Miracle-dz/UniFAR-FTUs huggingface dataset:
Multitarget Activities of Müller Glial Cells and Low-Density Lipoprotein Receptor-Related Protein 1 in Proliferative Retinopathies

Müller glial cells (MGCs), the main glial component of the retina, play an active role in retinal homeostasis during development and pathological processes. They strongly monitor retinal environment and, in response to retinal imbalance, activate neuroprotective mechanisms mainly characterized by the increase of glial fibrillary acidic protein (GFAP). Under these circumstances, if homeostasis is not reestablished, the retina can be severely injured and GFAP contributes to neuronal degeneration, as they occur in several proliferative retinopathies such as diabetic retinopathy, sickle cell retinopathy and retinopathy of prematurity. In addition, MGCs have an active participation in inflammatory responses releasing proinflammatory mediators and metalloproteinases to the extracellular space and vitreous cavity. MGCs are also involved in the retinal neovascularization and matrix extracellular remodeling during the proliferative stage of retinopathies. Interestingly, low-density lipoprotein receptor-related protein 1 (LRP1) and its ligand α2-macroglobulin (α2M) are highly expressed in MGCs and they have been established to participate in multiple cellular and molecular activities with relevance in retinopathies. However, the exact mechanism of regulation of retinal LRP1 in MGCs is still unclear. Thus, the active participation of MGCs and LRP1 in these diseases, strongly supports the potential interest of them for the design of novel therapeutic approaches. In this review, we discuss the role of LRP1 in the multiple MGCs activities involved in the development and progression of proliferative retinopathies, identifying opportunities in the field that beg further research in this topic area. Summary Statement MGCs and LRP1 are active players in injured retinas, participating in key features such as gliosis and neurotoxicity, neovascularization, inflammation, and glucose control homeostasis during the progression of ischemic diseases, such as proliferative retinopathies.
Engineering large end-to-end correlations in finite fermionic chains

We explore deformations of finite chains of independent fermions which give rise to large correlations between their extremes. After a detailed study of the Su-Schrieffer-Heeger (SSH) model, the trade-off curve between end-to-end correlations and the energy gap of the chains is obtained using machine-learning techniques, paying special attention to the scaling behavior with the chain length. We find that edge-dimerized chains, where the second and penultimate hoppings are reinforced, are very often close to the optimal configurations. Our results allow us to conjecture that, given a fixed gap, the maximal attainable correlation falls exponentially with the system size. Study of the entanglement entropy and contour of the optimal configurations suggest that the bulk entanglement pattern is minimally modified from the clean case.
Communication Networks and Individual Resilience for Individual Well-Being During a Time of Crisis

ABSTRACT The deprivation of offline communication necessitated by the COVID-19 pandemic raises questions about whether and how external social resources and internal ability lead individuals to maintain their well-being. However, most research on the two factors, especially during the COVID-19 pandemic, has been based on cross-sectional survey data during the early lockdowns and focused on each factor separately. Combining the two lines of research, this study investigates how individuals’ communication networks and resilience interacted with each other and influenced individual well-being at two time points during the COVID-19 pandemic. Based on the two-wave online panel survey data gathered from 708 Korean adults, this study suggests that individual well-being depends on strong ties and emotional support, and that their offline support influences their well-being differently depending on their level of resilience. Implications for understanding the transformed roles of communication networks and the complex dynamics of offline support together with individual resilience on individual well-being are discussed.
Moduli of Riemann Surfaces, Transcendental Aspects

This is an informal set of lecture notes on moduli spaces of curves based on a set of lectures given at the ICTP last summer. It begins at an elementary level and discusses the genus 1 case in detail. The notes then give an informal treatement of Teichmuller space and higher genus moduli spaces. The point of view is generally topological and analytical.
ARHGAP44 expression is associated with the metastasis of osteosarcoma and is a promising prognostic biomarker

Osteosarcoma (OS) is the most domain primary malignant bone tumor. Treatment resistances and metastases result in a decreasing 5‐year overall survival rate of OS. However, Rho GTPase‐activating protein 44 (ARHGAP44) has not been well studied in OS. The OS patient data were obtained from Therapeutically Applicable Research to Generate Effective Treatments and Gene Expression Omnibus databases. We utilized Survival and Survminer package for survival analysis based on Kaplan–Meier method. The association between ARHGAP44 expression with the prognosis of OS was determined by Wilcoxon rank‐sum test and multivariate Cox regression analysis. The real‐time polymerase chain reaction and western blotting were conducted to validate the results. Gene set enrichment analysis was done to find significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The OS sample ARHGAP44 expression level was significantly higher than that in normal samples, which was validated in cell lines. High ARHGAP44 expression was associated with metastasis of OS. The OS patients with high ARHGAP44 expression had worse prognosis compared with low ARHGAP44 expression OS patients. In total, 10 KEGG pathways significantly activated in high ARHGAP44 expression OS patients, such as Hedgehog signaling pathway, Steroid biosynthesis, and so on. In summary, high ARHGAP44 expression was closely correlated with the metastasis and poor prognosis of OS. ARHGAP44 was a potential prognostic biomarker for OS.
Columnar Lesions in Barrel Cortex Persistently Degrade Object Location Discrimination Performance

