2 storage, with chemical reactions occurring when coal is exposed to CO2-saturated brine. However, limited studies have been conducted to reveal the effect of chemical reaction, particularly to unveil how this importantly affects the coal seam porosity at the micrometer scale. In this study, the CO2 geological storage is simulated using a high-temperature and high-pressure reactor containing CO2-saturated brine and coal samples. The samples in the previous study on the effect of CO2 on coal mostly contained high content of carbonate minerals and sulfide minerals. However, the tested Collie coal samples, which are characterized by high content of kaolinite and siderite, are rarely used. This coal was quantitatively analyzed using a scanning electron microscope before and after reaction. The results show that the microstructure of coal matrix was largely changed due to acid exposure. Kaolinite and siderite in the coal matrix were dissolved, the size and morphology of the cleats increased, and the absolute effective porosity also increased significantly. Most importantly, the connectivity of cleat network was improved, leading to an increase in CO2 storage space and coal seam permeability. Therefore, it is concluded that the microstructure changes of coal can be measured on a microscopic scale, and it is better to be quantitatively evaluated to improve the accuracy and reliability of CO2 storage in deep coal seams.
Climate Extreme and Agriculture Development: Fresh Insight From Top Agri-Economics
Authors: lisha liu , Maneengam Apichit , Chupradit Supat , Albasher Gadah , Alamri Ohoud , Alsultan Nouf Ahmed , Dar Afzal Ahmed
Published: January 2022

A range of studies have been observed, covering the title of climate change and its linkage with the agriculture sector. This would justify the claim that changing environment has its several outcomes for which the agriculture sector cannot be ignored. The purpose of this study is to investigate the impact of various climate change dynamics and modelling on the four indicators of agriculture sector. Overall, five panel economies were selected having highest level of agriculture output in the world economy. The time duration of the study was during 1990–2018 with yearly data as collected from world development indicator or WDI. The study analysis was conducted while applying four panel regression models like ordinary least square, fixed effect estimator, least square dummy variable, and finally the random effect. For better understanding, study findings are empirically explained. The results confirm that both positive and negative impact of various proxies of climate change on agriculture dimension of selected economies. More specifically, it is observed that higher climate change in the form of carbon emission from different sources are causing a downturn effect on the agriculture export while at the same time, they are causing an up-ward shift in the agriculture import of selected economies. Besides, study has reasonably disrobed various policy implications both in theoretical and practical perspective. However, some limitations are also under observation. Firstly, this study considers the limited number of explanatory variables for reflecting the changing climate trends among top five agriculture economies of the world. However, there are still range of other factors which can be observed in the future studies to examine their influence on the selected indicators of agriculture industry. Secondly, this study has applied traditional panel models where no implication is observed for the dynamic panel methods like Generalized methods of Moments or GMM. Thirdly, this study has not provided any evidence for the cross-country analysis. Fourthly, this study has limited time span along with missing examination of both short run and long as well. Future studies may address these limitations for better implication in both theoretical and practical perspective.
Pressures on Boreal Riparian Vegetation: A Literature Review
Authors: Hoppenreijs Jacqueline H. T. , Eckstein R. Lutz , Lind Lovisa
Published: January 2022

Riparian zones are species-rich and functionally important ecotones that sustain physical, chemical and ecological balance of ecosystems. While scientific, governmental and public attention for riparian zones has increased over the past decades, knowledge on the effects of the majority of anthropogenic disturbances is still lacking. Given the increasing expansion and intensity of these disturbances, the need to understand simultaneously occurring pressures grows. We have conducted a literature review on the potential effects of anthropogenic pressures on boreal riparian zones and the main processes that shape their vegetation composition. We visualised the observed and potential consequences of flow regulation for hydropower generation, flow regulation through channelisation, the climate crisis, forestry, land use change and non-native species in a conceptual model. The model shows how these pressures change different aspects of the flow regime and plant habitats, and we describe how these changes affect the extent of the riparian zone and dispersal, germination, growth and competition of plants. Main consequences of the pressures we studied are the decrease of the extent of the riparian zone and a poorer state of the area that remains. This already results in a loss of riparian plant species and riparian functionality, and thus also threatens aquatic systems and the organisms that depend on them. We also found that the impact of a pressure does not linearly reflect its degree of ubiquity and the scale on which it operates. Hydropower and the climate crisis stand out as major threats to boreal riparian zones and will continue to be so if no appropriate measures are taken. Other pressures, such as forestry and different types of land uses, can have severe effects but have more local and regional consequences. Many pressures, such as non-native species and the climate crisis, interact with each other and can limit or, more often, amplify each other’s effects. However, we found that there are very few studies that describe the effects of simultaneously occurring and, thus, potentially interacting pressures. While our model shows where they may interact, the extent of the interactions thus remains largely unknown.
Downregulation of MARC2 Promotes Immune Escape and Is Associated With Immunosuppression of Hepatocellular Carcinoma
Authors: Wu Dehai , Liang Shuhang , Guo Hongrui , Zhang Shugeng , Yang Guangchao , Yuan Yubin , Liu Lianxin
Published: January 2022

