bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mini-batch optimization enables training of ODE models on large-scale datasets
Authors: Stapor Paul , Schmiester Leonard , Wierling Christoph , Lange Bodo M.H. , Weindl Daniel , Hasenauer Jan 
Published: December 2019

AbstractQuantitative dynamical models are widely used to study cellular signal processing. A critical step in modeling is the estimation of unknown model parameters from experimental data. As model sizes and datasets are steadily growing, established parameter optimization approaches for mechanistic models become computationally extremely challenging. However, mini-batch optimization methods, as employed in deep learning, have better scaling properties. In this work, we adapt, apply, and benchmark mini-batch optimization for ordinary differential equation (ODE) models thereby establishing a direct link between dynamic modeling and machine learning. On our main application example, a large-scale model of cancer signaling, we benchmark mini-batch optimization against established methods, achieving better optimization results and reducing computation by more than an order of magnitude. We expect that our work will serve as a first step towards mini-batch optimization tailored to ODE models and enable modeling of even larger and more complex systems than what is currently possible.
Prioritized neural processing of social threats during perceptual decision-making
Authors: El Zein M. , Mennella R. , Sequestro M. , Meaux E. , Wyart V. , Grèzes J. 
Published: December 2019

AbstractEmotional signals, notably those signaling threat, benefit from prioritized processing in the human brain. Yet, it remains unclear whether perceptual decisions about the emotional, threat-related aspects of stimuli involve specific or similar neural computations compared to decisions about their non-threatening/non-emotional components. We developed a novel behavioral paradigm in which participants performed two different detection tasks (emotion vs. color) on the same, two-dimensional visual stimuli. Electroencephalographic (EEG) activity in a cluster of central electrodes reflected the amount of perceptual evidence around 100ms following stimulus onset, when the decision concerned emotion, not color. Second, participants’ choice could be predicted earlier for emotion (240ms) than for color (380ms) by the mu (10Hz) rhythm, which reflects motor preparation. Taken together, these findings indicate that perceptual decisions about threat-signaling dimensions of facial displays are associated with prioritized neural coding in action-related brain regions, supporting the motivational value of socially relevant signals.
Astral microtubule crosslinking safeguards uniform nuclear distribution in the Drosophila syncytium
Authors: Deshpande Ojas , de-Carvalho Jorge , Vieira Diana V. , Telley Ivo A. 
Published: December 2019

AbstractThe early insect embryo develops as a multinucleated cell distributing the genome uniformly to the cell cortex. Mechanistic insight for nuclear positioning beyond cytoskeletal requirements is missing. Contemporary hypotheses propose actomyosin driven cytoplasmic movement transporting nuclei, or repulsion of neighbor nuclei driven by microtubule motors. Here, we show that microtubule crosslinking by Feo and Klp3A is essential for nuclear distribution and internuclear distance maintenance in Drosophila. Germline knockdown causes irregular, less dense nuclear delivery to the cell cortex and smaller distribution in ex vivo embryo explants. A minimal internuclear distance is maintained in explants from control embryos but not from Feo inhibited embryos, following micromanipulation assisted repositioning. A dimerization deficient Feo abolishes nuclear separation in embryo explants while the full-length protein rescues the genetic knockdown. We conclude that Feo and Klp3A crosslinking of antiparallel microtubule overlap generates a length-regulated mechanical link between neighboring microtubule asters. Enabled by a novel experimental approach, our study illuminates an essential process of embryonic multicellularity.
A machine learning based approach to the segmentation of micro CT data in archaeological and evolutionary sciences
Authors: O’Mahoney Thomas , Mcknight Lidija , Lowe Tristan , Mednikova Maria , Dunn Jacob 
Published: December 2019

AbstractSegmentation of high-resolution tomographic data is often an extremely time-consuming task and until recently, has usually relied upon researchers manually selecting materials of interest slice by slice. With the exponential rise in datasets being acquired, this is clearly not a sustainable workflow. In this paper, we apply the Trainable Weka Segmentation (a freely available plugin for the multiplatform program ImageJ) to typical datasets found in archaeological and evolutionary sciences. We demonstrate that Trainable Weka Segmentation can provide a fast and robust method for segmentation and is as effective as other leading-edge machine learning segmentation techniques.
Intramembrane cleavage of TREM2 is determined by its intrinsic structural dynamics
Authors: Steiner Andrea , Schlepckow Kai , Brunner Bettina , Steiner Harald , Haass Christian , Hagn Franz 
Published: December 2019

