bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of reference genes for RT-qPCR data normalisation in aging studies
Authors: González-Bermúdez Lourdes , Anglada Teresa , Genescà Anna , Martín Marta , Terradas Mariona 
Published: September 2019

AbstractAging is associated with changes in gene expression levels that affect cellular functions and predispose to age-related diseases. The use of candidate genes whose expression remains stable during aging is required to correctly address the age-associated variations in expression levels. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) has become a powerful approach for sensitive gene expression analysis. Reliable RT-qPCR assays rely on the normalisation of the results to stable reference genes. Taken these data together, here we evaluated the expression stability of eight frequently used reference genes in three aging models: oncogene-induced senescence (OIS), in vitro and in vivo aging. Using NormFinder and geNorm algorithms, we identified that the most stable reference gene pairs were PUM1 and TBP in OIS, GUSB and PUM1 for in vitro aging and GUSB and OAZ1 for in vivo aging. To validate these candidates, we used them to normalise the expression data of CDKN1A, APOD and TFRC genes, whose expression is known to be affected during OIS, in vitro and in vivo aging. This study demonstrates that accurate normalisation of RT-qPCR data is crucial in aging research and provides a specific subset of stable reference genes for future aging studies.
Tissue-specific mouse mRNA isoform networks
Authors: Kandoi Gaurav , Dickerson Julie A. 
Published: September 2019

AbstractAlternative Splicing produces multiple mRNA isoforms of genes which have important diverse roles such as regulation of gene expression, human heritable diseases, and response to environmental stresses. However, little has been done to assign functions at the mRNA isoform level. Functional networks, where the interactions are quantified by their probability of being involved in the same biological process are typically generated at the gene level. We use a diverse array of tissue-specific RNA-seq datasets and sequence information to train random forest models that predict the functional networks. Since there is no mRNA isoform-level gold standard, we use single isoform genes co-annotated to Gene Ontology biological process annotations, Kyoto Encyclopedia of Genes and Genomes pathways, BioCyc pathways and protein-protein interactions as functionally related (positive pair). To generate the non-functional pairs (negative pair), we use the Gene Ontology annotations tagged with “NOT” qualifier. We describe 17 Tissue-spEcific mrNa iSoform functIOnal Networks (TENSION) following a leave-one-tissue-out strategy in addition to an organism level reference functional network for mouse. We validate our predictions by comparing its performance with previous methods, randomized positive and negative class labels, updated Gene Ontology annotations, and by literature evidence. We demonstrate the ability of our networks to reveal tissue-specific functional differences of the isoforms of the same genes. All scripts and data from TENSION are available at:https://doi.org/10.25380/iastate.c.4275191.
Additive effects of connectivity provided by different habitat types drive plant assembly
Authors: Uroy Léa , Mony Cendrine , Ernoult Aude 
Published: September 2019

AbstractHow connectivity affects plant assemblages is a central issue in landscape ecology. So far, empirical studies have produced contradictory results, possibly because studies: (1) inaccurately assess connectivity by prioritizing the respective effect of the type of habitat on plant assemblages and (2) omit the range of possible plant responses to connectivity depending on dispersal vectors. We focused on three dominant habitat types in agricultural landscapes (woodland, grassland and cropland), and analysed the effect of connectivity on herbaceous plant assemblage similarity for three primary dispersal modes (animal-dispersed, wind-dispersed and unassisted). Using circuit theory, we measured connectivity provided by woodland, grassland and cropland habitats independently. The similarity of plant assemblages was evaluated relative to the random expectation based on the regional pool. Overall, plant assemblage similarity in woodlands and temporary grasslands was dependent on connectivity, but not in wheat croplands. Only animal-dispersed species responded to connectivity. The similarity of animal-dispersed assemblages in woodlands was increased by the connectivity provided by woodland habitats, but was reduced by cropland habitats, whereas in temporary grasslands, similarity was increased by the connectivity provided by cropland habitats. Our results suggest that animal-dispersed species supplement their dispersal pathways, thus improving our knowledge of plant assembly rules in fragmented landscapes.
Design and manufacture of 3D cell culture plate for mass production of cell-spheroids
Authors: Lee Dongkyoung , Pathak Shiva , Jeong Jee-Heon 
Published: September 2019

