Miracle-dz/UniFAR-FTUs huggingface dataset:
Dicamba drift alters patterns of chewing herbivory in three common agricultural weeds

How agricultural regimes, such as novel herbicide exposure, may influence plant-herbivore interactions and specifically patterns of plant herbivory has come under increased interest in recent years due to rapidly changing herbicide use in agroecosystems. This paper examines patterns of plant herbivory using three common agricultural weeds exposed to low doses of dicamba, a synthetic auxin herbicide that is exponentially increasing in use given the adoption of dicamba tolerant crops. We used a replicated field study to examine how the amount and type of chewing herbivory may be altered in Ipomoea purpurea (common morning glory, Convolvulaceae), Datura stramonium (jimsonweed, Solanaceae), and Abutilon theophrasti (velvetleaf, Malvaceae) exposed to dicamba drift (i.e., 1% of the field dose). We found an increase in chewing herbivory damage when plants were exposed to dicamba and changes in the type of herbivory following exposure. Chewing herbivory differed among species in the presence of dicamba drift: A. theophrasti and D. stramonium showed more total leaf-chewing herbivory than controls, but I. purpurea showed no difference in the overall amount of herbivory. We also found that the type of herbivory was significantly altered in drift. A. theophrasti and I. purpurea both exhibited declines in hole feeding but increases in margin feeding, whereas D. stramonium showed no such changes. Overall, our results show that herbicide drift can induce shifts in plant-herbivore interactions, highlighting the need for mechanistic studies to uncover the cause underlying the shifts and comparative studies on weed communities to understand long-term consequences.
Focal exocytosis of Syntaxin 3 and TRPML1 at pseudopodia of nascent phagosomes

Macrophages clear invading pathogens by phagocytosis. Phagocytosis is a complex mechanism involving the local expansion of the membrane, cytoskeletal remodeling, and the delivery of phagosomal proteins to the nascent phagosomes. However, the organelle trafficking events underlying this are largely unclear. Here, we show in human blood monocyte-derived macrophages that TRPML1, a calcium channel involved in the phagocytic process, is delivered to phagosomes in Syntaxin 3-positive vesicles. Syntaxin 3 is a SNARE protein previously shown to mediate the secretion of IL-6 by macrophages. Total Internal Reflection Microscopy (TIRF) revealed that Syntaxin 3 positive compartments carry TRPML1 to pseudopodia for focal exocytosis at the nascent phagosomes during E. coli uptake. Using siRNA knockdown, we show that both Syntaxin 3 and TRPML1 are required for E. coli uptake. Moreover, using TRPML1 agonists we show that increased TRPML1 activity leads to increased E. coli uptake, whereas calcium chelation decreased intracellular E. coli load. Understanding the membrane trafficking pathways is critical for understanding how macrophages clear invading pathogens. Key findings Syntaxin 3 positive vesicles are delivered at the plasma membrane site of phagocytosis. Syntaxin 3-positive vesicles carry TRPML1 to pseudopodia. Bacterial phagocytosis correlates with Syntaxin 3 and TRPML1 expression levels. Bacterial phagocytosis depends on calcium flux through TRPML1. Syntaxin-3 vesicles carry the cytokine interleukin-6.
Genetic associations with resistance to Meloidogyne enterolobii in guava (Psidium sp.) using cross-genera SNPs and comparative genomics to Eucalyptus highlight evolutionary conservation across the Myrtaceae

