bluuebunny/crossref_metadata_2025_split huggingface dataset:
Audiograms of howling monkeys: are extreme loud calls the result of runaway selection?
Authors: Ramsier Marissa A. , Cunningham Andrew J. , Patiño May R. , Glander Kenneth E. , Dominy Nathaniel J. 
Published: February 2019

AbstractThe eponymous vocalizations of howling monkeys (genusAlouatta) are associated with territorial defense and male-male competition, yet the extreme loudness of howls, which are among the loudest vocalizations of any terrestrial mammal, have yet to be fully explained. Loudness facilitates long-distance sound propagation but the effectiveness of any vocal signal depends in part on the auditory capabilities of the intended receiver, and the auditory sensitivities of howling monkeys are unknown. To better understand the evolution of loud calls, we used the auditory brainstem response (ABR) method to estimate the auditory sensitivities ofAlouatta palliata. The mean estimated audiogram of four wild-caught adults displayed a w-shaped pattern with two regions of enhanced sensitivity centered at 0.7-1.0 and 11.3 kHz. The lower-frequency region of auditory sensitivity is pitched moderately higher than the fundamental frequencies of howling, whereas the higher-frequency region corresponds well with harmonics in an infant distress call, thewrah-ha. Fitness advantages from detecting infants amid low-frequency background noise, including howling, could explain the incongruity between our ABR thresholds and the fundamental frequencies of howling. Attending to infant calls is expected to enhance reproductive success within an infanticidal genus, and we suggest that the extraordinary loudness of male howling is an indirect (runaway) result of positive feedback between the selective pressures of hearing infant distress calls and deterring infanticide.
MoMI-G: Modular Multi-scale Integrated Genome Graph Browser
Authors: Yokoyama Toshiyuki T. , Sakamoto Yoshitaka , Seki Masahide , Suzuki Yutaka , Kasahara Masahiro 
Published: February 2019

ABSTRACTLong-read sequencing allows more sensitive and accurate discovery of structural variants (SVs). While more and more SVs are being identified, a number of them are difficult to visualize using existing SV visualization tools. Therefore, methods to visualize SVs such as nested or large SVs of over a megabase pair need to be developed. To this end, we developed MOdular Multi-scale Integrated Genome graph browser, MoMI-G, a web-based genome browser to visualize SVs, genes, repeats, and other annotations as a variation graph with paths. This browser allows more intuitive recognition of large, nested, and potentially more complex SVs. MoMI-G has view modules for different scales, which allow users to view the whole genome down to nucleotide-level alignments of long reads. Alignments spanning reference alleles and those spanning alternative alleles are shown in the same view. Users can customize the view, if they are not satisfied with the preset views. In addition, MoMI-G has Interval Card Deck, a feature for rapid manual inspection of hundreds of SVs. Herein, we describe the utility of MoMI-G by using representative examples of large and nested SVs found in two cell lines, LC-2/ad and CHM1. MoMI-G is freely available at https://github.com/MoMI-G/MoMI-G under the MIT license.
A scalar Poincaré map for struggling in Xenopus tadpoles
Authors: Olenik Mark , Houghton Conor 
Published: February 2019

