bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering cytoplasmic acetyl-CoA synthesis decouples lipid production from nitrogen starvation in the oleaginous yeast Rhodosporidium azoricum
Authors: Donzella Silvia , Cucchetti Daniela , Capusoni Claudia , Rizzi Aurora , Galafassi Silvia , Chiara Gambaro , Compagno Concetta 
Published: November 2019

AbstractBackgroundOleaginous yeasts are able to accumulate very high levels of neutral lipids especially under condition of excess of carbon and nitrogen limitation (medium with high C/N ratio). This makes necessary the use of two-steps processes in order to achieve high level of biomass and lipid. To simplify the process, the decoupling of lipid synthesis from nitrogen starvation, by establishing a cytosolic acetyl-CoA formation pathway alternative to the one catalysed by ATP-citrate lyase, can be useful.ResultsIn this work, we introduced a new cytoplasmic route for acetyl-CoA (AcCoA) formation inRhodosporidium azoricumby overexpressing genes encoding for homologous phosphoketolase (Xfpk) and heterologous phosphotransacetylase (Pta). The engineered strain PTAPK4 exhibits higher lipid content and produces higher lipid concentration than the wild type strain when it was cultivated in media containing different C/N ratios. In a bioreactor process performed on glucose/xylose mixture, to simulate an industrial process for lipid production from lignocellulosic materials, we obtained an increase of 89% in final lipid concentration by the engineered strain in comparison to the wild type. This indicates that the transformed strain can produce higher cellular biomass with a high lipid content than the wild type. The transformed strain furthermore evidenced the advantage over the wild type in performing this process, being the lipid yields 0.13 and 0.05, respectively.ConclusionOur results show that the overexpression of homologous Xfpk and heterologous Pta activities inR. azoricumcreates a new cytosolic AcCoA supply that decouples lipid production from nitrogen starvation. This metabolic modification allows improving lipid production in cultural conditions that can be suitable for the development of industrial bioprocesses using lignocellulosic hydrolysates.
The assessment of xenogeneic bone immunotoxicity and risk management study
Authors: Sun Xiaoxia , Liu Chenghu , Shi Yanping , Li Chunling , Sun Likui , Hou Li , Wang Xin 
Published: November 2019

Abstract
Background
Xenogeneic bone has been widely used in a variety of clinical bone-related disease to promote bone healing and restore bone defects. However, the adverse effects of immune system limit its application in the clinic. The aim of this study was to evaluate xenogeneic bone safety of immunotoxicity and explore the methods for immune risk supervision.

Results
Xenogeneic bone, which is freeze-dried bovine cancellous bone, was implanted into the muscle of mice. On day 7, 14 and 28, the effects of xenogeneic bone were examined on humoral immunity and cellular immunity, including the levels of IgG, IgM, C3, inflammatory factors (TNF-α, IL-6), alkaline phosphatase (ALP) and the lymphocyte phenotype. The data showed that xenogeneic bone implantation had no potential to induce immune responses not only in humoral immunity but also in cellular immunity. To reveal the risk of immunogenicity, the residual DNA and the clearance of α-gal epitope were analyzed in 2 different bones (bone 1 is deproteinized bone, bone 2 is acellular and defatted bone). It was suggested that DNA of xenogeneic bone can be limited to < 50 ng per mg dry weight for the repair or regeneration with the acceptable immune risk. And α-gal clearance of xenogeneic bone could be an effective risk factor for improving xenograft quality management.

Conclusions
Through the detection of xenogeneic bone immunotoxicity, our findings indicated that the supervisions of risk factors could contribute to reduce the immune risk. And the risk factors under the acceptable limitation could decrease or replace animal experiment. However, it still needs to be studied on the limitation of α-gal epitope to predict rejection of xenogeneic bone more accurately.
Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke
Authors: Salmeron Kathleen E. , Maniskas Michael E. , Edwards Danielle N. , Wong Raymond , Rajkovic Ivana , Trout Amanda , Rahman Abir A. , Hamilton Samantha , Fraser Justin F. , Pinteaux Emmanuel , Bix Gregory J. 
Published: November 2019

Abstract
Background
Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et al., J Cereb Blood Flow Metab 37:3531–3543, 2017; Hill et al., Lancet Neurol 11:942–950, 2012; Amaro et al., Stroke 47:2874–2876, 2016).

Methods
Transient stroke was induced in mice via one of two methods. One group of mice were subjected to tandem ipsilateral common carotid artery and middle cerebral artery occlusion, while another group underwent the filament-based middle cerebral artery occlusion. We have recently developed an animal model of intra-arterial (IA) drug administration after recanalization (Maniskas et al., J Neurosci Met 240:22–27, 2015). Sub groups of the mice were treated with either saline or Il-1α, wherein the drug was administered either acutely (immediately after surgery) or subacutely (on the third day after stroke). This was followed by behavioral and histological analyses.

