Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of Exocyst Function in Pollen Tube Growth by Phosphorylation of Exocyst Subunit EXO70C2

Exocyst is a heterooctameric protein complex crucial for the tethering of secretory vesicles to the plasma membrane during exocytosis. Compared to other eukaryotes, exocyst subunit EXO70 is represented by many isoforms in land plants whose cell biological and biological roles, as well as modes of regulation remain largely unknown. Here, we present data on the phospho-regulation of exocyst isoform EXO70C2, which we previously identified as a putative negative regulator of exocyst function in pollen tube growth. A comprehensive phosphoproteomic analysis revealed phosphorylation of EXO70C2 at multiple sites. We have now performed localization and functional studies of phospho-dead and phospho-mimetic variants of Arabidopsis EXO70C2 in transiently transformed tobacco pollen tubes and stably transformed Arabidopsis wild type and exo70C2 mutant plants. Our data reveal a dose-dependent effect of AtEXO70C2 overexpression on pollen tube growth rate and cellular architecture. We show that changes of the AtEXO70C2 phosphorylation status lead to distinct outcomes in wild type and exo70c2 mutant cells, suggesting a complex regulatory pattern. On the other side, phosphorylation does not affect the cytoplasmic localization of AtEXO70C2 or its interaction with putative secretion inhibitor ROH1 in the yeast two-hybrid system.
Rapid Gardos Hereditary Xerocytosis Diagnosis in 8 Families Using Reticulocyte Indices

Gardos channelopathy (Gardos-HX) or type 2 stomatocytosis/xerocytosis is a hereditary hemolytic anemia due to mutations in the KCNN4 gene. It is rarer than inherited type 1 xerocytosis due to PIEZO1 mutations (Piezo1-HX) and its diagnosis is difficult given the absence of a specific clinical or biological phenotype. We report here that this diagnosis can be sped up using red blood cell (RBC) indices performed on an ADVIA 2120 (Siemens®) analyzer, which measures reticulocyte mean corpuscular volume (rMCV) and mean corpuscular hemoglobin concentration (rMCHC). We studied reticulocyte indices in 3 new and 12 described patients (8 families) with Gardos-HX, 11 subjects presented the recurrent p.Arg352His mutation, 4 cases (two families) carried a private KCNN4 mutation. They were compared to 79 described patients (49 families) with Piezo1-HX. Surprisingly, in Gardos-HX cases, rMCV revealed to be smaller than MCV and rMCHC higher than MCHC, in contrast with normal or Piezo1-HX RBC. Consequently, ΔMCV (rMCV-MCV) was −0.9 ± 5 fL vs. 19.8 ± 3 fL (p < 0.001) in Gardos compared with Piezo1-HX and ΔMCHC (rMCHC-MCHC) was 18.7 ± 13 vs. −50 ± 8.7 g/L (p < 0.001). A threshold of 8.6 fL for ΔMCV and −5.5 g/L for ΔMCHC could discriminate between Gardos and Piezo1-HX with 100% sensitivity and specificity, regardless of age, mutation or splenectomy status. Consequently, we showed that reticulocytes indices are useful to suggest Gardos-HX on blood count results, allowing to rapidly target these patients for gene analysis. In addition, these parameters may prove useful as a ‘functional tool’ in interpreting new KCNN4 variants.
Organic Acids as Alternatives for Antibiotic Growth Promoters Alter the Intestinal Structure and Microbiota and Improve the Growth Performance in Broilers

