bluuebunny/crossref_metadata_2025_split huggingface dataset:
Power analysis for spatial omics
Authors: Baker Ethan A. G. , Schapiro Denis , Dumitrascu Bianca , Vickovic Sanja , Regev Aviv 
Published: January 2022

AbstractAs spatially-resolved multiplex profiling of RNA and proteins becomes more prominent, it is increasingly important to understand the statistical power available to test specific hypotheses when designing and interpreting such experiments. Ideally, it would be possible to create an oracle that predicts sampling requirements for generalized spatial experiments. However, the unknown number of relevant spatial features and the complexity of spatial data analysis makes this challenging. Here, we enumerate multiple parameters of interest that should be considered in the design of a properly powered spatial omics. We introduce a method for tunable in silico tissue generation, and use it with spatial profiling datasets to construct an exploratory computational framework for single cell spatial power analysis. Finally, we demonstrate that our framework can be applied across diverse spatial data modalities and tissues of interest.
Retinal waves align the concentric orientation map in mouse superior colliculus to the center of vision
Authors: Teh Kai Lun , Sibille Jérémie , Kremkow Jens 
Published: January 2022

ABSTRACTNeurons in the mouse superior colliculus (SC) are arranged in an orientation preference map that has a concentric organization, which is aligned to the center of vision and the optic flow experienced by the mouse. The developmental mechanisms that underlie this functional map remain unclear. Here, we propose that the spatiotemporal properties of spontaneous retinal waves during development provide a scaffold to establish the concentric orientation map in the mouse SC and its alignment to the optic flow. We test this hypothesis by modelling the orientation-tuned SC neurons that receive ON/OFF retinal inputs. Our results suggest that the stage III retinal wave properties, namely OFF delayed response and the wave propagation direction bias, are key factors that regulate the spatial organization of the SC orientation map. Specifically, the OFF delay mediates the establishment of orientation-tuned SC neurons by segregating their ON/OFF receptive subfields, the wave-like activities facilitate the formation of a concentric pattern, and the wave direction biases align the orientation map to the center of vision. Taken together, our model suggests that retinal waves may play an instructive role in establishing functional properties of SC neurons and provides a promising mechanism for explaining the correlations between the optic flow and the SC orientation map.
3D Visualisation of trans-syncytial nanopores provides a pathway for paracellular diffusion across the human placental syncytiotrophoblast
Authors: Lewis Rohan M , Baskaran Harikesan , Green Jools , Tashev Stanimir , Paleologou Eleni , Lofthouse Emma M , Cleal Jane K , Page Anton , Chatelet David S , Goggin Patricia , Sengers Bram G 
Published: January 2022

AbstractThe placental syncytiotrophoblast, a syncytium without cell-cell junctions, is the primary barrier between the mother and the fetus. Despite no apparent anatomical pathway for paracellular diffusion of solutes across the syncytiotrophoblast size-dependent paracellular diffusion is observed. Here we report data demonstrating that the syncytiotrophoblast is punctuated by trans-syncytial nanopores (TSNs). These membrane-bound TSNs directly connect the maternal and fetal facing sides of the syncytiotrophoblast, providing a pathway for paracellular diffusion between the mother and fetus. Mathematical modelling of TSN permeability based on their 3D geometry suggests that 10-37 million TSNs per cm3 of placental tissue could explain experimentally observed placental paracellular diffusion. TSNs may mediate physiological hydrostatic and osmotic pressure homeostasis between the maternal and fetal circulations but also expose the fetus to pharmaceuticals, environmental pollutants and nanoparticles.
Multisensory information about changing object properties can be used to quickly correct predictive force scaling for object lifting
Authors: Polanen Vonne van 
Published: January 2022

