Miracle-dz/UniFAR-FTUs huggingface dataset:
Dissection of a rice OsMac1 mRNA 5’ UTR to uncover regulatory elements that are responsible for its efficient translation

The untranslated regions (UTRs) of mRNAs are involved in many posttranscriptional regulatory pathways. The rice OsMac1 mRNA has three splicing variants of the 5’ UTR (UTRa, UTRb, and UTRc), which include a CU-rich region and three upstream open reading frames (uORFs). UTRc contains an additional 38-nt sequence, termed sp38, which acts as a strong translational enhancer of the downstream ORF; reporter analysis revealed translational efficiencies >15-fold higher with UTRc than with the other splice variants. Mutation analysis of UTRc demonstrated that an optimal sequence length of sp38, rather than its nucleotide sequence is essential for UTRc to promote efficient translation. In addition, the 5’ 100 nucleotides of CU-rich region contribute to UTRc translational enhancement. Strikingly, three uORFs did not reveal their inhibitory potential within the full-length leader, whereas deletion of the 5’ leader fragment preceding the leader region with uORFs nearly abolished translation. Computational prediction of UTRc structural motifs revealed stem-loop structures, termed SL1-SL4, and two regions, A and B, involved in putative intramolecular interactions. Our data suggest that SL4 binding to Region-A and base pairing between Region-B and the UTRc 3’end are critically required for translational enhancement. Since UTRc is not capable of internal initiation, we presume that the three-dimensional leader structures can allow translation of the leader downstream ORF, likely allowing the bypass of uORFs.
Effect of ionic liquid pretreatment on lignocellulosic biomass from oilseeds

In this study,three kinds of ionic liquid,including 1-butyl-3-methylimidazolium chloride([Bmim]Cl),1-butyl-3-methylimidazolium bromide([Bmim]Br)and 1-octyl-3-methylimidazolium chloride([Omim]Cl),were selected to pretreat the lignocellulosic parts of oilseeds:peanut husk,peanut straw and cole straw.The untreated and pretreated materials were investigated through the compositional,enzymatic hydrolysis and structural analysis.Among the untreated materials,peanut straw with the highest sugar yield 54.31% and the lowest lignin content was considered as the preferable substrate for biofuels production.After ionic liquid pretreatment,the effect of[Bmim]Cl on sugar yield was more significant, which lead to 85.43%sugar yield for peanut straw.The structural changes were also analyzed by scanning electron microscope(SEM)and Fourier transform-infrared(FT-IR). Among the raw materials,peanut straw's morphological structure was distinctive with broken surface,incompact structural and lower crystallinity.After pretreatment,all material turned to be more porous and rough than before.On the basis,the mechanism of lignocellulose's dissolution by ionic liquid with different cation and anion were also discussed. The results showed that the chlorine and[Bmim]+were vital on the effect of ionic liquid pretreatment.
Study on the Extraction Technology with Ultrasound-assisted and Deproteinization Technology of Polysaccharide from Sinonov Acula Constricta

In this paper the polysaccharide was extracted from the Sinonov acula constricta by ultrasound-assisted method.The optimum conditions obtained by the orthogonal test as follow: ultrasonic power 440 W,ultrasonic extraction time 60 min,extraction temperature 80 ℃ and material to water ratio 1∶30(g/mL). With these conditions,the highest extracting amount of polysaccharide reached to 8.31 %. The effect of deproteinization was evaluated through the comparation of the Sevaq method and the trichloroacetic acid(TCA)method.The experimental results indicate that the TCA method has the higher deproteinization rate and lower polysaccharides loss rate.For 3 times of deproteinization by TCA method,the results were: the deproteinization rate 69.75 % and the polysaccharides loss rate 26.68 %.
Biological effects of secondary metabolites of Inula racemosa on the parasitoid Bracon hebetor