AbstractSequence variants of the microglial expressed TREM2 (triggering receptor expressed on myeloid cells 2) are a major risk factor for late onset Alzheimer’s disease. TREM2 requires a stable interaction with DAP12 in the membrane to initiate signaling, which is terminated by TREM2 ectodomain shedding and subsequent intramembrane cleavage by γ-secretase. To understand the structural basis for the specificity of the intramembrane cleavage event, we determined the solution structure of the TREM2 transmembrane helix (TMH). Due to the presence of a charged amino acid in the membrane region the TREM2-TMH adopts a kinked structure with increased flexibility. Charge removal leads to TMH stabilization and reduced dynamics, similar to its structure in complex with DAP12. Strikingly, these dynamical features perfectly correlate with the site of the initial γ-secretase cleavage event. These data suggest an unprecedented cleavage mechanism by γ-secretase where flexible TMH regions are identified to initiate substrate cleavage.
Infection risk and extensive parental care govern the molecular evolution of Toll-like receptors in birds
Authors: Zhang Zhechun , Liang Dan , Chen Guoling , Zou Fasheng , Lei Fumin , Dong Lu , Griesser Michael , Liu Yang 
Published: December 2019

SummaryThe arms race between pathogens and the immune system of their hosts is a critical evolutionary force that affects the ecology and life history of organisms. An increased infection risk selects for adaptations in immune genes that encode receptors involved in pathogen recognition and the initiation of innate immune responses, including Toll-like receptor (TLR) genes. Although recent studies assessed the evolution of major histocompatibility complex (MHC) genes, the ecological and evolutionary processes that drive the evolution of immune genes across major phylogenetic lineages remain unstudied. Moreover, trade-offs between immune responses and other energy-demanding vital functions may limit the resource allocation into costly immune functions, and therefore affect the evolution of immune genes. Here we assess the evolutionary patterns of six TLR genes across 121 bird species, covering 95% of extant orders that represent diverse ecologies and life histories. Selection analyses revealed that all six TLR genes show strong signs of purifying selection, while few sites underwent episodic positive selection. Comparative phylogenetic analyses showed that the intensity of positive selection of TLR genes is associated with long-distance migration, extensive parental care (i.e., altricality and prolonged parent-offspring association), and a large body size (a proxy of increased longevity). Together, these results suggest that the evolution of immune genes is characterized by episodic positive selection, and is shaped by an increased inflection risk and extensive parental care that buffers the costs of immune functions.
Active monomer RTR-1 derived from the root of Rhodomyrtus tomentosa induces apoptosis in gastric carcinoma cells by inducing ER stress and inhibiting the STAT3 signalling pathway
Authors: Zhang Xiangqiang , Cheng Jinxia , He Peiyan , Zhu Jinyan , Chen Zhixian , Miao Shenyu , Wang Guocai , Jiang Jianwei , Wang Yuechun 
Published: December 2019

AbstractObjectiveRhodomyrtus tomentosa, a flowering plant belonging to the Myrtaceae family, is considered an antitumour substance with versatile biological and pharmacological activities.And RTR-1 is an active monomer purified from the root of Rhodomyrtus tomentosa. However, the detail of the mechanisms of anti-cancer activity of RTR-1 remains to be elucidated and the effect on gastric cancer cells is unknown.MethodsCell proliferation was determined by MTT and clone formation assay. The effect of RTR-1 on cell cycle and apoptosis was analyzed utilizing flow cytometry, respectively. Moreover, western blotting was used to detect the expression of cell cycle- and apoptosis-related protein.ResultsBased on MTT and clone formation assay, we noticed that RTR-1 inhibited the proliferation of gastric carcinoma (BGC823 and SGC7901) cells in a dose- and time-dependent manner. Furthermore, the results of flow cytometry and western blotting showed that RTR-1 induced cell cycle arrest in the G2/M phase through the ATM-Chk2-p53-p21 signalling pathway and induced cell apoptosis by inhibiting the signal transducers and activators of transcription 3 (STAT3) pathway and activating the endoplasmic reticulum stress (ER stress) pathway.ConclusionTaken together, these results demonstrate that RTR-1 induces cell cycle arrest and promotes apoptosis in gastric carcinoma, indicating its potential application for gastric cancer therapy.
Comparative In-Vitro Physicochemical Evaluation and Dissolution Profiling of Glibenclamide 5mg tablet Marketed in Addis Ababa, Ethiopia
Authors: Kebede Selass , Abuye Habtamu , Abraham Woldemichael , Suleman Sultan , Belew Sileshi 
Published: December 2019

