Miracle-dz/UniFAR-FTUs huggingface dataset:
A coupled role for CsMYB75 and CsGSTF1 in anthocyanin hyperaccumulation in purple tea

Cultivars of purple tea (Camellia sinensis) that accumulate anthocyanins in place of catechins are currently attracting global interest in their use as functional health beverages. RNA-seq of normal (LJ43) and purple Zijuan (ZJ) cultivars identified the transcription factor CsMYB75 and phi (F) class glutathione transferase CsGSTF1 as being associated with anthocyanin hyperaccumulation. Both genes mapped as a quantitative trait locus (QTL) to the purple bud leaf color (BLC) trait in F1 populations, with CsMYB75 promoting the expression of CsGSTF1 in transgenic tobacco (Nicotiana tabacum). Although CsMYB75 elevates the biosynthesis of both catechins and anthocyanins, only anthocyanins accumulate in purple tea, indicating selective downstream regulation. As glutathione transferases in other plants are known to act as transporters (ligandins) of flavonoids, directing them for vacuolar deposition, the role of CsGSTF1 in selective anthocyanin accumulation was investigated. In tea, anthocyanins accumulate in multiple vesicles, with the expression of CsGSTF1 correlated with BLC, but not with catechin content, in diverse germplasm. Complementation of the Arabidopsis tt19-8 mutant, which is unable to express the orthologous ligandin AtGSTF12, restored anthocyanin accumulation, but did not rescue the transparent testa phenotype, confirming that CsGSTF1 did not function in catechin accumulation. Consistent with a ligandin function, transient expression of CsGSTF1 in Nicotiana occurred in the nucleus, cytoplasm and membrane. Furthermore, RNA-Seq of the complemented mutants exposed to 2% sucrose as a stress treatment showed unexpected roles for anthocyanin accumulation in affecting the expression of genes involved in redox responses, phosphate homeostasis and the biogenesis of photosynthetic components, as compared with non-complemented plants.
Causal effects of blood lipids on amyotrophic lateral sclerosis: a Mendelian randomization study

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disorder that is predicted to increase across the globe by ~70% in the following decades. Understanding the disease causal mechanism underlying ALS and identifying modifiable risks factors for ALS hold the key for the development of effective preventative and treatment strategies. Here, we investigate the causal effects of four blood lipid traits that include high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG) on the risk of ALS. By leveraging instrument variables from multiple large-scale genome-wide association studies in both European and East Asian populations, we carry out one of the largest and most comprehensive Mendelian randomization analyses performed to date on the causal relationship between lipids and ALS. Among the four lipids, we found that only LDL is causally associated with ALS and that higher LDL level increases the risk of ALS in both the European and East Asian populations. Specifically, the odds ratio of ALS per one standard deviation (i.e. 39.0 mg/dL) increase of LDL is estimated to be 1.14 (95% CI 1.05 - 1.24, p = 1.38E-3) in the European and population and 1.06 (95% CI 1.00 - 1.12, p = 0.044) in the East Asian population. The identified causal relationship between LDL and ALS is robust with respect to the choice of statistical methods and is validated through extensive sensitivity analyses that guard against various model assumption violations. Our study provides important evidence supporting the causal role of higher LDL on increasing the risk of ALS, paving ways for the development of preventative strategies for reducing the disease burden of ALS across multiple nations.
FLCN is a novel Rab11A-interacting protein that is involved in the Rab11A-mediated recycling transport

