bluuebunny/crossref_metadata_2025_split huggingface dataset:
A controlled thermoalgesic stimulation device to identify novel pain perception biomarkers
Authors: Ibero Maider Núñez , Camino-Pontes Borja , Diez Ibai , Erramuzpe Asier , Gutiérrez Endika Martínez , Stramaglia Sebastiano , Álvarez-Cienfuegos Javier Ortiz , Cortes Jesus M. 
Published: July 2020

AbstractObjectiveTo develop a new device that will help identify physiological markers of pain perception by reading the brain’s electrical activity and the bodies hemodynamic interactions while applying thermoalgesic stimulation. Methods: We designed a compact prototype that generates well-controlled thermal stimuli using a computer driven Peltier cell while simultaneously capturing electroencephalography (EEG) and photoplethysmography (PPG) signals as the stimuli are varied. The study was performed on 35 healthy subjects (mean age 30.46 years, SD 4.93 years; 20 males, 15 females) and to account for the inter-subject variability in the tolerance to thermal pain, we first determined the heat pain threshold (HPT) for each subject, defined as the maximum temperature that the subject can withstand when the Peltier cell gradually increases the temperature. Subsequently, we defined the pain parameters associated with a stimulation temperature equivalent to 90% of the HPT, comparing this to the no-pain state (control) in the absence of thermoalgesic stimulation. Results: Both the one-dimensional and the two-dimensional spectral entropy (SE) obtained from both the EEG and PPG signals could differentiate the condition of pain. In particular, the PPG SE was significantly reduced in association with pain, while the SE for EEG increased slightly. Moreover, significant discrimination occurred within a specific range of frequencies, 26-30 Hz for EEG and about 5-10 Hz for PPG. Conclusion: Hemodynamics, brain dynamics and their interactions can discriminate thermal pain perception. Significance: The possibility of monitoring on-line variations in thermal pain perception using a similar device and algorithms may be of interest to study different pathologies that affect the peripheral nervous system, such as small fiber neuropathies, fibromyalgia or painful diabetic neuropathy.
Sleep deprivation triggers somatostatin neurons in prefrontal cortex to initiate nesting and sleep via the preoptic and lateral hypothalamus
Authors: Tossell Kyoko , Yu Xiao , Soto Berta Anuncibay , Vicente Mikal , Miracca Giulia , Giannos Panagiotis , Miao Andawei , Hsieh Bryan , Ma Ying , Yustos Raquel , Vyssotski Alexei L. , Constandinou Tim , Franks Nicholas P. , Wisden William 
Published: July 2020

AbstractAnimals undertake specific behaviors before sleep. Little is known about whether these innate behaviors, such as nest building, are actually an intrinsic part of the sleep-inducing circuitry. We found, using activity-tagging genetics, that mouse prefrontal cortex (PFC) somatostatin/GABAergic (SOM/GABA) neurons, which become activated during sleep deprivation, induce nest building when opto-activated. These tagged neurons induce sustained global NREM sleep if their activation is prolonged metabotropically. Sleep-deprivation-tagged PFC SOM/GABA neurons have long-range projections to the lateral preoptic (LPO) and lateral hypothalamus (LH). Local activation of tagged PFC SOM/GABA terminals in LPO and the LH induced nesting and NREM sleep respectively. Our findings provide a circuit link for how the PFC responds to sleep deprivation by coordinating sleep preparatory behavior and subsequent sleep.
Phylogeny of the species-richPileaLindl. (Urticaceae) supports its revised delimitation and infrageneric classification, including the resurrection ofAchudemiaBlume
Authors: Fu Long-Fei , Wen Fang , Maurin Olivier , Rodda Michele , Wei Yi-Gang , Monro Alexandre K. 
Published: July 2020

