bluuebunny/crossref_metadata_2025_split huggingface dataset:
Separating neural oscillations from aperiodic 1/f activity: challenges and recommendations
Authors: Gerster Moritz , Waterstraat Gunnar , Litvak Vladimir , Lehnertz Klaus , Schnitzler Alfons , Florin Esther , Curio Gabriel , Nikulin Vadim 
Published: October 2021

AbstractElectrophysiological power spectra typically consist of two components: An aperiodic part usually following an 1/f power law P∝1/fβand periodic components appearing as spectral peaks. While the investigation of the periodic parts, commonly referred to as neural oscillations, has received considerable attention, the study of the aperiodic part has only recently gained more interest. The periodic part is usually quantified by center frequencies, powers, and bandwidths, while the aperiodic part is parameterized by the y-intercept and the 1/f exponent β. For investigation of either part, however, it is essential to separate the two components.In this article, we scrutinize two frequently used methods, FOOOF (Fitting Oscillations & One-Over-F) and IRASA (Irregular Resampling Auto-Spectral Analysis), that are commonly used to separate the periodic from the aperiodic component. We evaluate these methods using diverse spectra obtained with electroencephalography (EEG), magnetoencephalography (MEG), and local field potential (LFP) recordings relating to three independent research datasets. Each method and each dataset poses distinct challenges for the extraction of both spectral parts. The specific spectral features hindering the periodic and aperiodic separation are highlighted by simulations of power spectra emphasizing these features. Through comparison with the simulation parameters defined a priori, the parameterization error of each method is quantified. Based on the real and simulated power spectra, we evaluate the advantages of both methods, discuss common challenges, note which spectral features impede the separation, assess the computational costs, and propose recommendations on how to use them.
Thermal boldness: Volunteer exploration of extreme temperatures in Drosophila melanogaster
Authors: Navas Carlos A. , Agudelo-Cantero Gustavo A. , Loeschcke Volker 
Published: October 2021

AbstractA dominant perception is that small and motile ectothermic animals must use behavior to avoid exposure to critical or sub-critical temperatures impairing physiological performance. Concomitantly, volunteer exploration of extreme environments by some individuals may promote physiological adjustments and enhance ecological opportunity. Here we introduce to the literature a Thermal Decision System (TDS) which is fully modular, thermally stable, versatile, and adaptable to study navigation through thermal landscapes in insects and other small motile animals. We used a specific setting of the TDS to investigate volunteer navigation through critical cold and hot temperatures in Drosophila melanogaster. We demonstrate that a thermally bold behavior (volunteer crossings through a Critical Temperature Zone, CTZ) characterized a fraction of flies in a sample, and that such a fraction was higher in an outbred population relative to isofemale lines. As set, the TDS generated a thermal gradient within the cold and hot CTZs, and the exploration of this gradient by flies did not relate simply with a tendency to be thermally bold. Mild fasting affected thermal exploration and boldness in complex manners, but thermal boldness was evident in both fasted and fed flies. Also, thermal boldness was not associated with individual critical temperatures. Finally, some flies showed consistent thermal boldness, as flies that performed an extreme thermal cross were more likely to perform a second cross compared with untested flies. We hypothesize that a simple “avoidance principle” is not the only behavioral drive for D. melanogaster facing extreme temperatures over space, and that this pattern may characterize other small motile ectothermic animals with analogous natural history. The physiological correlates, genetic architecture, and interspecific variation of thermal boldness deserve further consideration.
Effects of early and late life environments on ageing
Authors: Sanghvi Krish , Iglesias-Carrasco Maider , Zajitschek Felix , Kruuk Loeske E.B. , Head Megan L. 
Published: October 2021

