Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of DYRK1B, PPARG, and CEBPB Expression Patterns in Adipose-Derived Stem Cells from Patients carrying DYRK1B R102C and Healthy Individuals During Adipogenesis

Background Metabolic syndrome (MetS) is a group of signs and symptoms that are associated with higher risk of Type 2 Diabetes Mellitus (T2DM) and Cardiovascular Diseases (CVDs). The major risk factor for developing MetS is abdominal obesity that is caused by increase in adipocyte size or number. Adipocyte number multiplication is caused by differentiation of mesenchymal stem cells into adipose tissue. Numerous studies have evaluated the expression of key transcription factors including PPARG and CEBPB during adipocyte differentiation in murine cells such as 3T3-L1 cell line. In order to comprehend the expression changes during the process of fat accumulation in adipose tissue derived stem cells (ASCs), we compared the expression of DYRK1B, PPARG, and CEBPB in undifferentiated and differentiated ASCs into mature adipocytes between the patient (harboring DYRK1b R102C) and control (healthy individuals) groups. Methods Gene expression was evaluated on eighth days pre-induction and day 1, 5 and 15 post-induction. The pluripotent capacity of ASCs and the potential for differentiation into adipocyte were confirmed by flow cytometry analysis of surface markers (CD34, CD44, CD105 and CD90), and Oil red O staining, respectively. Expression of DYRK1B, PPARG, and CEBPB were assessed by RT-PCR in patients’ and normal individuals’ samples. Results The expression of DYRK1B kinase and transcription factors (CEBPB and PPARG) are significantly higher in adipose derived stem cells harboring DYRK1b R102C compared to non-carriers on day 5 and 15 during adipocyte differentiation. These proteins may be suitable targets for therapeutic strategies in obesity and obesity related disorders like metabolic syndrome. Furthermore, AZ191 exhibited a potent and selectively inhibitory activity toward DYRK1B and CEBPB. Conclusion CEBPB, PPARA and DYRK1B contribute to adipogenesis and the development of metabolic syndrome; thus, they can be harnessed in developing therapeutic agents against metabolic syndrome.
Computational modelling of trans-synaptic nanocolumns, a modulator of synaptic transmission

Nanocolumns are trans-synaptic structures which align presynaptic vesicles release sites and postsynaptic receptors. However, how these nano structures shape synaptic signaling remains little understood. Given the difficulty to probe submicroscopic structures experimentally, computer modelling is a usefull approach to investigate the possible functional impacts of nanocolumns. In our in silico model, as has been experimentally observed, a nanocolumn is characterized by a tight distribution of postsynaptic receptors aligned with the presynaptic vesicle release site and by the presence of trans-synaptic molecules which can modulate neurotransmitter diffusion. We found that nanocolumns can play an important role in reinforcing synaptic current mostly when the presynaptic vesicle contains a small number of neurotransmitters. We also show that synapses with and without nanocolumns could have differentiated responses to spontaneous or evoked events. Our work provides a new methodology to investigate in silico the role of the submicroscopic organization of the synapse. Author summary Neurotransmitter release, diffusion, and binding to postsynaptic receptors are key steps in synaptic transmission. However, the submicroscopic arrangement of receptors and presynaptic sites of neurotransmitter release remains little investigated. Experimental observations revealed the presence of trans-synaptic nanocolumns which span both the pre and post synaptic sites and fine tune the position of the post synaptic receptors. The functional impact of these nanocolumns (i.e. their influence on synaptic current) is both little understood and difficult to investigate experimentally. Here we construct a novel in silico model to investigate the functional impact of nanocolumns and show that they could play a functional role in reinforcing weak synapses.
High Expression of Glycolytic Genes in Clinical Glioblastoma Patients Correlates With Lower Survival