AbstractShort-term synaptic plasticity is widely found in many areas of the central nervous system. In particular, it is believed that synaptic depression can act as a mechanism to allow simple networks to generate a range of different firing patterns. The locomotor circuit of hatchling Xenopus tadpoles produces two types of behaviours: swimming and the slower, stronger struggling movement that is associated with rhythmic bends of the whole body. Struggling is accompanied by anti-phase bursts in neurons on each side of the spinal cord and is believed to be governed by a short-term synaptic depression of commissural inhibition. To better understand burst generation in struggling, we study a minimal network of two neurons coupled through depressing inhibitory synapses. Depending on the strength of the synaptic conductance between the two neurons, such a network can produce symmetric n – n anti-phase bursts, where neurons fire n spikes in alternation, with the period of such solutions increasing with the strength of the synaptic conductance. Relying on the timescale disparity in the model, we reduce the eight-dimensional network equations to a fully explicit scalar Poincaré burst map. This map tracks the state of synaptic depression from one burst to the next, and captures the complex bursting dynamics of the network. Fixed points of this map are associated with stable burst solutions of the full network model, and are created through fold bifurcations of maps. We derive conditions that describe period increment bifurcations between stable n – n and (n + 1) – (n + 1) bursts, producing a full bifurcation diagram of the burst cycle period. Predictions of the Poincaré map fit excellently with numerical simulations of the full network model, and allow the study of parameter sensitivity for rhythm generation.
Mutagenesis oforcoimpairs foraging but not oviposition in the hawkmothManduca sexta
Authors: Fandino Richard A. , Haverkamp Alexander , Bisch-Knaden Sonja , Zhang Jin , Bucks Sascha , Thi Tu-Anh Nguyen , Werkenthin Achim , Ryback Jürgen , Stengl Monika , Knaden Markus , Hansson Bill S. , Große-Wilde Ewald 
Published: February 2019

AbstractPlant volatile detection through olfaction plays a crucial role in insect behaviors.In vivo, the odorant receptor co-receptororcois an obligatory component for the function of odorant receptors (ORs), a major receptor family involved in insect olfaction. We used CRISPR-Cas9 targeted mutagenesis to knock-out (KO)orcoin a neurophysiological model species, the hawkmothManduca sexta. M. sextaand its host, the Sacred Datura (Datura wrightii) share a model insect-plant relationship based on mutualistic and antagonistic life history traits.D. wrightiiis the innately preferred nectar-source and oviposition host forM. sexta. Hence, the hawkmoth is an important pollinator while theM. sextalarvae are specialized herbivores of the plant. We generated anorcoKO through CRISPR-Cas9 to test the consequences of a loss of OR-mediated olfaction in this insect-plant relationship. Neurophysiological characterization revealed severely reduced antennal and antennal lobe responses to representative odorants emitted byD. wrightii. In a wind-tunnel setting with a flowering plant,orcoKO hawkmoths showed disrupted flight orientation and an ablated proboscis extension response to the natural stimulus. However, when testing the oviposition behavior of mated females encountering a non-flowering plant, there was no difference betweenorcoKO and wild type females regarding upwind flight orientation and number of eggs laid. Overall, OR-mediated olfaction is essential for foraging and pollination behaviors, but plant-seeking and oviposition behaviors appear largely unaffected.Significance statementInsects detect plant volatiles mainly through the expression of ORs and IRs on the antennal olfactory sensory neurons (OSNs). In vivo, Orco is an obligate partner for OR, but not IR function and ORs mediate a vast spectrum of olfactory perception. We applied CRISPR-Cas9 inM. sextato mutate theorcogene and determine the physiological and behavioral implication of a loss of Orco receptor function in a semi-ecological interaction with D. wrightii. We found that while behaviors related to foraging were largely disrupted, other sensory modalities outside Orco function determine the relationship between an ovipositing female and its plant host. These results have implications toward understanding the olfactory basis of insect-plant interactions shaping our ecological and agricultural landscapes.
A quantitative model of human neurodegenerative diseases involving protein aggregation
Authors: Kepp Kasper P. 
Published: February 2019

AbstractHuman neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis involve protein aggregation and share many other similarities. It is widely assumed that the protein aggregates exhibit a specific molecular mode of toxic action. This paper presents a simple mathematical model arguing that clinical cognitive status relates to the energy available after subtracting cell maintenance due to general turnover of the misfolded proteins, rather than a specific toxic molecular action per se. Proteomic cost minimization can explain why highly expressed proteins changed less during evolution, leaving more energy for reproducing microorganisms on longer evolutionary timescales. In higher organisms, the excess energy instead defines cognitive capability, and the same equations remarkably apply. Proteomic cost minimization can explain why late-onset neurodegenerative diseases involve protein aggregation. The model rationalizes clinical ages of symptom onset for patients carrying pathogenic protein mutations: Unstable or aggregation-prone mutations confer a direct energy cost of turnover, but other risk modifiers also change the available cellular energy as ultimately defining clinical outcome. Proteomic cost minimization is consistent with current views on biomarker histories, explains conflicting data on overexpression models, and is supported by specific experiments showing that proteasome activity is required to confer toxicity to pathogenic mutants. The mechanism and model lend promise to a quantitative personalized medicine of neurodegenerative disease.
Stimulus-aware spatial filtering for single-trial neural response and temporal response function estimation in high-density EEG with applications in auditory research
Authors: Das Neetha , Vanthornhout Jonas , Francart Tom , Bertrand Alexander 
Published: February 2019