AbstractThe safety of medicines is an essential part of patient safety. Global drug safety depends on strong national systems that monitor the development and quality of medicines. Poor quality medicines do not meet official standards for strength, quality, purity, packaging and labelling. Hence, this study determinesin-vitroquality attributes of glibenclamide 5mg tablet marketed in Addis Ababa according to USP-38 drug monograph specifications. All tested brands meet the requirements for physical inspection & complied specification for friability and hardness. Besides, the tested brands met USP 38 specification for assay (99.96% to 108.85%) and for content uniformity (AV values ranges from 3.35 to 10.04).In-vitrorelease tests were carried out in phosphate buffer of 7.5 and 8.5 pH and showed drug release of ≥ 75%, met USP 38 requirements. However, significant difference with respect to dissolution profile among tested brands GL4 and GL6 were confirmed with comparator product through model independent approach. Moreover, DE values were studied and confirmed that GL4 and GL6 were not therapeutically interchangeable with innovator product.
Is vectorial transmission of Trypanosoma cruzi an efficient route to support high infection rates in sylvatic hosts?
Authors: Cordovez Juan Manuel , Santos-Vega Mauricio , Erazo Diana , Sanabria Camilo , Rendón Lina María , Guhl Felipe 
Published: December 2019

AbstractChagas disease is caused by the parasite Trypanosoma cruzi and it is transmitted to humans by the triatomine bug Rhodnius prolixus. The main insect vector in the Andean countries presents sylvatic and domestic cycles involving humans, insects and reservoirs (e.g small mammals). It is commonly assumed that vectorial transmission is the main route for parasite spread between hosts. Recent studies have reported high percentages (21-80%) of infected opossums (Didelphis marsupialis) in the sylvatic cycle, raising the question of whether such a high proportion of infected could be only maintained by vectorial transmission, a seemingly inefficient pathway. To address this question, we formulated a mathematical model that describes the sylvatic transmission dynamics considering vectors and hosts and parametrized with field data. Our results show that vectorial transmission it is not sufficient to explain such high percentages of infected host-mammals reported in the literature. Here we propose oral transmission as an alternate route of transmission that may increase the number of infected individuals found in field studies.
Species, causes, and outcomes of wildlife rehabilitation in New York State
Authors: Hanson Melissa , Hollingshead Nicholas , Schuler Krysten , Siemer William F. , Martin Patrick , Bunting Elizabeth M. 
Published: December 2019

AbstractWildlife rehabilitation is a publicly popular though highly controversial practice. State wildlife agencies frequently debate the ecological impact of rehabilitation. Analysis of case records could inform that debate by clarifying and quantifying the causes for rehabilitation, species involved, and treatment outcomes. This information could aid in the ability of regulatory agencies and rehabilitators to make informed decisions and gain insight into causes of species decline. In New York, rehabilitators are licensed by the Department of Environmental Conservation (NYSDEC) and thus, are required to submit annual reports. Between 2012-2014, 59,370 individual wildlife cases were seen by licensed rehabilitators comprising 31,229 (52.6%) birds, 25,490 (42.9%) mammals, 2,423 (4.1%) reptiles, and 73 (0.1%) amphibians. We identified patterns among taxonomic representation, reasons for presentation, and disposition. Major causes of presentation were trauma (n = 22,672, 38.2%) and orphaning (n = 21,876, 36.8%), with habitat loss (n =3,746, 6.3%), infectious disease (n = 1,992, 3.4%), and poisoning or toxin exposure (n = 864, 1.5%) playing lesser roles. The overall release rate for animals receiving care was 50.2%; 45.4% were either euthanized or died during the rehabilitation process. A relatively small number (0.3%) were permanently non-releasable and placed in captivity, and 4.1% had unknown outcomes. In comparison to data from 1989, wildlife submissions have increased (annual mean 12,583 vs 19,790), as has the release rate, from 44.4% to 50.2%. Utilizing a large data set allowed us to fill knowledge gaps, which can help inform management by both the rehabilitators and the state agencies that regulate them, deepening understanding of the scope and impacts of wildlife rehabilitation.
Deletion of mouseSetd4promotes the recovery of hematopoietic failure
Authors: Feng Xing , Lu Huimei , Yue Jingyin , Shettigar Megha , Liu Jingmei , Denzin Lisa K , Shen Zhiyuan 
Published: December 2019