ABSTRACTSensory information about object properties, such as size or material, can be used to make an estimate of object weight and to generate an accurate motor plan to lift the object. When object properties change, the motor plan needs to be corrected based on the new information. The current study investigated whether such corrections could be made quickly, after the movement was initiated. Participants had to grasp and lift objects of different weights that could be indicated with different cues. During the reaching phase, the cue could change to indicate a different weight and participants had to quickly adjust their planned forces in order to lift the object skilfully. The object weight was cued with different object sizes (Experiment 1) or materials (Experiment 2) and the cue was presented in different sensory modality conditions: visually, haptically or both (visuohaptic). Results showed that participants could adjust their planned forces based on both size and material and in all sensory modality conditions. Furthermore, the findings indicate that visual and haptic information were integrated in the visuohaptic condition, although the multisensory condition did not outperform the conditions with one sensory modality. These results suggest that motor plans can be quickly corrected based on sensory information about object properties from different sensory modalities. These findings provide insights into the information that can be shared between brain areas for the online control of hand-object interactions.
Sampling-based Bayesian inference in recurrent circuits of stochastic spiking neurons
Authors: Zhang Wen-Hao , Wu Si , Josić Krešimir , Doiron Brent 
Published: January 2022

AbstractTwo facts about cortex are widely accepted: neuronal responses show large spiking variability with near Poisson statistics and cortical circuits feature abundant recurrent connections between neurons. How these spiking and circuit properties combine to support sensory representation and information processing is not well understood. We build a theoretical framework showing that these two ubiquitous features of cortex combine to produce optimal sampling-based Bayesian inference. Recurrent connections store an internal model of the external world, and Poissonian variability of spike responses drives flexible sampling from the posterior stimulus distributions obtained by combining feedforward and recurrent neuronal inputs. We illustrate how this framework for sampling-based inference can be used by cortex to represent latent multivariate stimuli organized either hierarchically or in parallel. A neural signature of such network sampling are internally generated differential correlations whose amplitude is determined by the prior stored in the circuit, which provides an experimentally testable prediction for our framework.
Topology of connective tissues: a key parameter in cellular heterogeneity, beyond composition and stiffness
Authors: Chen Changchong , Ibrahim Zeinab , Marchand Marion F. , Piolot Tristan , Kamboj Sahil , Carreiras Franck , Yamada Ayako , Schanne-Klein Marie-Claire , Chen Yong , Lambert Ambroise , Aimé Carole 
Published: January 2022

AbstractCellular plasticity is essential in physiological contexts, including pathological ones. It is the basis of morphogenesis and organogenesis, as well as tumorigenesis and metastasis. The extracellular matrix (ECM) is a key player in the generation of cellular heterogeneity. Advances in our understanding of cell plasticity rely on our ability to provide relevantin vitromodels. This requires to catch the characteristics of the tissues that are essential for controlling cell fate. To do this, we must consider the diversity of tissues, the diversity of physiological contexts, and the constant remodeling of ECM along these processes. To this aim, we have fabricated a library of ECM models for reproducing the scaffold of connective tissues and basement membrane with different biofabrication routes based on the electrospining and drop casting of biopolymers. Using a combination of multiphoton imaging and nanoindentation, we show that we can vary independently protein composition, topology of connective tissues and stiffness of ECM models. Reproducing the features of a tissue and physiological context in turns allows to generate the complexity of the phenotypic landscape associated with the epithelial-to-mesenchymal transition (EMT) in human ovarian cancer. We show that EMT shift cannot be directly correlated with a unique ECM feature, which reflects the multidimensionality of living environments. Very importantly, our combinatorial approach allows us to providein vitromodels, where the impact of the topological cues on cellular phenotypes can be revealed, beyond protein composition and stiffness of the ECM matrix. On this line, this work is a further step towards the development of ECM models recapitulating the constantly remodeled scaffolding environment that cells face and provides new insights for the development of cell-free matrices.
Simulated docking reveals putative channels for the transport of long-chain fatty acids in Vibrio cholerae
Authors: Turgeson Andrew , Giles David , Harris Bradley 
Published: January 2022

