bluuebunny/crossref_metadata_2025_split huggingface dataset:
TET2 modulates proliferation and migration of vascular smooth muscle cells via LEMD2/NOX1/NOX4 signaling pathway
Authors: Xie Y L , Qin Y C , Li A H , Yan Z Q , Qiao Z D ,   Shanghai Jiaotong University
Published: October 2021

Abstract

Background
Ten-eleven translocation 2 (TET2), a widely reported DNA hydroxymethylation enzyme, is involved in active DNA demethylation. TET2 may play an critical role in numerous cellular processes by regulating the level of DNA hydroxymethylation and altering gene expression. TET2 expression was proved to be down-regulated in aorta of spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto rats (WKY) as well as in VSMCs subjected to15% cyclic stretch compared to 5% cyclic stretch. However, whether TET2 regulates vascular smooth muscle cells (VSMCs) proliferation and migration and its underlying mechanisms remains unclear.

Purpose
The present study aims to investigate whether TET2 affects VSMC proliferation and migration and its possible underlying mechanisms.

Methods
TET2 knockdown rat VSMC was established using crispr/Cas9 method. Different expression genes were identified by next generation sequencing (NGS) between TET2 knockdown VSMC and control VSMCs while differentially hydroxymethylated promoter region were identified by hydroxymethylcytosine DNA immunoprecipitation (hMeDIP) sequencing. Expression of mRNA and proteins was detected by qRT-PCR and western blot respectively. The proliferation and migration of VSMCs were assessed by EdU assay, flowcytometry assay, and wound healing assay. LEMD2 overexpression and knockdown stable VSMC lines were established through Lentiviral infection.

Results
The EdU assay and wound healing assay show that knockdown of TET2 enhanced proliferation and migration of VSMCs. NGS identified 123 differentially expressed genes (91 up-regulated and 32 down-regulated) between TET2 knockdown VSMCs and control VSMCs while hMeDIP sequencing identified 166 genes with differentially hydroxymethylated promoter region (68 up-regulated and 98 down-regulated) between TET2 knockdown VSMCs and control VSMCs. Through comparing these sequencing results, we identified a gene named as LEMD2 simultaneously present in both sequencing results. Expression of LEMD2 at mRNA and protein level was significantly increased in TET2 knockdown VSMCs compared to control VSMCs. Then we successfully established LEMD2 overexpression and knockdown stable VSMC lines and found that overexpression of LEMD2 enhanced proliferation and migration of VSMCs while knockdown of LEMD2 inhibited proliferation and migration of VSMCs. Furthermore, overexpression of LEMD2 up-regulated the expression of NOX1 and down-regulated the expression of NOX4 while knockdown of LEMD2 show the opposite effect.

Conclusion
The present study confirmed that TET2 modulates VSMC proliferation and migration via LEMD2/NOX1/NOX4. The ROS level may be involved in VSMC proliferation and migration.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National natural science foundation of China
Omega-3 fatty acids differentially reduced expression of neutrophil degranulation-associated proteins in endothelial cells during IL-6 exposure
Authors: Sherratt S C R , Libby P , Bhatt D L , Dawoud H , Malinski T , Mason R P 
Published: October 2021

Abstract

Background
Neutrophil degranulation contributes to atherogenesis and tissue injury. Mixed omega-3 fatty acid (n3-FA) formulations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have failed to reduce CV events compared to EPA only (REDUCE-IT), but the mechanisms are not understood.

Purpose
The purpose of this study was to compare the effects of EPA and DHA on expression of proteins linked to neutrophil degranulation in the vascular endothelium in vitro.

Methods
Human umbilical vein endothelial cells (HUVECs) were pretreated with EPA or DHA at equimolar levels (10 μM) for 2 h, then challenged with IL-6 at 12 ng/ml for 24 h. Proteomic analysis was performed using LC/MS to measure relative protein expression. Only significant (p&lt;0.05) changes between treatment groups &gt;1-fold were analyzed.

Results
In the Reactome “neutrophil degranulation” pathway, EPA and DHA downregulated 27 and 14 proteins, respectively, (p=9.97E-9 and 5.30E-4, respectively) relative to IL-6 alone. There were 12 protein changes common to both n3-FAs, including heme oxygenase-2 and ferritin light chain. EPA downregulated 15 proteins unlike DHA, including peroxiredoxin-6 and mitogen-activated protein kinase-1 (MAPK1). A combined 21 proteins downregulated by EPA and DHA versus IL-6 were upregulated by IL-6 alone relative to vehicle. EPA also increased expression of Rho-associated protein kinase-1 (ROCK-1), a protein downregulated by IL-6 alone and unaffected by DHA.

