bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Aerosol Extinction Efficiency Hinders Visibility Improvement in Eastern China
Authors: Liu Jingyi , Ren Chuanhua , Huang Xin , Nie Wei , Wang Jiaping , Sun Peng , Chi Xuguang , Ding Aijun
Published: October 2020

Though China has witnessed substantial particular matter pollution mitigation owing to the strict emission control in recent years, the frequency of haze events with low visibility is not improved as much as expected, especially in cold seasons. Here, 6‐year wintertime observations, satellite retrievals, a thermodynamic model, and theoretical calculation were integrated to better understand the complex influence of aerosol chemical composition and hygroscopic behaviors on visibility impairment. We found that the proportion of nitrate in aerosol mass concentration increased by approximately 10% from 2013 to 2018. Such a transition in aerosol chemical compositions together with increasing ambient humidity in past years jointly enhanced aerosol extinction efficiency, and the elevated proportion of nitrate played an increasingly critical role after 2017. The increased aerosol extinction efficiency is responsible for the less improved visibility despite large decrease in aerosol mass concentrations in eastern China.
A Universal Form of Power Law Relationships for River and Stream Channels
Authors: Xu Fan , Coco Giovanni , Zhou Zeng , Townend Ian , Guo Leicheng , He Qing
Published: October 2020

The description of the geomorphic characteristics in power law forms has been the subject of research, over the past 70 years, and has become the cornerstone of regime theory. However, just why power functions should represent such geomorphic relationships remains poorly understood. Hence, differences in the values of the regime exponents observed for different river systems remain largely unexplained. To address this issue, we derived generic forms of the power law relationships without postulating any power functions of the discharge. The theoretical approach accurately captures the systematic variations of the regime exponents shown by a number of large data sets from previous research. We also explain how frictional resistance is responsible for the systematic variability of regime exponents. Overall, our study provides a robust mechanism to describe the variations of the exponents, along with a deductive explanation of the power laws at the core of fluvial hydraulic geometry.
Widespread Mesoscale Dipoles in the Global Ocean
Authors: Ni Qinbiao , Zhai Xiaoming , Wang Guihua , Hughes Chris W.
Published: October 2020

Mesoscale eddies are ubiquitous and energetic features in the ocean. Although eddies are known to form dipoles from time to time, it is unclear how often they do so. Using satellite altimetry data, here we show that mesoscale dipoles are surprisingly widespread in the global ocean. About 30–40% of the mesoscale eddies identified in altimeter data are paired up as dipoles, and the percentage is even higher in energetic regions such as the Gulf Stream and the Southern Ocean. Composite analysis involving Argo float data further reveals that these mesoscale dipoles have a relatively uniform three‐dimensional structure. We find that the presence of mesoscale dipoles can strongly enhance wind Ekman pumping velocity and lead to deep‐reaching vertical motions inside the dipoles via eddy deformation and frontogenesis. Such strong vertical exchanges promoted by mesoscale dipoles may play an important role in regulating the Earth's biogeochemical processes.
SET8 suppression mediates high glucose-induced vascular endothelial inflammation via the upregulation of PTEN
Authors: Shen Xuefang , Chen Xiangyuan , Wang Jing , Liu Jing , Wang Zhiyao , Hua Qing , Wu Qichao , Su Yanguang , He Huanzhong , Hu Yuqin , Meng Zhipeng , Xiong Wanxia , Zhu Minmin
Published: October 2020

Hyperglycemia-mediated endothelial inflammation participates in the pathogenesis of cardiovascular complications in subjects with diabetes. Previous studies reported that phosphatase and tensin homolog deleted on chromosome ten (PTEN) and SET8 participate in high glucose-mediated endothelial inflammation. In this study, we hypothesize that SET8 regulates PTEN expression, thus contributing to high glucose-mediated vascular endothelial inflammation. Our data indicated that plasma soluble intercellular adhesion molecule-1 (sICAM-1) and endothelial selectin (e-selectin) were increased in patients with diabetes and diabetic rats. PTEN expression was augmented in the peripheral blood mononuclear cells of patients with diabetes and in the aortic tissues of diabetic rats. Our in vitro study indicated that high glucose increased monocyte/endothelial adhesion, endothelial adhesion molecule expression and p65 phosphorylation in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose led to endothelial inflammation via upregulation of PTEN. Furthermore, high glucose inhibited SET8 expression and histone H4 lysine 20 methylation (H4K20me1), a downstream target of SET8. SET8 overexpression reversed the effects of high-glucose treatment. shSET8-mediated endothelial inflammation was counteracted by siPTEN. Furthermore, SET8 was found to interact with FOXO1. siFOXO1 attenuated high glucose-mediated endothelial inflammation. FOXO1 overexpression-mediated endothelial inflammation was counteracted by siPTEN. H4K20me1 and FOXO1 were enriched in the PTEN promoter region. shSET8 increased PTEN promoter activity and augmented the positive effect of FOXO1 overexpression on PTEN promoter activity. Our in vivo study indicated that SET8 was downregulated and FOXO1 was upregulated in the peripheral blood mononuclear cells of patients with diabetes and the aortic tissues of diabetic rats. In conclusion, SET8 interacted with FOXO1 to modulate PTEN expression in vascular endothelial cells, thus contributing to hyperglycemia-mediated endothelial inflammation.
The role of integrins in inflammation and angiogenesis
Authors: Mezu-Ndubuisi Olachi J. , Maheshwari Akhil
Published: October 2020

