Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-Wide Identification of Direct Targets of the TTG1–bHLH–MYB Complex in Regulating Trichome Formation and Flavonoid Accumulation in Arabidopsis Thaliana

Extensive studies have shown that the MBW complex consisting of three kinds of regulatory proteins, MYB and basic helix–loop–helix (bHLH) transcription factors and a WD40 repeat protein, TRANSPARENT TESTA GLABRA1 (TTG1), acts in concert to promote trichome formation and flavonoid accumulation in Arabidopsis thaliana. TTG1 functions as an essential activator in these two biological processes. However, direct downstream targets of the TTG1-dependent MBW complex have not yet been obtained in the two biological processes at the genome-wide level in A. thaliana. In the present study, we found, through RNA sequencing and quantitative real-time PCR analysis, that a great number of regulatory and structural genes involved in both trichome formation and flavonoid accumulation are significantly downregulated in the young shoots and expanding true leaves of ttg1-13 plants. Post-translational activation of a TTG1-glucocorticoid receptor fusion protein and chromatin immunoprecipitation assays demonstrated that these downregulated genes are directly or indirectly targeted by the TTG1-dependent MBW complex in vivo during trichome formation and flavonoid accumulation. These findings further extend our understanding of the role of TTG1-dependent MBW complex in the regulation of trichome formation and flavonoid accumulation in A. thaliana.
Downregulation of MHC Class II by Ubiquitination Is Required for the Migration of CD206+ Dendritic Cells to Skin-Draining Lymph Nodes

Key Points MHCII molecule upregulation is not required for the development of skin moDCs. Skin CD206+ moDCs do not migrate to LNs in the absence of MHCII ubiquitination. GM-CSF restores the migration of skin moDCs by upregulating CCR7 and IRF4. Dendritic cells (DCs) are critical players in skin homeostasis. A subset of mannose receptor (CD206)–expressing monocyte-derived DCs was found in skin, and their migratory counterpart is present in skin-draining lymph nodes (sdLNs). Skin CD206+ DCs were shown to upregulate MHC class II (MHCII) progressively, raising the question of whether this feature affects their biology. In this study, we assessed the role of MHCII regulation in the development and migration of these cells in mouse models expressing differential MHCII levels. Using CD206 as a surrogate marker, we found that skin CD206+ DCs develop in an MHCII-independent manner. However, their migration to sdLNs was affected by overexpression rather than absence or lower expression of MHCII. Accordingly, B16 tumor growth was exacerbated in mice overexpressing MHCII in the absence of ubiquitination. Mechanistically, CD206+ DCs from these mice showed decreased IRF4 and CCR7 expression. LPS, which is known to promote monocyte-derived DC recruitment to sdLNs, partially improved these defects. However, GM-CSF delivery restored CD206+ DC migration by promoting IRF4 expression. Collectively, these data show that MHCII downregulation is crucial for IRF4-dependent migration of CD206+ DCs to sdLNs in health and disease.
Quality of Work Life and Organizational Performance: Workers’ Feelings of Contributing, or Not, to the Organization’s Productivity

This is a pioneering study on the relationship between quality of work life and the employee’s perception of their contribution to organizational performance. It unveils the importance of subjective and behavioral components of quality of work life and their influence on the formation of the collaborator’s individual desire to contribute to strengthening the organization’s productivity. The results obtained indicate that for workers: feeling their supervisors’ support through listening to their concerns and by sensing they take them on board; being integrated in a good work environment; and feeling respected both as professionals and as people; positively influence their feeling of contributing to organizational performance. The results are particularly relevant given the increased weight of services in the labor market, together with intensified automation and digitalization of collaborators’ functions. The findings also contribute to the ongoing debate about the need for more work on the subjective and behavioral components of so-called smart and learning organizations, rather than focusing exclusively on remuneration as the factor stimulating organizational productivity based on the collaborator’s contribution.
UDP‐Glucuronosyltransferase (UGT)‐mediated attenuations of cytochrome P450 3A4 activity: UGT isoform‐dependent mechanism of suppression

