bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heightened condition dependent expression of structural colouration in the faces, but not wings, of male and female flies
Authors: White Thomas E. , Locke Amy , Latty Tanya 
Published: June 2021

AbstractStructurally coloured sexual signals are a conspicuous and widespread class of ornament used in mate choice, though the extent to which they encode information on the quality of their bearers is not fully resolved. Theory predicts that signalling traits under strong sexual selection as ‘honest’ indicators should evolve to be more developmentally integrated and exaggerated than nonsexual traits, thereby leading to heightened condition dependence. Here we test this prediction through examination of the sexually dimorphic faces and wings of the cursorial fly Lispe cana. Males and females possess structural UV-white and golden faces, respectively, and males present their faces and wings to females during close-range, ground-based courtship displays, thereby creating the opportunity for mutual inspection. Across a field-collected sample of individuals, we found that the appearance of the faces of both sexes scaled positively with individual condition, though along separate axes. Males in better condition expressed brighter faces as modelled according to conspecific flies, whereas condition scaled with facial saturation in females. We found no such relationships for their wing interference pattern nor abdomens, with the latter included as a nonsexual control. Our results suggest that the structurally coloured faces, but not the iridescent wings, of male and female Lispe cana are reliable guides to individual quality and support the broader potential for structural colours as honest signals. They also highlight the potential for mutual mate choice in this system, while arguing for one of several alternate signalling roles for wing interferences patterns among the myriad taxa which bear them.
Monitoring group activity of hamsters and mice as a novel tool to evaluate COVID-19 progression, convalescence and rVSV-ΔG-spike vaccination efficacy
Authors: Melamed Sharon , Politi Boaz , Grauer Ettie , Achdout Hagit , Aftalion Moshe , Gur David , Tamir Hadas , Yahalom-Ronen Yfat , Maimon Shlomy , Yitzhak Efi , Weiss Shay , Rosner Amir , Erez Noam , Yitzhaki Shmuel , Shapira Shmuel C , Paran Nir , Mamroud Emanuelle , Vagima Yaron , Israely Tomer 
Published: June 2021

AbstractCOVID-19 pandemic initiated a worldwide race toward the development of treatments and vaccines. Small animal models were the Syrian golden hamster and the K18-hACE2 mice infected with SARS-CoV-2 to display a disease state with some aspects of the human COVID-19. Group activity of animals in their home cage continuously monitored by the HCMS100 was used as a sensitive marker of disease, successfully detecting morbidity symptoms of SARS-CoV-2 infection in hamsters and in K18-hACE2 mice. COVID-19 convalescent hamsters re-challenged with SARS-CoV-2, exhibited minor reduction in group activity compared to naive hamsters. To evaluate rVSV-ΔG-spike vaccination efficacy against SARS-CoV-2, we used the HCMS100 to monitor group activity of hamsters in their home cage. Single-dose rVSV-ΔG-spike vaccination of immunized group showed a faster recovery compared to the non-immunized infected hamsters, substantiating the efficacy of rVSV-ΔG-spike vaccine. HCMS100 offers non-intrusive, hands-free monitoring of a number of home cages of hamsters or mice modeling COVID-19.
TRβ Agonism Induces Tumor Suppression and Enhances Drug Efficacy in Anaplastic Thyroid Cancer in Female Mice
Authors: Gillis Noelle E. , Cozzens Lauren M. , Wilson Emily R. , Smith Noah M. , Tomczak Jennifer A. , Bolf Eric L. , Carr Frances E. 
Published: June 2021

