bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Pricing Algorithm Based on Reward-Punishment Mechanism for Supply and Demand Balancing
Authors: Chen Xiaofei , Weng Liguo , Zhu Haiyan , Lian Deqiang
Published: June 2021

Demand response (DR) is a powerful tool to maintain the stability of the power system and maximize the profit of the electricity market, where the customers engage in the pricing scheme and adjust their electricity demand proactively based on the price. In DR programs, most existing works are based on the assumption that the prediction of the electricity demand from customers is always accurate and trustworthy, which will lead to high cost and fluctuation of the electricity market once the prediction is obeyed. In this paper, we design a reward and punishment mechanism to constrain customers’ dishonest behaviors and propose a novel pricing algorithm based on the reward and punishment mechanism to relax the assumption, which guarantees the total electricity demands of all customers are within a secure range and obtain the maximum profit of the supplier. Meanwhile, we obtain the optimal demand and provide a upper and lower bound of the proposed price for the electricity market. In addition to a single type of customer, we also consider multiple types of customers, each of whom has different characteristics to prices. Extensive simulation results are constructed to demonstrate the effectiveness of the proposed algorithm compared with other pricing algorithms. It also shows that the average electricity consumption of a whole community is mostly affected by the residents’ electricity consumption and the balance of the supply and all types of customers is achieved under the proposed pricing algorithm.
Genotyping and Whole-Genome Resequencing of Welsh Sheep Breeds Reveal Candidate Genes and Variants for Adaptation to Local Environment and Socioeconomic Traits
Authors: Sweet-Jones James , Lenis Vasileios Panagiotis , Yurchenko Andrey A. , Yudin Nikolay S. , Swain Martin , Larkin Denis M.
Published: June 2021

Background

Advances in genetic tools applied to livestock breeding has prompted research into the previously neglected breeds adapted to harsh local environments. One such group is the Welsh mountain sheep breeds, which can be farmed at altitudes of 300 m above sea level but are considered to have a low productive value because of their poor wool quality and small carcass size. This is contrary to the lowland breeds which are more suited to wool and meat production qualities, but do not fare well on upland pasture. Herein, medium-density genotyping data from 317 individuals representing 15 Welsh sheep breeds were used alongside the whole-genome resequencing data of 14 breeds from the same set to scan for the signatures of selection and candidate genetic variants using haplotype- and SNP-based approaches.

Results

Haplotype-based selection scan performed on the genotyping data pointed to a strong selection in the regions of GBA3, PPARGC1A, APOB, and PPP1R16B genes in the upland breeds, and RNF24, PANK2, and MUC15 in the lowland breeds. SNP-based selection scan performed on the resequencing data pointed to the missense mutations under putative selection relating to a local adaptation in the upland breeds with functions such as angiogenesis (VASH1), anti-oxidation (RWDD1), cell stress (HSPA5), membrane transport (ABCA13 and SLC22A7), and insulin signaling (PTPN1 and GIGFY1). By contrast, genes containing candidate missense mutations in the lowland breeds are related to cell cycle (CDK5RAP2), cell adhesion (CDHR3), and coat color (MC1R).

Conclusion

We found new variants in genes with potentially functional consequences to the adaptation of local sheep to their environments in Wales. Knowledge of these variations is important for improving the adaptative qualities of UK and world sheep breeds through a marker-assisted selection.
lme4GS: An R-Package for Genomic Selection
Authors: Caamal-Pat Diana , Pérez-Rodríguez Paulino , Crossa José , Velasco-Cruz Ciro , Pérez-Elizalde Sergio , Vázquez-Peña Mario
Published: June 2021

Genomic selection (GS) is a technology used for genetic improvement, and it has many advantages over phenotype-based selection. There are several statistical models that adequately approach the statistical challenges in GS, such as in linear mixed models (LMMs). An active area of research is the development of software for fitting LMMs mainly used to make genome-based predictions. The lme4 is the standard package for fitting linear and generalized LMMs in the R-package, but its use for genetic analysis is limited because it does not allow the correlation between individuals or groups of individuals to be defined. This article describes the new lme4GS package for R, which is focused on fitting LMMs with covariance structures defined by the user, bandwidth selection, and genomic prediction. The new package is focused on genomic prediction of the models used in GS and can fit LMMs using different variance–covariance matrices. Several examples of GS models are presented using this package as well as the analysis using real data.
The Inducible lac Operator-Repressor System Is Functional in Zebrafish Cells
Authors: Nishizaki Sierra S. , McDonald Torrin L. , Farnum Gregory A. , Holmes Monica J. , Drexel Melissa L. , Switzenberg Jessica A. , Boyle Alan P.
Published: June 2021

Background

Zebrafish are a foundational model organism for studying the spatio-temporal activity of genes and their regulatory sequences. A variety of approaches are currently available for editing genes and modifying gene expression in zebrafish, including RNAi, Cre/lox, and CRISPR-Cas9. However, the lac operator-repressor system, an E. coli lac operon component which has been adapted for use in many other species and is a valuable, flexible tool for inducible modulation of gene expression studies, has not been previously tested in zebrafish.

Results

Here we demonstrate that the lac operator-repressor system robustly decreases expression of firefly luciferase in cultured zebrafish fibroblast cells. Our work establishes the lac operator-repressor system as a promising tool for the manipulation of gene expression in whole zebrafish.