AbstractAcquired hematopoietic failure is commonly caused by therapeutic and accidental exposure to toxic agents to the bone marrow (BM). Efficient recovery from the BM failure is not only dictated by the intrinsic sensitivity and proliferation capacity of the hematopoietic stem and progenitor cells, but also nourished by the BM environment niche. Identification of genetic factors that improve the recovery from hematopoietic failure is essential. Vertebrate SETD4 is a poorly characterized, putative non-histone methyl-transferase whose physiological substrates have not yet been fully identified. By inducingSetd4deletion in adult mice, we found that loss ofSetd4improved the survival of whole body irradiation induced BM failure. This was associated with improved recoveries of long-term and short-term hematopoietic stem cells (HSC), and early progenitor cells. BM transplantation analyses surprisingly showed that the improved recovery was not due to a radiation resistance of theSetd4deficient HSC, but thatSetd4deficient HSC were actually more sensitive to radiation. However, theSetd4deficient mice were better recipients for allogeneic HSC transplantation. Furthermore, there was an enhanced splenic erythropoiesis inSetd4deficient mice. These findings not only revealed a previously unrecognized role of theSetd4as a unique modulator of hematopoiesis, but also underscored the critical role of the BM niche in the recovery of hematopoietic failure. These studies also implicatedSetd4as a potential target for therapeutic inhibition to improve the conditioning of the BM niche prior to allogeneic transplantation.Key pointsDeletion ofSetd4in adult mice improved the survival from hematopoietic failure.Setd4deficiency sensitized HSCs to radiation, but improved bone marrow environment niche.The study suggests that SETD4 as a potential inhibitory target to improve bone marrow niche function for recovery of bone marrow failure.
A new analytical pipeline for the study of the onset of mammary gland oncogenesis based on mammary organoid transplantation and organ clearing
Authors: Lagoutte Emilie , Villeneuve Clémentine , Fraisier Vincent , Krndija Denis , Deugnier Marie-Ange , Chavrier Philippe , Rossé Carine 
Published: December 2019

AbstractMetastasis formation is a multi-step process starting from the dissemination of transformed carcinomatous cells from the primary tumor and could occur at a very early stage of oncogenesis, before primary tumor detection. The adult mammary gland provides a unique model to investigate epithelial cell dissemination processes. Tissue clearing techniques allow imaging samples of large volume. uDSICO clearing, one of the latest tissue clearing technique developed, provides optical imaging of whole organ due to organ clearing and tissue size reduction. We wanted to take advantage of this technique to study rare events occurring in vivo.Here, we have established a new analytical pipeline exploiting the regenerative properties of the mammary epithelium following orthotropic transplantation of organoids together with the uDISCO organ size reduction and clearing method to study early cell dissemination in the mammary gland. As proof of concept, we analyzed the localization of epithelial cells overexpressing the oncogenic protein atypical protein kinase C iota (aPKCi+) in the normal mammary gland and we were able to visualize epithelial aPKCi+ cells, surrounded by normal epithelial cells, escaping from the normal mammary epithelium and disseminating into the surrounding stroma.
Demand for Multiplatform and Meta-analytic Approaches in Transcriptome Profiling
Authors: Tombácz Dóra , Torma Gábor , Gulyás Gábor , Moldován Norbert , Snyder Michael , Boldogkői Zsolt 
Published: December 2019