ABSTRACTThyroid hormone receptor beta (TRβ) is a recognized tumor suppressor in numerous solid cancers. The molecular signaling of TRβ has been elucidated in several cancer types through re-expression models. Remarkably, the potential impact of selective activation of endogenous TRβ on tumor progression remains largely unexplored. We used cell-based andin vivoassays to evaluate the effects of the TRβ agonist Sobetirome (GC-1) on a particularly aggressive and dedifferentiated cancer, anaplastic thyroid cancer (ATC). Here we report that GC-1 reduced the tumorigenic phenotype, decreased cancer stem-like cell populations, and induced re-differentiation of the ATC cell lines with different mutational backgrounds. Of note, this selective activation of TRβ amplified the effects of therapeutic agents in blunting the aggressive cell phenotype and stem-cell growth. In xenograft assays, GC-1 alone inhibited tumor growth and was as effective as the kinase inhibitor, Sorafenib. These results indicate that selective activation of TRβ not only induces a tumor suppression programde novobut enhances the effectiveness of anti-cancer agents revealing potential novel combination therapies for ATC and other aggressive solid tumors.
FMRI multi-scale cortical spontaneous activity: 7T vs. 3T
Authors: Xing Xiu-Xia , Jiang Chao , Gao Xiao , Wang Yin-Shan , Zuo Xi-Nian 
Published: June 2021

AbstractThis paper describes the use of the Human Connectome Project (HCP) data for mapping the distribution of spontaneous activity in the human brain across different spatial scales, magnets and individuals. Specifically, the resting-state functional MRI signals acquired under the HCP 3 tesla (T) and 7T magnet protocols were measured by computational methods at multiple spatial scales across the cerebral cortex using: 1) an amplitude metric on a single measuring unit (ALFF), 2) a functional homogeneity metric on a set of neighboring measuring units (ReHo) and 3) a homotopic functional connectivity metric on pairs of symmetric measuring units between the two hemispheres (VMHC). Statistical assessments on these measurements revealed that all the raw metrics were enhanced by the higher magnetic field, highlighting their dependence on magnet field strength. Measurement reliability of these global measurements were moderate to high and comparable between between 3T and 7T magnets. The differences in these measurements introduced by the higher magnetic field were spatially dependent and varied according to specific cortical regions. Specifically, the spatial contrasts of ALFF were enhanced by the 7T magnet within the anterior cortex while weakened in the posterior cortex. This is opposite for ReHo and VMHC. This scale-dependent phenomena also held true for measurement reliabilities, which were enhanced by the 7T magnet for ReHo and VMHC and weakened for ALFF. These reliability differences were primarily located in high-order associate cortex, reflecting the corresponding changes of individual differences: higher between-subject variability and lower within-subject variability for ReHo and VMHC, lower between-subject variability and higher within-subject variability for ReHo and VMHC with respect to higher magnetic field strength. Our work, for the first time, demonstrates the spatial-scale dependence of spontaneous cortical activity measurements in the human brain and their test-retest reliability across different magnet strengths, and discussed about the statistical implications for experimental design using resting-state fMRI.
A dual allosteric pathway drives human mitochondrial Lon
Authors: Gesé Genís Valentín , Shahzad Saba , Pardo-Hernández Carlos , Wramstedt Anna , Falkenberg Maria , Hällberg B. Martin 
Published: June 2021

AbstractThe hexameric, barrel-forming, AAA+ protease Lon is critical for maintaining mitochondrial matrix protein homeostasis. Efficient substrate processing by Lon requires the coordinated action of six protomers. Despite Lon’s importance for human health, the molecular bases for Lon’s substrate recognition and processing remain unclear. Here, we use a combination of biochemistry and electron cryomicroscopy (cryo-EM) to unveil the structural and functional basis for full-length human mitochondrial Lon’s degradation of mitochondrial transcription factor A (TFAM). We show how opposing protomers in the Lon hexamer barrel interact through their N-terminal domains to give what resembles three feet above the barrel and help to form a triangular pore located just above the entry pore to the barrel. The interactions between opposing protomers constitute a primary allosteric regulation of Lon activity. A secondary allosteric regulation consists of an inter-subunit signaling element in the ATPase domains. By considering the ATP or ADP load in each protomer, we show how this dual allosteric mechanism in Lon achieves coordinated ATP hydrolysis and substrate processing. This mechanism enforces sequential anti-clockwise ATP hydrolysis resulting in a coordinated hand-over-hand translocation of the substrate towards the protease active sites.
Incorporating outlier information into diffusion MR tractogram filtering for robust structural brain connectivity and microstructural analyses
Authors: Sairanen Viljami , Ocampo-Pineda Mario , Granziera Cristina , Schiavi Simona , Daducci Alessandro 
Published: June 2021