Cytochrome P450 (CYP, P450) 3A4 is involved in the metabolism of 50% of drugs and its catalytic activity in vivo is not explained only by hepatic expression levels. We previously demonstrated that UDP‐glucuronosyltransferase (UGT) 2B7 suppressed CYP3A4 activity through an interaction. In the present study, we target UGT1A9 as another candidate modulator of CYP3A4.
The Computational Analysis Conducted on miRNA Target Sites in Association with SNPs at 3’UTR of ADHD-implicated Genes

Background: Attention-deficit/hyperactivity disorder (ADHD) is a frequent chronic neuropsychiatric disorder in which different factors including environmental, genetic, and epigenetic factors play an important role in its pathogenesis. One of the effective epigenetic factors is recognized as MicroRNAs (miRNAs). On the other hand, it has been indicated that the single nucleotide polymorphism (SNPs) present within 3'UTR (3' untranslated region) of mRNAs can influence the regulation of miRNA-mediated gene and susceptibility to a diversity of human diseases. Methods: The purpose of this study was to analyze the SNPs within the 3'UTR of miRNA target genes associated with ADHD . 3'UTR genetic variants were identified in all genes associated with ADHD using DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases. miRNA's target prediction databases were applied in order to predict the miRNA binding sites. 124 SNPs with MAF>0.05 were identified located in the binding site of the miRNA of 35 genes amongst 51 genes associated with ADHD. Results: Bioinformatics analysis predicted 81 MRE (miRNA recognition elements)-creating SNPs, 101 MRE-breaking SNPs, 61 MRE-enhancing SNPs, and finally predicted 41 MRE-decreasing SNPs in the 3'UTR of ADHD-implicated genes. These candidate SNPs within these genes miRNA binding sites can alter the miRNAs binding, and consequently, lead to mRNA gene regulation. Conclusion: Therefore, these miRNA and MRE-SNPs may play important roles in ADHD, and because of that, they would be valuable for further investigation in the field of functional verification.
QUERY METHOD FOR NEAREST REGION OF SPATIAL LINE SEGMENT BASED ON HILBERT CURVE GRID

In order to solve the problem that the existing research results cannot effectively deal with the problem of the nearest region query of spatial line segment in the spatial database, the query method for the nearest region of spatial line segment based on Hilbert curve grids (HLNR) is proposed. The query method is mainly used to find the region which is the nearest neighbor of the line segment. We determine whether there are obstacles between the query line segment and the region set, and two HLNR query methods are proposed. One is the nearest region query method of spatial line segment based on Hilbert curve grid (HLNR query) in the barrier free environment, and the other is the HLNR query method in the obstacle environment (OHLNR query). The query method for HLNR is based on the Hilbert curve and grids characteristics. The query method for OHLNR can filter out a large number of non-candidates and non-effect obstacles in the pruning process. Theoretical research and experimental results show that the query method for nearest region of spatial line segment based on Hilbert curve grids has higher performance in searching.
Mixed Functionalization of Organic Ligands in UiO-66: A Tool to Design Metal–Organic Frameworks for Tailored Microextraction