Glioblastoma (GBM), the most aggressive brain tumor, is associated with a median survival at diagnosis of 16-20 months and limited treatment options. The key hallmark of GBM is altered tumor metabolism and marked increase in the rate of glycolysis. Aerobic glycolysis along with elevated glucose consumption and lactate production supports rapid cell proliferation and GBM growth. In this study, we examined the gene expression profile of metabolic targets in GBM samples from patients with low grade glioma (LGG) and GBM. We found that gene expression of glycolytic enzymes is up-regulated in GBM samples and significantly associated with an elevated risk for developing GBM. Our findings of clinical outcomes showed that GBM patients with high expression of HK2 and PKM2 in the glycolysis related genes and low expression of genes involved in mitochondrial metabolism-SDHB and COX5A related to tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS), respectively, was associated with poor patient overall survival. Surprisingly, expression levels of genes involved in mitochondrial oxidative metabolism are markedly increased in GBM compared to LGG but was lower compared to normal brain. The fact that in GBM the expression levels of TCA cycle and OXPHOS-related genes are higher than those in LGG patients suggests the metabolic shift in GBM cells when progressing from LGG to GBM. These results are an important step forward in our understanding of the role of metabolic reprogramming in glioma as drivers of the tumor and could be potential prognostic targets in GBM therapies.
Time-resolved, integrated analysis of clonally evolving genomes

Clonal genome evolution is a key aspect for parthenogenetic species and cancer. While many studies describe precise landscapes of clonal evolution in cancer, few determine the underlying evolutionary parameters from molecular data, and even fewer integrate theory with data. We derived theoretical results linking mutation rate, time, expansion dynamics, and clinical parameters. We then inferred time-resolved estimates of evolutionary parameters from mutation accumulation, mutational signatures and selection. Using this framework, we traced the speciation of the clonally evolving marbled crayfish population to a time window between 1986 and 1990, which is consistent with biological records. We also used our framework to analyze a published dataset of glioblastoma samples, which identified tumor expansion patterns, cell survival at resection, and selective forces as important factors for tumor development. In conclusion, our framework allowed a time-resolved, integrated analysis of key parameters in clonally evolving genomes, and provided novel insights into the evolutionary age of marbled crayfish and the progression of glioblastoma.
The mechanical and morphological properties of systemic and pulmonary arteries differ in the earth boa, a snake without ventricular pressure separation

The walls of the mammalian aorta and pulmonary artery are characterized by diverging morphologies and mechanical properties, which has been correlated with high systemic and low pulmonary blood pressures, as a result of intraventricular pressure separation in the mammalian ventricle. However, the relation between intraventricular pressure separation and diverging aortic and pulmonary artery wall morphologies and mechanical characteristics is not understood. The snake cardiovascular system poses a unique model for the study of this question, since representatives both with and without intraventricular pressure separation exist. In this study we perform uniaxial tensile testing on vessel samples taken from the aortas and pulmonary arteries of the earth boa, Acrantophis madagascariensis, a species without intraventricular pressure separation. We then compare these morphological and mechanical characteristics with samples from the ball python, Python regius, and the yellow anaconda, Eunectes notaeus, species with and without intraventricular pressure separation, respectively. Strikingly, we find that although the aortas and pulmonary arteries of A. madagascariensis respond similarly to the same intramural blood pressures, they diverge strongly in morphology, and that this is a common attribute among species without intraventricular pressure separation in this study. In contrast, P. regius aortas and pulmonary arteries diverge both morphologically and in terms of their mechanical properties. Altogether our data indicate that intraventricular pressure separation does not explain diverging aortic and pulmonary artery morphologies. Following the Law of Laplace, we propose that thin pulmonary arteries represent a mechanism to protect the fragile pulmonary vascular bed by reducing the blood volume that passes through, to which genetic factors may contribute more strongly than physiological parameters.
Neural mechanisms underlying anxiety-related deficits of attentional inhibition: direct ERP evidence from the Pd component

