Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulating CRISPR-Cas Genome Editing Using Guide-Complementary DNA Oligonucleotides

CRISPR-Cas has revolutionized genome editing and has a great potential for applications, such as correcting human genetic disorders. To increase the safety of genome editing applications, CRISPR-Cas may benefit from strict control over Cas enzyme activity. Previously, anti-CRISPR proteins and designed oligonucleotides have been proposed to modulate CRISPR-Cas activity. Here we report on the potential of guide-complementary DNA oligonucleotides as controlled inhibitors of Cas9 ribonucleoprotein complexes. First, we show that DNA oligonucleotides down-regulate Cas9 activity in human cells, reducing both on and off-target cleavage. We then used in vitro assays to better understand how inhibition is achieved and under which conditions. Two factors were found to be important for robust inhibition: the length of the complementary region, and the presence of a PAM-loop on the inhibitor. We conclude that DNA oligonucleotides can be used to effectively inhibit Cas9 activity both ex vivo and in vitro.
Vexitoxins: a novel class of conotoxin-like venom peptides from predatory gastropods of the genus Vexillum

Venoms of predatory marine cone snails (the family Conidae, order Neogastropoda) are intensely studied because of the broad range of biomedical applications of the neuropeptides that they contain, conotoxins. Meanwhile anatomy in some other neogastropod lineages strongly suggests that they have evolved similar venoms independently of cone snails, nevertheless their venom composition remains unstudied. Here we focus on the most diversified of these lineages, the genus Vexillum (the family Costellariidae). We have generated comprehensive multi-specimen, multi-tissue RNA-Seq data sets for three Vexillum species, and supported our findings in two species by proteomic profiling. We show that venoms of Vexillum are dominated by highly diversified short cysteine-rich peptides that in many aspects are very similar to conotoxins. Vexitoxins possess the same precursor organization, display overlapping cysteine frameworks and share several common post-translational modifications with conotoxins. Some vexitoxins show detectable sequence similarity to conotoxins, and are predicted to adopt similar domain conformations, including a pharmacologically relevant inhibitory cysteine-know motif (ICK). The tubular gL of Vexillum is a notably more recent evolutionary novelty than the conoidean venom gland. Thus, we hypothesize lower divergence between the toxin genes, and their ‘somatic’ counterparts compared to that in conotoxins, and we find support for this hypothesis in the molecular evolution of the vexitoxin cluster V027. We use this example to discuss how future studies on vexitoxins can inform origin and evolution of conotoxins, and how they may help addressing standing questions in venom evolution.
Supporting Self-Regulated Learning in Distance Learning Contexts at Higher Education Level: Systematic Literature Review

Shifting learning to distant formats especially at the higher education level has been unprecedented during the past decade. Diverse digital learning media have been emerging which allow learner autonomy, and at the same time, require the ability of efficient regulation of various aspects of the learning process for sustainable academic progress. In this context, supporting students in self-regulated learning (SRL) in an optimal way becomes an important factor for their academic success. The present study attempts through a systematic review of 38 studies to provide an overview of the interventions identified as supporting all areas of SRL (metacognitive, cognitive, motivational and emotional), in its three phases (preparatory, performance, appraisal) in distance education environments at the higher education level. As the study results show, there are a number of SRL support interventions available with proven positive effect on SRL. However, their distribution has been found to be uneven. Whereas metacognition regulation and the performance phase of learning is vastly investigated, the emotion regulation, and the preparatory and appraisal phases of the SRL cycle are somewhat underexplored. As complex and multi-component as the process of SRL is, the combination of various interventions, and specific features, for more comprehensive support has also been found beneficial. Additionally, it has been revealed that the emotion regulation, in most cases, is closely related to motivation regulation, and similar interventions support these two. Future studies can further explore the efficiency and relevance of the identified interventions, taking closer look at the effects of various digital media, learner characteristics as well as different levels of education on learners’ self-regulation needs.
Synergistic Interaction of Piperine and Thymol on Attenuation of the Biofilm Formation, Hyphal Morphogenesis and Phenotypic Switching in Candida albicans