The mixed-ligand strategy was selected as an approach to tailor a metal–organic framework (MOF) with microextraction purposes. The strategy led to the synthesis of up to twelve UiO-66-based MOFs with different amounts of functionalized terephthalate ligands (H-bdc), including nitro (-NO2) and amino (-NH2) groups (NO2-bdc and NH2-bdc, respectively). Increases of 25% in ligands were used in each case, and different pore environments were thus obtained in the resulting crystals. Characterization of MOFs includes powder X-ray diffraction, infrared spectroscopy, and elemental analysis. The obtained MOFs with different degrees and natures of functionalization were tested as sorbents in a dispersive miniaturized solid-phase extraction (D-µSPE) method in combination with high-performance liquid chromatography (HPLC) and diode array detection (DAD), to evaluate the influence of mixed functionalization of the MOF on the analytical performance of the entire microextraction method. Eight organic pollutants of different natures were studied, using a concentration level of 5 µg· L−1 to mimic contaminated waters. Target pollutants included carbamazepine, 4-cumylphenol, benzophenone-3, 4-tert-octylphenol, 4-octylphenol, chrysene, indeno(1,2,3-cd)pyrene, and triclosan, as representatives of drugs, phenols, polycyclic aromatic hydrocarbons, and disinfectants. Structurally, they differ in size and some of them present polar groups able to form H-bond interactions, either as donors (-NH2) or acceptors (-NO2), permitting us to evaluate possible interactions between MOF pore functionalities and analytes’ groups. As a result, extraction efficiencies can reach values of up to 60%, despite employing a microextraction approach, with four main trends of behavior being observed, depending on the analyte and the MOF.
Tau Misfolding Efficiently Propagates between Individual Intact Hippocampal Neurons

Neurofibrillary tangles, formed of misfolded, hyperphosphorylated tau protein, are a pathological hallmark of several neurodegenerations, including Alzheimer's disease. Tau pathology spreads between neurons and propagates misfolding in a prion-like manner throughout connected neuronal circuits. Tauopathy is accompanied by significant neuronal death, but the relationships between initial tau misfolding, propagation across connected neurons and cytotoxicity remain unclear. Neurofibrillary tangles, formed of misfolded, hyperphosphorylated tau protein, are a pathological hallmark of several neurodegenerations, including Alzheimer's disease. Tau pathology spreads between neurons and propagates misfolding in a prion-like manner throughout connected neuronal circuits. Tauopathy is accompanied by significant neuronal death, but the relationships between initial tau misfolding, propagation across connected neurons and cytotoxicity remain unclear. In particular the immediate functional consequence of tau misfolding for the individual neuron is not well understood. Here, using microfluidic devices to recreate discretely organized neuronal connections, we show that the spread and propagation of misfolded tau between individual murine neurons is rapid and efficient; it occurs within days. The neurons containing and propagating tau pathology display selective axonal transport deficits but remain viable and electrically competent. Therefore, we demonstrate that seed-competent misfolded tau species do not acutely cause cell death, but instead initiate discrete cellular dysfunctions. SIGNIFICANCE STATEMENT Public awareness of progressive neurodegenerations such as dementias associated with aging or repetitive head trauma is rising. Protein misfolding underlies many neurodegenerative diseases including tauopathies, where the misfolded tau protein propagates pathology through connected brain circuits in a prion-like manner. Clinically, these diseases progress over the course of years. Here we show that the underlying protein misfolding propagates rapidly between individual neurons. Presence of misfolded tau is not directly cytotoxic to the neuron; the cells remain viable with limited deficits. This suggests that neurons with tau pathology could be rescued with a therapeutic disease modifier and highlights an under-appreciated time window for such therapeutic intervention.
Therapy Locations in Early Intervention: A Pilot Survey of Parents' and Therapists' Perspectives

Parents and therapists in 7 of Washington's early intervention programs were surveyed about which therapy locations provide the most opportunities for child development and family support. Forty-three parents and 59 therapists working in more than one therapy location completed and returned the questionnaires. The majority of respondents perceived the center as providing the most opportunities for child development, whereas there was no substantial difference in ratings between the home and the center as providing the most opportunities for family support. Therapy in community locations was perceived as providing the least amount of opportunities for child development and for family support. Qualitative data highlighted the importance of parent choice and professional opinion when deciding therapy locations.
SERF engages in a fuzzy complex that accelerates primary nucleation of amyloid proteins

