Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole-genome comparison of endogenous retrovirus segregation across wild and domestic host species populations

Significance Retroviruses have invaded vertebrate hosts during millions of years by occasional germline infections, which were transmitted to the host offspring through generations as inherited endogenous retroviruses (ERVs). Thus, ERVs provide a remarkable record of virus–host interactions. State-of-the-art sequencing methods facilitate ERV identification to decipher their long-term associations with host species. By expanding the scope beyond presence or absence in a single reference genome assembly, it is possible to estimate ERV frequencies and spread in related wild and domestic host populations. Here we demonstrate a considerable ERV makeup variance in wild and domestic rabbit populations, which offers insights into retrovirus–host coevolution and an extension to common strategies in population comparative genomics. Although recent advances in sequencing and computational analyses have facilitated use of endogenous retroviruses (ERVs) for deciphering coevolution among retroviruses and their hosts, sampling effects from different host populations present major challenges. Here we utilize available whole-genome data from wild and domesticated European rabbit (Oryctolagus cuniculus sp.) populations, sequenced as DNA pools by paired-end Illumina technology, for identifying segregating reference as well as nonreference ERV loci, to reveal their variation along the host phylogeny and domestication history. To produce new viruses, retroviruses must insert a proviral DNA copy into the host nuclear DNA. Occasional proviral insertions into the host germline have been passed down through generations as inherited ERVs during millions of years. These ERVs represent retroviruses that were active at the time of infection and thus present a remarkable record of historical virus–host associations. To examine segregating ERVs in host populations, we apply a reference library search strategy for anchoring ERV-associated short-sequence read pairs from pooled whole-genome sequences to reference genome assembly positions. We show that most ERVs segregate along host phylogeny but also uncover radiation of some ERVs, identified as segregating loci among wild and domestic rabbits. The study targets pertinent issues regarding genome sampling when examining virus–host evolution from the genomic ERV record and offers improved scope regarding common strategies for single-nucleotide variant analyses in host population comparative genomics.
Intra-Renal Angiotensin Levels Are Increased in High-Fructose Fed Rats in the Extracorporeal Renal Perfusion Model

Overconsumption of fructose leads to metabolic syndrome as a result of hypertension, insulin resistance, and hyperlipidemia. In this study, the renal function of animals submitted to high fructose intake was analyzed from weaning to adulthood using in vivo and ex vivo methods, being compared with a normal control group. We investigated in ex vivo model of the role of the renin Angiotensin system (RAS) in the kidney. The use of perfused kidney from animals submitted to 8-week fructose treatment showed that high fructose intake caused metabolic and cardiovascular alterations that were consistent with other studies. Moreover, the isolated perfused kidneys obtained from rats under high fructose diet showed a 33% increase in renal perfusion pressure throughout the experimental period due to increased renal vascular resistance and a progressive fall in the glomerular filtration rate, which reached a maximum of 64% decrease. Analysis of RAS peptides in the high fructose group showed a threefold increase in the renal concentrations of angiotensin I (Ang I) and a twofold increase in angiotensin II (Ang II) levels, whereas no change in angiotensin 1-7 (Ang 1-7) was observed when compared with the control animals. We did not detect changes in angiotensin converting enzyme (ACE) activity in renal tissues, but there is a tendency to decrease. These observations suggest that there are alternative ways of producing Ang II in this model. Chymase the enzyme responsible for Ang II formation direct from Ang I was increased in renal tissues in the fructose group, confirming the alternative pathway for the formation of this peptide. Neprilysin (NEP) the Ang 1-7 forming showed a significant decrease in activity in the fructose vs. control group, and a tendency of reduction in ACE2 activity. Thus, these results suggest that the Ang 1-7 vasodilator peptide formation is impaired in this model contributing with the increase of blood pressure. In summary, rats fed high fructose affect renal RAS, which may contribute to several deleterious effects of fructose on the kidneys and consequently an increase in blood pressure.
Advances and Current Challenges Associated with the Use of Human Induced Pluripotent Stem Cells in Modeling Neurodegenerative Disease

One of the most profound advances in the last decade of biomedical research has been the development of human induced pluripotent stem cell (hiPSC) models for identification of disease mechanisms and drug discovery. Human iPSC technology has the capacity to revolutionize healthcare and the realization of personalized medicine, but differentiated tissues derived from stem cells come with major criticisms compared to native tissue, including variability in genetic backgrounds, a lack of functional maturity, and differences in epigenetic profiles. It is widely believed that increasing complexity will lead to improved clinical relevance, so methods are being developed that go from a single cell type to various levels of 2-D coculturing and 3-D organoids. As this inevitable trend continues, it will be essential to thoroughly understand the strengths and weaknesses of more complex models and to develop criteria for assessing biological relevance. We believe the payoff of robust, high-throughput, clinically meaningful human stem cell models could be the elimination of often inadequate animal models. To facilitate this transition, we will look at the challenges and strategies of complex model development through the lens of neurodegeneration to encapsulate where the disease-in-a-dish field currently is and where it needs to go to improve.
Local Frequency Interpretation and Non-Local Self-Similarity on Graph for Point Cloud Inpainting