The present study aimed to investigate the effects of organic acids (OA) as alternatives for antibiotic growth promoters (AGP) on growth performance, intestinal structure, as well as intestinal microbial composition and short-chain fatty acids (SCFAs) profiles in broilers. A total of 336 newly hatched male Arbor Acres broiler chicks were randomly allocated into 3 dietary treatments including the basal diet [negative control (NC)], the basal diet supplemented with 5 mg/kg flavomycin, and the basal diet supplemented with OA feed additives. Each treatment had eight replicates with 14 birds each. The results showed that AGP and OA promoted growth during day 22–42 compared with the NC group (P < 0.05). OA significantly increased the jejunal goblet cell density and ileal villus height on day 42 compared with the NC group (P < 0.05). Meanwhile, OA up-regulated the mRNA expression of jejunal barrier genes (Claudin-3 and ZO-1) relative to the NC group (P < 0.05). Significant changes of microbiota induced by the OA were also found on day 42 (P < 0.05). Several SCFAs-producing bacteria like Ruminococcaceae, Christensenellaceae, and Peptococcaceae affiliated to the order Clostridiales were identified as biomarkers of the OA group. Higher concentrations of SCFAs including formic acid and butyric acid were observed in the cecum of OA group (P < 0.05). Simultaneously, the abundance of family Ruminococcaceae showed highly positive correlations with the body weight and mRNA level of ZO-1 on day 42 (P < 0.05). However, AGP supplementation had the higher mRNA expression of Claudin-2, lower goblet cell density of jejunum, and decreased Firmicutes to Bacteroidetes ratio, suggesting that AGP might have a negative impact on intestinal immune and microbiota homeostasis. In conclusion, the OA improved growth performance, intestinal morphology and barrier function in broilers, which might be attributed to the changes of intestinal microbiota, particularly the enrichment of SCFAs-producing bacteria, providing a more homeostatic and healthy intestinal microecology.
Functional Characterization of Two Thioredoxin Proteins of Toxoplasma gondii Using the CRISPR-Cas9 System

Toxoplasmosis caused by infection with Toxoplasma gondii is an important parasitic zoonosis with a worldwide distribution. In this study, we examined the functions of two thioredoxins (namely CTrp26 and CTrx1) of T. gondii tachyzoites by generation of HA tag strains or gene deficient parasites in Type I RH strain (ToxoDB#10). Immunofluorescence analysis (IFA) was used to investigate the subcellular localization of the thioredoxins (Trxs). Results of IFA showed that both CTrp26 and CTrx1 were located in the cytoplasm of T. gondii. Functional characterizations of CTrp26 and CTrx1-deficient parasites were performed by plaque assay, intracellular replication, egress, H2O2 resistance, detection of reactive oxygen species (ROS) level and total antioxidant capacity (T-AOC) assays in vitro, as well as mouse infection in vivo. Our results showed that deletion of CTrp26 or CTrx1 did not influence the ability of T. gondii RH strain to replicate, egress, form plaque, resist H2O2 exposure, maintain the ROS level, and T-AOC, and also did not serve as virulence factors in Kunming mice. Taken together, these results provide new properties of the two Trxs. Although they are not essential for RH strain, they may have roles in other strains of this parasite due to their different expression patterns, which warrants future research.
Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics

Cancer is a set of complex pathologies that has been recognized as a major public health problem worldwide for decades. A myriad of therapeutic strategies is indeed available. However, the wide variability in tumor physiology, response to therapy, added to multi-drug resistance poses enormous challenges in clinical oncology. The last years have witnessed a fast-paced development of novel experimental and translational approaches to therapeutics, that supplemented with computational and theoretical advances are opening promising avenues to cope with cancer defiances. At the core of these advances, there is a strong conceptual shift from gene-centric emphasis on driver mutations in specific oncogenes and tumor suppressors—let us call that the silver bullet approach to cancer therapeutics—to a systemic, semi-mechanistic approach based on pathway perturbations and global molecular and physiological regulatory patterns—we will call this the shrapnel approach. The silver bullet approach is still the best one to follow when clonal mutations in driver genes are present in the patient, and when there are targeted therapies to tackle those. Unfortunately, due to the heterogeneous nature of tumors this is not the common case. The wide molecular variability in the mutational level often is reduced to a much smaller set of pathway-based dysfunctions as evidenced by the well-known hallmarks of cancer. In such cases “shrapnel gunshots” may become more effective than “silver bullets”. Here, we will briefly present both approaches and will abound on the discussion on the state of the art of pathway-based therapeutic designs from a translational bioinformatics and computational oncology perspective. Further development of these approaches depends on building collaborative, multidisciplinary teams to resort to the expertise of clinical oncologists, oncological surgeons, and molecular oncologists, but also of cancer cell biologists and pharmacologists, as well as bioinformaticians, computational biologists and data scientists. These teams will be capable of engaging on a cycle of analyzing high-throughput experiments, mining databases, researching on clinical data, validating the findings, and improving clinical outcomes for the benefits of the oncological patients.
Dynamics of ataxin-1 in spinocerebellar ataxia type 1