Results
We now show in the above-mentioned mouse stroke models (transient tandem ipsilateral common carotid artery (CCA) and middle cerebral artery occlusion (MCA) occlusion, MCA suture occlusion) that IL-1α is neuroprotective when acutely given either intravenously (IV) or IA at low sub-pathologic doses. Furthermore, while IV administration induces transient hemodynamic side effects without affecting systemic markers of inflammation, IA delivery further improves overall outcomes while eliminating these side effects. Additionally, we show that delayed/subacute IV IL-1α administration ameliorates functional deficit and promotes neurorepair.

Conclusions
Taken together, our present study suggests for the first time that IL-1α could, unexpectedly, be an effective ischemic stroke therapy with a broad therapeutic window.
Development of caesarean section prediction models: secondary analysis of a prospective cohort study in two sub-Saharan African countries
Authors: de Souza Hayala C. C. , Perdoná Gleici S. C. , Marcolin Alessandra C. , Oyeneyin Lawal O. , Oladapo Olufemi T. , Mugerwa Kidza , Souza João Paulo 
Published: November 2019

Abstract
Background
Caesarean section is recommended in situations in which vaginal birth presents a greater likelihood of adverse maternal or perinatal outcomes than normal. However, it is associated with a higher risk of complications, especially when performed without a clear medical indication. Since labour attendants have no standardised clinical method to assist in this decision, statistical tools developed based on multiple labour variables may be an alternative. The objective of this paper was to develop and evaluate the accuracy of models for caesarean section prediction using maternal and foetal characteristics collected at admission and through labour.

Method
This is a secondary analysis of the World Health Organization’s Better Outcomes in Labour Difficulty prospective cohort study in two sub-Saharan African countries. Data were collected from women admitted for labour and childbirth in 13 hospitals in Nigeria as well as Uganda between 2014 and 2015. We applied logistic regression to develop different models to predict caesarean section, based on the time when intrapartum assessment was made. To evaluate discriminatory capacity of the various models, we calculated: area under the curve, diagnostic accuracy, positive predictive value, negative predictive value, sensitivity and specificity.

Results
A total of 8957 pregnant women with 12.67% of caesarean births were used for model development. The model based on labour admission characteristics showed an area under the curve of 78.70%, sensitivity of 63.20%, specificity of 78.68% and accuracy of 76.62%. On the other hand, the models that applied intrapartum assessments performed better, with an area under the curve of 93.66%, sensitivity of 80.12%, specificity of 89.26% and accuracy of 88.03%.

Conclusion
It is possible to predict the likelihood of intrapartum caesarean section with high accuracy based on labour characteristics and events. However, the accuracy of this prediction is considerably higher when based on information obtained throughout the course of labour.
Characterizing the composition, metabolism and physiological functions of the fatty liver in Rana omeimontis tadpoles
Authors: Zhu Wei , Zhang Meihua , Chang Liming , Zhu Wenbo , Li Cheng , Xie Feng , Zhang Huan , Zhao Tian , Jiang Jianping 
Published: November 2019

Abstract
Background
Fat storage is required for the life cycle of many organisms. The primary fat depot for most vertebrates is white adipose tissue. However, in primitive vertebrates (e.g., agnathan group and elasmobranchs), the liver is usually responsible for fat storage. Among the vertebrates, amphibians have a unique status, as their larvae live in the water and exhibit some primitive traits that are similar to fish. Although it has been recognized that adult frogs use their abdominal white adipose tissue as a primary fat depot, how tadpoles store their fat is still inconclusive. The metabolic traits and physiological functions of primitive fat depots may have wide-ranging implications on the pathology of abnormal lipid deposition in mammals and the evolution of fat storage.

Results
Rana omeimontis tadpoles used their liver as the primary fat depot. In sufficiently fed tadpoles at stage 30–31, the hepatosomatic index (HSI) reached up to 7%, and triglycerides (TG) accounted for 15% of liver weight. Their liver resembled white adipose tissue in histological morphology, characterized by polygonal hepatocytes filled with fat. Their liver metabolic composition was unique, characterized by the dominance of maltotriose, arachidonic acid and dipeptides in soluble carbohydrates, free fatty acids and amino acids. Hepatic fat was the major metabolic fuel of fasted R. omeimontis tadpoles, which had similar reserve mobilization and allocation patterns as mammals. From a developmental perspective, hepatic fat was important to fuel late metamorphic climax. Interestingly, starvation induced accelerated metamorphosis in tadpoles with high HSI (4.96 ± 0.21%). However, this phenomenon was not observed in tadpoles with low HSI (2.71 ± 0.16%), even though they had similar initial body weight and developmental stage. Hepatic fat abundance was the most prominent difference between the two groups.