The incidence of fungal infections has significantly increased in recent years due to the emergence of antifungal resistance. Biofilm formation is considered to be a major contributor to both the infectious diseases and to antimicrobial resistance. Consequently, biofilm-associated infections are often problematic to treat with existing therapeutics. Adhesion of C. albicans to the host surface or implanted materials followed by hyphal invasion and biofilm formation enhances C. albicans pathogenicity and virulence. Thus, developing a therapeutic agent that inhibits candidal adherence, biofilm development and morphological switching could improve clinical management of infections. The present investigation studied two emerging and alternatives strategies, namely antibiofilm and combinatorial approach, to attenuate biofilm formation and the expression of Candida virulence factors. Piperine and thymol are major bioactive components of pepper and thyme, respectively. These phytochemicals are known to possess numerous biological activities, including recently reported antibiofilm effects against C. albicans. The minimum biofilm inhibitory concentration (MBIC) of both phytochemicals was determined to be 32 µg/ml. The phytochemical treatment of Candida biofilms using piperine and thymol revealed synergistic effects at four different combinations of concentrations, i.e. 8 and 8, 8 and 4, 8 and 2 and 4 and 8 µg/ml. These synergistic combinations resulted in the significant reduction in adherence of Candida, hyphal extension and morphological transformation. Moreover, limited exposure of synergistic combinations controlled the hyphal elongation. Results were validated through the gene expression analysis. Results from the present investigation suggest that piperine and thymol can be synergistically employed for the treatment of biofilm-associated C. albicans infection.
WAFNRLTG: A Novel Model for Predicting LncRNA Target Genes Based on Weighted Average Fusion Network Representation Learning Method

Long non-coding RNAs (lncRNAs) do not encode proteins, yet they have been well established to be involved in complex regulatory functions, and lncRNA regulatory dysfunction can lead to a variety of human complex diseases. LncRNAs mostly exert their functions by regulating the expressions of target genes, and accurate prediction of potential lncRNA target genes would be helpful to further understanding the functional annotations of lncRNAs. Considering the limitations in traditional computational methods for predicting lncRNA target genes, a novel model which was named Weighted Average Fusion Network Representation learning for predicting LncRNA Target Genes (WAFNRLTG) was proposed. First, a novel heterogeneous network was constructed by integrating lncRNA sequence similarity network, mRNA sequence similarity network, lncRNA-mRNA interaction network, lncRNA-miRNA interaction network and mRNA-miRNA interaction network. Next, four popular network representation learning methods were utilized to gain the representation vectors of lncRNA and mRNA nodes. Then, the representations of lncRNAs and target genes in the heterogeneous network were obtained with the weighted average fusion network representation learning method. Finally, we merged the representations of lncRNAs and related target genes to form lncRNA-gene pairs, trained the XGBoost classifier and predicted potential lncRNA target genes. In five-cross validations on the training and independent datasets, the experimental results demonstrated that WAFNRLTG obtained better AUC scores (0.9410, 0.9350) and AUPR scores (0.9391, 0.9350). Moreover, case studies of three common lncRNAs were performed for predicting their potential lncRNA target genes and the results confirmed the effectiveness of WAFNRLTG. The source codes and all data of WAFNRLTG can be freely downloaded at https://github.com/HGDYZW/WAFNRLTG.
On Some Journal Citation Properties: Math-Net.Ru as a Case

