Miracle-dz/UniFAR-FTUs huggingface dataset:
A high-throughput multiplex array for antigen-specific serology with automated analysis

High-throughput customizable CBA automated script-based analysis The utility of high-throughput systems to evaluate antigen-specific antibody (Ab) has been highlighted by the SARS-CoV-2 pandemic. Pathogen-specific Ab levels are often used to assess protection following vaccination and, in the case of novel pathogens, an indication of prior exposure. Several platforms exist to visualize antigen-specific Ab, however most are not quantitative and are difficult to scale for population level studies. Additionally, the sensitivity across platforms differs making direct comparisons between studies difficult. Cytometric bead arrays (CBA) are an attractive platform for antigen-specific Ab measurements as they can be used to assess Ab reactivity against several antigens and of several isotypes to be performed simultaneously. Additionally, CBAs exhibit high sensitivity and can be designed to provide quantitative measurements. Using commercially available particles, a biotin-Streptavidin bead loading strategy, and the inclusion of indirect standards, we describe a flexible system that can be modified to include a variety of antigens. Here we describe two arrays, focused on antigens derived from either β-coronaviruses or influenza virus. To support the high-throughput capacity of this system, we developed a suit of automated software tools, the CBA Toolbox, to process raw data into antigen-reactive IgM, IgA, and IgG concentrations. We describe quality control requirements, assay performance, and normalizations to accurately quantitate antigen-specific Ig.
RAVEN: development of a novel volumetric extrusion-based system for small-scale Additive Manufacturing

Recent technological advances in the field of Additive Manufacturing (AM) and the increasing need in Regenerative Medicine (RM) for devices that better and better mimic native tissues architecture are showing limitations in the current scaffolds fabrication techniques. A switch from the typical layer-by-layer approach is needed to achieve precise control on fibers orientation and pores dimension and morphology. In this work a new AM apparatus, the RAVEN (Robot-Assisted Volumetric ExtrusioN) system, is presented. RAVEN is based on a 7-DOF robotic arm and an FDM extruder and allows for volumetric extrusion of polymeric filaments. The development process, namely the robotic motion optimization, the optimization towards small-scale trajectories, the custom-made hardware/software interfaces, and the different printing capabilities are hereby presented. The successful results are promising towards future advanced applications such as in vivo bioprinting, in which the ability of the robot to change its configuration while printing will be crucial.
RNAi-mediated knockdown of two orphan G protein-coupled receptors reduces fecundity in the yellow fever mosquito Aedes aegypti

G-protein coupled receptors (GPCRs) control numerous physiological processes in insects, including reproduction. While many GPCRs have known ligands, orphan GPCRs do not have identified ligands in which they bind. Advances in genomic sequencing and phylogenetics provide the ability to compare orphan receptor protein sequences to sequences of characterized GPCRs, and thus gain a better understanding of their potential function. Our study investigated two orphan GPCRs, AAEL003647 and AAEL019988, in the yellow fever mosquito, Aedes aegypti. From our phylogenetic analysis, we found that AAEL003647 is orthologous to the SIFamide-2/SMYamide receptor, while AAEL019988 is orthologous to the Trapped in endoderm (Tre1) receptor of Drosophila melanogaster. Tissue-specific expression analysis revealed that both receptors had highest expression in the ovaries, suggesting they may be important for reproduction. We then used RNA interference (RNAi) to knock down both genes and found a significant reduction in the number of eggs laid per individual female mosquito, suggesting both receptors are important for Ae. aegypti reproduction.
XMAP: Cross-population fine-mapping by leveraging genetic diversity and accounting for confounding bias

