bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variation in Japanese Holstein cattle for EBL development
Authors: Inagaki Yasuko , Kobayashi Tomoko , Suda Yoshihito , Kusama Kazuya , Imakawa Kazuhiko 
Published: October 2020

Abstract

Background
Infection with bovine leukemia virus (BLV), the causative agent for enzootic bovine leukosis (EBL), is increasing in dairy farms of Japan. The tendency of tumor development following BLV infection in certain cow families and bull lines has previously been described. We therefore hypothesized the existence of a genetic component which differentiates cattle susceptibility to the disease.

Results
We analyzed routinely collected large-scale data including postmortem inspection data, which were combined with pedigree information and epidemiological data of BLV infection. A total of 6,022 postmortem inspection records of Holstein cattle, raised on 226 farms served by a regional abattoir over 10 years from 2004 to 2015, were analyzed for associations between sire information and EBL development. We then identified statistically the relative susceptibility to EBL development for the progeny of specific sires and paternal grandsires (PGSs). The heritability of EBL development was calculated as 0.19. Similarly, proviral loads (PVLs) of progeny from identified sires and PGSs were analyzed, but no significant differences were found.

Conclusions
These observations suggest that because EBL development in our Holstein population is, at least in part, influenced by genetic factors independent of PVL levels, genetic improvement for lower incidence of EBL development in cattle notwithstanding BLV infection is possible.
Social capital, policy fairness, and subjective life satisfaction of earthquake survivors in Wenchuan, China: a longitudinal study based on post-earthquake survey data
Authors: Wang Dianxi , Li Danyang 
Published: October 2020

AbstractBackgroundExisting research has rarely examined an earthquake’s sustained impact and the trajectory of the earthquake survivors’ life satisfaction over time. This study aims to analyze longitudinal changes in life satisfaction of Wenchuan earthquake survivors and the impact of social capital and government relief policy.MethodsThis research applied a hierarchical linear model to longitudinal survey data collected after the earthquake. The survey was divided into three waves and was collected from Deyang City and Mianyang City of Sichuan Province. A random sampling method was used; a sample of 225 participants had valid responses over three waves of the survey.ResultsThis study found that a survivor’s social capital and the perception of the fairness of government relief policy have a significant effect on the trajectory of life satisfaction post-disaster. First, the initial life satisfaction of those with high social capital was significantly higher than of those with low social capital, whilst survivors with high social capital had a lower rate of change in life satisfaction. Second, one year after the earthquake, those who felt government policy was unfair had a lower life satisfaction than those who felt it was fair. However, from the first year to the fourth year after the disaster, survivors who believed that the government policy was unfair experienced a higher rate of change in life satisfaction than those who did not. Third, the fairness of government relief policy moderates the relationship between survivors’ social capital and changes in life satisfaction. A fair policy of relief can reduce the negative impact of the lack of individual social capital on life satisfaction.ConclusionsSurvivors reconstruct life satisfaction through their social network and the perception of the fairness of the government’s post-disaster relief policy. Therefore, to promote the improvement of life satisfaction of survivors, it is necessary to cultivate social capital and ensure fairness of the relief policy.
Switching of vascular cells towards atherogenesis, and other factors contributing to atherosclerosis: a systematic review
Authors: Shafi Ovais 
Published: October 2020