ABSTRACTFatty acids (FA) play an important role in biological functions, such as membrane homeostasis, metabolism, and as signaling molecules. FadL is the only known protein that uptakes long-chain fatty acids in Gram-negative bacteria, and this uptake has traditionally been thought to be limited to fatty acids up to 18 carbon atoms in length. Recently however, it was found Vibrio cholerae has the ability to uptake fatty acids greater than 18 carbon atoms and this uptake corresponds to higher bacterial survivability. Using E. coli’s FadL as a template, V. cholerae FadL homologs vc1042, vc1043, and vca0862 have been folded, simulated on an atomistic level using molecular dynamics, and analyzed revealing the FadL transport channels. For vc1042 and vc1043 these transport channels have more structural accommodations for the many rigid unsaturated bonds of long-chain polyunsaturated fatty acids, while vca0862 was found to lack transport channels within the signature beta barrel of FadL proteins.IMPORTANCEFatty acids are important precursors for membrane phospholipids as well as energy sources for bacteria. V. cholerae’s uptake of long-chain fatty acids has not been studied to the atomistic level at this point, and by doing so, the resulting putative pathways show important structural details of the transport protein. Not only do the transport channels have unique differences between one another, the predicted transport mechanics of V. cholerae’s protein homologs differ substantially from the E. coli FadL’s pathway found from X-ray crystallography studies.
Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity
Authors: Søraas Arne , Grødeland Gunnveig , Granerud Beathe Kiland , Ueland Thor , Lind Andreas , Fevang Børre , Murphy Sarah , Huse Camilla , Nygaard Anders Benteson , Steffensen Anne Katrine , al-Baldawi Huda , Holberg-Petersen Mona , Andresen Lise Lima , Ågnes Camilla , Ranheim Trine , Schanke Ylva , Istre Mette , Dahl John Arne , Chopra Adity , Dudman Susanne , Kaarbø Mari , Andersen Jan Terje , Vaage Eline Benno , Tran Trung The , Vaage John Torgils , Michelsen Annika E. , Müller Fredrik , Aukrust Pål , Halvorsen Bente , Børresdatter Dahl Tuva , Holter Jan Cato , Lund-Johansen Fridtjof 
Published: January 2022

ABSTRACTBackgroundThe Omicron variant of SARS-CoV-2 is now overtaking the Delta variant in many countries. Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron may indicate that the higher rate of transmission is due to evasion from vaccine-induced immunity. However, there is little information about activation of recall responses to Omicron in vaccinated individuals.MethodsWe measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively.FindingsInfection with Omicron or Delta led to a rapid and similar increase in antibodies to the SARS-CoV-2 spike and nucleocapsid proteins and spike peptide-induced interferon gamma in whole blood. Both the Omicron and the Delta infected patients had a mild and transient increase in inflammatory parameters.InterpretationThe results suggest that vaccine-induced immunological memory yields similar coverage for the Omicron and Delta variants.
Contributions of age and clinical depression to metacognitive performance
Authors: Culot Catherine , Lauwers Tina , Fantini-Hauwel Carole , Madani Yamina , Schrijvers Didier , Morrens Manuel , Gevers Wim 
Published: January 2022