ABSTRACTThe white matter structures of the human brain can be represented using diffusion-weighted MRI tractography. Unfortunately, tractography is prone to find false-positive streamlines causing a severe decline in its specificity and limiting its feasibility in accurate structural brain connectivity analyses. Filtering algorithms have been proposed to reduce the number of invalid streamlines but the currently available filtering algorithms are not suitable to process data that contains motion artefacts which are typical in clinical research. We augmented the Convex Optimization Modelling for Microstructure Informed Tractography (COMMIT) filtering algorithm to adjust for these signal drop-out motion artifacts. We demonstrate with comprehensive Monte-Carlo whole brain simulations and in vivo infant data that our robust algorithm is capable in properly filtering tractography reconstructions despite these artefacts. We evaluated the results using parametric and non-parametric statistics and our results demonstrate that if not accounted for, motion artefacts can have severe adverse effect in the human brain structural connectivity analyses as well as in microstructural property mappings. In conclusion, the usage of robust filtering methods to mitigate motion related errors in tractogram filtering is highly beneficial especially in clinical studies with uncooperative patient groups such as infants. With our presented robust augmentation and open-source implementation, robust tractogram filtering is readily available.HighlightsWe present a novel augmentation to tractogram filtering method that accounts for subject motion related signal dropout artefacts in diffusion weighted images.Our method is validated with realistic Monte-Carlo whole brain simulations and evaluated with in vivo infant data.We show that even if data has 10% of motion corrupted slices our method is capable to mitigate their effect in structural brain connectivity analyses and microstructural mapping.
Quantifying spinal cord vascular permeability in the mouse using intravital imaging
Authors: Da Vitoria Lobo M.E. , Bates David O , Arkill Kenton P , Hulse R.P. 
Published: June 2021

AbstractSensory perception and motor dexterity is coordinated by in part distinct anatomical centres in the spinal cord. Importantly the spinal cord is the first modulatory relay hub for coordinating sensory and motor inputs to allow control of an organisms response to a sensory experience and to orientate proprioceptive outputs. This is whilst communicating with higher centres within the brain to undertake greater complex neurophysiological function such as pain perception. This begins to outline the complexity of the nervous system communication. To allow this integral system to function efficiently neuronal homeostasis needs to be maintained with energy expenditure matched by proficient delivery of nutrients. This factor introduces the vascular system that extensively interacts in a multifaceted manner with differing aspects of the nervous system. Part of this multi-factoral interaction is through the heterogenic cellular makeup of the vascular network that delivers and modulates the molecular transport of such nutrients to spinal cord tissues, but also controlling penetration and migration of harmful pathogens and agents. Therefore the spinal cord is susceptible to any alterations in the microvessel integrity (e.g. vascular leakage) and/or function (e.g. cessated blood flow) of this vascular network, which principally occurs in times of pathology. Typically investigations into microvessel function have utilised histological and/or tracer based in-vivo assays. Methodologies such as evans blue extravasation have been used inconjunction with in-vitro cell biology assays such as transwell assays to determine microvessel integrity or function that only provides snapshots of developing vasculopathy. Adopting in-vivo imaging approaches, allow for real time functional measurements of the ongoing physiological function within the spinal cord, providing direct measurement of the vascular processes in play, including vascular architecture, blood flow and/or permeability. This technique in mouse allow for direct visualisation of cellular and/or mechanistic influence upon vascular function through utilising disease, transgenic and/or viral approaches. This combination of attributes allows for in depth real time understanding of the function of the vascular network within the spinal cord.
The mating system affects the temperature sensitivity of male and female fertility
Authors: Baur Julian , Jagusch Dorian , Michalak Piotr , Koppik Mareike , Berger David 
Published: June 2021