Integrins are heterodimeric transmembrane cell adhesion molecules made up of alpha (α) and beta (β) subunits arranged in numerous dimeric pairings. These complexes have varying affinities to extracellular ligands. Integrins regulate cellular growth, proliferation, migration, signaling, and cytokine activation and release and thereby play important roles in cell proliferation and migration, apoptosis, tissue repair, as well as in all processes critical to inflammation, infection, and angiogenesis. This review presents current evidence from human and animal studies on integrin structure and molecular signaling, with particular emphasis on signal transduction in infants. We have included evidence from our own laboratory studies and from an extensive literature search in databases PubMed, EMBASE, Scopus, and the electronic archives of abstracts presented at the annual meetings of the Pediatric Academic Societies. To avoid bias in identification of existing studies, key words were short-listed prior to the actual search both from anecdotal experience and from PubMed’s Medical Subject Heading (MeSH) thesaurus.

Impact

Integrins are a family of ubiquitous αβ heterodimeric receptors that interact with numerous ligands in physiology and disease. Integrins play a key role in cell proliferation, tissue repair, inflammation, infection, and angiogenesis.

This review summarizes current evidence from human and animal studies on integrin structure and molecular signaling and promising role in diseases of inflammation, infection, and angiogenesis in infants.

This review shows that integrin receptors and ligands are novel therapeutic targets of clinical interest and hold promise as novel therapeutic targets in the management of several neonatal diseases.
Bone health effects of androgen-deprivation therapy and androgen receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer
Authors: Hussain Arif , Tripathi Abhishek , Pieczonka Christopher , Cope Diane , McNatty Andrea , Logothetis Christopher , Guise Theresa
Published: October 2020

Background

Osteoporosis is a skeletal disorder characterized by compromised bone strength, resulting in increased fracture risk. Patients with prostate cancer may have multiple risk factors contributing to bone fragility: advanced age, hypogonadism, and long-term use of androgen-deprivation therapy. Despite absence of metastatic disease, patients with nonmetastatic castrate-resistant prostate cancer receiving newer androgen receptor inhibitors can experience decreased bone mineral density. A systematic approach to bone health care has been hampered by a simplistic view that does not account for heterogeneity among prostate cancer patients or treatments they receive. This review aims to raise awareness in oncology and urology communities regarding the complexity of bone health, and to provide a framework for management strategies for patients with nonmetastatic castrate-resistant prostate cancer receiving androgen receptor inhibitor treatment.

Methods

We searched peer-reviewed literature on the PubMed database using key words “androgen-deprivation therapy,” “androgen receptor inhibitors,” “bone,” “bone complications,” and “nonmetastatic prostate cancer” from 2000 to present.

Results

We discuss how androgen inhibition affects bone health in patients with nonmetastatic castrate-resistant prostate cancer. We present data from phase 3 trials on the three approved androgen receptor inhibitors with regard to effects on bone. Finally, we present management strategies for maintenance of bone health.

Conclusions

In patients with nonmetastatic castrate-resistant prostate cancer, aging, and antiandrogen therapy contribute to bone fragility. Newer androgen receptor inhibitors were associated with falls or fractures in a small subset of patients. Management guidelines include regular assessment of bone density, nutritional guidance, and use of antiresorptive bone health agents when warranted.
Beyond arbitrium: identification of a second communication system in Bacillus phage phi3T that may regulate host defense mechanisms
Authors: Bernard Charles , Li Yanyan , Lopez Philippe , Bapteste Eric
Published: October 2020

The evolutionary stability of temperate bacteriophages at low abundance of susceptible bacterial hosts lies in the trade-off between the maximization of phage replication, performed by the host-destructive lytic cycle, and the protection of the phage-host collective, enacted by lysogeny. Upon Bacillus infection, Bacillus phages phi3T rely on the “arbitrium” quorum sensing (QS) system to communicate on their population density in order to orchestrate the lysis-to-lysogeny transition. At high phage densities, where there may be limited host cells to infect, lysogeny is induced to preserve chances of phage survival. Here, we report the presence of an additional, host-derived QS system in the phi3T genome, making it the first known virus with two communication systems. Specifically, this additional system, coined “Rapφ-Phrφ”, is predicted to downregulate host defense mechanisms during the viral infection, but only upon stress or high abundance of Bacillus cells and at low density of population of the phi3T phages. Post-lysogenization, Rapφ-Phrφ is also predicted to provide the lysogenized bacteria with an immediate fitness advantage: delaying the costly production of public goods while nonetheless benefiting from the public goods produced by other non-lysogenized Bacillus bacteria. The discovered “Rapφ-Phrφ” QS system hence provides novel mechanistic insights into how phage communication systems could contribute to the phage-host evolutionary stability.
Mating type specific transcriptomic response to sex inducing pheromone in the pennate diatom Seminavis robusta
Authors: Bilcke Gust , Van den Berge Koen , De Decker Sam , Bonneure Eli , Poulsen Nicole , Bulankova Petra , Osuna-Cruz Cristina Maria , Dickenson Jack , Sabbe Koen , Pohnert Georg , Vandepoele Klaas , Mangelinckx Sven , Clement Lieven , De Veylder Lieven , Vyverman Wim
Published: October 2020

