Miracle-dz/UniFAR-FTUs huggingface dataset:
Chromatin Remodelers Interact with Eya1 and Six2 to Target Enhancers to Control Nephron Progenitor Cell Maintenance

Significance Statement Understanding how the precise gene expression states that define nephron progenitor cell identity are established and maintained is crucial for developing approaches to repair or regenerate the damaged nephron. Combination of Eya1-Six1/2 has been explored in inducing nephron progenitor–like cell reprogramming. This study uncovers a critical role for chromatin-remodeling SWI/SNF complex through interactions with Eya1-Six2 in nephron fate induction and maintenance and identifies critical factors, including Pbx1, as direct targets of SWI/SNF and Eya1-Six2. The properties of chromatin remodelers as transcriptional coregulators and Pbx1 in hematopoietic stem cell self-renewal suggest that they may be combined with Eya1-Six1/2 in reprogramming nephrons. Background Eya1 is a critical regulator of nephron progenitor cell specification and interacts with Six2 to promote NPC self-renewal. Haploinsufficiency of these genes causes kidney hypoplasia. However, how the Eya1-centered network operates remains unknown. Methods We engineered a 2×HA-3×Flag-Eya1 knock-in mouse line and performed coimmunoprecipitation with anti-HA or -Flag to precipitate the multitagged-Eya1 and its associated proteins. Loss-of-function, transcriptome profiling, and genome-wide binding analyses for Eya1's interacting chromatin-remodeling ATPase Brg1 were carried out. We assayed the activity of the cis-regulatory elements co-occupied by Brg1/Six2 in vivo. Results Eya1 and Six2 interact with the Brg1-based SWI/SNF complex during kidney development. Knockout of Brg1 results in failure of metanephric mesenchyme formation and depletion of nephron progenitors, which has been linked to loss of Eya1 expression. Transcriptional profiling shows conspicuous downregulation of important regulators for nephrogenesis in Brg1-deficient cells, including Lin28, Pbx1, and Dchs1-Fat4 signaling, but upregulation of podocyte lineage, oncogenic, and cell death–inducing genes, many of which Brg1 targets. Genome-wide binding analysis identifies Brg1 occupancy to a distal enhancer of Eya1 that drives nephron progenitor–specific expression. We demonstrate that Brg1 enrichment to two distal intronic enhancers of Pbx1 and a proximal promoter region of Mycn requires Six2 activity and that these Brg1/Six2-bound enhancers govern nephron progenitor–specific expression in response to Six2 activity. Conclusions Our results reveal an essential role for Brg1, its downstream pathways, and its interaction with Eya1-Six2 in mediating the fine balance among the self-renewal, differentiation, and survival of nephron progenitors.
Enthusiastic but Inconsistent: Graduate Teaching Assistants’ Perceptions of Their Role in the CURE Classroom

Despite growing evidence of positive student outcomes from course-based undergraduate research experiences (CUREs), little consideration has been given to employing graduate teaching assistants (GTAs) as CURE instructors. GTAs may be novice researchers and/or teachers and likely vary in their interest in teaching a CURE. Guided by expectancy-value theory, we explored how GTAs’ self-efficacy and values regarding teaching a CURE impact motivation and perceptions of their roles as CURE instructors. Using a multiple case study design, we interviewed nine GTAs who taught a network CURE at one research institution. Though most GTAs held a relatively high value for teaching a CURE for a range of reasons, some GTAs additionally perceived high costs associated with teaching the CURE. Through the interview data, we established three profiles to describe GTA perceptions of their role as CURE instructors: “Student Supporters,” “Research Mentors,” and “Content Deliverers. ” Those implementing GTA-led CUREs should consider that GTAs likely have different perceptions of both their role in the classroom and the associated costs of teaching a CURE. The variability in GTA perceptions of CUREs implies that undergraduate students of different GTAs are unlikely to experience the CURE equivalently.
Supervised Multisensory Calibration Signals Are Evident in VIP But Not MSTd

