bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bighorn sheep gut microbiomes associate with genetic and spatial structure across a metapopulation
Authors: Couch Claire E. , Arnold Holly K. , Crowhurst Rachel S. , Jolles Anna E. , Sharpton Thomas J. , Witczak Marci F. , Epps Clinton W. , Beechler Brianna R. 
Published: April 2020

AbstractStudies in laboratory animals demonstrate important relationships between environment, host traits, and microbiome composition. However, host-microbiome relationships in natural systems are understudied. Here, we investigate metapopulation-scale microbiome variation in a wild mammalian host, the desert bighorn sheep (Ovis canadensis nelsoni). We sought to identify over-represented microbial clades and understand how landscape variables and host traits influence microbiome composition across the host metapopulation. To address these questions, we performed 16S sequencing on fecal DNA samples from thirty-nine bighorn sheep across seven loosely connected populations in the Mojave Desert and assessed relationships between microbiome composition, environmental variation, geographic distribution, and microsatellite-derived host population structure and heterozygosity. We first used a phylogenetically-informed algorithm to identify bacterial clades conserved across the metapopulation. Members of genusRuminococcaceae, genusLachnospiraceae, and familyChristensenellaceae R7 groupwere among the clades over-represented across the metapopulation, consistent with their known roles as rumen symbionts in domestic livestock. Additionally, compositional variation among hosts correlated with individual-level geographic and genetic structure, and with population-level differences in genetic heterozygosity. This study identifies microbiome community variation across a mammalian metapopulation, potentially associated with genetic and geographic population structure. Our results imply that microbiome composition may diverge in accordance with landscape-scale environmental and host population characteristics.
Determining organ weight toxicity with Bayesian causal models: Improving on the analysis of relative organ weights
Authors: Lazic Stanley E. , Semenova Elizaveta , Williams Dominic P. 
Published: April 2020

AbstractRegulatory authorities require animal toxicity tests for new chemical entities. Organ weight changes are accepted as a sensitive indicator of chemically induced organ damage, but can be difficult to interpret because changes in organ weight might reflect chemically-induced changes in overall body weight. A common solution is to calculate the relative organ weight (organ to body weight ratio), but this inadequately controls for the dependence on body weight – a point made by statisticians for decades, but which has not been widely adopted. The recommended solution is an analysis of covariance (ANCOVA), but it is rarely used, possibly because both the method of statistical correction and the interpretation of the output may be unclear to those with minimal statistical training. Using relative organ weights can easily lead to incorrect conclusions, resulting in poor decisions, wasted resources, and an ethically questionable use of animals. We propose to cast the problem into a causal modelling framework as it directly assesses questions of scientific interest, the results are easy to interpret, and the analysis is simple to perform with freely available software. Furthermore, by taking a Bayesian approach we can model unequal variances, control for multiple testing, and directly provide evidence of safety.
Polymorphism of nucleotide binding domain-like receptor protein 3 (NLRP3) increases susceptibility of total urinary arsenic to renal cell carcinoma
Authors: Chung Chi-Jung , Bao Bo-Ying , Lin Ying-Chin , Huang Ya-Li , Shiue Horng-Sheng , Ao Pui-Lam , Pu Yeong-Shiau , Huang Chao-Yuan , Hsueh Yu-Mei 
Published: April 2020

AbstractOur study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08–1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p interaction = 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure.
Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration
Authors: Wang Yanjie , Rhee Kun-Do , Pellegrini Matteo , Yang Xian-Jie 
Published: April 2020