AbstractObjective. Neural responses recorded using electroencephalography (EEG) and magnetoencephalography (MEG) can be used to study how our brain functions, as well as for various promising brain computer interface (BCI) applications. However, a common problem is the low signal to noise ratio (SNR) which makes it challenging to estimate task-related neural responses or the temporal response function (TRF) describing the linear relationship between the stimulus and the neural response, particularly over short data windows. To address these, we present an algorithm that takes advantage of the multi-channel nature of the recordings, and knowledge of the presented stimulus, to achieve a joint noise reduction and dimensionality reduction using spatial filtering. Methods. Forward modeling is used to project the stimulus onto the electrode space. The second-order statistics of this estimated desired signal and the raw neural data are used to estimate spatial filters that maximize the SNR of the neural response, based on a generalized eigenvalue decomposition. Main Results. 1. For synthesized EEG data, over a range of SNRs, our filtering resulted in significantly better TRF estimates from 20 s trials, compared to unfiltered EEG data. 2. On a dataset from 28 subjects who listened to a single-talker stimulus, our method resulted in correlations between predicted neural responses and the original EEG data that were significantly higher compared to standard approaches. 3. On a dataset of 16 subjects attending to 1 speaker in a two-speaker scenario, our method resulted in attention decoding accuracies which were higher compared to existing forward modelling methods. Significance. Our algorithm presents a data-driven way to denoise and reduce dimensionality of neural data, thus aiding further analysis, by utilizing the knowledge of the stimulus. The method is computationally efficient, and does not require repeated trials, thereby relieving experiment design from the necessity of presenting repeated stimuli to the subjects.
The IDH-Tau-EGFR triad defines diffuse glioma pathology by controlling mesenchymal differentiation and neo-vascular fitness
Authors: Gargini Ricardo , Segura-Collar Berta , Hernández-SanMiguel Esther , Garcia-Escudero Vega , Romero-Bravo Andrés , Herránz Beatriz , Núñez Felipe J , García-Pérez Daniel , Ayuso-Sacido Angel , Seoane Joan , Sepúlveda-Sánchez Juan M. , Hernández-Laín Aurelio , Castro María G. , García-Escudero Ramón , Ávila Jesús , Sánchez-Gómez Pilar 
Published: February 2019

SUMMARYClassification of gliomas as wild-type or mutantIDH1/2tumors has profound clinical implications. However, how these two groups of gliomas progress, in a microenvironment-dependent manner, is still a pending question. Here we describe that the expression of Tau is epigenetically induced by mutant IDH1/2, whereas is almost absent from tumors withEGFR/PTENmutations. Moreover,Tau (MAPT)expression is inversely correlated with overall survival inEGFR-amplified gliomas. Using orthotopicEGFR-related models, we have observed that Tau overexpression or microtubule stabilizers impair the mesenchymal transformation of glioma cells, with profound changes in tumor vasculature and a significant decrease in tumor burden. However, epithelial-to-mesenchymal transformedEGFR-mutant cells, acting as pericytes, induce neo-vasculogenesis and favor aggressive glioma growth, a process that is no longer sensitive to Tau. Altogether our data indicate that the genomic background controls glioma aggressiveness by modifying the vascular microenvironment.GRAPHICAL ABSTRACT
Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models
Authors: Cladel Nancy M. , Jiang Pengfei , Li Jingwei J. , Peng Xuwen , Cooper Timothy K. , Majerciak Vladimir , Balogh Karla K. , Meyer Thomas J. , Brendle Sarah A. , Budgeon Lynn R. , Shearer Debra A. , Munden Regina , Cam Maggie , Vallur Raghavan , Christensen Neil D. , Zheng Zhi-Ming , Hu Jiafen 
Published: February 2019

