bluuebunny/crossref_metadata_2025_split huggingface dataset:
CNN-based diagnosis models for canine ulcerative keratitis
Authors: Kim Joon Young , Lee Ha Eun , Choi Yeon Hyung , Lee Suk Jun , Jeon Jong Soo 
Published: October 2019

AbstractThe purpose of this methodological study was to develop a convolutional neural network (CNN), which is a recently developed deep-learning-based image recognition method, to determine corneal ulcer severity in dogs. The CNN model was trained with images for which corneal ulcer severity (normal, superficial, and deep) were previously classified by veterinary ophthalmologists’ diagnostic evaluations of corneal photographs from patients who visited the Veterinary Medical Teaching Hospital (VMTH) at Konkuk University and 3 different veterinary ophthalmology specialty hospitals in Korea. The original images (depicting normal corneas (36) and corneas with superficial (47) ulcers, deep (47) ulcers), flipped images (total 520), rotated images (total 520), and both flipped and rotated images (total 1,040) were labeled, learned and evaluated with GoogLeNet, ResNet, and VGGNet models, and the severity of each corneal ulcer image was determined. To accomplish this task, models based on TensorFlow, an open-source software library developed by Google, were used, and the labeled images were converted into TensorFlow record (TFRecord) format. The models were fine-tuned using a CNN model trained on the ImageNet dataset and then used to predict severity. Most of the models achieved accuracies of over 90% when classifying superficial and deep corneal ulcers, and ResNet and VGGNet achieved accuracies over 90% for classifying normal corneas, corneas with superficial ulcers, and corneas with deep ulcers. This study proposes a method to effectively determine corneal ulcer severity in dogs by using a CNN and concludes that multiple image classification models can be used in the veterinary field.
The impact of exposure to cafeteria diet during pregnancy or lactation on offspring growth and adiposity before weaning
Authors: George Grace , Draycott Sally A. V. , Muir Ronan , Clifford Bethan , Elmes Matthew J. , Langley-Evans Simon C. 
Published: October 2019

AbstractExposure to maternal obesity during early-life can have adverse consequences for offspring growth and adiposity. We aimed to assess the relative contributions of exposure to maternal obesity, induced by a highly varied cafeteria diet, during pregnancy and lactation on these measures in rat offspring prior to weaning. Female Wistar rats were fed either a control (C) or cafeteria diet (O) for 8 weeks before mating, throughout pregnancy and lactation. Offspring were cross-fostered at birth to a dam on the same (CC,OO) or alternate diet prior to birth (CO,OC). Feeding a cafeteria diet based on 40 different foods, was associated with a sustained period of elevated energy intake before birth and during lactation (up to 1.7-fold), through increased sugar, total fat and saturated fat intake, and lower protein consumption. Cafeteria fed dams sustained greater weight than animals fed a control chow diet and greater perirenal adiposity by the end of lactation. Exposure to obesity during pregnancy was associated with lower offspring birth weight and body weight in early-postnatal life. In contrast, exposure during lactation alone reduced offspring weight but increased adiposity in male CO offspring before weaning. This research highlights that exposure to maternal obesity during lactation alone can programme adiposity in a sex specific manner.
Antibacterial, angiogenic, and osteogenic activities of Ca, P, Co, F, and Sr compound doped titania coatings with different Sr content
Authors: Zhou Jianhong , Wang Xiaoli , Zhao Lingzhou 
Published: October 2019

AbstractTitanium implants are often combined with microporous titania coatings simultaneously doped with various elements to enhance their antibacterial, angiogenic and osteogenic activities. To evaluate how Sr doping levels affect properties of titania coatings simultaneously doped with Ca, P, Co and F (TiCPCF coatings), we prepared coatings with Sr contents equal to 6, 11 and 18 wt% (TiCPCF-S6, TiCPCF-S11 and TiCPCF-S18, respectively) using micro-arc oxidation of titanium. Sr presence in TiCPCF coatings did not affect their phase compositions, microstructure, surface wettability, roughness, and adhesion to titanium. Antibacterial, angio- and osteo-genic activities of all the coatings were evaluated. Sr incorporation improved mesenchymal stem cell proliferation, osteogenic differentiation and implant osseointegration. TiCPCF-S11 showed the most optimum Sr content judging by its enhanced osteogenic activity. While Sr incorporation did not weaken angiogenic and antibacterial abilities of TiCPCF. Thus TiCPCF-S11 coating is a very strong candidate to be used as a next-generation bone implant material.
Antimicrobial peptide, cLF36, affects performance and intestinal morphology, microflora, junctional proteins, and immune cells in broilers challenged with E. coli
Authors: Daneshmand Ali , Kermanshahi Hassan , Sekhavati Mohammad Hadi , Javadmanesh Ali , Ahmadian Monireh 
Published: October 2019