Significance Although amyloids are the hallmarks for several neurodegenerative diseases, it is becoming evident that small oligomers are the toxic species leading to disease rather than the amyloids themselves. The vital first step of amyloid formation, primary nucleation, is difficult to monitor, making it relatively underexplored. Here we combine aggregation assays and cutting-edge native mass spectrometry to study the recently discovered and very highly conserved protein SERF in its unusual ability to accelerate primary nucleation of disease-related amyloid-prone proteins. We find that SERF exhibits a high degree of plasticity and forms fuzzy, highly extended complexes with amyloid-prone proteins. Our findings suggest that proteins are much more structurally diverse in the early stages of amyloid formation than previously assumed. The assembly of small disordered proteins into highly ordered amyloid fibrils in Alzheimer’s and Parkinson’s patients is closely associated with dementia and neurodegeneration. Understanding the process of amyloid formation is thus crucial in the development of effective treatments for these devastating neurodegenerative diseases. Recently, a tiny, highly conserved and disordered protein called SERF was discovered to modify amyloid formation in Caenorhabditis elegans and humans. Here, we use kinetics measurements and native ion mobility-mass spectrometry to show that SERF mainly affects the rate of primary nucleation in amyloid formation for the disease-related proteins Aβ40 and α-synuclein. SERF’s high degree of plasticity enables it to bind various conformations of monomeric Aβ40 and α-synuclein to form structurally diverse, fuzzy complexes. This structural diversity persists into early stages of amyloid formation. Our results suggest that amyloid nucleation is considerably more complex than age-related conversion of Aβ40 and α-synuclein into single amyloid-prone conformations.
iEEGview: an open-source multifunction GUI-based Matlab toolbox for localization and visualization of human intracranial electrodes

Objective. The precise localization of intracranial electrodes is a fundamental step relevant to the analysis of intracranial electroencephalography (iEEG) recordings in various fields. With the increasing development of iEEG studies in human neuroscience, higher requirements have been posed on the localization process, resulting in urgent demand for more integrated, easy-operation and versatile tools for electrode localization and visualization. With the aim of addressing this need, we develop an easy-to-use and multifunction toolbox called iEEGview, which can be used for the localization and visualization of human intracranial electrodes. Approach. iEEGview is written in Matlab scripts and implemented with a GUI. From the GUI, by taking only pre-implant MRI and post-implant CT images as input, users can directly run the full localization pipeline including brain segmentation, image co-registration, electrode reconstruction, anatomical information identification, activation map generation and electrode projection from native brain space into common brain space for group analysis. Additionally, iEEGview implements methods for brain shift correction, visual location inspection on MRI slices and computation of certainty index in anatomical label assignment. Main results. All the introduced functions of iEEGview work reliably and successfully, and are tested by images from 28 human subjects implanted with depth and/or subdural electrodes. Significance. iEEGview is the first public Matlab GUI-based software for intracranial electrode localization and visualization that holds integrated capabilities together within one pipeline. iEEGview promotes convenience and efficiency for the localization process, provides rich localization information for further analysis and offers solutions for addressing raised technical challenges. Therefore, it can serve as a useful tool in facilitating iEEG studies.
Self-Healing Electrode with High Electrical Conductivity and Mechanical Strength for Artificial Electronic Skin.

The self-healing electrode is an electrical conductor that can recover internal damage by itself like human skin. Since self-healing electrodes are based on polymers and hydrogels, it is still limited in low electrical conductivity and mechanical strength. Herein, we designed an electrically conductive, mechanically strong and printable self-healing electrode using liquid crystal graphene oxide (LCGO) and silver nanowires (AgNWs). The conductive ink was easily prepared by simply mixing LCGO and AgNWs solutions. The ultrathin (3 m thick) electrode can be printed in various shapes such as a butterfly in a freestanding state. The maximum conductivity and strength of the LCGO/AgNWs composite were 17,800 S/cm and 4.2 MPa, values that are respectively 24 and 4 times higher than for a previous self-healing electrode. The LCGO/AgNWs composite has self-healed internal damage in ambient condition with moisture, and consequently recovered 96.8% of its electrical conductivity and 95% of its mechanical toughness compared to undamaged state. The electrical properties of the composite exhibited a metallic tendency. Therefore, these results suggest that the composite can be used as an artificial electronic skin that detects environmental conditions such as compression and temperature. The self-healing artificial electronic skin could be applied to human condition monitoring and robotic sensing systems.
Modeling the dynamics of Plasmodium falciparum gametocytes in humans during malaria infection

