Miracle-dz/UniFAR-FTUs huggingface dataset:
Blocking autofluorescence in brain tissues affected by ischemic stroke, hemorrhagic stroke, or traumatic brain injury

Autofluorescence is frequently observed in animal tissues, interfering with an experimental analysis and leading to inaccurate results. Sudan black B (SBB) is a staining dye widely used in histological studies to eliminate autofluorescence. In this study, our objective was to characterize brain tissue autofluorescence present in three models of acute brain injury, including collagenase-induced intracerebral hemorrhage (ICH), traumatic brain injury (TBI), and middle cerebral artery occlusion, and to establish a simple method to block autofluorescence effectively. Using fluorescence microscopy, we examined autofluorescence in brain sections affected by ICH and TBI. In addition, we optimized a protocol to block autofluorescence with SBB pretreatment and evaluated the reduction in fluorescence intensity. Compared to untreated, pretreatment with SBB reduced brain tissue autofluorescence in the ICH model by 73.68% (FITC), 76.05% (Tx Red), and 71.88% (DAPI), respectively. In the TBI model, the ratio of pretreatment to untreated decreased by 56.85% (FITC), 44.28% (Tx Red), and 46.36% (DAPI), respectively. Furthermore, we tested the applicability of the protocol using immunofluorescence staining or Cyanine-5.5 labeling in the three models. SBB treatment is highly effective and can be applied to immunofluorescence and fluorescence label imaging techniques. SBB pretreatment effectively reduced background fluorescence but did not significantly reduce the specific fluorescence signal and greatly improved the signal-to-noise ratio of fluorescence imaging. In conclusion, the optimized SBB pretreatment protocol blocks brain section autofluorescence of the three acute brain injury models.
An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses

The human immunodeficiency virus (HIV), responsible of the Acquired Immune Deficiency Syndrome (AIDS), continues to be a major global public health issue with any cure or vaccine available. The Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is induced by interferons and plays a critical role in the immune response. ISG15 is a modifier protein that covalently binds to its targets via a reversible bond, a process known as ISGylation, which is the best-characterized activity of this protein to date. However, ISG15 can also interact with intracellular proteins via non-covalent binding or act as a cytokine in the extracellular space after secretion. In previous studies we proved the adjuvant effect of ISG15 when delivered by a DNA-vector in heterologous prime-boost combination with a Modified Vaccinia virus Ankara (MVA)-based recombinant virus expressing HIV-1 antigens Env/Gag-Pol-Nef (MVA-B). Here we extended these results evaluating the adjuvant effect of ISG15 when expressed by an MVA vector. For this, we generated and characterized two novel MVA recombinants expressing different forms of ISG15, the wild-type ISG15GG (able to perform ISGylation) or the mutated ISG15AA (unable to perform ISGylation). In mice immunized with the heterologous DNA prime/MVA boost regimen, the expression of the mutant ISG15AA from MVA-Δ3-ISG15AA vector in combination with MVA-B induced an increase in the magnitude and quality of HIV-1-specific CD8 T cells as well as in the levels of IFN-I released, providing a better immunostimulatory activity than the wild-type ISG15GG. Our results confirm the importance of ISG15 as an immune adjuvant in the vaccine field and highlights its role as a potential relevant component in HIV-1 immunization protocols.
Ammonium-nitrate mixtures dominated by NH4 +-N promote the growth of pecan (Carya illinoinensis) through enhanced N uptake and assimilation

Nitrogen (N) limits plant productivity, and its uptake and assimilation may be regulated by N sources, N assimilating enzymes, and N assimilation genes. Mastering the regulatory mechanisms of N uptake and assimilation is a key way to improve plant nitrogen use efficiency (NUE). However, it is poorly known how these factors interact to influence the growth process of pecans. In this study, the growth, nutrient uptake and N assimilation characteristics of pecan were analyzed by aeroponic cultivation at varying NH 4 + / NO 3 − ratios (0/0, 0/100,25/75, 50/50, 75/25,100/0 as CK, T1, T2, T3, T4, and T5). The results showed that T4 and T5 treatments optimally promoted the growth, nutrient uptake and N assimilating enzyme activities of pecan, which significantly increased aboveground biomass, average relative growth rate (RGR), root area, root activity, free amino acid (FAA) and total organic carbon (TOC) concentrations, nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), glutamate synthase (Fd-GOGAT and NADH-GOGAT), and glutamate dehydrogenase (GDH) activities. According to the qRT-PCR results, most of the N assimilation genes were expressed at higher levels in leaves and were mainly significantly up-regulated under T1 and T4 treatments. Correlation analysis showed that a correlation between N assimilating enzymes and N assimilating genes did not necessarily exist. The results of partial least squares path model (PLS-PM) analysis indicated that N assimilation genes could affect the growth of pecan by regulating N assimilation enzymes and nutrients. In summary, we suggested that the NH 4 + / NO 3 − ratio of 75:25 was more beneficial to improve the growth and NUE of pecan. Meanwhile, we believe that the determination of plant N assimilation capacity should be the result of a comprehensive analysis of N concentration, N assimilation enzymes and related genes.
Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study

