Miracle-dz/UniFAR-FTUs huggingface dataset:
The Macro-Autophagy-Related Protein Beclin-1 Immunohistochemical Expression Correlates With Tumor Cell Type and Clinical Behavior of Uveal Melanoma

Uveal melanoma, in spite of its rarity, represents the most common primitive intraocular malignant neoplasm of the adults; it affects choroid, ciliary bodied and iris and remains clinically silent for a long time, being accidentally discovered by routine ophthalmic exams. Prognosis of uveal melanoma is poor and frequently characterized by liver metastases, within 10–15 years from diagnosis. Autophagy is a multi-step catabolic process by which cells remove damaged organelles and proteins and recycle nutrients. It has been hypothesized that in early stages of tumorigenesis autophagy has a tumor suppressor role while, in more advanced stages, it may represent a survival mechanism of neoplastic cells in response to stress. Several proteins related to autophagy cascade have been investigated in numerous subtypes of human cancer, with overall controversal results. In this paper we studied the immunohistochemical expression of 3 autophagy related proteins (Beclin-1, p62 and ATG7) in a cohort of 85 primary uveal melanoma treated by primary enucleation (39 with metastasis and 46 non metastatic) and correlated their expression with clinico-pathological parameters and blood vascular microvessel density, in order to investigate the potential prognostic role of autophagy in this rare neoplasm. We found that high immunohistochemical levels of Beclin-1 correlated with a lower risk of metastasis and higher disease-free survival times, indicating a positive prognostic role for Beclin-1 in uveal melanoma. No statistically significative differences regarding the expression of ATG7 and p62 between metastatic and non metastatic patients was detected.
Autoimmunity in Focal Segmental Glomerulosclerosis: A Long-Standing Yet Elusive Association

Focal segmental glomerulosclerosis (FSGS) is a histological term that describes a pathologic renal entity affecting both adults and children, with a wide array of possible underlying etiologies. Podocyte damage with scarring, the hallmark of this condition, leads to altered permeability of the glomerular barrier, which may result in massive proteinuria and relentless renal function deterioration. A definite cause of focal segmental glomerulosclerosis can be confirmed in a minority of cases, while most forms have been traditionally labeled as primary or idiopathic. Despite this definition, increasing evidence indicates that primary forms are a heterogenous group rather than a single disease entity: several circulating factors that may affect glomerular permeability have been proposed as potential culprits, and both humoral and cellular immunity have been implicated in the pathogenesis of the disease. Consistently, immunosuppressive drugs are considered as the cornerstone of treatment for primary focal segmental glomerulosclerosis, but response to these agents and long-term outcomes are highly variable. In this review we provide a summary of historical and recent advances on the pathogenesis of primary focal segmental glomerulosclerosis, focusing on implications for its differential diagnosis and treatment.
Development of SNP-Based Genomic Tools for the Canadian Bison Industry: Parentage Verification and Subspecies Composition

Genomic technologies have been increasingly applied in livestock production due to their utility in production management and animal genetic improvement. The current project aimed to develop genomic resources for the Canadian bison industry, specifically a parentage verification tool and a subspecies composition tool. Both products stand to help with building and maintaining purebred and crossbred bison populations, and in turn bison conservation and production. The development of this genomic toolkit proceeded in two stages. In the single-nucleotide polymorphism (SNP) discovery and selection stage, raw sequence information from 41 bison samples was analyzed, and approximately 52.5 million candidate biallelic SNPs were discovered from 21 samples with high sequence quality. A set of 19,954 SNPs (2,928 for parentage verification and 17,026 for subspecies composition) were then selected for inclusion on an Axiom myDesign custom array. In the refinement and validation stage, 480 bison were genotyped using the custom SNP panel, and the resulting genotypes were analyzed to further filter SNPs and assess tool performance. In various tests using real and simulated genotypes, the two genomic tools showed excellent performance for their respective tasks. Final SNP sets consisting of 191 SNPs for parentage and 17,018 SNPs for subspecies composition are described. As the first SNP-based genomic toolkit designed for the Canadian bison industry, our results may provide a new opportunity in improving the competitiveness and profitability of the industry in a sustainable manner.
The Mediating Role of Resilience and Self-Esteem Between Life Events and Coping Styles Among Rural Left-Behind Adolescents in China: A Cross-Sectional Study