Background. Polyglutamine expansion disorders are caused by an expansion of the polyglutamine (polyQ) tract in the disease related protein, leading to severe neurodegeneration. All polyQ disorders are hallmarked by the presence of intracellular aggregates containing the expanded protein in affected neurons. The polyQ disorder SpinoCerebellar Ataxia 1 (SCA1) is caused by a polyQ-expansion in the ataxin-1 protein, which is thought to lead to nuclear aggregates. Methodology/Principal Findings. Using advanced live cell fluorescence microscopy and a filter retardation assay we show that nuclear accumulations formed by polyQ-expanded ataxin-1 do not resemble aggregates of other polyQ-expanded proteins. Instead of being static, insoluble aggregates, nuclear accumulations formed by the polyQ-expanded ataxin-1 showed enhanced intracellular kinetics as compared to wild-type ataxin-1. During mitosis, ataxin-1 accumulations redistributed equally among daughter cells, in contrast to polyQ aggregates. Interestingly, polyQ expansion did not affect the nuclear-cytoplasmic shuttling of ataxin-1 as proposed before. Conclusions/Significance. These results indicate that polyQ expansion does not necessarily lead to aggregate formation, and that the enhanced kinetics may affect the nuclear function of ataxin-1. The unexpected findings for a polyQ-expanded protein and their consequences for ongoing SCA1 research are discussed.
When a Circle Becomes the Letter O: Young Children’s Conceptualization of Learning and Its Relation With Theory of Mind Development

In two independent yet complementary studies, the current research explored the developmental changes of young children’s conceptualization of learning, focusing the role of knowledge change and learning intention, and its association with their developing theory of mind (ToM) ability. In study 1, 75 children between 48 and 86 months of age (M = 65.45, SD = 11.45, 36 girls) judged whether a character with or without a genuine knowledge change had learned. The results showed that younger children randomly attributed learning between genuine knowledge change and accidental coincidence that did not involve knowledge change. Children’s learning judgments in familiar contexts improved with age and correlated with their ToM understanding. However, the correlation was no longer significant once age was held constant. Another sample of 72 children aged between 40 and 90 months (M = 66.87, SD = 11.83, 31 girls) participated in study 2, where children were asked to judge whether the story protagonists intended to learn and whether they eventually learned. The results suggested that children over-attributed learning intention to discovery and implicit learning. Stories with conflict between the learning intention and outcome appeared to be most challenging for children. Children’s intention judgment was correlated with their ToM understanding, and ToM marginally predicted intention judgment when the effect of age was accounted for. The implication of the findings for school readiness was discussed. Training studies and longitudinal designs in the future are warranted to better understand the relation between ToM development and children’s learning understanding.
Genome-Wide Analysis of Transposable Elements and Satellite DNAs in Spinacia Species to Shed Light on Their Roles in Sex Chromosome Evolution

Sex chromosome evolution has mostly been studied in species with heteromorphic sex chromosomes. The Spinacia genus serves as an ideal model for investigating evolutionary mechanisms underlying the transition from homomorphic to heteromorphic sex chromosomes. Among evolutionary factors, repetitive sequences play multiple roles in sex chromosome evolution while their forces have not been fully explored in Spinacia species. Here, we identified major repetitive sequence classes in male and female genomes of Spinacia species and their ancestral relative sugar beet to elucidate the evolutionary processes of sex chromosome evolution using next-generation sequencing (NGS) data. Comparative analysis revealed that the repeat elements of Spinacia species are considerably higher than of sugar beet, especially the Ty3/Gypsy and Ty1/Copia retrotransposons. The long terminal repeat retroelements (LTR) Angela, Athila, and Ogre may be accounted for the higher proportion of repeats in the spinach genome. Comparison of the repeats proportion between female and male genomes of three Spinacia species indicated the different representation in Spinacia tetrandra samples but not in the S. oleracea or S. turkestanica samples. From these results, we speculated that emergence of repetitive DNA sequences may correlate the formation of sex chromosome and the transition from homomorphic sex chromosomes to heteromorphic sex chromosomes as heteromorphic sex chromosomes exclusively existed in Spinacia tetrandra. Three novel sugar beet-specific satellites were identified and confirmed by fluorescence in situ hybridization (FISH); six out of eight new spinach-specific satellites were mapped to the short arm of sex chromosomes. A total of 141 copies of SolSat01-171-s were found in the sex determination region (SDR). Thus, the accumulation of satellite DNA on the short arm of chromosome 1 may be involved in the sex chromosome evolution in Spinacia species. Our study provides a fundamental resource for understanding repeat sequences in Spinacia species and their roles in sex chromosome evolution.
Heat Shock-Induced Dephosphorylation of Eukaryotic Elongation Factor 1BδL by Protein Phosphatase 1

