bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synovial fluid lubricin increases in spontaneous canine cruciate ligament rupture
Authors: Wang Yuyan , Gludish David W. , Hayashi Kei , Todhunter Rory J. , Krotscheck Ursula , Johnson Philippa J. , Cummings Bethany P. , Su Jin , Reesink Heidi L. 
Published: October 2020

AbstractLubricin is an important boundary lubricant and chondroprotective glycoprotein in synovial fluid. Both increased and decreased synovial fluid lubricin concentrations have been reported in experimental post-traumatic osteoarthritis (PTOA) animal models and in naturally occurring joint injuries in humans and animals, with no consensus about how lubricin is altered in different species or injury types. Increased synovial fluid lubricin has been observed following intra-articular fracture in humans and horses and in human late-stage osteoarthritis; however, it is unknown how synovial lubricin is affected by knee-destabilizing injuries in large animals. Spontaneous rupture of cranial cruciate ligament (RCCL), the anterior cruciate ligament equivalent in quadrupeds, is a common injury in dogs often accompanied by OA. Here, clinical records, radiographs, and synovial fluid samples from 30 dogs that sustained RCCL and 9 clinically healthy dogs were analyzed. Synovial fluid lubricin concentrations were nearly 16-fold greater in RCCL joints as compared to control joints, while IL-2, IL-6, IL-8, and TNF-α concentrations did not differ between groups. Synovial fluid lubricin concentrations were correlated with the presence of radiographic OA and were elevated in three animals sustaining RCCL injury prior to the radiographic manifestation of OA, indicating that lubricin may be a potential biomarker for early joint injury.
Ninjurin 1 dodecamer peptide containing the N-terminal adhesion motif (N-NAM) exerts proangiogenic effects in HUVECs and in the postischemic brain
Authors: Kim Seung-Woo , Lee Hye-Kyung , Seol Song-I. , Davaanyam Dashdulam , Lee Hahnbie , Lee Ja-Kyeong 
Published: October 2020

AbstractNerve injury-induced protein 1 (Ninjurin 1, Ninj1) is a cell adhesion molecule responsible for cell-to-cell interactions between immune cells and endothelial cells. In our previous paper, we have shown that Ninj1 plays an important role in the infiltration of neutrophils in the postischemic brain and that the dodecamer peptide harboring the Ninj1 N-terminal adhesion motif (N-NAM, Pro26-Asn37) inhibits infiltration of neutrophils in the postischemic brain and confers robust neuroprotective and anti-inflammatory effects. In the present study, we examinedt the pro-angiogenic effect of N-NAM using human umbilical vein endothelial cells (HUVECs) and rat MCAO (middle cerebral artery occlusion) model of stroke. We found that N-NAM promotes proliferation, migration, and tube formation of HUVECs and demonstrate that the suppression of endogenous Ninj1 is responsible for the N-NAM-mediated pro-angiogenic effects. Importantly, a pull-down assay revealed a direct binding between exogenously delivered N-NAM and endogenous Ninj1 and it is N-terminal adhesion motif dependent. In addition, N-NAM activated the Ang1-Tie2 and AKT signaling pathways in HUVECs, and blocking those signaling pathways with specific inhibitors suppressed N-NAM-induced tube formation, indicating critical roles of those signaling pathways in N-NAM-induced angiogenesis. Moreover, in a rat MCAO model, intranasal administration of N-NAM beginning 4 days post-MCAO (1.5 µg daily for 3 days) augmented angiogenesis in the penumbra of the ipsilateral hemisphere of the brain and significantly enhanced total vessel lengths, vessel densities, and pro-angiogenic marker expression. These results demonstrate that the 12-amino acid Ninj1 peptide, which contains the N-terminal adhesion motif of Ninj1, confers pro-angiogenic effects and suggest that those effects might contribute to its neuroprotective effects in the postischemic brain.
An innovative approach for determining the customized refractive index of ectatic corneas in cataractous patients
Authors: Pirhadi Shiva , Maghooli Keivan , Jadidi Khosrow 
Published: October 2020