AbstractBackgroundOnset, development and progression of atherosclerosis are complex multistep processes. Many aspects of atherogenesis are not yet properly known. This study investigates the changes in vasculature that contribute to switching of vascular cells towards atherogenesis, focusing mainly on ageing.MethodsDatabases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving atherogenesis, vascular homeostasis, aging, gene expression, signaling pathways, angiogenesis, vascular development, vascular cell differentiation and maintenance, vascular stem cells, endothelial and vascular smooth muscle cells.ResultsAtherogenesis is a complex multistep process that unfolds in a sequence. It is caused by alterations in: epigenetics and genetics, signaling pathways, cell circuitry, genome stability, heterotypic interactions between multiple cell types and pathologic alterations in vascular microenvironment. Such alterations involve pathological changes in: Shh, Wnt, NOTCH signaling pathways, TGF beta, VEGF, FGF, IGF 1, HGF, AKT/PI3K/ mTOR pathways, EGF, FOXO, CREB, PTEN, several apoptotic pathways, ET – 1, NF-κB, TNF alpha, angiopoietin, EGFR, Bcl − 2, NGF, BDNF, neurotrophins, growth factors, several signaling proteins, MAPK, IFN, TFs, NOs, serum cholesterol, LDL, ephrin, its receptor pathway, HoxA5, Klf3, Klf4, BMPs, TGFs and others.This disruption in vascular homeostasis at cellular, genetic and epigenetic level is involved in switching of the vascular cells towards atherogenesis. All these factors working in pathologic manner, contribute to the development and progression of atherosclerosis.ConclusionThe development of atherosclerosis involves the switching of gene expression towards pro-atherogenic genes. This happens because of pathologic alterations in vascular homeostasis. When pathologic alterations in epigenetics, genetics, regulatory genes, microenvironment and vascular cell biology accumulate beyond a specific threshold, then the disease begins to express itself phenotypically. The process of biological ageing is one of the most significant factors in this aspect as it is also involved in the decline in homeostasis, maintenance and integrity.The process of atherogenesis unfolds sequentially (step by step) in an interconnected loop of pathologic changes in vascular biology. Such changes are involved in ‘switching’ of vascular cells towards atherosclerosis.
Mitochondrial DNA drives noncanonical inflammation activation via cGAS–STING signaling pathway in retinal microvascular endothelial cells
Authors: Guo Yue , Gu Ruiping , Gan Dekang , Hu Fangyuan , Li Gang , Xu Gezhi 
Published: October 2020

Abstract

Background
Pathological stimuli cause mitochondrial damage and leakage of mitochondrial DNA (mtDNA) into the cytosol, as demonstrated in many cell types. The cytosolic mtDNA then drives the activation of noninfectious inflammation. Retinal microvascular endothelial cells (RMECs) play an important role in the inner endothelial blood–retinal barrier (BRB). RMEC dysfunction frequently occurs in posterior-segment eye diseases, causing loss of vision. In this study, we investigated the involvement of cytosolic mtDNA in noninfectious immune inflammation in RMECs under pathological stimuli.

Methods
RMECs were stimulated with 100 ng/ml lipopolysaccharide (LPS), 200 μM hydrogen peroxide (H2O2), or 25 mM d-glucose. After 24 h, immunofluorescent staining was used to detect the opening of the mitochondrial permeability transition pore (MPTP). Cytosolic mtDNA was detected with immunofluorescent staining and PCR after stimulation. mtDNA was then isolated and used to transfect RMECs in vitro, and the protein levels of cGAS were evaluated with western blotting. Real-time PCR was used to examine cGAS mRNA expression levels at different time points after mtDNA stimulation. The activation of STING was detected with immunofluorescent staining 6 h after mtDNA stimulation. Western blotting was used to determine the expression of STING and IFNβ, the phosphorylation status of TBK1, IRF3, and nuclear factor-κB (NF-κB) P65, and the nuclear translocation of IRF3 and NF-κB P65 at 0, 3, 6, 12, and 24 h. The mRNA expression of proinflammatory cytokines CCL4, CXCL10, and IFNB1, and transcription factor IRF1 were determined with real-time PCR, together with the concentrations of intercellular adhesion molecule 1 (ICAM-1) mRNA.

Results
Pathological stimuli caused mtDNA to leak into the cytosol by opening the MPTP in RMECs after 24 h. Cytosolic mtDNA regulated the expression of cGAS and the distribution of STING in RMECs. It promoted ICAM-1, STING and IFNβ expression, TBK1, IRF3, and NF-κB phosphorylation and the nuclear translocation in RMECs at 12 and 24 h after its transfection. The mRNAs of proinflammatory cytokines CCL4, CXCL10, and IFNB1, and transcription factor IRF1 were significantly elevated at 12 and 24 h after mtDNA stimulation.

Conclusions
Pathological stimulation induces mtDNA escape into the cytosol of RMECs. This cytoplasmic mtDNA is recognized by the DNA sensor cGAS, increasing the expression of inflammatory cytokines through the STING–TBK1 signaling pathway.
Targeting connexin 43 provides anti-inflammatory effects after intracerebral hemorrhage injury by regulating YAP signaling
Authors: Yu Hailong , Cao Xiang , Li Wei , Liu Pinyi , Zhao Yuanyuan , Song Lilong , Chen Jian , Chen Beilei , Yu Wenkui , Xu Yun 
Published: October 2020

Abstract

Background
In the central nervous system (CNS), connexin 43 (Cx43) is mainly expressed in astrocytes and regulates astrocytic network homeostasis. Similar to Cx43 overexpression, abnormal excessive opening of Cx43 hemichannels (Cx43Hcs) on reactive astrocytes aggravates the inflammatory response and cell death in CNS pathologies. However, the role of excessive Cx43Hc opening in intracerebral hemorrhage (ICH) injury is not clear.