AbstractCiliary neurotrophic factor (CNTF) has been tested in clinical trials for human retinal degeneration due to its potent neuroprotective effects in various animal models. To decipher CNTF-triggered molecular events in the degenerating retina, we performed high-throughput RNA sequencing analyses using the Rds/Prph2 (P216L) transgenic mouse as a preclinical model for retinitis pigmentosa. In the absence of CNTF treatment, transcriptome alterations were detected at the onset of rod degeneration compared with wild type mice, including reduction of key photoreceptor transcription factors Crx, Nrl, and rod phototransduction genes. Short-term CNTF treatments caused further declines of photoreceptor transcription factors accompanied by marked decreases of both rod- and cone-specific gene expression. In addition, CNTF triggered acute elevation of transcripts in the innate immune system and growth factor signaling. These immune responses were sustained after long-term CNTF exposures that also affected neuronal transmission and metabolism. Comparisons of transcriptomes also uncovered common pathways shared with other retinal degeneration models. Cross referencing bulk RNA-seq with single-cell RNA-seq data revealed the CNTF responsive cell types, including Müller glia, rod and cone photoreceptors, and bipolar cells. Together, these results demonstrate the influence of exogenous CNTF on the retinal transcriptome landscape and illuminate likely CNTF impacts in degenerating human retinas.
Phenology of reproductive condition varies with age and spring weather conditions in male Myotis daubentonii and M. nattereri (Chiroptera: Vespertilionidae)
Authors: Linton Danielle M. , Macdonald David W. 
Published: April 2020

AbstractWe examine the extent to which intrinsic and extrinsic factors influence reproductive phenology in male bats at the population level. Using data from thirteen breeding seasons (2006–2018), encompassing the reproductive histories of 1546 Myotis daubentonii and 530 M. nattereri males, we compare rates of sexual maturation and the temporal distribution of phases of spermatogenesis between juvenile (born that season) and adult (born in previous seasons) males. We found that (i) higher proportions of M. daubentonii (50.81%) than M. nattereri (12.85%) became sexually mature as juveniles, (ii) the proportion of juveniles in reproductive condition per annum was influenced by spring weather conditions, (iii) in both species males that reached puberty as juveniles had higher body mass, on average, than immature juveniles, (iv) older males (aged ≥4 years old) commenced spermatogenesis earlier than young adult males (aged 1–3 years old), whilst juveniles that commenced spermatogenesis did so later in the year than adults, in both species, and (v) M. daubentonii commenced and completed spermatogenesis earlier than M. nattereri in the equivalent age class. Our findings suggest that selection pressure exists for early mating readiness and synchronisation with female receptivity.
Virtual monoenergetic images and post-processing algorithms effectively reduce CT artifacts from intracranial aneurysm treatment
Authors: Zopfs David , Lennartz Simon , Pennig Lenhard , Glauner Andreas , Abdullayev Nuran , Bremm Johannes , Große Hokamp Nils , Persigehl Thorsten , Kabbasch Christoph , Borggrefe Jan , Laukamp Kai Roman 
Published: April 2020

AbstractTo evaluate artifact reduction by virtual monoenergetic images (VMI) and metal artifact reduction algorithms (MAR) as well as the combination of both approaches (VMIMAR) compared to conventional CT images (CI) as standard of reference. In this retrospective study, 35 patients were included who underwent spectral-detector CT (SDCT) with additional MAR-reconstructions due to artifacts from coils or clips. CI, VMI, MAR and VMIMAR (range: 100–200 keV, 10 keV-increment) were reconstructed. Region-of-interest based objective analysis was performed by assessing mean and standard deviation of attenuation (HU) in hypo- and hyperdense artifacts from coils and clips. Visually, extent of artifact reduction and diagnostic assessment were rated. Compared to CI, VMI ≥ 100 keV, MAR and VMIMAR between 100–200 keV increased attenuation in hypoattenuating artifacts (CI/VMI200keV/MAR/VMIMAR200keV, HU: −77.6 ± 81.1/−65.1 ± 103.2/−36.9 ± 27.7/−21.1 ± 26.7) and decreased attenuation in hyperattenuating artifacts (HU: 47.4 ± 32.3/42.1 ± 50.2/29.5 ± 18.9/20.8 ± 25.8). However, differences were only significant for MAR in hypodense and VMIMAR in hypo- and hyperdense artifacts (p < 0.05). Visually, hypo- and hyperdense artifacts were significantly reduced compared to CI by VMI≥140/100keV, MAR and VMIMAR≥100keV. Diagnostic assessment of surrounding brain tissue was significantly improved in VMI≥100keV, MAR and VMIMAR≥100keV. The combination of VMI and MAR facilitates a significant reduction of artifacts adjacent to intracranial coils and clips. Hence, if available, these techniques should be combined for optimal reduction of artifacts following intracranial aneurysm treatment.
Oligocene incursion of the Paratethys seawater to the Junggar Basin, NW China: insight from multiple isotopic analysis of carbonate
Authors: Li Qian , Li Long , Zhang Yuanyuan , Guo Zhaojie 
Published: April 2020