AbstractIn a recent article, Depledge and colleagues reported a study of the herpes simplex virus type 1 (HSV-1) transcriptome using direct RNA sequencing (dRNA-Seq) on nanopore arrays. The authors provided a useful dataset on full-length viral and host RNA molecules. In this study, we reanalyzed the published dataset and compared it with data generated by our group and others. Our comparative study clearly demonstrated the need for multiplatform and meta-analytic approaches for transcriptome profiling to obtain reliable results.
Antibody responses to immunization require sensory neurons
Authors: Tynan Aisling , Tsaava Téa , Gunasekaran Manojkumar , Snee Isabel , Mak Tak W. , Olofsson Peder , Andersson Ulf , Chavan Sangeeta S. , Tracey Kevin J. 
Published: December 2019

AbstractMammals store memories in the nervous and immune systems. Sensory neurons have been implicated in enhancing neurological memory, but whether neurons participate during immunity to novel antigens is unknown. Here, mice rendered deficient in transient receptor potential vanilloid 1 (TRPV1)-expressing sensory neurons, termed “nociceptors,” fail to develop competent antibody responses to KLH and hapten-NP. Moreover, selective optogenetic stimulation of TRPV1 neurons during immunization significantly enhanced antibody responses to antigens. Thus, TRPV1 nociceptors mediate antibody responses to novel antigen, and stimulating TRPV1 nociceptors enhances antibody responses during immunization. This is the first genetic and selective functional evidence that nociceptors are required during immunization to produce antigen-specific antibodies.SummaryThe first genetic and selective functional evidence showing that TRPV1-expressing nociceptors are required for competent antibody responses to novel antigen, and stimulating TRPV1 nociceptors enhances antibody responses to novel antigen.
Taxonomical and functional diversity ofSaprolegnialesin Anzali lagoon, Iran
Authors: Masigol Hossein , Khodaparast Seyed Akbar , Mostowfizadeh-Ghalamfarsa Reza , Rojas-Jimenez Keilor , Woodhouse Jason Nicholas , Neubauer Darshan , Grossart Hans-Peter 
Published: December 2019

AbstractStudies on the diversity, distribution and ecological role ofSaprolegniales(Oomycota) in freshwater ecosystems are currently receiving attention due to a greater understanding of their role in carbon cycling in various aquatic ecosystems. In this study, we characterized severalSaprolegnialesspecies isolated from Anzali lagoon, Gilan province, Iran, using morphological and molecular methods. Four species ofSaprolegniawere identified, includingS. anisosporaandS. diclinaas first reports for Iran. Evaluation of the ligno-, cellulo- and chitinolytic activities were also measured using plate assay methods. Most of theSaprolegnialesisolates were obtained in autumn and nearly 50% of the strains showed chitinolytic and cellulolytic activities. However, only a fewSaprolegnialesstrains showed lignolytic activities. This study has important implications for better understanding the ecological niche of oomycetes, and to differentiate them from morphologically similar but functional different aquatic fungi in freshwater ecosystems.
Phylogenetic inference identifies two eumetazoan TRPM clades and an 8th family of TRP channel, TRP soromelastatin (TRPS)
Authors: Himmel Nathaniel J. , Gray Thomas R. , Cox Daniel N. 
Published: December 2019

AbstractTRP melastatins (TRPMs) are most well-known as cold and menthol sensors, but are in fact broadly critical for life, from ion homeostasis to reproduction. Yet the evolutionary relationship between TRPM channels remains largely unresolved, particularly with respect to the placement of several highly divergent members. To characterize the evolution of TRPM and like channels, we performed a large-scale phylogenetic analysis of >1,300 TRPM-like sequences from 14 phyla (Annelida, Arthropoda, Brachiopoda, Chordata, Cnidaria, Echinodermata, Hemichordata, Mollusca, Nematoda, Nemertea, Phoronida, Priapulida, Tardigrada, and Xenacoelomorpha), including sequences from a variety of recently sequenced genomes that fill what would otherwise be substantial taxonomic gaps. These findings suggest: (1) The previously recognized TRPM family is in fact two distinct families, including canonical TRPM channels, and an 8th major, previously undescribed family of animal TRP channel, TRP soromelastatin (TRPS); (2) two TRPM clades predate the last bilaterian-cnidarian ancestor; and (3) the vertebrate-centric trend of categorizing TRPM channels as 1-8 is inappropriate for most phyla, including other chordates.