Objective The real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D. Methods We leveraged publicly available genome-wide association study (GWAS) summary data to perform MR analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen were used. The summary statistic data for T1D (n = 264,137) were obtained from the latest release from the FinnGen consortium as the outcome of interest. The selection of instrumental variables conformed strictly to a series of preset inclusion and exclusion criteria. MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods were used to assess the causal association. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. Results At the phylum level, only Bacteroidetes was indicated to have causality on T1D (OR = 1.24, 95% CI = 1.01-1.53, P = 0.044) in the IVW analysis. When it comes to their subcategories, Bacteroidia class (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P FDR = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P FDR = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10-4, P FDR = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected. Conclusions The present study reports that Bacteroidetes phylum, Bacteroidia class, and Bacteroidales order causally increase T1D risk, whereas Eubacterium eligens group genus, which belongs to the Firmicutes phylum, causally decreases T1D risk. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa’s role in the pathophysiology of T1D.
The effects of microplastic on the thermal profile of sand: implications for marine turtle nesting grounds

Introduction Microplastics (i.e., plastic debris smaller than 5mm) found in coastal areas can impact the marine habitat used by endangered species since they may alter sand properties including temperature and permeability. Such alterations may pose a significant threat to marine turtle populations as nest productivity, sexual development, and hatchling fitness are dependent on conditions within the nest, which incubate in the sand. Given that there is a record of microplastic presence at marine turtle nesting sites, this study was conducted to explore the potential influence of microplastics on the thermal profile of sediment typical of marine turtle nesting habitat. Methods The experiment was conducted at the Florida State University Coastal and Marine Laboratory where the temperatures of containers of sand mixed with 5-30% v/v of either black or white microplastics were recorded from July to September 2018. Results The addition of microplastics in the sand resulted in an increase in temperature – 0.017°C for each 1% v/v increase in microplastic. However, the color of the microplastic did not have a significant effect on sand temperature. Overall, the container with 30% v/v black particles had the highest mean temperature increase of 0.58°C (± 0.34°C) over the control. Discussion The results obtained from this study indicate that extreme concentrations of microplastics could be an issue for marine turtles as any changes in sand temperature may affect the sex ratio of hatchlings and/or alter nest productivity.
BAP1 deficient human and mouse uveal melanomas up-regulate a shared EMT pathway

Monosomy 3 is a negative indicator for uveal melanoma (UM). A key tumor suppressor on chromosome 3 is the deubiquitinase BAP1, which usually has a second hit in cases with monosomy 3. Here, we investigated the role of Bap1 loss in the GNAQQ209L mouse UM model. We found that heterozygous Bap1 mutations increased the proportion of lung lesions reaching an unusually large size and permitted the growth of liver lesions. Comparison of RNAseq data from mouse and human UM identified a set of 270 genes differentially expressed in the same direction when BAP1 is mutant. The most significant pathway in this gene set was Epithelial to Mesenchymal Transition (EMT). The expression of five apical junction complex genes known to be down-regulated in association with EMT was very significantly correlated with survival in human UM patients. Activation of EMT through Bap1 deficiency could increase melanoma plasticity and adaptation to new microenvironments.
Computational insights on the destabilizing mutations in the binding site of 3CL-protease SARS-CoV-2 Omicron (VOC)

The COVID-19 (Corona Virus Disease 19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is causing enormous difficulties in the world’s economies and there is uncertainty as to whether the current prophylactic measures will offer adequate protection globally after the appearance of virus variants that like that indicated as Omicron emerged in the presence of global vaccine-based immunization. While several studies are available describing the main differences in the spike protein of Omicron compared to the other variants previously emerged, there was no structural insights into the 3CL-protease (3CLpro) associated to the new variant. Herein, we performed a computational study based on genomic data and amino acid sequences available in the most updated COVID-19-related databases that allowed us to build up in silico the 3D structure of Omicron 3CLpro. Moreover, by molecular dynamics simulation we demonstrated that currently available drugs acting as inhibitors of the SARS-CoV-2 main protease could be less effective in the case of Omicron variant due to the different chemical interactions in the binding site occurred after the recent amino acid mutations. Ultimately, our study highlights the need of exploiting in silico and in vitro methods to discover novel 3CLpro inhibitors starting from the computationally based structure we presented herein, and more in general to direct the major efforts to targeting the most conserved 3CLpro regions that appeared unchanged in the context of the Omicron variant.
Pupil size predicts the onset of exploration in brain and behavior