Sexual reproduction is a fundamental phase in the life cycle of most diatoms. Despite its role as a source of genetic variation, it is rarely reported in natural circumstances and its molecular foundations remain largely unknown. Here, we integrate independent transcriptomic datasets to prioritize genes responding to sex inducing pheromones (SIPs) in the pennate diatom Seminavis robusta. We observe marked gene expression changes associated with SIP treatment in both mating types, including an inhibition of S phase progression, chloroplast division, mitosis, and cell wall formation. Meanwhile, meiotic genes are upregulated in response to SIP, including a sexually induced diatom specific cyclin. Our data further suggest an important role for reactive oxygen species, energy metabolism, and cGMP signaling during the early stages of sexual reproduction. In addition, we identify several genes with a mating type specific response to SIP, and link their expression pattern with physiological specialization, such as the production of the attraction pheromone diproline in mating type − (MT−) and mate-searching behavior in mating type + (MT+). Combined, our results provide a model for early sexual reproduction in pennate diatoms and significantly expand the suite of target genes to detect sexual reproduction events in natural diatom populations.
The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence
Authors: Rabbie Roy , Ferguson Peter , Wong Kim , Couturier Dominique-Laurent , Moran Una , Turner Clinton , Emanuel Patrick , Haas Kerstin , Saunus Jodi M. , Davidson Morgan R. , Lakhani Sunil R. , Shivalingam Brindha , Long Georgina V. , Parkinson Christine , Osman Iman , Scolyer Richard A. , Corrie Pippa , Adams David J.
Published: October 2020

Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAFV600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance.
Correlative serum biomarker analyses in the phase 2 trial of lenvatinib-plus-everolimus in patients with metastatic renal cell carcinoma
Authors: Lee Chung-Han , Motzer Robert J. , Glen Hilary , Michaelson M. D. , Larkin James , Minoshima Yukinori , Kanekiyo Michio , Ikezawa Hiroki , Sachdev Pallavi , Dutcus Corina E. , Funahashi Yasuhiro , Voss Martin H.
Published: October 2020

Background

No biomarkers have been established to predict treatment efficacy in renal cell carcinoma (RCC). In an exploratory retrospective analysis of a Phase 2 study, we constructed composite biomarker scores (CBSs) to predict progression-free survival (PFS) and overall survival (OS) in patients with metastatic RCC randomised to receive lenvatinib-plus-everolimus.

Methods

Of 40 biomarkers tested, the 5 most strongly associated with PFS (HGF, MIG, IL-18BP, IL-18, ANG-2) or OS (TIMP-1, M-CSF, IL-18BP, ANG-2, VEGF) were used to make a 5-factor PFS-CBS or OS-CBS, respectively. A 2-factor CBS was generated with biomarkers common to PFS-CBS and OS-CBS. Patients were divided into groups accordingly (5-factor-CBS high: 3−5, CBS-low: 0–2; 2-factor-CBS high: 1–2, CBS-low: 0).

Results

PFS/OS with lenvatinib-plus-everolimus were significantly longer in the 5-factor CBS-high group versus the CBS-low group (P = 0.0022/P < 0.0001, respectively). In the CBS-high group, PFS/OS were significantly longer with lenvatinib-plus-everolimus versus everolimus (P < 0.001/P = 0.0079, respectively); PFS was also significantly longer with lenvatinib-plus-everolimus versus lenvatinib (P = 0.0046). The 5-factor-CBS had a predictive role in PFS and OS after multivariate analysis. Similar trends were observed with the 2-factor-CBS for PFS (i.e., lenvatinib-plus-everolimus versus everolimus).

Conclusions

The 5-factor CBS may identify patients with metastatic RCC who would benefit from lenvatinib-plus-everolimus versus everolimus; additional validation is required.

Clinical trial registration

The clinical trial registration number is NCT01136733.
Suppression of pancreatic cancer liver metastasis by secretion-deficient ITIH5
Authors: Young Eric D. , Manley Sharon J. , Beadnell Thomas C. , Shearin Alexander E. , Sasaki Ken , Zimmerman Rosalyn , Kauffman Evan , Vivian Carolyn J. , Parasuram Aishwarya , Iwakuma Tomoo , Grandgenett Paul M. , Hollingsworth Michael A. , O’Neil Maura , Welch Danny R.
Published: October 2020

Background

Previously, we identified ITIH5 as a suppressor of pancreatic ductal adenocarcinoma (PDAC) metastasis in experimental models. Expression of ITIH5 correlated with decreased cell motility, invasion and metastasis without significant inhibition of primary tumour growth. Here, we tested whether secretion of ITIH5 is required to suppress liver metastasis and sought to understand the role of ITIH5 in human PDAC.

Methods

We expressed mutant ITIH5 with deletion of the N-terminal secretion sequence (ITIH5Δs) in highly metastatic human PDAC cell lines. We used a human tissue microarray (TMA) to compare ITIH5 levels in uninvolved pancreas, primary and metastatic PDAC.

Results

Secretion-deficient ITIH5Δs was sufficient to suppress liver metastasis. Similar to secreted ITIH5, expression of ITIH5Δs was associated with rounded cell morphology, reduced cell motility and reduction of liver metastasis. Expression of ITIH5 is low in both human primary PDAC and matched metastases.