Several variant proteins are produced from EEF1D, including two representative proteins produced via alternative splicing machinery. One protein is the canonical translation eukaryotic elongation factor eEF1Bδ1, and the other is the heat shock-responsive transcription factor eEF1BδL. eEF1Bδ1 is phosphorylated by cyclin-dependent kinase 1 (CDK1), but the machinery controlling eEF1BδL phosphorylation and dephosphorylation has not been clarified. In this study, we found that both proteins were dephosphorylated under heat shock and proteotoxic stress, and this dephosphorylation was inhibited by okadaic acid. Using proteins with mutations at putative phosphorylated residues, we revealed that eEF1Bδ1 and eEF1BδL are phosphorylated at S133 and S499, respectively, and these residues are both CDK1 phosphorylation sites. The eEF1BδL S499A mutant more strongly activated HSPA6 promoter-driven reporter than the wild-type protein and S499D mutant. Furthermore, protein phosphatase 1 (PP1) was co-immunoprecipitated with eEF1Bδ1 and eEF1BδL, and PP1 dephosphorylated both proteins in vitro. Thus, this study clarified the role of phosphorylation/dephosphorylation in the functional regulation of eEF1BδL during heat shock.
Recent Advances in Non‐nucleophilic Mg Electrolytes

High-performance electrolyte is still a roadblock for the development of rechargeable magnesium (Mg) batteries. Grignard-type electrolytes were once the only choice in the early stage of rechargeable Mg batteries research. However, due to their nucleophilic nature and high reactivity, Grignard-type electrolytes have inherent safety issues and low oxidation stability, which restrict the development of rechargeable Mg batteries in terms of practical application. Recently, emerging novel Mg battery systems such as Mg-S, Mg-O2/air batteries also require non‐nucleophilic electrolytes with high oxidation stability. This short review summarizes recent advances in non‐nucleophilic Mg electrolytes and aims to provide insights into electrochemical properties and active Mg ion structure of such electrolytes.
Why Educational Neuroscience Needs Educational and School Psychology to Effectively Translate Neuroscience to Educational Practice

The emerging discipline of educational neuroscience stands at a crossroads between those who see great promise in integrating neuroscience and education and those who see the disciplinary divide as insurmountable. However, such tension is at least partly due to the hitherto predominance of philosophy and theory over the establishment of concrete mechanisms and agents of change. If educational neuroscience is to move forward and emerge as a distinct discipline in its own right, the traditional boundaries and methods must be bridged, and an infrastructure must be in place that allows for collaborative and productive exchange. In the present paper, we argue that school psychologists have the potential to fulfill this need and represent important agents of change in establishing better connections between research and practice. More specifically, we use the National Association of School Psychologists (NASP) (2020) Domains of Practice to highlight several areas where school psychology can actively support forging connections between neuroscience and educational practice. School psychologists represent untapped potential in their knowledge, skillset, and placement to serve a vital role in building the bridge between neuroscience and education.
Smoothing HCCI Heat Release with Vaporization-Cooling-Induced Thermal Stratification using Ethanol

