bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing the synthesis and purification of MS2 virus like particles
Authors: Hashemi Khadijeh , Ghahramani Seno Mohammad Mahdi , Ahmadian Mohammad Reza , Malaekeh-Nikouei Bizhan , Bassami Mohammad Reza , Dehghani Hesam , Afkhami-Goli Amir 
Published: October 2021

AbstractIntroducing bacteriophage MS2 virus-like particles (VLPs) as gene and drug delivery tools increases the demand for optimizing their production and purification procedure. PEG precipitation method is used efficiently to purify VLPs, while the effects of pH and different electrolytes on the stability, size, and homogeneity of purified MS2 VLPs, and the encapsulated RNA sequences remained to be elucidated. In this regard, a vector, capable of producing VLP with an shRNA packed inside was prepared. The resulting VLPs in different buffers/solutions were assessed for their size, polydispersity index, and ability to protect the enclosed shRNA. We report that among Tris, HEPES, and PBS, with or without NaNO3, and also NaNO3 alone in different pH and ionic concentrations, the 100 mM NaNO3-Tris buffer with pH:8 can be used as a new and optimal MS2 VLP production buffer, capable of inhibiting the VLPs aggregation. These VLPs show a size range of 27-30 nm and suitable homogeneity with minimum 12-month stability at 4 °C. Moreover, the resulting MS2 VLPs were highly efficient and stable for at least 48 h in conditions similar to in vivo. These features of MS2 VLPs produced in the newly introduced buffer make them an appropriate candidate for therapeutic agents’ delivery.
An evaluation of multi-species empirical tree mortality algorithms for dynamic vegetation modelling
Authors: Thrippleton Timothy , Hülsmann Lisa , Cailleret Maxime , Bugmann Harald 
Published: October 2021

AbstractTree mortality is key for projecting forest dynamics, but difficult to portray in dynamic vegetation models (DVMs). Empirical mortality algorithms (MAs) are often considered promising, but little is known about DVM robustness when employing MAs of various structures and origins for multiple species. We analysed empirical MAs for a suite of European tree species within a consistent DVM framework under present and future climates in two climatically different study areas in Switzerland and evaluated their performance using empirical data from old-growth forests across Europe. DVM projections under present climate showed substantial variations when using alternative empirical MAs for the same species. Under climate change, DVM projections showed partly contrasting mortality responses for the same species. These opposing patterns were associated with MA structures (i.e. explanatory variables) and occurred independent of species ecological characteristics. When comparing simulated forest structure with data from old-growth forests, we found frequent overestimations of basal area, which can lead to flawed projections of carbon sequestration and other ecosystem services. While using empirical MAs in DVMs may appear promising, our results emphasize the importance of selecting them cautiously. We therefore synthesize our insights into a guideline for the appropriate use of empirical MAs in DVM applications.
Effects of pre-pregnancy body mass index on pregnancy and perinatal outcomes in women based on a retrospective cohort
Authors: Xie Donghua , Yang Wenzhen , Wang Aihua , Xiong Lili , Kong Fanjuan , Liu Zhiyu , Xie Zhiqun , Wang Hua 
Published: October 2021

