bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural crest-related NXPH1/α-NRXN signaling opposes neuroblastoma malignancy by inhibiting metastasis
Authors: Fanlo-Escudero Lucía , Gómez-González Soledad , Sangrador Irene , Gautier Emmanuel L. , Usieto Susana , Rebollo Elena , Vila-Ubach Mònica , Carcaboso Ángel M. , Celià-Terrassa Toni , Lavarino Cinzia , Martí Elisa , Le Dréau Gwenvael 
Published: November 2021

AbstractNeuroblastoma is a pediatric cancer that can present as low- or high-risk tumors (LR-NBs and HR-NBs), the latter group showing poor prognosis due to metastasis and strong resistance to current therapy. NBs are known to originate from alterations to cells in the sympatho-adrenal lineage derived from the neural crest, but whether LR-NBs and HR-NBs differ in the way they exploit the transcriptional program underlying their developmental origin remains unclear. Here, we compared the transcriptional landscapes of primary samples of LR-NBs, HR-NBs and human fetal adrenal gland, and thereby identified the transcriptional signature associated to NB formation that further distinguishes LR-NBs from HR-NBs. The majority of the genes comprising this signature belong to the core sympatho-adrenal developmental program, are associated with favorable patient prognosis and with diminished disease progression. The top candidate gene of this list, Neurexophilin-1 (NXPH1), encodes a ligand of the transmembrane receptors α-Neurexins (α-NRXNs). Our functional in vivo and in vitro assays reveal that NXPH1/α-NRXN signaling has a dual impact on NB behavior: whereas NXPH1 and α-NRXN1 promote NB tumor growth by stimulating cell proliferation, they conversely inhibit the ability of NB cells to form metastases. Our findings uncover a module of the neural crest-derived sympatho-adrenal developmental program that opposes neuroblastoma malignancy by impeding metastasis, and pinpoint NXPH1/α-NRXN signaling as a promising target to treat HR-NBs.
Paleozoic Protein Fossils Illuminate the Evolution of Vertebrate Genomes and Transposable Elements
Authors: Frith Martin C. 
Published: November 2021

AbstractGenomes hold a treasure trove of protein fossils: fragments of formerly protein-coding DNA, which mainly come from transposable elements (TEs) or host genes. These fossils reveal ancient evolution of TEs and genomes, and many fossils have been exapted to perform diverse functions important for the host’s fitness. However, old and highly-degraded fossils are hard to identify, standard methods (e.g. BLAST) are not optimized for this task, and few Paleozoic protein fossils have been found.Here, a recently optimized method is used to find protein fossils in vertebrate genomes. It finds Paleozoic fossils predating the amphibian/amniote divergence from most major TE categories, including virus-related Polinton and Gypsy elements. It finds 10 fossils in the human genome (8 from TEs and 2 from host genes) that predate the last common ancestor of all jawed vertebrates, probably from the Ordovician period. It also finds types of transposon and retrotransposon not found in human before. These fossils have extreme sequence conservation, indicating exaptation: some have evidence of gene-regulatory function, and they tend to lie nearest to developmental genes. Some ancient fossils suggest “genome tectonics”, where two fragments of one TE have drifted apart by up to megabases, possibly explaining gene deserts and large introns.This paints a picture of great TE diversity in our aquatic ancestors, with patchy TE inheritance by later vertebrates, producing new genes and regulatory elements on the way. Host-gene fossils too have contributed anciently-conserved DNA segments. This paves the way to further studies of ancient protein fossils.
Chloroplast transit peptides often require downstream unstructured sequence in Chlamydomonas reinhardtii
Authors: Caspari OD 
Published: November 2021