ABSTRACTPileaLindl., with 933 published names is the largest genus within the Urticaceae.Pileawas last monographed in 1869 and whilst the monophyly of the genus has been proposed by previous authors, this has been based on incomplete taxon sampling and the failure to resolve the position of key taxa. We aimed to generate a robust phylogeny forPileaand allied genera that could provide a framework for testing the monophyly ofPilea, revising its delimitation and for answering broader scientific questions about this species-rich genus. To do so, we sought to sample taxa representative of previous infrageneric classifications and with anomalous inflorescences or flower configurations and to use the resulting phylogeny to evaluate the delimitation ofPileaand to establish an infrageneric classification. In addition, we included a representative of the Polynesian genusHaroldiellawhich, morphologically, is very similar toPilea. Using Sanger sequence data from two plastid and one nuclear regions we constructed a phylogeny using Bayesian Inference, Maximum Likelihood and Maximum Parsiomony approaches. We used our phylogeny to evaluate the informativness of 19 morphological traits and applied both to delimit a monophyletic genus and infrageneric sections. Our results recoveredPileaas paraphyletic with respect toLecanthus, a consequence of the recovery of a monophyletic clade comprising sectionsAchudemiaandSmithiella, neither of which had been adequately sampled in previous studies. We also recoveredPileaas polyphyletic with respect toHaroldiella. We identified isomery between male and female flowers, flower part number and male sepal arrangement as being phylogenetically informative traits that can be used to delimit two genera,Achudemia, including sectionSmithiella, recovered as sister toLecanthus, andPilea, includingHaroldiella, recovered as sister to both. On the basis of our evaluation of both morphological traits and phylogenetic relationships we propose a new infrageneric classification for the genus comprising seven sections, five of which we describe for the first time, §TrimerisY.G.Wei & A.K.Monro, §LecanthoidesC.J.Chen, §AngulataL.F.Fu & Y.G.Wei, §TetramerisC.J.Chen, §VerrucosaL.F.Fu & Y.G.Wei, §PlatanifloraL.F.Fu & Y.G.Wei and §LeiocarpaL.F.Fu & Y.G.Wei. We also identify a trend of decreasing merism and fruit size, and increasing species-richness asPileadiverges. In addition, we recover strong geographical structure within our phylogeny, sufficient to propose thatPileaoriginated in the IndoMalaya biogeographic domain.
Human bone mesoscale 3D structure revisited by plasma focused ion beam serial sectioning
Authors: Binkley Dakota Marie , Deering Joseph , Yuan Hui , Gourrier Aurélien , Grandfield Kathryn 
Published: July 2020

AbstractVisualizing bone mineralization and collagen microfibril organization at intermediate scales between the nanometer and the 100s of microns range, the mesoscale, is still an important challenge. Similarly, visualizing cellular components which locally affect the tissue structure requires a precision of a few tens of nanometers at maximum while spanning several tens of micrometers. To address this issue, we employed a plasma focused ion beam (PFIB) equipped with a scanning electron microscope (SEM) to sequentially section nanometer-scale layers of demineralized and mineralized human femoral lamellar bone over volumes of approximately 46 × 40 × 9 μm3, and 29 × 26 × 9 μm3, respectively. This large scale view retained high enough resolution to visualize the collagen microfibrils while partly visualizing the lacuno-canalicular network (LCN) in three-dimensions (3D). We showed that serial sectioning can be performed on mineralized sections, and does not require demineralization. Moreover, this method revealed ellipsoidal mineral clusters, noted by others in high resolution studies, as a ubiquitous motif in lamellar bone over tens of microns, suggesting a heterogeneous and yet regular pattern of mineral deposition past the single collagen fibril level. These findings are strong evidence for the need to revisit bone mineralization over multi-length scales.Graphical Abstract
Brain-wide electrical dynamics encode an appetitive socioemotional state
Authors: Mague Stephen D. , Talbot Austin , Blount Cameron , Duffney Lara J. , Walder-Christensen Kathryn K. , Adamson Elise , Bey Alexandra L. , Ndubuizu Nkemdilim , Thomas Gwenaёlle , Hughes Dalton N. , Sinha Saurabh , Fink Alexandra M. , Gallagher Neil M. , Fisher Rachel L. , Jiang Yong-hui , Carlson David E. , Dzirasa Kafui 
Published: July 2020

