bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D printed scaffold combined to 2D osteoinductive coatings to repair a critical-size mandibular bone defect
Authors: Bouyer Michael , Garot Charlotte , Machillot Paul , Vollaire Julien , Fitzpatrick Vincent , Morand Sanela , Boutonnat Jean , Josserand Véronique , Bettega Georges , Picart Catherine 
Published: December 2020

Abstractthe reconstruction of large bone defects (12 cm3) remains a challenge for clinicians. We developed a new critical-size mandibular bone defect model on a mini-pig, close to human clinical issues. We analyzed the bone reconstruction obtained by a 3D printed scaffold made of clinical-grade PLA, coated with a polyelectrolyte film delivering an osteogenic bioactive molecule (BMP-2). We compared the results (CT-scan, μCT, histology) to the gold standard solution, bone autograft. We demonstrated that the dose of BMP-2 delivered from the scaffold significantly influenced the amount of regenerated bone and the repair kinetics, with a clear BMP-2 dose-dependence. Bone was homogeneously formed inside the scaffold without ectopic bone formation. The bone repair was as good as for the bone autograft. The BMP-2 doses applied in our study were reduced 20 to 75-fold compared to the commercial collagen sponges used in the current clinical applications, without any adverse effects. 3D printed PLA scaffolds loaded with reduced doses of BMP-2 can be a safe and simple solution for large bone defects faced in the clinic.
Does male mate choice select for female colouration in a promiscuous primate species?
Authors: Rigaill Lucie , Garcia Cécile 
Published: December 2020

AbstractThe traditional view of sex roles and sexual selection emphasises the evolution of male ornaments as a result of female mate choice and male-male competition. Female ornaments are now receiving more attention, although their roles in mating decision are still less well understood, especially considering cases in which colourful ornaments are expressed by both sexes. In this study, we analysed whether female skin colouration (luminance and redness of the face and hindquarters) influenced male mate choice and sexual behaviours in relation to intra-cycle (cycle phase), inter-cycle (number of consecutive cycles, conceptive nature of the cycle), and inter-individual (age, social rank, weight, and parity) variation in a captive population of Japanese macaques (Macaca fuscata). Males did not preferentially choose darker/redder females. Moreover, males did not appear to use female skin colouration to apportion their mating efforts on the most fertile period of the menstrual cycle or during cycles that lead to conception, or to discriminate between females. To our knowledge, our study is among the few to report a lack of male choice for female colouration in a species where both sexes potentially display ornamentation. While female colouration appeared to contain information about intra-cycle, inter-cycle, and inter-individual variation in fecundity, this study further demonstrates that this trait may not have been sexually selected and that males mated regardless of such variation across females. This study adds to the growing research on the role and evolution of female colouration in the context of sexual signalling and mate attraction.
Lightweight Reinforcement Algorithms for autonomous, scalable intra-cortical Brain Machine Interfaces
Authors: Shaikh Shoeb , So Rosa , Sibindi Tafadzwa , Libedinsky Camilo , Basu Arindam 
Published: December 2020

AbstractIntra-cortical Brain Machine Interfaces (iBMIs) with wireless capability could scale the number of recording channels by integrating an intention decoder to reduce data rates. However, the need for frequent retraining due to neural signal non-stationarity is a big impediment. This paper presents an alternate paradigm of online reinforcement learning (RL) with a binary evaluative feedback in iBMIs to tackle this issue. This paradigm eliminates time-consuming calibration procedures. Instead, it relies on updating the model on a sequential sample-by-sample basis based on an instantaneous evaluative binary feedback signal. However, batch updates of weight in popular deep networks is very resource consuming and incompatible with constraints of an implant. In this work, using offline open-loop analysis on pre-recorded data, we show application of a simple RL algorithm - Banditron -in discrete-state iBMIs and compare it against previously reported state of the art RL algorithms – Hebbian RL, Attention gated RL, deep Q-learning. Owing to its simplistic single-layer architecture, Banditron is found to yield at least two orders of magnitude of reduction in power dissipation compared to state of the art RL algorithms. At the same time, post-hoc analysis performed on four pre-recorded experimental datasets procured from the motor cortex of two non-human primates performing joystick-based movement-related tasks indicate Banditron performing significantly better than state of the art RL algorithms by at least 5%, 10%, 7% and 7% in experiments 1, 2, 3 and 4 respectively. Furthermore, we propose a non-linear variant of Banditron, Banditron-RP, which gives an average improvement of 6%, 2% in decoding accuracy in experiments 2,4 respectively with only a moderate increase in power consumption.
Conformational diversity of CDR region during affinity maturation determines the affinity and stability of Sars-Cov-1 VHH-72 nanobody
Authors: George Suji 
Published: December 2020