AbstractEarly and late life environments can interact in complex ways to influence the fitness of individuals. Most studies investigating effects of the environment on fitness focus on environments experienced and traits expressed at a single point in an organism’s life. However, environments vary with time, thus the environments organisms experience at different ages may interact to affect how traits change throughout life. Here, we test whether thermal stress experienced during development leads individuals to cope better with thermal stress as adults. We manipulated temperature during both development and adulthood and measured a range of life-history traits, including senescence, in male and female seed beetles,Callosobruchus maculatus. We found that favourable developmental conditions increased reproductive performance of females (i.e. silver-spoon effects). In contrast, non-reproductive traits such as lifespan and survival senescence were only affected by adult environments- high adult temperatures decreased longevity and survival. Additionally, developmental and adult environments interacted to affect age-dependent changes in male weight. Overall, our results show that effects of early and late environments can be both sex- and trait- specific, and that a full understanding of how environments interact to affect fitness and ageing requires the integrated study of conditions experienced during different stages of ontogeny.
Cyperus rotundus root extract inhibits progress of lymphedema in mouse tail model
Authors: Pandey Nikhil , Mishra Priyanka , Tripathi Yamini.B. 
Published: October 2021

AbstractLymphedema is clinically manifested as swelling due to abnormal accumulation of interstitial fluid attributed to inefficient fluid uptake and reduced lymphatic flow. Here we have evaluated the effect of Cyperus rotundus root (CRR) ethanolic extract in a mouse tail model of lymphedema and hypothesized that Cyperus rotundus plant known for its anti-inflammatory effect through inhibition of TNF alpha will be effective in managing this condition. The skin was removed after leaving 1cm of distance from the base of the trunk. Cut was introduced in sterile condition. The animals were divided into Experimental control(EC) and Cyperus rotundus (CRR) treated groups. A change in tail volume around the wound was monitored upto the 20 days. Kinetics of the swelling was calculated for statistical significance. Further TS of upper part of the wound was stained with H&E stain and documented for histological changesRESULTSIn EC group, gradual rise in swelling was recorded, which peaked on 10th day and continued up to 15th day, followed by gradual decrease. In CR extract treated group, the swelling was significantly low and peak was obtained on 8th day, while in EC group the swelling was significantly higher and peak was obtained 11th day. The histological section show, fibrous band intersection the lobules of adipocyte and lymphatic vascular channel and muscles in the sub epithelium region in the EC group, which was very less in CRR group.CONCLUSIONSPolar fraction of CRR significantly prevents the progress of lymphedema and which lays an important role of this plant as for the drug development in future.
Simulation atomic force microscopy to predict correlated conformational dynamics in proteins from topographic imaging
Authors: Flechsig Holger 
Published: October 2021

AbstractAtomic force microscopy (AFM) of proteins can detect only changes within the scanned molecular surface, missing all motions in other regions and thus information about functionally relevant conformational couplings. We show that simulation AFM can overcome this drawback by reconstruction of 3D molecular structures from topographic AFM images. A proof of principle demonstration is provided for an in-silico AFM experiment visualizing the conformational dynamics of a membrane transporter. The application shows that the alternating access mechanism underlying its operation can be retrieved from only AFM imaging of one membrane side. Simulation AFM is implemented in the freely available BioAFMviewer software platform, providing the convenient applicability to better understand experimental AFM observations.
Effect of different ambient temperatures on reproductive outcome and wellbeing of lactating females in two mouse strains
Authors: Kolbe Thomas , Lassnig Caroline , Poelzl Andrea , Palme Rupert , Auer Kerstin E. , Rülicke Thomas 
Published: October 2021

AbstractAmbient temperature is an important non-biotic environmental factor influencing immunological and oncological parameters in laboratory mice. It is under discussion which temperature is more appropriate and whether the commonly used room temperature in rodent facilities of about 21°C represents a chronic cold stress or the 30°C of the thermoneutral zone constitutes heat stress for the animals. In this study we selected the physiological challenging period of lactation to investigate the influence of a cage temperature of 20°C, 25°C, and 30°C, respectively, on reproductive performance and stress hormone levels in two frequently used mouse strains. We found that more pups were weaned from B6D2F1 hybrids compared to C57BL/6N mothers and that the number of weaned pups was strongly reduced if mothers of both strains were kept at 30°C. Furthermore, at 30°C mothers and pups showed reduced body weight at weaning and offspring had longer tails. Despite pronounced temperature effects on reproductive parameters, we did not find any impact on adrenocortical activity in breeding and control mice. Independent of the ambient temperature however, we found that females raising pups showed elevated levels of fecal corticosterone metabolites (FCMs) compared to controls. Increased levels of stress hormone metabolites were measured specially around birth and during the third week of lactation. Our results provide no evidence for reduced or improved wellbeing of lactating mice at different ambient temperatures, but we found that a 30°C cage temperature impairs reproductive performance.
Fetal programming by sodium saccharin and damage on male offspring reproductive
Authors: Godoi Alana Rezende , Fioravante Vanessa Caroline , Santos Beatriz Melo , Martinez Francisco Eduardo , Felipe Pinheiro Patricia Fernanda 
Published: October 2021