AbstractThe Cenozoic retreat of the Paratethys Sea, as well as uplift of the Tibet plateau and global cooling, have been considered as the main mechanisms for the onset of the Asian monsoon. However, due to the weak constraints on the time and path of the Paratethys Sea, the relative contribution of each of the three factors to the onset of the Asian monsoon remains debatable. Previous studies on the retreat process of the Paratethys suggested that its east coastline had already withdrawn from the Chinese Tianshan area to the west by the Oligocene. Here, we provide a new perspective on this discussion through the study of the Oligocene Anjihaihe dolomite from the northern Chinese Tianshan. Through the comparisons of carbon, oxygen, magnesium, and strontium isotope compositions between the dolomite beds and their interlayered precursor lacustrine limestone beds, we show that the Anjihaihe dolomites were formed at the end of the Oligocene from dolomitization by a fluid characterized by high δ18O, low δ26Mg, low temperature, relatively poor in carbon and Sr. This fluid was likely derived from seawater from the close-by Paratethys Sea at the time. This discovery suggests a larger Paratethys Sea during the Oligocene than previously thought and may have important implications to understand the evolution of the palaeogeography in the Chinese Tianshan region and the onset of the Asian monsoon.
Deep Equatorial Pacific Ocean Oxygenation and Atmospheric CO2 Over The Last Ice Age
Authors: Marcantonio Franco , Hostak Ryan , Hertzberg Jennifer E. , Schmidt Matthew W. 
Published: April 2020

AbstractVentilation of carbon stored in the deep ocean is thought to play an important role in atmospheric CO2 increases associated with Pleistocene deglaciations. The presence of this respired carbon has been recorded by an array of paleoceanographic proxies from various locations across the global ocean. Here we present a new sediment core from the Eastern Equatorial Pacific (EEP) Ocean spanning the last 180,000 years and reconstruct high-resolution 230Th-derived fluxes of 232Th and excess barium, along with redox-sensitive uranium concentrations to examine past variations in dust delivery, export productivity, and bottom-water oxygenation, respectively. Our bottom-water oxygenation record is compared to other similar high-resolution records from across the Pacific and in the Southern Ocean. We suggest that the deep Pacific is a site of respired carbon storage associated with periods of decreased global atmospheric CO2 concentration during the LGM, confirming the conclusions from a wealth of previous studies. However, our study is the first to show a similar relationship beyond the last glacial, extending to at least 70,000 years.
UTMD inhibit EMT of breast cancer through the ROS/miR-200c/ZEB1 axis
Authors: Shi Dandan , Guo Lu , Sun Xiao , Shang Mengmeng , Meng Dong , Zhou Xiaoying , Liu Xinxin , Zhao Yading , Li Jie 
Published: April 2020