Objective: This study aims to explore the association between life events and coping styles, and how resilience and self-esteem mediate the association. Methods: A cross-sectional study was conducted among 981 left-behind adolescents (LBAs) in five junior high schools in Hunan Province, China, from April 13 to April 20, 2020. We utilized self-designed sociodemographic questionnaire, Adolescent Self-Rating Life Events Checklist, Resilience Scale Chinese Adolescent, Rosenberg Self-Esteem Scale, and Simplified Coping Style Questionnaire to assess the mental health of LBAs. Statistic description, Pearson correlation analysis, and structural equation model were adopted to analyze the data. Results: Results revealed that life events could negatively predict resilience (β = −0.29, P < 0.001) and self-esteem (β = −0.39, P < 0.001) and positively predict LBAs' positive coping style (β = 0.28, P < 0.001) and negative coping style (β = 0.21, P < 0.001). Self-esteem could also positively predict the resilience of LBAs (β = 0.62, P < 0.001); resilience could negatively predict the negative coping style (β = −0.21, P < 0.001) and positively predict the positive coping style (β = 0.79, P < 0.001). Life events not only have direct effects on negative coping style (β = 0.21) and positive coping style (β = 0.28) but also have indirect effects on coping styles by affecting resilience (β = −0.29) and self-esteem (β = −0.39). The total effect of life events on coping styles was 0.32, where 34.37% was mediated by resilience and self-esteem. Conclusion: We proved that resilience and self-esteem mediated most of the effects of life events on coping styles. The findings had important implications for interventions to promote mental health of LBAs, particularly the enhancement of resilience and self-esteem.
Light Limitation and Depth-Variable Sedimentation Drives Vertical Reef Compression on Turbid Coral Reefs

Turbid coral reefs experience high suspended sediment loads and low-light conditions that vertically compress the maximum depth of reef growth. Although vertical reef compression is hypothesized to further decrease available coral habitat as environmental conditions on reefs change, its causative processes have not been fully quantified. Here, we present a high-resolution time series of environmental parameters known to influence coral depth distribution (light, turbidity, sedimentation, currents) within reef crest (2–3 m) and reef slope (7 m) habitats on two turbid reefs in Singapore. Light levels on reef crests were low [mean daily light integral (DLI): 13.9 ± 5.6 and 6.4 ± 3.0 mol photons m–2 day–1 at Kusu and Hantu, respectively], and light differences between reefs were driven by a 2-fold increase in turbidity at Hantu (typically 10–50 mg l–1), despite its similar distance offshore. Light attenuation was rapid (KdPAR: 0.49–0.57 m–1) resulting in a shallow euphotic depth of <11 m, and daily fluctuations of up to 8 m. Remote sensing indicates a regional west-to-east gradient in light availability and turbidity across southern Singapore attributed to spatial variability in suspended sediment, chlorophyll-a and colored dissolved organic matter. Net sediment accumulation rates were ∼5% of gross rates on reefs (9.8–22.9 mg cm–2 day–1) due to the resuspension of sediment by tidal currents, which contribute to the ecological stability of reef crest coral communities. Lower current velocities on the reef slope deposit ∼4 kg m2 more silt annually, and result in high soft-sediment benthic cover. Our findings confirm that vertical reef compression is driven from the bottom-up, as the photic zone contracts and fine silt accumulates at depth, reducing available habitat for coral growth. Assuming no further declines in water quality, future sea level rise could decrease the depth distribution of these turbid reefs by a further 8–12%. This highlights the vulnerability of deeper coral communities on turbid reefs to the combined effects of both local anthropogenic inputs and climate-related impacts.
Think Hard or Think Smart: Network Reconfigurations After Divergent Thinking Associate With Creativity Performance

Evidence suggests divergent thinking is the cognitive basis of creative thoughts. Neuroimaging literature using resting-state functional connectivity (RSFC) has revealed network reorganizations during divergent thinking. Recent studies have revealed the changes of network organizations when performing creativity tasks, but such brain reconfigurations may be prolonged after task and be modulated by the trait of creativity. To investigate the dynamic reconfiguration, 40 young participants were recruited to perform consecutive Alternative Uses Tasks (AUTs) for divergent thinking and two resting-state scans (before and after AUT) were used for mapping the brain reorganizations after AUT. We split participants into high- and low-creative groups based on creative achievement questionnaire (CAQ) and targeted on reconfigurations of the two brain networks: (1) default-mode network (DMN) and (2) the network seeded at the left inferior frontal gyrus (IFG) because the between-group difference of AUT-induced brain activation located at the left IFG. The changes of post-AUT RSFCs (DMN and IFGN) indicated the prolonged effect of divergent thinking. More specifically, the alterations of RSFCIFG−AG and RSFCIFG−IPL (AG: angular gyrus, IPG: inferior parietal lobule) in the high-creative group had positive relationship with their AUT performances (originality and fluency), but not found in the low-creative group. Furthermore, the RSFC changes of DMN did not present significant relationships with AUT performances. The findings not only confirmed the possibility of brain dynamic reconfiguration following divergent thinking, but also suggested the distinct IFGN reconfiguration between individuals with different creativity levels.
Direct tracking of single proviruses reveals HIV-1/LEDGF complexes excluded from virus-induced membraneless organelles

