Miracle-dz/UniFAR-FTUs huggingface dataset:
Interference of mycotoxin binders with ELISA, HPLC and LC-MS/MS analysis of aflatoxins in maize and maize gluten

ABSTRACT The aim of this study was to investigate the impact of mycotoxin binders on the determination of aflatoxins in maize and maize gluten using various analytical methods, including ELISA, HPLC and LC-MS/MS. Three types of commercially available mycotoxin binders, yeast cell wall, mineral, and a mixture of mineral and bacterium, were investigated at inclusion levels of 0.1%, 0.2% and 0.4%. The binders were added to maize and maize gluten contaminated with aflatoxins at concentrations between 6.9 and 26.7 μg kg−1. The samples were analysed and the values were compared with corresponding controls (samples without binders) using ANOVA. The yeast cell wall binder had no significant effect (p=0.05) on the concentration of aflatoxins measured in either maize or maize gluten at any of the three inclusion levels, regardless of which analytical method was used. The mineral binder and the mixed mineral and bacterium binder had no significant effect (p=0.05) on the measured aflatoxin concentrations in either maize or maize gluten at any of the three inclusion levels when analysis was conducted using LC-MS/MS. Inclusion of these binders resulted in significant lower (p<0.01) detection of aflatoxins in both maize and maize gluten when analysis was conducted using ELISA; the effect was dose-dependent. They also resulted in significant lower detection of aflatoxins in maize extracted by methanol/water (70/30 v/v) (p<0.0001) and in maize gluten extracted by acetonitrile/water (80/20 v/v) (p<0.05) when analysis was conducted using HPLC. However, neither the mineral binder nor the mixed mineral and bacterium binder had significant effects (p=0.05) on aflatoxin concentrations measured in maize using HPLC, when extracted by acetonitrile/water (80/20 v/v). The study demonstrated that mycotoxin binders could result in underestimation of the levels of aflatoxin contamination, depending on the nature of the binder, the extraction solvent used in the analytical method, and the composition of tested sample.
Fully Adaptive Practical Time-Varying Output Formation Tracking for High-Order Nonlinear Stochastic Multiagent System With Multiple Leaders

Fully adaptive practical time-varying output formation tracking issues of high-order nonlinear stochastic multiagent systems with multiple leaders are researched, where the adaptive fuzzy-logic system (FLS) is introduced for estimating the mismatched integrated uncertain items. Distinctive with former results, stochastic noise is considered in the dynamics, and the followers are required for achieving the time-varying output formation tracking in probability of the convex combination of the leaders’ outputs. First, a fully adaptive practical time-varying output formation tracking protocol is put forward, which only utilizes the neighboring relative information, and the global interaction topology information is not used. Besides, the designed protocol employs the adaptive FLSs to estimate the mismatched uncertainties of the followers and the leaders, and the uncertain boundary functions of the stochastic noise. Then, the design process of control protocol and parameter adaptive update law is summarized within four steps in an algorithm. Third, the stability and the properties of the proposed protocol and algorithm are analyzed by employing the Lyapunov theories and stochastic stability theories. Finally, numerical simulation results illustrate the effectiveness of achieved protocol and algorithm.
Nonhuman primate models of hippocampal development and dysfunction

Nonhuman primates provide highly valuable animal models that have significantly advanced our understanding of numerous behavioral and biological phenomena in humans. Here, we reviewed a series of developmental neuropsychological studies that informed us on the timing of development of the hippocampus and of hippocampal-dependent cognitive functions in primates. Data indicate that, in primates, the emergence of adult-like proficiency on behavioral tasks sensitive to hippocampal dysfunction is a stepwise process and reflects the gradual maturation of different hippocampal circuits and their connections with other neural structures. Profound and persistent memory loss resulting from insult to the hippocampus in infancy was absent in early infancy but became evident later in childhood and persisted in adulthood, indicating very little sparing or recovery of function. Finally, the early hippocampal insult resulted in both adaptive and maladaptive neuroplasticity: i.e., sparing contextual memory, but affecting working memory processes as well as emotional reactivity and hypothalamic–pituitary–adrenal (HPA) axis functioning. The results provide significant information on the emergence of hippocampal-dependent functions in humans, on the time course of memory impairment in human cases with early hippocampal insult, and on the clinical implication of the hippocampus in developmental neuropsychiatric disorders.
Engineering a CRISPR Interference System To Repress a Class 1 Integron in Escherichia coli

