Miracle-dz/UniFAR-FTUs huggingface dataset:
The Use of Reduced Models to Generate Irregular, Broad-Band Signals That Resemble Brain Rhythms

The brain produces rhythms in a variety of frequency bands. Some are likely by-products of neuronal processes; others are thought to be top-down. Produced entirely naturally, these rhythms have clearly recognizable beats, but they are very far from periodic in the sense of mathematics. The signals are broad-band, episodic, wandering in amplitude and frequency; the rhythm comes and goes, degrading and regenerating. Gamma rhythms, in particular, have been studied by many authors in computational neuroscience, using reduced models as well as networks of hundreds to thousands of integrate-and-fire neurons. All of these models captured successfully the oscillatory nature of gamma rhythms, but the irregular character of gamma in reduced models has not been investigated thoroughly. In this article, we tackle the mathematical question of whether signals with the properties of brain rhythms can be generated from low dimensional dynamical systems. We found that while adding white noise to single periodic cycles can to some degree simulate gamma dynamics, such models tend to be limited in their ability to capture the range of behaviors observed. Using an ODE with two variables inspired by the FitzHugh-Nagumo and Leslie-Gower models, with stochastically varying coefficients designed to control independently amplitude, frequency, and degree of degeneracy, we were able to replicate the qualitative characteristics of natural brain rhythms. To demonstrate model versatility, we simulate the power spectral densities of gamma rhythms in various brain states recorded in experiments.
Development of a cardiovascular magnetic resonance‐compatible large animal isolated heart model for direct comparison of beating and arrested hearts

Cardiac motion results in image artefacts and quantification errors in many cardiovascular magnetic resonance (CMR) techniques, including microstructural assessment using diffusion tensor cardiovascular magnetic resonance (DT‐CMR). Here, we develop a CMR‐compatible isolated perfused porcine heart model that allows comparison of data obtained in beating and arrested states. Ten porcine hearts (8/10 for protocol optimisation) were harvested using a donor heart retrieval protocol and transported to the remote CMR facility. Langendorff perfusion in a 3D‐printed chamber and perfusion circuit re‐established contraction. Hearts were imaged using cine, parametric mapping and STEAM DT‐CMR at cardiac phases with the minimum and maximum wall thickness. High potassium and lithium perfusates were then used to arrest the heart in a slack and contracted state, respectively. Imaging was repeated in both arrested states. After imaging, tissue was removed for subsequent histology in a location matched to the DT‐CMR data using fiducial markers. Regular sustained contraction was successfully established in six out of 10 hearts, including the final five hearts. Imaging was performed in four hearts and one underwent the full protocol, including colocalised histology. The image quality was good and there was good agreement between DT‐CMR data in equivalent beating and arrested states. Despite the use of autologous blood and dextran within the perfusate, T2 mapping results, DT‐CMR measures and an increase in mass were consistent with development of myocardial oedema, resulting in failure to achieve a true diastolic‐like state. A contiguous stack of 313 5‐μm histological sections at and a 100‐μm thick section showing cell morphology on 3D fluorescent confocal microscopy colocalised to DT‐CMR data were obtained. A CMR‐compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent colocalised histology, without the need for onsite preclinical facilities.
Integration of WAVE and OpenFlow for Realization of SDN-based VANETs in ns-3

While software defined networking (SDN) has been widely deployed in wired networks within the cloud data centers, its applications with both a wireless control and data channel have not been fully realized. One particular use case is vehicular ad hoc networks (VANET), where SDN has been touted as an effective method to control vehicles’ data traffic in a centralized manner. Several studies explored how SDN switches can be utilized on connected vehicles to shape the data traffic by enabling multi-hop communications through their Dedicated Short Range Communication (DSRC) interfaces. However, evaluation of research for SDN-based VANETs became a challenge due to lack of testbeds and realistic simulation tools that will support VANET features in conjunction with SDN. In this paper, we present a new framework that will enable SDN-based VANET simulation in ns-3. Specifically, we demonstrate how ns-3 SDN module can be expanded to support DSRC interfaces in addition to their default CSMA-CD interface. By considering a platooning application use case, we implemented an SDN-based VANET simulation that will enable multi-hop communication through the DSRC interfaces of the vehicles and road side units (RSUs). We not only explain the details of the implementation within the ns-3 OpenFlow (OF13) switch module but also provide some sample experiment results under a variety of conditions. The results show that the implementation is robust and closely simulates the actual behavior of SDN’s control and data channels.
Pathogenicity of Highly Pathogenic Avian Influenza Virus (H5N1) in Adult Mute Swans

Adult, healthy mute swans were experimentally infected with highly pathogenic avian influenza virus A/Cygnus cygnus/Germany/R65/2006 subtype H5N1. Immunologically naive birds died, whereas animals with preexisting, naturally acquired avian influenza virus–specific antibodies became infected asymptomatically and shed virus. Adult mute swans are highly susceptible, excrete virus, and can be clinically protected by preexposure immunity.
Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines Running head: HCV evasion to NKG2D-mediated response