The N-reductive enzyme system (NRES), composed of MARC1, MARC2, CYB5, and CYB5R, is responsible for the reduction of N-oxygenated compounds and participates in several physiological processes. For example, MARC2 serves as an important prognostic indicator and is downregulated in hepatocellular carcinoma, and the downregulation of MARC2 is critical to the regulation of lipid metabolism and cell cycle progression. However, the role of MARC2 in tumor immune microenvironment modification had not previously been investigated. In this study, we found that downregulation of MARC2 was associated with the differentiation of CD4+T cells into regulatory T cells (Tregs). Furthermore, restoring the expression of MARC2 could increase the expression of HLA-C and B2M via PPARA-related lipid metabolism signaling pathways, which could facilitate tumor antigen presentation to the tumor-infiltrating T cells. Additionally, MARC2 expression negatively correlated with several immune checkpoints. The immune checkpoint burden was generated based on 28 MARC2-related immune checkpoints. Patients with a higher immune checkpoint burden were predicted to have a poorer prognosis and a lower level of activated CD8+ T cells. The results showed that expression of the NRES is a prognostic indicator of hepatocellular carcinoma and MARC2 contributes significantly to predict the prognosis. Finally, loss of MARC2 in HCC patients was found to facilitate immune escape and was associated with immunosuppression.
Prognostic Biomarker DDOST and Its Correlation With Immune Infiltrates in Hepatocellular Carcinoma
Authors: Zhu Changyu , Xiao Hua , Jiang Xiaolei , Tong Rongsheng , Guan Jianmei
Published: January 2022

Background: Dolichyl-diphosphooligosaccharide–protein glycosyltransferase non-catalytic subunit (DDOST) is an important enzyme in the process of high-mannose oligosaccharide transferring in cells. Increasing DDOST expression is associated with impairing liver function and the increase of hepatic fibrosis degrees, hence exacerbating the liver injury. However, the relation between DDOST and hepatocellular carcinoma (HCC) has not been revealed yet.

Method: In this study, we evaluated the prognostic value of DDOST in HCC based on data from The Cancer Genome Atlas (TCGA) database. The relationship between DDOST expression and clinical-pathologic features was evaluated by logistic regression, the Wilcoxon signed-rank test, and Kruskal–Wallis test. Prognosis-related factors of HCC including DDOST were evaluated by univariate and multivariate Cox regression and the Kaplan–Meier method. DDOST-related key pathways were identified by gene set enrichment analysis (GSEA). The correlations between DDOST and cancer immune infiltrates were investigated by the single-sample gene set enrichment analysis (ssGSEA) of TCGA data.

Results: High DDOST expression was associated with poorer overall survival and disease-specific survival of HCC patients. GSEA suggested that DDOST is closely correlated with cell cycle and immune response via the PPAR signaling pathway. ssGSEA indicated that DDOST expression was positively correlated with the infiltrating levels of Th2 cells and negatively correlated with the infiltration levels of cytotoxic cells.

Conclusion: All those findings indicated that DDOST was correlated with prognosis and immune infiltration in HCC.
Immediate-Early, Early, and Late Responses to DNA Double Stranded Breaks
Authors: Kieffer Shaylee R. , Lowndes Noel F.
Published: January 2022

