bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional analysis of KIT gene structural mutations causing porcine dominant white phenotype by using genome edited mouse models
Authors: Sun Guangjie , Liang Xinyu , Qin Ke , Qin Yufeng , Shi Xuan , Cong Peiqing , Mo Deling , Liu Xiaohong , Chen Yaosheng , He Zuyong 
Published: July 2019

AbstractDominant white phenotype in pigs is considered to be caused by two structural mutations inKITgene, including a 450-kb duplication encompassing the entireKITgene, and a splice mutation (G > A) at the first base in intron 17, which leads to the deletion of exon 17 in matureKITmRNA, and the production of KIT protein lacking a critical catalytic domain of kinase. However, this speculation has not yet been validated by functional studies. Here, by using CRISPR/Cas9 technology, we created two mouse models mimicing the structural mutations ofKITgene in dominant white pigs, including the splice mutation mouse modelKITD17/+with exon 17 of one allele ofKITgene deleted, and duplication mutation mouse modelKITDup/+with one allele ofKITgene coding sequence (CDS) duplicated. We found that each mutation individually can not cause dominant white phenotype. Splice mutation homozygote is lethal and heterozygous mice present piebald coat. Inconsistent with previous speculation, we foundKITgene duplication mutation did not confer the patched phenotype, and had no obvious impact on coat color. Interestingly, combination of these two mutations lead to dominant white phenotype. Further molecular analysis revealed that combination of these two structural mutations could inhibit the kinase activity of the KIT protein, thus reduce the phosphorylation level of PI3K and MAPK pathway associated proteins, which may be related to the observed impaired migration of melanoblasts during embryonic development, and eventually lead to dominant white phenotype. Our study provides a further insight into the underlying genetic mechanisms of porcine dominant white coat colour.Author summaryKIT plays a critical role in control of coat colour in mammals. Two mutation coexistence inKITare considered to be the cause of theDominant whitephenotype in pigs. One mutation is a 450-kb large duplication encompassing the entireKITgene, another mutation is a splice mutation causing the skipping of KIT exon 17. The mechanism of these two mutations of KIT on coat color formation has not yet been validated. In this study, by using genome edited mouse models, we found each structural mutation individual does not lead dominant white phenotype, but combination of these two mutations could lead to a nearly complete white coat colour similar to pig dominant white phenotype, possibly due to the inhibition of the kinase activity of the KIT protein, thus its signalling function on PI3K and MAPK pathways, leading to impaired migration of melanoblasts during embryonic development, and eventually lead to dominant white phenotype. Our study provides a further insight into the underlying genetic mechanisms of porcine dominant white coat colour.
A dynamic cell recruitment process drives growth of the Drosophila wing by overscaling the Vestigial expression pattern
Authors: Muñoz-Nava Luis Manuel , Alvarez Hugo Ariel , Flores-Flores Marycruz , Chara Osvaldo , Nahmad Marcos 
Published: July 2019

AbstractOrgans mainly attain their size by cell growth and proliferation, but sometimes also grow through recruitment of undifferentiated cells. Here we investigate the participation of cell recruitment in establishing the pattern of Vestigial (Vg), the product of the wing selector gene in Drosophila. We find that the Vg pattern overscales along the dorsal-ventral (DV) axis of the wing imaginal disc,i.e., it expands faster than the DV length of the pouch. The overscaling of the Vg pattern cannot be explained by differential proliferation, apoptosis, or oriented-cell divisions, but can be recapitulated by a mathematical model that explicitly considers cell recruitment. By impairing cell recruitment genetically, we find that the Vg pattern almost perfectly scales and adult wings are approximately 20% smaller. Furthermore, using fluorescent reporter tools, we provide direct evidence that cell recruitment takes place in a specific time between early and mid third-instar larval development. Altogether, our work quantitatively shows when, how, and by how much cell recruitment shapes the Vg pattern and drives growth of the Drosophila wing.
Predicting long-term Type 2 Diabetes with Support Vector Machine using Oral Glucose Tolerance Test
Authors: Abbas Hasan , Alic Lejla , Erraguntla Madhav , Ji Jim , Abdul-Ghani Muhammad , Abbasi Qammer , Qaraqe Marwa 
Published: July 2019