As 3D scanning devices and depth sensors mature, point clouds have attracted increasing attention as a format for 3D object representation, with applications in various fields such as tele-presence, navigation, and heritage reconstruction. However, point clouds usually exhibit holes of missing data, mainly due to the limitation of acquisition techniques and complicated structure. Further, point clouds are defined on irregular non-Euclidean domains, which are challenging to address especially with conventional signal processing tools. Hence, leveraging on recent advances in graph signal processing, we propose an efficient point cloud inpainting method, exploiting both the local smoothness and the non-local self-similarity in point clouds. Specifically, we first propose a frequency interpretation in graph nodal domain, based on which we derive the smoothing and denoising properties of a graph-signal smoothness prior in order to describe the local smoothness of point clouds. Second, we explore the characteristics of non-local self-similarity, by globally searching for the most similar area to the missing region. The similarity metric between two areas is defined based on the direct component and the anisotropic graph total variation of normals in each area. Finally, we formulate the hole-filling step as an optimization problem based on the selected most similar area and regularized by the graph-signal smoothness prior. Besides, we propose voxelization and automatic hole detection methods for the point cloud prior to inpainting. The experimental results show that the proposed approach outperforms four competing methods significantly, both in objective and subjective quality.
Monitoring of Marine Biofilm Formation Dynamics at Submerged Solid Surfaces With Multitechnique Sensors

Biofouling on artificial and biotic solid substrata was studied in several locations in the Baltic Sea brackish water (Gulf of Gdansk) during a three-year period with contact angle wettability, confocal microscopy and photoacoustic spectroscopy techniques. As a reference, the trophic state of water body was determined from chemical analyses according to the following parameters: pH, dissolved O2, phosphate, nitrite, nitrate, ammonium etc. concentrations and further correlated to the determined biofilm characterizing parameters by means of Spearman’s rank correlation procedure. Biofilm adhesive surface properties (surface free energy, work of adhesion etc.) were obtained with the contact angle hysteresis (CAH) approach using an automatic captive bubble solid surface wettability sensor assigned for in-situ, on-line and quasi-continuous measurements of permanently submerged samples (Pogorzelski et al., 2013, Pogorzelski and Szczepanska, 2014). Structural and morphological biofilm features (biovolume, substratum coverage, area to volume ratio, spatial spreading, mean thickness and roughness) were determined from confocal reflection microscopy (COCRM) data. Photosynthetic properties (photosynthetic energy storage (ES), photoacoustic amplitude and phase spectra) of biofilm communities exhibited a seasonal variability as indicated by a novel closed-cell type photoacoustic spectroscopy (PAS) system. That allowed mathematical modeling of a marine biofilm under steady state, in particular the specific growth rates μi, and the conditioning or induction times λi to be derived from simultaneous multitechnique signals. A set of the established biofilm structural and physical parameters could be modern water body trophic state indexes.
A Hybrid Approach for Trajectory Control Design

This work presents a methodology to design trajectory tracking feedback control laws, which embed non-parametric statistical models, such as Gaussian Processes (GPs). The aim is to minimize unmodeled dynamics such as undesired slippages. The proposed approach has the benefit of avoiding complex terramechanics analysis to directly estimate from data the robot dynamics on a wide class of trajectories. Experiments in both real and simulated environments prove that the proposed methodology is promising.
Microbial esterases and ester prodrugs: An unlikely marriage for combating antibiotic resistance

The rise of antibiotic resistance necessitates the search for new platforms for drug development. Prodrugs are common tools for overcoming drawbacks typically associated with drug formulation and delivery, with ester prodrugs providing a classic strategy for masking polar alcohol and carboxylic acid functionalities and improving cell permeability. Ester prodrugs are normally designed to have simple ester groups, as they are expected to be cleaved and reactivated by a wide spectrum of cellular esterases. However, a number of pathogenic and commensal microbial esterases have been found to possess significant substrate specificity and can play an unexpected role in drug metabolism. Ester protection can also introduce antimicrobial properties into previously nontoxic drugs through alterations in cell permeability or solubility. Finally, mutation to microbial esterases is a novel mechanism for the development of antibiotic resistance. In this review, we highlight the important pathogenic and xenobiotic functions of microbial esterases and discuss the development and application of ester prodrugs for targeting microbial infections and combating antibiotic resistance. Esterases are often overlooked as therapeutic targets. Yet, with the growing need to develop new antibiotics, a thorough understanding of the specificity and function of microbial esterases and their combined action with ester prodrug antibiotics will support the design of future therapeutics.
The Streptococcus pyogenes Shr protein captures human hemoglobin using two structurally unique binding domains