AbstractThe aim of this study is to determine the customized refractive index of ectatic corneas and also propose a method for determining the corneal and IOL power in these eyes. Seven eyes with moderate and severe corneal ectatic disorders, which had been under cataract surgery, were included. At least three months after cataract surgery, axial length, cornea, IOL thickness and the distance between IOL from cornea, and aberrometry were measured. All the measured points of the posterior and anterior parts of the cornea converted to points cloud and surface by using the MATLAB and Solidworks software. The implanted IOLs were designed by Zemax software. The ray tracing analysis was performed on the customized eye models, and the corneal refractive index was determined by minimizing the difference between the measured aberrations from the device and resulted aberrations from the simulation. Then, by the use of preoperative corneal images, corneal power was calculated by considering the anterior and posterior parts of the cornea and refractive index of 1.376 and the customized corneal refractive index in different regions and finally it was entered into the IOL power calculation formulas. The corneal power in the 4 mm region and the Barrett formula resulted the prediction error of six eyes within ± 1 diopter. It seems that using the total corneal power along with the Barrett formula can prevent postoperative hyperopic shift, especially in eyes with advanced ectatic disorders.
Integrative ecological and molecular analysis indicate high diversity and strict elevational separation of canopy beetles in tropical mountain forests
Authors: Floren Andreas , von Rintelen Thomas , Hebert Paul D. N. , de Araujo Bruno Cancian , Schmidt Stefan , Balke Michael , Narakusumo Raden Pramesa , Peggie Djunijanti , Ubaidillah Rosichon , von Rintelen Kristina , Müller Tobias 
Published: October 2020

AbstractTropical mountain forests contribute disproportionately to terrestrial biodiversity but little is known about insect diversity in the canopy and how it is distributed between tree species. We sampled tree-specific arthropod communities from 28 trees by canopy fogging and analysed beetle communities which were first morphotyped and then identified by their DNA barcodes. Our results show that communities from forests at 1100 and 1700 m a.s.l. are almost completely distinct. Diversity was much lower in the upper forest while community structure changed from many rare, less abundant species to communities with a pronounced dominance structure. We also found significantly higher beta-diversity between trees at the lower than higher elevation forest where community similarity was high. Comparisons on tree species found at both elevations reinforced these results. There was little species overlap between sites indicating limited elevational ranges. Furthermore, we exploited the advantage of DNA barcodes to patterns of haplotype diversity in some of the commoner species. Our results support the advantage of fogging and DNA barcodes for community studies and underline the need for comprehensive research aimed at the preservation of these last remaining pristine forests.
Assembly of the durian chloroplast genome using long PacBio reads
Authors: Shearman Jeremy R. , Sonthirod Chutima , Naktang Chaiwat , Sangsrakru Duangjai , Yoocha Thippawan , Chatbanyong Ratchanee , Vorakuldumrongchai Siriporn , Chusri Orwintinee , Tangphatsornruang Sithichoke , Pootakham Wirulda 
Published: October 2020

AbstractWe have assembled the complete sequence of the Durio zibethinus chloroplast genome using long PacBio reads. Durian is a valuable commercial tree that produces durian fruit, which is popular in Southeast Asia. The chloroplast genome assembled into a single 143 kb cyclic contig that contained 111 genes. There were 46 short direct repeats (45 to 586 bp) and five short inverted repeats (63 to 169 bp). The long reads that were used for the assembly span the entire chloroplast with > 10 kb overlaps and multiple long reads join the start of the contig to the end of the contig. The durian chloroplast was found to lack the large inverted repeat that is common in chloroplast genomes. An additional 24 durian varieties were sequenced and compared to the assembly and found to also lack the large inverted repeat. There were nine SNPs among the varieties.
Haploinsufficiency due to a novel ACO2 deletion causes mitochondrial dysfunction in fibroblasts from a patient with dominant optic nerve atrophy
Authors: Neumann Marie Anne-Catherine , Grossmann Dajana , Schimpf-Linzenbold Simone , Dayan Dana , Stingl Katarina , Ben-Menachem Reut , Pines Ophry , Massart François , Delcambre Sylvie , Ghelfi Jenny , Bohler Jill , Strom Tim , Kessel Amit , Azem Abdussalam , Schöls Ludger , Grünewald Anne , Wissinger Bernd , Krüger Rejko 
Published: October 2020