AbstractThe affinity maturation of Sars-Cov-1 VHH-72 nanobody from its germline predecessor has been studied at the molecular level. The effect of somatic mutations accumulated during affinity maturation process on flexibility, stability and affinity of the germline and affinity matured nanobody was studied. Affinity maturation results in loss of local flexibility in CDR of H3 and this resulted in a gain of affinity towards the antigen. Further affinity maturation was found to destabilize the nanobody. Mechanistically the loss of flexibility of the CDR H3 is due to the redistribution of hydrogen bond network due to somatic mutation A50T, also this contributes significantly to the destability of the nanobody. Unlike antibody, in nanobody the framework region is highly conserved and structural diversity in CDR is the determining factor in diverse antigen binding and also a factor contributing to the stability. This study provide insights into the interrelationship between flexibility, stability and affinity during affinity maturation in a nanobody.
Voltage-based inhibitory synaptic plasticity: network regulation, diversity, and flexibility
Authors: Pedrosa Victor , Clopath Claudia 
Published: December 2020

AbstractNeural networks are highly heterogeneous while homeostatic mechanisms ensure that this heterogeneity is kept within a physiologically safe range. One of such homeostatic mechanisms, inhibitory synaptic plasticity, has been observed across different brain regions. Computationally, however, inhibitory synaptic plasticity models often lead to a strong suppression of neuronal diversity. Here, we propose a model of inhibitory synaptic plasticity in which synaptic updates depend on presynaptic spike arrival and postsynaptic membrane voltage. Our plasticity rule regulates the network activity by setting a target value for the postsynaptic membrane potential over a long timescale. In a feedforward network, we show that our voltage-dependent inhibitory synaptic plasticity (vISP) model regulates the excitatory/inhibitory ratio while allowing for a broad range of postsynaptic firing rates and thus network diversity. In a feedforward network in which excitatory and inhibitory neurons receive correlated input, our plasticity model allows for the development of co-tuned excitation and inhibition, in agreement with recordings in rat auditory cortex. In recurrent networks, our model supports memory formation and retrieval while allowing for the development of heterogeneous neuronal activity. Finally, we implement our vISP rule in a model of the hippocampal CA1 region whose pyramidal cell excitability differs across cells. This model accounts for the experimentally observed variability in pyramidal cell features such as the number of place fields, the fields sizes, and the portion of the environment covered by each cell. Importantly, our model supports a combination of sparse and dense coding in the hippocampus. Therefore, our voltage-dependent inhibitory plasticity model accounts for network homeostasis while allowing for diverse neuronal dynamics observed across brain regions.
In situ characterization of the 3D microanatomy of the pancreas and pancreatic cancer at single cell resolution
Authors: Kiemen Ashley , Braxton Alicia M. , Grahn Mia P. , Han Kyu Sang , Babu Jaanvi Mahesh , Reichel Rebecca , Amoa Falone , Hong Seung-Mo , Cornish Toby C. , Thompson Elizabeth D. , Wood Laura D. , Hruban Ralph H. , Wu Pei-Hsun , Wirtz Denis 
Published: December 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer. Accumulating evidence indicates the tumor microenvironment is highly associated with tumorigenesis through regulation of cellular physiology, signaling systems, and gene expression profiles of cancer cells. Yet the mechanisms by which the microenvironment evolves from normal pancreas architecture to precursor lesions and invasive cancer is poorly understood. Obtaining high-content and high-resolution information from a complex tumor microenvironment in large volumetric landscapes represents a key challenge in the field of cancer biology. To address this challenge, we established a novel method to reconstruct three-dimensional (3D) centimeter-scale tissues containing billions of cells from serially sectioned histological samples, utilizing deep learning approaches to recognize eight distinct tissue subtypes from hematoxylin and eosin stained sections at micrometer and single-cell resolution. Using samples from a range of normal, precancerous, and invasive pancreatic cancer tissue, we map in 3D modes of cancer invasion in the tumor microenvironment, and emphasize the need for further 3D quantification of biological systems.
Recruitment of Env to the HIV-1 T cell virological synapse by targeted and sustained Env recycling
Authors: Wang Lili , Sandmeyer Alice , Hübner Wolfgang , Li Hongru , Huser Thomas , Chen Benjamin K. 
Published: December 2020