Fine-mapping prioritizes risk variants identified by genome-wide association studies (GWASs), serving as a critical step to uncover biological mechanisms underlying complex traits. However, several major challenges still remain for existing fine-mapping methods. First, the strong linkage disequilibrium among variants can limit the statistical power and resolution of fine-mapping. Second, it is computationally expensive to simultaneously search for multiple causal variants. Third, the confounding bias hidden in GWAS summary statistics can produce spurious signals. To address these challenges, we develop a statistical method for cross-population fine-mapping (XMAP) by leveraging genetic diversity and accounting for confounding bias. By using cross-population GWAS summary statistics from global biobanks and genomic consortia, we show that XMAP can achieve greater statistical power, better control of false positive rate, and substantially higher computational efficiency for identifying multiple causal signals, compared to existing methods. Importantly, we show that the output of XMAP can be integrated with single-cell datasets, which greatly improves the interpretation of putative causal variants in their cellular context at single-cell resolution.
Quorum-sensing gene regulates hormetic effects induced by sulfonamides in Comamonadaceae

ABSTRACT Hormesis is a toxicological phenomenon whereby exposure to low-dose stress results in the stimulation of various biological endpoints. Among these, the induction of cell proliferation by antibiotics is critical, but the underlying molecular mechanisms remain poorly understood. Here, we showed that sulfonyl-containing chemicals (e.g., sulfonamides) can induce cell proliferation hormesis in Comamonas testosteroni. An investigation of the hormesis mechanism revealed that low-dose sulfonamides potentially interact with the LuxR-type quorum-sensing protein LuxR solo, thereby triggering the transcription of 3-ketoacyl-CoA thiolase, a key enzyme of fatty acid β-oxidation. This provides additional ATP, NADPH, and acetyl-CoA for macromolecule biosynthesis, allowing cells to synthesize sufficient nucleotides to support rapid cell growth. Our work reports on a previously unknown mechanism for the hormetic effect and highlights its generality in the Comamonadaceae family. IMPORTANCE Antibiotics can induce dose-dependent hormetic effects on bacterial cell proliferation, i.e., low-dose stimulation and high-dose inhibition. However, the underlying molecular basis has yet to be clarified. Here, we showed that sulfonamides play dual roles as a weapon and signal against Comamonas testosteroni that can modulate cell physiology and phenotype. Subsequently, through investigating the hormesis mechanism, we proposed a comprehensive regulatory pathway for the hormetic effects of Comamonas testosteroni low-level sulfonamides and determined the generality of the observed regulatory model in the Comamonadaceae family. Considering the prevalence of Comamonadaceae in human guts and environmental ecosystems, we provide critical insights into the health and ecological effects of antibiotics. Antibiotics can induce dose-dependent hormetic effects on bacterial cell proliferation, i.e., low-dose stimulation and high-dose inhibition. However, the underlying molecular basis has yet to be clarified. Here, we showed that sulfonamides play dual roles as a weapon and signal against Comamonas testosteroni that can modulate cell physiology and phenotype. Subsequently, through investigating the hormesis mechanism, we proposed a comprehensive regulatory pathway for the hormetic effects of Comamonas testosteroni low-level sulfonamides and determined the generality of the observed regulatory model in the Comamonadaceae family. Considering the prevalence of Comamonadaceae in human guts and environmental ecosystems, we provide critical insights into the health and ecological effects of antibiotics.
Compact motion representation based on global features for semantic image sequence coding

For dynamic scene analysis, numerous studied developed derivation methods of qualitative motion features from a dense apparent velocity vector field (optical flow). However, this qualitative information cannot be used for image sequence reconstruction because no explicit reconstruction criterion is introduced within the feature identification process itself. This study proposes a new algorithmic approach which tries to solve the crucial trade-off between a small amount of motion parameters--viewed as assistance data in a motion compensated interpolation scheme for image sequence coding--and high quality of reconstruction. This approach could be described as a tentative step towards semantic coding scheme using global--and thus compact-- motion labels which characterize a restricted class of 3-D physical motions even if no 3-D measurements are required. This paper is structured as follows: after a brief introduction where the general framework is described, we present a hierarchy of affine models for motion field representation and the explicit derivation of global motion features associated with a simplified version of a linear model. The identification procedure, essentially based on minimization techniques using steepest descent methods, is shown. After all these initial requirements, we introduce the more efficient and new algorithmic step; it is concerned with the use of a deterministic relaxation scheme to smooth the motion vector field and improve the accuracy of the motion estimator, especially within regions where large magnitudes of motion are located. We also introduce a temporal linking operator which appears quite natural in the framework of iterative estimation methods where initial values are required. Finally, results on real image sequences are given; performances are expressed in terms of convergence speed, reconstruction quality, compactness of the motion representation and qualitative or quantitative efficiency of the motion estimation scheme.
The positioning mechanics of microtubule asters in Drosophila embryo explants