AbstractACO2 is a mitochondrial protein, which is critically involved in the function of the tricarboxylic acid cycle (TCA), the maintenance of iron homeostasis, oxidative stress defense and the integrity of mitochondrial DNA (mtDNA). Mutations in the ACO2 gene were identified in patients suffering from a broad range of symptoms, including optic nerve atrophy, cortical atrophy, cerebellar atrophy, hypotonia, seizures and intellectual disabilities. In the present study, we identified a heterozygous 51 bp deletion (c.1699_1749del51) in ACO2 in a family with autosomal dominant inherited isolated optic atrophy. A complementation assay using aco1-deficient yeast revealed a growth defect for the mutant ACO2 variant substantiating a pathogenic effect of the deletion. We used patient-derived fibroblasts to characterize cellular phenotypes and found a decrease of ACO2 protein levels, while ACO2 enzyme activity was not affected compared to two age- and gender-matched control lines. Several parameters of mitochondrial function, including mitochondrial morphology, mitochondrial membrane potential or mitochondrial superoxide production, were not changed under baseline conditions. However, basal respiration, maximal respiration, and spare respiratory capacity were reduced in mutant cells. Furthermore, we observed a reduction of mtDNA copy number and reduced mtDNA transcription levels in ACO2-mutant fibroblasts. Inducing oxidative stress led to an increased susceptibility for cell death in ACO2-mutant fibroblasts compared to controls. Our study reveals that a monoallelic mutation in ACO2 is sufficient to promote mitochondrial dysfunction and increased vulnerability to oxidative stress as main drivers of cell death related to optic nerve atrophy.
Towards refining Raman spectroscopy-based assessment of bone composition
Authors: Shah Furqan A. 
Published: October 2020

AbstractVarious compositional parameters are derived using intensity ratios and integral area ratios of different spectral peaks and bands in the Raman spectrum of bone. The$$\nu $$ν1-,$$\nu $$ν2-,$$\nu $$ν3-,$$\nu $$ν4PO43−, and$$\nu_{1} $$ν1CO32−bands represent the inorganic phase while amide I, amide III, Proline, Hydroxyproline, Phenylalanine, δ(CH3), δ(CH2), and$$\nu $$ν(C–H) represent the organic phase. Here, using high-resolution Raman spectroscopy, it is demonstrated that all PO43−bands of bone either partially overlap with or are positioned close to spectral contributions from the organic component. Assigned to the organic component, a shoulder at 393 cm−1compromises accurate estimation of$$\nu $$ν2PO43−integral area, i.e., phosphate/apatite content, with implications for apatite-to-collagen and carbonate-to-phosphate ratios. Another feature at 621 cm−1may be inaccurately interpreted as$$\nu $$ν4PO43−band broadening. In the 1020–1080 cm−1range, the ~ 1047 cm−1$$\nu $$ν3PO43−sub-component is obscured by the 1033 cm−1Phenylalanine peak, while the ~ 1076 cm−1$$\nu $$ν3PO43−sub-component is masked by the$$\nu $$ν1CO32−band. With$$\nu $$ν1PO43−peak broadening,$$\nu $$ν2PO43−integral area increases exponentially and individual peaks comprising the$$\nu $$ν4PO43−band merge together. Therefore,$$\nu $$ν2PO43−and$$\nu $$ν4PO43−band profiles are sensitive to changes in mineral crystallinity.
The effects of fructose and metabolic inhibition on hepatocellular carcinoma
Authors: Dewdney Brittany , Alanazy Mohammed , Gillman Rhys , Walker Sarah , Wankell Miriam , Qiao Liang , George Jacob , Roberts Alexandra , Hebbard Lionel 
Published: October 2020

AbstractHepatocellular carcinoma is rapidly becoming one of the leading causes of cancer-related deaths, largely due to the increasing incidence of non-alcoholic fatty liver disease. This in part may be attributed to Westernised diets high in fructose sugar. While many studies have shown the effects of fructose on inducing metabolic-related liver diseases, little research has investigated the effects of fructose sugar on liver cancer metabolism. The present study aimed to examine the metabolic effects of fructose on hepatocellular carcinoma growth in vitro and in vivo. Fructose sugar was found to reduce cell growth in vitro, and caused alterations in the expression of enzymes involved in the serine-glycine synthesis and pentose phosphate pathways. These biosynthesis pathways are highly active in cancer cells and they utilise glycolytic by-products to produce energy and nucleotides for growth. Hence, the study further investigated the efficacy of two novel drugs that inhibit these pathways, namely NCT-503 and Physcion. The study is the first to show that the combination treatment of NCT-503 and Physcion substantially inhibited hepatocellular carcinoma growth in vitro and in vivo. The combination of fructose diet and metabolism-inhibiting drugs may provide a unique metabolic environment that warrants further investigation in targeting hepatocellular carcinoma.
SNP-SNP interactions of oncogenic long non-coding RNAs HOTAIR and HOTTIP on gastric cancer susceptibility
Authors: Abdi Esmat , Latifi-Navid Saeid , Zahri Saber , Kholghi-Oskooei Vahid , Mostafaiy Behdad , Yazdanbod Abbas , Pourfarzi Farhad 
Published: October 2020