AbstractMale infertility is responsible for 20-70% of infertility in couples. We investigated the effects of fetal programming with sodium saccharin consumption in testis structure and function and in male offspring fertility. Feed intake and efficiency, organ and fat weight, quantification and expression of AR and PCNA proteins, sperm count and hormonal dosages were performed. Changes in consumption were found in the final weeks of the experiment. Decreases in the expression and quantification of AR and PCNA, tubular diameter and luminal volume, and increase in epithelial and interstitial relative volumes were observed. Lower sperm count and transit and lower estradiol concentration were also found. The consumption of sodium saccharin by the dams programmed the male offspring affecting the HPG axis with alterations in Sertoli cell proliferation, AR expression and quantification, and sperm count. We hypothesize that these changes may be due to the reduction of estradiol that caused the loosening of the tight junctions of the blood-testis-barrier (BTB), causing cell losses during spermatogenesis, also reflecting, under the decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. Sodium saccharin programming directly affected the reproductive parameters of male offspring and adult fertility.
SURFMAP: a software for mapping in two dimensions protein surface features
Authors: Schweke Hugo , Mucchielli Marie-Hélène , Chevrollier Nicolas , Gosset Simon , Lopes Anne 
Published: October 2021

ABSTRACTMolecular cartography using two-dimensional (2D) representation of protein surfaces has been shown to be very promising for protein surface analysis. Here, we present SURFMAP, a free standalone and easy-to-use software that enables the fast and automated 2D projection of either predefined features of protein surface (i.e., electrostatic potential, Kyte-Doolittle hydrophobicity, stickiness, and surface relief) or any descriptor encoded in the temperature factor column of a PDB file. SURFMAP uses a pseudo-cylindrical sinusoidal “equal-area” projection that has the advantage of preserving the area measures. It provides the user with (i) 2D maps that enable the easy and visual analysis of protein surface features of interest and (ii) maps in a text file format allowing the fast and straightforward quantitative comparison of 2D maps of homologous proteins.
KRAS is vulnerable to reversible switch-II pocket engagement in cells
Authors: Vasta James D. , Peacock D. Matthew , Zheng Qinheng , Walker Joel A. , Zhang Ziyang , Zimprich Chad A. , Thomas Morgan R. , Beck Michael T. , Binkowski Brock F. , Corona Cesear R. , Robers Matthew B. , Shokat Kevan M. 
Published: October 2021

AbstractCurrent small molecule inhibitors of KRAS(G12C) bind irreversibly in the switch-II pocket, exploiting the strong nucleophilicity of the acquired cysteine as well as the preponderance of the GDP-bound form of this mutant. Nevertheless, many oncogenic KRAS mutants lack these two features, and it remains unknown whether targeting the switch-II pocket is a practical therapeutic approach for KRAS mutants beyond G12C. Here we use NMR spectroscopy and a novel cellular KRAS engagement assay to address this question by examining a collection of SII-P ligands from the literature and from our own laboratory. We show that the switch-II pockets of many GTP hydrolysis-deficient KRAS hotspot (G12, G13, Q61) mutants are accessible using non-covalent ligands, and that this accessibility is not necessarily coupled to the GDP state of KRAS. The results we describe here emphasize the switch-II pocket as a privileged drug binding site on KRAS and unveil new therapeutic opportunities in RAS-driven cancer.
Connexin Hemichannels with Prostaglandin Release in Anabolic Function of Bone to Mechanical Loading
Authors: Zhao Dezhi , Riquelme Manuel A. , Guda Teja , Tu Chao , Xu Huiyun , Gu Sumin , Jiang Jean X. 
Published: October 2021