ABSTRACTHIV-1 infection is enhanced by cell-cell adhesions between infected and uninfected T cells called virological synapses (VS). VS are initiated by the interactions of cell-surface HIV-1 envelope glycoprotein (Env) and CD4 on target cells and act as sites of viral assembly and viral transfer between cells. To study the process that recruits and retains HIV-1 Env at the VS, a replication-competent HIV-1 clone carrying an Env-sfGFP fusion protein was designed to enable live tracking of Env within infected cells. Using surface pulse-labeling of Env and fluorescence recovery after photobleaching (FRAP) studies, we observed targeted accumulation and sustained recycling of Env between the endocytic recycling compartment (ERC) and the VS. We observed dynamic exchange of Env at the VS while the viral structural protein, Gag, was largely immobile at the VS. The disparate exchange rates of Gag and Env at the synapse indicate that retention of Env is not likely to be maintained by entrapment into an immobile Gag lattice or through immobilizing interactions with CD4 on the target cell. A FRAP study of an Env endocytosis mutant showed that recycling is required for the rapid exchange of Env at the VS. We conclude that the mechanism of Env accumulation at the VS and incorporation into nascent particles involves continuous internalization and targeted secretion rather than irreversible interactions with the budding virus.
Uncovering the Organization of Neural Circuits with Generalized Phase Locking Analysis
Authors: Safavi Shervin , Panagiotaropoulos Theofanis I. , Kapoor Vishal , Ramirez-Villegas Juan F. , Logothetis Nikos K. , Besserve Michel 
Published: December 2020

AbstractDespite the considerable progress ofin vivoneural recording techniques, inferring the biophysical mechanisms underlying large scale coordination of brain activity from neural data remains challenging. One obstacle is the difficulty to link high dimensional functional connectivity measures to mechanistic models of network activity. We address this issue by investigating spike-field coupling (SFC) measurements, which quantify the synchronization between, on the one hand, the action potentials produced by neurons, and on the other hand a mesoscopic “field” signals, reflecting subthreshold activities at possibly multiple recording sites. As the number of recording sites gets large, the amount of pairwise SFC measurements becomes overwhelmingly challenging to interpret. We developGeneralized Phase Locking Analysis(GPLA) as a dimensionality reduction of this multivariate SFC. GPLA describes the dominant coupling between field activity and neural ensembles across space and frequencies, thereby providing rich yet interpretable information. In particular, we show that GPLA features arebiophysically interpretablewhen used in conjunction with appropriate network models, such that we can identify the influence of underlying circuit properties on these features. We demonstrate the statistical benefits and interpretability of this approach in various computational models and Utah array recordings. The results suggest that GPLA used jointly with biophysical modeling can help uncover the contribution of recurrent microcircuits to the spatio-temporal dynamics observed in multi-channel experimental recordings.
Recognition of discrete export signals in early flagellar subunits during bacterial Type III secretion
Authors: Bryant Owain J. , Dhillon Paraminder , Hughes Colin , Fraser Gillian M. 
Published: December 2020

