Miracle-dz/UniFAR-FTUs huggingface dataset:
CRISPR-dependent base editing screens identify separation of function mutants of RADX with altered RAD51 regulatory activity

RAD51 forms nucleoprotein filaments to promote homologous recombination, replication fork reversal, and fork protection. Numerous factors regulate the stability of these filaments and improper regulation leads to genomic instability and ultimately disease including cancer. RADX is a single stranded DNA binding protein that modulates RAD51 filament stability. Here, we utilize a CRISPR-dependent base editing screen to tile mutations across RADX to delineate motifs required for RADX function. We identified separation of function mutants of RADX that bind DNA and RAD51 but have a reduced ability to stimulate its ATP hydrolysis activity. Cells expressing these RADX mutants accumulate RAD51 on chromatin, exhibit replication defects, have reduced growth, accumulate DNA damage, and are hypersensitive to DNA damage and replication stress. These results indicate that RADX must bind RAD51 and promote RAD51 ATP turnover to regulate RAD51 and genome stability during DNA replication.
Synergistic genomic mechanisms of adaptation to ocean acidification in a coral holobiont

Ocean acidification, caused by anthropogenic CO2 emissions, is predicted to have major consequences for reef-building corals, jeopardizing the scaffolding of the most biodiverse marine habitats. However, whether corals can adapt to ocean acidification and how remains unclear. We addressed these questions by re-examining transcriptome and genome data of Acropora millepora coral holobionts from volcanic CO2 seeps with end-of-century pH levels. We show that adaptation to ocean acidification is a wholistic process involving the three main compartments of the coral holobiont. We identified 441 coral host candidate adaptive genes involved in calcification, response to acidification, and symbiosis; population genetic differentiation in dinoflagellate photosymbionts; and consistent transcriptional microbiome activity despite microbial community shifts. Coral holobionts from natural analogues to future ocean conditions harbor beneficial genetic variants with far-reaching rapid adaptation potential. In the face of climate change, these populations require immediate conservation strategies as they could become key to coral reef survival.
Fluctuating selection facilitates the discovery of broadly effective but difficult to reach adaptive outcomes in yeast

Evolutionary compromises are thought to be common under fluctuating selection because the mutations that best enable adaptation to one environmental context can often be detrimental in others. Yet, prior experimental work has shown that generalists can sometimes perform as well as specialists in their own environments. Here we use a highly replicated evolutionary experiment (N = 448 asexual lineages of the brewer’s yeast) to show that even though fluctuation between two environmental conditions often induces evolutionary compromises (at least early on), it can also help reveal difficult to reach adaptive outcomes that ultimately improve performance in both environments. Specifically, we begin by showing that yeast adaptation to chemical stress can involve fitness tradeoffs with stress-free environments and that, accordingly, lineages that are repeatedly exposed to occasional stress tend to respond by trading performance for breadth of adaptation. We then show that on rare occasions, fluctuating selection leads to the evolution of no-cost generalists that can even outcompete constant selection specialists in their own environments. We propose that the discovery of these broader and more effective adaptive outcomes under fluctuating selection could be partially facilitated by changes in the adaptive landscape that result from having to deal with fitness tradeoffs across different environmental conditions. Overall, our findings indicate that reconciling the short- and long-term evolutionary consequences of fluctuating selection could significantly improve our understanding of the evolution of specialization and generalism.
Rational engineering of an elevator-type metal transporter ZIP8 reveals a conditional selectivity filter critically involved in determining substrate specificity

Engineering of transporters to alter substrate specificity as desired holds great potential for applications, including metabolic engineering. However, the lack of knowledge on molecular mechanisms of substrate specificity hinders designing effective strategies for transporter engineering. Here, we applied an integrated approach to rationally alter the substrate preference of ZIP8, a Zrt-/Irt-like protein (ZIP) metal transporter with multiple natural substrates, and uncovered the determinants of substrate specificity. By systematically replacing the differentially conserved residues with the counterparts in the zinc transporter ZIP4, we created a zinc-preferring quadruple variant (Q180H/E343H/C310A/N357H), which exhibited largely reduced transport activities towards Cd^2+, Fe^2+, and Mn^2+ whereas increased activity toward Zn^2+. Combined mutagenesis, modeling, covariance analysis, and computational studies revealed a conditional selectivity filter which functions only when the transporter adopts the outward-facing conformation. The demonstrated approach for transporter engineering and the gained knowledge about substrate specificity will facilitate engineering and mechanistic studies of other transporters. An integrated experimental and computational approach reveals an ion selectivity filter in multi-metal transporter ZIP8 that is rationally engineered to increase preference toward Zn^2+ over Cd^2+.
Near ultraviolet excited Eu 3+ doped Li 3 Ba 2 La 3 (WO 4 ) 8 red phosphors for white light emitting diodes