AbstractMechanical stimulation, such as physical exercise, is essential for bone formation and health. Here, we demonstrate the critical role of osteocytic Cx43 hemichannels in anabolic function of bone in response to mechanical loading. Two transgenic mouse models, R76W and Δ130-136, expressing dominant-negative Cx43 mutants in osteocytes were adopted. Mechanical loading of tibial bone increased cortical bone mass and mechanical properties in wild-type and gap junction-impaired R76W mice through increased PGE2, endosteal osteoblast activity, and decreased sclerostin. These anabolic responses were impeded in gap junction/hemichannel-impaired Δ130-136 mice and accompanied by increased endosteal osteoclast activity. Specific inhibition of Cx43 hemichannels by Cx43(M1) antibody suppressed PGE2secretion and impeded loading-induced endosteal osteoblast activity, bone formation and anabolic gene expression. PGE2administration rescued the osteogenic response to mechanical loading impeded by impaired hemichannels. Together, osteocytic Cx43 hemichannels could be a potential new therapeutic target for treating bone loss and osteoporosis.
Human 5’-tailed Mirtrons are Processed by RNaseP
Authors: Zia M. Farid , Peter Jacob , Hoover Johnathan , Chen Kuan-hui E. , Flynt Alex 
Published: October 2021

ABSTRACTApproximately a thousand microRNAs (miRNAs) are documented from human cells. A third appear to transit non-canonical pathways that typically bypass processing by Drosha, the dedicated nuclear miRNA producing enzyme. The largest class of non-canonical miRNAs are mirtrons which eschew Drosha to mature through spliceosome activity. While mirtrons are found in several configurations, the vast majority of human mirtron species are 5’-tailed. For these mirtrons, a 3’ splice site defines the 3’ end of their hairpin precursor while a “tail” of variable length separates the 5’ base of the hairpin from the nearest splice site. How this tail is removed is not understood. Here we examine sequence motifs in 5’-tailed mirtrons and interactions with RNA turnover processes to characterize biogenesis processes. Through studying the high confidence 5’-tailed mirtron, hsa-miR-5010, we identify RNaseP as necessary and sufficient for “severing” the 5’ tail of this mirtron. Further, depletion of RNaseP activity globally decreased 5’-tailed mirtron expression implicating this endoribonuclease in biogenesis of the entire class. Moreover, as 5’-tailed mirtron biogenesis appears to be connected to tRNA processing we found a strong correlation between accumulation of tRNA fragments (tRFs) and 5’-tailed mirtron abundance. This suggests that dysregulation of tRNA processing seen in cancers may also impact expression of the ∼400 5’-tailed mirtrons encoded in the human genome.SUMMARYAbundant non-canonical human miRNAs referred to as tailed mirtrons are processed by RNaseP, which “severs” tail nucleotides to yield a precursor hairpin suitable for Dicer processing. Biogenesis of these miRNAs is correlated with tRFs, which are also products of RNaseP processing.
Integrating Subclonal Response Heterogeneity to Define Cancer Organoid Therapeutic Sensitivity
Authors: Kratz Jeremy D. , Rehman Shujah , Johnson Katherine A. , Gillette Amani A. , Sunil Aishwarya , Favreau Peter F. , Pasch Cheri A. , Miller Devon , Zarling Lucas C. , Yeung Austin H. , Clipson Linda , Anderson Samantha J. , DeZeeuw Alyssa K. , Sprackling Carley M. , Lemmon Kayla K. , Abbott Daniel E. , Burkard Mark E. , Bassetti Michael F. , Eickhoff Jens C. , Foley Eugene F. , Heise Charles P. , Kimple Randall J. , Lawson Elise H. , LoConte Noelle K. , Lubner Sam J. , Mulkerin Daniel L. , Matkowskyj Kristina A. , Sanger Cristina B. , Uboha Nataliya V. , Mcilwain Sean J. , Ong Irene M. , Carchman Evie H. , Skala Melissa C. , Deming Dustin A. 
Published: October 2021