AbstractType III Secretion Systems (T3SS) deliver subunits from the bacterial cytosol to nascent cell surface flagella. Early flagellar subunits that form the rod and hook substructures are unchaperoned and contain their own export signals. A gate recognition motif (GRM) docks them at the FlhBc component of the FlhAB-FliPQR export gate, but the gate must then be opened and subunits must be unfolded to pass through the flagellar channel. This induced us to seek further signals on the subunits. Here, we identify a second signal at the extreme N-terminus of flagellar rod and hook subunits and determine that key to the signal is its hydrophobicity. We show that the two export signal elements are recognised separately and sequentially, as the N-terminal signal is recognised by the flagellar export machinery only after subunits have docked at FlhBCviathe GRM. The position of the N-terminal hydrophobic signal in the subunit sequence relative to the GRM appeared to be important, as a FlgD deletion variant (FlgDshort), in which the distance between the N-terminal signal and the GRM was shortened, ‘stalled’ at the export machinery and was not exported. The attenuation of motility caused by FlgDshortwas suppressed by mutations that destabilised the closed conformation of the FlhAB-FliPQR export gate, suggesting that the hydrophobic N-terminal signal might trigger opening of the flagellar export gate.
Cross-Platform Omics Prediction procedure: a game changer for implementing precision medicine in patients with stage-III melanoma
Authors: Wang Kevin Y.X. , Pupo Gulietta M. , Tembe Varsha , Patrick Ellis , Strbenac Dario , Schramm Sarah-Jane , Thompson John F. , Scolyer Richard A. , Mueller Samuel , Tarr Garth , Mann Graham J. , Yang Jean Y.H. 
Published: December 2020

AbstractThere is no consensus methodology that can account for the variation in omics signatures when they are acquired across different platforms and times. This poses a significant barrier to the implementation of valuable biomarkers into clinical practice. We present a novel procedure (Cross-Platform Omics Prediction) that accounts for these variations and demonstrate its utility in three risk models for different diseases that is suitable for prospective and multi-centre clinical implementation.
Blunting of insulin-stimulated glucose uptake in brown adipose tissue induces systemic metabolic dysregulation in female mice
Authors: Picatoste Belén , Yammine Lucie , Leahey Rosemary , Soares David , Cohen Paul , McGraw Timothy E. 
Published: December 2020

SummaryThe role of brown adipose tissue (BAT) in thermogenesis is widely appreciated, whereas its more recently described role in whole-body metabolism is not as well understood. Here we demonstrate that deletion of Rab10 from brown adipocytes reduces insulin-stimulated glucose transport by inhibiting translocation of the GLUT4 glucose transporter to the plasma membrane. This blunting of glucose uptake into brown adipocytes induces glucose intolerance and insulin-resistance in female but not male mice. The defect in glucose uptake does not affect the thermogenic function of BAT, and the dysregulation of whole-body metabolism is independent of the thermogenic function of BAT, thereby revealing a metabolism-specific role for BAT in female mice. The reduced glucose uptake induced by RAB10 deletion disrupts ChREBP regulation of the expression of de novo lipogenesis-related (DNL) genes, providing a link between DNL in BAT and whole-body metabolic regulation that is independent of thermogenesis.
Life-history dynamics: damping time, demographic dispersion and generation time
Authors: Jiang Sha , Jaggi Harman , Zuo Wenyun , Oli Madan K. , Gaillard Jean-Michel , Tuljapurkar Shripad 
Published: December 2020