Abstract Primary sensory cortices display functional topography, suggesting that even small cortical volumes may underpin perception of specific stimuli. Traditional loss-of-function approaches have a relatively large radius of effect (>1 mm), and few studies track recovery following loss-of-function perturbations. Consequently, the behavioral necessity of smaller cortical volumes remains unclear. In the mouse primary vibrissal somatosensory cortex (vS1), “barrels” with a radius of ∼150 μm receive input predominantly from a single whisker, partitioning vS1 into a topographic map of well defined columns. Here, we train animals implanted with a cranial window over vS1 to perform single-whisker perceptual tasks. We then use high-power laser exposure centered on the barrel representing the spared whisker to produce lesions with a typical volume of one to two barrels. These columnar-scale lesions impair performance in an object location discrimination task for multiple days without disrupting vibrissal kinematics. Animals with degraded location discrimination performance can immediately perform a whisker touch detection task with high accuracy. Animals trained de novo on both simple and complex whisker touch detection tasks showed no permanent behavioral deficits following columnar-scale lesions. Thus, columnar-scale lesions permanently degrade performance in object location discrimination tasks.
Overcoming tensions between family-centered care and fidelity within Early Intervention implementation research

The Part C Early Intervention system has been a focus of translational efforts in the autism field, as it is an entry point to services during a critical window of early development. Although Early Intervention systems are perceived as a promising setting in which to implement evidence-based practices for autism, implementation efforts seldom account for the unique service delivery model of Early Intervention systems, which emphasize family-centered care. The principles of family-centered care may at times pose tradeoffs to the implementation of manualized evidence-based practices and, thus, are pertinent to consider within implementation research being conducted within these systems. This commentary highlights family-centered care as an important factor of service delivery in Early Intervention systems that deserve greater attention. We lay out how family-centered care provides a framework for evaluating evidence-based practice adaptation in Early Intervention systems, how it may impact the adoption and implementation of evidence-based practices, and directions for future research to evaluate the impact of family-centered care alongside evidence-based practice delivery. Measuring family-centered care as part of research within Early Intervention systems may shift the autism field to a more balanced view of fidelity as both delivering core evidence-based practice components in a manner that closely align with fundamental tenants of Early Intervention systems. Lay Abstract Early Intervention systems provide therapeutic services to families of young children birth to 3 years with developmental delays and are considered a natural access point to services for young children and their families. Research studies in the autism field have been interested in training providers to deliver evidence-based practices in Early Intervention systems to increase access to services for young children with an increased likelihood of being autistic. However, research has often overlooked that Early Intervention systems prioritize family-centered care, an approach to working with families that honors and respects their values and choices and that provides supports to strengthen family functioning. This commentary points out that family-centered care deserves greater attention in research being done in Early Intervention systems. We describe how family-centered care may shape how interventions are delivered, and discuss directions for future research to evaluate the impact of family-centered care alongside intervention delivery.
Divided attention effects in visual search are caused by objects not by space

Divided attention effects have been observed across a variety of stimuli and perceptual tasks, which have given rise to both object-based and space-based theories of divided attention. Object-based theories assert that processing information from multiple objects is limited, whereas space-based theories assert that processing information from multiple locations is limited. Extant results in the literature are collectively inconsistent with both simple object-based theories and simple space-based theories of divided attention. Using a visual search task with the extended simultaneous-sequential method to reveal capacity limitations, we found evidence of limited-capacity processing of object properties and unlimited-capacity processing of feature contrast. We found no evidence of a separate spatial limitation. A multiple pathway processing theory can account for these and a large body of previous results. According to this theory, tasks that require object processing must follow a limited-capacity pathway and therefore incur divided attention effects. Tasks that depend on only feature contrast can follow a separate unlimited-capacity processing pathway and therefore do not incur divided attention effects.
Reply to Li et al., “Kappa Values in Testing the Concordance: Comments on a Recent Article about Nasopharyngeal Swabs for SARS-CoV-2 Detection”

aDepartment of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA bDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA cBeth Israel Deaconess Medical Center, Boston, Massachusetts, USA dDivision of Clinical Informatics, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA eHarvard Medical School, Boston, Massachusetts, USA
Spectral weights of doublon in interacting Hofstadter model