Loss or rearrangement of genetic information can result from incorrect responses to DNA double strand breaks (DSBs). The cellular responses to DSBs encompass a range of highly coordinated events designed to detect and respond appropriately to the damage, thereby preserving genomic integrity. In analogy with events occurring during viral infection, we appropriate the terms Immediate-Early, Early, and Late to describe the pre-repair responses to DSBs. A distinguishing feature of the Immediate-Early response is that the large protein condensates that form during the Early and Late response and are resolved upon repair, termed foci, are not visible. The Immediate-Early response encompasses initial lesion sensing, involving poly (ADP-ribose) polymerases (PARPs), KU70/80, and MRN, as well as rapid repair by so-called ‘fast-kinetic’ canonical non-homologous end joining (cNHEJ). Initial binding of PARPs and the KU70/80 complex to breaks appears to be mutually exclusive at easily ligatable DSBs that are repaired efficiently by fast-kinetic cNHEJ; a process that is PARP-, ATM-, 53BP1-, Artemis-, and resection-independent. However, at more complex breaks requiring processing, the Immediate-Early response involving PARPs and the ensuing highly dynamic PARylation (polyADP ribosylation) of many substrates may aid recruitment of both KU70/80 and MRN to DSBs. Complex DSBs rely upon the Early response, largely defined by ATM-dependent focal recruitment of many signalling molecules into large condensates, and regulated by complex chromatin dynamics. Finally, the Late response integrates information from cell cycle phase, chromatin context, and type of DSB to determine appropriate pathway choice. Critical to pathway choice is the recruitment of p53 binding protein 1 (53BP1) and breast cancer associated 1 (BRCA1). However, additional factors recruited throughout the DSB response also impact upon pathway choice, although these remain to be fully characterised. The Late response somehow channels DSBs into the appropriate high-fidelity repair pathway, typically either ‘slow-kinetic’ cNHEJ or homologous recombination (HR). Loss of specific components of the DSB repair machinery results in cells utilising remaining factors to effect repair, but often at the cost of increased mutagenesis. Here we discuss the complex regulation of the Immediate-Early, Early, and Late responses to DSBs proceeding repair itself.
Gelsolin Attenuates Neonatal Hyperoxia-Induced Inflammatory Responses to Rhinovirus Infection and Preserves Alveolarization
Authors: Cui Tracy X. , Brady Alexander E. , Zhang Ying-Jian , Fulton Christina T. , Popova Antonia P.
Published: January 2022

Prematurity and bronchopulmonary dysplasia (BPD) increase the risk of asthma later in life. Supplemental oxygen therapy is a risk factor for chronic respiratory symptoms in infants with BPD. Hyperoxia induces cell injury and release of damage-associated molecular patterns (DAMPs). Cytoskeletal filamentous actin (F-actin) is a DAMP which binds Clec9a, a C-type lectin selectively expressed on CD103+ dendritic cells (DCs). Co-stimulation of Clec9a and TLR3 induces maximal proinflammatory responses. We have shown that neonatal hyperoxia (a model of BPD) increases lung IL-12+Clec9a+CD103+ DCs, pro-inflammatory responses and airway hyperreactivity following rhinovirus (RV) infection. CD103+ DCs and Clec9a are required for these responses. Hyperoxia increases F-actin levels in bronchoalveolar lavage fluid (BALF). We hypothesized that the F-actin severing protein gelsolin attenuates neonatal hyperoxia-induced Clec9a+CD103+ DC-dependent pro-inflammatory responses to RV and preserves alveolarization. We exposed neonatal mice to hyperoxia and treated them with gelsolin intranasally. Subsequently we inoculated the mice with RV intranasally. Alternatively, we inoculated normoxic neonatal mice with BALF from hyperoxia-exposed mice (hyperoxic BALF), RV and gelsolin. We analyzed lung gene expression two days after RV infection. For in vitro studies, lung CD11c+ cells were isolated from C57BL/6J or Clec9agfp-/- mice and incubated with hyperoxic BALF and RV. Cells were analyzed by flow cytometry. In neonatal mice, gelsolin blocked hyperoxia-induced Il12p40, TNF-α and IFN-γ mRNA and protein expression in response to RV infection. Similar effects were observed when gelsolin was co-administered with hyperoxic BALF and RV. Gelsolin decreased F-actin levels in hyperoxic BALF in vitro and inhibited hyperoxia-induced D103lo DC expansion and inflammation in vivo. Gelsolin also attenuated hyperoxia-induced hypoalveolarization. Further, incubation of lung CD11c+ cells from WT and Clec9agfp-/- mice with hyperoxic BALF and RV, showed Clec9a is required for maximal hyperoxic BALF and RV induced IL-12 expression in CD103+ DCs. Finally, in tracheal aspirates from mechanically ventilated human preterm infants the F-actin to gelsolin ratio positively correlates with FiO2, and gelsolin levels decrease during the first two weeks of mechanical ventilation. Collectively, our findings demonstrate a promising role for gelsolin, administered by inhalation into the airway to treat RV-induced exacerbations of BPD and prevent chronic lung disease.
Altered Frequencies and Functions of Innate Lymphoid Cells in Melanoma Patients Are Modulated by Immune Checkpoints Inhibitors
Authors: Cristiani Costanza Maria , Capone Mariaelena , Garofalo Cinzia , Madonna Gabriele , Mallardo Domenico , Tuffanelli Marilena , Vanella Vito , Greco Marta , Foti Daniela Patrizia , Viglietto Giuseppe , Ascierto Paolo Antonio , Spits Hergen , Carbone Ennio
Published: January 2022