AbstractBackgroundPivotal for adaptive behaviour is the ability to judge whether our performance is correct or not, even in the absence of external feedback. This metacognitive ability can be measured using confidence ratings. Past research suggests that overall confidence (confidence bias) is lower in Major Depressive Disorder (MDD). Less is known about the ability of MDD patients to discriminate correct from incorrect performance (metacognitive efficiency).MethodsThe perceptual metacognitive performance of 17 aged MDD patients (62-89 years) was tested and compared to an age matched as well as a young control group (21-28 years). The younger control group was included to disentangle the effects of age and MDD on metacognitive performance. Indeed, earlier studies found an increased confidence bias but a decreased metacognitive efficiency with age.ResultsOur results showed no difference in confidence bias nor in metacognitive efficiency between MDD patients and age-matched control participants. Importantly, aged participants, including both aged controls and MDD patients, demonstrated lower metacognitive efficiency compared to young participants. This metacognitive deficit found in aged participants was specifically driven by an overconfidence on incorrect trials.ConclusionsThe relation between MDD and confidence bias may not be as robust as previously claimed. Furthermore, our results point to the importance of age rather than MDD for metacognitive efficiency. This could have important clinical implications as the observation of lower metacognitive abilities in patients is not necessarily caused by the depression.LimitationsSample size was relatively small. Some clinical variables such as anxiety, or medication were not controlled.
Development of the First Tractable Genetic System for Parvimonas micra, a Ubiquitous Pathobiont in Human Dysbiotic Disease
Authors: Higashi Dustin L. , McGuire Sean , Abdelrahman Yasser , Zou Zhengzhong , Qin Hua , Anderson David , Palmer Elizabeth A. , Kreth Jens , Merritt Justin 
Published: January 2022

AbstractParvimonas micra is a Gram-positive obligate anaerobe and a typical member of the human microbiome. P. micra is among the most highly enriched species at numerous sites of mucosal dysbiotic disease and is closely associated with the development of multiple types of malignant tumors. Despite its strong association with disease, surprisingly little is known about P. micra pathobiology, which is directly attributable to its longstanding genetic intractability. To address this problem, we directly isolated a collection of P. micra strains from odontogenic abscess clinical specimens and then screened these isolates for natural competence. Amazingly, all of the P. micra clinical isolates exhibited various levels of natural competence, including the reference strain ATCC 33270. By exploiting this ability, we were able to employ cloning-independent methodologies to engineer and complement a variety of targeted chromosomal genetic mutations directly within low passage clinical isolates. To create the first P. micra genetic system, we employed renilla-based bioluminescence for highly sensitive reporter studies. This reporter system was then applied for the development of the novel Theo+ theophylline-inducible riboswitch for tunable gene expression studies over a broad dynamic range. Finally, we demonstrate the feasibility of generating Mariner-based Tn-seq libraries for forward genetic screening in P. micra. With the availability of a highly efficient transformation protocol and the current suite of genetic tools, P. micra should now be considered as a fully genetically tractable organism suitable for molecular genetic research. The methods presented here provide a clear path to investigate the understudied role of P. micra in polymicrobial infections and tumorigenesis.
Role of posterodorsal medial amygdala urocortin-3 in pubertal timing in female mice
Authors: Ivanova Deyana , Li Xiao-Feng , Liu Yali , McIntyre Caitlin , Fernandes Cathy , Lass Geffen , Kong Lingsi , O’Byrne Kevin T 
Published: January 2022

AbstractPost-traumatic stress disorder impedes pubertal development and disrupts pulsatile LH secretion in humans and rodents. The posterodorsal sub-nucleus of the medial amygdala (MePD) is an upstream modulator of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator, pubertal timing, as well as emotional processing and anxiety. Psychosocial stress exposure alters neuronal activity within the MePD increasing the expression of Urocortin3 (Ucn3) and its receptor corticotropin-releasing factor type-2 receptor (CRFR2) while enhancing the inhibitory output from the MePD to key hypothalamic reproductive centres. We test the hypothesis that psychosocial stress, processed by the MePD, is relayed to the hypothalamic GnRH pulse generator to delay puberty in female mice. We exposed C57Bl6/J female mice to the predator odor, 2,4,5-Trimethylthiazole (TMT), during pubertal transition and examined the effect on pubertal timing, pre-pubertal LH pulses and anxiety-like behaviour. Subsequently, we virally infected Ucn3-cre-tdTomato female mice with stimulatory DREADDs targeting MePD Ucn3 neurons and determined the effect on pubertal timing and pre-pubertal LH pulse frequency. Exposure to TMT during pubertal development delayed puberty, suppressed pre-pubertal LH pulsatility and enhanced anxiety-like behaviour, while activation of MePD Ucn3 neurons reduced LH pulse frequency and delayed puberty. Early psychosocial stress exposure decreases GnRH pulse generator frequency delaying puberty while inducing anxiety-behaviour in female mice, an effect potentially involving Ucn3 neurons in the MePD.
AICAR-mediated selection of karyotypically normal cells in Pallister-Killian syndrome patient-derived skin fibroblasts
Authors: Salzano Emanuela , Kaur Maninder , Jacko Anastasia M , McEldrew Deborah , Raible Sarah E , Krantz Ian D , Izumi Kosuke 
Published: January 2022