AbstractThis study investigated the effects of an antimicrobial peptide (AMP), cLF36, on growth performance and the histophysiological changes of the intestine in E. coli-challenged broiler chickens. A total number of 360 day old male chicks were randomly assigned to 4 groups of 6 replicates as follows: T1) negative control diet based on corn-soybean meal without E. coli challenge and additives; T2) positive control diet based on corn-soybean meal and challenged with E. coli without any additives; T3) positive control diet challenged with E. coli and supplemented with 20 mg AMP (cLF36)/kg diet; T4) positive control diet challenged with E. coli and supplemented with 45 mg antibiotic (bacitracin methylene disalicylate)/kg diet. Results showed that T3 improved growth performance and the jejunal morphology of E. coli-challenged chickens similar to those of T4. While antibiotic non-selectively decreased the population of ileal bacteria, AMP increased the population of Lactobacillus spp. and decreased harmful bacteria in the ileum of E. coli-challenged chickens. Supplementing E. coli-challenged chickens with AMP improved the gene expression of immune cells and upregulated the expression of tight junction proteins compared to other challenged groups. In conclusion, although cLF36 beneficially affected growth performance and the intestinal morphology of E. coli-challenged chickens similar to those of the antibiotic group, this AMP drastically improved the intestinal microbiome, immune cells, and junctional proteins compared to other E. coli-challenged birds, and can be nominated as an alternative for growth promoter antibiotics.
A robust bacterial assay for high-throughput screening of human 4-hydroxyphenylpyruvate dioxygenase inhibitors
Authors: Neuckermans Jessie , Mertens Alan , De Win Dinja , Schwaneberg Ulrich , De Kock Joery 
Published: October 2019

AbstractHereditary tyrosinemia type 1 (HT1) and alkaptonuria (AKU) are inherited metabolic disorders caused by defective enzymes involved in tyrosine catabolism. Nitisinone, an ex-herbicide and member of the β-triketone family, is therapeutically applied to prevent accumulation of toxic metabolites in patients by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD). Here, we developed a colorimetric bacterial whole-cell screening system that allows quantifying the inhibitory effects of human HPD inhibitors in a high-throughput and a robust fashion. The principle of our screening system is based on the degradation of tyrosine through 4-hydroxyphenylpyruvate into homogentisate by human HPD expressed in E. coli and subsequent production of a soluble melanin-like pigment. With the aim to optimise the assay, we tested different E. coli strains, expression and reaction temperatures, and time-points for supplementing the substrate. We found that in our assay the addition of prototypical β-triketone HPD inhibitors decreases pigment production in a dose-dependent manner with increasing inhibitor concentrations. In addition, plate uniformity, signal variability and spatial uniformity assessment showed that we have developed a robust high-throughput screening assay that is simple to use, cost-effective and enables identification and evaluation of novel therapeutic human HPD inhibitors for the treatment of tyrosine-related metabolic disorders.
Deciphering bacterial and fungal endophyte communities in leaves of two maple trees with green islands
Authors: Wemheuer Franziska , Wemheuer Bernd , Daniel Rolf , Vidal Stefan 
Published: October 2019