Monoclonal antibodies targeting immune checkpoints improved clinical outcome of patients with malignant melanoma. However, the mechanisms are not fully elucidated. Since immune check-point receptors are also expressed by helper innate lymphoid cells (ILCs), we investigated the capability of immune checkpoints inhibitors to modulate ILCs in metastatic melanoma patients as well as melanoma cells effects on ILC functions. Here, we demonstrated that, compared to healthy donors, patients showed a higher frequency of total peripheral ILCs, lower percentages of CD117+ ILC2s and CD117+ ILCs as well as higher frequencies of CD117- ILCs. Functionally, melanoma patients also displayed an impaired TNFα secretion by CD117- ILCs and CD117+ ILCs. Nivolumab therapy reduced the frequency of total peripheral ILCs but increased the percentage of CD117- ILC2s and enhanced the capability of ILC2s and CD117+ ILCs to secrete IL-13 and TNFα, respectively. Before Nivolumab therapy, high CCL2 serum levels were associated with longer Overall Survival and Progression Free Survival. After two months of treatment, CD117- ILC2s frequency as well as serum concentrations of IL-6, CXCL8 and VEGF negatively correlated with both the parameters. Moreover, melanoma cells boosted TNFα production in all ILC subsets and increased the number of IL-13 producing ILC2s in vitro. Our work shows for the first time that PD-1 blockade is able to affect ILCs proportions and functions in melanoma patients and that a specific subpopulation is associated with the therapy response.
Inactivated Rabies Virus Vectored MERS-Coronavirus Vaccine Induces Protective Immunity in Mice, Camels, and Alpacas
Authors: Chi Hang , Wang Yanqun , Li Entao , Wang Xiwen , Wang Hualei , Jin Hongli , Han Qiuxue , Wang Zhenshan , Wang Xinyue , Zhu Airu , Sun Jing , Zhuang Zhen , Zhang Lu , Ye Jingmeiqi , Wang Haijun , Feng Na , Hu Mingda , Gao Yuwei , Zhao Jincun , Zhao Yongkun , Yang Songtao , Xia Xianzhu
Published: January 2022

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emergent coronavirus that has caused frequent zoonotic events through camel-to-human spillover. An effective camelid vaccination strategy is probably the best way to reduce human exposure risk. Here, we constructed and evaluated an inactivated rabies virus-vectored MERS-CoV vaccine in mice, camels, and alpacas. Potent antigen-specific antibody and CD8+ T-cell responses were generated in mice; moreover, the vaccination reduced viral replication and accelerated virus clearance in MERS-CoV-infected mice. Besides, protective antibody responses against both MERS-CoV and rabies virus were induced in camels and alpacas. Satisfyingly, the immune sera showed broad cross-neutralizing activity against the three main MERS-CoV clades. For further characterization of the antibody response induced in camelids, MERS-CoV-specific variable domains of heavy-chain-only antibody (VHHs) were isolated from immunized alpacas and showed potent prophylactic and therapeutic efficacies in the Ad5-hDPP4-transduced mouse model. These results highlight the inactivated rabies virus-vectored MERS-CoV vaccine as a promising camelid candidate vaccine.
Density-Dependent Prophylaxis in Freshwater Snails Driven by Oxylipin Chemical Cues
Authors: Friesen Olwyn C. , Li Chen-Hua , Sykes Ellen M. E. , Stout Jake M. , Aukema Harold M. , Kumar Ayush , Detwiler Jillian T.
Published: January 2022