1AbstractThe N-terminal sequence stretch that defines subcellular targeting for most nuclear encoded chloroplast proteins is usually considered identical to the sequence that is cleaved upon import. Yet here this study shows that for nine out of ten tested Chlamydomonas chloroplast transit peptides, additional sequence past the cleavage site is required to enable chloroplast targeting. Using replacements of native post-cleavage residues with alternative sequences points to a role for unstructured sequence at mature protein N-termini.
Near atomic structure of the inner ring of the Saccharomyces cerevisiae nuclear pore complex
Authors: Li Zongqiang , Chen Shuaijiabin , Zhao Liang , Huang Guoqiang , Pi Xiong , Sun Shan , Wang Peiyi , Sui Sen-Fang 
Published: November 2021

AbstractNuclear pore complexes (NPCs) mediate bidirectional nucleocytoplasmic transport of substances in eukaryotic cells. However, the accurate molecular arrangement of NPCs remains enigmatic owing to their huge size and highly dynamic nature. Here we determined the structure of the asymmetric unit of the inner ring (IR monomer) at 3.73 Å resolution by single-particle cryo-electron microscopy, and created an atomic model of the intact IR consisting of 192 copies from 8 subunits. In each IR monomer, two approximately parallel rhomboidal structures of the inner and outer layers are sandwiched with the Z-shaped Nup188-Nup192 middle layer and Nup188, Nup192 and Nic96 link all subunits to constitute a relatively stable IR monomer, while the intact IR is assembled by loose and instable interactions between IR monomer. These structures reveal various interaction modes and extensive flexible connections in the assembly, providing a structural basis for the stability and malleability of IR.One-Sentence SummaryAccurate structure of inner ring reveals its assembly and function in dilation and constriction of nuclear pore complex.
Proteomic Characterization of Serum Small Extracellular Vesicles in Human Breast Cancer
Authors: Xu Ganfei , Huang Weiyi , Du Shaoqian , Huang Minjing , Lyu Jiacheng , Zhou Fei , Zhu Rongxuan , Cao Yuan , Xv Jingxuan , Li Ning , Yu Guoying , Jiang Binghua , Gires Olivier , Zhou Lei , Zhang Hongwei , Ding Chen , Wang Hongxia 
Published: November 2021

AbstractThere is a lack of comprehensive understanding of breast cancer (BC) specific sEVs characteristics and composition on BC unique proteomic information from human samples. Here, we interrogated the proteomic landscape of sEVs in 167 serum samples from patients with BC, benign mammary disease (BD) and from healthy donors (HD). The analysis provides a comprehensive landscape of serum sEVs with totally 9,589 proteins identified, considerably expanding the panel of sEVs markers. Of note, serum BC-sEVs protein signatures were distinct from those of BD and HD, representing stage- and molecular subtype-specific patterns. We constructed specific sEVs protein identifiers that could serve as a liquid biopsy tool for diagnosis and classification of BC from benign mammary disease, molecular subtypes, as well as assessment of lymph node metastasis. We also identified 11 potential survival biomarkers for distant metastasis. This work may provide reference value for the accurate diagnosis and monitoring of BC progression using serum sEVs.
Genetic and thermal variation influence adaptation to fluctuating temperature in the seed beetle, Callosobruchus maculatus
Authors: Ivimey-Cook Edward , Piani Claudio , Hung Wei-Tse , Berg Elena C. 
Published: November 2021

SummaryClimate change is associated with both the increase in mean and variability of thermal conditions. The use of more realistic thermal regimes is therefore the most appropriate laboratory method to correctly predict population responses to thermal heterogeneity. However, both the long- and short-term implications of evolving under such conditions are not well understood. Here, we examined the effect of fluctuating daily temperatures on several key life history traits in the seed beetle, Callosobruchus maculatus, that was exposed to a short-term thermal switch into a novel environment. Populations were kept for 19 generations at one of two temperatures: constant control temperature (T=29°C) or a fluctuating daily cycle (Tmean=33°C, Tmax=40°C, and Tmin=26°C) and were subsequently exposed to a switch to the opposite condition. We found that beetles that had evolved in stressful environments were smaller in size when switched to a constant 29°C and had far greater reproductive fitness compared to beetles from both the constant control and continuously stressful 33°C environments. This suggests that beetles raised in environments with stressful fluctuating temperatures were more phenotypically plastic and had greater genetic variability than control treatment beetles and indicates that populations that experience fluctuations in temperature may be better able to respond to short-term changes in environmental conditions.
On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation
Authors: Jeziorska D.M. , Tunnacliffe E.A.J. , Brown J.M. , Ayyub H. , Sloane-Stanley J. , Sharpe J.A. , Lagerholm B.C. , Babbs C. , Smith A.J.H. , Buckle V.J. , Higgs D.R. 
Published: November 2021