Tropical fruit tree species constitute a yet untapped supply of outstanding diversity of taste and nutritional value, barely developed from the genetics standpoint, with scarce or no genomic resources to tackle the challenges arising in modern breeding practice. We generated a de novo genome assembly of the Psidium guajava, the super fruit “apple of the tropics”, and successfully transferred 14,268 SNP probesets from Eucalyptus to Psidium at the nucleotide level, to detect genomic loci linked to resistance to the root knot nematode (RKN) Meloidogyne enterolobii derived from the wild relative P. guineense. Significantly associated loci with resistance across alternative analytical frameworks, were detected at two SNPs on chromosome 3 in a pseudo-assembly of Psidium guajava genome built using a syntenic path approach with the Eucalyptus grandis genome to determine the order and orientation of the contigs. The P. guineense-derived resistance response to RKN and disease onset is conceivably triggered by mineral nutrients and phytohormone homeostasis or signaling with the involvement of the miRNA pathway. Hotspots of mapped resistance quantitative trait loci and functional annotation in the same genomic region of Eucalyptus provide further indirect support to our results, highlighting the evolutionary conservation of genomes across genera of Myrtaceae in the adaptation to pathogens. Marker assisted introgression of the resistance loci mapped should accelerate the development of improved guava cultivars and hybrid rootstocks.
An automation workflow for high-throughput manufacturing and analysis of scaffold-supported 3D tissue arrays

The success rate of bringing novel cancer therapies to the clinic remains extremely low due to the lack of relevant pre-clinical culture models that capture the complexity of human tumours. Patient-derived organoids have emerged as a useful tool to model patient and tumour heterogeneity to begin addressing this need. Scaling these complex culture models while enabling stratified analysis of different cellular sub-populations remains a challenge, however. One strategy to enable higher throughput organoid cultures that also enables easy image-based analysis is the Scaffold-supported Platform for Organoid-based Tissues (SPOT) platform. SPOT allows the generation of flat, thin and dimensionally-defined microtissues in both 96- and 384-well plate footprints and is compatible with tumour organoid culture and downstream image-based readouts. SPOT manufacturing is currently a manual process however, limiting the use of SPOT to perform larger-scale screening. In this study, we integrate and optimize an automation approach to generate tumour-mimetic 3D engineered microtissues in SPOT using a liquid handler, and show comparable within-sample and between-sample variation as the standard manual manufacturing process. Furthermore, we develop a liquid handler-supported whole-cell extraction protocol and as a proof-of-value demonstration, we generate 3D complex tissues containing different proportions of tumour and stromal cells and perform single-cell-based end-point analysis to demonstrate the impact of co-culture on the tumour cell population specifically. We also demonstrate we can incorporate primary patient-derived organoids into the pipeline to capture patient-level tumour heterogeneity. We envision that this automated workflow integrated with 96/384-SPOT and multiple cell types and patient-derived organoid models will provide opportunities for future applications in high-throughput screening for novel personalized therapeutic targets. This pipeline also allows the user to assess dynamic cell responses using high-content longitudinal imaging or downstream single-cell-based analyses.
Annotation of biologically relevant ligands in UniProtKB using ChEBI

Motivation To provide high quality, computationally tractable annotation of binding sites for biologically relevant (cognate) ligands in UniProtKB using the chemical ontology ChEBI (Chemical Entities of Biological Interest), to better support efforts to study and predict functionally relevant interactions between proteins and small molecule ligands. Results We structured the data model for cognate ligand binding site annotations in UniProtKB and performed a complete reannotation of all cognate ligand binding sites using stable unique identifiers from ChEBI, which we now use as the reference vocabulary for all such annotations. We developed improved search and query facilities for cognate ligands in the UniProt website, REST API and SPARQL endpoint that leverage the chemical structure data, nomenclature, and classification that ChEBI provides. Availability Binding site annotations for cognate ligands described using ChEBI are available for UniProtKB protein sequence records in several formats (text, XML, and RDF), and are freely available to query and download through the UniProt website (www.uniprot.org), REST API (www.uniprot.org/help/api), SPARQL endpoint (sparql.uniprot.org/), and FTP site (https://ftp.uniprot.org/pub/databases/uniprot/). Contact alan.bridge@sib.swiss Supplementary information Supplementary Table 1.
Structural and functional insights into the type III-E CRISPR-Cas immunity