AbstractTumor heterogeneity is predicted to confer inferior clinical outcomes, however modeling heterogeneity in a manner that still represents the tumor of origin remains a formidable challenge. Sequencing technologies are limited in their ability to identify rare subclonal populations and predict response to the multitude of available treatments for patients. Patient-derived organotypic cultures have significantly improved the modeling of cancer biology by faithfully representing the molecular features of primary malignant tissues. Patient-derived cancer organoid (PCO) cultures contain numerous individual organoids with the potential to recapitulate heterogeneity, though PCOs are most commonly studied in bulk ignoring any diversity in the molecular profile or treatment response. Here we demonstrate the advantage of evaluating individual PCOs in conjunction with cellular level optical metabolic imaging to characterize the largely ignored heterogeneity within these cultures to predict clinical therapeutic response, identify subclonal populations, and determine patient specific mechanisms of resistance.
Post-injury born oligodendrocytes integrate into the glial scar and inhibit growth of regenerating axons by premature myelination
Authors: Xing Jian , Rheaume Bruce A. , Kim Juhwan , Lukomska Agnieszka , Sajid Muhammad S. , Damania Ashiti , Trakhtenberg Ephraim F. 
Published: October 2021

ABSTRACTPathologies of the central nervous system (CNS) white matter often result in permanent functional deficits because mature mammalian projection neurons fail to regenerate long-distance axons after injury. A major barrier to axonal regenerative research is that the CNS axons that regenerate in response to experimental treatments stall growth before reaching their post-synaptic targets. Here, we test the hypothesis that premature, de novo, myelination of regenerating axons stalls their growth, even after bypassing the glial scar. To test this hypothesis, first, we used single cell RNA-seq (scRNA-seq) and immunohistological analysis to investigate whether post-injury born oligodendrocytes integrate into the glial scar after optic nerve injury. Then, we used a multiple sclerosis model of demyelination concurrently with the stimulation of axon regeneration by Pten knockdown (KD) in projection neurons after optic nerve injury. We found that post-injury born oligodendrocytes integrate into the glial scar, where they are susceptible to the demyelination treatment, which prevented premature myelination, and thereby enhanced Pten KD-stimulated axon regeneration. We also present a website for comparing the gene expression of scRNA-seq-profiled optic nerve oligodendrocytes under physiological and pathophysiological conditions.SIGNIFICANCE STATEMENTMyelin debris from degenerating axons along with reactive astrocytes in the glial scar inhibit CNS axon regeneration. However, even with the recently developed experimental approaches which activate axons to regenerate passed the glial scar, almost all axons still stall growth before reaching their post-synaptic targets. Here, we show that post-injury born oligodendrocytes integrate into the glial scar, and that other than myelin debris, live oligodendrocytes prematurely myelinating the regenerating axons inhibit growth, even if the axons have already regenerated passed the glial scar.
Maf is a regulator of differentiation for gut immune epithelial cell Microfold cell (M cell)
Authors: George Joel Johnson , Arrojo Martins Fábio Tadeu , Martin-Diaz Laura , Viiri Keijo 
Published: October 2021

AbstractMicrofold cells (M cells) are a specialized subset of epithelial intestinal cells responsible for immunosurveillance of the gastrointestinal tract. M cells are located in the Peyer’s patches and are crucial for monitoring and the transcytosis of antigens, microorganisms, and pathogens via their mature receptor GP2. A mature M cell with Gp2 receptor aids in the uptake of antigens, which are passed through the single layer of epithelium and presented to underlying antigen-presenting cells and processed further down-stream with B cells, T cells, and dendritic cells. Recent studies revealed several transcription factors and ligands responsible for the development and differentiation of mature M cells however, an exhaustive list of factors remains to be elucidated. Our recent work on the epigenetic regulation of M cell development found 12 critical transcription factors that were controlled by the polycomb recessive complex 2. Musculoaponeurotic fibrosarcoma transcription factor (Maf) was identified as a gene regulated by the polycomb repressive complex (PRC2) during the development of M cells. In this paper, we explore Maf’s critical role in M cell differentiation and maturation. Maf falls under the purview of RANKL signaling, is localized in the Peyer’s patches of the intestine, and is expressed by M cells. Given that, complete knockout of the Maf gene leads to a lethal phenotype, organoids isolated from Maf knockout mice and treated with RANKL exhibited impaired M cell development and a significant decrease in Gp2 expression. These findings reveal that Maf is an important regulator for M cell development and differentiation.