AbstractDetermining the mechanisms by which genes are switched on and off during development and differentiation is a key aim of current biomedical research. Gene transcription has been widely observed to occur in a discontinuous fashion, with short bursts of activity interspersed with longer periods of inactivity. It is currently not known if or how this dynamic behaviour changes as mammalian cells differentiate. To investigate this, using a newly developed on-microscope analysis, we monitored mouse α-globin transcription in live cells throughout sequential stages of erythropoiesis. We find that changes in the overall levels ofα-globin transcription are most closely associated with changes in the fraction of time a gene spends in the active transcriptional state. We identify differences in the patterns of transcriptional bursting throughout differentiation, with maximal transcriptional activity occurring in the mid-phase of differentiation. Early in differentiation, we observe increased fluctuation in the patterns of transcriptional activity whereas at the peak of gene expression, in early and intermediate erythroblasts, transcription appears to be relatively stable and efficient. Later during differentiation asα-globin expression declines, we again observed more variability in transcription within individual cells. We propose that the observed changes in transcriptional behaviour may reflect changes in the stability of enhancer-promoter interactions and the formation of active transcriptional compartments as gene expression is turned on and subsequently declines at sequential stages of differentiation.
Layer-specific developmentally precise axon targeting of transient suppressed-by-contrast retinal ganglion cells (tSbC RGCs)
Authors: Tien Nai-Wen , Badea Tudor C. , Kerschensteiner Daniel 
Published: November 2021

AbstractThe mouse retina encodes diverse visual features in the spike trains of more than 40 retinal ganglion cell (RGC) types. Each RGC type innervates a specific subset of the more than 50 retinorecipient brain areas. Our catalog of RGC types and feature representations is nearing completion. Yet, we know little about where specific RGC types send their information. Furthermore, the developmental strategies by which RGC axons choose their targets and pattern their terminal arbors remain obscure. Here we identify a genetic intersection (Cck-Cre and Brn3cCKOAP) that selectively labels transient Suppressed-by-Contrast (tSbC) RGCs, a member of an evolutionarily conserved functionally mysterious RGC subclass. We find that tSbC RGCs selectively innervate the dorsolateral and ventrolateral geniculate nuclei of the thalamus (dLGN and vLGN), the superior colliculus (SC), and the nucleus of the optic tract (NOT). They binocularly innervate dLGN and vLGN but project only contralaterally to SC and NOT. In each target, tSbC RGC axons occupy a specific sublayer, suggesting that they restrict their input to specific circuits. The tSbC RGC axons span the length of the optic tract by birth and remain poised there until they simultaneously innervate their four targets around postnatal day five. The tSbC RGC axons make no errors in choosing their targets and establish mature stratification patterns from the outset. This precision is maintained in the absence of Brn3c. Our results provide the first map of SbC inputs to the brain, revealing a narrow target set, unexpected laminar organization, target-specific binocularity, and developmental precision.Significance statementIn recent years, we have learned a lot about the visual features encoded by retinal ganglion cells (RGCs), the eye’s output neurons. In contrast, we know little about where RGCs send their information and how RGC axons, which carry this information, target specific brain areas during development. Here, we develop an intersectional strategy to label a unique RGC type, the tSbC RGC, and map its projections. We find that tSbC RGC axons are highly selective. They innervate few retinal targets and restrict their arbors to specific sublayers within these targets. The selective tSbC RGC projection patterns develop synchronously and without trial and error, suggesting molecular determinism and coordination.
STAMP: Simultaneous Training and Model Pruning for Low Data Regimes in Medical Image Segmentation
Authors: Dinsdale Nicola K. , Jenkinson Mark , Namburete Ana I. L. 
Published: November 2021