AbstractDiabetes is a large healthcare burden worldwide. There is substantial evidence that lifestyle modifications and drug intervention can prevent diabetes, therefore, an early identification of high risk individuals is important to design targeted prevention strategies. In this paper, we present an automatic tool that uses machine learning techniques to predict the development of type 2 diabetes mellitus (T2DM). Data generated from an oral glucose tolerance test (OGTT) was used to develop a predictive model based on the support vector machine (SVM). We trained and validated the models using the OGTT and demographic data of 1,492 healthy individuals collected during the San Antonio Heart Study. This study collected plasma glucose and insulin concentrations before glucose intake and at three time-points thereafter (30, 60 and 120 min). Furthermore, personal information such as age, ethnicity and body-mass index was also a part of the dataset. Using 11 oral glucose tolerance test (OGTT) measurements, we have deduced 61 features, which are then assigned a rank and the top ten features are shortlisted using Minimum Redundancy Maximum Relevance feature selection algorithm. All possible combinations of the 10 best ranked features were used to generate SVM based prediction models. This research shows that an individual’s plasma glucose levels, and the information derived therefrom have the strongest predictive performance for the future development of T2DM. Significantly, insulin and demographic features do not provide additional performance improvement for diabetes prediction. The results of this work identify the parsimonious clinical data needed to be collected for an efficient prediction of T2DM. Our approach shows an average accuracy of 96.80 % and a sensitivity of 80.09 % obtained on a holdout set.
Tissue-specific changes in size and shape of the ligaments and tendons of the porcine knee during post-natal growth
Authors: Cone Stephanie G. , Piercy Hope E. , Lambeth Emily P. , Ru Hongyu , Piedrahita Jorge A. , Spang Jeffrey T. , Fordham Lynn A. , Fisher Matthew B. 
Published: July 2019

AbstractPrior studies have analyzed growth of musculoskeletal tissues between species or across body segments; however, little research has assessed the differences in similar tissues within a single joint. Here we studied changes in the length and cross-sectional area of four ligaments and tendons, (anterior cruciate ligament, patellar tendon, medial collateral ligament, lateral collateral ligament) in the tibiofemoral joint of female Yorkshire pigs through high-field magnetic resonance imaging throughout growth. Tissue lengths increased by 4-to 5-fold from birth to late adolescence across the tissues while tissue cross-sectional area increased by 10-20-fold. The anterior cruciate ligament and lateral collateral ligament showed allometric growth favoring change in length over change in cross-sectional area while the patellar tendon and medial collateral ligament grow in an isometric manner. Additionally, changes in the length and cross-sectional area of the anterior cruciate ligament did not increase as much as in the other ligaments and tendon of interest. Overall, these findings suggest that musculoskeletal soft tissue morphometry can vary within tissues of similar structure and within a single joint during post-natal growth.
Reducing expression of dynamin-related protein 1 increases radiation sensitivity of glioblastoma cells
Authors: Cheng Wen-Yu , Chow Kuan-Chih , Chiao Ming-Tsang , Yang Yi-Chin , Shen Chiung-Chyi 
Published: July 2019