Microtubule asters are essential in localizing the action of microtubules in processes including mitosis and organelle positioning. In large cells, such as the one-cell sea urchin embryo, aster dynamics are dominated by hydrodynamic pulling forces. However, in systems with more densely positioned nuclei such as the early Drosophila embryo, which packs around 6000 nuclei within the syncytium in a crystalline-like order, it is unclear what processes dominate aster dynamics. Here, we take advantage of a cell cycle regulation Drosophila mutant to generate embryos with multiple asters, independent from nuclei. We use an ex vivo assay to further simplify this biological system to explore the forces generated by and between asters. Through live imaging, drug and optical perturbations, and theoretical modelling, we demonstrate that these asters likely generate an effective pushing force over short distances. Significance Statement Using cytosolic explants from Drosophila syncytial embryos combined with quantitative microscopy and perturbations, de-Carvalho et al., reveal the mechanical forces separating Drosophila microtubule asters. Aster separation drives precise nuclear positioning in multinucleated embryo cells, a vital process for tissue formation and gene expression during subsequent embryo development.
The patterns of codon usage between chordates and arthropods are different but co-evolving with mutational biases

Different frequencies amongst codons that encode the same amino acid (i.e. synonymous codons) have been observed in multiple species. Studies focused on uncovering the forces that drive such codon usage bias showed that a combined effect of mutational biases and translational selection works to produce different frequencies of synonymous codons. However, only few have been able to measure and distinguish between these forces that may leave similar traces on the coding regions. Here, we have developed a codon model that allows the disentangling of mutation, selection on amino acids and synonymous codons, and GC–biased gene conversion (gBGC) which we employed on an extensive dataset of 415 chordates and 191 arthropods. We found that chordates need 15 more synonymous codon categories than arthropods to explain the empirical codon frequencies, which suggests that the extent of codon usage can vary greatly between animal phyla. Moreover, methylation at CpG sites seems to partially explain these patterns of codon usage bias in chordates but not in arthropods. Our findings also demonstrate that GC–rich codons are disfavoured in both phyla when mutations are GC– biased, and the opposite is true when mutations are AT–biased. This indicates that selection on the genomic coding regions might act primarily to stabilise its GC/AT content. Our study shows that the degree of synonymous codon usage varies considerably among animals, but is likely governed by a common underlying dynamic. Significance statement The reasons for the differential usage of codons encoding for the same amino acid has puzzled scientist for decades. By examining the frequencies of synonymous codons in different species, this study presents a novel model that sheds light on the underlying factors that drive differences in codon usage between chordates and arthropods. Our analysis unveiled more extensive codon usage patterns in chordates compared to arthropods. Moreover, the study highlights that genome–wide selection acts to balance mutational biases favouring G/C alleles. This research provides valuable insights into our understanding of the complex interplay between mutational biases and selection forces in shaping the variation at the synonymous sites, and has important implications for future studies of genome evolution and adaptation.
Dopamine D1 and NMDA receptor co-regulation of protein translation in cultured nucleus accumbens neurons