AbstractTo mitigate effects of climate change it is important to understand species’ responses to increasing temperatures. This has often been done by studying survival or activity at temperature extremes. Before such extremes are reached, however, effects on fertility may already be apparent.Sex differences in the thermal sensitivity of fertility (TSF) could impact species persistence under climate warming because female fertility is typically more limiting to population growth than male fertility. However, little is known about sex differences in TSF.Here we first demonstrate that the mating system can strongly influence TSF using the seed beetle Callosobruchus maculatus. We exposed populations carrying artificially induced mutations to two generations of short-term experimental evolution under alternative mating systems, manipulating the opportunity for natural and sexual selection on the mutations. We then measured TSF in males and females subjected to juvenile or adult heat stress.Populations kept under natural and sexual selection had higher fitness, but similar TSF, compared to control populations kept under relaxed selection. However, females had higher TSF than males, and strikingly, this sex difference had increased over only two generations in populations evolving under sexual selection.We hypothesized that an increase in male-induced harm to females during mating had played a central role in driving this evolved sex difference, and indeed, remating under conditions limiting male harassment of females reduced both male and female TSF. Moreover, we show that manipulation of mating system parameters in C. maculatus generates intraspecific variation in the sex difference in TSF equal to that found among a diverse set of studies on insects.Our study provides a causal link between the mating system and TSF. Sexual conflict, (re)mating rates, and genetic responses to sexual selection differ among ecological settings, mating systems and species. Our study therefore also provides mechanistic understanding for the variability in previously reported TSFs which can inform future experimental assays and predictions of species responses to climate warming.
A new behavioral and neural marker of social vision
Authors: Abassi Etienne , Papeo Liuba 
Published: June 2021

AbstractResearch on face perception has revealed highly specialized visual mechanisms such as configural processing, and provided markers of interindividual differences –including disease risks and alterations– in visuoperceptual abilities that traffic in social cognition. Is face perception unique in degree or kind of mechanisms, and in its relevance for social cognition? Combining functional MRI and behavioral methods, we address the processing of an uncharted class of socially relevant stimuli: minimal social scenes involving configurations of two bodies spatially close and face-to-face as if interacting (hereafter, facing dyads). We report category-specific activity for facing (vs. non-facing) two-body configurations in selective areas of the visual cortex. That activity shows face-like signatures of configural processing –i.e., stronger response, and greater susceptibility to stimulus inversion for facing (vs. non-facing) dyads–, and is predicted by performance-based measures of body-dyad perception (i.e., accuracy in a fast visual categorization task). Moreover, individual performance in body-dyad perception is reliable, stable-over-time and correlated with the individual social sensitivity, coarsely captured by the Autism-Spectrum Quotient. Further analyses clarify the relationship between single-body and body-dyad perception. We propose that facing dyads are processed through highly specialized mechanisms (and brain areas), analogously to other biologically/socially relevant stimuli such as faces. Like face perception, facing-dyad perception can reveal basic visual processes that lay the foundations for understanding others, their relationships and interactions.Significance statementWith its specialization to faces and biological motion, vision houses the foundations of human social ability. Using a multimodal approach (meta-analysis, fMRI, visual-perception tasks and self-administered survey), we introduce a new class of visual stimuli –minimal social scenes with two face-to-face bodies–, whose processing highlights new behavioral and neural markers of visuoperceptual abilities that traffic in social cognition. Behavioral and neural effects of body-dyad perception reveal the recruitment of specialized configural processing, previously described for face perception. Furthermore, individual performance in body-dyad perception is stable over time, and predicts an individual’s social sensitivity, measured in terms of autism-spectrum traits. Thus, body-dyad perception reveals uncharted aspects of visual functioning and specialization, which may critically contribute to human social life.
Informing shigellosis prevention and control through pathogen genomics
Authors: Bengtsson Rebecca J. , Simpkin Adam J. , Pulford Caisey V. , Low Ross , Rasko David A. , Rigden Daniel J. , Hall Neil , Barry Eileen M. , Tennant Sharon M. , Baker Kate S. 
Published: June 2021