AbstractTo investigate the prevalence of underweight, overweight and obesity as defined by pre-pregnancy body mass index (BMI) and the relationship between pre-pregnancy BMI and pregnancy and perinatal outcomes in women based on a retrospective cohort. Women registered via the Free Pre-pregnancy Health Check (FPHC) program from 2017 to 2019 in Hunan Province, China, were included to the study cohort. The data regarding maternal characteristics, pregnancy outcomes, and infant characteristics were retrieved from the surveillance system of the FPHC program. Logistic regressions were performed to calculate odds ratios (ORs) and adjusted odds ratios (AORs) with 95% confidence intervals (95% CIs) to assess the associations between pre-pregnancy BMIs and the outcomes. Among a total of 398,368 women, 54,238 (13.62%) were underweight (BMI < 18.5 kg/m2), 51,251 (12.87%) were overweight (24.0 kg/m2 ≤ BMI < 28.0 kg/m2), and 10,399 (2.61%) were obese (BMI ≥ 28.0 kg/m2). Underweight occurred more commonly in the 20–24 years old (17.98%), Han Chinese (13.89), college-educated (16.09%), rural (13.74%), and teacher/public servant/office clerk (16.09%) groups. Obesity occurred more often in the older than 35-year-old (4.48%), minority (3.64%), primary school or below (4.98%), urban (3.06%), and housewife (3.14%) groups (P < 0.001). Compared with the normal BMI group, underweight was associated with increased risk of low birth weight (LBW) (AOR = 1.25) and small-for-gestational age (SGA) (AOR = 1.11), but protected against gestational hypertensive disorder (GHD) (AOR = 0.85), gestational diabetes mellitus (GDM) (AOR = 0.69), macrosomia (AOR = 0.67), post-term pregnancy (AOR = 0.76), and cesarean-section (AOR = 0.81). Overweight and obesity were associated with increased risk of GHD (AOR = 1.28, 2.47), GDM (AOR = 1.63, 3.02), preterm birth (AOR = 1.18, 1.47), macrosomia (AOR = 1.51, 2.11), large-for-gestational age (LGA) (AOR = 1.19, 1.35), post-term pregnancy (AOR = 1.39, 1.66), and cesarean- section (AOR = 1.60, 2.05). Pre-pregnancy underweight is relatively common in Hunan Province, China. Pre-pregnancy underweight to some extent is associated with better maternal outcomes, but it has certain adverse effects on neonatal outcomes. Pre-pregnancy overweight, especially obesity, has a substantial adverse effect on pregnancy and perinatal outcomes.
Different roles of conserved tyrosine residues of the acylated domains in folding and activity of RTX toxins
Authors: Lepesheva Anna , Osickova Adriana , Holubova Jana , Jurnecka David , Knoblochova Sarka , Espinosa-Vinals Carlos , Bumba Ladislav , Skopova Karolina , Fiser Radovan , Osicka Radim , Sebo Peter , Masin Jiri 
Published: October 2021

AbstractPore-forming repeats in toxins (RTX) are key virulence factors of many Gram-negative pathogens. We have recently shown that the aromatic side chain of the conserved tyrosine residue 940 within the acylated segment of the RTX adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) plays a key role in target cell membrane interaction of the toxin. Therefore, we used a truncated CyaA-derived RTX719 construct to analyze the impact of Y940 substitutions on functional folding of the acylated segment of CyaA. Size exclusion chromatography combined with CD spectroscopy revealed that replacement of the aromatic side chain of Y940 by the side chains of alanine or proline residues disrupted the calcium-dependent folding of RTX719 and led to self-aggregation of the otherwise soluble and monomeric protein. Intriguingly, corresponding alanine substitutions of the conserved Y642, Y643 and Y639 residues in the homologous RtxA, HlyA and ApxIA hemolysins from Kingella kingae, Escherichia coli and Actinobacillus pleuropneumoniae, affected the membrane insertion, pore-forming (hemolytic) and cytotoxic capacities of these toxins only marginally. Activities of these toxins were impaired only upon replacement of the conserved tyrosines by proline residues. It appears, hence, that the critical role of the aromatic side chain of the Y940 residue is highly specific for the functional folding of the acylated domain of CyaA and determines its capacity to penetrate target cell membrane.
Pachychoroid disease and its association with retinal vein occlusion: a case–control study
Authors: Keidel Leonie F. , Zwingelberg Sarah , Schworm Benedikt , Luft Nikolaus , Herold Tina , Priglinger Siegfried G. , Siedlecki Jakob 
Published: October 2021