Secondary plant metabolites play an important role in mediating interactions among plants, insect herbivores, and their parasitoids. These defensive compounds not only affect the growth and development of herbivores, but also influence their natural enemies. In the present study, the diet‐mediated effect of hexane extract of Inula racemosa (Hooker fil.) (Asteraceae) was evaluated on the growth and development of the gregarious ectoparasitoid Bracon hebetor (Say) (Hymenoptera: Braconidae) using a polyphagous pest, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae), as its host. The influence of various concentrations of I. racemosa extract was recorded on B. hebetor’s parasitization behavior on its host larvae. The parasitism rate of naive female wasps decreased significantly when host larvae were reared on treated diet, but no adverse effect of plant extract was recorded on the viability of eggs. Detrimental effects of the plant extract were also detected in the form of reduced survival and delayed development of the parasitoid. Ingestion of hexane‐extract‐supplemented diet by S. litura adversely affected the emergence and parasitism rate of adults from the first generation of B. hebetor. In conclusion, consumption of I. racemosa extract by S. litura had a negative impact on various biological parameters of B. hebetor, although lower concentrations of plant extract had no adverse effects. There is a need to study the possible effects of secondary metabolites on these trophic interactions under natural conditions.
Surgical data science and artificial intelligence for surgical education

Surgical data science (SDS) aims to improve the quality of interventional healthcare and its value through the capture, organization, analysis, and modeling of procedural data. As data capture has increased and artificial intelligence (AI) has advanced, SDS can help to unlock augmented and automated coaching, feedback, assessment, and decision support in surgery. We review major concepts in SDS and AI as applied to surgical education and surgical oncology.
Cytoplasmic switch of ARS2 isoforms promotes nonsense-mediated mRNA decay and arsenic sensitivity

The life of RNA polymerase II (RNAPII) transcripts is shaped by the dynamic formation of mutually exclusive ribonucleoprotein complexes (RNPs) that direct transcript biogenesis and turnover. A key regulator of RNA metabolism in the nucleus is the scaffold protein ARS2 (arsenic resistance protein 2), bound to the cap binding complex (CBC). We report here that alternative splicing of ARS2’s intron 5, generates cytoplasmic isoforms that lack 270 amino acids from the N-terminal of the protein and are functionally distinct from nuclear ARS2. Switching of ARS2 isoforms within the CBC in the cytoplasm has dramatic functional consequences, changing ARS2 from a NMD inhibitor to a NMD promoter that enhances the binding of UPF1 to NCBP1, ERF1 and DHX34, favouring SURF complex formation, SMG7 recruitment and transcript degradation. ARS2 isoform exchange is also relevant during arsenic stress, where cytoplasmic ARS2 promotes a global response to arsenic in a CBC-independent manner. We propose that ARS2 isoform switching promotes the proper recruitment of RNP complexes during NMD and the cellular response to arsenic stress. The existence of non-redundant ARS2 isoforms is relevant for cell homeostasis, stress response, and cancer treatment.
In silico analysis and molecular investigation of the nuclear shuttle protein-interacting kinase 1 (NIK1) in six Solanaceous species

The first layer of innate immunity in plants is initiated through the perception of microbe-associated molecular patterns (MAMPs) or damage-associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs). MAMP/DAMP perception initiates downstream defense responses, a process which ultimately leads to pattern triggered immunity (PTI). In Arabidopsis, the nuclear shuttle protein-interacting kinase 1 (NIK1), among other PRRs, is one of the most important central components of PTI signaling and kinase signaling cascade, since it is involved in the plant antiviral response against geminiviruses. Despite the characterization of the structure and function of the NIK1 receptors made by some groups, studies related to NIK1 importance in the current gene-editing era are missing. By simple in silico analysis, in this study we investigated the NIK1 homologues from six Solanaceous plant species including: tomato (Solanum lycopersicum), potato (Solanum tuberosum), Solanum pennellii, eggplant (Solanum melongena), pepper (Capsicum annum), and Nicotiana benthamiana. The phylogenetic analyses of different NIK1 proteins from Arabidopsis and six Solanaceous plants revealed nine different clades. As expected, we found that these NIK1 orthologs have similar genomic structures suggesting a similar function. We could identify that SotubNIK1, SolyNIK1, SopenNIK1, CANIK1, NibenNIK1, SmeNIK1 have the highest sequence homology with AtNIK1. Additionally, the conserved protein kinase domain (PKD) that is present in NIK1 from Arabidopsis thaliana was bioinformatically analyzed and found in other species. As this highly conserved NIK1 region is present in several crops of economic importance, its potential is highlighted as a possible target site for gene editing, to develop crops tolerant to geminiviral infections.
Arabidopsis Topless-related 1 mitigates physiological damage and growth penalties of induced immunity