Behavioral evidence shows that anxious individuals tend to be distracted by irrelevant stimulation not only for threat-related stimuli but also for non-emotional neutral stimuli. These findings suggest that anxious individuals may have a general impairment of attentional control, especially inhibition function. However, the neural mechanism underlying the anxiety-related impairment in attentional control is unclear. Here, in a visual search task with geometric stimuli, we examined attentional processing of the non-emotional neutral distractor on participants with different levels of anxiety, using the event-related-potential (ERP) indices of attentional selection (N2 posterior contralateral [N2pc]) and top-down inhibition (distractor positivity [Pd]). We found that distractor-evoked Pd amplitudes were negatively correlated with trait-anxiety scores, i.e., the higher the level of anxiety, the worse the ability of attentional inhibition. In contrast, the amplitudes of distractor-evoked N2pc did not vary with anxiety levels, suggesting that trait-anxiety level does not affect stimulus-driven attentional capture. We also observed attentional processing of target stimuli and found that the peak latency of target-evoked N2pc was delayed as anxiety levels rise, suggesting that anxiety impairs the efficiency of top-down attentional selection of the target. The present study provides direct neurophysiological evidence for general anxiety-related impairment of attentional control.
Extreme hot weather has stronger impacts on avian reproduction in forests than in cities

Climate change and urbanization are among the most salient human-induced changes affecting Earth’s biota. Extreme weather events can have high biological impacts and are becoming more frequent recently. In cities, the urban heat island can amplify the intensity and frequency of hot weather events. However, the joint effects of heat events and urban microclimate on wildlife are unclear, as urban populations may either suffer more from increased heat stress or become adapted to warmer temperatures. Here we test whether the effects of hot weather on reproductive success of great tits (Parus major) are exacerbated or dampened in urban environments compared to forest habitats. By studying two urban and two forest populations over six years, we show that 14-16 days-old nestlings have smaller body mass and tarsus length, and suffer increased mortality when they experience a higher number of hot days during the nestling period. The negative effects of hot weather on body mass and survival are significantly stronger in forests than in urban areas, where these effects are dampened or even reversed. These results suggest that urban birds are less vulnerable to extreme hot weather conditions than their non-urban conspecifics, possibly by adaptively evolving or flexibly adjusting nestling physiology to tolerate heat stress, and/or by adjusting parental behavior in response to heat. This finding highlights that endothermic vertebrates may be able to adapt to heat stress, which may help their populations cope with the joint challenges of climate change and urbanization. Significance statement Extreme weather events are becoming more frequent due to climate change and can have substantial effects on reproduction and survival of wild animals. Urban heat island can amplify the frequency of extreme hot weather events, making it potentially more harmful for city-dwelling organisms. Alternatively, urban populations living in warmer environments may adapt to better tolerate heat. We investigated these alternatives by comparing nestling development and survival between urban and forest great tit (Parus major) populations. We found that urban populations are less vulnerable to heat: nestling body mass and survival decreased rapidly with the increasing number of hot days in forests, while these effects were dampened in urban broods. Thus, urban populations may become adapted to better tolerate heat events.
Oxidative Assets Toward Biomolecules and Cytotoxicity of New Oxindolimine-Copper(II) and Zinc(II) Complexes

A new oxindolimine ligand derived from isatin (1H-indole-2,3-dione) and 2-aminomethylbenzimidazole was synthesized, leading to two novel complexes after metalation with copper(II) perchlorate or zinc(II) chloride, [Cu(isambz)2](ClO4)2 (complex 1) and [Zn(isambz)Cl2] (complex 2). This new ligand was designed as a more lipophilic compound, in a series of oxindolimine–metal complexes with antitumor properties, having DNA, mitochondria, and some proteins, such as CDK1 kinase and topoisomerase IB, as key targets. The new complexes had their reactivity to human serum albumin (HSA) and DNA, and their cytotoxicity toward tumor cells investigated. The binding to CT-DNA was monitored by circular dichroism (CD) spectroscopy and fluorescence measurements using ethidium bromide in a competitive assay. Consequent DNA cleavage was verified by gel electrophoresis with complex 1, in nmolar concentrations, with formation of linear DNA (form III) after 60 min incubation at 37 °C, in the presence of hydrogen peroxide, which acts as a reducing agent. Formation of reactive oxygen species (ROS) was observed, monitored by spin trapping EPR. Interaction with HSA lead to α-helix structure disturbance, and formation of a stable radical species (HSA–Tyr·) and carbonyl groups in the protein. Despite showing oxidative ability to damage vital biomolecules such as HSA and DNA, these new complexes showed moderate cytotoxicity against hepatocellular carcinoma (HepG2) and neuroblastoma (SHSY5Y) cells, similarly to previous compounds in this series. These results confirm DNA as an important target for these compounds, and additionally indicate that oxidative damage is not the leading mechanism responsible for their cytotoxicity. Additionally, this work emphasizes the importance of ligand characteristics and of speciation in activity of metal complexes.
Design and Research of Smart Neck Helmets Based on the KANO-QFD Model and TRIZ Theory