AbstractMany cortical and subcortical regions contribute to complex social behavior; nevertheless, the network level architecture whereby the brain integrates this information to encode appetitive socioemotional behavior remains unknown. Here we measure electrical activity from eight brain regions as mice engage in a social preference assay. We then use machine learning to discover an explainable brain network that encodes the extent to which mice chose to engage another mouse. This socioemotional network is organized by theta oscillations leading from prelimbic cortex and amygdala that converge on ventral tegmental area, and network activity is synchronized with brain-wide cellular firing. The network generalizes, on a mouse-by-mouse basis, to encode socioemotional behaviors in healthy animals, but fails to encode an appetitive socioemotional state in a ‘high confidence’ genetic mouse model of autism. Thus, our findings reveal the architecture whereby the brain integrates spatially distributed activity across timescales to encode an appetitive socioemotional brain state in health and disease.
Docosahexaenoic acid (DHA), a nutritional supplement, modulates steroid insensitivity in asthma
Authors: Panda Lipsa , Gheware Atish P , Jaiswal Ashish , Saha Dhurjhoti , Desiraju Bapu Koundinya , Rehman Rakhshinda , Ray Archita , Dutta Joytri , Singh Sabita , Yadav Manish Kumar , Sowpati Divya Tej , Chattopadhyay Samit , SubbaRao Madhunapantula V. , Mahesh Padukudru Anand , Prakash Y. S. , Chowdhury Shantanu , Agrawal Anurag , Ghosh Balaram , Mabalirajan Ulaganathan 
Published: July 2020

AbstractAsthmatics with poor steroid responsiveness are now found to use health services at higher frequency and contribute to socio-economic burden disproportionately. We have previously shown that a ω-6 fatty acid metabolite leads to a severe and steroid insensitive asthma-like condition in mice. Here, we investigated the role of retinoid-x-receptor gamma (RXRγ) and Docosahexaenoic acid (DHA), a ω3 fatty acid rexinoid ligand of RXR, on the features of steroid insensitivity in asthmatic condition. RXRγ was found to be reduced in the lungs of human asthmatics and mice with steroid insensitive allergic airway inflammation. RXRγ knockdown in naïve mice led to spontaneous asthma like features whereas RXRγ knockdown in allergic mice led to steroid insensitive asthma features. We observed while RXRγ binds to the glucocorticoid receptor (GR) gene and regulates its transcription, DHA increases the GRα expression in human bronchial epithelial cells and reverses the steroid insensitive features in mice with allergic airway inflammation. Docosahexaenoic acid (DHA), a ligand of RXR, was reduced in the sera of steroid-insensitive asthmatics. We conclude that DHA may prove to be a promising steroid sensitizing agent for the treatment of steroid insensitive asthmatics.SummaryThe molecular regulation of glucocorticoid receptor by retinoid-x-receptor gamma (RXRgama) has an implication in steroid insensitive asthma as we found that Docosahexaenoic acid (DHA), a nutritional supplement and natural ligand of RXRgamma, improves steroid sensitivity in steroid insensitive mice model of asthma and DHA levels are found to be low in steroid insensitive asthmatic patients.
Comparative analysis of clonal evolution among patients with right-sided colon cancer, left-sided colon cancer and rectal cancer
Authors: Banerjee Santasree , Zhang Xianxiang , Kuang Shan , Wang Jigang , Li Lei , Fan Guangyi , Luo Yonglun , Sun Shuai , Han Peng , Wu Qingyao , Yang Shujian , Ji Xiaobin , Li Yong , Deng Li , Tian Xiaofen , Wang Zhiwei , Zhang Yue , Wu Kui , Zhu Shida , Bolund Lars , Yang Huanming , Xu Xun , Liu Junnian , Lu Yun , Liu Xin 
Published: July 2020

AbstractBackgroundTumor multi-region sequencing reveals intratumor heterogeneity (ITH) and clonal evolution which play a key role in progression and metastases of the tumor. However, large-scale high depths multiregional sequencing of colorectal cancer (CRC) has not been well studied. In addition, the comparative analysis among right-sided colon cancer (RCC), left-sided colon cancer (LCC) and rectal cancer (RC) patients as well as the study of lymph node metastasis (LN) with extranodal tumor deposits (ENTD) from evolutionary perspective remain unknown.ResultsIn this prospective study, we recruited different stages of 68 CRC patients with RCC (18), LCC (20) and RC (30). We performed high-depth whole exome sequencing (WES) of 206 tumor regions including 176 primary tumors, 19 LN and 11 ENTD samples. Our results showed ITH with a Darwinian pattern of evolution. We identified that the evolution pattern of LCC and RC was more complex and divergent than RCC, suggesting the evolutionary diversity in the initiation and progression of LCC and RC. Genetic and evolutionary evidences found that both LN and ENTD were of polyclonal in origin. Moreover, ENTD was a distinct entity from LN and evolved later.ConclusionsIn conclusion, our study showed the Darwinian pattern of evolution with differences in clonal evolution between RCC with LCC and RC.
Plasma membrane localization of paralogous leucine permeases Bap2 and Bap3 is regulated by Bul1
Authors: Maheswaran S , Bhat Paike Jayadeva 
Published: July 2020