AbstractGenetic variants within oncogenic long non-coding RNAs HOTAIR and HOTTIP may affect their gene expression levels, thereby modifying genetic susceptibility to gastric cancer (GC). In a hospital-based study in Ardabil—a very high-risk area in North-West Iran, 600 blood samples from 300 GC patients and 300 healthy controls were recruited for genotyping. Seven HOTAIR (i.e., rs17720428, rs7958904, rs1899663, and rs4759314) and HOTTIP (i.e., rs3807598, rs17501292, and rs1859168) ‘tag’ single nucleotide polymorphisms (SNPs) were genotyped by the Infinium HTS platform. The rs17720428, rs7958904, and rs1899663 tagSNPs significantly increased GC risk under dominant models by 1.5-, 1.57-, and 1.5-fold, respectively. The G-C-T-A haplotype of HOTAIR tagSNPs increased the risk of GC by 1.31-fold. No significant association was found between HOTTIP SNPs and the risk of GC. HOTAIR and HOTTIP variants were also not associated with any clinicopathologic characteristics. The SNP-SNP interaction of HOTAIR rs17720428/rs7958904 with HOTTIP rs1859168 was associated with an increased risk of GC (rs17720428 TG-rs1859168 CC, OR = 1.76; rs7958904 GC-rs1859168 CC, OR = 1.85; rs7958904 CC-rs1859168 CC, OR = 1.86). Interestingly, the SNP-SNP interaction of HOTAIR rs1899663 with HOTTIP rs1859168 strongly increased the risk of GC (rs1899663 GT-rs1859168 CC, OR = 4.3; rs1899663 TT-rs1859168 CC, OR = 9.37; rs1899663 TT-rs1859168 CA, OR = 6.59). We showed that the HOTAIR rs17720428, rs7958904, and rs1899663 tagSNPs and their interactions with the HOTTIP rs1859168 polymorphism significantly increased the risk of GC. Specifically, novel SNP-SNP interactions between HOTAIR and HOTTIP tagSNPs have a larger impact than individual SNP effects on GC risk, thereby providing us with valuable information to reveal potential biological mechanisms for developing GC.
Immune characterization of pre-clinical murine models of neuroblastoma
Authors: Webb Emily R. , Lanati Silvia , Wareham Carol , Easton Alistair , Dunn Stuart N. , Inzhelevskaya Tatyana , Sadler Freja M. , James Sonya , Ashton-Key Margaret , Cragg Mark S. , Beers Stephen A. , Gray Juliet C. 
Published: October 2020

AbstractImmunotherapy offers a potentially less toxic, more tumor-specific treatment for neuroblastoma than conventional cytotoxic therapies. Accurate and reproducible immune competent preclinical models are key to understanding mechanisms of action, interactions with other therapies and mechanisms of resistance to immunotherapy. Here we characterized the tumor and splenic microenvironment of two syngeneic subcutaneous (NXS2 and 9464D), and a spontaneous transgenic (TH-MYCN) murine model of neuroblastoma, comparing histological features and immune infiltrates to previously published data on human neuroblastoma. Histological sections of frozen tissues were stained by immunohistochemistry and immunofluorescence for immune cell markers and tumor architecture. Tissues were dissociated by enzymatic digestion, stained with panels of antibodies to detect and quantify cancer cells, along with lymphocytic and myeloid infiltration by flow cytometry. Finally, we tested TH-MYCN mice as a feasible model for immunotherapy, using prior treatment with cyclophosphamide to create a therapeutic window of minimal residual disease to favor host immune development. Immune infiltration differed significantly between all the models. TH-MYCN tumors were found to resemble immune infiltration in human tumors more closely than the subcutaneous models, alongside similar GD2 and MHC class I expression. Finally, TH-MYCN transgenic mice were administered cyclophosphamide alone or in combination with an anti-GD2 or anti-4-1BB monoclonal antibody, which resulted in increase in survival in both combination therapies. The TH-MYCN transgenic mouse is a promising in vivo model for testing immunotherapy compounds and combination therapy in a preclinical setting.
Arabidopsis phenotyping reveals the importance of alcohol dehydrogenase and pyruvate decarboxylase for aerobic plant growth
Authors: Ventura Irene , Brunello Luca , Iacopino Sergio , Valeri Maria Cristina , Novi Giacomo , Dornbusch Tino , Perata Pierdomenico , Loreti Elena 
Published: October 2020