In order to better serve the safety protection of urban residents during cycling, the KANO model is used to analyze the problems encountered by users wearing helmets during cycling. Combined with QFD, the weighted average analysis of user needs and the importance of engineering measures of product technical characteristics is carried out and users are found. We used TRIZ innovative invention principles to analyze the key requirements and converted them into TRIZ standard problems. We used the corresponding invention measures to improve the existing problems of the helmet and verified the rationality of the design through finite element analysis. Through the KANO-QFD model combined with the TRIZ innovative invention principle, the helmet is optimized to improve its safety.
Mechanistic insight into the activation and negative regulation of plant leucine-rich repeat receptor kinases

Plants integrate external and internal signaling cues to coordinate growth and development. Many of these signaling cues are perceived at the cell surface by plant unique membrane receptor kinases (RKs). Leucine-rich repeat RKs (LRR-RKs) are the most abundant RK family in plants, sensing small molecule, peptide or protein ligands with their extracellular domain. Many LRR-RKs rely on SERK-family co-receptors for receptor activation. How SERKs can contribute to the specific binding of diverse ligands and thus to the activation of different LRR-RKs is poorly understood. The work presented here dissects the contribution of different SERK-interfaces to negative regulation by BIR-proteins as well as to receptor activation. SERKs discriminate ligand-bound and free receptor and thus act as a ‘relay’ to transduce a signal across the membrane. These insights into the activation and negative regulation of LRR-RK signaling in mechanistic detail will help to further extend our understanding of RK signaling in plants.
AGG: A Novel Intelligent Network Traffic Prediction Method Based on Joint Attention and GCN-GRU

Timely and accurate network traffic prediction is a necessary means to realize network intelligent management and control. However, this work is still challenging considering the complex temporal and spatial dependence between network traffic. In terms of spatial dimension, links connect different nodes, and the network traffic flowing through different nodes has a specific correlation. In terms of spatial dimension, not only the network traffic at adjacent time points is correlated, but also the importance of distant time points is not necessarily less than the nearest time point. In this paper, we propose a novel intelligent network traffic prediction method based on joint attention and GCN-GRU (AGG). The AGG model uses GCN to capture the spatial features of traffic, GRU to capture the temporal features of traffic, and attention mechanism to capture the importance of different temporal features, so as to realize the comprehensive consideration of the spatial-temporal correlation of network traffic. The experimental results on an actual dataset show that, compared with other baseline models, the AGG model has the best performance in experimental indicators, such as root mean square error (RMSE), mean absolute error (MAE), accuracy (ACC), determination coefficient ( R 2 ), and explained variance score (EVS), and has the ability of long-term prediction.
Mobile Applications Accessibility: An Evaluation of the Local Portuguese Press