Conclusion

Our results lay the groundwork for the development of lac-based reporter assays in zebrafish, and adds to the tools available for investigating dynamic gene expression in embryogenesis. We believe this work will catalyze the development of new reporter assay systems to investigate uncharacterized regulatory elements and their cell-type specific activities.
Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment
Authors: Bourgeois Christine , Gorwood Jennifer , Olivo Anaelle , Le Pelletier Laura , Capeau Jacqueline , Lambotte Olivier , Béréziat Véronique , Lagathu Claire
Published: June 2021

White adipose tissue (AT) contributes significantly to inflammation – especially in the context of obesity. Several of AT’s intrinsic features favor its key role in local and systemic inflammation: (i) large distribution throughout the body, (ii) major endocrine activity, and (iii) presence of metabolic and immune cells in close proximity. In obesity, the concomitant pro-inflammatory signals produced by immune cells, adipocytes and adipose stem cells help to drive local inflammation in a vicious circle. Although the secretion of adipokines by AT is a prime contributor to systemic inflammation, the lipotoxicity associated with AT dysfunction might also be involved and could affect distant organs. In HIV-infected patients, the AT is targeted by both HIV infection and antiretroviral therapy (ART). During the primary phase of infection, the virus targets AT directly (by infecting AT CD4 T cells) and indirectly (via viral protein release, inflammatory signals, and gut disruption). The initiation of ART drastically changes the picture: ART reduces viral load, restores (at least partially) the CD4 T cell count, and dampens inflammatory processes on the whole-body level but also within the AT. However, ART induces AT dysfunction and metabolic side effects, which are highly dependent on the individual molecules and the combination used. First generation thymidine reverse transcriptase inhibitors predominantly target mitochondrial DNA and induce oxidative stress and adipocyte death. Protease inhibitors predominantly affect metabolic pathways (affecting adipogenesis and adipocyte homeostasis) resulting in insulin resistance. Recently marketed integrase strand transfer inhibitors induce both adipocyte adipogenesis, hypertrophy and fibrosis. It is challenging to distinguish between the respective effects of viral persistence, persistent immune defects and ART toxicity on the inflammatory profile present in ART-controlled HIV-infected patients. The host metabolic status, the size of the pre-established viral reservoir, the quality of the immune restoration, and the natural ageing with associated comorbidities may mitigate and/or reinforce the contribution of antiretrovirals (ARVs) toxicity to the development of low-grade inflammation in HIV-infected patients. Protecting AT functions appears highly relevant in ART-controlled HIV-infected patients. It requires lifestyle habits improvement in the absence of effective anti-inflammatory treatment. Besides, reducing ART toxicities remains a crucial therapeutic goal.
Response to Oxidative Burst-Induced Hypoxia Is Associated With Macrophage Inflammatory Profiles as Revealed by Cellular Genome-Wide Association
Authors: Emam Mehdi , Tabatabaei Saeid , Sargolzaei Mehdi , Mallard Bonnie
Published: June 2021

Background

In mammalian species, hypoxia is a prominent feature of inflammation. The role of hypoxia in regulating macrophage responses via alteration in metabolic pathways is well established. Recently, oxidative burst-induced hypoxia has been shown in murine macrophages after phagocytosis. Despite the available detailed information on the regulation of macrophage function at transcriptomic and epigenomic levels, the association of genetic polymorphism and macrophage function has been less explored. Previously, we have shown that host genetics controls approximately 80% of the variation in an oxidative burst as measured by nitric oxide (NO-). Further studies revealed two clusters of transcription factors (hypoxia-related and inflammatory-related) are under the genetic control that shapes macrophages’ pro-inflammatory characteristics.

Material and Methods

In the current study, the association between 43,066 autosomal Single Nucleic Polymorphism (SNPs) and the ability of MDMs in production of NO- in response to E. coli was evaluated in 58 Holstein cows. The positional candidate genes near significant SNPs were selected to perform functional analysis. In addition, the interaction between the positional candidate genes and differentially expressed genes from our previous study was investigated.

Results

Sixty SNPs on 22 chromosomes of the bovine genome were found to be significantly associated with NO- production of macrophages. The functional genomic analysis showed a significant interaction between positional candidate genes and mitochondria-related differentially expressed genes from the previous study. Further examination showed 7 SNPs located in the vicinity of genes with roles in response to hypoxia, shaping approximately 73% of the observed individual variation in NO- production by MDM. Regarding the normoxic condition of macrophage culture in this study, it was hypothesized that oxidative burst is responsible for causing hypoxia at the cellular level.

Conclusion

The results suggest that the genetic polymorphism via regulation of response to hypoxia is a candidate step that perhaps shapes macrophage functional characteristics in the pathway of phagocytosis leading to oxidative burst, hypoxia, cellular response to hypoxia and finally the pro-inflammatory responses. Since all cells in one individual carry the same alleles, the effect of genetic predisposition of sensitivity to hypoxia will likely be notable on the clinical outcome to a broad range of host-pathogen interactions.
Evaluation of Alpha-Ketoglutarate Supplementation on the Improvement of Intestinal Antioxidant Capacity and Immune Response in Songpu Mirror Carp (Cyprinus carpio) After Infection With Aeromonas hydrophila
Authors: Wu Di , Fan Ze , Li Jinnan , Zhang Yuanyuan , Wang Chang’an , Xu Qiyou , Wang Liansheng
Published: June 2021