Transcriptional corepressors of the Topless family are important regulators of plant hormone and immunity signaling. The lack of a genome-wide profile of their chromatin associations limits understanding of transcriptional regulation in plant immune responses. Chromatin immunoprecipitation with sequencing (ChIP-seq) was performed on GFP-tagged Topless-related 1 (TPR1) expressed in Arabidopsis thaliana lines with and without constitutive immunity dependent on Enhanced Disease Susceptibility 1 (EDS1). RNA-seq profiling of pathogen-infected tpl/tpr mutants and assessments of growth and physiological parameters were employed to determine TPL/TPR roles in transcriptional immunity and defense homeostasis. TPR1 bound to promoter regions of ~1,400 genes and ~10% of the detected binding required EDS1 immunity signaling. A tpr1 tpl tpr4 (t3) mutant displayed mildly enhanced defense-related transcriptional reprogramming upon bacterial infection but not increased bacterial resistance. Bacteria or pep1 phytocytokine-challenged t3 plants exhibited, respectively, photosystem II dysfunction and exacerbated root growth inhibition. Transgenic expression of TPR1 restored the t3 physiological defects. We propose that TPR1 and TPL-family proteins function in Arabidopsis to reduce detrimental effects associated with activated transcriptional immunity.
H3K9me2 genome-wide distribution in the holocentric insect Spodoptera frugiperda (Lepidoptera: Noctuidae)

Background Eukaryotic genomes are packaged by Histone proteins in a structure called chromatin. There are different chromatin types. Euchromatin is typically associated with decondensed, transcriptionally active regions and heterochromatin to more condensed regions of the chromosomes. Methylation of Lysine 9 of Histone H3 (H3K9me) is a conserved biochemical marker of heterochromatin. In many organisms, heterochromatin is usually localized at telomeric as well as pericentromeric regions but can also be found at interstitial chromosomal loci. This distribution may vary in different species depending on their general chromosomal organization. Holocentric species such as Spodoptera frugiperda (Lepidoptera: Noctuidae) possess dispersed centromeres instead of a monocentric one and thus no observable pericentromeric compartment. To identify the localization of heterochromatin in such species we performed ChIP-Seq experiments and analyzed the distribution of the heterochromatin marker H3K9me2 in the Sf9 cell line and whole 4th instar larvae (L4) in relation to RNA-Seq data. Results In both samples we measured an enrichment of H3K9me2 at the (sub) telomeres, rDNA loci, and satellite DNA sequences, which could represent dispersed centromeric regions. We also observed that density of H3K9me2 is positively correlated with transposable elements and protein-coding genes. But contrary to most model organisms, H3K9me2 density is not correlated with transcriptional repression. Conclusion This is the first genome-wide ChIP-Seq analysis conducted in S. frugiperda for H3K9me2. Compared to model organisms, this mark is found in expected chromosomal compartments such as rDNA and telomeres. However, it is also localized at numerous dispersed regions, instead of the well described large pericentromeric domains, indicating that H3K9me2 might not represent a classical heterochromatin marker in Lepidoptera.
Global Effects of a PD Risk-SNP at the Alpha-Synuclein Locus

SUMMARY One of the most significant Parkinson’s disease (PD) risk variants, rs356182, is located at the PD-associated locus near the alpha-synuclein encoding gene, SNCA. SNCA-proximal variants, including rs356182, are thought to function in PD via allele-specific regulatory effects on SNCA expression. However, this interpretation discounts the complex activity of genetic enhancers and possible nonconical effects of alpha-synuclein. Here we investigate a novel risk mechanism for rs356182. We use CRISPR-Cas9 in LUHMES cells, a model for dopaminergic neurons, to generate precise hemizygous lesions at rs356182. The PD-protective (A/-), PD-risk (G/-), and WT (A/G) strains are differentiated into dopaminergic neurons then compared transcriptionally and morphologically. We observe effects not typically ascribed to SNCA; hundreds of differentially expressed genes associated with neuronal differentiation and axonogenesis. Together, the data implicate a risk mechanism for rs356182 in which the risk-allele (G) is associated with abnormal neuronal differentiation. We speculate the disease-relevant effect originates as a diminished population of DA neurons leading to the predisposition for PD later in life.
Structural-functional connectivity mapping of the insular cortex: A combined data-driven and meta-analytic topic mapping