AbstractAlcohol dehydrogenase (ADH) and pyruvate decarboxylase (PDC) are key to the establishment of the fermentative metabolism in plants during oxygen shortage. Most of the evidence that both ADH and PDC are required for plant tolerance to hypoxia comes from experiments performed by limiting oxygen in the environment, such as by exposing plants to gaseous hypoxia or to waterlogging or submergence. However, recent experiments have shown that hypoxic niches might exist in plants grown in aerobic conditions. Here, we investigated the importance of ADH and PDC for plant growth and development under aerobic conditions, long-term waterlogging and short-term submergence. Data were collected after optimizing the software associated with a commercially-available phenotyping instrument, to circumvent problems in separation of plants and background pixels based on colour features, which is not applicable for low-oxygen stressed plants due to the low colour contrast of leaves with the brownish soil. The results showed that the growth penalty associated with the lack of functional ADH1 or both PDC1 and PDC2 is greater under aerobic conditions than in hypoxia, highlighting the importance of fermentative metabolism in plants grown under normal, aerobic conditions.
Modeling the dynamics of antibody–target binding in living tumors
Authors: Tang Yu , Cao Yanguang 
Published: October 2020

AbstractAntibodies have become an attractive class of therapeutic agents for solid tumors, mainly because of their high target selectivity and affinity. The target binding properties of antibodies are critical for their efficacy and toxicity. Our lab has developed a bioluminescence resonance energy transfer (BRET) imaging approach that directly supports the measurement of the binding dynamics between antibodies and their targets in the native tumor environment. In the present study, we have developed a spatially resolved computational model analyzing the longitudinal BRET imaging data of antibody–target binding and exploring the mechanisms of biphasic binding dynamics between a model antibody cetuximab and its target, the epidermal growth factor receptor (EGFR). The model suggested that cetuximab is bound differently to EGFR in the stroma-rich area than in stroma-poor regions, which was confirmed by immunofluorescence staining. Compared to the binding in vitro, cetuximab bound to EGFR to a “slower-but-tighter” degree in the living tumors. These findings have provided spatially resolved characterizations of antibody–target binding in living tumors and have yielded many mechanistic insights into the factors that affect antibody interactions with its targets and treatment efficacy.
On the interpretability of predictors in spatial data science: the information horizon
Authors: Behrens Thorsten , Viscarra Rossel Raphael A. 
Published: October 2020

AbstractTwo important theories in spatial modelling relate to structural and spatial dependence. Structural dependence refers to environmental state-factor models, where an environmental property is modelled as a function of the states and interactions of environmental predictors, such as climate, parent material or relief. Commonly, the functions are regression or supervised classification algorithms. Spatial dependence is present in most environmental properties and forms the basis for spatial interpolation and geostatistics. In machine learning, modelling with geographic coordinates or Euclidean distance fields, which resemble linear variograms with infinite ranges, can produce similar interpolations. Interpolations do not lend themselves to causal interpretations. Conversely, with structural modeling, one can, potentially, extract knowledge from the modelling. Two important characteristics of such interpretable environmental modelling are scale and information content. Scale is relevant because very coarse scale predictors can show nearly infinite ranges, falling out of what we call the information horizon, i.e. interpretation using domain knowledge isn’t possible. Regarding information content, recent studies have shown that meaningless predictors, such as paintings or photographs of faces, can be used for spatial environmental modelling of ecological and soil properties, with accurate evaluation statistics. Here, we examine under which conditions modelling with such predictors can lead to accurate statistics and whether an information horizon can be derived for scale and information content.