Ethanol and ethanol/gasoline blends are being widely considered as alternative fuels for light-duty automotive applications. At the same time, HCCI combustion has the potential to provide high efficiency and ultra-low exhaust emissions. However, the application of HCCI is typically limited to low and moderate loads because of unacceptably high heat-release rates (HRR) at higher fueling rates. This work investigates the potential of lowering the HCCI HRR at high loads by using partial fuel stratification to increase the in-cylinder thermal stratification. This strategy is based on ethanol's high heat of vaporization combined with its true single-stage ignition characteristics. Using partial fuel stratification, the strong fuel-vaporization cooling produces thermal stratification due to variations in the amount of fuel vaporization in different parts of the combustion chamber. The low sensitivity of the autoignition reactions to variations of the local fuel concentration allows the temperature variations to govern the combustion event. This results in a sequential autoignition event from leaner and hotter zones to richer and colder zones, lowering the overall combustion rate compared to operation with a uniform fuel/air mixture. The amount of partial fuel stratification was varied by adjusting the fraction of fuel injected late to produce stratification, and also by changingmore » the timing of the late injection. The experiments show that a combination of 60-70% premixed charge and injection of 30-40 % of the fuel at 80{sup o}CA before TDC is effective for smoothing the HRR. With CA50 held fixed, this increases the burn duration by 55% and reduces the maximum pressure-rise rate by 40%. Combustion stability remains high but engine-out NO{sub x} has to be monitored carefully. For operation with strong reduction of the peak HRR, ISNO{sub x} rises to around 0.20 g/kWh for an IMEP{sub g} of 440 kPa. The single-cylinder HCCI research engine was operated naturally aspirated without EGR at 1200 rpm, and had low residual level using a CR = 14 piston. « less
Transcatheter Closure of Patent Ductus Arteriosus in Premature Infants With Very Low Birth Weight

Background: The aim of this study was to describe our experience with transcatheter device closure of patent ductus arteriosus (PDA) in symptomatic low-birth-weight premature infants. Methods: We performed a retrospective study of infants born with a birth body weight of < 2,000 g and admitted to National Cheng Kung University Hospital from September 2014 to December 2019. Basic demographic and clinical information as well as echocardiographic and angiographic data were recorded. Results: Twenty-five premature infants (11 boys and 14 girls) born at gestational ages ranging between 22 and 35 weeks (mean, 25 weeks) were identified. The mean age at procedure was 34.5 ± 5.5 days, and the mean weight was 1,209 ± 94 g (range, 478–1,980 g). The mean diameter of the PDA was 3.4 ± 0.2 mm (range, 2.0–5.4 mm). The following devices were used in this study: Amplatzer Ductal Occluder II additional size (n = 20), Amplatzer Vascular Plug I (n = 1), and Amplatzer Vascular Plug II (n = 4). Complete closure was achieved in all patients. The mean follow-up period was 30.1 ± 17.3 months (range, 6–68 months). In total, 3 patients had left pulmonary artery (LPA) stenosis and 1 patient had coarctation of the aorta during the follow-up period. Younger procedure age and smaller procedure body weight were significantly associated with these obstructions. Conclusions: Performing transcatheter PDA closure in symptomatic premature infants weighing more than 478 g is feasible using currently available devices; moreover, the procedure serves as an alternative to surgery.
Aminated graphite oxides and their composites with copper-based metal–organic framework: in search for efficient media for CO2 sequestration

New composites of a copper-based metal–organic framework and graphite oxide modified by urea (GO-U) were synthesized. The materials and the parent composite components were characterized using X-ray diffraction, FT-IR spectroscopy, potentiometric titration, sorption of nitrogen, thermal analysis, elemental analysis, Raman spectroscopy, UV-Vis spectroscopy, and scanning electron microscopy. The introduction of GO-U does not prevent the formation of MOF crystal structure. The synergistic effect of the composite formation is clearly seen in the surface features. The new materials exhibit a unique texture, high porosity and nitrogen enriched surface chemistry. Incorporation of amino groups in the specific chemical and structural environment enhances CO2 adsorption. Therefore, this kind of composites has a potential application in CO2 capture technologies to remit global warming.
Realizability Without Symmetry

In categorical realizability, it is common to construct categories of assemblies and modest sets from applicative structures. In this paper, we introduce several classes of applicative structures and apply the categorical realizability construction to them. Then we obtain closed multicategories, closed categories and skew closed categories, which are more general categorical structures than Cartesian closed categories and symmetric monoidal closed categories. Moreover, we give the necessary and suﬃcient conditions for obtaining closed multicategories and closed categories of assemblies. 2012 ACM Subject Classiﬁcation Theory of computation → Categorical semantics