While animal aggregations can benefit the fitness of group members, the behaviour may also lead to higher risks of parasite infection as group density increases. Some animals are known to moderate their investment in immunity relative to the risk of infection. These animals exhibit density-dependent prophylaxis (DDP) by increasing their immune investment as group density increases. Despite being documented in many taxa, the mechanisms of DDP remain largely unexplored. Snails are known to aggregate and experience large fluctuations in density and serve as required hosts for many parasites. Further, they are known to use chemical cues to aggregate. To test whether freshwater snails exhibit DDP and investigate the role that chemical signaling compounds may play in triggering this phenomenon, we performed four experiments on the freshwater snail Stagnicola elodes, which is a common host for many trematode parasite species. First, we tested if DDP occurred in snails in laboratory-controlled conditions (control vs snail-conditioned water) and whether differences in exposure to chemical cues affected immune function. Second, we used gas chromatography to characterize fatty acids expressed in snail-conditioned water to determine if precursors for particular signaling molecules, such as oxylipins, were being produced by snails. Third, we characterized the oxylipins released by infected and uninfected field-collected snails, to better understand how differences in oxylipin cocktails may play a role in inducing DDP. Finally, we tested the immune response of snails exposed to four oxylipins to test the ability of specific oxylipins to affect DDP. We found that snails exposed to water with higher densities of snails and raised in snail-conditioned water had higher counts of haemocytes. Additionally, lipid analysis demonstrated that fatty acid molecules that are also precursors for oxylipins were present in snail-conditioned water. Trematode-infected snails emitted 50 oxylipins in higher amounts, with 24 of these oxylipins only detected in this group. Finally, oxylipins that were higher in infected snails induced naïve snails to increase their immune responses compared to sham-exposed snails. Our results provide evidence that snails exhibit DDP, and the changes in oxylipins emitted by infected hosts may be one of the molecular mechanisms driving this phenomenon.
Interleukins and Ischemic Stroke
Authors: Zhu Hua , Hu Siping , Li Yuntao , Sun Yao , Xiong Xiaoxing , Hu Xinyao , Chen Junjing , Qiu Sheng
Published: January 2022

Ischemic stroke after cerebral artery occlusion is one of the major causes of chronic disability worldwide. Interleukins (ILs) play a bidirectional role in ischemic stroke through information transmission, activation and regulation of immune cells, mediating the activation, multiplication and differentiation of T and B cells and in the inflammatory reaction. Crosstalk between different ILs in different immune cells also impact the outcome of ischemic stroke. This overview is aimed to roughly discuss the multiple roles of ILs after ischemic stroke. The roles of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-16, IL-17, IL-18, IL-19, IL-21, IL-22, IL-23, IL-32, IL-33, IL-34, IL-37, and IL-38 in ischemic stroke were discussed in this review.
Based on Genetic Algorithm to Analyze the Anti-Penetration Properties and Optimize the Structure of Ti-Al3Ti-Al Laminated Composites
Authors: Li Yaoming , Zhang Huang , Yuan Meini
Published: January 2022

A coupled finite-element genetic algorithm technique was used to optimize the arrangement order and layer thickness ratios of Ti-Al3Ti-Al laminated composites. Moreover, the damage evolution, energy conversion, and stress distribution of TC4-Al3Ti-Al laminated composites under impact were analyzed. The results showed that TC4-Al3Ti-Al laminated composites with a layer thickness ratio of 3:14:4 have optimum anti-penetration properties; the projectile kinetic energy is mainly converted into the internal energy of the bullet target system; during the penetration process of TC4-Al3Ti-Al targets, the TC4 layer is shear failure, the Al layer is a petal-like failure, the failure mode of Al3Ti layer is fragmentation; with the number of layer increases, the anti-penetration properties of TC4-Al3Ti-Al targets are gradually increasing. However, when the number of layers is more than 30 layers, the number of layers has little effect on the anti-penetration performance of these composites.
F0F1-ATPase Contributes to the Fluoride Tolerance and Cariogenicity of Streptococcus mutans
Authors: Li Cheng , Qi Cai , Yang Sirui , Li Zhengyi , Ren Biao , Li Jiyao , Zhou Xuedong , Cai Huawei , Xu Xin , Peng Xian
Published: January 2022

The phenotypic traits of Streptococcus mutans, such as fluoride tolerance, are usually associated with genotypic alterations. The aim of this study was to identify adaptive mutations of S. mutans to gradient fluoride concentrations and possible relationships between the mutations and fluoride tolerance. We identified a highly resistant S. mutans strain (FR1000) with a novel single nucleotide polymorphism (SNP, −36G→T) in the promoter region of F0F1-ATPase gene cluster (SMU_1527-SMU_1534) resistant to 1,000 ppm fluoride using the whole-genome Illumina PE250 sequencing. Thus, a −36G→T F0F1-ATPase promoter mutation from the parental strain S. mutans UA159 was constructed and named UA159-T. qRT-PCR showed that the F0F1-ATPase gene expression of both FR1000 and UA159-T was up-regulated, and fluoride tolerance of UA159-T was significantly improved. Complementation of Dicyclohexylcarbodiimide (DCCD), a specific inhibitor of F0F1-ATPase, increased fluoride susceptibility of FR1000 and UA159-T. Intracellular fluoride concentrations of fluoride tolerance strains were higher compared to UA159 strain as demonstrated by 18F analysis. Further validation with rat caries models showed that UA159-T caused more severe caries lesions under fluoride exposure compared with its parental UA159 strain. Overall, the identified −36G→T mutation in the promoter region of F0F1-ATPase gene drastically contributed to the fluoride tolerance and enhanced cariogenicity of S. mutans. These findings provided new insights into the mechanism of microbial fluoride tolerance, and suggested F0F1-ATPase as a potential target for suppressing fluoride resistant strains.
Promiscuity in Lichens Follows Clear Rules: Partner Switching in Cladonia Is Regulated by Climatic Factors and Soil Chemistry
Authors: Škvorová Zuzana , Černajová Ivana , Steinová Jana , Peksa Ondřej , Moya Patricia , Škaloud Pavel
Published: January 2022