The type III-E CRISPR-Cas system comprises a Cas effector (gRAMP), a TPR-CHAT and several ancillary proteins. However, both the structural features of gRAMP and the immunity mechanism remain unknown for this system. Here, we report a series of structures of gRAMP-crRNA, either its alone or in complex with target RNA or TPR-CHAT (called Craspase), and Craspase complexed with cognate (CTR) or non-cognate target RNA (NTR). Importantly, the 3’ anti-tag region of NTR and CTR bind at two distinct channels in the Craspase, and CTR with a non-complementary 3’ anti-tag induces a marked conformational change of the TPR-CHAT, which allosterically activates its protease activity to cleave an ancillary protein Csx30. This cleavage then triggers an abortive infection as the antiviral strategy of the type III-E system. Together, our study provides crucial insights into both the catalytic mechanism of the gRAMP and the immunity mechanism of the type III-E CRISPR-Cas system.
Physiological and behavioural resistance of malaria vectors in rural West-Africa : a data mining study to address their fine-scale spatiotemporal heterogeneity, drivers, and predictability

Insecticide resistance and behavioural adaptation of malaria mosquitoes affect the efficacy of long-lasting insecticide nets - currently the main tool for malaria vector control. To develop and deploy complementary, efficient and cost-effective control interventions, a good understanding of the drivers of these physiological and behavioural traits is needed. In this data-mining exercise, we modelled a set of indicators of physiological resistance to insecticide (prevalence of three target-site mutations) and behavioural resistance phenotypes (early- and late-biting, exophagy) of anopheles mosquitoes in two rural areas of West-Africa, located in Burkina Faso and Cote d’Ivoire. To this aim, we used mosquito field collections along with heterogeneous, multi-source and multi-scale environmental data. The objectives were i) to assess the small-scale spatial and temporal heterogeneity of physiological resistance to insecticide and behavioural resistance phenotypes, ii) to better understand their drivers, and iii) to assess their spatio-temporal predictability, at scales that are consistent with operational action. The explanatory variables covered a wide range of potential environmental determinants of vector resistance to insecticide or behavioural resistance phenotypes : vector control, human availability and nocturnal behaviour, macro and micro-climatic conditions, landscape, etc. The resulting models revealed many statistically significant associations, although their predictive powers were overall weak. We interpreted and discussed these associations in light of several topics of interest, such as : respective contribution of public health and agriculture in the selection of physiological resistances, biological costs associated with physiological resistances, biological mechanisms underlying biting behaviour, and impact of micro-climatic conditions on the time or place of biting. To our knowledge, our work is the first modeling insecticide resistance and feeding behaviour of malaria vectors at such fine spatial scale with such a large dataset of both mosquito and environmental data.
Genetic effects of sequence-conserved enhancer-like elements on human complex traits

Non-coding sequences that are evolutionarily conserved and bio-chemically active offer clues to mechanistic interpretations of human genome-wide association studies (GWAS). However, their genetic effects have not been systematically examined across a wide range of human tissues and traits. Here we develop a simple method to identify functional elements exhibiting high levels of human-mouse sequence conservation and enhancer-like biochemical activity, which scales well to 313 epigenomic datasets across 106 tissues and cell types. Combining these elements with 468 GWAS of European (EUR) and East Asian (EAS) ancestries, we identify tissue-specific enrichments of heritability and causal variants for many traits, as well as candidate genes that are functionally relevant to body mass index (BMI) and schizophrenia but were not reported in previous GWAS. Our findings provide a comprehensive assessment of how sequence-conserved enhancer-like elements affect complex traits, and reinforce the importance of integrating evolutionary and biochemical data to elucidate human disease genetics.
Mechanical and Heat Hyperalgesia upon Withdrawal from Chronic Intermittent Ethanol Vapor depends on Sex, Exposure Duration and Blood Alcohol Concentration in Mice