Microbial multidrug resistance (MDR) poses a huge threat to human health. Bacterial acquisition of MDR relies primarily on class 1 integron-involved horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs). To date, no strategies other than the use of antibiotics can efficiently cope with MDR. Here, we report that an engineered CRISPR interference (CRISPRi) system can markedly reduce MDR by blocking a class 1 integron in Escherichia coli. Using CRISPRi to block plasmid R388 class 1 integron, E. coli recombinants showed halted growth upon exposure to relevant antibiotics. ABSTRACT Microbial multidrug resistance (MDR) poses a huge threat to human health. Bacterial acquisition of MDR relies primarily on class 1 integron-involved horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs). To date, no strategies other than the use of antibiotics can efficiently cope with MDR. Here, we report that an engineered CRISPR interference (CRISPRi) system can markedly reduce MDR by blocking a class 1 integron in Escherichia coli. Using CRISPRi to block plasmid R388 class 1 integron, E. coli recombinants showed halted growth upon exposure to relevant antibiotics. A microplate alamarBlue assay showed that both subgenomic RNAs (sgRNAs) R3 and R6 led to 8- and 32-fold decreases in half-maximal inhibitory concentrations (IC50) for trimethoprim and sulfamethoxazole, respectively. Reverse transcription and quantitative PCR (RT-qPCR) revealed that the strain employing sgRNA R6 exhibited 97% and 84% decreases in the transcriptional levels of the dfrB2 cassette and sul1, two typical ARGs, respectively. RT-qPCR analysis also demonstrated that the strain recruiting sgRNA R3 showed a 96% decrease in the transcriptional level of intI1, and a conjugation assay revealed a 1,000-fold decrease in HGT rates of ARGs. Overall, the sgRNA R3 targeting the 31 bp downstream of the Pc promoter on the intI1 nontemplate strand outperformed other sgRNAs in reducing integron activity. Furthermore, this CRISPRi system is reversible, genetically stable, and titratable by varying the concentration of the inducer. To our knowledge, this is the first report on exploiting a CRISPRi system to reduce the class 1 integron in E. coli. This study provides valuable insights for future development of CRISPRi-based antimicrobial agents and cellular therapy to suppress MDR.
Using Testing as a Learning Tool

Objective. The purpose of this review is to discuss some principles from cognitive psychology regarding the benefits of testing and translate those findings into practical applications for instruction and studying. Findings. Testing or retrieval practice is superior to re-study for promoting long-term retention. The benefits of testing can be see with open-ended responses (eg, cued or free recall) and multiple choice questions. The use of multiple-choice questions during testing may have an additional benefit as it may stabilize information that is stored in memory but temporarily inaccessible due to disuse (eg, marginal knowledge). Summary. Testing can have multiple learning benefits. We emphasize that incorporating opportunities for retrieval after teaching is an essential component of lasting learning. In addition, retrieval practice can be incorporated in all aspects of instruction.
Promotion of BR Biosynthesis by miR444 Is Required for Ammonium-Triggered Inhibition of Root Growth1