In this article, two-particle Greens functions are computed for different strengths of interactions for particles in Hofstadter lattices, providing informations on spectral weights of doublons. The calculations are performed for a finite lattice without disorder. The splitting in spectra under the effect of external magnetic field for non-interacting and interacting pairs are compared.
Proximal ear hole injury heals by limited regeneration during the early postnatal phase in mice

Ear pinna is a particular feature of mammals that shows several repair responses depending on age. Two millimeter hole made in the pinna of middle‐aged female mice heals due to partial reconstitution of new tissues (limited regeneration), whereas a hole punched in the ear of young mice forms a scar tissue. In these studies, the injury is made in the center of the ear pinna, but little is known about the type of reparative response along the proximodistal polarity of the ear. This study evaluated the effect of pinna polarity, age, and sex in the ear hole‐repairing response in Balb/c mice. Proximal injuries were repaired more efficiently by limited regeneration than wounds made in the middle region. Non‐injured ear histological analysis revealed a higher presence of muscle, adipose tissue, cartilage, and larger blood vessels in the proximal ear area, which could influence ear hole closure by limited regeneration. To evaluate the healing response during ear growth, we punched a standard hole in the proximal area of the ear on postnatal day 21 and 8‐month‐old mice (adults). Thirty‐five days after the wound, both groups reached the same wound closure, despite the greater proportional size of holes made in the younger mice. Ear growth also improved ear hole closure in male mice. These results suggest that ear growth accelerates hole closure, providing an example of enhanced regenerative abilities in growing structures. Finally, hole closure kinetics in the growing ear indicated an early re‐differentiation phase exhibited at 14 days post‐wound. In conclusion, ear topography and growth positively influenced the healing response to ear holes, making it a tractable model to study in mammals.
Guide for collecting and reporting metadata on protocol variables and parameters from slide-based histotechnology assays to enhance reproducibility

ABSTRACT The central tenet of scientific research is the rigorous application of the scientific method to experimental design, analysis, interpretation, and reporting of results. In order to confer validity to a hypothesis, experimental details must be transparent and results must be reproducible. Failure to achieve this minimum indicates a deficiency in rationale, design, and/or execution, necessitating further experimental refinement or hypothesis reformulation. More importantly, rigorous application of the scientific method advances scientific knowledge by enabling others to identify weaknesses or gaps that can be exploited by new ideas or technology that inevitably extend, improve, or refine a hypothesis. Experimental details, described in manuscript materials and methods, are the principal vehicle used to communicate procedures, techniques, and resources necessary for experimental reproducibility. Recent examination of the biomedical literature has shown that many published articles lack sufficiently detailed methodological information to reproduce experiments. There are few broadly established practice guidelines and quality assurance standards in basic biomedical research. The current paper provides a framework of best practices to address the lack of reporting of detailed materials and methods that is pervasive in histological slide-based assays. Our goal is to establish a structured framework that highlights the key factors necessary for thorough collection of metadata and reporting of slide-based assays.
Free ISG15 inhibits Pseudorabies virus infection by positively regulating type I IFN signaling

Interferon-stimulated gene 15 (ISG15) is strongly upregulated during viral infections and exerts pro-viral or antiviral actions. While many viruses combat host antiviral defenses by limiting ISG expression, PRV infection notably increases expression of ISG15. However, studies on the viral strategies to regulate ISG15-mediated antiviral responses are limited. Here, we demonstrate that PRV-induced free ISG15 and conjugated proteins accumulation require viral gene expression. Conjugation inhibition assays showed that ISG15 imposes its antiviral effects via unconjugated (free) ISG15 and restricts the viral release. Knockout of ISG15 in PK15 cells interferes with IFN-β production by blocking IRF3 activation and promotes PRV replication. Mechanistically, ISG15 facilitates IFNα-mediated antiviral activity against PRV by accelerating the activation and nuclear translocation of STAT1 and STAT2. Furthermore, ISG15 facilitated STAT1/STAT2/IRF9 (ISGF3) formation and ISGF3-induced IFN-stimulated response elements (ISRE) activity for efficient gene transcription by directly interacting with STAT2. Significantly, ISG15 knockout mice displayed enhanced susceptibility to PRV, as evidenced by increased mortality and viral loads, as well as more severe pathology caused by excessive production of the inflammatory cytokines. Our studies establish the importance of free ISG15 in IFNα-induced antiviral immunity and in the control of viral infections.
Statistics of voids in the two‐degree Field Galaxy Redshift Survey