Approximately half of patients with alcohol use disorder (AUD) report pain and this can be severe during withdrawal. However, many questions remain regarding the importance of sex, blood alcohol concentration (BAC), time course, and pain modality. To examine the impact of sex and BAC on the time course of the development of mechanical and heat hyperalgesia, we characterized a mouse model of Chronic Alcohol Withdrawal Induced Pain (CAWIP) in the presence or absence the alcohol dehydrogenase inhibitor, pyrazole. Male and female C57BL/6J mice underwent chronic intermittent ethanol vapor (CIEV) ± pyrazole exposure for 4 weeks, 4 days/week to induce ethanol dependence. Hind paw sensitivity to the plantar application of mechanical (von Frey filaments) and radiant heat stimuli were measured during weekly observations at 1, 3, 5, 7, 24, and 48 hr after cessation of ethanol exposure. In the presence of pyrazole, males developed mechanical hyperalgesia after the first week of CIEV exposure, peaking at 48 hours after cessation of ethanol. By contrast, females did not develop mechanical hyperalgesia until the fourth week; this also required pyrazole and did not peak until 48 hours. Heat hyperalgesia was consistently observed only in females exposed to ethanol and pyrazole; this developed after the first weekly session and peaked at 1 hour. We conclude that CAWIP develops in a sex –, time –, and BAC – dependent manner in C57BL/6J mice.
Mechanism and Control of Spalling for Friable Sandstone Pillars in a Room and Pillar Mine

The ability to efficiently control sandstone pillar spalling is extremely important in ensuring the safety and highefficiency production of sandstone mines. The increase in size is usually suggested as a remedy for pillar spalling, but none of the suggested remedies reflect the influences of geotechnical properties of rock mass on stability control. Some sandstone mining practices have proven that increasing the size of pillars cannot effectively control pillar spalling. The relationship between the strength of St. Peter sandstone pillar and pillar loads was theoretically analyzed in the current study, in order to examine the influences of geotechnical parameters of sandstone on the stability of pillars and control pillar spalling. The key geotechnical parameters that influence the stability of sandstone pillars were also examined. Subsequently, the pillar instability mechanism and influences of geotechnical parameters on pillar stability were investigated by Finite Difference Method. Finally, a ground control method using shotcrete on pillar was proposed for increasing the stability of pillars. Results demonstrate that compressive stress on the St. Peter sandstone pillar is considerably larger than the compressive strength after mining, resulting in the evident deformation of most regions. The relation curves of displacement at the pillar top with internal friction angle and cohesion are in the power functional distributions, but the change of cohesion is more significant in the pillar strength. The displacement at the pillar top gradually decreases with the increase in internal friction angle, whereas the plastic failure regions of pillars gradually decrease from the bottom to the upper parts with the increase in cohesion. A field industrial test proves that shotcrete on pillars can increase pillar strength, which effectively controls the pillar spalling. Research results provide theoretical and practical guidelines to enhance the stability of pillars under the same geotechnical circumstances.
Sometimes R 2 > r 2 yx 1 + r 2 yx 2 : Correlated Variables are Not Always Redundant

Abstract An extreme example of regression on two variables is presented in which there is almost no correlation between y and x 1 and y and x 2, yet the coefficient of determination is 1. This example illustrates the often counter-intuitive nature of multivariate relationships and is also relevant to discussions on multicollinearity and variable selection techniques.
A numerical method for solving the Vlasov equation

A numerical procedure is derived for the solution of the Vlasov-Poisson system of equations in two phase-space variables. Derivatives with respect to the phase-space variables are approximated by a weighted sum of the values of the distribution function at property chosen neighboring points. The resulting set of ordinary differential equations is then solved by using an appropriate time intergration scheme. The accuracy of the proposed method is tested with some simple model problems. The results for the free streaming case, linear Landau damping, and nonlinear Landau damping are investigated and compared with those of the splitting scheme. The proposed method is found to be very accurate and efficient.
Title article: Functional characterization of Pa LAX1, a putative auxin permease, in heterologous plant systems