ABSTRACT The Birt–Hogg–Dubé (BHD) syndrome related protein FLCN has recently been implicated in the vesicular trafficking processes by interacting with several Rab family GTPases. In the previous studies, we have shown that FLCN could inhibit the binding of overexpressed PAT1, which is a membrane-bound amino acid transporter, to the lysosome in human embryonic kidney 293 cells. This tends to stabilize the lysosomal amino acid pool that is a critical signal to activate the mTORC1 signaling pathway. However, the mechanisms of FLCN during this process remain unexplored. Here we report that FLCN can bind through its C-terminal DENN-like domain to the recycling transport regulator, Rab11A. Suppression of either Rab11A or FLCN facilitated the localization of the overexpressed PAT1 to the lysosome and inhibited its targeting on the plasma membrane. As a consequence, the mTORC1 was down-regulated. The in vitro GEF activity assay does not support FLCN modifies the Rab11A activity directly. Instead, we found FLCN promoted the loading of PAT1 on Rab11A. Our data uncover a function of FLCN in the Rab11A-mediated recycling pathway and might provide new clues to understand BHD. This article has an associated First Person interview with the first author of the paper. Summary: FLCN regulates the Rab11A-mediated recycling transport pathway.
Developmental carryover effects of ocean warming and acidification in corals from a potential climate refugium, the Gulf of Aqaba

ABSTRACT Coral reefs are degrading from the effects of anthropogenic activities, including climate change. Under these stressors, their ability to survive depends upon existing phenotypic plasticity, but also transgenerational adaptation. Parental effects are ubiquitous in nature, yet empirical studies of these effects in corals are scarce, particularly in the context of climate change. This study exposed mature colonies of the common reef-building coral Stylophora pistillata from the Gulf of Aqaba to seawater conditions likely to occur just beyond the end of this century during the peak planulae brooding season (Representative Concentration Pathway 8.5: pH −0.4 and +5°C beyond present day). Parent and planulae physiology were assessed at multiple time points during the experimental incubation. After 5 weeks of incubation, the physiology of the parent colonies exhibited limited treatment-induced changes. All significant time-dependent changes in physiology occurred in both ambient and treatment conditions. Planulae were also resistant to future ocean conditions, with protein content, symbiont density, photochemistry, survival and settlement success not significantly different compared with under ambient conditions. High variability in offspring physiology was independent of parental or offspring treatments and indicate the use of a bet-hedging strategy in this population. This study thus demonstrates weak climate-change-associated carryover effects. Furthermore, planulae display temperature and pH resistance similar to those of adult colonies and therefore do not represent a larger future population size bottleneck. The findings add support to the emerging hypothesis that the Gulf of Aqaba may serve as a coral climate change refugium aided by these corals' inherent broad physiological resistance. Summary: Exposing mature scleractinian corals to predicted next-century temperature and pH did not significantly alter parent or offspring physiology or recruitment success in a recognized coral climate refugium.
The SOS system: A complex and tightly regulated response to DNA damage

Genomes of all living organisms are constantly threatened by endogenous and exogenous agents that challenge the chemical integrity of DNA. Most bacteria have evolved a coordinated response to DNA damage. In Escherichia coli, this inducible system is termed the SOS response. The SOS global regulatory network consists of multiple factors promoting the integrity of DNA as well as error‐prone factors allowing for survival and continuous replication upon extensive DNA damage at the cost of elevated mutagenesis. Due to its mutagenic potential, the SOS response is subject to elaborate regulatory control involving not only transcriptional derepression, but also post‐translational activation, and inhibition. This review summarizes current knowledge about the molecular mechanism of the SOS response induction and progression and its consequences for genome stability. Environ. Mol. Mutagen. 60:368–384, 2019. © 2018 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.
The effect of the optical design of multifocal contact lenses on choroidal thickness