AbstractA 3D cell culture is preferred to 2D cell culture since it allows cells to grow in all directionsin vitro, similar to how they wouldin vivo. 3D cell culture plates currently used in tissue engineering research have limited access to control the geometry. Furthermore, 3D cell culture plate manufacturing methods are relatively complex, time-consuming, labor-intensive, and expensive. Therefore, a design and manufacturing method, which has relatively low cost, high throughput, and high size flexibility, is proposed. Cell culture plate was fabricated by computer aided design and manufacturing software using polydimethylsiloxane as a plate constituent. With the successfully-developed 3D cell culture plate, the morphology and viability of the cultured mesenchymal stem cells were tested.The mesenchymal stem cells seeded on the newly-fabricated 3D cell culture plate aggregated to form 3D spheroids within 24 h of incubation and well-maintained their viability. Thus, due to the capacity of mass production of the cell spheroids with a desired cell viability, the newly-fabricated plate has a great promise to prepare 3D cell spheroids for experimental as well as clinical applications.
Tissue-engineered blood-brain barrier models via directed differentiation of human induced pluripotent stem cells
Authors: Grifno Gabrielle N. , Farrell Alanna M. , Linville Raleigh M. , Arevalo Diego , Kim Joo Ho , Gu Luo , Searson Peter C. 
Published: September 2019

AbstractThree-dimensional (3D) tissue-engineered models of the blood-brain barrier (BBB) recapitulate in vivo shear stress, cylindrical geometry, and cell-ECM interactions. Here we address four issues associated with BBB models: cell source, barrier function, cryopreservation, and matrix stiffness. We reproduce a directed differentiation of brain microvascular endothelial cells (dhBMECs) from two fluorescently labeled human induced pluripotent stem cell lines (hiPSCs) and demonstrate physiological permeability of Lucifer yellow over six days. Microvessels formed from cryopreserved dhBMECs show expression of BBB markers and maintain physiological barrier function comparable to non-cryopreserved cells. Microvessels displaying physiological barrier function are formed in collagen I hydrogels with stiffness matching that of human brain. The dilation response of microvessels was linear with increasing transmural pressure and was dependent on matrix stiffness. Together these results advance capabilities for tissue-engineered BBB models.
Molecular phenotyping using networks, diffusion, and topology: soft tissue sarcoma
Authors: Mathews James C. , Pouryahya Maryam , Moosmüller Caroline , Kevrekidis Yannis G. , Deasy Joseph O. , Tannenbaum Allen 
Published: September 2019

AbstractMany biological datasets are high-dimensional yet manifest an underlying order. In this paper, we describe an unsupervised data analysis methodology that operates in the setting of a multivariate dataset and a network which expresses influence between the variables of the given set. The technique involves network geometry employing the Wasserstein distance, global spectral analysis in the form of diffusion maps, and topological data analysis using the Mapper algorithm. The prototypical application is to gene expression profiles obtained from RNA-Seq experiments on a collection of tissue samples, considering only genes whose protein products participate in a known pathway or network of interest. Employing the technique, we discern several coherent states or signatures displayed by the gene expression profiles of the sarcomas in the Cancer Genome Atlas along the TP53 (p53) signaling network. The signatures substantially recover the leiomyosarcoma, dedifferentiated liposarcoma (DDLPS), and synovial sarcoma histological subtype diagnoses, and they also include a new signature defined by activation and inactivation of about a dozen genes, including activation of serine endopeptidase inhibitor SERPINE1 and inactivation of TP53-family tumor suppressor gene TP73.
Spinal arthritis in invasive cane toads is linked to rate of dispersal as well as to latitude
Authors: Brown Gregory P. , Schwarzkopf Lin , Alford Ross A. , Bower Deborah , Shine Richard 
Published: September 2019

AbstractInitial research on the spread of cane toads (Rhinella marina) through tropical Australia reported a high incidence of spinal arthritis (spondylosis) in toads at the invasion front (where toads disperse rapidly), but not in areas colonized earlier (where toads are more sedentary). The idea that spondylosis was a cost of rapid dispersal was challenged by wider spatial sampling which linked rates of spondylosis to hot (tropical) climates rather than to dispersal rates. Here, the authors of these competing interpretations collaborate to reinterpret the data. Our reanalysis supports both previous hypotheses; rates of spondylosis are higher in populations established by fast-dispersing toads, and are higher in tropical than in temperate environments; they are also higher in larger toads. The functional reason for climatic effects is unclear, but might involve effects on the soil-living bacteria involved in the induction of spondylosis; and/or may reflect higher movement (as opposed to dispersal) or more pronounced dry-season aggregation rates of toads in tropical conditions.
Multiplexed ultrasound beam summation for side lobe reduction
Authors: Ilovitsh Asaf , Ilovitsh Tali , Ferrara Katherine W. 
Published: September 2019