AbstractPallister-Killian Syndrome (PKS) is a mosaic aneuploidy syndrome typically caused by the presence of a supernumerary marker isochromosome containing two extra copies of the short arm of chromosome 12 (iso-chromosome 12p or tetrasomy 12p). This isochromosome is always present in a mosaicism state that has tissue limited distribution. PKS is characterized by severe neurodevelopmental delay, intellectual disability, multisystem involvement and congenital malformations including typical dysmorphic features and skin pigmentation anomalies.Aneuploid cells, irrespective of the identity of the supernumerary chromosome, including cancer cells, yeast cells and mouse embryonic fibroblasts (MEFs), have been demonstrated to present a disruption of protein homeostasis and increased basal stress levels; resulting in a greater sensitivity to chemical compounds inducing cellular energy stress compared to euploid cell lines. The burden of trisomy 21 has also been recently shown to impair the proteostasis network in lymphoblastoid cell lines and fibroblasts obtained from individuals with Down syndrome.In this study, we demonstrate that AICAR, 5-Aminoimidazole-4-carboxamide ribonucleotide, a known energy stress inducing drug with antiproliferative effects on aneuploidy cancer cells and MEFs, is also able to selectively eliminate cells carrying the isochromosme12p in PKS clones in a time and dosage dependent manner. Collectively, our results indirectly provide evidence of increased basal energy and proteotoxic stress in PKS cells carrying isochromosome 12p, and suggest a potential therapeutic drug-based strategy that, selectively acting as a stressor for aneuploid cells, may establish the euploid state in PKS and a broader spectrum of human mosaic disorders.
Design and Characterization of Lipid Nanocarriers for Oral Delivery of Immunotherapeutic Peptides
Authors: Calderón-Colón Xiomara , Zhang Yichuan , Tiburzi Olivia , Wang Jialu , Raimondi Giorgio , Patrone Julia 
Published: January 2022

AbstractThe use of therapeutic proteins and peptides is of great interest for the treatment of many diseases, and advances in nanotechnology offer a path toward their stable delivery via preferred routes of administration. In this study, we sought to design and formulate a nanostructured lipid carrier (NLC) containing a nominal antigen (insulin peptide) for oral delivery. We utilized the design of experiments (DOE) statistical method to determine the dependencies of formulation variables on physicochemical particle characteristics including particle size, polydispersity (PDI), melting point, and latent heat of melting. The particles were determined to be non-toxic in vitro, readily taken up by primary immune cells, and found to accumulate in regional lymph nodes following oral administration. We believe that this platform technology could be broadly useful for the treatment of autoimmune diseases by supporting the development of oral delivery-based antigen specific immunotherapies.Highlights3-5 bullets, 85 char or lessA Design of Experiments method led the formulation of biocompatible nanoparticlesNLC accumulate into gut-draining lymphatic tissues following oral administrationNLC protect their antigen cargo and promote its presentationNLC formulation is well-suited for oral delivery of immunomodulatory agentsGraphical AbstractThe development of nanostructured lipid carriers containing a nominal antigen (insulin peptide) for oral delivery consists on (1) nanoparticle formulation using a statistical method, (2) in-vitro studies to assess cellular toxicity and uptake and T cell activation, and (3) in-vivo studies to assess bio-distribution.