We have isolated the cDNA of the gene Pa LAX1 from a wild cherry tree ( Prunus avium ). The gene and its product are highly similar in sequences to both the cDNAs and the corresponding protein products of AUX/LAX- type genes, coding for putative auxin influx carriers. We have prepared and characterized transformed tobacco ( Nicotiana tabacum ) and Arabidopsis ( Arabidopsis thaliana ) plants carrying the gene Pa LAX1 . We have proved that constitutive overexpression of Pa LAX1 is accompanied by changes in the content and distribution of free indole-3-acetic acid, the major endogenous auxin. The increase in free indole-3-acetic acid content in transgenic plants resulted in various phenotype changes, typical for the ‘auxin-overproducing’ plants. The uptake of synthetic auxin, 2,4-dichlorophenoxyacetic acid, was three times higher in transgenic lines compared to the wild type lines and the treatment with the auxin uptake inhibitor, 1-naphthoxyacetic acid, reverted the changes caused by the expression of Pa LAX1. Moreover, the agravitropic response could be restored by expression of Pa LAX1 in the mutant aux1 plants, which are deficient in auxin influx carrier activity. Based on our data, we have concluded that the product of the gene Pa LAX1 promotes the uptake of auxin into cells and, as a putative auxin influx carrier, it affects the content and distribution of free endogenous auxin in transgenic plants. which only the transgene and not a putative endogene of AUX/LAX family; this set of primers gave a clear single product corresponding to Pa LAX1 transgene/mRNA in both Arabidopsis and tobacco while no amplification product was detected in either PCR or RT-PCR reactions performed on wild-type control plants. In all transgenic lines obtained, we confirmed the stable presence of the transgene as well as its expression on the mRNA level.
SelectionCalcineurin on T Cell Activation and Thymic Effects of a Constitutively Active Form of

Calcineurin is a calcium/calmodulin-dependent phosphatase whose activity is required for the induction of T cell lymphokine production and proliferation. Although its speciﬁc role in T cell development is less well deﬁned, studies with the immunosuppressive drugs cyclosporin A and FK-506 suggest that it is involved in both positive and negative selection of immature thymocytes. To more completely characterize a role for calcineurin in T cell development in vivo, we have generated transgenic mice that express an activated form of this enzyme in thymocytes and peripheral T cells. We ﬁnd that the transgene causes a block in early thymic development, resulting in a reduction in the steady-state number of CD4 and CD8 double positives, but not on the number of mature T cells. We also ﬁnd that thymocytes and mature T cells expressing this transgene are more sensitive to signals through their TCR. In thymocytes this sensitivity difference is manifested as an increase in positive selection, although negative selection seems to remain unaffected. Therefore, these studies conﬁrm and extend past reports that suggested a role for calcineurin in thymic development and selection. The Journal of Immunology, 2000, 165: 3713–3721.
Research progress of laser trimming: a mini review

The purpose of this paper is to review laser trimming and precision control of alloy strip resistors, which is extensively applied for electronic vehicles and other power electronics. This mini review especially introduces the laser trimming of background, methodology, mechanism, influencing factor and main problem in details. The existing problems and the future development trend of laser trimming are also discussed.
Improving Online Interactive Modules: An Iterative Design Model

— With the promotion of online and interactive learning, instructors may be tempted to include arbitrarily the latest technologies into their modules without considering the ramifications on students and their learning processes. Instead, we propose that online and interactive modules should be carefully designed using multiple levels of review to ensure clarity of instruction, ease of use of interactive components, and engagement of the students with the material and any related activities. This paper documents the process to design and improve an online module using an iterative process involving instructional designers, student pilot tests, and a focus group. Feedback from these constituents enabled instructors to optimize instructional design to maximize learning opportunities and achievement in online environments.
New Technologies for Producing Bicycle Hub Forging

The paper presents the results of research on two new forging processes for producing bicycle hub forgings in a three-slide forging press. The first process is related to producing a forging with an axial cavity by flashless forging. The other one concerns the production of a forging from a tube billet. The potential benefits offered by these two new forging processes compared to the conventional hammer forging method for producing hubs are discussed. The designed processes are verified theoretically via numerical simulations. The first of the proposed processes is also subjected to experimental verification. The results demonstrate that the new technologies allow obtaining good quality products. A comparison is made between material and energy consumption in the two analyzed processes and in conventional hammer forging. It is found that the application of the forging process in a three-slide forging press leads to a considerable decrease in manufacturing costs.