The local press has always played a central role in the Portuguese society. Recently, new innovative technological projects to develop mobile applications and focus on local journalism in Portugal have emerged. These initiatives allow the development of better and more appealing services for local users. However, due to the important social role of the local press, this also brings along some responsibilities. Our main research goal is to study the accessibility issues in local journalism in Portugal. To this end, we first describe the current situation of local journalism in Portugal and some accessibility issues raised by the appearance of mobile applications. We then develop a simple checklist that allows the assessment of whether these applications have prevented social exclusion and facilitated the access of local information to a wide range of users, including disabled citizens. This tool provides the regional news publisher with information to improve its democratization of access to local information in Portugal. Using the cognitive walkthrough method, we illustrate the proposed framework by presenting case studies of five mobile applications in Portuguese local and regional press. This study concludes that despite the great potential that mobile applications showcase, several accessibility issues have not been properly addressed.
Comparing Twitter and Instagram as platforms for party leader communication Findings from the 2017 Norwegian election

While social media have become key in contemporary political campaigns, different platforms feature differing affordances, allowing for varying functionalities. Even more importantly, different platforms are populated by different user groups. As Twitter has received large amounts of scholarly attention, comparisons of how and why different social media platforms are used for political communication are less abundant. This study looks at the differences between Twitter and Instagram as platforms for top politicians, describing and explaining how they allow for interaction with different types of audiences. The study gauges the interaction patterns emerging from activity undertaken by Norwegian party leaders on Twitter and Instagram during the 2017 Norwegian elections and shows how use of these two platforms differ not only in terms of the volume and structure of the activities — but also with regard to what types of other users the party leaders choose to interact with on the studied platforms and why we see differences between them.
Interferon Lambda in the Pathogenesis of Inflammatory Bowel Diseases

Interferon λ (IFN-λ) is critical for host viral defense at mucosal surfaces and stimulates immunomodulatory signals, acting on epithelial cells and few other cell types due to restricted IFN-λ receptor expression. Epithelial cells of the intestine play a critical role in the pathogenesis of Inflammatory Bowel Disease (IBD), and the related type II interferons (IFN-γ) have been extensively studied in the context of IBD. However, a role for IFN-λ in IBD onset and progression remains unclear. Recent investigations of IFN-λ in IBD are beginning to uncover complex and sometimes opposing actions, including pro-healing roles in colonic epithelial tissues and potentiation of epithelial cell death in the small intestine. Additionally, IFN-λ has been shown to act through non-epithelial cell types, such as neutrophils, to protect against excessive inflammation. In most cases IFN-λ demonstrates an ability to coordinate the host antiviral response without inducing collateral hyperinflammation, suggesting that IFN-λ signaling pathways could be a therapeutic target in IBD. This mini review discusses existing data on the role of IFN-λ in the pathogenesis of inflammatory bowel disease, current gaps in the research, and therapeutic potential of modulating the IFN-λ-stimulated response.
Virtual Screening on Marine Natural Products for Discovering TMPRSS2 Inhibitors

Although SARS-CoV-2 entry to cells strictly depends on angiotensin-converting enzyme 2 (ACE2), the virus also needs transmembrane serine protease 2 (TMPRSS2) for its spike protein priming. It has been shown that the entrance of SARS-CoV-2 through ACE2 can be blocked by cellular TMPRSS2 blockers. The main aim of this study was to find potential inhibitor(s) of TMPRSS2 through virtual screening against a homology model of TMPRSS2 using the library of marine natural products (MNPs). The homology modeling technique for generating a three-dimensional structure of TMPRSS2 was applied. Molecular docking, MM-GBSA and absorption, distribution, metabolism, excretion (ADME) evaluations were performed to investigate the inhibitory activity of marine natural products (MNPs) against TMPRSS2 and their pharmacokinetic properties. Camostat and nafamostat mesylate were used as the standard inhibitory molecules. Seven MNPs were able to inhibit TMPRSS2 better than the standard compounds. MNP 10 with CAS number 107503-09-3, called Watasenia β-D- Preluciferyl glucopyrasoiuronic acid, was found to be the best inhibitor of TMPRSS2 with acceptable pharmacokinetic properties. Herein, for the first time, a new marine natural product was introduced with potent inhibitory effects against TMPRSS2. MNP 10 exhibited favorable drug-like pharmacokinetic properties and it promises a novel TMPRSS2 blocker to combat SARS-CoV-2.