Multisensory plasticity enables our senses to dynamically adapt to each other and the external environment, a fundamental operation that our brain performs continuously. We searched for neural correlates of adult multisensory plasticity in the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP) in 2 male rhesus macaques using a paradigm of supervised calibration. We report little plasticity in neural responses in the relatively low-level multisensory cortical area MSTd. In contrast, neural correlates of plasticity are found in higher-level multisensory VIP, an area with strong decision-related activity. Accordingly, we observed systematic shifts of VIP tuning curves, which were reflected in the choice-related component of the population response. This is the first demonstration of neuronal calibration, together with behavioral calibration, in single sessions. These results lay the foundation for understanding multisensory neural plasticity, applicable broadly to maintaining accuracy for sensorimotor tasks. SIGNIFICANCE STATEMENT Multisensory plasticity is a fundamental and continual function of the brain that enables our senses to adapt dynamically to each other and to the external environment. Yet, very little is known about the neuronal mechanisms of multisensory plasticity. In this study, we searched for neural correlates of adult multisensory plasticity in the dorsal medial superior temporal area (MSTd) and the ventral intraparietal area (VIP) using a paradigm of supervised calibration. We found little plasticity in neural responses in the relatively low-level multisensory cortical area MSTd. By contrast, neural correlates of plasticity were found in VIP, a higher-level multisensory area with strong decision-related activity. This is the first demonstration of neuronal calibration, together with behavioral calibration, in single sessions.
Detangling the mechanisms and timing of MHC‐dependent sexual selection using Soay sheep

Immune defence is a key component of fitness, and individuals are expected to have evolved preferences for mates that ensure immunocompetent offspring. Potential preferences include those for mates with specific heritable immune gene profiles (“good genes”) or for immunogenetically dissimilar mates to increase offspring immune gene diversity. The major histocompatibility complex (MHC) is by far the most investigated immune gene in mate choice studies, but we still know very little about its role in sexual selection for genetic benefits. In this issue of Molecular Ecology, Huang et al. capitalize on the extraordinary wealth of behavioural, life history and genetic/genomic data from the free‐living Soay sheep population on the Island of Hirta to address this problem. While the authors find evidence of both pre‐ and postcopulatory MHC‐based sexual selection, postcopulatory MHC‐dissimilar mate choice is indistinguishable from genome‐wide effects, suggesting it is a byproduct of inbreeding avoidance in Soay sheep. The study's comprehensive sampling ensures that inferences are generalizable to the entire population and provides a gold standard for studies investigating immune gene‐based sexual selection.
A Learning-Based Stable Servo Control Strategy Using Broad Learning System Applied for Microrobotic Control

As the controller parameter adjustment process is simplified significantly by using learning algorithms, the studies about learning-based control attract a lot of interest in recent years. This article focuses on the intelligent servo control problem using learning from desired demonstrations. Compared with the previous studies about the learning-based servo control, a control policy using the broad learning system (BLS) is developed and first applied to a microrobotic system, since the advantages of the BLS, such as simple structure and no-requirement for retraining when new demos’ data is provided. Then, the Lyapunov theory is skillfully combined with the complex learning algorithm to derive the controller parameters’ constraints. Thus, the final control policy not only can obtain the movement skills of the desired demonstrations but also have the strong ability of generalization and error convergence. Finally, simulation and experimental examples verify the effectiveness of the proposed strategy using MATLAB and a microswimmer trajectory tracking system.
Psychosocial Contributors to Depressive Symptoms in Hispanic Patients With Type 2 Diabetes