Studies have found reduced myopia progression with multifocal contact lenses, albeit with an unclear mechanism behind their protective effect. It is hypothesized that the induced myopic defocus of the addition zones of the multifocal contact lenses leads to choroidal thickening and therefore inhibits eye growth. In the current study, the effect of the optical design of multifocal contact lenses on choroidal thickness was investigated. Eighteen myopic participants wore four different contact lenses ((1) single-vision lenses corrected for distance, (2) single-vision lenses with +2.50 D full-field defocus, (3) Multifocal center-distance design, (4) Multifocal center-near design, both with addition power +2.50 D) for 30 min each on their right eye. Automated analysis of the macular choroidal thickness and vitreous chamber depth were performed before and after the wear of each of the contact lenses. Peripheral refraction profiles in primary gaze were obtained using eccentric photorefraction prior to contact lens wear. Choroidal thickness and vitreous chamber depth showed no significant differences to baseline with any of the contact lenses (all p > 0.05). Choroidal thickness increased by +2.1 ± 11.1 μm with the Multifocal center-distance design, by +2.0 ± 11.1 μm with the full-field defocus lens, followed by the Multifocal center-near design with +1.6 ± 11.3 μm and the single-vision contact lens correcting for distance with +0.9 ± 11.2 μm. Multifocal contact lenses have no significant influence on choroidal thickness after short-term wear. Therefore, changes in choroidal thickness might not be the main contributor to the protective effect of multifocal contact lenses in myopia control.
A Clinical Prognostic Score to Predict Survival of Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Patients Receiving First-Line Chemotherapy: A Retrospective Analysis

Background Although several complicated models have been built to evaluate the prognosis of NSCLC patients receiving chemotherapy, simple economic models are still needed to give a preliminary survival assessment of these patients. Material/Methods This study retrospectively assessed the clinical and biological parameters of 223 patients with advanced NSCLC. Univariate and multivariate analyses of overall survival (OS) and progression-free survival (PFS) for the parameters and the prognostic score were assessed. Results Performance status (PS) score=1, smoking history, fibrinogenemia, thrombocytosis, increased lactate dehydrogenase (LDH) level, and anemia were independent predictors of poor prognosis in the univariate analysis of OS and were assessed in multivariate analysis. There was a significant difference in PS=1 (HR=2.134, p<0.0001), increased LDH level (HR=1.508, p=0.014), thrombocytosis (HR=1.547, p=0.012), and smoking history (HR=1.491, p=0.008), based on which the patients were classified into 3 risk groups: low risk (0–1 points), moderate risk (2 points), and high risk (3–5 points). At p values of <0.0001, the median OS was 565, 340, and 273 days and the median progression-free survival was 250, 209, and 135 days, respectively in these 3 risk groups. Conclusions We established a new prognostic score model using PS, LDH level, PLT count, and smoking history to predict the survival of patients receiving first-line chemotherapy for advanced NSCLC, which might be useful in clinical practice.
How Does Language Influence Performance, Fear and Attitudes towards Mathematics at Primary School Level in Zimbabwe?

This mixed-methods (QUANT-qual) study compares test performances of two classes of 52 (26 in each class) Grade 5 learners in a multiple choice Maths test written in English language (Group A) and the same test but with questions written in Shona language (Group B), respectively. The paper also examines the role of language in the development of attitudes and fear of mathematics by learners at the same primary school in Gokwe district, Zimbabwe. Results showed that there were significant differences (in favour of the English language) between Group A’s performance and Group B’s performance. Other findings were that teachers had mixed feelings towards the use of mother tongue in teaching and learning primary school mathematics, but generally agreed that the language of instruction and/or learning affect performance in mathematics, attitudes towards mathematics and fear of mathematics. The paper concludes that using mother tongue as a medium of instruction in the teaching of mathematics in the Zimbabwean junior primary schools is desirable but the feasibility could not be established. It is recommended, among other things, that there is need for further research and policy formulation on the language of learning/instruction at various school levels in Zimbabwe.
Eating Frequency Is Not Associated with Obesity in Chinese Adults