In this study, we examined structural and functional profiles of the insular cortex and mapped associations with well-described functional networks (FNs) throughout the brain using diffusion tensor imaging (DTI) and resting-state functional connectivity (RSFC) data. We used a data-driven method to independently estimate the structural-functional connectivity of the insular cortex. Data were obtained from the Human Connectome Project comprising 108 adult participants. Overall, we observed moderate to high associations between the structural and functional mapping scores of three different insular subregions: the posterior insula (associated with the sensorimotor network: RSFC, DTI = 50% and 72%, respectively), dorsal anterior insula (associated with ventral attention: RSFC, DTI = 83% and 83%, respectively), and ventral anterior insula (associated with the frontoparietal: RSFC, DTI = 42% and 89%, respectively). Further analyses utilized meta-analytic decoding maps to demonstrate specific cognitive and affective as well as gene expression profiles of the three subregions reflecting the core properties of the insular cortex. In summary, given the central role of the insular in the human brain, our results revealing correspondence between DTI and RSFC mappings provide a complementary approach and insight for clinical researchers to identify dysfunctional brain organization in various neurological disorders associated with insular pathology.
MLKL D144K mutation activates the necroptotic activity of the N-terminal MLKL domain

Mixed-lineage kinase domain-like protein (MLKL) is an essential effector protein of necroptotic cell death. The four-helix bundle domain (4HB) presented by the first 125 amino acids of the N-terminal domain is sufficient for its necroptotic activity. However, it has been proposed that the subsequent helix H6 of the brace region has a regulatory effect on its necroptotic activity. How the brace region restrains the necroptotic activity of the N-terminal domain of MLKL is currently unknown. Here, we demonstrate the importance of helix H6 to constrain the necroptotic activity. A single amino acid mutation D144K was able to activate the necroptotic activity of the N-terminal domain of MLKL by removing helix H6 away from 4HB domain. This enabled protein’s oligomerization and membrane translocation. Moreover, a biophysical comparison revealed that helix H6 becomes partially unstructured due to D144K mutation, leading to a lower overall thermodynamic stability of the mutant protein compared to the wild type.
Differential effects of high versus low linear energy transfer (LET) radiation on type-I interferon (IFNβ) and TREX1 responses

Purpose Cancer cells produce innate immune signals following radiation damage, with STING pathway signaling as a critical mediator. High linear energy transfer (LET) radiations create larger numbers of DNA double-strand breaks (DSBs) per unit dose than low-LET radiations and may therefore be more immunogenic. We studied the dose response characteristics of pro-immunogenic type-I interferon, interferon-beta (IFNβ), and its reported suppressor signal, three-prime repair exonuclease 1 (TREX1), in vitro with low-LET x-rays and high-LET fast neutrons. Methods Merkel cell carcinoma cells (MCC) were irradiated by graded doses of x-rays (1-24 Gy) or fast neutrons (1-8 Gy). IFNβ was measured as a function of dose via ELISA assay, and exonuclease TREX1 expression via immunofluorescence microscopy. The Monte Carlo damage simulation (MCDS) was used to model fast neutron relative biological effectiveness for DSB induction (RBEDSB) and compared to laboratory measurements of the RBE for IFNβ production (RBEIFNβ) and TREX1 upregulation (RBETREX1). RBEIFNβ models were also applied to radiation transport simulations to quantify the potential secretion of IFNβ in representative clinical beams. Results Peak IFNβ secretion occurred at 5.7 Gy for fast neutrons and at 14.0 Gy for x-rays, i.e., an effective RBEIFNβ of 2.5 ± 0.2. The amplitude (peak value) of secreted IFNβ signal did not significantly differ between x-rays and fast neutrons (P > 0.05). TREX1 signal increased linearly with absorbed dose, with a four-fold higher upregulation per unit dose for fast neutrons relative to x-rays (RBETREX1 of 4.0 ± 0.1). Monte Carlo modeling of IFNβ suggests Bragg peak-to-entrance ratios of IFNβ production of 40, 100, and 120 for proton, alpha, and carbon ion beams, respectively, a factor of 10-20-fold higher compared to their corresponding physical dose peak-to-entrance ratios. The spatial width of the Bragg peak for IFNβ production is also a factor of two smaller. Conclusion High-LET fast neutrons initiate a larger IFNβ response per unit absorbed dose than low-LET x-rays (i.e., RBEIFNβ value of 2.5). The RBE value for IFNβ is quite similar to data reported in the literature for DSB induction and cellular, post-irradiation micronucleation formation for neutrons and x-rays. The increased IFNβ release after high-LET radiation may be a contributing factor in stimulating a systemic anti-tumor, adaptive immune response (abscopal effect). However, our results indicate that TREX1 anti-inflammatory signaling in vitro for MCC cells is larger per unit dose for fast neutrons than for x-rays (RBETREX1 of 4.0). Given these competing effects, additional studies are needed to clarify whether or not high-LET radiations are therapeutically advantageous over low-LET radiation for pro-inflammatory immune signaling in other cell lines in vitro and for in vivo cancer models.
EXTRACTION TECHNOLOGY OF OLIGOMERIC PROANTHOCYANIDINS