AbstractThe development of a retinal vein occlusion (RVO) is multifactorial. This study investigates pachychoroid as a risk factor for RVO or as an entity sharing common pathophysiology with RVO. A database screening at the University Eye Hospital, Ludwig-Maximilian University Munich, Germany was performed for patients diagnosed with central or branch RVO (CRVO/BRVO). In every patient a complete ophthalmologic examination was performed, including posterior segment enhanced depth spectral domain optical coherence tomography (EDI-SD-OCT). The SD-OCT scans of respective partner eyes without history of RVO were compared to an age- and refraction-matched, randomly recruited normal control group. In total, 312 eyes of 312 patients were included in this study, with 162 eyes in the RVO and 150 eyes in the control group. A significantly higher subfoveal choroidal thickness (SFCT) was found in the RVO (310.3 ± 72.5 (94 to 583) µm) as compared to the control group (237.0 ± 99.0 (62 to 498); p < 0.00001). Moreover, the RVO group showed a significantly higher prevalence of a symptomatic pachychoroid (22 vs. 9 eyes; odds ratio: 2.46; 95 CI: 1.10 to 5.53; p = 0.029). Since pachychoroid disease represents a bilateral entity, it might be a risk factor for RVO, or share risk factors with RVO.
Effect and mechanism of vitamin D activation disorder on liver fibrosis in biliary atresia
Authors: Sun Song , Xu Menghua , Zhuang Peijun , Chen Gong , Dong Kuiran , Dong Rui , Zheng Shan 
Published: October 2021

AbstractTo investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-β1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-β1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.
Optimization studies of stir casting parameters and mechanical properties of TiO2 reinforced Al 7075 composite using response surface methodology
Authors: Adediran Adeolu A. , Akinwande Abayomi A. , Balogun Oluwatosin A. , Olorunfemi Bayode J. , M. Saravana Kumar 
Published: October 2021

AbstractStir casting is a common metallurgical route in the casting of aluminum composites. Series of work done in this aspect considered the development of the composites with fixed stir casting parameters without applying an optimization approach. These parameters affect the microstructure and performance of the composites. The study is focused on the optimization of the stir casting parameters in the production of Al 7075 reinforced with TiO2 microparticles for performance improvement. Three stir casting parameters of stirring temperature, speed, and time were varied and optimized using the central composite design technique of the response surface method. Properties evaluated were ultimate tensile strength, hardness, impact strength, elastic modulus, and compressive strength. ANOVA results showed that the three stir casting parameters had a significant impact on the property responses. Five quadratic models were established for the properties linking them to the factors. The models were confirmed to be statistically significant at a confidence level of 95% and variations were observed to be < 5%. The interaction profile of the parameters as per response surface was analyzed. Contour plots associated with each interaction gave different ranges of stirring parameters in which each property can be maximized. Simultaneous optimization of the properties using Minitab 19 software showcased 779.3 °C, 574.2 rpm, and 22.5 min as the optimal stir casting parameters for temperature, speed and time respectively.
Elexacaftor is a CFTR potentiator and acts synergistically with ivacaftor during acute and chronic treatment
Authors: Shaughnessy Ciaran A. , Zeitlin Pamela L. , Bratcher Preston E. 
Published: October 2021

AbstractCystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), which lead to early death due to progressive lung disease. The development of small-molecule modulators that directly interact with CFTR to aid in protein folding (“correctors”) and/or increase channel function (“potentiators”) have proven to be highly effective in the therapeutic treatment of CF. Notably, incorporation of the next-generation CFTR corrector, elexacaftor, into a triple combination therapeutic (marketed as Trikafta) has shown tremendous clinical promise in treating CF caused by F508del-CFTR. Here, we report on a newly-described role of elexacaftor as a CFTR potentiator. We explore the acute and chronic actions, pharmacology, and efficacy of elexacaftor as a CFTR potentiator in restoring function to multiple classes of CFTR mutations. We demonstrate that the potentiating action of elexacaftor exhibits multiplicative synergy with the established CFTR potentiator ivacaftor in rescuing multiple CFTR class defects, indicating that a new combination therapeutic of ivacaftor and elexacaftor could have broad impact on CF therapies.
Characterizing the genomic variation and population dynamics of Plasmodium falciparum malaria parasites in and around Lake Victoria, Kenya
Authors: Osborne Ashley , Manko Emilia , Takeda Mika , Kaneko Akira , Kagaya Wataru , Chan Chim , Ngara Mtakai , Kongere James , Kita Kiyoshi , Campino Susana , Kaneko Osamu , Gitaka Jesse , Clark Taane G. 
Published: October 2021