Conclusions

Metastasis suppression by ITIH5 may be mediated by an intracellular mechanism. In human PDAC, loss of ITIH5 may be an early event and ITIH5-low PDAC cells in primary tumours may be selected for liver metastasis. Further defining the ITIH5-mediated pathway in PDAC could establish future therapeutic exploitation of this biology and reduce morbidity and mortality associated with PDAC metastasis.
Versatile direct-writing of dopants in a solid state host through recoil implantation
Authors: Fröch Johannes E. , Bahm Alan , Kianinia Mehran , Mu Zhao , Bhatia Vijay , Kim Sejeong , Cairney Julie M. , Gao Weibo , Bradac Carlo , Aharonovich Igor , Toth Milos
Published: October 2020

Modifying material properties at the nanoscale is crucially important for devices in nano-electronics, nanophotonics and quantum information. Optically active defects in wide band gap materials, for instance, are critical constituents for the realisation of quantum technologies. Here, we demonstrate the use of recoil implantation, a method exploiting momentum transfer from accelerated ions, for versatile and mask-free material doping. As a proof of concept, we direct-write arrays of optically active defects into diamond via momentum transfer from a Xe+ focused ion beam (FIB) to thin films of the group IV dopants pre-deposited onto a diamond surface. We further demonstrate the flexibility of the technique, by implanting rare earth ions into the core of a single mode fibre. We conclusively show that the presented technique yields ultra-shallow dopant profiles localised to the top few nanometres of the target surface, and use it to achieve sub-50 nm positional accuracy. The method is applicable to non-planar substrates with complex geometries, and it is suitable for applications such as electronic and magnetic doping of atomically-thin materials and engineering of near-surface states of semiconductor devices.
One-pot biocatalytic route from cycloalkanes to α,ω‐dicarboxylic acids by designed Escherichia coli consortia
Authors: Wang Fei , Zhao Jing , Li Qian , Yang Jun , Li Renjie , Min Jian , Yu Xiaojuan , Zheng Gao-Wei , Yu Hui-Lei , Zhai Chao , Acevedo-Rocha Carlos G. , Ma Lixin , Li Aitao
Published: October 2020

Aliphatic α,ω‐dicarboxylic acids (DCAs) are a class of useful chemicals that are currently produced by energy-intensive, multistage chemical oxidations that are hazardous to the environment. Therefore, the development of environmentally friendly, safe, neutral routes to DCAs is important. We report an in vivo artificially designed biocatalytic cascade process for biotransformation of cycloalkanes to DCAs. To reduce protein expression burden and redox constraints caused by multi-enzyme expression in a single microbe, the biocatalytic pathway is divided into three basic Escherichia coli cell modules. The modules possess either redox-neutral or redox-regeneration systems and are combined to form E. coli consortia for use in biotransformations. The designed consortia of E. coli containing the modules efficiently convert cycloalkanes or cycloalkanols to DCAs without addition of exogenous coenzymes. Thus, this developed biocatalytic process provides a promising alternative to the current industrial process for manufacturing DCAs.
Manganese-mediated reductive functionalization of activated aliphatic acids and primary amines
Authors: Li Zhan , Wang Ke-Feng , Zhao Xin , Ti Huihui , Liu Xu-Ge , Wang Honggen
Published: October 2020

Alkyl carboxylic acids as well as primary amines are ubiquitous in all facets of biological science, pharmaceutical science, chemical science and materials science. By chemical conversion to redox-active esters (RAE) and Katritzky’s N-alkylpyridinium salts, respectively, alkyl carboxylic acids and primary amines serve as ideal starting materials to forge new connections. In this work, a Mn-mediated reductive decarboxylative/deaminative functionalization of activated aliphatic acids and primary amines is disclosed. A series of C-X (X = S, Se, Te, H, P) and C-C bonds are efficiently constructed under simple and mild reaction conditions. The protocol is applicable to the late-stage modification of some structurally complex natural products or drugs. Preliminary mechanistic studies suggest the involvement of radicals in the reaction pathway.
Frontier orbitals and quasiparticle energy levels in ionic liquids
Authors: Kahk Juhan Matthias , Kuusik Ivar , Kisand Vambola , Lovelock Kevin R. J. , Lischner Johannes
Published: October 2020

Ionic liquids play an important role in many technological applications and a detailed understanding of their frontier molecular orbitals is required to optimize interfacial barriers, reactivity and stability with respect to electron injection and removal. In this work, we calculate quasiparticle energy levels of ionic liquids using first-principles many-body perturbation theory within the GW approximation and compare our results to various mean-field approaches, including semilocal and hybrid density-functional theory and Hartree–Fock. We find that the mean-field results depend qualitatively and quantitatively on the treatment of exchange–correlation effects, while GW calculations produce results that are in excellent agreement with experimental photoelectron spectra of gas phase ion pairs and ionic liquids. These results establish the GW approach as a valuable tool for understanding the electronic structures of ionic liquids.
A unique clade of light-driven proton-pumping rhodopsins evolved in the cyanobacterial lineage
Authors: Hasegawa Masumi , Hosaka Toshiaki , Kojima Keiichi , Nishimura Yosuke , Nakajima Yu , Kimura-Someya Tomomi , Shirouzu Mikako , Sudo Yuki , Yoshizawa Susumu
Published: October 2020