Eu3+ doped Li3Ba2La3(WO4)8 red phosphors were synthesized by the solid state reaction method. A pure phase was confirmed by the X-ray diffraction pattern. Diffuse reflection spectra, photoluminescence spectra, decay curves, quantum yields, and temperature-dependence luminescence spectra were measured. The Eu3+ ions can substitute the La3+ ions completely without decreasing the emission intensity obviously and the quantum yields can keep at about 95%. The activation energy from the bottom of 5D0 level to the 5D0-charge transfer state crossover is 0.24eV. All the results indicate that the Eu3+ doped Li3Ba2La3(WO4)8 can serve as a near ultraviolet excited red phosphor for white light emitting diodes.
Tree Species Classification in UAV Remote Sensing Images Based on Super-Resolution Reconstruction and Deep Learning

We studied the use of self-attention mechanism networks (SAN) and convolutional neural networks (CNNs) for forest tree species classification using unmanned aerial vehicle (UAV) remote sensing imagery in Dongtai Forest Farm, Jiangsu Province, China. We trained and validated representative CNN models, such as ResNet and ConvNeXt, as well as the SAN model, which incorporates Transformer models such as Swin Transformer and Vision Transformer (ViT). Our goal was to compare and evaluate the performance and accuracy of these networks when used in parallel. Due to various factors, such as noise, motion blur, and atmospheric scattering, the quality of low-altitude aerial images may be compromised, resulting in indistinct tree crown edges and deficient texture. To address these issues, we adopted Real-ESRGAN technology for image super-resolution reconstruction. Our results showed that the image dataset after reconstruction improved classification accuracy for both the CNN and Transformer models. The final classification accuracies, validated by ResNet, ConvNeXt, ViT, and Swin Transformer, were 96.71%, 98.70%, 97.88%, and 98.59%, respectively, with corresponding improvements of 1.39%, 1.53%, 0.47%, and 1.18%. Our study highlights the potential benefits of Transformer and CNN for forest tree species classification and the importance of addressing the image quality degradation issues in low-altitude aerial images.
Validation of FY-4A Temperature Profiles by Radiosonde Observations in Taklimakan Desert in China