In uncertain environments, intelligent decision-makers exploit actions that have been rewarding in the past, but also explore actions that could be even better. Several neuromodulatory systems are implicated in exploration, based, in part, on work linking exploration to pupil size–a peripheral correlate of neuromodulatory tone and index of arousal. However, pupil size could instead track variables that make exploration more likely, like volatility or reward, without directly predicting either exploration or its neural bases. Here, we simultaneously measured pupil size, exploration, and neural population activity in the prefrontal cortex while two rhesus macaques explored and exploited in a dynamic environment. We found that pupil size under constant luminance specifically predicted the onset of exploration, beyond what could be explained by reward history. Pupil size also predicted disorganized patterns of prefrontal neural activity at both the single neuron and population levels, even within periods of exploitation. Ultimately, our results support a model in which pupil-linked mechanisms promote the onset of exploration via driving the prefrontal cortex through a critical tipping point where prefrontal control dynamics become disorganized and exploratory decisions are possible.
Expansion of novel biosynthetic gene clusters from diverse environments using SanntiS

Natural products biosynthesised by microbes are an important component of the pharmacopeia with a vast array of biomedical and industrial applications, in addition to their key role in mediating many ecological interactions. One approach for the discovery of these metabolites is the identification of biosynthetic gene clusters (BGCs), genomic units which encode the molecular machinery required for producing the natural product. Genome mining has revolutionised the discovery of BGCs, yet metagenomic assemblies represent a largely untapped source of natural products. The imbalanced distribution of BGC classes in existing databases restricts the generalisation of detection patterns and limits the ability of mining methods to recognise a broader spectrum of BGCs. This problem is further intensified in metagenomic datasets, where BGC genes may be incomplete. This work presents SanntiS, a new machine learning-based tool for identifying BGCs. SanntiS achieved high precision and recall in both genomic and metagenomic datasets, effectively capturing a broad range of BGCs. Application of SanntiS to MGnify metagenomic assemblies led to a resource containing 1.9 million BGC predictions with associated contextual data from diverse biomes and demonstrates a significant fraction of novelty compared to equivalent isolate genomes datasets. Subsequent experimental validation of a novel antimicrobial peptide detected solely by SanntiS, further demonstrates the potential of this approach for uncovering novel bioactive compounds.
A combination of convergent extension and differential adhesion explains the shapes of elongating gastruloids

Gastruloids have emerged as highly useful in vitro models of mammalian gastrulation. One of the most striking features of 3D gastruloids is their elongation, which mimics the extension of the embryonic anterior-posterior axis. Although axis extension is crucial for development, the underlying mechanism has not been fully elucidated in mammalian species. Gastruloids provide an opportunity to study this morphogenic process in vitro. Here, we measure and quantify the shapes of elongating gastruloids and show, by Cellular Potts model simulations, that a combination of convergent extension and differential adhesion can explain the observed shapes. We reveal that differential adhesion alone is insufficient and also directly observe hallmarks of convergent extension by time-lapse imaging of gastruloids. Finally, we show that gastruloid elongation can be abrogated by inhibition of the Rho kinase pathway, which is involved in convergent extension in vivo. All in all, our study demonstrates, how gastruloids can be used to elucidate morphogenic processes in embryonic development.
Gigahertz single-electron pumping in silicon with an accuracy better than 9.2 parts in 107

High-speed and high-accuracy pumping of a single electron is crucial for realizing an accurate current source, which is a promising candidate for a quantum current standard. Here, using a high-accuracy measurement system traceable to primary standards, we evaluate the accuracy of a Si tunable-barrier single-electron pump driven by a single sinusoidal signal. The pump operates at frequencies up to 6.5 GHz, producing a current of more than 1 nA. At 1 GHz, the current plateau with a level of about 160 pA is found to be accurate to better than 0.92 ppm (parts per million), which is a record value for 1-GHz operation. At 2 GHz, the current plateau offset from 1ef (∼320 pA) by 20 ppm is observed. The current quantization accuracy is improved by applying a magnetic field of 14 T, and we observe a current level of 1ef with an accuracy of a few ppm. The presented gigahertz single-electron pumping with a high accuracy is an important step towards a metrological current standard.
NEW TOOLS FOR ROUGH APPROXIMATIONS IN BITOPOLOGICAL SPACES

ABSTRACT The purpose of this paper is to introduce a class of open sets in bitopological spaces. This clan is based on closure and interior operators with respect to the two topologies. Properties and characterization of the new clan are obtained and some examples and counter examples are given. The suggested clan can be used in the context of generalized rough set approximation which is widely applied in the fields of artificial intelligence and knowledge discovery. Keywords: Bitopological spaces, Rough sets, Information systems.
Using SAS PROC MIXED to Fit Multilevel Models, Hierarchical Models, and Individual Growth Models