AbstractCharacterising the genomic variation and population dynamics of Plasmodium falciparum parasites in high transmission regions of Sub-Saharan Africa is crucial to the long-term efficacy of regional malaria elimination campaigns and eradication. Whole-genome sequencing (WGS) technologies can contribute towards understanding the epidemiology and structural variation landscape of P. falciparum populations, including those within the Lake Victoria basin, a region of intense transmission. Here we provide a baseline assessment of the genomic diversity of P. falciparum isolates in the Lake region of Kenya, which has sparse genetic data. Lake region isolates are placed within the context of African-wide populations using Illumina WGS data and population genomic analyses. Our analysis revealed that P. falciparum isolates from Lake Victoria form a cluster within the East African parasite population. These isolates also appear to have distinct ancestral origins, containing genome-wide signatures from both Central and East African lineages. Known drug resistance biomarkers were observed at similar frequencies to those of East African parasite populations, including the S160N/T mutation in the pfap2mu gene, which has been associated with delayed clearance by artemisinin-based combination therapy. Overall, our work provides a first assessment of P. falciparum genetic diversity within the Lake Victoria basin, a region targeting malaria elimination.
Accuracy of flow-void diameters on MR images in diagnosing uterine arteriovenous malformations in patients with pregnancy-related diseases
Authors: Chen Hui-zhu , Zhao Fu-min , Liu Ling-jun , Dai Xiao-hui , Li Xue-sheng , Ning Gang , Guo Ying-kun 
Published: October 2021

AbstractTo evaluate the “flow void” diameter in patients with pregnancy-related diseases with and without uterine AVMs and assess the diagnostic performance of unenhanced MRI for uterine AVMs. From May 2014 to April 2019, 79 patients with pregnancy-related diseases were included, including 36 with and 43 without uterine AVMs confirmed by DSA. On MRI, the diameter of the most prominent “flow void” (hereinafter referred to as fv-D) was measured and compared between patients with and without uterine AVMs. The diagnostic performance of fv-D was estimated with receiver operating characteristic curves. The “flow void” sign was observed in patients with and without uterine AVMs (P > 0.05). The fv-D was significantly larger in patients with uterine AVMs in the myometrium and parametrium than in patients without uterine AVMs (P < 0.0001). The fv-D achieved a reliable diagnostic performance in the myometrium (sensitivity 80.6%, specificity 60.5%, negative predictive value 78.8%, positive predictive value 63%, AUC 0.727, cut-off: > 1.33 mm) and parametrium (sensitivity 97.2%, specificity 67.4%, negative predictive value 96.7%, positive predictive value 71.4%, AUC 0.881, cut-off > 2.6 mm). On MRI, fv-D could diagnose uterine AVMs. The fv-D had a much higher diagnostic efficiency in the parametrium than in the myometrium. The parametrium fv-D greatly improved the diagnostic sensitivity and provides a more accurate, noninvasive method of investigating possible uterine AVMs.
Association of clinically relevant carpal tunnel syndrome with type of work and level of education: a general-population study
Authors: Möllestam Kamelia , Englund Martin , Atroshi Isam 
Published: October 2021

AbstractCarpal tunnel syndrome (CTS) is a common cause of work disability. The association with occupational load and education level has not been established in general-population studies. The purpose of this study was to investigate the association of clinically relevant CTS with work and education. From the Healthcare Register of Skane region (population 1.2 million) in southern Sweden we identified all individuals, aged 17–57 years, with first-time physician-made CTS diagnosis during 2004–2008. For each case we randomly sampled 4 referents, without a CTS diagnosis, from the general population matched by sex, age, and residence. We retrieved data about work and education from the national database. The study comprised 5456 individuals (73% women) with CTS and 21,667 referents. We found a significant association between physician-diagnosed CTS and type of work and level of education in both women and men. Compared with white-collar workers, the odds ratio (OR) for CTS among blue-collar workers was 1.67 (95% CI 1.54–1.81) and compared with light work, OR in light-moderate work was 1.37 (1.26–1.50), moderate work 1.70 (1.51–1.91), and heavy manual labor 1.96 (1.75–2.20). Compared with low-level education, OR for CTS in intermediate level was 0.82 (0.76–0.89) and high-level 0.48 (0.44–0.53). In women and men there is significant association with a dose–response pattern between clinically relevant CTS and increasing manual work load and lower education level. These findings could be important in design and implementation of preventive measures.
Genetic targeting of adult Renshaw cells using a Calbindin 1 destabilized Cre allele for intersection with Parvalbumin or Engrailed1
Authors: Lane Alicia R. , Cogdell Indeara C. , Jessell Thomas M. , Bikoff Jay B. , Alvarez Francisco J. 
Published: October 2021