The atmospheric temperature profiles (ATPs) retrieved through the geostationary Interferometric Infrared Sounder (GIIRS) onboard the FY-4A satellite (GIIRS/FY-4A) can effectively fill the gap of the scarce conventional sounding data in the Taklimakan Desert (TD), the second largest desert in the world, with an area of 330,000 square kilometers. In this study, we take the experimental radiosonde observations (RAOB) from one RAOB station in the hinterland of TD and seven conventional radiosondes in the oasis region around the desert as the true values and analyze the bias distribution characteristics of GIIRS/FY-4A ATPs with quality control (QC) flags 0 or 1 for this region. In addition, a bias comparison is made with GIIRS/FY-4A ATPs, and the fifth generation ECMWF atmospheric reanalysis of the global climate (ERA5) ATPs. The results show that (1) Missing measurements in GIIRS/FY-4A ATPs are the most frequent in the near-surface layer, accounting for more than 80% of all the retrieved grid points. The averaged total proportion of GIIRS/FY-4A ATPs with QC marks 0 or 1 is about 33.06%. (2) The root mean square error (RMSE) of GIIRS/FY-4A ATPs is less than 3 K, smaller than that of ERA5 ATPs. The RMSE of ERA5 ATPs can exceed 10 K in the desert hinterland. The absolute mean biases of GIIRS/FY-4A ATPs and ERA5 ATPs are, respectively, smaller than 3 K and 2 K, the former being slightly larger. The correlation coefficients of GIIRS/FY-4A ATPs with ERA5 ATPs and RAOB ATPs are higher than 0.98 and 0.99, respectively, and the correlation between GIIRS/FY-4A ATPs and RAOB ATPs is inferior to the latter. (3) The overall atmospheric temperature retrieved by GIIRS/FY-4A is 0.08 K higher than the temperature of RAOB, on average, while the overall temperature from ERA5 is 0.13 K lower than that of RAOB, indicating that the temperature profile obtained by integrating GIIRS/FY-4A ATPs and ERA5 ATPs may be much closer to RAOB ATPs. (4) The probability density of the GIIRS/FY-4A ATP biases in the TD region generally follows the Gaussian distribution so that it can be effectively assimilated in the 3-D variational assimilation modules. The probability density distribution characteristics of the GIIRS/FY-4A ATP biases in the desert hinterland and oasis are not much different. However, due to the fusion analysis of the relatively rich multi-source conventional observation data from the oasis stations, the probability density of ERA5 ATPs biases at the oasis stations is nearer to Gaussian distribution than that of the GIIRS/FY-4A ATPs. In the desert hinterland, where conventional observation is not enough, the probability density distributions of the ATPs biases from ERA5 and GIIRS/FY-4A are alike. Therefore, the GIIRS FY4A can contribute to a more accurate estimation of ERA5 ATPs in the TD region.
University students’ perspectives on diagnostic testing in mathematics

Many universities issue mathematical diagnostic tests to incoming first-year students, covering a range of the basic concepts with which they should be comfortable from secondary school. As far as many lecturers are concerned, the purpose of this test is to determine the students' mathematical knowledge on entry. It should also provide an early indication of which students are likely to need additional help, and hopefully encourage such students to avail of extra support mechanisms at an early stage. However, it is not clear that students recognize these intentions and there is a fear that students who score poorly in the test will have their confidence further damaged in relation to mathematics and will be reluctant to seek help. To this end, a questionnaire was developed to explore students’ perspectives on diagnostic testing. Analysis of responses received to the questionnaire provided an interesting insight into students’ perspectives including the optimum time to conduct such a test, their views on the aims of diagnostic testing, whether they feel that testing is a good idea, and their attitudes to the support systems put in place to help those who scored poorly in the test.
Entropy-Conditioned Syncope of Vowels in Latin and Ibero-Romance

In this paper, I contrast Old Spanish and Latin, showing that post-tonic syllables are subject to vowel syncope because they in fact carry less overt information via actual utterance. This is measured in terms of entropy, using maximum likelihood estimates from a trigram model of Latin segments. For the hypothesis to be correct, the entropy of the probability distribution from the summation of all maximum likelihood estimates of vowels after a stressed syllable should be lower than that of vowels after an unstressed syllable. I discuss the methodology of my experiment as well as frame my findings in optimality-theoretic terms.
Role of vitamin C and SVCT2 in neurogenesis

Different studies have established the fundamental role of vitamin C in proliferation, differentiation, and neurogenesis in embryonic and adult brains, as well as in in vitro cell models. To fulfill these functions, the cells of the nervous system regulate the expression and sorting of sodium-dependent vitamin C transporter 2 (SVCT2), as well as the recycling of vitamin C between ascorbic acid (AA) and dehydroascorbic acid (DHA) via a bystander effect. SVCT2 is a transporter preferentially expressed in neurons and in neural precursor cells. In developmental stages, it is concentrated in the apical region of the radial glia, and in adult life, it is expressed preferentially in motor neurons of the cerebral cortex, starting on postnatal day 1. In neurogenic niches, SVCT2 is preferentially expressed in precursors with intermediate proliferation, where a scorbutic condition reduces neuronal differentiation. Vitamin C is a potent epigenetic regulator in stem cells; thus, it can induce the demethylation of DNA and histone H3K27m3 in the promoter region of genes involved in neurogenesis and differentiation, an effect mediated by Tet1 and Jmjd3 demethylases, respectively. In parallel, it has been shown that vitamin C induces the expression of stem cell-specific microRNA, including the Dlk1–Dio3 imprinting region and miR-143, which promotes stem cell self-renewal and suppresses de novo expression of the methyltransferase gene Dnmt3a. The epigenetic action of vitamin C has also been evaluated during gene reprogramming of human fibroblasts to induced pluripotent cells, where it has been shown that vitamin C substantially improves the efficiency and quality of reprogrammed cells. Thus, for a proper effect of vitamin C on neurogenesis and differentiation, its function as an enzymatic cofactor, modulator of gene expression and antioxidant is essential, as is proper recycling from DHA to AA by various supporting cells in the CNS.
Genetic characterization and whole-genome sequencing-based genetic analysis of influenza virus in Jining City during 2021–2022