Abstract The ultimate goal of HIV-1 is integration into the host chromatin to optimize the release of high levels of viral progeny and discretely coexist with the host. To uncover the HIV-1 DNA fate in the nuclear landscape we directly tracked the viral DNA (vDNA) and the viral RNA (vRNA) by coupling HIV-1 ANCHOR technology with RNA FISH or MCP-MS2 RNA-tagging bacterial system. Our computational imaging analysis revealed that proviral forms are early located in proximity of the nuclear periphery of mitotic and non-mitotic cells. We also observed that HIV-1 infection prompts clustering formation of the host factor CPSF6 restructuring membraneless organelles enriched in both viral proteins and speckle factors. Interestingly, we observed that integrase proteins are retained in CPSF6 clusters, while the late retrotranscribed DNA was excluded from HIV-induced membranelless organelles (HIV-1 MLOs), indicating that those structures are not proviral sites, but orchestrate viral events prior to the integration step. HIV-1 MLOs are in the vicinity of pre-existing LEDGF clusters. Importantly, we identified actively transcribing proviruses localize, outside HIV-1 MLOs, in LEDGF-abundant regions, known to be active chromatin sites. This study highlights single functional host-proviral complexes in their nuclear landscape, which is markedly restructured by HIV-1 to favor viral replication.
Brief Report: The Virucidal Efficacy of Oral Rinse Components Against SARS-CoV-2 In Vitro

The ability of widely-available mouthwashes to inactivate SARS-CoV-2 in vitro was tested using a protocol capable of detecting a 5-log10 reduction in infectivity, under conditions mimicking the naso/oropharynx. During a 30 second exposure, two rinses containing cetylpyridinium-chloride and a third with ethanol/ethyl lauroyl arginate eliminated live virus to EN14476 standards (>4-log10 reduction), while others with ethanol/essential oils and povidone-iodine (PVP-I) eliminated virus by 2-3-log10. Chlorhexidine or ethanol alone displayed little or no ability to inactivate virus. Studies are warranted to determine whether these formulations can inactivate virus in the human oropharynx in vivo, and whether this might impact transmission risk.
Oxygen-dependent changes in HIF binding partners and post-translational modifications regulate stability and transcriptional activity

Adaption of cells to low oxygen environments is an essential process mediated in part by the Hypoxia Inducible Factors (HIFs). Like other transcription factors, the stability and transcriptional activity of HIFs, and consequently the hypoxic response, are regulated by post-translational modification (PTM) and changes in biomolecular interactions. However, our current understanding of PTM-mediated regulation of HIFs is primarily based on in vitro protein fragment-based studies, with validation typically having been conducted by in cellulo fragment expression and hypoxia mimicking drugs. Consequently, we still lack an understanding of true oxygen deprivation signaling via HIFα. Using an immunoprecipitation-based, mass spectrometry approach, we characterize the regulation of in cellulo expressed full-length HIF-1α and HIF-2α, in terms of both PTM and binding partners, in response to normoxia (21% oxygen) and hypoxia (1% oxygen). These studies revealed that a change in oxygen tension significantly alters the complexity and composition of HIF-α protein interaction networks, with HIF-2α in particular having an extended hypoxia-induced interactome, most notably with mitochondrial-associated proteins. Both HIFα isoforms are heavily covalently modified: we define ~40 different sites of PTM on each of HIF-1α and HIF-2α, comprising 13 different PTM types, including multiple cysteine modifications and a highly unusual phosphocysteine. Over 80% of the PTMs identified are novel, and approximately half exhibit oxygen-dependency under these conditions. Combined with domain and evolutionary analysis of >225 vertebrate species, we validate Ser31 phosphorylation on HIF-1α as a regulator of transcription, and propose functional roles for Thr406, Thr528 and Ser581 on HIF-2α.
Dissociable effects of subliminal incentives on initiation and velocity control of goal-directed eye movements

Over the last decades, several studies have demonstrated that conscious and unconscious reward incentives both affect performance in physical and cognitive tasks, suggesting that goal-pursuit can arise from an unconscious will. Whether the planning of goal-directed saccadic eye movements during an effortful task can also be affected by subliminal reward cues has not been systematically investigated. We employed a novel task where participants had to make several eye movements back and forth between a fixation point and a number of peripheral targets. The total number of targets visited by the eyes in a fixed amount of time determined participants’ monetary gain. The magnitude of the reward at stake was briefly shown at the beginning of each trial and was masked by pattern images superimposed in time. We found that when reward cues were fully visible and thus consciously perceived, higher reward enhanced all saccade parameters. However, a dissociation was observed between the effects of subliminal rewards on saccade initiation and peak velocities. While truly subliminal reward cues did increase the number of saccades, they did not enhance saccades’ peak velocity. Additionally, participants who had reached a truly subliminal level of reward perception showed a decrement in accuracy as a function of reward across all visibility levels, as saccade endpoint error was larger when higher reward incentives were expected. This suboptimal speed-accuracy trade-off did not occur in the supraliminal group. These results suggest that although saccades’ initiation can be triggered by subconscious mechanisms, conscious awareness is required to optimally adjust the velocity and accuracy of eye movements based on the expected rewards.
Melt into the group Electrophysiological Evidence of Gestalt Perception of Human Dyad