In order to proliferate and mount an infection, many bacterial pathogens need to acquire iron from their host. The most abundant iron source in the body is the oxygen transporter hemoglobin (Hb). Streptococcus pyogenes, a potentially lethal human pathogen, uses the Shr protein to capture Hb on the cell surface. Shr is an important virulence factor, yet the mechanism by which it captures Hb and acquires its heme is not well-understood. Here, we show using NMR and biochemical methods that Shr binds Hb using two related modules that were previously defined as domains of unknown function (DUF1533). These hemoglobin-interacting domains (HIDs), called HID1 and HID2, are autonomously folded and independently bind Hb. The 1.5 Å resolution crystal structure of HID2 revealed that it is a structurally unique Hb-binding domain. Mutagenesis studies revealed a conserved tyrosine in both HIDs that is essential for Hb binding. Our biochemical studies indicate that HID2 binds Hb with higher affinity than HID1 and that the Hb tetramer is engaged by two Shr receptors. NMR studies reveal the presence of a third autonomously folded domain between HID2 and a heme-binding NEAT1 domain, suggesting that this linker domain may position NEAT1 near Hb for heme capture.
Unifying the Dropout Family Through Structured Shrinkage Priors

Dropout regularization of deep neural networks has been a mysterious yet effective tool to prevent overfitting. Explanations for its success range from the prevention of "co-adapted" weights to it being a form of cheap Bayesian inference. We propose a novel framework for understanding multiplicative noise in neural networks, considering continuous distributions as well as Bernoulli (i.e. dropout). We show that multiplicative noise induces structured shrinkage priors on a network's weights. We derive the equivalence through reparametrization properties of scale mixtures and not via any approximation. Given the equivalence, we then show that dropout's usual Monte Carlo training objective approximates marginal MAP estimation. We analyze this MAP objective under strong shrinkage, showing the expanded parametrization (i.e. likelihood noise) is more stable than a hierarchical representation. Lastly, we derive analogous priors for ResNets, RNNs, and CNNs and reveal their equivalent implementation as noise.
A global view of Gyroporus: molecular phylogenetics, diversity patterns, and new species

ABSTRACT Gyroporus (Gyroporaceae, Boletales) is a highly diverse genus of poroid ectomycorrhizal mushrooms with a nearly worldwide distribution. Previous attempts to unravel the diversity within this genus proved difficult due to the presence of semicryptic species and ambiguous results from analysis of ribosomal RNA markers. In this study, we employ a combined morphotaxonomic and phylogenetic approach to delimit species and elucidate geographic and evolutionary patterns in Gyroporus. For phylogenetic analyses, the protein-coding genes atp6 (mitochondrial adenosine triphosphate [ATP] synthase subunit 6) and rpb2 (nuclear second largest subunit of RNA polymerase II) were selected based on their utility in studies of Boletales. We infer several distinct clades, most notably one corresponding to G. castaneus as a speciose Northern Hemisphere group, another unifying G. cyanescens and like entities, and a third group unifying G. longicystidiatus and a New World sister species. Also notable is the recovery of a sister relationship between the cyanescens and longicystidiatus clades. We formally describe five new species of Gyroporus, outline a number of provisional species, and briefly discuss distributional patterns. This study provides an important scaffold for future work on this well-known but poorly understood genus of fungi.
Unsupervised Online Video Object Segmentation With Motion Property Understanding

Unsupervised video object segmentation aims to automatically segment moving objects over an unconstrained video without any user annotation. So far, only few unsupervised online methods have been reported in the literature, and their performance is still far from satisfactory because the complementary information from future frames cannot be processed under online setting. To solve this challenging problem, in this paper, we propose a novel unsupervised online video object segmentation (UOVOS) framework by construing the motion property to mean moving in concurrence with a generic object for segmented regions. By incorporating the salient motion detection and the object proposal, a pixel-wise fusion strategy is developed to effectively remove detection noises, such as dynamic background and stationary objects. Furthermore, by leveraging the obtained segmentation from immediately preceding frames, a forward propagation algorithm is employed to deal with unreliable motion detection and object proposals. Experimental results on several benchmark datasets demonstrate the efficacy of the proposed method. Compared to state-of-the-art unsupervised online segmentation algorithms, the proposed method achieves an absolute gain of 6.2%. Moreover, our method achieves better performance than the best unsupervised offline algorithm on the DAVIS-2016 benchmark dataset. Our code is available on the project website: https://www.github. com/visiontao/uovos.
Cognitive and Affective Theory of Mind in Mild Cognitive Impairment and Parkinson’s Disease: Preliminary Evidence from the Italian Version of the Yoni Task