AbstractGreen islands (the re-greening of senescent leaf tissues) are particularly evident on leaves infected with fungal pathogens. To date, there is only a limited number of studies investigating foliar endophytic microorganisms in phytopathogen-infected leaves. Here, we analysed bacterial and fungal endophyte communities in leaves without green islands (control leaves; CL), within green island areas (GLA) and the surrounding yellow leaf areas (YLA) of leaves with green islands of Acer campestre and A. platanoides. GLA samples of A. campestre and A. platanoides were dominated by Sawadaea polyfida and S. bicornis, respectively, suggesting that these fungi might be responsible for the green islands. We detected a higher fungal richness and diversity in CL compared to GLA samples of A. campestre. Leaf status (CL, GLA, YLA) significantly altered the composition of fungal communities of A. campestre. This was related to differences in fungal community composition between YLA and GLA samples. Site was the main driver of bacterial communities, suggesting that bacterial and fungal endophytes are shaped by different factors. Overall, we observed Acer species-specific responses of endophyte communities towards the presence of green islands and/or leaf type, which might be attributed to several fungi and bacteria specifically associated with one Acer species.
Global areas of low human impact (‘Low Impact Areas’) and fragmentation of the natural world
Authors: Jacobson Andrew P. , Riggio Jason , M. Tait Alexander , E. M. Baillie Jonathan 
Published: October 2019

AbstractHabitat loss and fragmentation due to human activities is the leading cause of the loss of biodiversity and ecosystem services. Protected areas are the primary response to this challenge and are the cornerstone of biodiversity conservation efforts. Roughly 15% of land is currently protected although there is momentum to dramatically raise protected area targets towards 50%. But, how much land remains in a natural state? We answer this critical question by using open-access, frequently updated data sets on terrestrial human impacts to create a new categorical map of global human influence (‘Low Impact Areas’) at a 1 km2resolution. We found that 56% of the terrestrial surface, minus permanent ice and snow, currently has low human impact. This suggests that increased protected area targets could be met in areas minimally impacted by people, although there is substantial variation across ecoregions and biomes. While habitat loss is well documented, habitat fragmentation and differences in fragmentation rates between biomes has received little attention. Low Impact Areas uniquely enabled us to calculate global fragmentation rates across biomes, and we compared these to an idealized globe with no human-caused fragmentation. The land in Low Impact Areas is heavily fragmented, compromised by reduced patch size and core area, and exposed to edge effects. Tropical dry forests and temperate grasslands are the world’s most impacted biomes. We demonstrate that when habitat fragmentation is considered in addition to habitat loss, the world’s species, ecosystems and associated services are in worse condition than previously reported.
Comparisons of lung and gluteus transcriptome profiles between yaks at different ages
Authors: Xin Jin-Wei , Chai Zhi-Xin , Zhang Cheng-Fu , Zhang Qiang , Zhu Yong , Cao Han-Wen , Ji Qiu-Mei , Zhong Jin-Cheng 
Published: October 2019

AbstractThe yak,Bos grunniens, is the only large mammal in the Qinghai-Tibet Plateau and has been bred to provide meat, milk, and transportation. Previous studies indicate that the immune system contributes to the yak’s adaptation to high-altitude environments. In order to further investigate changes in immune function during yak development, we compared the transcriptome profiles of gluteus and lung tissues among yaks at 6, 30, 60, and 90 months of age. Analyses of significantly differentially expressed genes (DEGs) in lung tissues revealed that immune function was more activated at 6-months and less activated at 90-months than in the 30 and 60-month-old animals. DEG exploration in gluteal tissues revealed that immune functions were more highly activated at both 6 and 90-months, compared with 30 and 60-months. Immune system activation in the muscle and lung tissues of 30-month-old yaks may increase their resistance to infections, while decreased may be due to aging. Furthermore, the higher immune activation status in the gluteal tissues in 90-month-old yaks could be due to muscle injury and subsequent regeneration, which is supported by the fact that 5 unigenes related with muscle injury and 3 related to muscle regeneration displayed greater expression levels at 90-months than at 30 and 60-months. Overall, the present study highlights the important role of the immune system in yak development, which will facilitate future investigations.
Epilepsy and neuropsychiatric comorbidities in mice carrying a recurrent Dravet syndrome SCN1A missense mutation
Authors: Ricobaraza Ana , Mora-Jimenez Lucia , Puerta Elena , Sanchez-Carpintero Rocio , Mingorance Ana , Artieda Julio , Nicolas Maria Jesus , Besne Guillermo , Bunuales Maria , Gonzalez-Aparicio Manuela , Sola-Sevilla Noemi , Valencia Miguel , Hernandez-Alcoceba Ruben 
Published: October 2019