As an intermediate substance of the tricarboxylic acid cycle and a precursor substance of glutamic acid synthesis, the effect of alpha-ketoglutarate on growth and protein synthesis has been extensively studied. However, its prevention and treatment of pathogenic bacteria and its mechanism have not yet been noticed. To evaluate the effects of alpha-ketoglutarate on intestinal antioxidant capacity and immune response of Songpu mirror carp, a total of 360 fish with an average initial weight of 6.54 ± 0.08 g were fed diets containing alpha-ketoglutarate with 1% for 8 weeks. At the end of the feeding trial, the fish were challenged with Aeromonas hydrophila for 2 weeks. The results indicated that alpha-ketoglutarate supplementation significantly increased the survival rate of carp after infection with Aeromonas hydrophila (P < 0.05), and the contents of immune digestion enzymes including lysozyme, alkaline phosphatase and the concentration of complement C4 were markedly enhanced after alpha-ketoglutarate supplementation (P < 0.05). Also, appropriate alpha-ketoglutarate increased the activities of total antioxidant capacity and catalase and prevented the up-regulation in the mRNA expression levels of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 (P < 0.05). Furthermore, the mRNA expression levels of toll-like receptor 4 (TLR4), and nuclear factor kappa-B (NF-κB) were strikingly increased after infection with Aeromonas hydrophila (P < 0.05), while the TLR4 was strikingly decreased with alpha-ketoglutarate supplementation (P < 0.05). Moreover, the mRNA expression levels of tight junctions including claudin-1, claudin-3, claudin-7, claudin-11 and myosin light chain kinases (MLCK) were upregulated after alpha-ketoglutarate supplementation (P < 0.05). In summary, the appropriate alpha-ketoglutarate supplementation could increase survival rate, strengthen the intestinal enzyme immunosuppressive activities, antioxidant capacities and alleviate the intestinal inflammation, thereby promoting the intestinal immune responses and barrier functions of Songpu mirror carp via activating TLR4/MyD88/NF-κB and MLCK signaling pathways after infection with Aeromonas hydrophila.
Phosphoinositide 3-Kinase p110 Delta Differentially Restrains and Directs Naïve Versus Effector CD8+ T Cell Transcriptional Programs
Authors: Spinelli Laura , Marchingo Julia M. , Nomura Aneela , Damasio Marcos P. , Cantrell Doreen A.
Published: June 2021

Phosphoinositide 3-kinase p110 delta (PI3K p110δ) is pivotal for CD8+ T cell immune responses. The current study explores PI3K p110δ induction and repression of antigen receptor and cytokine regulated programs to inform how PI3K p110δ directs CD8+ T cell fate. The studies force a revision of the concept that PI3K p110δ controls metabolic pathways in T cells and reveal major differences in PI3K p110δ regulated transcriptional programs between naïve and effector cytotoxic T cells (CTL). These differences include differential control of the expression of cytolytic effector molecules and costimulatory receptors. Key insights from the work include that PI3K p110δ signalling pathways repress expression of the critical inhibitory receptors CTLA4 and SLAMF6 in CTL. Moreover, in both naïve and effector T cells the dominant role for PI3K p110δ is to restrain the production of the chemokines that orchestrate communication between adaptive and innate immune cells. The study provides a comprehensive resource for understanding how PI3K p110δ uses multiple processes mediated by Protein Kinase B/AKT, FOXO1 dependent and independent mechanisms and mitogen-activated protein kinases (MAPK) to direct CD8+ T cell fate.
RPL22 Overexpression Promotes Psoriasis-Like Lesion by Inducing Keratinocytes Abnormal Biological Behavior
Authors: Zeng Jinrong , Zhang Yue , Zhang Hanyi , Zhang Yuezhong , Gao Lihua , Tong Xiaoliang , Xie Yajie , Hu Qian , Chen Chunli , Ding Shu , Lu Jianyun
Published: June 2021

Background

Keratinocytes of psoriasis have anti-apoptotic properties including delayed apoptosis process, accelerated proliferation metabolism and postponed differentiation process. However, the specific mechanism leading to the abnormal biological behavior of keratinocytes remains unclear.

Objectives

We investigated the role of increased RPL22 expression in regulating the abnormal biological behavior of keratinocytes and the mechanism of regulation of RPL22 expression in skin lesions of psoriatic patients.

Methods

We examined clinical samples and utilized cytokine-induced cell and IMQ-treated mouse models. We determined the expression and functions of RPL22 in vitro and in vivo.

Results

We showed that RPL22 expression was significantly increased in the skin lesions of psoriasis patients and IMQ-treated psoriatic-like mice. Such increased expression is attributed to hyperacetylation of histone H3K27 in the promoter region of RPL22. Interestingly, overexpression of RPL22 enhanced keratinocyte proliferation by increasing cyclinD1 expression and accelerated CD4+T cells recruitment via upregulating CXCL10 expression. Finally, we demonstrated that RPL22 overexpression promoted psoriasiform phenotypes in IMQ-induced mouse skins.