The prevalence of overweight and obesity has been increasing globally. Recent studies suggest that eating frequency (EF) might be a factor influencing the development of overweight and obesity. This study aims to explore the association between eating frequency and obesity in Chinese adults. A cross-sectional study was conducted in Wuhan, China, from March to June 2016. A self-administered questionnaire and 24-h dietary recall were used to collect data on sociodemographic variables, lifestyle factors, nutrition knowledge, and eating frequency. Participants were divided into four groups according to eating frequency and meal timing: traditional time pattern (TTP), traditional time plus late snack pattern (TTLSP), irregular time pattern (ITP), and all-day pattern (ADP). We performed the chi-squared test and multiple logistic regression to assess associations among variables using JMP statistical software version 14.0. 0 (SAS Institute Inc., Cary, NC, USA). Respondents were Chinese adults (N = 2290; range 29–74 years; 1162 men). Lower education level, higher food budget, and lower nutrition knowledge were associated with higher likelihood of irregular EF patterns (TTLSP, ITP, or ADP). Men, non-smokers, and participants with less physical activity, lower education level, or lower nutrition knowledge were more likely to be obese. Body mass index (BMI) categorization was significantly different among EF pattern groups (χ2 = 25.40, p = 0.003); however, this association was no longer significant in the regression model after adjustment for age, sex, education, smoking, food budget, nutrition knowledge, and physical activity. Thus, EF is not associated with obesity in Chinese adults.
Functional regulatory mechanism of smooth muscle cell-restricted LMOD1 coronary artery disease locus

Recent genome-wide association studies (GWAS) have identified multiple new loci which appear to alter coronary artery disease (CAD) risk via arterial wall-specific mechanisms. One of the annotated genes encodes LMOD1 (Leiomodin 1), a member of the actin filament nucleator family that is highly enriched in smooth muscle-containing tissues such as the artery wall. However, it is still unknown whether LMOD1 is the causal gene at this locus and also how the associated variants alter LMOD1 expression/function and CAD risk. Using epigenomic profiling we recently identified a non-coding regulatory variant, rs34091558, which is in tight linkage disequilibrium (LD) with the lead CAD GWAS variant, rs2820315. Herein we demonstrate through expression quantitative trait loci (eQTL) and statistical fine-mapping in GTEx, STARNET, and human coronary artery smooth muscle cell (HCASMC) datasets, rs34091558 is the top regulatory variant for LMOD1 in vascular tissues. Position weight matrix (PWM) analyses identify the protective allele rs34091558-TA to form a conserved Forkhead box O3 (FOXO3) binding motif, which is disrupted by the risk allele rs34091558-A. FOXO3 chromatin immunoprecipitation and reporter assays show reduced FOXO3 binding and LMOD1 transcriptional activity by the risk allele, consistent with effects of FOXO3 downregulation on LMOD1. LMOD1 knockdown results in increased proliferation and migration and decreased cell contraction in HCASMC, and immunostaining in atherosclerotic lesions in the SMC lineage tracing reporter mouse support a key role for LMOD1 in maintaining the differentiated SMC phenotype. These results provide compelling functional evidence that genetic variation is associated with dysregulated LMOD1 expression/function in SMCs, together contributing to the heritable risk for CAD.
Non‐canonical activation of CREB mediates neuroprotection in a Caenorhabditis elegans model of excitotoxic necrosis