AbstractDravet Syndrome (DS) is an encephalopathy with epilepsy associated with multiple neuropsychiatric comorbidities. In up to 90% of cases, it is caused by functional happloinsufficiency of the SCN1A gene, which encodes the alpha subunit of a voltage-dependent sodium channel (Nav1.1). Preclinical development of new targeted therapies requires accessible animal models which recapitulate the disease at the genetic and clinical levels. Here we describe that a C57BL/6 J knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V) presents a full spectrum of DS manifestations. This includes 70% mortality rate during the first 8 weeks of age, reduced threshold for heat-induced seizures (4.7 °C lower compared with control littermates), cognitive impairment, motor disturbances, anxiety, hyperactive behavior and defects in the interaction with the environment. In contrast, sociability was relatively preserved. Electrophysiological studies showed spontaneous interictal epileptiform discharges, which increased in a temperature-dependent manner. Seizures were multifocal, with different origins within and across individuals. They showed intra/inter-hemispheric propagation and often resulted in generalized tonic-clonic seizures. 18F-labelled flourodeoxyglucose positron emission tomography (FDG-PET) revealed a global increase in glucose uptake in the brain of Scn1aWT/A1783V mice. We conclude that the Scn1aWT/A1783V model is a robust research platform for the evaluation of new therapies against DS.
Loss of secretin results in systemic and pulmonary hypertension with cardiopulmonary pathologies in mice
Authors: Zaw Aung Moe , Sekar Revathi , Mak Sarah O. K. , Law Helen K. W. , Chow Billy K. C. 
Published: October 2019

AbstractMore than 1 billion people globally are suffering from hypertension, which is a long-term incurable medical condition that can further lead to dangerous complications and death if left untreated. In earlier studies, the brain-gut peptide secretin (SCT) was found to be able to control blood pressure by its cardiovascular and pulmonary effects. For example, serum SCT in patients with congestive heart failure was one-third of the normal level. These observations strongly suggest that SCT has a causal role in blood pressure control, and in this report, we used constitutive SCT knockout (SCT−/−) mice and control C57BL/6N mice to investigate differences in the morphology, function, underlying mechanisms and response to SCT treatment. We found that SCT−/− mice suffer from systemic and pulmonary hypertension with increased fibrosis in the lungs and heart. Small airway remodelling and pulmonary inflammation were also found in SCT−/− mice. Serum NO and VEGF levels were reduced and plasma aldosterone levels were increased in SCT−/− mice. Elevated cardiac aldosterone and decreased VEGF in the lungs were observed in the SCT−/− mice. More interestingly, SCT replacement in SCT−/− mice could prevent the development of heart and lung pathologies compared to the untreated group. Taken together, we comprehensively demonstrated the critical role of SCT in the cardiovascular and pulmonary systems and provide new insight into the potential role of SCT in the pathological development of cardiopulmonary and cardiovascular diseases.
Human amniotic membrane conditioned medium inhibits proliferation and modulates related microRNAs expression in hepatocarcinoma cells
Authors: Riedel Rodrigo , Pérez-Pérez Antonio , Carmona-Fernández Antonio , Jaime Mariana , Casale Roberto , Dueñas José Luis , Guadix Pilar , Sánchez-Margalet Víctor , Varone Cecilia L. , Maymó Julieta L. 
Published: October 2019