Protein translation is essential for some forms of synaptic plasticity. We used nucleus accumbens (NAc) medium spiny neurons (MSN), co-cultured with cortical neurons to restore excitatory synapses, to examine whether dopamine modulates protein translation in NAc MSN. FUNCAT was used to measure translation in MSNs under basal conditions and after disinhibiting excitatory transmission using the GABAA receptor antagonist bicuculline (2 hr). Under basal conditions, translation was not altered by the D1-class receptor (D1R) agonist SKF81297 or the D2-class receptor (D2R) agonist quinpirole. Bicuculline alone robustly increased translation. This was reversed by quinpirole but not SKF81297. It was also reversed by co-incubation with the D1R antagonist SCH23390, but not the D2R antagonist eticlopride, suggesting dopaminergic tone at D1Rs. This was surprising because no dopamine neurons are present. An alternative explanation is that bicuculline activates translation by increasing glutamate tone at NMDA receptors (NMDAR) within D1R/NMDAR heteromers, which have been described in other cell types. Supporting this, immunocytochemistry and proximity ligation assays revealed D1/NMDAR heteromers on NAc cells both in vitro and in vivo. Further, bicuculline’s effect was reversed to the same extent by SCH23390 alone, the NMDAR antagonist APV alone, or SCH23390+APV. These results suggest that: 1) excitatory synaptic transmission stimulates translation in NAc MSNs, 2) this is opposed when glutamate activates D1R/NMDAR heteromers, even in the absence of dopamine, and 3) antagonist occupation of D1Rs within the heteromers prevents their activation. Our study is the first to suggest a role for D2 receptors and D1R/NMDAR heteromers in regulating protein translation.
Preclinical Screening of Splice-Switching Antisense Oligonucleotides in PDAC Organoids

Aberrant alternative splicing is emerging as a cancer hallmark and a potential therapeutic target. It is the result of dysregulated splicing factors or genetic alterations in splicing-regulatory cis-elements. Targeting individual altered splicing events associated with cancer-cell dependencies is a potential therapeutic strategy, but several technical limitations need to be addressed. Patient-derived organoids (PDOs) are a promising platform to recapitulate key aspects of disease states and to facilitate drug development for precision medicine. Here, we report an efficient antisense-oligonucleotide (ASO) transfection method to systematically evaluate and screen individual splicing events as therapeutic targets in pancreatic ductal adenocarcinoma (PDAC) organoids. This optimized delivery method allows fast and efficient screening of ASOs that reverse oncogenic alternative splicing. In combination with advancements in chemical modifications and ASO-delivery strategies, this method has the potential to accelerate the discovery of anti-tumor ASO drugs that target pathological alternative splicing.
Response inhibition and error-monitoring in cystinosis (CTNS gene mutations): Behavioral and electrophysiological evidence of a diverse set of difficulties

Cystinosis, a rare lysosomal storage disease, is characterized by cystine crystallization and accumulation within tissues and organs, including the kidneys and brain. Its impact on neural function appears mild relative to its effects on other organs, but therapeutic advances have led to substantially increased life expectancy, necessitating deeper understanding of its impact on neurocognitive function. Behaviorally, some deficits in executive function have been noted in this population, but the underlying neural processes are not understood. Using standardized cognitive assessments and a Go/No-Go response inhibition task in conjunction with high-density electrophysiological recordings (EEG), we sought to investigate the behavioral and neural dynamics of inhibition of a prepotent response and of error monitoring (critical components of executive function) in individuals with cystinosis, when compared to age-matched controls. Thirty-seven individuals diagnosed with cystinosis (7-36 years old, 24 women) and 45 age-matched controls (27 women) participated in this study. Analyses focused on N2 and P3 No-Go responses and error-related positivity (Pe). Atypical inhibitory processing was shown behaviorally. Electrophysiological differences were additionally found between the groups, with individuals with cystinosis showing larger No-Go P3s. Error-monitoring was likewise different between the groups, with those with cystinosis showing reduced Pe amplitudes.
Motility-Induced Phase Separation Mediated by Bacterial Quorum Sensing

We study motility-induced phase separation (MIPS) in living active matter, in which cells interact through chemical signalling, or quorum sensing. In contrast to previous theories of MIPS, our multiscale continuum model accounts explicitly for genetic regulation of signal production and motility. Through analysis and simulations, we derive a new criterion for the onset of MIPS that depends on features of the genetic network. Furthermore, we identify and characterise a new type of oscillatory instability that occurs when gene regulation inside cells promotes motility in higher signal concentrations.
TaSPL14-7A is a conserved regulator controlling plant architecture and yield traits in common wheat (Triticum aestivum L.)