This paper presents a study of bibliographical references cited in articles published by MathNet.Ru journals. Based on data obtained from mathematical portal Math-Net.Ru, we built a journals citation graph, with its vertices denoting journals, and edges representing bibliographical references (citations) between papers published in these journals. To increase the reliability of the constructed graph, we chose a 2010-2021 citation time interval, when distribution of citing papers (papers that have cited other works) had stabilized at 3500-4500 citations per year. The structure of citation ageing is investigated; it is shown that the half-life of these citations is 8 years. So, the publication date of cited papers (papers that have been cited by other works) was limited to the year 2002. The constructed citation graph was found to have a small diameter and high density, indicating that there is a high level of research collaboration in Math-Net.Ru. It is shown that there is no Matthew effect as a pronounced advantage in the citations of leading journals in relation to less well-known ones. The adequacy of the Math-Net.Ru journal citation graph as a scientific collaboration model is confirmed by comparing the ranking of journals included the citation graph with their Science Index ranking in scientific electronic library eLIBRARY.RU. The two rankings were found to have a direct moderate relationship between themselves. A number of substantive conclusions are drawn from analysis of the citation graph.
Ultrastructure and functional morphology of the mouthparts in Raoiella mites (Tetranychoidea: Tenuipalpidae): how they use the cheliceral stylets during feeding

Abstract The flat mite genus Raoiella Hirst (Tenuipalpidae) has attracted considerable research interest due to the rapid spread of Raoiella indica Hirst which feeds most commonly on species of palms (Arecaceae). Raoiella are frequently observed with their stylets inserted into the leaf stomatal openings, suggesting they feed on this site. Herein, we use transmission electron microscopy (TEM), scanning electron microscopy (SEM), low temperature scanning electron microscopy (LTSEM) and light microscopy (LM) to describe the mouthpart organization and the feeding behavior found in R. indica and R. bauchani Beard & Ochoa. The feeding mechanism is also discussed based on their distinctive morphological aspects. The structure of the gnathosoma of Raoiella generally agrees with the organization previously observed in Brevipalpus and Cenopalpus. As in other tetranychoid mites, there is no anatomical connection between the inter-stylet tube and the food channel, corroborating the theory that the stylets are used to pierce plant tissue (and assumedly inject saliva) but play no role in sucking up fluid from damaged host cells. As in Brevipalpus, the adoral setae are mechanoreceptors that may help guide the mite to the site for feeding. The ultrastructure of supracoxal setae e remains enigmatic. We also present observations of possible epidermal feeding on Phoenix roebelenii O'Brien (Arecaceae) for R. indica. Raoiella indica were shown to penetrate both the guard cells of the stomata and the epidermis of P. roebelenii, suggesting that feeding via the epidermis could be possible on this host plant.
Viscoelasticity Investigation of Semiconductor NP (CdS and PbS) Controlled Biomimetic Nanoparticle Hydrogels

The viscoelastic properties of colloidal nanoparticles (NPs) make opportunities to construct novel compounds in many different fields. The interparticle forces of inorganic particles on colloidal NPs are important for forming a mechanically stable particulate network especially the NP-based soft matter in the self-assembly process. Here, by capping with the same surface ligand L-glutathione (GSH), two semiconductor NP (CdS and PbS) controlled biomimetic nanoparticle hydrogels were obtained, namely, CdS@GSH and PbS@GSH. The dependence of viscoelasticity of colloidal suspensions on NP sizes, concentrations, and pH value has been investigated. The results show that viscoelastic properties of CdS@GSH are stronger than those of PbS@GSH because of stronger surface bonding ability of inorganic particles and GSH. The hydrogels formed by the smaller NPs demonstrate the higher stiffness due to the drastic change of GSH configurations. Unlike the CdS@GSH hydrogel system, the changes of NP concentrations and pH value had great influence on the PbS@GSH hydrogel system. The higher the proportion of water in the small particle size PbS@GSH hydrogel system, the greater the mechanical properties. The stronger the alkalinity in the large particle size PbS@GSH hydrogel system, the greater the hardness and storage modulus. Solution˗state nuclear magnetic resonance (NMR) indicated that the ligand GSH forms surface layers with different thickness varying from different coordination modes which are induced by different semiconductor NPs. Moreover, increasing the pH value of the PbS@GSH hydrogel system will dissociate the surface GSH molecules to form Pb2+ and GSH complexes which could enhance the viscoelastic properties.
Designing Persuasive Food Conversational Recommender Systems With Nudging and Socially-Aware Conversational Strategies