AbstractHuman papillomavirus (HPV) infections are commonly thought to be strictly sexually transmitted. However, studies have demonstrated the presence of HPV in cancers of many non-sexual internal organs, raising the question as to how the viruses gain access to these sites. A possible connection between blood transfusion and HPV-associated disease has not received much attention. We show, in two animal models, that blood infected with papillomavirus yields infections at permissive sites. Furthermore, we demonstrate that blood from actively infected mice can transmit the infection to naïve animals. Finally, we report papillomavirus infections in the stomach tissues of animals infected via the blood. Stomach tissues are not known to be permissive for papillomavirus infection, although the literature suggests that HPVs may be associated with a subset of gastric cancers. These results indicate that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection and subsequent cancers.SUMMARYHuman papillomaviruses cause 5% of human cancers. Currently, blood banks do not screen for these viruses. We demonstrate that blood transfused from papillomavirus-infected animals produces infections in recipients. Public health implications are significant if the same is true for humans.DefinitionsLocal papillomavirus infection:An infection initiated by the direct application of virus or viral DNA to the site of infectionIntravenous (IV) papillomavirus infection:An infection resulting from blood-borne delivery of virus or viral DNA to the site of infection.
Formalin Tissue Fixation Biases Myelin-Sensitive MRI
Authors: Seifert Alan C. , Umphlett Melissa , Hefti Marco , Fowkes Mary , Xu Junqian 
Published: February 2019

AbstractPurposeChemical fixatives, such as formalin, form cross-links between proteins and affect the relaxation times and diffusion properties of tissue. These fixation-induced changes likely also affect myelin density measurements produced by quantitative magnetization transfer (qMT) and myelin water imaging (MWI). In this work, we evaluate these myelin-sensitive MRI methods for fixation-induced biases.MethodsWe perform qMT, MWI, and D2O-exchanged zero echo-time (ZTE) imaging on unfixed human spinal cord tissue, and repeat these measurements after 1 day and 31 days of formalin fixation.ResultsThe qMT bound pool fraction increased by 30.7±21.1% after 1 day of fixation and by 42.6±33.9% after 31 days of fixation. Myelin water fraction increased by 39.7±15.5% and 37.0±15.9% at these same time points, and mean T2of the myelin water pool nearly doubled. Reference-normalized D2O-exchanged ZTE signal intensity increased by 8.17±6.03% after 31 days of fixation, but did not change significantly after 1 day of fixation. After fixation, specimen cross-sectional area decreased by approximately 5%; after correction for shrinkage, changes in D2O-exchanged ZTE intensity were nearly eliminated.ConclusionF and MWF are significantly increased by formalin fixation, while D2O-exchanged ZTE intensity is minimally affected. Changes in qMT and MWI may be due, in part, to delamination and formation of vacuoles in the myelin sheath. D2O-exchanged signal intensity may be altered by fixation-induced changes in myelin lipid solid-state1H T1. We urge caution in the comparison of these measurements across subjects or specimens in different states, especially unfixed vs. fixed tissue.
Seasonal changes of airborne bacterial communities over Tokyo and influence of local meteorology
Authors: Uetake Jun , Tobo Yutaka , Uji Yasushi , Hill Thomas C. J. , DeMott Paul J. , Kreidenweis Sonia M. , Misumi Ryohei 
Published: February 2019