Climatic factors, soil chemistry and geography are considered as major factors affecting lichen distribution and diversity. To determine how these factors limit or support the associations between the symbiotic partners, we revise the lichen symbiosis as a network of relationships here. More than one thousand thalli of terricolousCladonialichens were collected at sites with a wide range of soil chemical properties from seven biogeographical regions of Europe. A total of 18 OTUs of the algal genusAsterochlorisand 181 OTUs ofCladoniamycobiont were identified. We displayed all realized pairwise mycobiont–photobiont relationships and performed modularity analysis. It revealed four virtually separated modules of cooperating OTUs. The modules differed in mean annual temperature, isothermality, precipitation, evapotranspiration, soil pH, nitrogen, and carbon contents. Photobiont switching was strictly limited to algae from one module, i.e., algae of similar ecological preferences, and only few mycobionts were able to cooperate with photobionts from different modules. Thus,Cladoniamycobionts generally cannot widen their ecological niches through photobiont switching. The modules also differed in the functional traits of the mycobionts, e.g., sexual reproduction rate, presence of soredia, and thallus type. These traits may represent adaptations to the environmental conditions that drive the differentiation of the modules. In conclusion, the promiscuity inCladoniamycobionts is strictly limited by climatic factors and soil chemistry.
The Resistance Mechanism Governs Physiological Adaptation of Escherichia coli to Growth With Sublethal Concentrations of Carbapenem
Authors: Schäfer Franca , Görner Pia , Woltemate Sabrina , Brandenberger Christina , Geffers Robert , Ziesing Stefan , Schlüter Dirk , Vital Marius
Published: January 2022

Factors governing resistance in carbapenem-resistant Enterobacteriaceae are manifold. Despite ample research efforts, underlying molecular mechanisms are still only partly understood. Furthermore, little is known on (eco)physiological consequences from resistance acquisition originating from distinct mechanisms in respective bacteria.

In this study, we examined physiological adaptation of Escherichia coli clinical isolates exhibiting two distinct resistance mechanisms–either carrying a carbapenemase (n = 4, CARB) or alterations in porin-encoding genes (n = 6, POR)–during growth with sublethal concentrations of ertapenem in chemostat culture. Basic growth parameters based on optical density and flow-cytometric analyses as well as global gene expression patterns using RNA-Seq were recorded. We demonstrate that strategies to deal with the antibiotic were distinct between strains of the two groups, where (increased) expression of carbapenemases was the major response in CARB, whereas wide-spread alterations in gene-expression that promoted a survival-like phenotype was observed in POR. The response in POR was accompanied with “costs of resistance” resulting in reduced growth efficiencies compared with CARB that are intrinsic to that group and were also observed during growth without antibiotic challenge, however, at lower levels. All strains showed similar minimal inhibitory concentrations and did not form phylogenetic groups, indicating that results cannot be attributed to distinct resistance levels or phylogenetic relationships, but are indeed based on the resistance mechanism.
Alterations of the Gut Microbiota in Patients With Severe Chronic Heart Failure
Authors: Sun Weiju , Du Debing , Fu Tongze , Han Ying , Li Peng , Ju Hong
Published: January 2022