AbstractTwo-way focusing, which relies on sweeping a focused beam across a field of view, is the conventional method for performing high-quality ultrasound imaging. Side lobes resulting from diffraction reduce the image contrast, thus degrade the image quality. In this paper, we present a new method for beam shaping the transmitted ultrasound waveform in order to reduce side lobes and improve image quality. The beam shaping is achieved by transmitting two different waveforms that are interlaced between the odd and even elements. One waveform generates a standard diffraction-limited single focus, and the second waveform generates two foci at the same focal depth as the single focus. The distance between the two foci is selected such that they will destructively interfere with the first order side lobes of the single focus, effectively eliminating these side lobes. A 7.5 dB side lobe reduction was measured experimentally at a depth of 60 mm, using a phased array transducer with a center frequency of 3 MHz. This real-time method utilizes standard receive beamforming, identical to traditional two-way focusing, and does not require post-processing. The method can be implemented with conventional ultrasound systems, without the need for additional components. The proposed method is described analytically, optimized via numerical simulation, and validated by experiments using wire targets, tissue-mimicking phantoms, and in vivo imaging of the rat bladder.
Energy balance model of mass balance and its sensitivity to meteorological variability on Urumqi River Glacier No.1 in the Chinese Tien Shan
Authors: Che Yanjun , Zhang Mingjun , Li Zhongqin , Wei Yanqiang , Nan Zhuotong , Li Huilin , Wang Shengjie , Su Bo 
Published: September 2019

AbstractEnergy exchanges between atmosphere and glacier surface control the net energy available for snow and ice melt. Based on the meteorological records in Urumqi River Glacier No.1 (URGN1) in the Chinese Tien Shan during the period of 2012–2015, an energy-mass balance model was run to assess the sensitivity of glacier mass balance to air temperature (T), precipitation (P), incoming shortwave radiation (Sin), relative humidity (RH), and wind speed (u) in the URGN1, respectively. The results showed that the glacier melting was mainly controlled by the net shortwave radiation. The glacier mass balance was very sensitivity to albedo for snow and the time scale determining how long the snow albedo approaches the albedo for firn after a snowfall. The net annual mass balance of URGN1 was decreased by 0.44 m w.e. when increased by 1 K in air temperature, while it was increased 0.30 m w.e. when decreased by 1 K. The net total mass balance increased by 0.55 m w.e. when increased precipitation by 10%, while it was decreased by 0.61 m w.e. when decreased precipitation by 10%. We also found that the change in glacier mass balance was non-linear when increased or decreased input condition of climate change. The sensitivity of mass balance to increase in Sin, u, and RH were at −0.015 m w.e.%−1, −0.020 m w.e.%−1, and −0.018 m w.e.%−1, respectively, while they were at 0.012 m w.e.%−1, 0.027 m w.e.%−1, and 0.017 m w.e.%−1 when decreasing in those conditions, respectively. In addition, the simulations of coupled perturbation for temperature and precipitation indicated that the precipitation needed to increase by 23% could justly compensate to the additional mass loss due to increase by 1 K in air temperature. We also found that the sensitivities of glacier mass balance in response to climate change were different in different mountain ranges, which were mainly resulted from the discrepancies in the ratio of snowfall to precipitation during the ablation season, the amount of melt energy during the ablation season, and precipitation seasonality in the different local regions.
PKN1 kinase-negative knock-in mice develop splenomegaly and leukopenia at advanced age without obvious autoimmune-like phenotypes
Authors: Siddique Salman Mahmud , Kubouchi Koji , Shinmichi Yuka , Sawada Nana , Sugiura Reiko , Itoh Yasushi , Uehara Shunsuke , Nishimura Kanae , Okamura Shunsuke , Ohsaki Hiroyuki , Kamoshida Shingo , Yamashita Yusuke , Tamura Shinobu , Sonoki Takashi , Matsuoka Hiroshi , Itoh Tomoo , Mukai Hideyuki 
Published: September 2019