We present a statistical analysis of voids in the two-degree Field Galaxy Redshift Survey (2dFGRS). In order to detect the voids, we have developed two robust algorithms. We define voids as non-overlapping maximal spheres empty of haloes or galaxies with mass or luminosity above a given value. We search for voids in cosmological N-Body simulations to test the performance of our void finders. We obtain and analyse the void statistics for several volume-limited samples for the North Galactic Pole (NGP) and the South Galactic Pole (SGP) constructed from the 2dFGRS full data release. We find that the results obtained from the NGP and the SGP are statistically compatible. From the results of several statistical tests we conclude that voids are essentially uncorrelated, with at most a mild anticorrelation and that at the 99.5 per cent confidence level there is a dependence of the void number density on redshift. We develop a technique to correct the distortion caused by the fact that we use the redshift as the radial coordinate. We calibrate this technique with mock catalogues and find that the correction might be of some relevance to carry out accurate inferences from void statistics. We study the statistics of the galaxies inside nine nearby voids. We find that galaxies in voids are not randomly distributed: they form structures like filaments. We also obtain the galaxy number density profile in voids. This profile follow a similar but steeper trend to that followed by haloes in voids.
Differential Regulation of the BDNF Gene in Cortical and Hippocampal Neurons

Brain-derived neurotrophic factor (BDNF) is a widely expressed neurotrophin that supports the survival, differentiation, and signaling of various neuronal populations. Although it has been well described that expression of BDNF is strongly regulated by neuronal activity, little is known whether regulation of BDNF expression is similar in different brain regions. Here, we focused on this fundamental question using neuronal populations obtained from rat cerebral cortices and hippocampi of both sexes. First, we thoroughly characterized the role of the best-described regulators of BDNF gene - cAMP response element binding protein (CREB) family transcription factors, and show that activity-dependent BDNF expression depends more on CREB and the coactivators CREB binding protein (CBP) and CREB-regulated transcriptional coactivator 1 (CRTC1) in cortical than in hippocampal neurons. Our data also reveal an important role of CREB in the early induction of BDNF mRNA expression after neuronal activity and only modest contribution after prolonged neuronal activity. We further corroborated our findings at BDNF protein level. To determine the transcription factors regulating BDNF expression in these rat brain regions in addition to CREB family, we used in vitro DNA pulldown assay coupled with mass spectrometry, chromatin immunoprecipitation (ChIP), and bioinformatics, and propose a number of neurodevelopmentally important transcription factors, such as FOXP1, SATB2, RAI1, BCL11A, and TCF4 as brain region-specific regulators of BDNF expression. Together, our data reveal complicated brain region-specific fine-tuning of BDNF expression. SIGNIFICANCE STATEMENT To date, majority of the research has focused on the regulation of brain-derived neurotrophic factor (BDNF) in the brain but much less is known whether the regulation of BDNF expression is universal in different brain regions and neuronal populations. Here, we report that the best described regulators of BDNF gene from the cAMP-response element binding protein (CREB) transcription factor family have a more profound role in the activity-dependent regulation of BDNF in cortex than in hippocampus. Our results indicate a brain region-specific fine tuning of BDNF expression. Moreover, we have used unbiased determination of novel regulators of the BDNF gene and report a number of neurodevelopmentally important transcription factors as novel potential regulators of the BDNF expression.
Combination of AIBP, apoA-I, and Aflibercept Overcomes Anti-VEGF Resistance in Neovascular AMD by Inhibiting Arteriolar Choroidal Neovascularization

Purpose Anti-VEGF resistance represents a major unmet clinical need in the management of choroidal neovascularization (CNV). We have previously reported that a combination of AIBP, apoA-I, and an anti-VEGF antibody overcomes anti-VEGF resistance in laser-induced CNV in old mice in prevention experiments. The purpose of this work is to conduct a more clinically relevant study to assess the efficacy of the combination of AIBP, apoA-I, and aflibercept in the treatment of anti-VEGF resistance of experimental CNV at different time points after laser photocoagulation. Methods To understand the pathobiology of anti-VEGF resistance, we performed comprehensive examinations of the vascular morphology of laser-induced CNV in young mice that are highly responsive to anti-VEGF treatment, and in old mice that are resistant to anti-VEGF therapy by indocyanine green angiography (ICGA), fluorescein angiography (FA), optical coherence tomography (OCT), and Alexa 568 isolectin labeled choroid flatmounts. We examined the efficacy of the combination therapy of AIBP, apoA-I, and aflibercept intravitreally delivered at 2, 4, and 7 days after laser photocoagulation in the treatment of CNV in old mice. Results Laser-induced CNV in young and old mice exhibited cardinal features of capillary and arteriolar CNV, respectively. The combination therapy and the aflibercept monotherapy were equally effective in treating capillary CNV in young mice. In old mice, the combination therapy was effective in treating anti-VEGF resistance by potently inhibiting arteriolar CNV, whereas aflibercept monotherapy was ineffective. Conclusions Combination therapy of AIBP, apoA-I, and aflibercept overcomes anti-VEGF resistance in experimental CNV in old mice by inhibiting arteriolar CNV.