Chronic heart failure (CHF) is the final outcome of almost all forms of cardiovascular diseases, remaining the main cause of mortality worldwide. Accumulating evidence is focused on the roles of gut microbial community in cardiovascular disease, but few studies have unveiled the alterations and further directions of gut microbiota in severe CHF patients. Aimed to investigate this deficiency, fecal samples from 29 CHF patients diagnosed with NYHA Class III-IV and 30 healthy controls were collected and then analyzed using bacterial 16S rRNA gene sequencing. As a result, there were many significant differences between the two groups. Firstly, the phylum Firmicutes was found to be remarkably decreased in severe CHF patients, and the phylum Proteobacteria was the second most abundant phyla in severe CHF patients instead of phylum Bacteroides strangely. Secondly, the α diversity indices such as chao1, PD-whole-tree and Shannon indices were significantly decreased in the severe CHF versus the control group, as well as the notable difference in β-diversity between the two groups. Thirdly, our result revealed a remarkable decrease in the abundance of the short-chain fatty acids (SCFA)-producing bacteria including genera Ruminococcaceae UCG-004, Ruminococcaceae UCG-002, Lachnospiraceae FCS020 group, Dialister and the increased abundance of the genera in Enterococcus and Enterococcaceae with an increased production of lactic acid. Finally, the alternation of the gut microbiota was presumably associated with the function including Cell cycle control, cell division, chromosome partitioning, Amino acid transport and metabolism and Carbohydrate transport and metabolism through SCFA pathway. Our findings provide the direction and theoretical knowledge for the regulation of gut flora in the treatment of severe CHF.
Distribution, Diversity and Roles of CRISPR-Cas Systems in Human and Animal Pathogenic Streptococci
Authors: Lemaire Coralie , Le Gallou Brice , Lanotte Philippe , Mereghetti Laurent , Pastuszka Adeline
Published: January 2022

Streptococci form a wide group of bacteria and are involved in both human and animal pathologies. Among pathogenic isolates, differences have been highlighted especially concerning their adaptation and virulence profiles. CRISPR-Cas systems have been identified in bacteria and many streptococci harbor one or more systems, particularly subtypes I-C, II-A, and III-A. Since the demonstration that CRISPR-Cas act as an adaptive immune system in Streptococcus thermophilus, a lactic bacteria, the diversity and role of CRISPR-Cas were extended to many germs and functions were enlarged. Among those, the genome editing tool based on the properties of Cas endonucleases is used worldwide, and the recent attribution of the Nobel Prize illustrates the importance of this tool in the scientific world. Another application is CRISPR loci analysis, which allows to easily characterize isolates in order to understand the interactions of bacteria with their environment and visualize species evolution. In this review, we focused on the distribution, diversity and roles of CRISPR-Cas systems in the main pathogenic streptococci.
Effects of Subcortical Atrophy and Alzheimer’s Pathology on Cognition in Elderly Type 2 Diabetes: The Alzheimer’s Disease Neuroimaging Initiative Study
Authors: Zhang Wen , Lu Jiaming , Qing Zhao , Zhang Xin , Zhao Hui , Bi Yan , Zhang Bing ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2022

Background

Subcortical atrophy and increased cerebral β-amyloid and tau deposition are linked to cognitive decline in type 2 diabetes. However, whether and how subcortical atrophy is related to Alzheimer’s pathology in diabetes remains unclear. This study therefore aimed to investigate subcortical structural alterations induced by diabetes and the relationship between subcortical alteration, Alzheimer’s pathology and cognition.

Methods

Participants were 150 patients with type 2 diabetes and 598 propensity score-matched controls without diabetes from the Alzheimer’s Disease Neuroimaging Initiative. All subjects underwent cognitive assessments, magnetic resonance imaging (MRI), and apolipoprotein E (ApoE) genotyping, with a subset that underwent amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) assays to determine cerebral β-amyloid deposition (n = 337) and CSF p-tau (n = 433). Subcortical structures were clustered into five modules based on Pearson’s correlation coefficients of volumes across all subjects: the ventricular system, the corpus callosum, the limbic system, the diencephalon, and the striatum. Using structural equation modeling (SEM), we investigated the relationships among type 2 diabetes, subcortical structural alterations, and AD pathology.

Results

Compared with the controls, the diabetic patients had significant reductions in the diencephalon and limbic system volumes; moreover, patients with longer disease duration (>6 years) had more severe volume deficit in the diencephalon. SEM suggested that type 2 diabetes, age, and the ApoE ε4 allele (ApoE-ε4) can affect cognition via reduced subcortical structure volumes (total effect: age > ApoE-ε4 > type 2 diabetes). Among them, age and ApoE-ε4 strongly contributed to AD pathology, while type 2 diabetes neither directly nor indirectly affected AD biomarkers.