miR444 promotes phytohormone brassinosteroid biosynthesis, conferring ammonium-triggered root elongation inhibition in rice. Rice (Oryza sativa), the staple food for almost half of the world’s population, prefers ammonium (NH4+) as the major nitrogen resource, and while NH4+ has profound effects on rice growth and yields, the underlying regulatory mechanisms remain largely unknown. Brassinosteroids (BRs) are a class of steroidal hormones playing key roles in plant growth and development. In this study, we show that NH4+ promotes BR biosynthesis through miR444 to regulate rice root growth. miR444 targeted five homologous MADS-box transcription repressors potentially forming homologous or heterogeneous complexes in rice. miR444 positively regulated BR biosynthesis through its MADS-box targets, which directly repress the transcription of BR-deficient dwarf 1 (OsBRD1), a key BR biosynthetic gene. NH4+ induced the miR444-OsBRD1 signaling cascade in roots, thereby increasing the amount of BRs, whose biosynthesis and signaling were required for NH4+-dependent root elongation inhibition. Consistently, miR444-overexpressing rice roots were hypersensitive to NH4+ depending on BR biosynthesis, and overexpression of miR444’s target, OsMADS57, resulted in rice hyposensitivity to NH4+ in root elongation, which was associated with a reduction of BR content. In summary, our findings reveal a cross talk mechanism between NH4+ and BR in which NH4+ activates miR444-OsBRD1, an undescribed BR biosynthesis-promoting signaling cascade, to increase BR content, inhibiting root elongation in rice.
Integrin αDβ2 influences cerebral edema, leukocyte accumulation and neurologic outcomes in experimental severe malaria

Malaria is an infectious disease of major worldwide clinical importance that causes a variety of severe, or complicated, syndromes including cerebral malaria, which is often fatal. Leukocyte integrins are essential for host defense but also mediate physiologic responses of the innate and adaptive immune systems. We previously showed that targeted deletion of the αD subunit (αD-/-) of the αDβ2 integrin, which is expressed on key leukocyte subsets in mice and humans, leads to absent expression of the integrin heterodimer on murine macrophages and reduces mortality in mice infected with Plasmodium berghei ANKA (P. berghei ANKA). To further identify mechanisms involved in the protective effect of αD deletion in this model of severe malaria we examined wild type C57BL/6 (WT) and αD-/- mice after P. berghei ANKA infection and found that vessel plugging and leukocyte infiltration were significantly decreased in the brains of αD-/- animals. Intravital microscopy demonstrated decreased rolling and adhesion of leukocytes in cerebral vessels of αD-/- mice. Flow cytometry analysis showed decreased T-lymphocyte accumulation in the brains of infected αD-/- animals. Evans blue dye exclusion assays demonstrated significantly less dye extravasation in the brains of αD-/- mice, indicating preserved blood-brain barrier integrity. WT mice that were salvaged from P. berghei ANKA infection by treatment with chloroquine had impaired aversive memory, which was not observed in αD-/- mice. We conclude that deletion of integrin αDβ2 alters the natural course of experimental severe malaria, demonstrating previously unrecognized activities of a key leukocyte integrin in immune-inflammatory responses that mediate cerebral involvement.
RIFT: Multi-Modal Image Matching Based on Radiation-Variation Insensitive Feature Transform

Traditional feature matching methods, such as scale-invariant feature transform (SIFT), usually use image intensity or gradient information to detect and describe feature points; however, both intensity and gradient are sensitive to nonlinear radiation distortions (NRD). To solve this problem, this paper proposes a novel feature matching algorithm that is robust to large NRD. The proposed method is called radiation-variation insensitive feature transform (RIFT). There are three main contributions in RIFT. First, RIFT uses phase congruency (PC) instead of image intensity for feature point detection. RIFT considers both the number and repeatability of feature points and detects both corner points and edge points on the PC map. Second, RIFT originally proposes a maximum index map (MIM) for feature description. The MIM is constructed from the log-Gabor convolution sequence and is much more robust to NRD than traditional gradient map. Thus, RIFT not only largely improves the stability of feature detection but also overcomes the limitation of gradient information for feature description. Third, RIFT analyses the inherent influence of rotations on the values of the MIM and realises rotation invariance. We use six different types of multi-modal image datasets to evaluate RIFT, including optical-optical, infrared-optical, synthetic aperture radar (SAR)-optical, depth-optical, map-optical, and day-night datasets. Experimental results show that RIFT is superior to SIFT and SAR-SIFT on multi-modal images. To the best of our knowledge, RIFT is the first feature matching algorithm that can achieve good performance on all the abovementioned types of multi-modal images. The source code of RIFT and the multi-modal image datasets are publicly available.11http://www.escience. cn/people/lijiayuan/index.html
4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers

Purpose: The success of checkpoint blockade against glioblastoma (GBM) has been disappointing. Anti–PD-1 strategies may be hampered by severe T-cell exhaustion. We sought to develop a strategy that might license new efficacy for checkpoint blockade in GBM. Experimental Design: We characterized 4-1BB expression in tumor-infiltrating lymphocytes (TIL) from human GBM. We implanted murine tumor models including glioma (CT2A), melanoma (B16), breast (E0771), and lung carcinomas intracranially and subcutaneously, characterized 4-1BB expression, and tested checkpoint blockade strategies in vivo. Results: Our data reveal that 4-1BB is frequently present on nonexhausted CD8+ TILs in human and murine GBM. In murine gliomas, 4-1BB agonism and PD-1 blockade demonstrate a synergistic survival benefit in a CD8+ T-cell–dependent manner. The combination decreases TIL exhaustion and improves TIL functionality. This strategy proves most successful against intracranial CT2A gliomas. Efficacy in all instances correlates with the levels of 4-1BB expression on CD8+ TILs, rather than with histology or with intracranial versus subcutaneous tumor location. Proffering 4-1BB expression to T cells licenses combination 4-1BB agonism and PD-1 blockade in models where TIL 4-1BB levels had previously been low and the treatment ineffective. Conclusions: Although poor T-cell activation and severe T-cell exhaustion appear to be limiting factors for checkpoint blockade in GBM, 4-1BB agonism obviates these limitations and produces long-term survival when combined with anti–PD-1 therapy. Furthermore, this combination therapy is limited by TIL 4-1BB expression, but not by the intracranial compartment, and therefore may be particularly well-suited to GBM.
Lessons from equilibrium statistical physics regarding the assembly of protein complexes

Significance In order to carry out their functions, most proteins assemble into multicomponent complexes. In the process of assembly, complexes need to discriminate their specific components from a mixture of hundreds of different proteins present in the cell. To assess some of the implications of this requirement, we develop a minimal model of self-assembly based on equilibrium statistical physics. We argue that the need to assemble reliably imposes fundamental constraints on the characteristics of complexes, which we support with analysis of available structural and compositional data. Our work constitutes only a step toward future theory of protein complex assembly, which will have to incorporate also nonequilibrium and kinetic aspects of this fundamental and rich, yet theoretically neglected, problem. Cellular functions are established through biological evolution, but are constrained by the laws of physics. For instance, the physics of protein folding limits the lengths of cellular polypeptide chains. Consequently, many cellular functions are carried out not by long, isolated proteins, but rather by multiprotein complexes. Protein complexes themselves do not escape physical constraints, one of the most important being the difficulty of assembling reliably in the presence of cellular noise. In order to lay the foundation for a theory of reliable protein complex assembly, we study here an equilibrium thermodynamic model of self-assembly that exhibits 4 distinct assembly behaviors: diluted protein solution, liquid mixture, “chimeric assembly,” and “multifarious assembly. ” In the latter regime, different protein complexes can coexist without forming erroneous chimeric structures. We show that 2 conditions have to be fulfilled to attain this regime: 1) The composition of the complexes needs to be sufficiently heterogeneous, and 2) the use of the set of components by the complexes has to be sparse. Our analysis of publicly available databases of protein complexes indicates that cellular protein systems might have indeed evolved so as to satisfy both of these conditions.
Deep learning-based attenuation correction in the absence of structural information for whole-body positron emission tomography imaging