Plant architecture is a crucial influencing factor of wheat yield and adaptation. In this study, we cloned and characterized TaSPL14, a homologous gene of the rice ideal plant architecture gene OsSPL14 in wheat. TaSPL14 homoeologs (TaSPL14-7A, TaSPL14-7B and TaSPL14-7D) exhibited similar expression patterns, and they were all preferentially expressed in stems at the elongation stage and in young spikes. Moreover, the expression level of TaSPL14-7A was higher than that of TaSPL14-7B and TaSPL14-7D. Overexpression of TaSPL14-7A in wheat resulted in significant changes in plant architecture and yield traits, including decreased tiller number and increased kernel size and weight. Three TaSPL14-7A haplotypes were identified in Chinese wheat core collection, and haplotype-based association analysis showed that TaSPL14-7A-Hap1/2 were significantly correlated with fewer tillers, larger kernels and higher kernel weights in modern cultivars. The haplotype effect resulted from a difference in TaSPL14-7A expression levels among genotypes, with TaSPL14-7A-Hap1/2 leading to higher expression levels than TaSPL14-7A-Hap3. As favorable haplotypes, TaSPL14-7A-Hap1/2 underwent positive selection during global wheat breeding over the last century. Together, the findings of our study provide insight into the function and genetic effects of TaSPL14 and provide a useful molecular marker for wheat breeding.
Vitamin C and vitamin D3 alleviate metabolic-associated fatty liver disease by regulating the gut microbiota and bile acid metabolism via the gut-liver axis

Background: Previous studies have demonstrated that both vitamin C (VC) and vitamin D3 (VD3) have therapeutic potential against metabolic disorders, including obesity, diabetes, and metabolic-associated fatty liver disease (MAFLD). However, it is unclear whether VC supplementation is associated with improving the intestinal flora and regulating the metabolism of bile acids via the gut-liver axis in MAFLD. There is still no direct comparison or combination study of these two vitamins on these effects. Methods: In this study, we employed biochemical, histological, 16S rDNA-based microbiological, non-targeted liver metabolomic, and quantitative real-time polymerase chain reaction analyses to explore the intervening effect and mechanism of VC and VD3 on MAFLD by using a high-fat diet (HFD)-induced obese mouse model. Results: Treatment of mice with VC and VD3 efficiently reversed the characteristics of MAFLD, such as obesity, dyslipidemia, insulin resistance, hepatic steatosis, and inflammation. VC and VD3 showed similar beneficial effects as mentioned above in HFD-induced obese mice. Interestingly, VC and VD3 reshaped the gut microbiota composition; improved gut barrier integrity; ameliorated oxidative stress and inflammation in the gut-liver axis; inhibited bile acid salt reflux-related ASBT; activated bile acid synthesis-related CYP7A1, bile acid receptor FXR, and bile acid transportation-related BSEP in the gut-liver axis; and improved bile secretion, thus decreasing the expression of FAS in the liver and efficiently ameliorating MAFLD in mice. Conclusion: Together, the results indicate that the anti-MAFLD activities of VC and VD3 are linked to improved gut-liver interactions via regulation of the gut microbiota and bile acid metabolism, and they may therefore prove useful in treating MAFLD clinically.
Dipole doping effect in MoS2 field effect transistors based on phase transition of ferroelectric polymer dopant

Molybdenum disulfide (MoS2) has great potential for next-generation electronic devices. On the other hand, stable doping methods are required to adjust its physical properties so MoS2 can be utilized in practical applications, such as transistors and photodetectors. On the other hand, a conventional doping method based on ion implantation is incompatible with 2D MoS2 because of the damage to the lattice structures of MoS2. This paper presents an n-type doping method for MoS2 field-effect transistors (FETs) using a poly (vinylidene fluoride-co-trifluoroethylene) (P (VDF-TrFE)) and polar polymer. The dipole moment of P (VDF-TrFE) provides n-type doping on MoS2 FETs. The polar phase formation in dopant films enhances the doping effects, and the relationship between phase transition and n-type doping states was investigated using optical and electrical characterization methods. Under the optimal doping conditions, the doped MoS2 FET achieved an improved field effect mobility of 34.4 cm2 V−1s–1, a negative shift in the threshold voltage by −25.6 V, and a high on-current of 21 μA compared to the pristine MoS2 FET.