AbstractThe placental stem cells have called the focus of attention for their therapeutic potential to treat different diseases, including cancer. There is plenty evidence about the antiproliferative, antiangiogenic and proapoptotic properties of the amniotic membrane. Liver cancer is the fifth cause of cancer in the world, with a poor prognosis and survival. Alternative treatments to radio- or chemotherapy have been searched. In this work we aimed to study the antiproliferative properties of the human amniotic membrane conditioned medium (AM-CM) in hepatocarcinoma cells. In addition, we have analyzed the regulation of pro and antiOncomiRs expression involved in hepatocarcinoma physiology. We have determined by 3H-thymidine incorporation assay that AM-CM inhibits DNA synthesis in HepG2 cells after 72 h of treatment. AM-CM pure or diluted at 50% and 25% also diminished HepG2 and HuH-7 cells viability and cell number. Furthermore, AM-CM induced cell cycle arrest in G2/M. When proliferation mechanisms were analyzed we found that AM-CM reduced the expression of both Cyclin D1 mRNA and protein. Nuclear expression of Ki-67 was also reduced. We observed that this CM was able to promote the expression of p53 and p21 mRNA and proteins, leading to cell growth arrest. Moreover, AM-CM induced an increase in nuclear p21 localization, observed by immunofluorescence. As p53 levels were increased, Mdm-2 expression was downregulated. Interestingly, HepG2 and HuH-7 cells treatment with AM-CM during 24 and 72 h produced an upregulation of antiOncomiRs 15a and 210, and a downregulation of proOncomiRs 206 and 145. We provide new evidence about the promising novel applications of human amniotic membrane in liver cancer.
Time origin and structural analysis of the induced CRISPR/cas9 megabase-sized deletions and duplications involving the Cntn6 gene in mice
Authors: Pristyazhnyuk Inna E. , Minina Julia , Korablev Alexey , Serova Irina , Fishman Veniamin , Gridina Maria , Rozhdestvensky Timofey S. , Gubar Leonid , Skryabin Boris V. , Serov Oleg L. 
Published: October 2019

AbstractIn a previous study using one-step CRISPR/Cas9 genome editing in mouse zygotes, we created five founders carrying a 1,137 kb deletion and two founders carrying the same deletion, plus a 2,274 kb duplication involving the Cntn6 gene (encoding contactin-6). Using these mice, the present study had the following aims: (i) to establish stage of origin of these rearrangements; (ii) to determine the fate of the deleted DNA fragments; and (iii) to estimate the scale of unpredicted DNA changes accompanying the rearrangements. The present study demonstrated that all targeted deletions and duplications occurred at the one-cell stage and more often in one pronucleus only. FISH analysis revealed that there were no traces of the deleted DNA fragments either within chromosome 6 or on other chromosomes. These data were consistent with the Southern blot analysis showing that chromosomes with deletion often had close to expected sizes of removed DNA fragments. High-throughput DNA sequencing of two homozygotes for duplication demonstrated that there were no unexpected significant or scale DNA changes either at the gRNA and joint sites or other genome sites. Thus, our data suggested that CRISPR/Cas9 technology could generate megabase-sized deletions and duplications in mouse gametes at a reasonably specific level.
A pharmacokinetic model of lead absorption and calcium competitive dynamics
Authors: Rădulescu Anca , Lundgren Steven 
Published: October 2019

AbstractLead is a naturally-occurring element. It has been known to man for a long time, and it is one of the longest established poisons. The current consensus is that no level of lead exposure should be deemed “safe”. New evidence regarding the blood levels at which morbidities occur has prompted the CDC to reduce the screening guideline of 10 μg/dl to 2 μg/dl. Measurable cognitive decline (reduced IQ, academic deficits) have been found to occur at levels below 10 μg/dl, especially in children. Knowledge of lead pharmacology allows us to better understand its absorption and metabolization, mechanisms that produce its medical consequences. Based upon an original and very simplified compartmental model of Rabinowitz (1973) with only three major compartments (blood, bone and soft tissue), extensive biophysical models sprouted over the following two decades. However, none of these models have been specifically designed to use new knowledge of lead molecular dynamics to understand its deleterious effects on the brain. We build and analyze a compartmental model of lead pharmacokinetics, focused specifically on addressing neurotoxicity. We use traditional phase space methods, parameter sensitivity analysis and bifurcation theory to study the transitions in the system’s behavior in response to various physiological parameters. We conclude that modeling the complex interaction of lead and calcium along their dynamic trajectory may successfully explain counter-intuitive effects on systemic function and neural behavior which could not be addressed by existing linear models. Our results encourage further efforts towards using nonlinear phenomenology in conjunction with empirically driven system parameters, to obtain a biophysical model able to provide clinical assessments and predictions.