Excitotoxicity, caused by exaggerated neuronal stimulation by Glutamate (Glu), is a major cause of neurodegeneration in brain ischemia. While we know that neurodegeneration is triggered by overstimulation of Glu‐receptors (GluRs), the subsequent mechanisms that lead to cellular demise remain controversial. Surprisingly, signaling downstream of GluRs can also activate neuroprotective pathways. The strongest evidence involves activation of the transcription factor cAMP response element‐binding protein (CREB), widely recognized for its importance in synaptic plasticity. Canonical views describe CREB as a phosphorylation‐triggered transcription factor, where transcriptional activation involves CREB phosphorylation and association with CREB‐binding protein. However, given CREB's ubiquitous cross‐tissue expression, the multitude of cascades leading to CREB phosphorylation, and its ability to regulate thousands of genes, it remains unclear how CREB exerts closely tailored, differential neuroprotective responses in excitotoxicity. A non‐canonical, alternative cascade for activation of CREB‐mediated transcription involves the CREB co‐factor cAMP‐regulated transcriptional co‐activator (CRTC), and may be independent of CREB phosphorylation. To identify cascades that activate CREB in excitotoxicity we used a Caenorhabditis elegans model of neurodegeneration by excitotoxic necrosis. We demonstrated that CREB's neuroprotective effect was conserved, and seemed most effective in neurons with moderate Glu exposure. We found that factors mediating canonical CREB activation were not involved. Instead, phosphorylation‐independent CREB activation in nematode excitotoxic necrosis hinged on CRTC. CREB‐mediated transcription that depends on CRTC, but not on CREB phosphorylation, might lead to expression of a specific subset of neuroprotective genes. Elucidating conserved mechanisms of excitotoxicity‐specific CREB activation can help us focus on core neuroprotective programs in excitotoxicity.
MAIA—A machine learning assisted image annotation method for environmental monitoring and exploration

Digital imaging has become one of the most important techniques in environmental monitoring and exploration. In the case of the marine environment, mobile platforms such as autonomous underwater vehicles (AUVs) are now equipped with high-resolution cameras to capture huge collections of images from the seabed. However, the timely evaluation of all these images presents a bottleneck problem as tens of thousands or more images can be collected during a single dive. This makes computational support for marine image analysis essential. Computer-aided analysis of environmental images (and marine images in particular) with machine learning algorithms is promising, but challenging and different to other imaging domains because training data and class labels cannot be collected as efficiently and comprehensively as in other areas. In this paper, we present Machine learning Assisted Image Annotation (MAIA), a new image annotation method for environmental monitoring and exploration that overcomes the obstacle of missing training data. The method uses a combination of autoencoder networks and Mask Region-based Convolutional Neural Network (Mask R-CNN), which allows human observers to annotate large image collections much faster than before. We evaluated the method with three marine image datasets featuring different types of background, imaging equipment and object classes. Using MAIA, we were able to annotate objects of interest with an average recall of 84.1% more than twice as fast as compared to “traditional” annotation methods, which are purely based on software-supported direct visual inspection and manual annotation. The speed gain increases proportionally with the size of a dataset. The MAIA approach represents a substantial improvement on the path to greater efficiency in the annotation of large benthic image collections.
Evaluating social network extraction for classic and modern fiction literature

The analysis of literary works has experienced a surge in computer-assisted processing. To obtain insights into the community structures and social interactions portrayed in novels the creation of social networks from novels has gained popularity. Many methods rely on identifying named entities and relations for the construction of these networks, but many of these tools are not specifically created for the literary domain. Furthermore, many of the studies on information extraction from literature typically focus on 19th century source material. Because of this, it is unclear if these techniques are as suitable to modern-day science fiction and fantasy literature as they are to those 19th century classics. We present a study to compare classic literature to modern literature in terms of performance of natural language processing tools for the automatic extraction of social networks as well as their network structure. We find that there are no significant differences between the two sets of novels but that both are subject to a high amount of variance. Furthermore, we identify several issues that complicate named entity recognition in modern novels and we present methods to remedy these.
Lipoprotein (a) and Low‐density lipoprotein apolipoprotein B metabolism following apheresis in patients with elevated lipoprotein(a) and coronary artery disease

Lipoprotein apheresis effectively lowers lipoprotein(a) [Lp(a)] and low‐density lipoprotein (LDL) by approximately 60%‐70%. The rebound of LDL and Lp(a) particle concentrations following lipoprotein apheresis allows the determination of fractional catabolic rate (FCR) and hence production rate (PR) during non‐steady state conditions. We aimed to investigate the kinetics of Lp(a) and LDL apolipoprotein B‐100 (apoB) particles in patients with elevated Lp(a) and coronary artery disease undergoing regular apheresis.