Microbial rhodopsin is a photoreceptor protein found in various bacteria and archaea, and it is considered to be a light-utilization device unique to heterotrophs. Recent studies have shown that several cyanobacterial genomes also include genes that encode rhodopsins, indicating that these auxiliary light-utilizing proteins may have evolved within photoautotroph lineages. To explore this possibility, we performed a large-scale genomic survey to clarify the distribution of rhodopsin and its phylogeny. Our surveys revealed a novel rhodopsin clade, cyanorhodopsin (CyR), that is unique to cyanobacteria. Genomic analysis revealed that rhodopsin genes show a habitat-biased distribution in cyanobacterial taxa, and that the CyR clade is composed exclusively of non-marine cyanobacterial strains. Functional analysis using a heterologous expression system revealed that CyRs function as light-driven outward H+ pumps. Examination of the photochemical properties and crystal structure (2.65 Å resolution) of a representative CyR protein, N2098R from Calothrix sp. NIES-2098, revealed that the structure of the protein is very similar to that of other rhodopsins such as bacteriorhodopsin, but that its retinal configuration and spectroscopic characteristics (absorption maximum and photocycle) are distinct from those of bacteriorhodopsin. These results suggest that the CyR clade proteins evolved together with chlorophyll-based photosynthesis systems and may have been optimized for the cyanobacterial environment.
Quantitative proteomic comparison of myofibroblasts derived from bone marrow and cornea
Authors: Saikia Paramananda , Crabb Jack S. , Dibbin Luciana L. , Juszczak Madison J. , Willard Belinda , Jang Geeng-Fu , Shiju Thomas Michael , Crabb John W. , Wilson Steven E.
Published: October 2020

Myofibroblasts are fibroblastic cells that function in wound healing, tissue repair and fibrosis, and arise from bone marrow (BM)-derived fibrocytes and a variety of local progenitor cells. In the cornea, myofibroblasts are derived primarily from stromal keratocytes and from BM-derived fibrocytes after epithelial-stromal and endothelial-stromal injuries. Quantitative proteomic comparison of mature alpha-smooth muscle actin (α-SMA)+ myofibroblasts (verified by immunocytochemistry for vimentin, α-SMA, desmin, and vinculin) generated from rabbit corneal fibroblasts treated with transforming growth factor (TGF) beta-1 or generated directly from cultured BM treated with TGF beta-1 was pursued for insights into possible functional differences. Paired cornea-derived and BM-derived α-SMA+ myofibroblast primary cultures were generated from four New Zealand white rabbits and confirmed to be myofibroblasts by immunocytochemistry. Paired cornea- and BM-derived myofibroblast specimens from each rabbit were analyzed by LC MS/MS iTRAQ technology using an Orbitrap Fusion Lumos Tribrid mass spectrometer, the Mascot search engine, the weighted average quantification method and the UniProt rabbit and human databases. From 2329 proteins quantified with ≥ 2 unique peptides from ≥ 3 rabbits, a total of 673 differentially expressed (DE) proteins were identified. Bioinformatic analysis of DE proteins with Ingenuity Pathway Analysis implicate progenitor-dependent functional differences in myofibroblasts that could impact tissue development. Our results suggest BM-derived myofibroblasts may be more prone to the formation of excessive cellular and extracellular material that are characteristic of fibrosis.
The relationship between fleas and small mammals in households of the Western Yunnan Province, China
Authors: Yin Jia-Xiang , Cheng Xiao-Ou , Luo Yun-Yan , Zhao Qiu-Fang , Wei Zhao-Fei , Xu Dan-Dan , Wang Meng-Di , Zhou Yun , Wang Xiu-Fang , Liu Zheng-Xiang
Published: October 2020

The Yunnan province has one of the most serious outbreaks of the plague epidemic in China. Small mammals and fleas are risk factors for the occurrence of plague in commensal plague foci. Understanding the relationship between fleas and small mammals will help control fleas and prevent the onset of the plague. Four hundred and twenty-one small mammals, belonging to 9 species, were captured. Of these, 170 small mammals (40.4%) were found infested with fleas. A total of 992 parasitic fleas (including 5 species) were collected. The number of Leptopsylla segnis and Xenopsylla cheopis accounted for 91.03% (903/992). The final multiple hurdle negative binomial regression model showed that when compared with Rattus tanezumi, the probability of flea infestation with Mus musculus as well as other host species decreased by 58% and 99%, respectively, while the number of flea infestations of the other host species increased by 4.71 folds. The probability of flea prevalence in adult hosts increased by 74%, while the number of fleas decreased by 76%. The number of flea infestations in small male mammals increased by 62%. The number of fleas in small mammals weighing more than 59 g has been multiplied by about 4. R. tanezumi is the predominant species in households in the west Yunnan province, while L.segnis and X. cheopis were dominant parasitic fleas. There is a strong relationship between the abundance of fleas and the characteristics of small mammals (e.g. Species, age, sex, and body weight).
Rosettes integrity protects Plasmodium vivax of being phagocytized
Authors: Albrecht Letusa , Lopes Stefanie C. P. , da Silva Ana Beatriz Iung Enembreck , Barbosa Vanessa , Almeida Rodrigo P. , Siqueira André M. , Leite Juliana Almeida , Bittencourt Najara C. , dos Santos Hellen Geremias , Bourgard Catarina , Garcia Luiz Fernando Cardoso , Kayano Ana Carolina A. V. , Soares Irene S. , Russell Bruce , Rénia Laurent , Lacerda Marcus V. G. , Costa Fabio T. M.
Published: October 2020