Methods
Hemin stimulation in primary cells and collagenase IV injection in C57BL/6J (B6) mice were used as ICH models in vitro and in vivo. After ICH injury, the Cx43 mimetic peptide Gap19 was used for treatment. Ethidium bromide (EtBr) uptake assays were used to measure the opening of Cx43Hcs. Western blotting and immunofluorescence were used to measure protein expression. qRT-PCR and ELISA were used to determine the levels of cytokines. Coimmunoprecipitation (Co-IP) and the Duolink in situ proximity ligation assay (PLA) were applied to measure the association between proteins.

Results
In this study, Cx43 expression upregulation and excessive Cx43Hc opening was observed in mice after ICH injury. Delayed treatment with Gap19 significantly alleviated hematoma volume and neurological deficits after ICH injury. In addition, Gap19 decreased inflammatory cytokine levels in the tissue surrounding the hematoma and decreased reactive astrogliosis after ICH injury in vitro and in vivo. Intriguingly, Cx43 transcriptional activity and expression in astrocytes were significantly increased after hemin stimulation in culture. However, Gap19 treatment downregulated astrocytic Cx43 expression through the ubiquitin-proteasome pathway without affecting Cx43 transcription. Additionally, our data showed that Gap19 increased Yes-associated protein (YAP) nuclear translocation. This subsequently upregulated SOCS1 and SOCS3 expression and then inhibited the TLR4-NFκB and JAK2-STAT3 pathways in hemin-stimulated astrocytes. Finally, the YAP inhibitor, verteporfin (VP), reversed the anti-inflammatory effect of Gap19 in vitro and almost completely blocked its protective effects in vivo after ICH injury.

Conclusions
This study provides new insight into potential treatment strategies for ICH injury involving astroglial Cx43 and Cx43Hcs. Suppression of abnormal astroglial Cx43 expression and Cx43Hc opening by Gap19 has anti-inflammatory and neuroprotective effects after ICH injury.
Circ_0001421 facilitates glycolysis and lung cancer development by regulating miR-4677-3p/CDCA3
Authors: Zhang Koudong , Hu Hang , Xu Juan , Qiu Limin , Chen Haitao , Jiang Xingzhi , Jiang Yongqian 
Published: October 2020

Abstract

Background
Lung cancer (LC) is a malignant tumor originating in the bronchial mucosa or gland of the lung. Circular RNAs (circRNAs) are proved to be key regulators of tumor progression. However, the regulatory effect of circ_0001421 on lung cancer tumorigenesis remains unclear.

Methods
The expression levels of circ_0001421, microRNA-4677-3p (miR-4677-3p) and cell division cycle associated 3 (CDCA3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methyl thiazolyl tetrazolium (MTT), Transwell and Tumor formation assays were performed to explore the role of circ_0001421 in LC. Glucose consumption and lactate production were examined by a Glucose assay kit and a Lactic Acid assay kit. Western blot was utilized to examine the protein levels of Hexokinase 2 (HK2) and CDCA3. The interaction between miR-4677-3p and circ_0001421 or CDCA3 was confirmed by dual-luciferase reporter assay.

Results
Circ_0001421 was increased in LC tissues and cells, and knockdown of circ_0001421 repressed cell proliferation, migration, invasion and glycolysis in vitro. Meanwhile, circ_0001421 knockdown inhibited LC tumor growth in vivo. Mechanistically, circ_0001421 could bind to miR-4677-3p, and CDCA3 was a target of miR-4677-3p. Rescue assays manifested that silencing miR-4677-3p or CDCA3 overexpression reversed circ_0001421 knockdown-mediated suppression on cell proliferation, migration, invasion and glycolysis in LC cells.