AbstractProtein kinase N1 (PKN1) knockout (KO) mice spontaneously form germinal centers (GCs) and develop an autoimmune-like disease with age. Here, we investigated the function of PKN1 kinase activity in vivo using aged mice deficient in kinase activity resulting from the introduction of a point mutation (T778A) in the activation loop of the enzyme. PKN1[T778A] mice reached adulthood without external abnormalities; however, the average spleen size and weight of aged PKN1[T778A] mice increased significantly compared to aged wild type (WT) mice. Histologic examination and Southern blot analyses of spleens showed extramedullary hematopoiesis and/or lymphomagenesis in some cases, although without significantly different incidences between PKN1[T778A] and WT mice. Additionally, flow cytometry revealed increased numbers in B220+, CD3+, Gr1+ and CD193+ leukocytes in the spleen of aged PKN1[T778A] mice, whereas the number of lymphocytes, neutrophils, eosinophils, and monocytes was reduced in the peripheral blood, suggesting an advanced impairment of leukocyte trafficking with age. Moreover, aged PKN1[T778A] mice showed no obvious GC formation nor autoimmune-like phenotypes, such as glomerulonephritis or increased anti-dsDNA antibody titer, in peripheral blood. Our results showing phenotypic differences between aged Pkn1-KO and PKN1[T778A] mice may provide insight into the importance of PKN1-specific kinase-independent functions in vivo.
New insights into prime Southern Ocean forage grounds for thriving Western Australian humpback whales
Authors: Bestley Sophie , Andrews-Goff Virginia , van Wijk Esmee , Rintoul Stephen R. , Double Michael C. , How Jason 
Published: September 2019

AbstractHumpback whale populations migrate extensively between winter breeding grounds and summer feeding grounds, however known links to remote Antarctic feeding grounds remain limited in many cases. New satellite tracks detail humpback whale migration pathways from Western Australia into the Southern Ocean. These highlight a focal feeding area during austral spring and early summer at the southern Kerguelen plateau, in a western boundary current where a sharp northward turn and retroflection of ocean fronts occurs along the eastern plateau edge. The topographic steering of oceanographic features here likely supports a predictable, productive and persistent forage ground. The spatial distribution of whaling catches and Discovery era mark-recaptures confirms the importance of this region to Western Australian humpback whales since at least historical times. Movement modelling discriminates sex-related behaviours, with females moving faster during both transit and resident periods, which may be a consequence of size or indicate differential energetic requirements. Relatively short and directed migratory pathways overall, together with high-quality, reliable forage resources may provide a partial explanation for the ongoing strong recovery demonstrated by this population. The combination of new oceanographic information and movement data provides enhanced understanding of important biological processes, which are relevant within the context of the current spatial management and conservation efforts in the Southern Ocean.
Intestinal inflammation increases convulsant activity and reduces antiepileptic drug efficacy in a mouse model of epilepsy
Authors: De Caro Carmen , Leo Antonio , Nesci Valentina , Ghelardini Carla , di Cesare Mannelli Lorenzo , Striano Pasquale , Avagliano Carmen , Calignano Antonio , Mainardi Paolo , Constanti Andrew , Citraro Rita , De Sarro Giovambattista , Russo Emilio 
Published: September 2019