Conclusions
EPA and DHA differentially modulated expression of proteins linked to neutrophil degranulation. The distinct effects of EPA on protein expression may contribute to reduced inflammation in vascular injury compared to DHA.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Amarin Pharma Inc., Elucida Research
Prospective analysis of inflammatory response markers, endothelial dysfunction and hemostasis parameters in COVID-19 associated pneumonia patients with and without type 2 diabetes mellitus
Authors: Petelina T , Musikhina N , Avdeeva K , Leonovich S , Gapon L , Gorbatenko E , Sharoyan Y , Zueva E , Yaroslavskaya E , Gultyaeva E , Kalyuzhnaya E , Shcherbinina A 
Published: October 2021

Abstract

Background
The coronavirus disease 2019 (COVID-19) has spread around the world with high cardiovascular complications and mortality. Patients with heart pathology and diabetes mellitus were at greatest risk. An accurate and timely laboratory diagnosis is a vital step to help manage cardiovascular disease during this pandemic.

Purpose
To conduct a prospective analysis of complete blood count parameters, inflammatory response, endothelial dysfunction of arterial wall and hemostasis in groups of patients undergoing COVID-19 associated pneumonia with and without type 2 diabetes mellitus (DM2); to highlight indicators of long-term adverse cardiovascular events.

Methods
The study was carried out within register on one-year cardiac follow-up of patients after COVID-19-associated pneumonia. Patients (n=380) were identified in the period from April to July 2020 according to the data of medical information system of monoinfectious hospital. At the moment, data of the first 65 patients with cardiovascular pathology are obtained. Group 1 included 53 patients without DM2 (mean age 47.83±15.86 years), group 2 consisted of 12 patients with DM2 (61.71±9.12 years). Baseline parameters of complete blood count, biochemistry and hemostasis were assessed on the day of hospitalization. In-depth analysis of laboratory parameters was carried out in 3 months.

Results
In group 1 significant decrease of coagulogram parameters: INR (p=0.004), fibrinogen, APTT, thrombocrit, large platelets level (p&lt;0.0001), CRP level, liver enzymes (p&lt;0.0001), leukocytes (p=0.015), erythrocytes (p=0.006) and increase in hematocrit (p&lt;0.0001) were registered in 3 months compared to baseline data. In group 2 positive dynamics of CRP (p=0.018), platelets (p=0046), APTT (p=0.043) and erythrocytes (p=0.028) were revealed, while CRP concentration remained higher than reference values in 3 months. In group 2 in-depth analysis of biomarkers revealed values exceeding normal levels: hs-CRP (4.72±3.33 mg/L), homocysteine (13.17±7.95 μmol/L), myeloperoxidase (47.6±38.51), NT-proBNP (154.56±127.30 mg/ml), P-selectin (141.29±124.71) TgFb1 (6549.86±1987.87 pg/ml). Correlation analysis detected positive association of homocysteine level with platelets level (p=0.002. R=0.998), myeloperoxidase with fibrinogen (p=0.012. R=0.865).

Conclusion
Three months after COVID-19 elevated levels of inflammatory markers (CRP, hs-CRP, homocysteine), endothelial dysfunction and thrombophilia (large platelets, P-selectin, TgFb1) are indicators of prolonged arterial inflammatory syndrome and increased predisposition to coagulopathy with thrombosis determining a very high risk of developing adverse cardiovascular events in patients with DM2.

Funding Acknowledgement
Type of funding sources: None.
A highly contiguous nuclear genome assembly of the mandarinfish Synchiropus splendidus (Syngnathiformes: Callionymidae)
Authors: Stervander Martin , Cresko William A 
Published: October 2021