Plasmodium vivax is the most prevalent cause of malaria outside of Africa. P. vivax biology and pathogenesis are still poorly understood. The role of one highly occurring phenotype in particular where infected reticulocytes cytoadhere to noninfected normocytes, forming rosettes, remains unknown. Here, using a range of ex vivo approaches, we showed that P. vivax rosetting rates were enhanced by plasma of infected patients and that total immunoglobulin M levels correlated with rosetting frequency. Moreover, rosetting rates were also correlated with parasitemia, IL-6 and IL-10 levels in infected patients. Transcriptomic analysis of peripheral leukocytes from P. vivax-infected patients with low or moderated rosetting rates identified differentially expressed genes related to human host phagocytosis pathway. In addition, phagocytosis assay showed that rosetting parasites were less phagocyted. Collectively, these results showed that rosette formation plays a role in host immune response by hampering leukocyte phagocytosis. Thus, these findings suggest that rosetting could be an effective P. vivax immune evasion strategy.
Demographic history and adaptive synonymous and nonsynonymous variants of nuclear genes in Rhododendron oldhamii (Ericaceae)
Authors: Hsieh Yi-Chiang , Chang Chung-Te , Chung Jeng-Der , Hwang Shih-Ying
Published: October 2020

Demographic events are important in shaping the population genetic structure and exon variation can play roles in adaptive divergence. Twelve nuclear genes were used to investigate the species-level phylogeography of Rhododendron oldhamii, test the difference in the average GC content of coding sites and of third codon positions with that of surrounding non-coding regions, and test exon variants associated with environmental variables. Spatial expansion was suggested by R2 index of the aligned intron sequences of all genes of the regional samples and sum of squared deviations statistic of the aligned intron sequences of all genes individually and of all genes of the regional and pooled samples. The level of genetic differentiation was significantly different between regional samples. Significantly lower and higher average GC contents across 94 sequences of the 12 genes at third codon positions of coding sequences than that of surrounding non-coding regions were found. We found seven exon variants associated strongly with environmental variables. Our results demonstrated spatial expansion of R. oldhamii in the late Pleistocene and the optimal third codon position could end in A or T rather than G or C as frequent alleles and could have been important for adaptive divergence in R. oldhamii.
Author Correction: Whole-genome and time-course dual RNA-Seq analyses reveal chronic pathogenicity-related gene dynamics in the ginseng rusty root rot pathogen Ilyonectria robusta
Authors: Guan Yiming , Chen Meili , Ma Yingying , Du Zhenglin , Yuan Na , Li Yu , Xiao Jingfa , Zhang Yayu
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Gallic acid nanoflower immobilized membrane with peroxidase-like activity for m-cresol detection
Authors: Dadi Seyma , Celik Cagla , Ocsoy Ismail
Published: October 2020

We report fabrication of new generation nanoflowers (NFs) using gallic acid (GA) and copper (II) ions (Cu2+) acted as an organic and inorganic component, respectively with effective peroxidase mimic activities in solution and on filter membrane. Unlike the typical protein NFs synthesis mechanism, gallic acid NFs (GA-NFs) was formed via coordination reaction between carboxyl groups of GA and Cu2+. The different morphologies of the GA-NFs were acquired based upon whether the carboxyl groups in gallic acid are active or not. The peroxidase mimic activity of the GA-NFs relied on the Fenton reaction in the presence of hydrogen peroxide (H2O2) was tested towards m-cresol as a function of concentration of the GA-NFs, m-cresol, H2O2 and reaction time. Under the optimized conditions, the oxidative coupling of m-cresol with 4-aminoantipyrine (4-AAP) was catalyzed by the GA-NFs dispersed in solution and adsorbed on filter paper to form an antipyrine dye and it was visually and spectrophotometrically recorded. The m-cresol with range of 0.05–0.5 mM was detected in 10 min and 15 min by using the GA-NFs in solution and on filter paper, respectively. We demonstrated that the NFs can be produced from non-protein molecules and GA-NFs can be used as a promising nanocatalyst for a variety of applications.
Paclitaxel exposure downregulates miR-522 expression and its downregulation induces paclitaxel resistance in ovarian cancer cells
Authors: Miyamoto Mayuko , Sawada Kenjiro , Nakamura Koji , Yoshimura Akihiko , Ishida Kyoso , Kobayashi Masaki , Shimizu Aasa , Yamamoto Misa , Kodama Michiko , Hashimoto Kae , Kimura Tadashi
Published: October 2020

Paclitaxel resistance is a critical challenge in ovarian cancer treatment. This study aimed to identify microRNAs (miRNAs) that modulate paclitaxel resistance for use as potential therapeutic targets in such settings. Paclitaxel-resistant cell lines were established using two ovarian cancer cell lines: SKOV3ip1 and HeyA8. The evaluation of miRNA polymerase chain reaction (PCR) arrays indicated that the expression of miR-522-3p was downregulated in paclitaxel-resistant cells. The restoration of miR-522-3p sensitized the resistant cells to paclitaxel, and its downregulation desensitized the parental cells. Using PCR arrays, we focused on E2F2, with the luciferase reporter assay revealing that it was a direct target for miR-522-3p. The paclitaxel-resistant cells showed stronger E2F2 expression than the parental cells, while E2F2 inhibition sensitized the resistant cells to paclitaxel. Forced E2F2 expression in the parental cells led to the acquisition of paclitaxel resistance, while miR-522-3p inhibited E2F2 expression and was associated with retinoblastoma protein phosphorylation attenuation, which resulted in G0/G1 arrest. The effects of miR-522-3p and E2F2 in ovarian cancer were examined using public databases, revealing that low miR-522-3p expression and high E2F2 expression were associated with significantly poorer overall survival. In conclusion, miR-522-3p attenuated the degree of paclitaxel resistance in vitro through the downregulation of E2F2; miR-522-3p supplementation may be a therapeutic target for paclitaxel-resistant ovarian cancer.
Ideal memcapacitors and meminductors are overunity devices
Authors: Jeltsema Dimitri , van der Schaft Arjan
Published: October 2020