AbstractTimeliness in expression and degradation of the nutrient permeases is crucial for any organism. InSaccharomyces cerevisiae, post translational regulation of nutrient permeases such as trafficking and turnover are poorly understood. We found that loss of a leucine permeaseBAP2, but not other permeases lead to severe growth retardation when the carbon source is glucose or galactose but not glycerol and lactate. Leucine prototrophy suppressed the retardation, showingBAP2andLEU2are synthetically lethal. We discovered that loss ofBUL1, an arrestin involved in trafficking of diverse permeases suppressed this lethality. The suppression required another leucine permease,BAP3. Our results suggest thatBUL1downregulate permeasesBAP2andBAP3present in plasma membrane through Rsp5 dependent endocytosis. We speculate that by regulating leucine importBUL1regulates the activity of TORC1.
Transcription-dependent domain-scale 3D genome organization in dinoflagellates
Authors: Marinov Georgi K. , Trevino Alexandro E. , Xiang Tingting , Kundaje Anshul , Grossman Arthur R. , Greenleaf William J. 
Published: July 2020

AbstractDinoflagellate chromosomes represent a unique evolutionary experiment, as they exist in a permanently condensed, liquid crystalline state, are not packaged by histones, and contain genes organized into polycistronic arrays, with minimal transcriptional regulation. We analyze the 3D genome ofBreviolum minutum, and find large topological domains without chromatin loops, demarcated by convergent gene array boundaries (“dinoTADs). Transcriptional inhibition degrades dinoTADs, implicating transcription-induced supercoiling as the primary topological force in dinoflagellates.
mTOR inhibitors as radiosensitizers in neuroendocrine neoplasms
Authors: Exner Samantha , Arrey Gerard , Prasad Vikas , Grötzinger Carsten 
Published: July 2020

AbstractPeptide receptor radioligand therapy (PRRT) has evolved as an important second-line treatment option in the management of inoperable and metastatic neuroendocrine neoplasms (NEN). Though high radiation doses can be delivered to the tumors, complete remission is still rare. Radiosensitization prior to PRRT is therefore considered to be a promising strategy to improve the treatment effect. In this study, effect and mechanism of mTOR inhibitors were investigated in a comprehensive panel of five NEN cell lines (BON, QGP-1, LCC-18, H727, UMC-11), employing assays for cellular proliferation, clonogenic survival, cell cycle modification and signaling. mTOR inhibition lead to growth arrest with a biphasic concentration-response pattern: a partial response at approximately 1 nM and full response at micromolar concentrations (8-48 μM). All cell lines demonstrated elevated p70S6K phosphorylation yet also increased phosphorylation of counterregulatory Akt. The pulmonary NEN cell line UMC-11 showed the lowest induction of phospho-Akt and strongest growth arrest by mTOR inhibitors. Radiation sensitivity of the cells (50% reduction versus control) was found to range between 4 and 8 Gy. Further, mTOR inhibition was employed together with irradiation to evaluate radiosensitizing effects of this combination treatment. mTOR inhibition was found to radiosensitize all five NEN cells in an additive manner with a moderate overall effect. The radiation-induced G2/M arrest was diminished under combination treatment, leading to an increased G1 arrest. Further investigation involving a suitable animal model as well as radioligand application such as177Lu-DOTATATE or177Lu-DOTATOC will have to demonstrate the full potential of this strategy for radiosensitization in NEN.
Trial-by-trial variability in cortical responses exhibits scaling in spatial correlations predicted from critical dynamics
Authors: Ribeiro Tiago L. , Yu Shan , Martin Daniel A. , Winkowski Daniel , Kanold Patrick , Chialvo Dante R. , Plenz Dietmar 
Published: July 2020

AbstractSimple sensory stimuli or motor outputs engage large populations of neurons in the mammalian cortex. When stimuli or outputs repeat, the robust population response contrasts with fluctuating responses of individual neurons, known as trial-by-trial variability. To understand this apparent discrepancy, a detailed identification of the underlying spatiotemporal correlations is required. Here, we analyze spatial correlations in the instantaneous fluctuations between neurons relative to the neuronal population. Using 2-photon imaging of visual and auditory responses in primary cortices of awake mice, we show that these correlations grow linearly with the size of the observed cortical area. We extend these observations to the cortical mesoscale by analyzing local field potentials in behaving nonhuman primates. In network simulations, we demonstrate this linear growth in spatial correlation to emerge at criticality. Our findings suggest that trial-by-trial variability is a signature of critical dynamics in cortex maintaining robust, long-range spatial correlations among neurons.
Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays
Authors: Tang Mei San , Case James Brett , Franks Caroline E. , Chen Rita E. , Anderson Neil W. , Henderson Jeffrey P. , Diamond Michael S. , Gronowski Ann M. , Farnsworth Christopher W. 
Published: July 2020