Conclusion
To the best of our knowledge, this is the first report that liver can be the primary fat depot in vertebrates with higher evolutionary status than bony fish. The unique hepatic histological and metabolic traits likely either guard their liver against lipotoxicity or make their hepatocytes adapt to fat accumulation. This fatty liver could be a primitive counterpart of mammalian white adipose tissue (WAT). In addition, our study showed that the hepatic reserves of tadpoles, especially TG content, may provide body condition signals to modulate metamorphosis.
The mechanism of miR-889 regulates osteogenesis in human bone marrow mesenchymal stem cells
Authors: Xu Gang , Ding Zheng , Shi Hui-feng 
Published: November 2019

Abstract
Background
Bone marrow mesenchymal stem cells (BMMSCs) can be used for bone regeneration in the specified condition. Osteogenic differentiation of BMMSCs is controlled by microRNAs (miRNAs) and other factors. This study was aimed to identify the role and mechanism of miR-889 in regulating the osteogenic differentiation of BMMSCs.

Methods
Osteoporosis patients and normal control bone tissues were collected and used PCR techniques to identify the change of miR-889 and WNT7A. Moreover, the dynamic change of miR-889 and WNT7A during osteogenic differentiation of BMMSCs was also measured. Bioinformatic analysis was performed to identify the target genes and potential pathways of miR-889. Then, we constructed miR-889 mimic and inhibitor, ALP staining, ARS, osteoblastic-related protein, and Wnt β-catenin signaling pathway-related protein were also measured. WNT7A siRNA was also used to verify the function of miR-889.

Results
In the present study, we showed that miR-889 expression was upregulated in osteoporosis patients than healthy control. However, the miR-889 expression was downregulated during osteogenic differentiation. Bioinformatics analysis found that miR-889 targets 666 genes and mainly through Wnt β-catenin signaling pathway. Administrated miR-889 mimic, the ALP activity, and calcium deposition were decreased than the control group, while miR-889 inhibitor shown the opposite trend. And miR-889 could bind the 3′UTR of WNT7A. We further used WNT7A siRNA to explore the function of miR-889, and the results revealed that co-cultured with miR-889 inhibitor and WNT7A siRNA was associated with a reduction of ALP activity and calcium deposition and osteoblastic-related proteins than miR-889 inhibitor alone.

Conclusion
Our results revealed that miR-889 plays a negative role in inducing osteogenic differentiation of BMSCs through Wnt β-catenin signaling pathway.
Pubertal timing and breast density in young women: a prospective cohort study
Authors: Houghton Lauren C. , Jung Seungyoun , Troisi Rebecca , LeBlanc Erin S. , Snetselaar Linda G. , Hylton Nola M. , Klifa Catherine , Van Horn Linda , Paris Kenneth , Shepherd John A. , Hoover Robert N. , Dorgan Joanne F. 
Published: November 2019

AbstractBackgroundEarlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk.MethodsFrom 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006–2008, 182 participants then aged 25–29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV.ResultsThe mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2–86.1. Age at thelarche was negatively associated with %DBV (ptrend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (ptrend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2–26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9–17.5%)).ConclusionsOur results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.
NanoSatellite: accurate characterization of expanded tandem repeat length and sequence through whole genome long-read sequencing on PromethION
Authors: De Roeck Arne , De Coster Wouter , Bossaerts Liene , Cacace Rita , De Pooter Tim , Van Dongen Jasper , D’Hert Svenn , De Rijk Peter , Strazisar Mojca , Van Broeckhoven Christine , Sleegers Kristel 
Published: November 2019

AbstractTechnological limitations have hindered the large-scale genetic investigation of tandem repeats in disease. We show that long-read sequencing with a single Oxford Nanopore Technologies PromethION flow cell per individual achieves 30× human genome coverage and enables accurate assessment of tandem repeats including the 10,000-bp Alzheimer’s disease-associatedABCA7VNTR. The Guppy “flip-flop” base caller and tandem-genotypes tandem repeat caller are efficient for large-scale tandem repeat assessment, but base calling and alignment challenges persist. We present NanoSatellite, which analyzes tandem repeats directly on electric current data and improves calling of GC-rich tandem repeats, expanded alleles, and motif interruptions.
Thioredoxin peroxidase secreted by Echinococcus granulosus (sensu stricto) promotes the alternative activation of macrophages via PI3K/AKT/mTOR pathway
Authors: Wang Hui , Zhang Chuan-Shan , Fang Bin-Bin , Li Zhi-De , Li Liang , Bi Xiao-Juan , Li Wen-Ding , Zhang Ning , Lin Ren-Yong , Wen Hao 
Published: November 2019