AbstractBackgroundDynamin-related protein 1 (DRP1) is a GTPase involved in mitochondrial fission, mitochondrial protein imports, and drug sensitivity, suggesting an association with cancer progression. This study is to evaluate the prognostic significance of DRP1 in glioblastoma multiforme (GBM).Material and MethodsDRP1 expression was measured by immunohistochemistry and Western blotting. Correlations between DRP1 expression and clinicopathological parameters were analyzed by statistical analysis. Differences in survival were compared by a log-rank test.ResultsDRP1 expression was detected in 87.2% (41/47) patients with GBM. Patients with higher DRP1 levels had worse survival (p = 0.0398). In vitro, silencing of DRP1 reduced cell proliferation, metastatic potential, and radiation resistance. The addition of shikonin inhibited DRP1 expression and increased drug uptake. Moreover, shikonin reduced the nuclear entry of DNA repair-associated enzymes and increased radiation sensitivity, suggesting that to reduce DRP1 expression could inhibit DNA repair and increase the radiation sensitivity of GBM cells.ConclusionOur results indicate that DRP1 overexpression is a prospective radio-resistant phenotype in GBM. Therefore, DRP1 could be a potential target for improving the effectiveness of radiation therapy.Abbreviations used are: ATAD3A, the ATPase family, AAA domain containing 3A; CIM, confocal immunofluorescence microscopy; DRP1, dynamin-related protein 1; ER, endoplasmic reticulum; GBM, glioblastoma multiforme; hHR23A, human homolog of yeast Rad23 protein A; IDH1, isocitrate dehydrogenase 1; MAM, mitochondria-associated membrane; MGMT, O6-methylguanine-DNA-methyltransferase; SAHA, suberoylanilide hydroxamic acid (vorinostat); TMZ, temozolomideTranslational RelevanceThis study shows that dynamin-related protein 1 (DRP1), an essential 80-kDa GTPase, which is involved in mitochondrial fission, and mitochondrial protein imports, is highly expressed in glioblastoma multiforme (GBM). Moreover, we demonstrate that DRP1 expression is closely associated with radiation sensitivity, cancer progression, and patients’ cumulative survival. In vitro, inhibition of DRP1 expression reduced the nuclear entry of DNA repair-associated enzymes, such as ATM, but increased radiation sensitivity and nuclear drug uptakes of glioblastoma cells. More importantly, the silencing of DRP1 induced cellular autophagy. These results indicate that DRP1 overexpression could be a prospective radio-resistant phenotype in GBM and a clinically important target for improving the effectiveness of radiation therapy.
Computational fluid dynamics simulation of changes in the morphology and airflow dynamics of the upper airways in OSAHS patients after treatment with oral appliances
Authors: Baolong Song , Yibo Li , Jianwei Sun , Yizhe Qi , Peng Li , Yongming Li , Zexu Gu 
Published: July 2019

AbstractObjectivesTo explore the changes of morphology and internal airflow in upper airways (UA) after the use of oral appliances (OAs) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS), and investigate the mechanisms by which OAs function as a therapy for OSAHS.MethodsEight OSAHS patients (all male, aged 37-58, mean age 46.25) underwent CT scans before and after OA use. Then, computational fluid dynamics(CFD) models were built on the base of the CT scans using Mimics and ANSYS ICEM CFD software. The internal airflow of the upper airways was simulated using ANSYS-FLUENT and the results were analyzed using ANSYS-CFD-Post. The data were analyzed to identify the most important changes of biomechanical properties between patients with and without OA intervention. Upper airway morphology and the internal airflow changes were compared using t-tests and Spearman correlation coefficient analysis.ResultsThe narrowest area of upper airways was found to be located in the lower bound of velopharynx, where the volume and pressure were statistically significantly increased (P<0.05) and the air velocity was statistically significantly decreased (P<0.05) in the presence of the OA(P<0.05). After wearing OA, pharyngeal resistance was significantly decreased (P<0.05), from 290.63 to 186.25Pa/L, and the airflow resistance of the pharynx has reduced by 35.9%.ConclusionThe enlargement of the upper airway after wearing the OA changed its airflow dynamics, which decreased the negative pressure and resistance in narrow areas of the upper airways. Thus, the collapsibility of the upper airways was reduced and patency was sustained.
Impact of Rigid Gas Permeable Contact Lenses Removal on Anterior and Posterior Corneal Surfaces in Keratoconus Patients
Authors: Itoi Motohiro , Kitazawa Koji , Higashihara Hisayo , Sotozono Chie 
Published: July 2019