Deriving accurate structural maps for attenuation correction (AC) of whole-body positron emission tomography (PET) remains challenging. Common problems include truncation, inter-scan motion, and erroneous transformation of structural voxel-intensities to PET µ-map values (e.g. modality artifacts, implanted devices, or contrast agents). This work presents a deep learning-based attenuation correction (DL-AC) method to generate attenuation corrected PET (AC PET) from non-attenuation corrected PET (NAC PET) images for whole-body PET imaging, without the use of structural information. 3D patch-based cycle-consistent generative adversarial networks (CycleGAN) is introduced to include NAC-PET-to-AC-PET mapping and inverse mapping from AC PET to NAC PET, which constrains NAC-PET-to-AC-PET mapping to be closer to one-to-one mapping. Since NAC PET images share similar anatomical structures to the AC PET image but lack contrast information, residual blocks, which aim to learn the differences between NAC PET and AC PET, are used to construct generators of CycleGAN. After training, patches from NAC PET images were fed into NAC-PET-to-AC-PET mapping to generate DL-AC PET patches. DL-AC PET image was then reconstructed through patch fusion. We conducted a retrospective study on 55 datasets of whole-body PET/CT scans to evaluate the proposed method. In comparing DL-AC PET with original AC PET, average mean error (ME) and normalized mean square error (NMSE) of the whole-body were 0.62% ± 1.26% and 0.72% ± 0.34%. The average intensity changes measured on sequential PET images with AC and DL-AC on both normal tissues and lesions differ less than 3%. There was no significant difference of the intensity changes between AC and DL-AC PET, which demonstrate DL-AC PET images generated by the proposed DL-AC method can reach a same level to that of original AC PET images. The method demonstrates excellent quantification accuracy and reliability and is applicable to PET data collected on a single PET scanner or hybrid platform with computed tomography (PET/CT) or magnetic resonance imaging (PET/MRI).
Native speakers like affixes, L2 speakers like letters? An overt visual priming study investigating the role of orthography in L2 morphological processing

In an overt visual priming experiment, we investigate the role of orthography in native (L1) and non-native (L2) processing of German morphologically complex words. We compare priming effects for inflected and derived morphologically related prime-target pairs versus otherwise matched, purely orthographically related pairs. The results show morphological priming effects in both the L1 and L2 group, with no significant difference between inflection and derivation. However, L2 speakers, but not L1 speakers, also showed significant priming for orthographically related pairs. Our results support the claim that L2 speakers focus more on surface-level information such as orthography during visual word recognition. This can cause orthographic priming effects in morphologically related prime-target pairs, which may conceal L1-L2 differences in morphological processing.
PySpacell: A Python Package for Spatial Analysis of Cell Images

Technologies such as microscopy, sequential hybridization, and mass spectrometry enable quantitative single‐cell phenotypic and molecular measurements in situ. Deciphering spatial phenotypic and molecular effects on the single‐cell level is one of the grand challenges and a key to understanding the effects of cell–cell interactions and microenvironment. However, spatial information is usually overlooked by downstream data analyses, which usually consider single‐cell read‐out values as independent measurements for further averaging or clustering, thus disregarding spatial locations. With this work, we attempt to fill this gap. We developed a toolbox that allows one to test for the presence of a spatial effect in microscopy images of adherent cells and estimate the spatial scale of this effect. The proposed Python module can be used for any light microscopy images of cells as well as other types of single‐cell data such as in situ transcriptomics or metabolomics. The input format of our package matches standard output formats from image analysis tools such as CellProfiler, Fiji, or Icy and thus makes our toolbox easy and straightforward to use, yet offering a powerful statistical approach for a wide range of applications. © 2019 International Society for Advancement of Cytometry
Site-Specific Siderocalin Binding to Ferric and Ferric-Free Enterobactin As Revealed by Mass Spectrometry

Both host and pathogen competitively manipulate coordination environments during bacterial infections. Human cells release the innate immune protein siderocalin (Scn, also known as lipocalin-2/Lcn2, neutrophil gelatinase-associated lipocalin/NGAL) that can inhibit bacterial growth by sequestering iron in a ferric complex with enterobactin (Ent), the ubiquitous Escherichia coli siderophore. Pathogenic E. coli use the virulence-associated esterase IroE to linearize the Ent cyclic trilactone to linear enterobactin (lin-Ent). We characterized lin-Ent interactions with Scn by using native mass spectrometry (MS) with hydrogen–deuterium exchange (HDX) and Lys/Arg specific covalent footprinting. These approaches support 1:1 binding of both Fe(III)-lin-Ent to Scn and iron-free lin-Ent to Scn. Both ferric and nonferric lin-Ent localize to all three pockets of the Scn calyx, consistent with Scn capture of lin-Ent both before and after Fe(III) chelation. These findings raise the possibility that Scn neutralizes both siderophores and siderophore-bound iron during infections. This integrated, MS-based approach circumvents the limitations that frustrate traditional structural approaches to examining Scn interactions with enterobactin-based ligands.