Conclusions

These findings suggested that RPL22 regulates keratinocytes abnormal biological behavior and contributes to the development of psoriatic phenotypes. Thus, RPL22 might be a novel potential molecular target for treatment of psoriasis.
“Corneal Nerves, CD11c+ Dendritic Cells and Their Impact on Ocular Immune Privilege”
Authors: Niederkorn Jerry Y.
Published: June 2021

The eye and the brain have limited capacities for regeneration and as such, immune-mediated inflammation can produce devastating consequences in the form of neurodegenerative diseases of the central nervous system or blindness as a result of ocular inflammatory diseases such as uveitis. Accordingly, both the eye and the brain are designed to limit immune responses and inflammation – a condition known as “immune privilege”. Immune privilege is sustained by physiological, anatomical, and regulatory processes that conspire to restrict both adaptive and innate immune responses.
Mitochondrial DNA Evaluation and Species Identification of Kemp’s Ridley Sea Turtle (Lepidochelys kempii) Bones After a 3-Year Exposure to Submerged Marine and Terrestrial Environments
Authors: Krestoff Elizabeth S. , Creecy James P. , Lord Wayne D. , Haynie Michelle L. , Coyer James A. , Sampson Kate
Published: June 2021

Because Kemp’s ridley sea turtles (Lepidochelys kempii) are critically endangered and closely related to the vulnerable olive ridleys (L. olivacea), it is essential for forensic investigations and conservation efforts to distinguish these species when only skeletal elements remain. DNA extraction and analysis by DNA sequencing of genetic markers is the only method to determine species identity reliably, yet these methods are significantly compromised when DNA becomes degraded. To evaluate the role that time and environment play in obtaining high-quality DNA sequencing data, we placed skeletal elements of a terrestrial mammal (Bos taurus) and L. kempii in a supratidal and subtidal environment for 3 years. Bi-annual sampling revealed that after 3 years, mitochondrial DNA (mtDNA) consistently identified each species from each environment. Our results show that mtDNA recovery from bone and identification for Kemp’s ridley sea turtles was possible up to 3 years in both environments. All sequencing data obtained was accurate and robust, but DNA sequencing results were not consistent after 664-days of exposure. Our findings led us to conclude that if sufficient DNA is extracted from bone samples, then high-quality sequence data can be obtained, and the resulting sequence data accurately reflects the reference sequence for the given gene marker. This study provides evidence that DNA can be extracted and analyzed from challenging biological substrates, like bone, when these substrates are exposed to seasonally dynamic maritime environmental conditions for up to 3-years.
Concentrating Solar Power Technologies: A Bibliometric Study of Past, Present and Future Trends in Concentrating Solar Power Research
Authors: Calderón Alejandro , Barreneche Camila , Prieto Cristina , Segarra Mercè , Fernández A. Inés
Published: June 2021

Bibliometric analysis is a key study in order to elucidate the relevance of a research field. This study will point out the main evolution of the research performed in a topic considering the significance of each sub-topic. This study aims to perform a bibliometric analysis in concentrating solar power (CSP) technology. CSP had a first commercial wave between 1984 and 1995. Between 1995 and 2005 there was a period of commercial inactivity. Nevertheless, since 2005 CSP commercial implementation has been accelerating. This topic accounts for almost 6,300 publications on relevant journals and conference proceedings. Regional analysis showed that China is becoming the most relevant country for CSP research. The European Union still leads the development and will continue that way at least in the short term. Authors’ keyword evolution analysis has been useful as an indirect measure of technological maturity. It was found that conference proceedings have an important effect in the overall CSP publications and need to be consider when working within this field. However, the journal publications have more impact since they are more frequently cited. Funding analysis had shown a direct relationship between funding and research output. Finally, it was concluded that inside the CSP field, parabolic trough has shown to have great relevance in the research output.
Bone Stress-Strain State Evaluation Using CT Based FEM
Authors: Gerasimov Oleg V. , Kharin Nikita V. , Fedyanin Artur O. , Bolshakov Pavel V. , Baltin Maxim E. , Statsenko Evgeny O. , Fadeev Filip O. , Islamov Rustem R. , Baltina Tatyana V. , Sachenkov Oskar A.
Published: June 2021

Nowadays, the use of a digital prototype in numerical modeling is one of the main approaches to calculating the elements of an inhomogeneous structure under the influence of external forces. The article considers a finite element analysis method based on computed tomography data. The calculations used a three-dimensional isoparametric finite element of a continuous medium developed by the authors with a linear approximation, based on weighted integration of the local stiffness matrix. The purpose of this study is to describe a general algorithm for constructing a numerical model that allows static calculation of objects with a porous structure according to its computed tomography data. Numerical modeling was carried out using kinematic boundary conditions. To evaluate the results obtained, computational and postprocessor grids were introduced. The qualitative assessment of the modeling data was based on the normalized error. Three-point bending of bone specimens of the pig forelimbs was considered as a model problem. The numerical simulation results were compared with the data obtained from a physical experiment. The relative error ranged from 3 to 15%, and the crack location, determined by the physical experiment, corresponded to the area where the ultimate strength values were exceeded, determined by numerical modeling. The results obtained reflect not only the effectiveness of the proposed approach, but also the agreement with experimental data. This method turned out to be relatively non-resource-intensive and time-efficient.
Propensity for Calcification in Serum Associates With 2-Year Cardiovascular Mortality in Ischemic Heart Failure With Reduced Ejection Fraction
Authors: Bojic Marija , Koller Lorenz , Cejka Daniel , Niessner Alexander , Bielesz Bernhard
Published: June 2021

Background: The propensity of serum to calcify, as assessed by the T50-test, associates with mortality in patients with chronic kidney disease. In chronic heart failure, phosphate and fibroblast growth factor-23 (FGF-23), which are important components of the vascular calcification pathway, have been linked to patient survival. Here, we investigated whether T50 associates with overall and cardiovascular survival in patients with chronic heart failure with reduced ejection fraction (HFrEF).