Unhealthy eating behavior is a major public health issue with serious repercussions on an individual’s health. One potential solution to overcome this problem, and help people change their eating behavior, is to develop conversational systems able to recommend healthy recipes. One challenge for such systems is to deliver personalized recommendations matching users’ needs and preferences. Beyond the intrinsic quality of the recommendation itself, various factors might also influence users’ perception of a recommendation. In this paper, we present Cora, a conversational system that recommends recipes aligned with its users’ eating habits and current preferences. Users can interact with Cora in two different ways. They can select pre-defined answers by clicking on buttons to talk to Cora or write text in natural language. Additionally, Cora can engage users through a social dialogue, or go straight to the point. Cora is also able to propose different alternatives and to justify its recipes recommendation by explaining the trade-off between them. We conduct two experiments. In the first one, we evaluate the impact of Cora’s conversational skills and users’ interaction mode on users’ perception and intention to cook the recommended recipes. Our results show that a conversational recommendation system that engages its users through a rapport-building dialogue improves users’ perception of the interaction as well as their perception of the system. In the second evaluation, we evaluate the influence of Cora’s explanations and recommendation comparisons on users’ perception. Our results show that explanations positively influence users’ perception of a recommender system. However, comparing healthy recipes with a decoy is a double-edged sword. Although such comparison is perceived as significantly more useful compared to one single healthy recommendation, explaining the difference between the decoy and the healthy recipe would actually make people less likely to use the system.
To Achieve Carbon Neutrality Targets in Pakistan: New Insights of Information and Communication Technology and Economic Globalization

In recent years, information and communication technology (ICT) is used in every sphere of life, from business to services, education to culture, infrastructure to transportation, and art to entertainment. The current study aims to assess the impact of ICT, economic growth, and globalization on CO2 emission in the context of Pakistan. For empirical estimation, the current study applied an innovative methodological approach called generalized linear model (GLM) and robust least square (ROBUSTLS) technique for the years 1990–2019. The key finding of this study shows that economic growth has a positive and significant effect on CO2 emission, which confirm that economic growth accelerates the rate of CO2 emission, while the study also reveals that ICT usage (more specifically ICT-internet and ICT-mobilesubscription) has a negative but significant effect on CO2 emission, which confirms that the usage of ICT (more specifically ICT-internet and ICT-mobile subscription) does not contribute positively to CO2 emission. Furthermore, the coefficient of globalization has a positive and significant effect on the CO2 emission, which confirms that globalization accelerates the CO2 emission in the country. Also, the results indicate that ICT usage (more specifically ICT-internet and ICT-mobile subscription) could boost economic growth and mitigate climate change. Based on the policy perspective, the government of Pakistan needs to strategically focus on the ICT sector and more specifically on technological innovations to promote sustainable economic growth in the country.
Tra2beta-Dependent Regulation of RIO Kinase 3 Splicing During Rift Valley Fever Virus Infection Underscores the Links Between Alternative Splicing and Innate Antiviral Immunity

Rift Valley fever virus (RVFV) is an emerging pathogen that has potential to cause severe disease in humans and domestic livestock. Propagation of RVFV strain MP-12 is negatively impacted by the actions of RIOK3, a protein involved in the cellular immune response to viral infection. During RVFV infection, RIOK3 mRNA is alternatively spliced to produce an isoform that correlates with the inhibition of interferon β signaling. Here, we identify splicing factor TRA2-β (also known as TRA2beta and hTRA2-β) as a key regulator governing the relative abundance of RIOK3 splicing isoforms. Using RT-PCR and minigenes, we determined that TRA2-β interaction with RIOK3 pre-mRNA was necessary for constitutive splicing of RIOK3 mRNA, and conversely, lack of TRA2-β engagement led to increased alternative splicing. Expression of TRA2-β was found to be necessary for RIOK3’s antiviral effect against RVFV. Intriguingly, TRA2-β mRNA is also alternatively spliced during RVFV infection, leading to a decrease in cellular TRA2-β protein levels. These results suggest that splicing modulation serves as an immune evasion strategy by RVFV and/or is a cellular mechanism to prevent excessive immune response. Furthermore, the results suggest that TRA2-β can act as a key regulator of additional steps of the innate immune response to viral infection.
Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis

Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal fibrotic lung disease that occurs primarily in middle-aged and elderly adults. It is a major cause of morbidity and mortality. With an increase in life expectancy, the economic burden of IPF is expected to continuously rise in the near future. Although the exact pathophysiological mechanisms underlying IPF remain not known. Significant progress has been made in our understanding of the pathogenesis of this devastating disease in last decade. The current paradigm assumes that IPF results from sustained or repetitive lung epithelial injury and subsequent activation of fibroblasts and myofibroblast differentiation. Persistent myofibroblast phenotype contributes to excessive deposition of the extracellular matrix (ECM) and aberrant lung repair, leading to tissue scar formation, distortion of the alveolar structure, and irreversible loss of lung function. Treatments of patients with IPF by pirfenidone and nintedanib have shown significant reduction of lung function decline and slowing of disease progression in patients with IPF. However, these drugs do not cure the disease. In this review, we discuss recent advances on the pathogenesis of IPF and highlight the development of novel therapeutic strategies against the disease.
Serum IgG Responses to gp15 and gp40 Protein-Derived Synthetic Peptides From Cryptosporidium parvum

Cryptosporidium spp. are responsible for moderate to severe diarrhea, mainly in children and immunocompromised patients. Using ELISA, the recognition of synthetic peptides generated from the sequences of the Cryptosporidium parvum gp40 and gp15 proteins by serum IgM and IgG antibodies from patients infected (cases) with Cryptosporidium hominis, C. parvum, and Cryptosporidium canis, and uninfected individuals (controls) was evaluated. A statistically significant difference (p = 0.0025) was found in terms of the recognition of peptides A133 and A32 between cases and controls. Additional studies are necessary to understand the potential of these peptides as vaccine candidates.
HCV Interplay With Mir34a: Implications in Hepatocellular Carcinoma

Since its identification, HCV has been considered one of the main causes of hepatitis and liver cancer. Currently, the molecular mechanisms of HCC development induced by HCV infection have not been sufficiently clarified. The recent discovery of novel treatments that inhibit HCV replication gave rise to new questions concerning HCC mechanisms. In particular, the HCV eradication mediated by new direct-acting antiviral (DAAs) drugs does not exclude the possibility of de novo HCC development; this finding opened more questions on the interplay between liver cells and the virus. Different groups have investigated the pathways leading to cancer recurrence in patients treated with DAAs. For this reason, we tried to gain molecular insights into the changes induced by HCV infection in the target liver cells. In particular, we observed an increase in microRNA34a (miR34a) expression following HCV infection of HCC cell line Huh7.5. In addition, Huh7.5 treated with extracellular vesicles (EVs) from the previously HCV-infected Huh7.5 underwent apoptosis. Since miR34 expression was increased in Huh7.5 EVs, we hypothesized a paracrine mechanism of viral infection mediated by miR34a cargo of EVs. The balance between viral infection and cell transformation may raise some questions on the possible use of antiviral drugs in association with antineoplastic treatment.
Evolution of assortative mating following selective introgression of pigmentation genes between two Drosophila species

Adaptive introgression is ubiquitous in animals but experimental support for its role in driving speciation remains scarce. In the absence of conscious selection, admixed laboratory strains of Drosophila asymmetrically and progressively lose alleles from one parental species and reproductive isolation against the predominant parent ceases after 10 generations. Here, we selectively introgressed during one year light pigmentation genes of D. santomea into the genome of its dark sibling D. yakuba, and vice versa. We found that the pace of phenotypic change differed between the species and the sexes, and identified through genome sequencing common as well as distinct introgressed loci in each species. Mating assays showed that assortative mating between introgressed flies and both parental species persisted even after four years (∼ 60 generations) from the end of the selection. Those results indicate that selective introgression of as low as 0.5% of the genome can beget morphologically-distinct and reproductively-isolated strains, two prerequisites for the delimitation of new species. Our findings hence represent a significant step towards understanding the genome-wide dynamics of speciation-through-introgression.