Abstract
The fish order Syngnathiformes has been referred to as a collection of misfit fishes, comprising commercially important fish such as red mullets as well as the highly diverse seahorses, pipefishes, and seadragons—the well-known family Syngnathidae, with their unique adaptations including male pregnancy. Another ornate member of this order is the species mandarinfish. No less than two types of chromatophores have been discovered in the spectacularly colored mandarinfish: the cyanophore (producing blue color) and the dichromatic cyano-erythrophore (producing blue and red). The phylogenetic position of mandarinfish in Syngnathiformes, and their promise of additional genetic discoveries beyond the chromatophores, made mandarinfish an appealing target for whole-genome sequencing. We used linked sequences to create synthetic long reads, producing a highly contiguous genome assembly for the mandarinfish. The genome assembly comprises 483 Mbp (longest scaffold 29 Mbp), has an N50 of 12 Mbp, and an L50 of 14 scaffolds. The assembly completeness is also high, with 92.6% complete, 4.4% fragmented, and 2.9% missing out of 4584 BUSCO genes found in ray-finned fishes. Outside the family Syngnathidae, the mandarinfish represents one of the most contiguous syngnathiform genome assemblies to date. The mandarinfish genomic resource will likely serve as a high-quality outgroup to syngnathid fish, and furthermore for research on the genomic underpinnings of the evolution of novel pigmentation.
uS5/Rps2 residues at the 40S ribosome entry channel enhance initiation at suboptimal start codons in vivo
Authors: Dong Jinsheng , Hinnebusch Alan G 
Published: October 2021

Abstract
The eukaryotic 43S pre-initiation complex (PIC) containing Met-tRNAiMet in a ternary complex (TC) with eIF2-GTP scans the mRNA leader for an AUG codon in favorable “Kozak” context. AUG recognition triggers rearrangement of the PIC from an open conformation to a closed state with more tightly bound Met-tRNAiMet. Yeast ribosomal protein uS5/Rps2 is located at the mRNA entry channel of the 40S subunit in the vicinity of mRNA nucleotides downstream from the AUG codon or rRNA residues that communicate with the decoding center, but its participation in start codon recognition was unknown. We found that nonlethal substitutions of conserved Rps2 residues in the entry channel reduce bulk translation initiation and increase discrimination against poor initiation codons. A subset of these substitutions suppress initiation at near-cognate UUG start codons in a yeast mutant with elevated UUG initiation, and also increase discrimination against AUG codons in suboptimal Kozak context, thus resembling previously described substitutions in uS3/Rps3 at the 40S entry channel or initiation factors eIF1 and eIF1A. In contrast, other Rps2 substitutions selectively discriminate against either near-cognate UUG codons, or poor Kozak context of an AUG or UUG start codon. These findings suggest that different Rps2 residues are involved in distinct mechanisms involved in discriminating against different features of poor initiation sites in vivo.
Fast mass lumped multiscale wave propagation modelling
Authors: Geevers Sjoerd , Maier Roland 
Published: October 2021

Abstract
In this paper we investigate the use of a mass lumped fully explicit time-stepping scheme for the discretization of the wave equation with underlying material parameters that vary at arbitrarily fine scales. We combine the leapfrog scheme for the temporal discretization with the multiscale technique known as localized orthogonal decomposition (LOD) for the spatial discretization. To speed up the method and to make it fully explicit, a special mass lumping approach is introduced that relies on an appropriate interpolation operator. This operator is also employed in the construction of the LOD and is a key feature of the approach. We prove that the method converges with second order in the energy norm, with a leading constant that does not depend on the scales at which the material parameters vary. We also illustrate the performance of the mass lumped method in a set of numerical experiments.
Severe Acute Respiratory Syndrome Coronavirus 2 Infection Induces Greater T-Cell Responses Compared to Vaccination in Solid Organ Transplant Recipients
Authors: Ferreira Victor H , Marinelli Tina , Ierullo Matthew , Ku Terrance , Hall Victoria G , Majchrzak-Kita Beata , Kulasingam Vathany , Humar Atul , Kumar Deepali 
Published: October 2021

Abstract
T-cell immunity associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination in solid organ transplant recipients (SOTRs) is poorly understood. To address this, we measured T-cell responses in 50 SOTRs with prior SARS-CoV-2 infection. The majority of patients mounted SARS-CoV-2–specific CD4+ T-cell responses against spike (S), nucleocapsid, and membrane proteins; CD8+ T-cell responses were generated to a lesser extent. CD4+ T-cell responses correlated with antibody levels. Severity of disease and mycophenolate dose were moderately associated with lower proportions of antigen-specific T cells. Relative to nontransplant controls, SOTRs had perturbations in both total and antigen-specific T cells, including higher frequencies of total PD-1+ CD4+ T cells. Vaccinated SOTRs (n = 55) mounted significantly lower proportions of S-specific polyfunctional CD4+ T cells after 2 doses, relative to unvaccinated SOTRs with prior coronavirus disease 2019. Together, these results suggest that SOTRs generate robust T-cell responses following natural infection that correlate with disease severity but generate comparatively lower T-cell responses following mRNA vaccination.
Evidence on cataract in low- and middle-income countries: an updated review of reviews using the evidence gap maps approach
Authors: Jolley Emma , Virendrakumar Bhavisha , Pente Vladimir , Baldwin Martin , Mailu Eunice , Schmidt Elena 
Published: October 2021