Purpose The purpose of this study is to identify psychosocial factors associated with depressive symptoms in Hispanic patients with diabetes and explore the extent to which their effects may vary by gender and acculturation. Methods The authors completed a secondary analysis of data from 247 Hispanic adults with type 2 diabetes. Gender and language groups were compared using chi-square and t tests. Hierarchical multiple regression was used to examine associations of depressive symptoms with perceived support, diabetes-related distress, and social and personal factors. Results Women reported less support than men. English speakers reported more depressive symptoms than Spanish speakers. When adjusting for age, gender, and acculturation, psychosocial factors significantly associated with depressive symptoms included less support received, greater emotional burden, and less ability to socialize or pursue normal activities because of diabetes. Conclusions Social support provided by family among less acculturated Hispanics may play an important role in reducing emotional burden and lowering the risk of comorbid depression. The quality of interpersonal relationships and the ability to continue normal activities may also be important. More acculturated Hispanic women with diabetes may be at greater risk for comorbid depression and worse health outcomes. Screening for depression and assessment of support needs is warranted for Hispanic women.
Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients With Advanced/Metastatic Solid Tumors or Lymphomas.

PURPOSE This phase I study assessed the safety, pharmacokinetics, and efficacy of MIW815 (ADU-S100), a novel synthetic cyclic dinucleotide that activates the stimulator of interferon genes (STING) pathway, in patients with advanced/metastatic cancers. EXPERIMENTAL DESIGN Patients (n = 47) received weekly intratumoral injections of MIW815, 50-6400 μg, 3-weeks-on/1-week-off. RESULTS A maximum tolerated dose was not reached. Most common treatment-related adverse events were pyrexia (17%), chills, and injection site pain (15%). MIW815 was rapidly absorbed from the injection site with dose-proportional pharmacokinetics, a rapid terminal plasma half-life (~24 minutes) and high interindividual variability. One patient had a partial response (Merkel cell carcinoma); two patients had unconfirmed partial responses (parotid cancer; myxofibrosarcoma). Lesion size was stable or decreased in 94% of evaluable, injected lesions. RNA expression and immune infiltration assessments in paired tumor biopsies did not reveal significant on-treatment changes. However, increases in inflammatory cytokines and peripheral blood T-cell clonal expansion suggested systemic immune activation. CONCLUSIONS MIW815 was well tolerated in patients with advanced/metastatic cancers. Clinical activity of single-agent MIW815 was limited in this first-in-human study, however, evidence of systemic immune activation was seen.
Light microscopic and heterogeneity analysis of astrocytes in the common marmoset brain

Astrocytes are abundant cells of the central nervous system (CNS) and are involved in processes including synapse formation/function, ion homeostasis, neurotransmitter uptake, and neurovascular coupling. Recent evidence indicates that astrocytes show diverse molecular, structural, and physiological properties within the CNS. This heterogeneity is reflected in differences in astrocyte structure, gene expression, functional properties, and responsiveness to injury/pathological conditions. Deeper investigation of astrocytic heterogeneity is needed to understand how astrocytes are configured to enable diverse roles in the CNS. While much has been learned about astrocytic heterogeneity in rodents, much less is known about astrocytic heterogeneity in the primate brain where astrocytes have greater size and complexity. The common marmoset (Callithrix jacchus) is a promising non‐human primate model because of similarities between marmosets and humans with respect to genetics, brain anatomy, and cognition/behavior. Here, we investigated the molecular and structural heterogeneity of marmoset astrocytes using an array of astrocytic markers, multi‐label confocal microscopy, and quantitative analysis. We used male and female marmosets and found that marmoset astrocytes show differences in expression of astrocytic markers in cortex, hippocampus, and cerebellum. These differences were accompanied by intra‐regional variation in expression of markers for glutamate/GABA transporters, and potassium and water channels. Differences in astrocyte structure were also found, along with complex interactions with blood vessels, microglia, and neurons. This study contributes to our knowledge of the cellular and molecular features of marmoset astrocytes and is useful for understanding the complex properties of astrocytes in the primate CNS.
Plasmatic endocannabinoids are decreased in subjects with ultra‐high risk of psychosis