AbstractTransient dynamics are crucial for understanding ecological and life-history dynamics. In this study, we analyze damping time, the time taken by a population to converge to a stable (st)age structure following a perturbation, for over 600 species of animals and plants. We expected damping time to be associated with both generation timeTcand demographic dispersionσbased on previous theoretical work. Surprisingly, we find that damping time (calculated from the population projection matrix) is approximately proportional toTcacross taxa on the log-log scale, regardless ofσ. The result suggests that species at the slow end of fast-slow continuum (characterized with long generation time, late maturity, low fecundity) are more vulnerable to external disturbances as they take more time to recover compared to species with fast life-histories. The finding on damping time led us to next examine the relationship between generation time and demographic dispersion. Our result reveals that the two life-history variables are positively correlated on a log-log scale across taxa, implying long generation time promotes demographic dispersion in reproductive events. Finally, we discuss our results in the context of metabolic theory and contribute to existing allometric scaling relationships.
Exposure to Traffic-Related Air Pollution is Associated with Greater Bacterial Diversity in the Lower Respiratory Tract of Children
Authors: Niemeier-Walsh Christine , Ryan Patrick H , Meller Jaroslaw , Ollberding Nicholas J. , Adhikari Atin , Reponen Tiina 
Published: December 2020

AbstractBackgroundExposure to particulate matter has been shown to increase the adhesion of bacteria to human airway epithelial cells. However, the impact of traffic-related air pollution (TRAP) on the respiratory microbiome is unknown.MethodsForty children were recruited through the Cincinnati Childhood Allergy and Air Pollution Study, a longitudinal cohort followed from birth through early adolescence. Saliva and induced sputum were collected at age 14 years. Exposure to TRAP was characterized from birth through the time of sample collection using a previously validated land-use regression model. Sequencing of the bacterial 16S and ITS fungal rRNA genes was performed on sputum and saliva samples. The relative abundance of bacterial taxa and diversity indices were compared in children with exposure to high and low TRAP. We also used multiple linear regression to assess the effect of TRAP exposure, gender, asthma status, and socioeconomic status on the alpha diversity of bacteria in sputum.ResultsWe observed higher bacterial alpha diversity indices in sputum than in saliva. The diversity indices for bacteria were greater in the high TRAP exposure group than the low exposure group. These differences remained after adjusting for asthma status, gender, and mother’s education. No differences were observed in the fungal microbiome between TRAP exposure groups.ConclusionOur findings indicate that exposure to TRAP in early childhood and adolescence may be associated with greater bacterial diversity in the lower respiratory tract. Asthma status does not appear to confound the observed differences in diversity. It is still unknown whether the development of asthma changes the lower respiratory tract microbiome or if an altered microbiome mediates a change in disease status. However, these results demonstrate that there may be a TRAP-exposure related change in the lower respiratory microbiota that is independent of asthma status.
High-throughput Single-cell CNV Detection Reveals Clonal Evolution During Hepatocellular Carcinoma Recurrence
Authors: Wu Liang , Wang Yuzhou , Jiang Miaomiao , Zhou Biaofeng , Sun Yunfan , Zhou Kaiqian , Xie Jiarui , Zhong Yu , Zhao Zhikun , Dean Michael , Hou Yong , Liu Shiping 
Published: December 2020

AbstractSingle-cell genomics provides substantial resources for dissecting cellular heterogeneity and cancer evolution, but classical DNA amplification-based methods are low-throughput and introduce coverage bias during sample preamplification. We developed asingle-cellDNA library preparation method withoutpreamplification innanolitre scale (scDPN). The method has a throughput of up to 1,800 cells per run for copy number variation (CNV) detection. Also, it has a lower level of amplification bias and noise than the multiple displacement amplification (MDA) method and showed high sensitivity and accuracy based on evaluation in cell lines and tumour tissues. We used this approach to profile the tumour clones in paired primary and relapsed tumour samples of hepatocellular carcinoma (HCC). We identified 3 clonal subpopulations with a multitude of aneuploid alterations across the genome. Furthermore, we observed that a minor clone of the primary tumour containing additional alterations in chromosomes 1q, 10q, and 14q developed into the dominant clone in the recurrent tumour, indicating clonal selection during recurrence in HCC. Overall, this approach provides a comprehensive and scalable solution to understand genome heterogeneity and evolution.