AbstractIntroductionCommercially available SARS-CoV-2 serological assays based on different viral antigens have been approved for the qualitative determination of anti-SARS-CoV-2 antibodies. However, there is limited published data associating the results from commercial assays with neutralizing antibodies.Methods67 specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys SARS-CoV-2, Abbott SARS-CoV-2 IgG, or EUROIMMUN SARS-CoV-2 IgG assays and 5 control specimens were analyzed for the presence of neutralizing antibodies to SARS-CoV-2. Correlation, concordance, positive percent agreement (PPA), and negative percent agreement (NPA) were calculated at several cutoffs. Results were compared in patients categorized by clinical outcomes.ResultsThe correlation between SARS-CoV-2 neutralizing titer (EC50) and the Roche, Abbott, and EUROIMMUN assays was 0.29, 0.47, and 0.46 respectively. At an EC50of 1:32, the concordance kappa with Roche was 0.49 (95% CI; 0.23-0.75), with Abbott was 0.52 (0.28-0.77), and with EUROIMMUN was 0.61 (0.4-0.82). At the same neutralizing titer, the PPA and NPA for the Roche was 100% (94-100) & 56% (30-80); Abbott was 96% (88-99) & 69% (44-86); and EUROIMMUN was 91% (80-96) & 81% (57-93) for distinguishing neutralizing antibodies. Patients who died, were intubated, or had a cardiac injury from COVID-19 infection had significantly higher neutralizing titers relative to those with mild symptoms.ConclusionCOVID-19 patients generate an antibody response to multiple viral proteins such that the calibrator ratios on the Roche, Abbott, and EUROIMMUN assays are all associated with SARS-CoV-2 neutralization. Nevertheless, commercial serological assays have poor NPA for SARS-CoV-2 neutralization, making them imperfect proxies for neutralization.
Ontogeny of the VIP+ interneuron sensory-motor circuit prior to active whisking
Authors: Vagnoni Cristiana , Baruchin Liad J. , Ghezzi Filippo , Ratti Sara , Molnár Zoltán , Butt Simon J. B. 
Published: July 2020

ABSTRACTDevelopment of the cortical circuits for sensory-motor processing require the coordinated integration of both columnar and long-range synaptic connections. To understand how this occurs at the level of individual neurons we have explored the timeline over which vasoactive intestinal peptide (VIP)-expressing interneurons integrate into mouse somatosensory cortex. We find a distinction in emergent long-range anterior-motor and columnar glutamatergic inputs onto layer (L)2 and L3 VIP+ interneurons respectively. In parallel, VIP+ interneurons form efferent connections onto both pyramidal cells and interneurons in the immediate column in an inside-out manner. Cell-autonomous deletion of the fate-determinant transcription factor,Prox1, spares long-range anterior-motor inputs onto VIP+ interneurons, but leads to deficits in local connectivity. This imbalance in the somatosensory circuit results in altered spontaneous and sensory-evoked cortical activityin vivo. This identifies a critical role for VIP+ interneurons, and more broadly interneuron heterogeneity, in formative circuits of neocortex.
The evolution of trait variance creates a tension between species diversity and functional diversity
Authors: Barabás György , Parent Christine , Kraemer Andrew , Van de Perre Frederik , De Laender Frederik 
Published: July 2020

AbstractIt seems intuitive that species diversity promotes functional diversity. For example, more plant species imply more diverse leaf chemistry and thus more kinds of food for herbivores. Here we argue that the evolution of functional trait variance challenges this view. We show that trait-based eco-evolutionary processes force species to evolve narrower trait breadths in tightly packed communities, in their effort to avoid competition with neighboring species. This effect is so strong as to reduce overall trait space coverage, overhauling the expected positive relationship between species- and functional diversity. Empirical data from Galápagos land snail communities proved consistent with this claim. As a consequence, trait data from species-poor communities may misjudge functional diversity in species-rich ones, and vice versa.