AbstractPurposeTo evaluate the impact of removal of rigid gas-permeable (RGP) contact lenses on the anterior and posterior cornea surfaces of eyes with keratoconus.MethodsEight eyes of 8 patients with keratoconus (KC) (age 34.3 ± 15.3 years; range 19–60 years) were enrolled. Anterior segment optical coherence tomography (AS-OCT) was performed at 1, 5, 10, 20, and 60 minutes after the patients removed their RGP contact lenses. Measurements included anterior and posterior best-fit sphere (BFS); elevation values and corneal surface areas; corneal thickness at the thinnest point; and the anterior-posterior ratio of the corneal surface (As/Ps) between 1 minute and 60 minutes after RGP contact lens removal.ResultsAnterior and posterior elevation values and corneal surface areas showed significant increases, whereas anterior and posterior BFS and central corneal thickness decreased significantly (P < 0.01) between 1 minute and 60 minutes after RGP contact lens removal. No statistically significant differences were found in the As/Ps ratio during the first hour after suspending RGP contact lens wear.ConclusionsWe found that the patients with keratoconus experienced significant changes in both the anterior and posterior corneal shape for 60 minutes after removal of RGP contact lenses.
A geometric approach to human stress based on stress-related surrogate measures
Authors: Kloucek Petr , von Gunten Armin 
Published: July 2019

AbstractWe present a predictive Geometric Stress Index (pGSI) and its relation to behavioural Entropy (b𝔼).b𝔼 is a measure of the complexity of an organism’s reactivity to stressors yielding patterns based on different behavioural and physiological variables selected as surrogate markers of stress (SMS). We present a relationship between pGSI andb𝔼 in terms of a power law model. This nonlinear relationship describes congruences in complexity derived from analyses of observable and measurable SMS patterns interpreted as stress. The adjective geometric refers to subdivision(s) of the domain derived from two SMS (heart rate variability and steps frequency) with respect to a positive/negative binary perceptron based on a third SMS (blood oxygenation). The presented power law allows for both quantitative and qualitative evaluations of the consequences of stress measured by pGSI. In particular, we show that elevated stress levels in terms of pGSI leads to a decrease of theb𝔼 of the blood oxygenation as a model of SMS.
Factors associated with unsuppressed viremia in women living with HIV on lifelong ART in a multi-country cohort study: US-PEPFAR PROMOTE study
Authors: Atuhaire Patience , Hanley Sherika , Yende-Zuma Nonhlanhla , Aizire Jim , Stranix-Chibanda Lynda , Makanani Bonus , Milala Beteniko , Cassim Haseena , Taha Taha , Fowler Mary Glenn 
Published: July 2019

AbstractBackgroundDespite recent efforts to scale-up lifelong combination antiretroviral therapy (cART) in sub-Saharan Africa, high rates of unsuppressed viremia persist among cART users, and many countries in the region fall short of the UNAIDS 2020 target to have 90% virally suppressed. We sought to determine the factors associated with unsuppressed viremia (defined for the purpose of this study as >200 copies/ml) among African women on lifelong cART.MethodsThis analysis was based on baseline data of the PROMOTE longitudinal cohort study at 8 sites in Uganda, Malawi, Zimbabwe and South Africa. The study enrolled 1987 women living with HIV who initiated lifelong cART at least 1 year previously to assesses long-term safety and effectiveness of cART. Socio-demographic, clinical, and cART adherence data were collected. We used multivariable Poisson regression with robust variance to identify factors associated with unsuppressed viremia.ResultsAt enrolment, 1947/1987 (98%) women reported taking cART. Of these, HIV-1 remained detectable in 293/1934 (15%), while 216/1934 (11.2%) were considered unsuppressed (>200 copies/ml). The following factors were associated with an increased risk of unsuppressed viremia: not having household electricity (adjusted prevalence rate ratio (aPRR) 1.74, 95% confidence interval (CI) 1.28-2.36, p<0.001); self-reported missed cART doses (aPRR 1.63, 95% CI 1.24-2.13, p<0.001); recent hospitalization (aPRR 2.48, 95% CI 1.28-4.80, p=0.007) and experiencing abnormal vaginal discharge in the last three months (aPRR 1.88; 95% CI 1.16-3.04, p=0.010). Longer time on cART (aPRR 0.75, 95% CI 0.64-0.88, p<0.001) and being older (aPRR 0.77, 95% CI 0.76-0.88, p<0.001) were associated with reduced risk of unsuppressed viremia.ConclusionSocioeconomic barriers such as poverty, not being married, young age, and self-reported missed doses remain key predictors of unsuppressed viremia. Targeted interventions are needed to improve cART adherence among women living with HIV with this risk factor profile.
Assessment of the optimum fertilizer rates and planting density for soybean production in China
Authors: Lv Jilong , He Ping , Wei Dan , Xu Xinpeng , Qiu Shaojun , Zhao Shicheng 
Published: July 2019