Renewed efforts to eliminate malaria have highlighted the potential to interrupt human-to-mosquito transmission — a process mediated by gametocyte kinetics in human hosts. Here we study the in vivo dynamics of Plasmodium falciparum gametocytes by establishing a framework which incorporates improved measurements of parasitemia, a novel gametocyte dynamics model and model fitting using Bayesian hierarchical inference. We found that the model provides an excellent fit to the clinical data from 17 volunteers infected with P. falciparum (3D7 strain) and reliably predicts observed gametocytemia. We estimated the sexual commitment rate and gametocyte sequestration time to be 0.54% (95% credible interval: 0.30–1.00%) per asexual replication cycle and 8.39 (6.54–10.59) days respectively. We used the data-calibrated model to investigate human-to-mosquito transmissibility, providing a method to link within-human host infection kinetics to epidemiological-scale infection and transmission patterns.
Parent-Reported Personality and Weight Transitions Across Adolescence.

Background: Adolescence is a critical transition point for body weight. Personality traits are associated consistently with weight and obesity risk in adulthood. We examined whether personality, particularly Conscientiousness (the tendency to be organized, disciplined, and responsible), is associated with weight outcomes between ages 13 and 17. Methods: Data are drawn from the Growing Up in Ireland suites of studies. Parents rated their child's personality at age 13, and trained staff measured weight and height at ages 13 and 17 (N = 4962). Logistic regression was used to predict risk of incident obesity and obesity remission between ages 13 and 17. Results: Among children who were not in the obesity category at age 13, higher Conscientiousness was associated with lower risk of moving into the obesity category by age 17, and, among children with obesity at age 13, Conscientiousness was associated with greater likelihood of moving to the nonobesity category by age 17. These associations were independent of sociodemographic characteristics, parent body mass index, and were similar across gender. The other five-factor model personality traits were unrelated to weight outcomes. Conclusions: Conscientiousness is one trait psychological factor implicated in weight transitions across a critical period during adolescence.
Parallels between stream and coastal water quality associated with groundwater discharge

Groundwater-surface water interactions drive water quality in both streams and the coastal ocean, where groundwater discharge occurs in streams as baseflow and along the coastline as submarine groundwater discharge (SGD). Groundwater contributions to streams and to the coastal ocean were quantified in three urban streams in Kāneʻohe Watershed, Hawaiʻi. We used radon as a groundwater tracer to show that baseflow contributions to streams ranged from 22 to 68% along their reaches leading to the coast of Kāneʻohe Bay. Total SGD was 4,500, 18,000, and 23,000 m3/day for the northwest, central, and southern sectors of the bay, respectively. Total groundwater (stream baseflow + SGD) dissolved nutrient fluxes were significantly greater than those sourced from stream surface runoff. The studied streams exhibited increasing nutrient levels downstream from groundwater inputs with high nutrient concentrations, negatively impacting coastal water quality. SGD dynamics were also assessed during the anomalously high perigean spring tides in 2017, where SGD was four times greater during the perigean spring tide compared to a spring tide and resulted in strong shifts in N:P ratios, suggesting that rising sea level stands may disrupt primary productivity with greater frequency. This study demonstrates the importance of considering baseflow inputs to streams to coastal groundwater budgets and suggests that coastal water quality may be improved through management and reduction of groundwater contaminants.