Methods: We measured T50, intact and c-terminal FGF-23 levels in a cohort of 306 HFrEF patients. Associations with overall and cardiovascular mortality were analyzed in survival analysis and Cox-regression models.

Results: After a median follow-up time of 3.2 years (25th−75th percentile: 2.0–4.9 years), 114 patients (37.3%) died due to any cause and 76 patients (24.8%) died due to cardiovascular causes. 139 patients (45.4%) had ischemic and 167 patients (54.6%) had non-ischemic HFrEF. Patients with ischemic HFrEF in the lowest T50-tertile had significantly greater 2-year cardiovascular mortality compared to patients in higher tertiles (p = 0.011). In ischemic but not in non-ischemic HFrEF, T50 was significantly associated with cardiovascular mortality in univariate (p = 0.041) and fully adjusted (p = 0.046) Cox regression analysis. Significant associations of intact and c-terminal FGF-23 with all-cause and cardiovascular mortality in univariate Cox regression analysis did not remain significant after adjustment for confounding factors.

Conclusion: T50 is associated with 2-year cardiovascular mortality in patients with ischemic HFrEF but not in non-ischemic HFrEF. More research on the role of T50 measurements in coronary artery disease is warranted.
Pre-Operative Prediction of Mediastinal Node Metastasis Using Radiomics Model Based on 18F-FDG PET/CT of the Primary Tumor in Non-Small Cell Lung Cancer Patients
Authors: Zheng Kai , Wang Xinrong , Jiang Chengzhi , Tang Yongxiang , Fang Zhihui , Hou Jiale , Zhu Zehua , Hu Shuo
Published: June 2021

Purpose: We investigated whether a fluorine-18-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based radiomics model (RM) could predict the pathological mediastinal lymph node staging (pN staging) in patients with non-small cell lung cancer (NSCLC) undergoing surgery.

Methods: A total of 716 patients with a clinicopathological diagnosis of NSCLC were included in this retrospective study. The prediction model was developed in a training cohort that consisted of 501 patients. Radiomics features were extracted from the 18F-FDG PET/CT of the primary tumor. Support vector machine and extremely randomized trees were used to build the RM. Internal validation was assessed. An independent testing cohort contained the remaining 215 patients. The performances of the RM and clinical node staging (cN staging) in predicting pN staging (pN0 vs. pN1 and N2) were compared for each cohort. The area under the curve (AUC) of the receiver operating characteristic curve was applied to assess the model's performance.

Results: The AUC of the RM [0.81 (95% CI, 0.771–0.848); sensitivity: 0.794; specificity: 0.704] for the predictive performance of pN1 and N2 was significantly better than that of cN in the training cohort [0.685 (95% CI, 0.644–0.728); sensitivity: 0.804; specificity: 0.568], (P-value = 8.29e-07, as assessed by the Delong test). In the testing cohort, the AUC of the RM [0.766 (95% CI, 0.702–0.830); sensitivity: 0.688; specificity: 0.704] was also significantly higher than that of cN [0.685 (95% CI, 0.619–0.747); sensitivity: 0.799; specificity: 0.568], (P = 0.0371, Delong test).

Conclusions: The RM based on 18F-FDG PET/CT has a potential for the pN staging in patients with NSCLC, suggesting that therapeutic planning could be tailored according to the predictions.
Larval Diet Abundance Influences Size and Composition of the Midgut Microbiota of Aedes aegypti Mosquitoes
Authors: MacLeod Hannah J. , Dimopoulos George , Short Sarah M.
Published: June 2021

The midgut microbiota of the yellow fever mosquito Aedes aegypti impacts pathogen susceptibility and transmission by this important vector species. However, factors influencing the composition and size of the microbiome in mosquitoes are poorly understood. We investigated the impact of larval diet abundance during development on the composition and size of the larval and adult microbiota by rearing Aedes aegypti under four larval food regimens, ranging from nutrient deprivation to nutrient excess. We assessed the persistent impacts of larval diet availability on the microbiota of the larval breeding water, larval mosquitoes, and adult mosquitoes under sugar and blood fed conditions using qPCR and high-throughput 16S amplicon sequencing to determine bacterial load and microbiota composition. Bacterial loads in breeding water increased with increasing larval diet. Larvae reared with the lowest diet abundance had significantly fewer bacteria than larvae from two higher diet treatments, but not from the highest diet abundance. Adults from the lowest diet abundance treatment had significantly fewer bacteria in their midguts compared to all higher diet abundance treatments. Larval diet amount also had a significant impact on microbiota composition, primarily within larval breeding water and larvae. Increasing diet correlated with increased relative levels of Enterobacteriaceae and Flavobacteriaceae and decreased relative levels of Sphingomonadaceae. Multiple individual OTUs were significantly impacted by diet including one mapping to the genus Cedecea, which increased with higher diet amounts. This was consistent across all sample types, including sugar fed and blood fed adults. Taken together, these data suggest that availability of diet during development can cause lasting shifts in the size and composition of the microbiota in the disease vector Aedes aegypti.
Pathological Features of Enterovirus 71-Associated Brain and Lung Damage in Mice Based on Quantitative Proteomic Analysis
Authors: Jin Yuefei , Li Dong , Sun Tiantian , Du Yue , Gao Yanlei , Ding Ronghua , Ji Wangquan , Zhang Weiguo , Yang Haiyan , Chen Shuaiyin , Duan Guangcai
Published: June 2021