Conclusion
Circ_0001421 promoted cell proliferation, migration, invasion and glycolysis in LC by regulating the miR-4677-3p/CDCA3 axis, which providing a new mechanism for LC tumor progression.
Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection
Authors: Caruffo Mario , Mandakovic Dinka , Mejías Madelaine , Chávez-Báez Ignacio , Salgado Pablo , Ortiz Daniela , Montt Liliana , Pérez-Valenzuela Javiera , Vera-Tamargo Francisca , Yánez José Manuel , Wacyk Jurij , Pulgar Rodrigo 
Published: October 2020

Abstract
Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is a severe bacterial disease in the Chilean salmon farming industry. Vaccines and antibiotics are the current strategies to fight SRS; however, the high frequency of new epizootic events confirms the need to develop new strategies to combat this disease. An innovative opportunity is perturbing the host pathways used by the microorganisms to replicate inside host cells through host-directed antimicrobial drugs (HDAD). Iron is a critical nutrient for P. salmonis infection; hence, the use of iron-chelators becomes an excellent alternative to be used as HDAD. The aim of this work was to use the iron chelator Deferiprone (DFP) as HDAD to treat SRS. Here, we describe the protective effect of the iron chelator DFP over P. salmonis infections at non-antibiotic concentrations, in bacterial challenges both in vitro and in vivo. At the cellular level, our results indicate that DFP reduced the intracellular iron content by 33.1% and P. salmonis relative load during bacterial infections by 78%. These findings were recapitulated in fish, where DFP reduced the mortality of rainbow trout challenged with P. salmonis in 34.9% compared to the non-treated group. This is the first report of the protective capacity of an iron chelator against infection in fish, becoming a potential effective host-directed therapy for SRS and other animals against ferrophilic pathogens.
Assessment of serum macrophage migration inhibitory factor (MIF), adiponectin, and other adipokines as potential markers of proteinuria and renal dysfunction in lupus nephritis: a cross-sectional study
Authors: Gamez-Nava Jorge Ivan , Diaz-Rizo Valeria , Perez-Guerrero Edsaul Emilio , Muñoz-Valle Jose Francisco , Saldaña-Cruz Ana Miriam , Fajardo-Robledo Nicte Selene , Jacobo-Cuevas Heriberto , Nava-Valdivia Cesar Arturo , Alcaraz-Lopez Miriam Fabiola , Trujillo Xochitl , Huerta Miguel , Cardona-Muñoz Ernesto German , Gonzalez-Lopez Laura 
Published: October 2020

AbstractBackgroundTo date, the association of serum macrophage migration inhibitory factor (MIF) and serum adipokines with lupus nephritis is controversial.ObjectiveTo assess the utility of serum MIF, leptin, adiponectin and resistin levels as markers of proteinuria and renal dysfunction in lupus nephritis.MethodsCross-sectional study including 196 systemic lupus erythematosus (SLE) patients and 52 healthy controls (HCs). Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal SLE involvement was investigated by renal-SLEDAI. MIF, adiponectin, leptin and resistin levels were quantified by ELISA. We assessed the correlations of quantitative variables by Spearman correlation (rs). Multivariable linear regression adjusted the variables associated with the severity of proteinuria.ResultsSLE patients had higher MIF (p = 0.02) and adiponectin (p < 0.001) than HCs. Patients with renal SLE involvement (n = 43) had higher adiponectin (19.0 vs 13.3 μg/mL,p = 0.002) and resistin (10.7 vs 8.9 ng/mL,p = 0.01) than patients with non-renal SLE (n = 153). Proteinuria correlated with high adiponectin (rs = 0.19,p < 0.009) and resistin (rs = 0.26,p < 0.001). MIF (rs = 0.27,p = 0.04). Resistin correlated with increased creatinine (rs = 0.18,p = 0.02). High renal-SLEDAI correlated with adiponectin (rs = 0.21,p = 0.004). Multiple linear regression showed that elevated adiponectin (p = 0.02), younger age (p = 0.04) and low MIF (p = 0.02) were associated with the severity of proteinuria. Low MIF and high adiponectin levels interacted to explain the association with the severity of proteinuria (R2 = 0.41).ConclusionsHigh adiponectin combined with low MIF concentrations int+eract to explain the severity of proteinuria in renal SLE. These findings highlight the relevance of adiponectin, resistin and MIF as markers of LN.
Targeted deletions of complement lectin pathway genes improve outcome in traumatic brain injury, with MASP-2 playing a major role
Authors: Mercurio D. , Oggioni M. , Fumagalli S. , Lynch N. J. , Roscher S. , Minuta D. , Perego C. , Ippati S. , Wallis R. , Schwaeble W. J. , De Simoni M.-G. 
Published: October 2020