It is rigorously proved that ideal memcapacitors and meminductors are not passive or cyclo-passive devices. Equivalently, this implies that there exist excitation profiles that allow to extract more energy from the device than it is supplied with; so that their energy conversion efficiency exceeds 100%. This means that ideal memcapacitors and meminductors violate the First Law of thermodynamics, and thus are non-physical as they constitute so-called overunity systems. An illustrative mechanical analogue is provided for which such an excitation profile is explicitly constructed. Hence ideal memcapacitors and meminductors are mathematical artefacts, and the question arises what this implies for the properties of non-ideal memcapacitors and meminductors (or, memcapacitive systems and meminductive systems), which do satisfy the First Law.
Multicompartment modeling of protein shedding kinetics during vascularized tumor growth
Authors: Machiraju Gautam B. , Mallick Parag , Frieboes Hermann B.
Published: October 2020

Identification of protein biomarkers for cancer diagnosis and prognosis remains a critical unmet clinical need. A major reason is that the dynamic relationship between proliferating and necrotic cell populations during vascularized tumor growth, and the associated extra- and intra-cellular protein outflux from these populations into blood circulation remains poorly understood. Complementary to experimental efforts, mathematical approaches have been employed to effectively simulate the kinetics of detectable surface proteins (e.g., CA-125) shed into the bloodstream. However, existing models can be difficult to tune and may be unable to capture the dynamics of non-extracellular proteins, such as those shed from necrotic and apoptosing cells. The models may also fail to account for intra-tumoral spatial and microenvironmental heterogeneity. We present a new multi-compartment model to simulate heterogeneously vascularized growing tumors and the corresponding protein outflux. Model parameters can be tuned from histology data, including relative vascular volume, mean vessel diameter, and distance from vasculature to necrotic tissue. The model enables evaluating the difference in shedding rates between extra- and non-extracellular proteins from viable and necrosing cells as a function of heterogeneous vascularization. Simulation results indicate that under certain conditions it is possible for non-extracellular proteins to have superior outflux relative to extracellular proteins. This work contributes towards the goal of cancer biomarker identification by enabling simulation of protein shedding kinetics based on tumor tissue-specific characteristics. Ultimately, we anticipate that models like the one introduced herein will enable examining origins and circulating dynamics of candidate biomarkers, thus facilitating marker selection for validation studies.
Metabolic profiling of Candida clinical isolates of different species and infection sources
Authors: Oliver Josidel Conceição , Laghi Luca , Parolin Carola , Foschi Claudio , Marangoni Antonella , Liberatore Andrea , Dias Amanda Latercia Tranches , Cricca Monica , Vitali Beatrice
Published: October 2020

Candida species are the most common cause of opportunistic fungal infections. Rapid identification and novel approaches for the characterization of these fungi are of great interest to improve the diagnosis and the knowledge about their pathogenic properties. This study aimed to characterize clinical isolates of Candida spp. by proteomics (MALDI-TOF MS) and metabolomics (1H-NMR), and to correlate their metabolic profiles with Candida species, source of infection and different virulence associated parameters. In particular, 49 Candida strains from different sources (blood, n = 15; vagina, n = 18; respiratory tract, n = 16), belonging mainly to C. albicans complex (61%), C. glabrata (20%) and C. parapsilosis (12%) species were used. Several extracellular and intracellular metabolites showed significantly different concentrations among isolates recovered from different sources of infection, as well as among different Candida species. These metabolites were mainly related to the glycolysis or gluconeogenesis, tricarboxylic acid cycle, nucleic acid synthesis and amino acid and lipid metabolism. Moreover, we found specific metabolic fingerprints associated with the ability to form biofilm, the antifungal resistance (i.e. caspofungin and fluconazole) and the production of secreted aspartyl proteinase. In conclusion, 1H-NMR-based metabolomics can be useful to deepen Candida spp. virulence and pathogenicity properties.
Characterization of the weathered basement rocks in the Dongping field from the Qaidam Basin, Western China: significance as gas reservoirs
Authors: Yang Wei , Wang Jiangong , Ma Feng , Zhang Yongshu , Bai Yadong , Sun Xiujian , Li Hongzhe , Zhang Jing , Wang Pu
Published: October 2020