The outbreaks of enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) have emerged as an emergency of global health due to its association with fatal encephalitis and subsequent neurogenic pulmonary edema; however, the molecular characteristics and pathological features underlying EV71-associated encephalitis and pulmonary edema remain largely unknown. In this study, we performed a proteomic analysis of fresh brain and lung tissues from EV71-infected mice at 7 days post infection. We detected a perturbed expression of 148 proteins in the brain and 78 proteins in the lung after EV71 expression. Further analysis showed that the dysregulated proteins in the brain are involved in a variety of fundamental biological pathways, including complement and coagulation cascades, innate and adaptive immune responses, platelet activation, and nitrogen metabolism, and those proteins in the lung participate in innate and adaptive immune responses, phagosome, arginine biosynthesis, and hypoxia-inducible factor 1 signaling pathway. Our results suggested that immune activation, complement and coagulation dysfunction, platelet activation, imbalance of nitrogen metabolism, and hypoxia could be involved in the pathogenesis of EV71, which explains the major clinical manifestation of hyperinflammatory status of severe HFMD cases. Our study provides further understanding of the molecular basis of EV71 pathogenesis.
Effects of Ribosomal Protein S10 Flexible Loop Mutations on Tetracycline and Tigecycline Susceptibility of Escherichia coli
Authors: Izghirean Norbert , Waidacher Claudia , Kittinger Clemens , Chyba Miriam , Koraimann Günther , Pertschy Brigitte , Zarfel Gernot
Published: June 2021

Tigecycline is a tetracycline derivative that is being used as an antibiotic of last resort. Both tigecycline and tetracycline bind to the small (30S) ribosomal subunit and inhibit translation. Target mutations leading to resistance to these antibiotics have been identified both in the 16S ribosomal RNA and in ribosomal proteins S3 and S10 (encoded by the rpsJ gene). Several different mutations in the S10 flexible loop tip residue valine 57 (V57) have been observed in tigecycline-resistant Escherichia coli isolates. However, the role of these mutations in E. coli has not yet been characterized in a defined genetic background. In this study, we chromosomally integrated 10 different rpsJ mutations into E. coli, resulting in different exchanges or a deletion of S10 V57, and investigated the effects of the mutations on growth and tigecycline/tetracycline resistance. While one exchange, V57K, decreased the minimal inhibitory concentration (MIC) (Etest) to tetracycline to 0.75 μg/ml (compared to 2 μg/ml in the parent strain) and hence resulted in hypersensitivity to tetracycline, most exchanges, including the ones reported previously in resistant isolates (V57L, V57D, and V57I) resulted in slightly increased MICs to tigecycline and tetracycline. The strongest increase was observed for the V57L mutant, with a MIC (Etest) to tigecycline of 0.5 μg/ml (compared to 0.125 μg/ml in the parent strain) and a MIC to tetracycline of 4.0 μg/ml. Nevertheless, none of these exchanges increased the MIC to the extent observed in previously described clinical tigecycline-resistant isolates. We conclude that, next to S10 mutations, additional mutations are necessary in order to reach high-level tigecycline resistance in E. coli. In addition, our data reveal that mutants carrying S10 V57 exchanges or deletion display growth defects and, in most cases, also thermosensitivity. The defects are particularly strong in the V57 deletion mutant, which is additionally cold-sensitive. We hypothesize that the S10 loop tip residue is critical for the correct functioning of S10. Both the S10 flexible loop and tigecycline are in contact with helix h31 of the 16S rRNA. We speculate that exchanges or deletion of V57 alter the positioning of h31, thereby influencing both tigecycline binding and S10 function.
The Impact of Fertilizer Amendments on Soil Autotrophic Bacteria and Carbon Emissions in Maize Field on the Semiarid Loess Plateau
Authors: Wang Jinbin , Xie Junhong , Li Lingling , Luo Zhuzhu , Zhang Renzhi , Wang Linlin , Jiang Yuji
Published: June 2021

Soil autotrophic bacteria play a crucial role in regulating CO2 fixation and crop productivity. However, the information is limited to how fertilization amendments alter soil autotrophic bacterial community, crop yield, and carbon emission efficiency (CEE). Here, we estimated the impact of the structure and co-occurrence network of soil autotrophic bacterial community on maize yield and CEE. A long-term field experiment was conducted with five fertilization treatments in semiarid Loess Plateau, including no amendment (NA), chemical fertilizer (CF), chemical fertilizer plus commercial organic fertilizer (SC), commercial organic fertilizer (SM), and maize straw (MS). The results showed that fertilization amendments impacted the structure and network of soil Calvin–Benson–Bassham (CBB) (cbbL) gene-carrying bacterial community via changing soil pH and NO3–N. Compared with no amendment, the cbbL-carrying bacterial diversity was increased under the SC, SM, and MS treatments but decreased under the CF treatment. Soil autotrophic bacterial network contained distinct microbial modules that consisted of closely associated microbial species. We detected the higher abundances of soil cbbL-carrying bacterial genus Xanthobacter, Bradyrhizobium, and Nitrosospira. Structural equation modeling further suggested that the diversity, composition, and network of autotrophic bacterial community had strongly positive relationships with CEE and maize yield. Taken together, our results suggest that soil autotrophic bacterial community may drive crop productivity and CEE, and mitigate the atmospheric greenhouse effect.
The Seasonal Flux and Fate of Dissolved Organic Carbon Through Bacterioplankton in the Western North Atlantic
Authors: Baetge Nicholas , Behrenfeld Michael J. , Fox James , Halsey Kimberly H. , Mojica Kristina D. A. , Novoa Anai , Stephens Brandon M. , Carlson Craig A.
Published: June 2021