Abstract
In 2014, Sightsavers developed the first evidence gap map (EGM) to assess the extent and quality of review-level evidence on cataract relevant to low-and middle-income countries. The EGM identified 52 studies across five broad themes. This paper reports the update of the EGM conducted in 2021 and changes to the extent and quality of the evidence base. We updated the EGM using the exact process conducted to develop the original. Searches were run to 14 September 2021, and two independent reviewers selected eligible studies, critically appraised them and extracted data using the Supporting the Use of Research Evidence checklist. A summary quality assessment was shared with the authors for comments. Forty-six new reviews were identified, and the EGM now includes 98 reviews. The new reviews predominantly focus on treatment and risk factors. The overall methodological quality was found to be improved, with 13/46 reporting high confidence in findings. EGMs remain a useful tool for policy-makers to make informed decisions and periodic updates are important to assess changes and to refine the focus for future research. The EGM highlights significant disparity in the topics addressed by reviews, with health system interventions particularly neglected.
Estimating inbreeding depression for growth and reproductive traits using pedigree and genomic methods in Argentinean Brangus cattle
Authors: Forneris Natalia S , Garcia-Baccino Carolina A , Cantet Rodolfo J C , Vitezica Zulma G 
Published: October 2021

Abstract
Inbreeding depression reduces the mean phenotypic value of important traits in livestock populations. The goal of this work was to estimate the level of inbreeding and inbreeding depression for growth and reproductive traits in Argentinean Brangus cattle, in order to obtain a diagnosis and monitor breed management. Data comprised 359,257 (from which 1,990 were genotyped for 40,678 single nucleotide polymorphisms [SNPs]) animals with phenotypic records for at least one of three growth traits: birth weight (BW), weaning weight (WW), and finishing weight (FW). For scrotal circumference (SC), 52,399 phenotypic records (of which 256 had genotype) were available. There were 530,938 animals in pedigree. Three methods to estimate inbreeding coefficients were used. Pedigree-based inbreeding coefficients were estimated accounting for missing parents. Inbreeding coefficients combining genotyped and nongenotyped animal information were also computed from matrix H of the single-step approach. Genomic inbreeding coefficients were estimated using homozygous segments obtained from a Hidden Markov model (HMM) approach. Inbreeding depression was estimated from the regression of the phenotype on inbreeding coefficients in a multiple-trait mixed model framework, either for the whole dataset or for the dataset of genotyped animals. All traits were unfavorably affected by inbreeding depression. A 10% increase in pedigree-based or combined inbreeding would result in a reduction of 0.34 to 0.39 kg in BW, 2.77 to 3.28 kg in WW, and 0.23 cm in SC. For FW, a 10% increase in pedigree-based, genomic, or combined inbreeding would result in a decrease of 8.05 to 11.57 kg. Genomic inbreeding based on the HMM was able to capture inbreeding depression, even in such a compressed genotyped dataset.
Grazing diverse combinations of tanniferous and nontanniferous legumes: implications for foraging behavior, performance, and hair cortisol in beef cattle
Authors: Lagrange Sebastian , MacAdam Jennifer W , Stegelmeier Bryan , Villalba Juan J 
Published: October 2021