AbstractRenshaw cells (RCs) are one of the most studied spinal interneurons; however, their roles in motor control remain enigmatic in part due to the lack of experimental models to interfere with RC function, specifically in adults. To overcome this limitation, we leveraged the distinct temporal regulation of Calbindin (Calb1) expression in RCs to create genetic models for timed RC manipulation. We used a Calb1 allele expressing a destabilized Cre (dgCre) theoretically active only upon trimethoprim (TMP) administration. TMP timing and dose influenced RC targeting efficiency, which was highest within the first three postnatal weeks, but specificity was low with many other spinal neurons also targeted. In addition, dgCre showed TMP-independent activity resulting in spontaneous recombination events that accumulated with age. Combining Calb1-dgCre with Parvalbumin (Pvalb) or Engrailed1 (En1) Flpo alleles in dual conditional systems increased cellular and timing specificity. Under optimal conditions, Calb1-dgCre/Pvalb-Flpo mice targeted 90% of RCs and few dorsal horn neurons; Calb1-dgCre/En1-Flpo mice showed higher specificity, but only a maximum of 70% of RCs targeted. Both models targeted neurons throughout the brain. Restricted spinal expression was obtained by injecting intraspinally AAVs carrying dual conditional genes. These results describe the first models to genetically target RCs bypassing development.
Synchrotron mechanism of X-ray and gamma-ray emissions in lightning and spark discharges
Authors: Petrov N. I. 
Published: October 2021

AbstractX-ray and γ-ray emissions observed in lightning and long sparks are usually connected with the bremsstrahlung of high-energy runaway electrons. Here, an alternative physical mechanism for producing X-ray and gamma-ray emissions caused by the polarization current and associated electromagnetic field moving with relativistic velocity along a curved discharge channel has been proposed. The existence of fast electromagnetic surface waves propagating along the lightning discharge channel at a speed close to the speed of light in vacuum is shown. The possibility of the production of microwave, X-ray and gamma-ray emissions by a polarization current pulse moving along a curved path via synchrotron radiation mechanism is pointed out. The existence of long tails in the power spectrum is shown, which explains observations of photon energies in the range of 10–100 MeV in the terrestrial gamma-ray flashes, as well as measured power spectrum of laboratory spark discharge.
Novel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis
Authors: Agrawal Sonia , Gample Suwarna , Yeware Amar , Sarkar Dhiman 
Published: October 2021

AbstractThe development of the latent phenotype of Mycobacterium tuberculosis (Mtb) in the human lungs is the major hurdle to eradicate Tuberculosis. We recently reported that exposure to nitrite (10 mM) for six days under in vitro aerobic conditions completely transforms the bacilli into a viable but non-cultivable phenotype. Herein, we show that nitrite (beyond 5 mM) treated Mtb produces nitric oxide (NO) within the cell in a dose-dependent manner. Our search for the conserved sequence of NO synthesizing enzyme in the bacterial system identified MRA2164 and MRA0854 genes, of which the former was found to be significantly up regulated after nitrite exposure. In addition, the purified recombinant MRA2164 protein shows significant nitrite dependent NO synthesizing activity. The knockdown of the MRA2164 gene at mRNA level expression resulted in a significantly reduced NO level compared to the wild type bacilli with a simultaneous return of its replicative capability. Therefore, this study first time reports that nitrite induces dormancy in Mtb cells through induced expression of the MRA2164 gene and productions of NO as a mechanism for maintaining non-replicative stage in Mtb. This observation could help to control the Tuberculosis disease, especially the latent phenotype of the bacilli.