Understanding how hepatitis C virus (HCV) induces and circumvents the host’s natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell mediated responses. We show that chronic HCV infection is associated with expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules, on hepatocytes. However, NKG2D expression is downmodulated on circulating NK cells, and consequently NK cell-mediated cytotoxic capacity and interferon-γ production are impaired. Using an endotoxin-free recombinant NS5A protein, we show that NS5A stimulation of monocytes through TLR4 promotes p38and PI3 kinase-dependent IL10 production, while inhibiting IL-12 production. In turn, IL-10 triggers secretion of TGFβ which downmodulates NKG2D expression on NK cells, leading to their impaired effector functions. Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5. 1 cells reproduce the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can antagonize the TGFβ effect and restore normal NKG2D expression on NK cells. We conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV infection, and demonstrate that this alteration can be prevented by exogenous IL-15, which could represent a meaningful adjuvant for therapeutic intervention. in se rm -0 05 19 63 1, v er si on 1 21 S ep 2 01 0
Elevated paternal glucocorticoid exposure prior to conception causes intergenerational shifts in offspring social and sexual behaviours and expression of major urinary protein pheromone

Studies have shown that paternal stress prior to conception can influence the innate behaviours of their offspring. The evolutionary benefits of such intergenerational adaptations continue to be speculated upon. Our group previously showed that glucocorticoid treatment of adult male breeders prior to conception leads to increased anxiety-related behaviours in male offspring. Here, we aimed to understand the transgenerational effects of paternal stress exposure on the social behaviour of progeny and its potential influence on adaptive fitness. We assessed social parameters including social reward, male attractiveness and social dominance, in the offspring (F 1 ) and grand-offspring (F 2 ). We report that paternal corticosterone-treatment was associated with increased display of subordination towards other male mice. Those mice were unexpectedly more attractive to female mice while expressing reduced levels of the key rodent pheromone Darcin, contrary to its conventional purpose. No overt differences of the prefrontal cortex transcriptome were found in F 1 offspring, implying that peripheral mechanisms are likely contributing to the phenotypic differences. Interestingly, no phenotypic differences were observed in the F 2 grand-offspring. Overall, our findings highlight the contribution of moderate paternal stress to an intergenerational adaptive response, informing future studies of adaptive fitness in rodents, humans and other species.
Neural plate progenitors give rise to both anterior and posterior pituitary cells

The pituitary is the master neuroendocrine gland, which regulates body homeostasis. It consists of the anterior pituitary/adenohypophysis (AH), which harbors hormones producing cells and the posterior pituitary/neurohypophysis (NH), which relays the direct passage of hormones from the brain to the periphery. It is widely accepted that the AH originates from the oral ectoderm (Rathke’s pouch) whereas the neural ectoderm contributes to the NH. Using single cell transcriptomics of the zebrafish pituitary we characterized cyp26b1-positive pituicyte of the NH and prop1-positive adenohypophyseal progenitors. We found that these cell types expressed common markers implying lineage relatedness. Genetic tracing revealed that in contrast to the prevailing dogma, neural plate precursors of both zebrafish (her4.3+) and mouse (Sox1+) contribute to both the neurohypophyseal and adenohypophyseal cells. We further show that pituicytes and prop1+ progenitors reside in close anatomical proximity and pituicyte-derived RA-degrading enzyme Cyp26b1 fine-tunes differentiation of prop1+ progenitors into hormone-producing cells. These results challenge the notion that AH cells are exclusively derived from non-neural ectoderm and demonstrate that a cross-talk between neuro- and adeno-hypophyseal cells fine-tunes the development of pituitary neuroendocrine cells.
PHAT: interpretable prediction of peptide secondary structures

19 Peptides have recently emerged as therapeutic molecules against various diseases, and the 20 secondary structure of peptides is a crucial determinant of their bioactivity. However, 21 accurately predicting peptide secondary structures remains a challenging task due to the lack 22 of peptide sequence data and low prediction efficiency caused by limitations in feature 23 engineering. Therefore, we developed PHAT, a deep learning framework based on a 24 hypergraph multi-head attention network and transfer learning for the prediction of peptide 25 secondary structures. Comparative results demonstrated the outstanding performance and 26 robustness of PHAT. In particular, PHAT automatically learns a set of biologically meaningful 27 knowledge on secondary sub-structures, overcoming the limitations of “black-box” in deep 28 learning-based models and providing good interpretability. Additionally, we demonstrated that 29 the structure information derived from PHAT significantly improved the performance of 30 downstream tasks such as the prediction of peptide toxicity and protein-peptide binding sites. 31 Importantly, we further explored the applicability of PHAT for contact map prediction, which 32 can aid in the reconstruction of peptide 3-D structures, thus highlighting the versatility of our 33 model. To facilitate the use of PHAT, we establish an online server which is accessible via 34 https://server.wei-group.net/PHAT/. We expect our work to assist in the design of functional 35 peptides and contribute to the advancement of structural biology research. 36 37
New functional vessels form after spinal cord injury in zebrafish