AbstractShigellaspp. are the leading bacterial cause of severe childhood diarrhoea in low- and middle-income countries (LMIC), are increasingly antimicrobial resistant and have no licensed vaccine. We performed genomic analyses of 1246 systematically collected shigellae from seven LMIC to inform control and identify factors that could limit the effectiveness of current approaches. We found thatS. sonneicontributes ≥20-fold more disease than otherShigellaspecies relative to its genomic diversity and highlight existing diversity and adaptative capacity amongS. flexnerithat may generate vaccine escape variants in <6 months. Furthermore, we show convergent evolution of resistance against the current recommended antimicrobial among shigellae. This demonstrates the urgent need to integrate existing genomic diversity into vaccine and treatment plans forShigella, and other pathogens.
pySuStaIn: a Python implementation of the Subtype and Stage Inference algorithm
Authors: Aksman Leon M. , Wijeratne Peter A. , Oxtoby Neil P. , Eshaghi Arman , Shand Cameron , Altmann Andre , Alexander Daniel C. , Young Alexandra L. 
Published: June 2021

AbstractProgressive disorders are highly heterogeneous. Symptom-based clinical classification of these disorders may not reflect the underlying pathobiology. Data-driven subtyping and staging of patients has the potential to disentangle the complex spatiotemporal patterns of disease progression. Tools that enable this are in high demand from clinical and treatment-development communities. Here we describe the pySuStaIn software package, a Python-based implementation of the Subtype and Stage Inference (SuStaIn) algorithm. SuStaIn unravels the complexity of heterogeneous diseases by inferring multiple disease progression patterns (subtypes) and individual severity (stages) from cross-sectional data. The primary aims of pySuStaIn are to enable widespread application and translation of SuStaIn via an accessible Python package that supports simple extension and generalization to novel modelling situations within a single, consistent architecture.Code metadataCurrent code version v1.0Permanent link to code/repository used of this code version https://github.com/ucl-pond/pySuStaInLegal Code License MITCode versioning system used gitSoftware code languages, tools, and services used PythonCompilation requirements, operating environments & dependencies Linux, Mac, WindowsSupport email for questions leon.aksman@loni.usc.edu, p.wijeratne@ucl.ac.uk, alexandra.young@kcl.ac.uk
Nonlinear transient amplification in recurrent neural networks with short-term plasticity
Authors: Wu Yue Kris , Zenke Friedemann 
Published: June 2021

AbstractTo rapidly process information, neural circuits have to amplify specific activity patterns transiently. How the brain performs this nonlinear operation remains elusive. Hebbian assemblies are one possibility whereby symmetric excitatory connections boost neuronal activity. However, such Hebbian amplification is often associated with dynamical slowing of network dynamics, non-transient attractor states, and pathological run-away activity. Feedback inhibition can alleviate these effects but typically linearizes responses and reduces amplification gain. At the same time, other alternative mechanisms rely on asymmetric connectivity, in conflict with the Hebbian doctrine. Here we propose nonlinear transient amplification (NTA), a plausible circuit mechanism that reconciles symmetric connectivity with rapid amplification while avoiding the above issues. NTA has two distinct temporal phases. Initially, positive feedback excitation selectively amplifies inputs that exceed a critical threshold. Subsequently, short-term plasticity quenches the run-away dynamics into an inhibition-stabilized network state. By characterizing NTA in supralinear network models, we establish that the resulting onset transients are stimulus selective and well-suited for speedy information processing. Further, we find that excitatory-inhibitory co-tuning widens the parameter regime in which NTA is possible. In summary, NTA provides a parsimonious explanation for how excitatory-inhibitory co-tuning and short-term plasticity collaborate in recurrent networks to achieve transient amplification.