SAS PROC MIXED is a flexible program suitable for fitting multilevel models, hierarchical linear models, and individual growth models. Its position as an integrated program within the SAS statistical package makes it an ideal choice for empirical researchers and applied statisticians seeking to do data reduction, management, and analysis within a single statistical package. Because the program was developed from the perspective of a “mixed” statistical model with both random and fixed effects, its syntax and programming logic may appear unfamiliar to users in education and the social and behavioral sciences who tend to express these models as multilevel or hierarchical models. The purpose of this paper is to help users familiar with fitting multilevel models using other statistical packages (e.g., HLM, MLwiN, MIXREG) add SAS PROC MIXED to their array of analytic options. The paper is written as a step-by-step tutorial that shows how to fit the two most common multilevel models: (a) school effects models, designed for data on individuals nested within naturally occurring hierarchies (e.g., students within classes); and (b) individual growth models, designed for exploring longitudinal data (on individuals) over time. The conclusion discusses how these ideas can be extended straighforwardly to the case of three level models. An appendix presents general strategies for working with multilevel data in SAS and for creating data sets at several levels.
Comparison of bootstrap estimation intervals to forecast arithmetic mean and median air passenger demand

ABSTRACT The aim of this paper is to compare passenger (pax) demand between airports based on the arithmetic mean (MPD) and the median pax demand (MePD). A three phases approach is applied. First phase, we use bootstrap procedures to estimate the distribution of the arithmetic MPD and the MePD for each block of routes distance; second phase, we use percentile, standard, bias corrected, and bias corrected accelerated methods to calculate bootstrap confidence bands for the MPD and the MePD; and third phase, we implement Monte Carlo (MC) experiments to analyse the finite sample performance of the applied bootstrap. Our results conclude that it is more meaningful to use the estimation of MePD rather than the estimation of MPD in the air transport industry. By carrying out MC experiments, we demonstrate that the bootstrap methods produce coverages close to the nominal for the MPD and the MePD.
Range Estimation Priority: A Method to Sift Out Weak-weighted Criteria in AHP

In this paper,it is shown priority vectors are full of deviations and uncertainties.This occurs due to the decision-makers' uncertainties and errors in comparisons as well as inconsistencies in judgment matrices in Analytical Hierarchy Process(AHP). The contribution to evaluation goals of the criteria with very weak weights may be submerged in such deviations and uncertainties,which makes those criteria meaningless and should be sifted out.The concept and method to sift such criteria out are proposed in this paper.This method allows decision-makers to identify and sift out weak-weighted criteria;this is especially helpful for decision-makers who want to build a set of criteria for a specific problem from a large set of criteria for general purposes.With downsizing in criteria numbers,decision-makers are expected to make fewer errors in judgment,and it's easier for judgment matrices to reach consistency.Moreover,the performance information of each alternative on those weak-weighted criteria is no more necessary,which further improves the usability of AHP.It's proved that this method is feasible,convenient and robust by the numerical case provided in this paper.
7-S model framework for assessment of challenges faced by teachers of children with autism spectrum disorders in the Limpopo province, South Africa

needs of people with autism are complex and require a range of integrated services that include health promotion, care and rehabilitation (WHO 2021). An integral part of the process of teaching students with autism is the provision of communication, the development of social skills and academic (traditional) training (Andrunyk, Shestakevych & Pasichnyk 2018). Background: The number of children with autism spectrum disorder (ASD) is rapidly increasing globally and requires a supportive educational system to meet the needs of these children. Aim: The study assessed challenges faced by teachers of children with ASD in the public special schools of the Limpopo province, South Africa. Setting: The study was conducted in seven public special schools in the Limpopo province, South Africa. Methods: Face-to-face semistructured interviews were conducted with 12 teachers regarding the challenges they face in educating children with ASD. Tesch’s inductive, descriptive open coding technique enabled the researcher to analyse and report, subthemes that emerged from this qualitative explorative and descriptive data. Measures to ensure trustworthiness and ethical considerations were carried out throughout the study. Results: Analysis of the interviews revealed that the structure and systems of special schools do not support the educational needs of children with ASD. The strategic plans and policy framework on inclusive education are not being executed adequately. Learning for ASD children is not supported because of substandard infrastructure, curricula, lack of teaching material, health practitioners, unbalanced teacher–learner ratio, inadequate staff skills, school culture, shared beliefs and lack of management support. Conclusion: The study revealed challenges faced by special education teachers indicating the influence on the provision of high-quality education to children with ASD. The Department of Basic Education at the national level should monitor all special schools regularly, provide the necessary support and ensure that the complex needs of children with ASD are met. Contribution: The study contributes to understanding of the challenges faced by teachers of children with ASD in providing high quality of education and affirm sound basis of advance information to monitor and evaluate the education of children with ASD in special public schools, which is within the scope of the journal.