Conclusion

Our study suggested the subcortical atrophy mediated the association of type 2 diabetes and cognitive decline. Although both type 2 diabetes and AD are correlated with subcortical neurodegeneration, type 2 diabetes have no direct or indirect effect on the cerebral amyloid deposition and CSF p-tau.
The Use of Neuroimaging for Predicting Sumatriptan Treatment Response in Patients With Migraine
Authors: Wu Jr-Wei , Lai Pi-Yi , Chen Yung-Lin , Wang Yen-Feng , Lirng Jiing-Feng , Chen Shu-Ting , Lai Kuan-Lin , Chen Wei-Ta , Wu Yu-Te , Wang Shuu-Jiun
Published: January 2022

Objectives

To identify the neuroimaging predictors for the responsiveness of patients to sumatriptan and use an independent cohort for external validation.

Methods

Structuralized headache questionnaire and 3-Tesla brain magnetic resonance imaging were performed in migraine patients. Regional brain volumes were automatically calculated using FreeSurfer version 6.0, including bilateral amygdala, anterior cingulated cortex, caudate, putamen, precuneus, orbitofrontal cortex, superior frontal gyri, middle frontal gyri, hippocampus, and parahippocampus. A sumatriptan-responder was defined as headache relief within 2 h after the intake of sumatriptan in at least two out of three treated attacks. We constructed a prediction model for sumatriptan response using the regional brain volume and validated it with an independent cohort of migraine patients.

Results

A total of 105 migraine patients were recruited, including 73 sumatriptan responders (69.5%) and 32 (30.5%) non-responders. We divided the migraine patients into derivation (n = 73) and validation cohorts (n = 32). In the derivation cohort, left hippocampal volume was larger in sumatriptan responders (responders vs. non-responders: 3,929.5 ± 403.1 vs. 3,611.0 ± 389.9 mm3, p = 0.002), and patients with a larger left hippocampal volume had a higher response rate to sumatriptan (>4,036.2 vs. ≤4,036.2 mm3: 92.0 vs. 56.3%, p = 0.001). Based on the findings, we constructed a prediction model using the cutoff value of 4,036.2 mm3, and we found that patients with a left hippocampal volume >4,032.6 mm3 had a higher response rate to sumatriptan than those with a left hippocampal volume ≤4,032.6 mm3 (84.6 vs. 42.1%, odds ratio [OR] = 7.6 [95% confidence interval = 1.3–44.0], p = 0.013) in the validation cohort.

Conclusion

Our study showed that left hippocampal volume is helpful to identify sumatriptan non-responders. This proof-of-concept study shows that left hippocampal volume could be used to predict the treatment response to sumatriptan in migraine patients.
Effect of Cognition Recovery by Repetitive Transcranial Magnetic Stimulation on Ipsilesional Dorsolateral Prefrontal Cortex in Subacute Stroke Patients
Authors: Kim Jongwook , Cha Byoungwoo , Lee Doyoung , Kim Jong Moon , Kim MinYoung
Published: January 2022

Objective

To demonstrate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the ipsilesional dorsolateral prefrontal cortex (DLPFC) on neurological recovery in patients with subacute phase stroke.

Methods

Patients with supratentorial hemispheric stroke who were hospitalized for intensive rehabilitation in the subacute phase were enrolled for this retrospective analysis. Two groups of patients were selected: the rTMS group who received high-frequency (20 Hz) rTMS ≥ 5 times over the ipsilesional DLPFC, and a control group who did not receive any rTMS. The patients were further divided into groups with right- or left-side brain lesions. Functional measurements for cognitive ability, mood, speech, and activities of daily living, which were assessed at baseline and at the 1-month follow-up as a routine clinical practice, were used for analyses.

Results

Among 270 patients with available clinical data, 133 (women, 51; age, 61.0 ± 13.8 years) met the inclusion criteria and were enrolled for analysis. There were no differences in demographic data and functional scores at baseline between the rTMS (n = 49) and control (n = 84) groups. The rTMS group showed a higher gain in the mini-mental status examination (MMSE) total score and subscores of all domains, forward digit span, and FIM-cognition than the control group (P < 0.05). Among the patients with left hemispheric lesions (n = 57), the rTMS group showed better outcomes in cognition and depression through scores of total and “attention and concentration” subscores of MMSE, FIM-cognition, and the geriatric depression scale (P < 0.05). Among the patients with right hemispheric lesions (n = 76), the rTMS group showed better outcomes in cognition through the MMSE total score and subscores of “attention and concentration,” “registration,” and “recall,” and scores of both forward and backward digit spans (P < 0.05).

Conclusion

High-frequency rTMS over the ipsilesional DLPFC has beneficial effects on the recovery of cognition on both sides as well as mood in patients with left-sided hemispheric lesions.