AbstractFertilization rate and planting density are important factors affecting crop yield. A large number of soybean [Glycine max (L.) Merr] field experimental data (1998-2017) were collected through different database sources to evaluate the optimum fertilizer rate and planting density for high yield of spring and summer soybean in China. The yield of spring and summer soybean gradually increased over year, with their average yields were 2610 and 2724 kg ha−1, respectively. Based on the fitted quadratic curve, the optimal rate of nitrogen (N), phosphorus (P), and potassium (K) fertilizers for high yield of summer soybean was 96 kg N ha−1, 80 kg P2O5 ha−1, and 126 kg K2O ha−1, and the corresponding yields were 3038, 2801 and 2305 kg ha−1, respectively. The optimal rate of N, P and K fertilizers for spring soybean was 71 kg N ha-1, 108 kg P2O5 ha-1 and 74 kg K2O ha−1, and the corresponding yields were 2932, 2834 and 2678 kg ha−1, respectively. The optimum density was 27×104 and 34×104 plants ha−1 under high yield for summer and spring soybean, respectively. Stepwise regression analysis showed that the P fertilizer had the greatest influence on the spring soybean yield followed by K fertilizer and planting density. For summer soybean, population density had the major effect on yield followed by P fertilizer. Overall, the P fertilization and planting density should be payed attention to increase soybean yield in different regions of China.
Drone-based effective counting and ageing of hippopotamus (Hippopotamus amphibius) in the Okavango Delta in Botswana
Authors: Inman Victoria L. , Kingsford Richard T. , Chase Michael J. , Leggett Keith E. A. 
Published: July 2019

AbstractAccurately estimating hippopotamus (Hippopotamus amphibius) numbers is difficult due to their aggressive nature, amphibious lifestyle, and habit of diving and surfacing. Traditionally, hippos are counted using aerial surveys and land/boat surveys. We compared estimates of numbers of hippos in a lagoon in the Okavango Delta, counted from land and video taken from a DJI Phantom 4™ drone, testing for effectiveness at three heights (40 m, 80 m, and 120 m) and four times of day (early morning, late morning, early afternoon, and late afternoon). In addition, we determined effectiveness for differentiating age classes (juvenile, subadult, and adult), based on visual assessment and measurements from drone images, at different times and heights. Estimates in the pool averaged 9.18 (± 0.25SE, range 1 – 14, n = 112 counts). Drone counts at 40 m produced the highest counts of hippos, 10.6% higher than land counts and drone counts at 80 m, and 17.6% higher than drone counts at 120 m. Fewer hippos were counted in the early morning, when the hippos were active and most likely submerged, compared to all other times of day, when they tended to rest in shallow water with their bodies exposed. We were able to assign age classes to similar numbers of hippos from land counts and counts at 40 m, although land counts were better at identifying juveniles and subadults. Early morning was the least effective time to age hippos given their active behaviour, increasingly problematic with increasing height. Use of a relatively low-cost drone provided a rigorous and repeatable method for estimating numbers and ages of hippos, but not in the early morning.
Farmers’ constraints, governmental support and climate change adaptation: Evidence from Guangdong Province, China
Authors: Xu Ying , Findlay Christopher 
Published: July 2019

While climate change is widely acknowledged, the role of government support in adaptation is less understood. We narrow this knowledge gap by modelling adaptation as a three‐stage process where a farmer sequentially decides: (i) whether there is a need for adaptation; (ii) whether there are constraints that prevent adaptation; and (iii) whether such constraints are removed through government support. We develop a triple‐hurdle model to describe this decision‐making process and empirically estimate the impact of government support using a rural household survey from Guangdong Province, China. It is found that government support is positively associated with raising the odds of adaptation by about one quarter. This magnitude is larger than the estimates in recent literature, suggesting government support is more effective for farmers bound by constraints. Therefore, for cost‐effective policy outcomes there is a need to identify the constraints and the farmers facing them.