AbstractAcquisition of high quality manual annotations is vital for the development of segmentation algorithms. However, to create them we require a substantial amount of expert time and knowledge. Large numbers of labels are required to train convolutional neural networks due to the vast number of parameters that must be learned in the optimisation process. Here, we develop the STAMP algorithm to allow the simultaneous training and pruning of a UNet architecture for medical image segmentation with targeted channelwise dropout to make the network robust to the pruning. We demonstrate the technique across segmentation tasks and imaging modalities. It is then shown that, through online pruning, we are able to train networks to have much higher performance than the equivalent standard UNet models while reducing their size by more than 85% in terms of parameters. This has the potential to allow networks to be directly trained on datasets where very low numbers of labels are available.
Evidence for alternate stable states in an Ecuadorian Andean Cloud Forest
Authors: Mariscal Chávez Ana , Thomas Daniel Churchill , Haffenden Austin , Manobanda Rocío , Duvauchelle Laurence , Defas William , Chinchero Miguel Angel , Simba Danilo , Jaramillo Edison , Roy Bitty A. , Peck Mika 
Published: November 2021

AbstractWe analyzed a set of historical data from rapid vegetation inventories in a tropical montane cloud forest in northern Andean Ecuador. Trees in plots from several types of forest were counted and measured, including: (1) primary forest, including mature and recently closed-canopy sites and naturally formed gaps, (2) abandoned pasture, and (3) intensively-farmed sites. The goal of the study was to understand in a specific period of time the similarities and differences among natural and anthropogenic disturbances and their potential long term effect on the forest plant community. We found that mature and intermediate close canopy sites are similar. Also old forest is quite resilient to gap-forming disturbance. Natural gaps are quickly colonized by old-forest-associated plant species, and return to an old-forest-type community of trees in a short time. In contrast, forests regenerating from anthropogenic disturbance appear to have multiple possible states: some regenerating forest sites where the anthropogenic disturbance were low are coming to closely resemble old-forest-type communities, but some where the anthropogenic disturbance was intense appear to be changing in a very different direction, which does not resemble any other vegetation community type currently in the forest. A major predictor of present ecological state is the type of land use before reforestation: pastures can occasionally transition back to the pre-disturbance state of forest. More intensively used sites, many of which are abandoned sugar cane plantations, do not return to a pre-disturbance ecological state, instead forming a new and different kind of forest, dominated by a different community of trees. We examined tree-seedling communities to understand the trajectory of the forest into the future, and find that new forest types may be forming that do not resemble any existing associationsintensive agricultural sites. We also found that Los Cedros is extremely diverse in tree species. We estimate approximately 500 species of tree in only the small southeastern area of the reserve that has been explored scientifically. Additionally, the forest tree community shows extremely rapid distance decay (beta-diversity), approaching near complete turn-over in the limited spatial extent of the study. This suggests that hundreds of other tree species remain to be observed in the reserve, in addition to the 350+ that are directly observed in the present study, including new observations of species with IUCN threatened-endangered status. We also highlight the conservation value of Reserva Los Cedros, which has managed to reverse deforestation within its boundaries despite a general trend of extensive deforestation in the surrounding region, and to protect large, contiguous areas of highly-endangered Andean primary cloud forest habitat.
NODeJ: an ImageJ plugin for 3D segmentation of nuclear objects
Authors: Dubos Tristan , Poulet Axel , Thomson Geoffrey , Péry Emilie , Chausse Frédéric , Tatout Christophe , Desset Sophie , van Wolfswinkel Josien C. , Jacob Yannick 
Published: November 2021