The vascular system is inefficiently repaired after spinal cord injury in mammals, resulting in secondary tissue damage and immune deregulation that contribute to the limited functional recovery. Unlike mammals, zebrafish can repair the spinal cord and restore motility, but the vascular response to injury has not been investigated. Here we describe the zebrafish spinal cord vasculature, from the body size-dependent vessel ingression during development to the stereotypic vessel organization and barrier specialisation in adulthood. After injury, vessels rapidly regrow into the lesion, preceding the glial bridge and regenerating axons. The initial vascularisation of the injured tissue is done by dysmorphic and leaky vessels. Dysfunctional vessels are later removed, as pericytes are recruited and the blood-spinal cord barrier is re-established. Vascular repair involves an early burst of angiogenesis, likely in response to pro-angiogenic factors detected in the injured spinal cord, including the Vegf pathway. However, the inhibition of the Vegfr2 using genetic and pharmacological methods was not able to efficiently block the formation of new blood vessels, suggesting that other signalling pathways are also involved in this process. This study demonstrates that zebrafish can successfully re-vascularise the spinal tissue, reinforcing the value of this organism as a regenerative model for spinal cord injury.
Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis

Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease. We analyzed longitudinal RNA sequencing (RNAseq) data from the whole blood of 74 TB progressors whose samples were grouped into four six-month intervals preceding diagnosis (the GC6-74 study). We additionally analyzed RNAseq data from an independent cohort of 90 TB patients with positron emission tomography-computed tomography (PET-CT) scan results which were used to categorize them into groups with high and low levels of lung damage (the Catalysis TB Biomarker study). These groups were compared to non-TB controls to obtain a complete whole blood transcriptional profile for individuals spanning from early stages of M.tb infection to TB diagnosis. The results revealed a steady increase in the number of genes that were differentially expressed in progressors at time points closer to diagnosis with 278 genes at 13–18 months, 742 at 7–12 months and 5,131 detected 1–6 months before diagnosis and 9,205 detected in TB patients. A total of 2,144 differentially expressed genes were detected when comparing TB patients with high and low levels of lung damage. There was a large overlap in the genes upregulated in progressors 1–6 months before diagnosis (86%) with those in TB patients. A comprehensive pathway analysis revealed a potent activation of neutrophil and platelet mediated defenses including neutrophil and platelet degranulation, and NET formation at both time points. These pathways were also enriched in TB patients with high levels of lung damage compared to those with low. These findings suggest that neutrophils and platelets play a critical role in TB pathogenesis, and provide details of the timing of specific effector mechanisms that may contribute to TB lung pathology. Author summary Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Human immune responses must be balanced to inhibit disease progression while limiting self-damage, however in defense against M.tb host responses have been implicated in lung damage and in driving progression of M.tb infection to severe lung disease. The identification of immune responses that are activated during the development of TB could provide potential targets for interventions that might suppress disease progression, and possibly limit tissue damage. Here we identify a subset of genes that function in several biological processes that are strongly activated in the late stages of TB development and in TB patients. The proteins encoded by these genes are known to degrade lung tissue and contribute to severe lung disease.
Longitudinal brain studies in adult zebrafish by MRI

Zebrafish (Danio rerio) has been successfully used for decades in developmental studies and disease modelling. The remarkable intake of zebrafish as a model system is partly due to its transparency during the early weeks of its development, allowing in vivo imaging of cellular and molecular processes. However, this key advantage wears off when tissues become opaque as the animal reaches juvenile and adult stages, rendering access to tissues for live imaging and longitudinal studies difficult. Here we aimed to provide a novel approach to image and assess tissue integrity of adult zebrafish using Magnetic Resonance Imaging (MRI) on live zebrafish suitable for longitudinal studies. We built a 3D-printed life support chamber and designed a protocol-directed sedation regime to recover adult zebrafish post scanning in a 9.4T MRI scanner. Our life support chamber is cheap and easy to create using 3D printing, allowing other groups to copy our template for quick setup. Additionally, we optimised the delivery of contrast agent to enhance brain signals in order to refine current delivery, usually delivered by intravenous in rodents. We show here that immersion in gadolinium was a viable alternative to intraperitoneal injection to reduce T1 relaxation times. This could lead to improved image contrast in adult zebrafish disease models. In conclusion, we provide here a detailed methodology to allow longitudinal studies of brain tissue integrity of adult zebrafish, combining safe and efficient delivery of contrast agent and live MRI. This technique can be used to bridge the gap between in vivo studies and longitudinal brain analysis in adult zebrafish which can be applied to the ever-growing number of adult zebrafish models of ageing and neurodegenerative diseases.
omicsGAT: Graph Attention Network for Cancer Subtype Analyses