Abstract
A diversity of forages with different types and concentrations of nutrients and plant secondary compounds may lead to complementary relationships that enhance cattle performance and welfare. We determined whether grazing combinations of tanniferous legumes (Lotus corniculatus, birdsfoot trefoil [BFT], Onobrychis viciifolia, sainfoin [SF]), and alfalfa [ALF] (Medicago sativa) influence foraging behavior, performance, and hair cortisol concentration in beef cattle compared with grazing the same legumes as monocultures. Twenty-one pairs of heifers grazed three spatial replications of seven treatments: monocultures of BFT, SF, or ALF, and all possible two- and three-way choices among strips of these legumes: SF-BFT, ALF-BFT, ALF-SF, and ALF-SF-BFT in two periods of 25 d each (adaptation phase + experimental period) during two consecutive years. The lowest incidence of grazing events occurred in the BFT treatment (42.0% of the total scans recorded; P &lt; 0.10), with the rest of the treatments ranging between 47.8% (SF-BFT) and 52.6% (ALF-SF) of the total scans recorded. Heifers selected a varied diet, preferring SF over BFT or ALF in a 46:27:27 ratio for the three-way choice, and in a 70:30 ratio for both two-way choices. Heifers preferred BFT over ALF (62:38 ratio) in a two-way choice. All treatments followed similar daily grazing patterns (P &gt; 0.10), with two major grazing events (1 h after sunrise and 3 h before dark). No differences among treatments were observed for the number of steps taken by heifers on a daily basis, motion index, or the percentage of time heifers spent standing (1,599, 5,356, and 45.3%, respectively; P &gt; 0.10), suggesting that heifers on choice treatments did not invest extra time in walking, searching, or patch switching activities relative to heifers grazing monocultures. Heifers grazing the three-way choice gained more body weight (1.27 kg/d) than the average gains observed for animals grazing in all legume monocultures (1.00 kg/d; P = 0.014) or two-way choices (0.97 kg/d; P = 0.007), suggesting a synergism among pasture species for the treatment with the highest diversity. No differences in hair cortisol concentration were observed among treatments, with values ranging between 1.4 (BFT) and 2.12 ng/g (three-way choice; P &gt; 0.10). Thus, forage diversity has the potential to enhance animal performance without affecting grazing efficiency, likely explained by the spatial arrangement of the forage species presented in the study.
Social Media Public Opinion as Flocks in a Murmuration: Conceptualizing and Measuring Opinion Expression on Social Media
Authors: Zhang Yini , Chen Fan , Rohe Karl 
Published: October 2021

Abstract
We propose a new way of imagining and measuring opinions emerging from social media. As people tend to connect with like-minded others and express opinions in response to current events on social media, social media public opinion is naturally occurring, temporally sensitive, and inherently social. Our framework for measuring social media public opinion first samples targeted nodes from a large social graph and identifies homogeneous, interactive, and stable networks of actors, which we call “flocks,” based on social network structure, and then measures and presents opinions of flocks. We apply this framework to Twitter and provide empirical evidence for flocks being meaningful units of analysis and flock membership predicting opinion expression. Through contextualizing social media public opinion by foregrounding the various homogeneous networks it is embedded in, we highlight the need to go beyond the aggregate-level measurement of social media public opinion and study the social dynamics of opinion expression using social media.
Chalcone-rich extracts from Lonchocarpus cultratus roots present in vitro leishmanicidal and immunomodulatory activity
Authors: Staffen Izabela Virginia , Banhuk Fernanda Weyand , Tomiotto-Pellissier Fernanda , da Silva Bortoleti Bruna Taciane , Pavanelli Wander Rogério , Ayala Thaís Soprani , Menolli Rafael Andrade 
Published: October 2021

Abstract

Objectives
This study aimed to evaluate the in vitro anti-Leishmania activity of chalcone-rich three extracts (LDR, LHR and LMR) from Lonchocarpus cultratus (Vell.) A.M.G. Azevedo & H.C. Lima against L. amazonensis. Also, the immunomodulatory and antioxidant capacity was assessed.

Methods
Successive extraction with hexane, dichloromethane and methanol were performed to obtain LHR, LDR and LMR extracts from L. cultratus roots, which were characterized by 1H NMR. Promastigotes, amastigotes and peritoneal macrophages were exposed to crescent concentrations of the three extracts, and after incubation, the inhibition rates were determined to both types of cells, and morphological analyses were performed on the parasite. The immunomodulatory activity was determined against stimulated macrophages.

Key findings
LDR, LHR and LMR inhibited promastigote cell growth (IC50 0.62 ± 0.3, 0.94 ± 0.5 and 1.28 ± 0.73 µg/ml, respectively) and reduced the number of amastigotes inside macrophages (IC50 1.36 ± 0.14, 1.54 ± 0.26 and 4.09 ± 0.88 µg/ml, respectively). The cytotoxicity against murine macrophages resulted in a CC50 of 13.12 ± 1.92, 92.93 ± 9.1 and &gt;300 µg/ml, resulting in high selectivity index to promastigotes and amastigotes. The extracts also inhibited the nitric oxide secretion in RAW 264.7 macrophages. The antioxidant capacity resulted in a higher scavenger LMR ability.

Conclusions
These results suggest that L. cultratus extracts have anti-Leishmania potential, are non-toxic, and immunosuppress macrophages in vitro.