Reservoir quality is a critical risk factor in basement reservoirs. Researches into basement reservoirs by petrographic analysis combined with X-ray diffraction, log identification, electron microscopy, field emission scanning electron microscopy, porosity and pulse-decay permeability and core analysis have provided insights into the characterization of the commonality, diversity and difference of the weathered basement rocks as gas reservoirs in the Dongping field. Geological structures, lithology and near-surface processes control the reservoir physical property together. From Wellblock Dp 3 to Wellblock Dp 17, the high uplift gradually transforms into the low slope area towards the center of basin, with the lithology changing as well, which results in different degrees of fracture development in the bedrock in different wellblocks. The basement lithologies are granite, granitic gneiss, and limestone with slate in Wellblock Dp3, Dp1 and Dp17, respectively. Though they all provide effective reservoir space for gas accumulation, the productivity of nature gas shows significant differences. Fractures are the main store space in the three wellblocks. The development of fractures gives rise to secondary porosity around them because of physical weathering and chemical dissolution, but they generate many inhomogeneous fractures and secondary solution pores, whether on the planar distribution or in vertical. In Wellblock Dp3, high angle fractures were generated under the action of structural stress mechanism, with a large number of secondary pores. The porosity is between 0.1 and 23.2%. In Wellblock Dp 1, low angle fractures were the main storage space, with plenty of solution pores mainly in melanocratic minerals. The porosity is between 0.1 and 18.8%. In Wellblock Dp 17, where short and dense fractures developed, the porosity is between 0.1 and 10.3%. The data indicate that the granite in the uplift in Wellblock Dp3 has better reservoir properties due to the stronger physical weathering and chemical dissolution. As the porosity gradually decreases towards the slope and low-lying area, the more favorable exploration area should be the uplift and slope area in the depression area. However, the effective caprock developed locally in Wellblock Dp3, which affected the gas accumulation. Meanwhile, the reservoirs’ petrophysical properties showed distintive variation with different depths in different wellblocks. High productivity layers are under the 200 m, 100 m and 200 m depths from the top of the basement rocks in Wellblock Dp 3, Wellblock Dp 1 and Wellblock Dp 17, respectively. This suggestion in this study will be of significance for guiding oil and gas exploration in front of the Altun Mountains.
MicroRNA-708 targeting ZNF549 regulates colon adenocarcinoma development through PI3K/AKt pathway
Authors: Zhao Zhidong , Qin Xianju
Published: October 2020

Colon adenocarcinoma (COAD) is the most common type of gastrointestinal cancer and is still the third leading cause of cancer-related mortality worldwide. Therefore, finding new and promising drugs to eradicate cancer may be a feasible method to treat COAD patients. Cys2-His2 zinc finger proteins (ZFPs) is one of the largest transcription factor family and many of them are highly involved in regulation of cell differentiation, proliferation, apoptosis, and neoplastic transformation. In this study, we identified a tumor-inhibiting factor, ZNF549, which expressed lowly in COAD tissues and COAD cell lines (HT29, HCT116, SW480, LoVo, and SW620). Overexpression of ZNF549 inhibit the ability of COAD cell proliferation and migration. On the contrary, decreasing the ZNF549 expression level promote the ability of COAD cell proliferation and migration. Through bioinformatics analysis, we found that ZNF549 was a potential target of hsa-miR-708-5p (miR-708-5p). Furthermore, we verified the possibility of miR-708-5p targeting the ZNF549 gene, and miR-708-5p inhibited the expression of ZNF549 by luciferase reporter assays, qRT-PCR and western blot assays. Moreover, the relationship between miR-708-5p and phosphatidylinositol 3-kinase/AKt (PI3K/AKt) signal pathway was elucidated. Overexpression and inhibition of miR-708-5p resulted in increased and decreased expression of p-AKt and p-PI3K in HCT116 cells, respectively. RT-qPCR and western blot assays results demonstrated that miR-708-5p regulated COAD cells development by promoting the process of Epithelial-mesenchymal transition (EMT) through PI3K/AKt signaling pathway. In summary, our findings demonstrated that ZNF549, the target gene of miR-708-5p, functions as a tumor suppressor to inhibit COAD cell lines proliferation and migration through regulate the PI3K/AKt signal pathway.
Inhibition of eNOS by L-NAME resulting in rat hind limb developmental defects through PFKFB3 mediated angiogenetic pathway
Authors: Wu Ziqiang , Yao Huan , Xu Huan , Wang Yang , Hu Wangming , Lou Guanhua , Zhang Lingling , Huang Cong , Jiang Cen , Zhou Shiyi , Shi Yaping , Chen Xiongbing , Yang Lan , Xu Yiming , Wang Yong
Published: October 2020

l-arginine/NOS/NO signaling pathway plays a critical role in controlling variety of vascular diseases. However, whether NOS inhibition by L-NAME suppresses late embryonic development is undefined. The aim of this study is to determine whether NOS inhibition by L-NAME is critical for late embryonic rat hind limb development. The pregnant rat at E13.5 administrated L-NAME by consecutive intraperitoneal injection. The embryos been harvested from E16.5 to E 20.5. Hematoxylin and Eosin Staining, Immunofluorescence and Immunohistochemistry performed to determine hind limb Vasculogenesis, HUVEC culture, Adenoviral PFKFB3 infection, Real time PCR and western blot were performed to determine whether l-arginine/NOS/NO pathway controlling late embryonic hind limb development through PFKFB3 mediated angiogenetic pathway. NOS inhibition by L-NAME resulting in late embryonic hind limb developmental defects characterized by severe hemorrhage. The in vivo studies showed that NOS inhibition strongly suppressed hind limb angiogenetic remodeling by impairing differentiation of endothelial cells and smooth muscle cells, and extracellular matrix synthesis. For underlie mechanism, our studies indicated that L-NAME treatment dramatically suppresses PFKFB3 expression in hematopoietic progenitor cells, tubulogenetic endothelial cells and smooth muscle cells. Knockdown of PFKFB3 dramatically inhibits the expression of angiogenetic genes, as well as tubulogenesis and extracellular matrix related genes. Taken together, our data in this study demonstrated that l-arginine-eNOS-NO pathway is important for rat hind limb development during late embryonic stage. This could be both a useful animal model and a promising therapeutic treatment for defects of late embryonic developmental hind limbs.