Motivation The use of high-throughput omics technologies is becoming increasingly popular in all facets of biomedical science. The mRNA sequencing (RNA-seq) method reports quantitative measures of more than tens of thousands of biological features. It provides a more comprehensive molecular perspective of studied cancer mechanisms compared to traditional approaches. Graph-based learning models have been proposed to learn important hidden representations from gene expression data and network structure to improve cancer outcome prediction, patient stratification, and cell clustering. However, these graph-based methods cannot rank the importance of the different neighbors for a particular sample in the downstream cancer subtype analyses. In this study, we introduce omicsGAT, a graph attention network (GAT) model to integrate graph-based learning with an attention mechanism for RNA-seq data analysis. The multi-head attention mechanism in omicsGAT can more effectively secure information of a particular sample by assigning different attention coefficients to its neighbors. Results Comprehensive experiments on The Cancer Genome Atlas (TCGA) breast cancer and bladder cancer bulk RNA-seq data, and primary diffuse gliomas single-cell RNA-seq data validate that (1) the proposed model can effectively integrate neighborhood information of a sample and learn an embedding vector to improve disease phenotype prediction, cancer patient stratification, and cell clustering of the sample. (2) The attention matrix generated from the multi-head attention coefficients provides more useful information compared to the sample correlation-based adjacency matrix. From the results, we can conclude that some neighbors play a more important role than others in cancer subtype analyses of a particular sample based on the attention coefficient. Availability and implementation Source code is available at: https://github.com/CompbioLabUCF/omicsGAT Supplementary information Supplementary data are available at BioRxiv online.
A lipopolysaccharide‐dependent phage infects a pseudomonad phytopathogen and can evolve to evade phage resistance

Bacterial pathogens are major causes of crop diseases, leading to significant production losses. For instance, kiwifruit canker, caused by the phytopathogen Pseudomonas syringae pv. actinidiae (Psa), has posed a global challenge to kiwifruit production. Treatment with copper and antibiotics, whilst initially effective, is leading to the rise of bacterial resistance, requiring new biocontrol approaches. Previously, we isolated a group of closely related Psa phages with biocontrol potential, which represent environmentally sustainable antimicrobials. However, their deployment as antimicrobials requires further insight into their properties and infection strategy. Here, we provide an in-depth examination of the genome of ΦPsa374-like phages and show that they use lipopolysaccharides (LPS) as their main receptor. Through proteomics and cryo-electron microscopy of ΦPsa374, we revealed the structural proteome and that this phage possess a T=9 capsid triangulation, unusual for myoviruses. Furthermore, we show that ΦPsa374 phage resistance arises in planta through mutations in a glycosyltransferase involved in LPS synthesis. Lastly, through in vitro evolution experiments we showed that phage-resistance is overcome by mutations in a tail fiber and structural protein of unknown function in ΦPsa374. This study provides new insight into the properties of ΦPsa374-like phages that informs their use as antimicrobials against Psa. Originality-Significance Statement The rise of phytopathogen resistance to agrichemicals poses a significant threat to crop production, and requires urgent attention. The work presented here examines a phage genus, members of which utilize LPS as a receptor, and show potential as biocontrol agents of Psa. Studies in planta showed the development of Psa resistance to the phage, whilst maintaining bacterial virulence. This finding underscores the importance of examining phages in their ecological context for the informed design of phage cocktails that are effective in phytopathogen control.
Genomic instability in patients with sex determination defects and germ cell cancer

The ability to transmit genetic information through generations depends on preservation of genome integrity. Genetic abnormalities affect cell differentiation, causing tissue specification defects and cancer. We addressed genomic instability in individuals with Differences of Sex Development (DSD), characterized by gonadal dysgenesis, infertility, high susceptibility for different types of cancer, especially Germ Cell Tumors (GCT), and in men with testicular GCTs. Whole proteome analysis of leukocytes, supported by specific gene expression assessment, and dysgenic gonads characterization, uncovered DNA damage phenotypes with altered innate immune response and autophagy. Further examination of DNA damage response revealed a reliance on deltaTP53, which was compromised by mutations in the transactivation domain in DSD-patients with GCT. Accordingly, drug-induced rescue of DNA damage was achieved by autophagy inhibition but not by stabilization of TP53 in DSD-patients’ blood in vitro. This study elucidates possibilities for prophylactic treatments of DSD patients as well as new diagnostic approaches of GCT. Teaser DNA damage phenotypes accompany aneuploidy of sex chromosomes and link to infertility and high propensity to germ cell tumor development.