AbstractRecent progress in Next Generation Sequencing allows us to explore the diversity of airborne microorganisms across time and space. However, few studies have used consecutive short-period samples to explore correlations between the seasonal variation of the microbiota and meteorology. In order to understand airborne bacterial community dynamics over Tokyo, including fine-scale correlations between airborne microorganisms and meteorological conditions, and the influence of local versus long-range transport of microbes, air samples were continuously taken from a platform at the 458-m level of the Tokyo Skytree (a 634-m-high broadcasting tower in Tokyo) from August 2016 to February 2017. Predicted source regions of airborne particles, from back trajectory analyses, changed abruptly from the Pacific Ocean to the Eurasian Continent in the beginning of October. However, microbial community composition and alpha and beta diversities were not affected by this meteorological regime shift, suggesting that long-range transport from ocean or continent was not the principal determinant controlling the local airborne microbiome. By contrast, local meteorology, especially relative humidity and wind speed, had significant relationships with both alpha diversities and beta diversity. Among four potential local source categories (soil, bay seawater, river, and pond), bay seawater and soil were constant and predominant sources. Statistical analyses suggest humidity is the most influential meteorological factor, most likely because it is correlated with soil moisture and hence negatively correlated with the dispersal of particles from the land surface.
Quantification of multicellular colonization in tumor metastasis using exome sequencing data
Authors: Nishino Jo , Watanabe Shuichi , Miya Fuyuki , Kamatani Takashi , Boroevich Keith A , Tsunoda Tatsuhiko 
Published: February 2019

AbstractMetastasis is a major cause of cancer-related mortality, and it is essential to understand how metastasis occurs in order to overcome it. One relevant question is the origin of a metastatic tumor cell population. Although the hypothesis of a single-cell origin for metastasis from a primary tumor has long been prevalent, several recent studies using mouse models have supported a multi-cellular origin of metastasis. Human bulk whole-exome sequencing (WES) studies also have demonstrated a multiple ‘clonal’ origin of metastasis, with different mutational compositions. Specifically, there has not yet been strong research to determine how many founder cells colonize a metastatic tumor. To address this question, we developed a method to quantify the ‘founder cell population size’ in a metastasis using paired WES data from primary and metachronous metastatic tumors. Simulation studies demonstrated the proposed method gives unbiased results with sufficient accuracy in the range of realistic settings. Applying the proposed method to real WES data from four colorectal cancer patients, all samples supported a multi-cellular origin of metastasis and the founder size was quantified, ranging from 3 to 15 cells. Such a wide-ranging founder sizes estimated by the proposed method suggests that there are large variations in genetic similarity between primary and metastatic tumors in the same subjects, which might be involved in (dis)similarity of drug responses between tumors.
Relationships between depressive symptoms and brain responses during emotional movie viewing emerge in adolescence
Authors: Gruskin David C. , Rosenberg Monica D. , Holmes Avram J. 
Published: February 2019

ABSTRACTAffective disorders such as major depression are common but serious illnesses characterized by altered processing of emotional information. Although the frequency and severity of depressive symptoms increase dramatically over the course of childhood and adolescence, much of our understanding of their neurobiological bases comes from work characterizing adults’ responses to static emotional information. As a consequence, relationships between depressive brain phenotypes and naturalistic emotional processing, as well as the manner in which these associations emerge over the lifespan, remain poorly understood. Here, we apply static and dynamic inter-subject correlation analyses to examine how brain function is associated with clinical and non-clinical depressive symptom severity in 112 children and adolescents (7-21 years old) who viewed an emotionally evocative clip from the film Despicable Me during functional MRI. Our results reveal that adolescents with greater depressive symptom severity exhibit atypical fMRI responses during movie viewing, and that this effect is stronger during less emotional moments of the movie. Furthermore, adolescents with more similar item-level depressive symptom profiles showed more similar brain responses during movie viewing. In contrast, children’s depressive symptom severity and profiles were unrelated to their brain response typicality or similarity. Together, these results indicate a developmental change in the relationships between brain function and depressive symptoms from childhood through adolescence. Our findings suggest that depressive symptoms may shape how the brain responds to complex emotional information in a dynamic manner sensitive to both developmental stage and affective context.