AbstractAs a potential drug/gene delivery system, the ultrasound-targeted microbubble destruction (UTMD) system can be used as a vehicle as well as increasing the permeability of biological barriers to enhance the effect of tumor treatment. However, the effect of UTMD in the tumor EMT process is unknown. In this study, we aimed to investigate the potential and mechanism of UTMD induced oxidative stress in inhibiting EMT of breast cancer. Human breast MDA231 cells were treated with microbubble (MB), ultrasound (US) and UTMD, respectively. The generation of oxidative stress, the levels of miR-200c, ZEB1 and vimentin, and the numbers of migratory cells were evaluated quantitatively and qualitatively by the measurement of intracellular reactive oxygen species (ROS), qRT-PCR, western blot assay, and transwell assay. Then, to evaluate the role of UTMD-induced oxidative stress and miR-200c in the epithelial-mesenchymal transition (EMT) inhibition, the ROS scavenger N-acetyl-L-cysteine (NAC) and miR-200c inhibitor were used before UTMD treatment. We found that UTMD induced oxidative stress, upregulated the expression of miR-200c, downregulated the expression of ZEB1 and vimentin and suppressed the MDA231 cell migration. The addition of NAC and miR-200c inhibitor had an opposite impact on the expression of miR-200c and ZEB1, thus hindered the effects of UTMD on MDA231 cells EMT. In conclusion, UTMD can inhibit the EMT characteristics of MDA231 cells. The mechanism may be related to the regulation of the miR-200c/ZEB1 axis through the generation of ROS induced by UTMD, which may provide a new strategy to prevent the tumor cells EMT under UTMD treatment.
Accuracy and stability of an arterial sensor for glucose monitoring in a porcine model using glucose clamp technique
Authors: Aberer Felix , Theiler-Schwetz Verena , Ziko Haris , Hausegger Bettina , Wiederstein-Grasser Iris , Hochfellner Daniel A. , Eller Philipp , Tomberger Georg , Ellmerer Martin , Mader Julia K , Bubalo Vladimir 
Published: April 2020

AbstractIntravascular glucose sensors have the potential to improve and facilitate glycemic control in critically ill patients and might overcome measurement delay and accuracy issues. This study investigated the accuracy and stability of a biosensor for arterial glucose monitoring tested in a hypo- and hyperglycemic clamp experiment in pigs. 12 sensors were tested over 5 consecutive days in 6 different pigs. Samples of sensor and reference measurement pairs were obtained every 15 minutes. 1337 pairs of glucose values (range 37–458 mg/dl) were available for analysis. The systems met ISO 15197:2013 criteria in 99.2% in total, 100% for glucose <100 mg/dl (n = 414) and 98.8% for glucose ≥100 mg/dl (n = 923). The mean absolute relative difference (MARD) during the entire glycemic range of all sensors was 4.3%. The MARDs within the hypoglycemic (<70 mg/dl), euglycemic (≥70–180 mg/dl) and hyperglycemic glucose ranges (≥180 mg/dl) were 6.1%, 3.6% and 4.7%, respectively. Sensors indicated comparable performance on all days investigated (day 1, 3 and 5). None of the systems showed premature failures. In a porcine model, the performance of the biosensor revealed a promising performance. The transfer of these results into a human setting is the logical next step.
Influence of different knee and ankle ranges of motion on the elasticity of triceps surae muscles, Achilles tendon, and plantar fascia
Authors: Liu Chun-Long , Zhou Ji-Ping , Sun Peng-Tao , Chen Bai-Zhen , Zhang Jun , Tang Chun-Zhi , Zhang Zhi-Jie 
Published: April 2020

AbstractStiffness is a valuable indicator of the functional capabilities of muscle-tendon-fascia. Twenty healthy subjects participated in this study in which the passive elastic properties of the medial gastrocnemius (MG), lateral gastrocnemius (LG), soleus muscles (SOL), Achilles tendon (AT, at 0 cm, 3 cm and 6 cm proximal to the calcaneus tubercle, corresponding to AT0cm, AT3cm and AT6cm, respectively) and plantar fascia (PF) were quantified when their knee was fully extended or flexed to 90° using shear wave elastography at 25° of dorsiflexion (DF25°), 0° (neutral position) of flexion, and 50° of plantar flexion (PF50°) of the ankle joint. The stiffnesses of the AT, MG, LG, SOL and the fascia with the knee fully extended were significantly higher than those with the knee flexed to 90° (p < 0.05), while the stiffness of the PF showed the opposite relationship (p < 0.05). When the knee was fully extended, the stiffness was higher in the LG than in the MG at PF50° and 0° (p < 0.01), and it was higher in the MG than in the LG at DF25° (p = 0.009). Nevertheless, regardless of the knee angle, the stiffness decreased from AT3cm > AT0cm > AT6cm at PF50° and 0° (p < 0.001), while the stiffness decreased from AT0cm > AT3cm > AT6cm at DF25°. Regardless of the knee and ankle angles, the stiffness of the PF increased in a proximal-to-distal direction (p < 0.001). These insights can be used to gain a more intuitive understanding of the relationships between the elastic properties of the muscle-tendon unit and its function.
Circular RNA expression profile of lung squamous cell carcinoma: identification of potential biomarkers and therapeutic targets
Authors: Wang Yawei , Zhang Haiyan , Wang Jian , Li Bei , Wang Xiuwen 
Published: April 2020