Background The influenza virus poses a significant threat to global public health due to its high mutation rate. Continuous surveillance, development of new vaccines, and public health measures are crucial in managing and mitigating the impact of influenza outbreaks. Methods Nasal swabs were collected from individuals with influenza-like symptoms in Jining City during 2021-2022. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect influenza A viruses, followed by isolation using MDCK cells. Additionally, nucleic acid detection was performed to identify influenza A H1N1, seasonal H3N2, B/Victoria, and B/Yamagata strains. Whole-genome sequencing was conducted on 24 influenza virus strains, and subsequent analyses included characterization, phylogenetic construction, mutation analysis, and assessment of nucleotide diversity. Results A total of 1,543 throat swab samples were collected. The study revealed the dominance of the B/Victoria influenza virus in Jining during 2021-2022. Whole-genome sequencing showed co-prevalence of B/Victoria influenza viruses in the branches of Victoria clade 1A.3a. 1 and Victoria clade 1A.3a. 2, with a higher incidence observed in winter and spring. Comparative analysis demonstrated lower similarity in the HA, MP, and PB2 gene segments of the 24 sequenced influenza virus strains compared to the Northern Hemisphere vaccine strain B/Washington/02/2019. Mutations were identified in all antigenic epitopes of the HA protein at R133G, N150K, and N197D, and the 17-sequence antigenic epitopes exhibited more than 4 amino acid variation sites, resulting in antigenic drift. Moreover, one sequence had a D197N mutation in the NA protein, while seven sequences had a K338R mutation in the PA protein. Conclusion This study highlights the predominant presence of B/Victoria influenza strain in Jining from 2021 to 2022. The analysis also identified amino acid site variations in the antigenic epitopes, contributing to antigenic drift.
Establishment of a dynamic nomogram including thyroid function for predicting the prognosis of acute ischemic stroke with standardized treatment

Purpose Many patients with acute ischemic stroke (AIS) cannot undergo thrombolysis or thrombectomy because they have missed the time window or do not meet the treatment criteria. In addition, there is a lack of an available tool to predict the prognosis of patients with standardized treatment. This study aimed to develop a dynamic nomogram to predict the 3-month poor outcomes in patients with AIS. Methods This was a retrospective multicenter study. We collected the clinical data of patients with AIS who underwent standardized treatment at the First People's Hospital of Lianyungang from 1 October 2019 to 31 December 2021 and at the Second People's Hospital of Lianyungang from 1 January 2022 to 17 July 2022. Baseline demographic, clinical, and laboratory information of patients were recorded. The outcome was the 3-month modified Rankin Scale (mRS) score. The least absolute shrinkage and selection operator regression were used to select the optimal predictive factors. Multiple logistic regression was performed to establish the nomogram. A decision curve analysis (DCA) was applied to assess the clinical benefit of the nomogram. The calibration and discrimination properties of the nomogram were validated by calibration plots and the concordance index. Results A total of 823 eligible patients were enrolled. The final model included gender (male; OR 0.555; 95% CI, 0.378–0.813), systolic blood pressure (SBP; OR 1.006; 95% CI, 0.996–1.016), free triiodothyronine (FT3; OR 0.841; 95% CI, 0.629–1.124), National Institutes of Health stroke scale (NIHSS; OR 18.074; 95% CI, 12.264–27.054), Trial of Org 10172 in Acute Stroke Treatment (TOAST; cardioembolic (OR 0.736; 95% CI, 0.396–1.36); and other subtypes (OR 0.398; 95% CI, 0.257–0.609). The nomogram showed good calibration and discrimination (C-index, 0.858; 95% CI, 0.830–0.886). DCA confirmed the clinical usefulness of the model. The dynamic nomogram can be obtained at the website: predict model (90-day prognosis of AIS patients). Conclusion We established a dynamic nomogram based on gender, SBP, FT3, NIHSS, and TOAST, which calculated the probability of 90-day poor prognosis in AIS patients with standardized treatment.
Editorial: Dietary supplements for preserving thyroid health: the scientific evidence-based view