It has been showed recently that the human brain has dedicated networks for perception of human bodies in synchronous motion or in situation of interaction. However, below motion and interaction, how does the brain process a simple plurality of humans in close positioning? We used EEG frequency tagging technique to investigate integration of human dyad elements in a global percept. We presented to participants images of two silhouettes, a man and a woman flickering at different frequencies (5.88 vs. 7.14 Hz). Clear response at these stimulation frequencies reflected response to dyad parts, both when the dyad was presented upright and inverted. However, an emerging intermodulation component (7.14 + 5.88 = 13.02 Hz), a nonlinear response regarded as an objective signature of holistic representation, was significantly enhanced in upright relatively to inverted position. Inversion effect was significant only for the intermodulation component as opposed to stimulation frequencies revealing that dyad configuration perception overrides structural properties of dyad elements. Inversion effect was not significant for a pair of non-human objects. Our results show that merely facing two humans in close positioning leads to perceptually bind them and suggest that the perception of individuals is of different nature when they form a plurality.
A functional pre-screening platform for identifying points of vulnerability in the cell death map of human melanoma tumors

Targeted drug therapy in melanoma patients carrying the BRAF V600E mutation provides temporary remission, often followed by relapse due to acquired drug resistance. Here we propose a functional approach to circumvent drug resistance by applying a personalized prescreening platform that maps points of vulnerability in each tumor, prior to drug treatment. This platform applies siRNAs targeting 81 apoptosis, autophagy and programmed necrosis genes in patient tumor cell cultures, identifying genes whose targeting maximizes cell killing by short-term BRAF inhibition. Melanoma tumors displayed large heterogeneity in the number and identities of soft-spots, providing different tumor-specific functional death signatures. The soft-spots were targeted by replacing functional siRNAs with small compound inhibitors for long-term treatment in combination with vemurafenib. This strategy reduced the number of drug-tolerant persister cells surviving treatment, and most importantly, the number of drug-resistant foci. Thus, prescreening melanoma tumors for soft-spots within the cell death network may enhance targeted drug therapy before resistance emerges, thereby reducing the odds of developing drug-resistant mutations, and preventing tumor relapse.
Track-To-Learn: A general framework for tractography with deep reinforcement learning

Diffusion MRI tractography is currently the only non-invasive tool able to assess the white-matter structural connectivity of a brain. Since its inception, it has been widely documented that tractography is prone to producing erroneous tracks while missing true positive connections. Anatomical priors have been conceived and implemented in classical algorithms to try and tackle these issues, yet problems still remain and the conception and validation of these priors is very challenging. Recently, supervised learning algorithms have been proposed to learn the tracking procedure implicitly from data, without relying on anatomical priors. However, these methods rely on labelled data that is very hard to obtain. To remove the need for such data but still leverage the expressiveness of neural networks, we introduce Track-To-Learn: A general framework to pose tractography as a deep reinforcement learning problem. Deep reinforcement learning is a type of machine learning that does not depend on ground-truth data but rather on the concept of “reward”. We implement and train algorithms to maximize returns from a reward function based on the alignment of streamlines with principal directions extracted from diffusion data. We show that competitive results can be obtained on known data and that the algorithms are able to generalize far better to new, unseen data, than prior machine learning-based tractography algorithms. To the best of our knowledge, this is the first successful use of deep reinforcement learning for tractography.
Effects of ontogeny and invasive crayfish on feeding ecology and mercury concentrations of predatory fishes

Lake food web structure dictates the flow of energy and contaminants to top predators, and addition of invasive species can shift these flows. We examined trophic position (TP), proportional reliance on the littoral zone (Proplittoral), and mercury (Hg) concentrations across the life-span of two predatory fishes, walleye (Sander vitreus) and northern pike (Esox lucius), in lakes with and without invasive virile crayfish (Faxonius virilis). The littoral zone was the dominant foraging zone for both species regardless of size, accounting for 59% and 80% of the diet of walleye and pike, respectively. Both species increased in TP and Hg with body size, as did crayfish. Walleye in crayfish-present lakes had lower Proplittoral, TP, and Hg concentrations compared with non-present lakes, but trophic magnification of Hg through the food web was consistent across all six lakes. These findings underscore a strong role for the littoral zone in channeling energy and contaminants to higher trophic levels and how invasive species can occupy new habitats at low abundance while altering food web structure and contaminant bioaccumulation.