Abstract
Emerging evidences indicated that exosomal circular RNAs (circRNAs) could serve as diagnostic biomarkers for cancers. However, the expression profiles and clinical significance of circRNAs in lung squamous cell carcinoma (LUSC) remain largely unknown. Herein, we analyzed circRNAs expression profile in six pairs of plasma exosome samples of LUSC patients using high-throughput sequencing. A total of 252 differentially expressed exosomal circRNAs were identified, including 133 up-regulated circRNAs and 119 down-regulated circRNAs. Subsequently, the circRNAs–miRNAs–mRNAs interaction network was built to investigate potential function of circRNAs. Three up-regulated circRNAs (hsa_circ_0014235, hsa_circ_0025580 and hsa_circ_0026403) were implied to participate in cancer-related pathways. QRT-PCR experiment confirmed the up-regulation of hsa_circ_0014235 and hsa_circ_0025580. Finally, clinical studies indicated that hsa_circ_0014235 and hsa_circ_0025580 could serve as novel diagnostic biomarkers for LUSC. Taken together, our study revealed exosomal circRNAs expression profile in LUSC for the first time and showed the important diagnostic potential for circRNAs in LUSC.
Factor XII blockade inhibits aortic dilatation in angiotensin II-infused apolipoprotein E-deficient mice
Authors: Moran Corey S. , Seto Sai-Wang , Biros Erik , Krishna Smriti M. , Morton Susan K. , Kleinschnitz Christoph , Panousis Con , Golledge Jonathan 
Published: April 2020

AbstractAbdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. Chronic inflammation and excessive matrix remodelling are considered important in AAA pathogenesis. Kinins are bioactive peptides important in regulating inflammation. Stimulation of the kinin B2 receptor has been previously reported to promote AAA development and rupture in a mouse model. The endogenous B2 receptor agonist, bradykinin, is generated from the kallikrein–kinin system following activation of plasma kallikrein by Factor XII (FXII). In the current study whole-body FXII deletion, or neutralisation of activated FXII (FXIIa), inhibited expansion of the suprarenal aorta (SRA) of apolipoprotein E-deficient mice in response to angiotensin II (AngII) infusion. FXII deficiency or FXIIa neutralisation led to decreased aortic tumor necrosis factor-α-converting enzyme (TACE/a disintegrin and metalloproteinase-17 (aka tumor necrosis factor-α-converting enzyme) (ADAM-17)) activity, plasma kallikrein concentration, and epithelial growth factor receptor (EGFR) phosphorylation compared with controls. FXII deficiency or neutralisation also reduced Akt1 and Erk1/2 phosphorylation and decreased expression and levels of active matrix metalloproteinase (Mmp)-2 and Mmp-9. The findings suggest that FXII, kallikrein, ADAM-17, and EGFR are important molecular mediators by which AngII induces aneurysm in apolipoprotein E-deficient mice. This could be a novel pathway to target in the design of drugs to limit AAA progression.
Perfecting DNA double-strand break repair on transcribed chromatin
Authors: Tan Xin Yi , Huen Michael S.Y. 
Published: April 2020

Abstract
Timely repair of DNA double-strand break (DSB) entails coordination with the local higher order chromatin structure and its transaction activities, including transcription. Recent studies are uncovering how DSBs trigger transient suppression of nearby transcription to permit faithful DNA repair, failing of which leads to elevated chromosomal aberrations and cell hypersensitivity to DNA damage. Here, we summarize the molecular bases for transcriptional control during DSB metabolism, and discuss how the exquisite coordination between the two DNA-templated processes may underlie maintenance of genome stability and cell homeostasis.