Abstract
The lectin pathway (LP) of complement activation is believed to contribute to brain inflammation. The study aims to identify the key components of the LP contributing to TBI outcome as possible novel pharmacological targets. We compared the long-term neurological deficits and neuropathology of wild-type mice (WT) to that of mice carrying gene deletions of key LP components after experimental TBI. WT or MASP-2 (Masp2−/−), ficolin-A (Fcna−/−), CL-11 (Colec11−/−), MASP-1/3 (Masp1−/−), MBL-C (Mbl2−/−), MBL-A (Mbl1−/−) or MBL−/− (Mbl1−/−/Mbl2−/−) deficient male C57BL/6J mice were used. Mice underwent sham surgery or TBI by controlled cortical impact. The sensorimotor response was evaluated by neuroscore and beam walk tests weekly for 4 weeks. To obtain a comparative analysis of the functional outcome each transgenic line was rated according to a health score calculated on sensorimotor performance. For selected genotypes, brains were harvested 6 weeks after injury for histopathological analysis. MASP-2−/−, MBL−/− and FCN-A−/− mice had better outcome scores compared to WT. Of these, MASP-2−/− mice had the best recovery after TBI, showing reduced sensorimotor deficits (by 33% at 3 weeks and by 36% at 4 weeks). They also showed higher neuronal density in the lesioned cortex with a 31.5% increase compared to WT. Measurement of LP functional activity in plasma from MASP-2−/− mice revealed the absence of LP functional activity using a C4b deposition assay. The LP critically contributes to the post-traumatic inflammatory pathology following TBI with the highest degree of protection achieved through the absence of the LP key enzyme MASP-2, underlining a therapeutic utility of MASP-2 targeting in TBI.
Wayfinding: How Ecological Perspectives of Navigating Dynamic Environments Can Enrich Our Understanding of the Learner and the Learning Process in Sport
Authors: Woods Carl T. , Rudd James , Robertson Sam , Davids Keith 
Published: October 2020

AbstractWayfinding is the process of embarking upon a purposeful, intentional, and self-regulated journey that takes an individual from an intended region in one landscape to another. This process is facilitated through an individual’s capacity to utilise temporally structured, functional actions embedded within a particular environmental niche. Thus, individuals learn of their performance landscapes by experiencing them through interactions, detecting and exploiting its many features to ‘find their way’. In this opinion piece, we argue that these ecological and anthropological conceptualisations of human navigation can, metaphorically, deepen our understanding of the learner and the learning process in sport, viewed through the lens of ecological dynamics. Specifically, we consider sports practitioners as (learning) landscape designers, and learners as wayfinders; individuals who learn to skilfully self-regulate through uncharted fields (composed of emergent problems) within performance landscapes through a deeply embodied and embedded perception-action coupling. We contend that, through this re-configuration of the learner and the learning process in sport, practitioners may better enact learning designs that afford learners exploratory freedoms, learning to perceive and utilise available opportunities for action to skilfully navigate through emergent performance-related problems. We conclude the paper by offering two practical examples in which practitioners have designed practice landscapes that situate learners as wayfinders and the learning process in sport as wayfinding.
‘Knowing as we go’: a Hunter-Gatherer Behavioural Model to Guide Innovation in Sport Science
Authors: Woods Carl T. , Robertson Sam , Rudd James , Araújo Duarte , Davids Keith 
Published: October 2020

AbstractWhere do novel and innovative ideas in sport science come from? How do researchers and practitioners collectively explore the dynamic landscape of inquiry, problem, solution and application? How do they learn to skilfully navigate from current place and practice toward the next idea located beyond their current vantage point? These questions are not just of philosophical value but are important for understanding how to provide high-quality support for athletes and sport participants at all levels of expertise and performance. Grounded in concepts from social anthropology, and theoretically positioned within an ecological dynamics framework, this opinion piece introduces a hunter-gatherer model of human behaviour based on wayfinding, situating it as a conceptual guide for implementing innovations in sport science. Here, we contend that the embedded knowledge of a landscape that guides a successful hunting and gathering party is germane to the pragmatic abduction needed to promote innovation in sport performance, leading to the inquisition of new questions and ways of resolving performance-preparation challenges. More specifically, exemplified through its transdisciplinarity, we propose that tohunt‘new ideas’ andgathertranslatable knowledge, sport science researchers and practitioners need to wayfind through uncharted regions located in new performance landscapes. It is through this process of navigation where individuals will deepen, enrich and grow current knowledge, ‘taking home’ new ideas as they find their way.