The onset of frank psychosis is usually preceded by a prodromal phase characterized by attenuated psychotic symptoms. Currently, research on schizophrenia prodromal phase (ultra‐high risk for psychosis [UHR]) has focused on the risk of developing psychosis, on the transition to full blown psychosis and on its prediction. Neurobiological differences between UHR individuals who fully recover (remitters) versus those who show persistent/progressive prodromal symptoms (nonremitters) have been little explored. The endocannabinoid system constitutes a neuromodulatory system that plays a major role in brain development, synaptic plasticity, emotional behaviours and cognition. It comprises two cannabinoid receptors (CB1/CB2), two endocannabinoid ligands, arachidonylethanolamide (AEA) and 2‐arachidonoylglycerol (2AG) along with their inactivation enzymes. Despite much evidence that the endocannabinoid system is imbalanced during psychosis, very little is known about it in UHR. Therefore, we aimed to quantify the plasma endocannabinoid levels in UHR and healthy controls (HC) and verify if these metabolites could differentiate between remitters and nonremitters. Circulating concentrations of AEA (p = .003) and 2AG (p < .001) were lower in UHR when compared with HC, with no difference between remitters and nonremitters. Regarding clinical evolution, it was observed that out of 91 UHRs initially considered, 16 had psychiatric complaints (3 years of follow‐up). Considering those subjects, there were weak correlations between clinical parameters and plasma concentrations of endocannabinoids. Our results suggest that the endocannabinoids are imbalanced before frank psychosis and that changes can be seen in plasma of UHR individuals. These molecules proved to be potential biomarkers to identify individuals in the prodromal phase of psychosis.
Reporting of recombinant adenovirus-based COVID-19 vaccine adverse events in online versions of three highly circulated US newspapers

ABSTRACT Newspapers’ reporting of adverse vaccine events may influence their readers vaccination behaviors. The purpose of this study was to examine the nature and extent of coverage of Johnson and Johnson (J & J) vaccine’s adverse events reported in the online versions of the three most widely circulated US daily newspapers from April 13–25, 2021. Articles were identified in published online versions of the three most widely cited newspapers in the United States, using several databases. Dedoose software was used to apply a mixed methods approach to the 110 articles identified. The seven overarching themes were as follows: (1) J & J vaccine characteristics (n = 78); (2) Description of the adverse events (n = 183); (3) Emphasis that it is a rare event and vaccine is still safe (n = 89); (4) Health authorities’ investigation (n = 55); (5) Pause in administering J & J vaccine (n = 83); (6) Vaccine fear and anxiety and increased hesitancy (n = 58); (7) J & J role and impact (n = 108). Each theme included a series of subthemes. Overall, the newspaper coverage was aligned with handling of the pause from authoritative health agencies in the US. The findings of this study help to better understand how the US media covered adverse events related to the J & J vaccine, and provides insight for public health professionals regarding acceptance COVID-19 vaccines. Monitoring media coverage related to vaccine adverse events may help public health officials to develop new approaches to adequately inform the public, prevent misinformation, and maintain the optimal vaccination uptake.
Detection of PKD1 and PKD2 Somatic Variants in Autosomal Dominant Polycystic Kidney Cyst Epithelial Cells by Whole-Genome Sequencing