AbstractBackgroundLarvae ofEchinococcus granulosus(sensu lato) dwell in host organs for a long time but elicit only a mild inflammatory response, which indicates that the resolution of host inflammation is necessary for parasite survival. The recruitment of alternatively activated macrophages (AAMs) has been observed in a variety of helminth infections, and emerging evidence indicates that AAMs are critical for the resolution of inflammation. However, whether AAMs can be induced byE. granulosus(s.l.) infection or thioredoxin peroxidase (TPx), one of the important molecules secreted by the parasite, remains unclear.MethodsThe activation status of peritoneal macrophages (PMs) derived from mice infected withE. granulosus(sensu stricto) was analyzed by evaluating the expression of phenotypic markers. PMs were then treatedin vivoandin vitrowith recombinant EgTPx (rEgTPx) and its variant (rvEgTPx) in combination with parasite excretory-secretory (ES) products, and the resulting activation of the PMs was evaluated by flow cytometry and real-time PCR. The phosphorylation levels of various molecules in the PI3K/AKT/mTOR pathway after parasite infection and antigen stimulation were also detected.ResultsThe expression of AAM-related genes in PMs was preferentially induced afterE. granulosus(s.s.) infection, and phenotypic differences in cell morphology were detected between PMs isolated fromE. granulosus(s.s.)-infected mice and control mice. The administration of parasite ES products or rEgTPx induced the recruitment of AAMs to the peritoneum and a notable skewing of the ratio of PM subsets, and these effects are consistent with those obtained afterE. granulosus(s.s.) infection. ES products or rEgTPx also induced PMs toward an AAM phenotypein vitro. Interestingly, this immunomodulatory property of rEgTPx was dependent on its antioxidant activity. In addition, the PI3K/AKT/mTOR pathway was activated after parasite infection and antigen stimulation, and the activation of this pathway was suppressed by pre-treatment with an AKT/mTOR inhibitor.ConclusionsThis study demonstrates thatE. granulosus(s.s.) infection and ES products, including EgTPx, can induce PM recruitment and alternative activation, at least in part,viathe PI3K/AKT/mTOR pathway. These results suggest that EgTPx-induced AAMs might play a key role in the resolution of inflammation and thereby favour the establishment of hydatid cysts in the host.
Spatial–temporal distribution of Aedes (Stegomyia) aegypti and locations of recycling units in southeastern Brazil
Authors: Piovezan Rafael , Visockas Alexandre , de Azevedo Thiago Salomão , Von Zuben Cláudio José , Sallum Maria Anice Mureb 
Published: November 2019

Abstract
Background
Dengue is an arbovirus disease that threatens approximately 200 million people annually worldwide. Aedes (Stegomyia) aegypti (Linnaeus, 1762) is anthropophilic mosquito, extremely well adapted to the urban environment and utilizes varied habitats for egg-laying and development. This study analysed the distribution of mosquito larvae and eggs in urban area of Santa Bárbara dʼOeste, São Paulo, Brazil. The spatial correlation between locations in which people store recyclable materials and the distribution of larvae and eggs were verified.

Methods
Larvae and ovitrap egg collections were conducted from 2014 to 2016. All persons who stored recyclable materials for living were registered and georeferenced. The Mann-Kendall test was used to verify spatial and temporal trends in the number of eggs and larvae/pupae. Euclidian distance map was constructed to correlate recyclable collectors and Ae. aegypti, and Moranʼs index was employed to verify their spatial autocorrelation and identification of groupings.

Results
A total of 137,825 eggs and 16,393 larvae were collected in different habitats from 2014 to 2016. The analyses showed that there was a spatial correlation between larvae and eggs collected, and these two kinds of surveys also presented a spatial correlation with the handling of recyclable materials. The results of the analyses showed significant spatial correlations between eggs and recyclable material collectors and between larvae and collectors.

Conclusion
The entomological surveillance conducted using ovitraps as a proxy for the presence of Ae. aegypti is an efficient and sensitive method for monitoring the presence of mosquitoes and the impact of interventions employed for decreasing vector populations. Mosquito surveys employing ovitraps should be used more often in routine activities aiming to control dengue through vector control interventions. The locations used to store recyclable materials have a significant relationship with the maintenance of the dengue virus infection in the area. Further studies will be needed to analyse the contribution of recyclable locations, for which there is no ideal infrastructure to minimize the potential use of these materials as mosquito habitats. The entomological surveillance focused on locations of recyclable materials involving interventions that are different from those commonly used in Ae. aegypti control.