AbstractBackgroundThe three-dimensional nuclear arrangement of chromatin impacts many cellular processes operating at the DNA level in animal and plant systems. Chromatin organization is a dynamic process that can be affected by biotic and abiotic stresses. Three-dimensional imaging technology allows to follow these dynamic changes, but only a few semi-automated processing methods currently exist for quantitative analysis of the 3D chromatin organization.ResultsWe present an automated method, Nuclear Object DetectionJ (NODeJ), developed as an imageJ plugin. This program segments and analyzes high intensity domains in nuclei from 3D images. NODeJ performs a Laplacian convolution on the mask of a nucleus to enhance the contrast of intra-nuclear objects and allows their detection. We reanalyzed public datasets and determined that NODeJ is able to accurately identify heterochromatin domains from a diverse set of Arabidopsis thaliana nuclei stained with DAPI or Hoechst. NODeJ is also able to detect signals in nuclei from DNA FISH experiments, allowing for the analysis of specific targets of interest.Conclusion and availabilityNODeJ allows for efficient automated analysis of subnuclear structures by avoiding the semi-automated steps, resulting in reduced processing time and analytical bias. NODeJ is written in Java and provided as an ImageJ plugin with a command line option to perform more high-throughput analyses. NODeJ can be downloaded from https://gitlab.com/axpoulet/image2danalysis/-/releases with source code, documentation and further information avaliable at https://gitlab.com/axpoulet/image2danalysis. The images used in this study are publicly available at https://www.brookes.ac.uk/indepth/images/ and https://doi.org/10.15454/1HSOIE.
Neural tracking as a diagnostic tool to assess the auditory pathway
Authors: Gillis Marlies , Van Canneyt Jana , Francart Tom , Vanthornhout Jonas 
Published: November 2021

AbstractWhen a person listens to sound, the brain time-locks to specific aspects of the sound. This is called neural tracking and it can be investigated by analysing neural responses (e.g., measured by electroencephalography) to continuous natural speech. Measures of neural tracking allow for an objective investigation of a range of auditory and linguistic processes in the brain during natural speech perception. This approach is more ecologically valid than traditional auditory evoked responses and has great potential for research and clinical applications. This article reviews the neural tracking framework and highlights three prominent examples of neural tracking analyses: neural tracking of the fundamental frequency of the voice (f0), the speech envelope and linguistic features. Each of these analyses provides a unique point of view into the human brain’s hierarchical stages of speech processing. F0-tracking assesses the encoding of fine temporal information in the early stages of the auditory pathway, i.e., from the auditory periphery up to early processing in the primary auditory cortex. Envelope tracking reflects bottom-up and top-down speechrelated processes in the auditory cortex and is likely necessary but not sufficient for speech intelligibility. Linguistic feature tracking (e.g. word or phoneme surprisal) relates to neural processes more directly related to speech intelligibility. Together these analyses form a multi-faceted objective assessment of an individual’s auditory and linguistic processing.
Allelic correlation is a marker of tradeoffs between barriers to transmission of expression variability and signal responsiveness in genetic networks
Authors: Boe Ryan H. , Ayyappan Vinay , Schuh Lea , Raj Arjun 
Published: November 2021

ABSTRACTAccurately functioning genetic networks should be responsive to signals but prevent transmission of stochastic bursts of expression. Existing data in mammalian cells suggests that such transcriptional “noise” is transmitted by some genes and not others, suggesting that noise transmission is tunable, perhaps at the expense of other signal processing capabilities.However, systematic claims about noise transmission in genetic networks have been limited by the inability to directly measure noise transmission. Here we build a mathematical framework capable of modeling allelic correlation and noise transmission. We find that allelic correlation and noise transmission correspond across a broad range of model parameters and network architectures. We further find that limiting noise transmission comes with the trade-off of being unresponsive to signals, and that within the parameter regimes that are responsive to signals, there is a further trade-off between response time and basal noise transmission. Using a published allele specific single cell RNA-sequencing dataset, we found that genes with high allelic odds ratios are enriched for cell-type specific functions, and that within multiple signaling pathways, factors which are upstream in the pathway have higher allelic odds ratios than downstream factors. Overall, our findings suggest that some degree of noise transmission is required to be responsive to signals, but that minimization of noise transmission can be accomplished by trading-off for a slower response time.