COPYRIGHT © 2023 Unfer, Koch, Benvenga and Leung. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Editorial PUBLISHED 13 June 2023 DOI 10.3389/fendo.2023. 1213082
A genetic regulatory see-saw of biofilm and virulence in MRSA pathogenesis

Staphylococcus aureus is one of the most common opportunistic human pathogens causing several infectious diseases. Ever since the emergence of the first methicillin-resistant Staphylococcus aureus (MRSA) strain decades back, the organism has been a major cause of hospital-acquired infections (HA-MRSA). The spread of this pathogen across the community led to the emergence of a more virulent subtype of the strain, i.e., Community acquired Methicillin resistant Staphylococcus aureus (CA-MRSA). Hence, WHO has declared Staphylococcus aureus as a high-priority pathogen. MRSA pathogenesis is remarkable because of the ability of this “superbug” to form robust biofilm both in vivo and in vitro by the formation of polysaccharide intercellular adhesin (PIA), extracellular DNA (eDNA), wall teichoic acids (WTAs), and capsule (CP), which are major components that impart stability to a biofilm. On the other hand, secretion of a diverse array of virulence factors such as hemolysins, leukotoxins, enterotoxins, and Protein A regulated by agr and sae two-component systems (TCS) aids in combating host immune response. The up- and downregulation of adhesion genes involved in biofilm formation and genes responsible for synthesizing virulence factors during different stages of infection act as a genetic regulatory see-saw in the pathogenesis of MRSA. This review provides insight into the evolution and pathogenesis of MRSA infections with a focus on genetic regulation of biofilm formation and virulence factors secretion.
Shooter ready? Integrating mental skills training in an advanced sniper course

Performance psychology has increased in usage and popularity; however, we contend that within the elite spheres of the military, there is a need for research and development to fit the context and environment. In this study, we describe an explorative case study on the integration of mental skill training techniques to an advanced sniper course in the Norwegian Armed Forces. We evaluate the impact through triangulation and examine results on the course, perceptions of the participants, and observations from the instructors. In addition, we conducted a 1-year follow-up to get participants' experience of translating the skills beyond the course. The results show that the mental skill training package influenced both results and performance in a positive manner; however, as a novel field, further research is warranted to establish a best practice to enhance performance for elite military forces.
Diet and obesity effects on cue-driven food-seeking: insights from studies of Pavlovian-instrumental transfer in rodents and humans

Our modern environment is said to be obesogenic, promoting the consumption of calorically dense foods and reducing energy expenditure. One factor thought to drive excess energy intake is the abundance of cues signaling the availability of highly palatable foods. Indeed, these cues exert powerful influences over food-related decision-making. Although obesity is associated with changes to several cognitive domains, the specific role of cues in producing this shift and on decision-making more generally, remains poorly understood. Here we review the literature examining how obesity and palatable diets affect the ability of Pavlovian cues to influence instrumental food-seeking behaviors by examining rodent and human studies incorporating Pavlovian-instrumental transfer (PIT) protocols. There are two types of PIT: (a) general PIT that tests whether cues can energize actions elicited in the pursuit of food generally, and (b) specific PIT which tests whether cues can elicit an action that earns a specific food outcome when faced with a choice. Both types of PIT have been shown to be vulnerable to alterations as a result of changes to diet and obesity. However, effects appear to be driven less by increases in body fat and more by palatable diet exposure per se. We discuss the limitations and implications of the current findings. The challenges for future research are to uncover the mechanisms underlying these alterations to PIT, which appear unrelated to excess weight itself, and to better model the complex determinants of food choice in humans.