AbstractWe studied the effects of intestinal inflammation on pentylenetetrazole (PTZ)-induced seizures in mice and the effects thereon of some antiepileptic and anti-inflammatory treatments to establish if a link may exist. The agents tested were: alpha-lactoalbumin (ALAC), a whey protein rich in tryptophan, effective in some animal models of epilepsy and on colon/intestine inflammation, valproic acid (VPA), an effective antiepileptic drug in this seizure model, mesalazine (MSZ) an effective aminosalicylate anti-inflammatory treatment against ulcerative colitis and sodium butyrate (NaB), a short chain fatty acid (SCFA) normally produced in the intestine by gut microbiota, important in maintaining gut health and reducing gut inflammation and oxidative stress. Intestinal inflammation was induced by dextran sulfate sodium (DSS) administration for 6 days. Drug treatment was started on day 3 and lasted 11 days, when seizure susceptibility to PTZ was measured along with intestinal inflammatory markers (i.e. NF-κB, Iκ-Bα, COX-2, iNOS), histological damage, disease activity index (DAI) and SCFA concentration in stools. DSS-induced colitis increased seizure susceptibility and while all treatments were able to reduce intestinal inflammation, only ALAC and NaB exhibited significant antiepileptic properties in mice with induced colitis, while they were ineffective as antiepileptics at the same doses in control mice without colitis. Interestingly, in DSS-treated mice, VPA lost part of its antiepileptic efficacy in comparison to preventing seizures in non-DSS-treated mice while MSZ remained ineffective in both groups. Our study demonstrates that reducing intestinal inflammation through ALAC or NaB administration has specific anticonvulsant effects in PTZ-treated mice. Furthermore, it appears that intestinal inflammation may reduce the antiepileptic effects of VPA, although we confirm that it decreases seizure threshold in this group. Therefore, we suggest that intestinal inflammation may represent a valid antiepileptic target which should also be considered as a participating factor to seizure incidence in susceptible patients and also could be relevant in reducing standard antiepileptic drug efficacy.
Risk of second primary malignancies in head and neck cancer patients treated with definitive radiotherapy
Authors: Ng Sweet Ping , Pollard Courtney , Kamal Mona , Ayoub Zeina , Garden Adam S. , Bahig Houda , Gunn G. Brandon , Frank Steven J. , Skinner Heath D. , Phan Jack , Berends Joel , Morrison William H. , Johnson Jason M. , Ferrarotto Renata , Sturgis Erich M. , Mohamed Abdallah S. R. , Lai Stephen Y. , Fuller Clifton D. , Rosenthal David I. 
Published: September 2019

AbstractSecond primary malignancy (SPM) may occur after index head and neck cancer (HNC) treatment. This study evaluated the prevalence and outcome of SPM in patients with HNC treated with definitive radiotherapy. Eligible patients include those with index mucosal HNC treated with definitive radiotherapy between 2000 and 2010. SPM was defined as an invasive cancer at a noncontiguous site diagnosed at least 6 months after completion of radiotherapy. Clinical data were collected, and the Kaplan–Meier method was used to estimate overall survival. In total, 1512 patients were studied. The majority of patients had index oropharyngeal cancer (86%). In all, 130 (9%) patients developed a SPM. The risk of SPM increased exponentially with time with 5-, 10-, and 15-year rates of 4, 10, and 25%. Half of SPMs were within the head and neck or thoracic regions. SPM rates were significantly higher (p < 0.0001) in current smokers and former smokers than never smokers with 5-, 10-, and 15-year risk being: never smoker (2, 4, 14%), former smokers with <10-pack year (5, 10, 23%), former smokers with ≥10-pack year (5, 14, 35%), and current smokers (6, 18, 32%). In total, 102 (78%) had subsequent curative-intent therapy. The 5-year overall survival from SPM was 44%. The majority of SPMs were in those with significant smoking history reflecting the same risk factor as for the index mucosal HNC. Nearly one in two patients with SPMs were salvaged underscoring the importance of regular surveillance for SPMs.
Engineering medium-range order and polyamorphism in a nanostructured amorphous alloy
Authors: Lan Si , Guo Chunyu , Zhou Wenzhao , Ren Yang , Almer Jon , Pei Chaoqun , Hahn Horst , Liu Chain-Tsuan , Feng Tao , Wang Xun-Li , Gleiter Herbert 
Published: September 2019

AbstractLike crystalline materials, the properties of amorphous materials can be tailored by tuning the local atomic-to-nanoscale structural configurations. Polyamorphism is evident by the coexistence of kinetically stabilized amorphous structures with tailorable short-to-medium-range orders, providing a viable means to engineer the degree of local order and heterogeneity. Here, we report experimental evidence of the coexistence of liquid-like and solid-like amorphous phases in a Ni82P18 amorphous alloy with enhanced thermal stability and plasticity prepared by pulsed electrodeposition. The two amorphous phases, of comparable volume fraction of ~50% each, have similar short-range order but are distinguished by packing at the medium-range length scale (>6 Å). Upon heating, a structure crossover at ~450 K was observed, where the liquid-like structure transforms to the solid-like structure, as evidenced by the enthalpy release and an anomalous contraction of atomic structure over the medium-range length scale, due to the metastable nature of the liquid-like structure.