ABSTRACT The aim of the study was to explore cognitive and affective dimensions of ToM using the computerized Yoni task in participants with amnestic Mild Cognitive Impairment (aMCI=16), early stage of Parkinson’s Disease (PD=14), and healthy controls (HC=18) Results demonstrated that the Yoni task was effective in discriminating between groups in 1th order cognitive dimension (MCI<PD=HC, pcorr<.05), and in 2nd order cognitive and affective dimensions (MCI<HC, pcorr <.05), highlighting a reduced ToM performance also in people with PD (MCI<PD<HC, pcorr <.05). Thus, the Yoni task represents a sensitive tool for detecting different dimensions of ToM impairment, across different clinical conditions.
Evolution of the Arsenal of Legionella pneumophila Effectors To Modulate Protist Hosts

Within the human host, Legionella pneumophila replicates within alveolar macrophages, leading to pneumonia. However, L. pneumophila is an aquatic generalist pathogen that replicates within a wide variety of protist hosts, including amoebozoa, percolozoa, and ciliophora. ABSTRACT Within the human host, Legionella pneumophila replicates within alveolar macrophages, leading to pneumonia. However, L. pneumophila is an aquatic generalist pathogen that replicates within a wide variety of protist hosts, including amoebozoa, percolozoa, and ciliophora. The intracellular lifestyles of L. pneumophila within the two evolutionarily distant hosts macrophages and protists are remarkably similar. Coevolution with numerous protist hosts has shaped plasticity of the genome of L. pneumophila, which harbors numerous proteins encoded by genes acquired from primitive eukaryotic hosts through interkingdom horizontal gene transfer. The Dot/Icm type IVb translocation system translocates ∼6,000 effectors among Legionella species and >320 effector proteins in L. pneumophila into host cells to modulate a plethora of cellular processes to create proliferative niches. Since many of the effectors have likely evolved to modulate cellular processes of primitive eukaryotic hosts, it is not surprising that most of the effectors do not contribute to intracellular growth within human macrophages. Some of the effectors may modulate highly conserved eukaryotic processes, while others may target protist-specific processes that are absent in mammals. The lack of studies to determine the role of the effectors in adaptation of L. pneumophila to various protists has hampered the progress to determine the function of most of these effectors, which are routinely studied in mouse or human macrophages. Since many protists restrict L. pneumophila, utilization of such hosts can also be instrumental in deciphering the mechanisms of failure of L. pneumophila to overcome restriction of certain protist hosts. Here, we review the interaction of L. pneumophila with its permissive and restrictive protist environmental hosts and outline the accomplishments as well as gaps in our knowledge of L. pneumophila-protist host interaction and L. pneumophila’s evolution to become a human pathogen.
Utilizing bioaugmentation to improve performance of a two-phase AnMBR treating sewage sludge

ABSTRACT Bioaugmentation in the acid-phase of a two-phase anaerobic membrane bioreactor (AnMBR) treating primary sludge was investigated as a means for targeting and improving hydrolysis and acetogenesis. Bioaugmentation was carried out using a proprietary bioculture blend containing a mixture of hydrolytic, acidogenic, and acetogenic microorganisms. This mixture was added on its own and in combination with recycled anaerobic sludge from the methane-phase of the AnMBR. Both bioaugmentation strategies had a positive effect on overall hydrolysis (25–38%), and acid-phase acetic acid generation (31–52%) compared to operation without bioaugmentation. This led to subsequent increases in average methane production (10–13%), and greater average solids reduction (25–55%). Microbial community analysis using 16S Illumina MiSeq generated sequences revealed increased relative abundance of Acetobacter and Syntrophomonas species in bioaugmented communities, suggesting these to be key players in improvements in process performance. However, in general the relative abundance of bioaugmented microorganisms within bioaugmented communities was relatively low, highlighting the need to optimize the bioculture composition and dosage. Overall, bioaugmentation was found to benefit the conversion of primary sludge to methane, when initial solubility was relatively low. Future work should optimize the bioculture composition and dosing strategy to improve its effectiveness and long-term stability, and minimize associated operating costs. GRAPHICAL ABSTRACT
Is This the Last Requiem for Simtuzumab?

In modern hepatology we sing the song for the advent of effective antifibrotic drugs for decades recalling the line of a masterpiece song of the late Leonard Cohen "a million candles burning for the help that never came". We realize but hardly accept that most likely such drugs will not work without resolving the causative problem of a liver disease such as in viral hepatitis. In liver diseases with so far unknown etiology as in primary sclerosing cholangitis (PSC), the task of successful antifibrotic treatment will even harder be pursued. This article is protected by copyright. All rights reserved.