The oceans teem with heterotrophic bacterioplankton that play an appreciable role in the uptake of dissolved organic carbon (DOC) derived from phytoplankton net primary production (NPP). As such, bacterioplankton carbon demand (BCD), or gross heterotrophic production, represents a major carbon pathway that influences the seasonal accumulation of DOC in the surface ocean and, subsequently, the potential vertical or horizontal export of seasonally accumulated DOC. Here, we examine the contributions of bacterioplankton and DOM to ecological and biogeochemical carbon flow pathways, including those of the microbial loop and the biological carbon pump, in the Western North Atlantic Ocean (∼39–54°N along ∼40°W) over a composite annual phytoplankton bloom cycle. Combining field observations with data collected from corresponding DOC remineralization experiments, we estimate the efficiency at which bacterioplankton utilize DOC, demonstrate seasonality in the fraction of NPP that supports BCD, and provide evidence for shifts in the bioavailability and persistence of the seasonally accumulated DOC. Our results indicate that while the portion of DOC flux through bacterioplankton relative to NPP increased as seasons transitioned from high to low productivity, there was a fraction of the DOM production that accumulated and persisted. This persistent DOM is potentially an important pool of organic carbon available for export to the deep ocean via convective mixing, thus representing an important export term of the biological carbon pump.
Lactosmart: A Novel Therapeutic Molecule for Antimicrobial Defense
Authors: Singh Jiya , Vijayan Viswanathan , Ahmedi Saiema , Pant Pradeep , Manzoor Nikhat , Singh Tej P. , Sharma Pradeep , Sharma Sujata
Published: June 2021

The problem of antibiotic resistance has prompted researchers around the globe to search for new antimicrobial agents. Antimicrobial proteins and peptides are naturally secreted by almost all the living organisms to fight infections and can be safer alternatives to chemical antibiotics. Lactoferrin (LF) is a known antimicrobial protein present in all body secretions. In this study, LF was digested by trypsin, and the resulting hydrolysates were studied with respect to their antimicrobial properties. Among the hydrolysates, a 21-kDa basic fragment of LF (termed lactosmart) showed promise as a new potent antimicrobial agent. The antimicrobial studies were performed on various microorganisms including Shigella flexneri, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli as well as fungal pathogens such as Candida albicans, Candida tropicalis, and Candida glabrata. In addition, the lipopolysaccharide (LPS)-binding properties of lactosmart were studied using surface plasmon resonance technique in vitro, along with docking of LPS and molecular dynamics (MD) simulation studies. The results showed that lactosmart had better inhibitory effects against pathogenic microorganisms compared to LF. The results of docking and MD simulation studies further validated the tighter binding of LPS to lactosmart compared to LF. The two LPS-binding sites have been characterized structurally in detail. Through these studies, it has been demonstrated that in native LF, only one LPS-binding site remains exposed due to its location being on the surface of the molecule. However, due to the generation of the lactosmart molecule, the second LPS-binding site gets exposed too. Since LPS is an essential and conserved part of the bacterial cell wall, the pro-inflammatory response in the human body caused by LPS can be targeted using the newly identified lactosmart. These findings highlight the immense potential of lactosmart in comparison to native LF in antimicrobial defense. We propose that lactosmart can be further developed as an antibacterial, antifungal, and antibiofilm agent.
A Redox-Based Autoinduction Strategy to Facilitate Expression of 5xCys-Tagged Proteins for Electrobiofabrication
Authors: Wang Sally , Tsao Chen-Yu , Motabar Dana , Li Jinyang , Payne Gregory F. , Bentley William E.
Published: June 2021

Biofabrication utilizes biological materials and biological means, or mimics thereof, for assembly. When interfaced with microelectronics, electrobiofabricated assemblies enable exquisite sensing and reporting capabilities. We recently demonstrated that thiolated polyethylene glycol (PEG-SH) could be oxidatively assembled into a thin disulfide crosslinked hydrogel at an electrode surface; with sufficient oxidation, extra sulfenic acid groups are made available for covalent, disulfide coupling to sulfhydryl groups of proteins or peptides. We intentionally introduced a polycysteine tag (5xCys-tag) consisting of five consecutive cysteine residues at the C-terminus of aStreptococcalprotein G to enable its covalent coupling to an electroassembled PEG-SH film. We found, however, that its expression and purification fromE. coliwas difficult, owing to the extra cysteine residues. We developed a redox-based autoinduction methodology that greatly enhanced the yield, especially in the soluble fraction ofE. coliextracts. The redox component involved the deletion ofoxyRS, a global regulator of the oxidative stress response and the autoinduction component integrated a quorum sensing (QS) switch that keys the secreted QS autoinducer-2 to induction. Interestingly, both methods helped when independently employed and further, when used in combination (i.e., autodinducedoxyRSmutant) the results were best—we found the highest total yield and highest yield in the soluble fraction. We hypothesize that the production host was less prone to severe metabolic perturbations that might reduce yield or drive sequestration of the -tagged protein into inclusion bodies. We expect this methodology will be useful for the expression of many such Cys-tagged proteins, ultimately enabling a diverse array of functionalized devices.
Zetaproteobacteria Pan-Genome Reveals Candidate Gene Cluster for Twisted Stalk Biosynthesis and Export
Authors: Koeksoy Elif , Bezuidt Oliver M. , Bayer Timm , Chan Clara S. , Emerson David
Published: June 2021