Visual Abstract Significance Statement Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2 (PKD1/2) in renal tubular epithelium. PKD1/2 somatic mutations were previously implicated in cyst formation, but studies of this second-hit model in ADPKD had significant technical limitations. Comprehensive analysis of renal cyst epithelium by whole-genome sequencing identified pathogenic inactivating somatic mutations of PKD1/2 in all 24 patients and in 93% of their 90 cysts. Short variant mutations occurred in 77% of cysts, and another 18% acquired chromosomal loss of heterozygosity encompassing PKD1/2, frequently at chromosomal fragile sites or in regions comprising chromosome microdeletion diseases/syndromes. These findings support a cellular recessive mechanism for renal cystogenesis in ADPKD caused by inactivating germline and somatic variants of PKD1/2. Background Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the development of multiple cysts in the kidneys. It is often caused by pathogenic mutations in PKD1 and PKD2 genes that encode polycystin proteins. Although the molecular mechanisms for cystogenesis are not established, concurrent inactivating germline and somatic mutations in PKD1 and PKD2 have been previously observed in renal tubular epithelium (RTE). Methods To further investigate the cellular recessive mechanism of cystogenesis in RTE, we conducted whole-genome DNA sequencing analysis to identify germline variants and somatic alterations in RTE of 90 unique kidney cysts obtained during nephrectomy from 24 unrelated participants. Results Kidney cysts were overall genomically stable, with low burdens of somatic short mutations or large-scale structural alterations. Pathogenic somatic “second hit” alterations disrupting PKD1 or PKD2 were identified in 93% of the cysts. Of these, 77% of cysts acquired short mutations in PKD1 or PKD2; specifically, 60% resulted in protein truncations (nonsense, frameshift, or splice site) and 17% caused non-truncating mutations (missense, in-frame insertions, or deletions). Another 18% of cysts acquired somatic chromosomal loss of heterozygosity (LOH) events encompassing PKD1 or PKD2 ranging from 2.6 to 81.3 Mb. 14% of these cysts harbored copy number neutral LOH events, while the other 3% had hemizygous chromosomal deletions. LOH events frequently occurred at chromosomal fragile sites, or in regions comprising chromosome microdeletion diseases/syndromes. Almost all somatic “second hit” alterations occurred at the same germline mutated PKD1/2 gene. Conclusions These findings further support a cellular recessive mechanism for cystogenesis in ADPKD primarily caused by inactivating germline and somatic variants of PKD1 or PKD2 genes in kidney cyst epithelium.
Individual tree damage dominates mortality risk factors across six tropical forests.

The relative importance of tree mortality risk factors remains unknown, especially in diverse tropical forests where species may vary widely in their responses to particular conditions. We present a new framework for quantifying the importance of mortality risk factors and apply it to compare 19 risks on 31,203 trees (1,977 species) in 14 one-year periods in six tropical forests. We defined a condition as a risk factor for a species if it was associated with at least a doubling of mortality rate in univariate analyses. For each risk, we estimated prevalence (frequency), lethality (difference in mortality between trees with and without the risk), and impact ("excess mortality" associated with the risk, relative to stand-level mortality). The most impactful risk factors were light limitation and crown/trunk loss; the most prevalent were light limitation and small size; the most lethal were leaf damage and wounds. Modes of death (standing, broken, and uprooted) had limited links with previous conditions and mortality risk factors. We provide the first ranking of importance of tree-level mortality risk factors in tropical forests. Future research should focus on the links between these risks, their climatic drivers, and the physiological processes to enable mechanistic predictions of future tree mortality.
A Multi-Scale Progressive Collaborative Attention Network for Remote Sensing Fusion Classification

With the development of remote sensing technology, panchromatic images (PANs) and multispectral images (MSs) can be easily obtained. PAN has higher spatial resolution, while MS has more spectral information. So how to use the two kinds of images’ characteristics to design a network has become a hot research field. In this article, a multi-scale progressive collaborative attention network (MPCA-Net) is proposed for PAN and MS’s fusion classification. Compared to the traditional multi-scale convolution operations, we adopt an adaptive dilation rate selection strategy (ADR-SS) to adaptively select the dilation rate to deal with the problem of category area’s excessive scale differences. For the traditional pixel-by-pixel sliding window sampling strategy, the patches which are generated by adjacent pixels but belonging to different categories contain a considerable overlap of information. So we change original sampling strategy and propose a center pixel migration (CPM) strategy. It migrates the center pixel to the most similar position of the neighborhood information for classification, which reduces network confusion and increases its stability. Moreover, due to the different spatial and spectral characteristics of PAN and MS, the same network structure for the two branches ignores their respective advantages. For a certain branch, as the network deepens, characteristic has different representations in different stages, so using the same module in multiple feature extraction stages is inappropriate. Thus we carefully design different modules for each feature extraction stage of the two branches. Between the two branches, because the strong mapping methods of directly cascading their features are too rough, we design collaborative progressive fusion modules to eliminate the differences. The experimental results verify that our proposed method can achieve competitive performance.