Extraction and separation of oligomeric proanthocyanidins(OPC) from larch bark and quantitative (determination) of OPC has been carried out.Results of orthogonal test indicated the optimum extraction condition of OPC as follows:ratio of liquor to material 10∶1,reflux extraction at 85 ℃ for 2 h with water.After ethanol precipitation,OPC was separated by ethyl acetate-ligroin system.Content of OPC was determined by normal butyl alcohol-hydrochloric acid method at 546 nm to be over 90%.
Scalability of Predictive Modeling Algorithms

This thesis has two main goals — (1) parallelize FAKE GAME by integration into, an open source machine learning framework, H2O, and (2) evaluation of anytime properties of machine learning algorithms and influence of hyperparameter optimization on them. To meet these objectives, I have integrated FAKE GAME into H2O and, in order to evaluate anytime properties, I have implemented, a new tool, called Benchmarker. The evaluation of anytime properties shows that for some problems FAKE GAME models outperform state-of-the-art models from H2O, in both, accuracy and performance. Moreover, the evaluation of hyper-parameter optimization show little success, when optimizing H2O machine learning algorithms. I hypothesise that the negligible performance improvement, and for some optimized models even lower performance than with default configuration, is caused by hyper-parameter automatic tuning, which is done by default in H2O for some hyper-parameters.
Effect of support on the behavior of Cu-based oxygen carriers during long-term CLC operation at temperatures above 1073 K

Chemical-Looping Combustion (CLC) is a combustion technology with CO2 capture that is characterized by its low energy penalties because the CO2 separation is inherent to the process. The CLC concept is based on the transfer of oxygen from the combustion air to fuel by means of an oxygen carrier (OC) in the form of a metal oxide. The OC circulates between two interconnected reactors, the fuel (FR) and the air reactor (AR). To scale up the CLC process for industrial application OC materials suitable to work at high temperatures are needed. Cu-based OCs had been proved to fulfill the requirements for an OC material, although operating temperatures lower than 1073 K were recommended due to its likely agglomeration problems. In this work, several Cu-based OCs have been developed by impregnation on different supports. The supports were prepared by thermal or chemical modifications of commercial γAl2O3 with the aim to reduce the interaction with the metal oxide. The behavior of the OCs was studied in a CLC conti.
Intranasal Administration of RBD Nanoparticles Confers Induction of Mucosal and Systemic Immunity against SARS-CoV-2

Mucosal immunity plays a significant role in host defense against viruses in the respiratory tract. Because the upper respiratory airway is a primary site of SARS-CoV-2 entry, immunization at the mucosa via the intranasal route could potentially lead to induction of local sterilizing immunity that protects against SARS-CoV-2 infection. In this study, we evaluated the immunogenicity of a receptor-binding domain (RBD) of SARS-CoV-2 spike glycoprotein loaded into N,N,N-trimethyl chitosan nanoparticles (RBD-TMC NPs). We showed that intranasal delivery of RBD-TMC NPs into mice induced robust local mucosal immunity, as evidenced by the presence of IgG and IgA responses in BALs and the lungs of immunized mice. Furthermore, mice intranasally administered with this platform of immunogens developed robust systemic antibody responses including serum IgG, IgG1, IgG2a, IgA and neutralizing antibodies. In addition, these immunized mice had significantly higher levels of activated splenic CD4+ and CD8+ cells compared with those that were administered with soluble RBD immunogen. Collectively, these findings shed light on an alternative route of vaccination that mimics the natural route of SARS-CoV-2 infection. This route of administration stimulated not only local mucosal responses but also the systemic compartment of the immune system.