Twisted stalks are morphologically unique bacterial extracellular organo-metallic structures containing Fe(III) oxyhydroxides that are produced by microaerophilic Fe(II)-oxidizers belonging to the Betaproteobacteria and Zetaproteobacteria. Understanding the underlying genetic and physiological mechanisms of stalk formation is of great interest based on their potential as novel biogenic nanomaterials and their relevance as putative biomarkers for microbial Fe(II) oxidation on ancient Earth. Despite the recognition of these special biominerals for over 150 years, the genetic foundation for the stalk phenotype has remained unresolved. Here we present a candidate gene cluster for the biosynthesis and secretion of the stalk organic matrix that we identified with a trait-based analyses of a pan-genome comprising 16 Zetaproteobacteria isolate genomes. The “stalk formation in Zetaproteobacteria” (sfz) cluster comprises six genes (sfz1-sfz6), of which sfz1 and sfz2 were predicted with functions in exopolysaccharide synthesis, regulation, and export, sfz4 and sfz6 with functions in cell wall synthesis manipulation and carbohydrate hydrolysis, and sfz3 and sfz5 with unknown functions. The stalk-forming Betaproteobacteria Ferriphaselus R-1 and OYT-1, as well as dread-forming Zetaproteobacteria Mariprofundus aestuarium CP-5 and Mariprofundus ferrinatatus CP-8 contain distant sfz gene homologs, whereas stalk-less Zetaproteobacteria and Betaproteobacteria lack the entire gene cluster. Our pan-genome analysis further revealed a significant enrichment of clusters of orthologous groups (COGs) across all Zetaproteobacteria isolate genomes that are associated with the regulation of a switch between sessile and motile growth controlled by the intracellular signaling molecule c-di-GMP. Potential interactions between stalk-former unique transcription factor genes, sfz genes, and c-di-GMP point toward a c-di-GMP regulated surface attachment function of stalks during sessile growth.
APP, PSEN1, and PSEN2 Variants in Alzheimer’s Disease: Systematic Re-evaluation According to ACMG Guidelines
Authors: Xiao Xuewen , Liu Hui , Liu Xixi , Zhang Weiwei , Zhang Sizhe , Jiao Bin
Published: June 2021

The strategies of classifying APP, PSEN1, and PSEN2 variants varied substantially in the previous studies. We aimed to re-evaluate these variants systematically according to the American college of medical genetics and genomics and the association for molecular pathology (ACMG-AMP) guidelines. In our study, APP, PSEN1, and PSEN2 variants were collected by searching Alzforum and PubMed database with keywords “PSEN1,” “PSEN2,” and “APP.” These variants were re-evaluated based on the ACMG-AMP guidelines. We compared the number of pathogenic/likely pathogenic variants of APP, PSEN1, and PSEN2. In total, 66 APP variants, 323 PSEN1 variants, and 63 PSEN2 variants were re-evaluated in our study. 94.91% of previously reported pathogenic variants were re-classified as pathogenic/likely pathogenic variants, while 5.09% of them were variants of uncertain significance (VUS). PSEN1 carried the most prevalent pathogenic/likely pathogenic variants, followed by APP and PSEN2. Significant statistically difference was identified among these three genes when comparing the number of pathogenic/likely pathogenic variants (P < 2.2 × 10–16). Most of the previously reported pathogenic variants were re-classified as pathogenic/likely pathogenic variants while the others were re-evaluated as VUS, highlighting the importance of interpreting APP, PSEN1, and PSEN2 variants with caution according to ACMG-AMP guidelines.
Human Schwann Cell Transplantation for Spinal Cord Injury: Prospects and Challenges in Translational Medicine
Authors: Monje Paula V. , Deng Lingxiao , Xu Xiao-Ming
Published: June 2021

The benefits of transplanting cultured Schwann cells (SCs) for the treatment of spinal cord injury (SCI) have been systematically investigated in experimental animals since the early 1990s. Importantly, human SC (hSC) transplantation for SCI has advanced to clinical testing and safety has been established via clinical trials conducted in the USA and abroad. However, multiple barriers must be overcome to enable accessible and effective treatments for SCI patients. This review presents available information on hSC transplantation for SCI with the intention to uncover gaps in our knowledge and discuss areas for future development. To this end, we introduce the historical progression of the work that supports existing and prospective clinical initiatives and explain the reasons for the choice of hSCs while also addressing their limitations as cell therapy products. A search of the relevant literature revealed that rat SCs have served as a preclinical model of reference since the onset of investigations, and that hSC transplants are relatively understudied, possibly due to the sophisticated resources and expertise needed for the traditional processing of hSC cultures from human nerves. In turn, we reason that additional experimentation and a reexamination of the available data are needed to understand the therapeutic value of hSC transplants taking into consideration that the manufacturing of the hSCs themselves may require further development for extended uses in basic research and clinical settings.