Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomics and phenomics enabled prebreeding improved early-season chilling tolerance in Sorghum

In temperate climates, earlier planting of tropical-origin crops can provide longer growing seasons, reduce water loss, suppress weeds, and escape post-flowering drought stress. However, chilling sensitivity of sorghum, a tropical-origin cereal crop, limits early planting and over 50 years of conventional breeding has been stymied by coinheritance of chilling tolerance (CT) loci with undesirable tannin and dwarfing alleles. In this study, phenomics and genomics-enabled approaches were used for prebreeding of sorghum early-season CT. Uncrewed aircraft systems (UAS) high-throughput phenotyping platform tested for improving scalability showed moderate correlation between manual and UAS phenotyping. UAS normalized difference vegetation index (NDVI) values from the chilling nested association mapping population detected CT QTL that colocialized with manual phenotyping CT QTL. Two of the four first-generation KASP molecular markers, generated using the peak QTL SNPs, failed to function in an independent breeding program as the CT allele was common in diverse breeding lines. Population genomic FST analysis identified SNP CT alleles that were globally rare but common to the CT donors. Second-generation markers, generated using population genomics, were successful in tracking the donor CT allele in diverse breeding lines from two independent sorghum breeding programs. Marker-assisted breeding, effective in introgressing CT allele from Chinese sorghums into chilling-sensitive US elite sorghums, improved early-planted seedling performance ratings in lines with CT alleles by up to 13–24% compared to the negative control under natural chilling stress. These findings directly demonstrate the effectiveness of high-throughput phenotyping and population genomics in molecular breeding of complex adaptive traits.
Online versus Cognitive Control: A Dividing Line between Physical Action and Motor Imagery

Recent work has shown that motor imagery is highly sensitive to tasks that interfere with executive resources, whereas physical actions are largely immune. This has been taken as support for the Motor-Cognitive model of motor imagery, and against the theory of Functional Equivalence. Here, we examined another prediction of the MCM, namely that an opposite pattern of effects would be observed when the information available for online control was reduced. This was tested in three experiments in which participants performed either physical actions or motor imagery. The experiments manipulated the quality of information available during the online control of movement through: 1) comparing movements made with or without visual feedback; 2) comparing movements made using foveal vs. peripheral vision; and 3) comparing physical to mimed actions. All three experiments found evidence in favour of the Motor-Cognitive model in that manipulations of online control affected motor imagery but not overt action. These same results were, however, inconsistent with a Functional Equivalence view. We discuss these results in the broader context of theoretical views on perceptual vs. motor imagery.
Astrophysical Background and Dark Matter Implication Based on Latest AMS-02 Data

The cosmic-ray (CR) positrons and antiprotons are often regarded as the collision products of CR nucleons with the interstellar medium. However, the predicted fluxes of CR positrons and antiprotons by the conventional models are not consistent with the experimental data from PAMELA, Fermi-LAT, AMS-02, etc. In this work, we choose the latest AMS-02 data to analyze the astrophysical background of CR positrons and antiprotons. QGSJET-II-04 is chosen as the hadronic interaction model. The GALPROP package is used to solve the propagation equation numerically. The results show that the predicted flux of CR positrons at low energies is consistent with AMS-02 data in the reacceleration and convection–diffusion (DCR) model. In the DCR model and the hadronic interaction model, QGSJET-II-04, the excess of CR antiprotons at low energies is excluded. The dark matter interpretation of the positron excess is analyzed with the total fluxes of CR electrons and positrons from AMS-02. The predicted best-fit mass of dark matter ranges from 400 GeV to 4 TeV. Moreover, in the above models the predicted flux of CR protons is completely consistent with AMS-02 data, which matches the hardening feature above 330 GeV.
CRISPR/FnCas12a-mediated efficient multiplex and iterative genome editing in bacterial plant pathogens without donor DNA templates

CRISPR-based genome editing technology is revolutionizing prokaryotic research, but it has been rarely studied in bacterial plant pathogens. Here, we have developed a targeted genome editing method with no requirement of donor templates for convenient and efficient gene knockout in Xanthomonas oryzae pv. oryzae (Xoo), one of the most important bacterial pathogens on rice, by employing the heterogenous CRISPR/Cas12a from Francisella novicida and NHEJ proteins from Mycobacterium tuberculosis. FnCas12a nuclease generated both small and large DNA deletions at the target sites as well as it enabled multiplex genome editing, gene cluster deletion and plasmid cure in the Xoo PXO99A strain. Accordingly, a non-TAL effector-free polymutant strain PXO99AD25E, which lacks all 25 Xop genes involved in Xoo pathogenesis, has been engineered through iterative genome editing. Whole-genome sequencing analysis indicated that FnCas12a did not have a noticeable off-target effect. In addition, we revealed that these strategies are also suitable for targeted genome editing in another bacterial plant pathogen Pseudomonas syringae pv. tomato (Pst). We believe that our bacterial genome editing method will greatly expand the CRISPR study on microorganisms and advance our understanding of the physiology and pathogenesis of Xoo.
Receptor Elimination by E3 Ubiquitin Ligase Recruitment (REULR): A Targeted Protein Degradation Toolbox

In recent years, targeted protein degradation (TPD) of plasma membrane proteins by hijacking the ubiquitin proteasome system (UPS) or the lysosomal pathway have emerged as novel therapeutic avenues in drug development to address and inhibit canonically difficult targets. While TPD strategies have been successful to target cell surface receptors, these approaches are limited by the availability of suitable binders to generate heterobifunctional molecules. Here, we present the development of a nanobody (VHH) based degradation toolbox termed REULR (Receptor Elimination by E3 Ubiquitin Ligase Recruitment). We generated human and mouse cross-reactive nanobodies against 5 transmembrane PA-TM-RING type E3 Ubiquitin Ligases (RNF218, RNF130, RNF167, RNF43, ZNRF3) covering a broad range and selectivity of tissue expression with which we characterized expression in human and mouse cell lines and immune cells (PBMCs). We demonstrate that heterobifunctional REULR molecules can enforce transmembrane E3 ligase interaction with a variety of disease relevant target receptors (EGFR, EPOR, PD-1) by induced proximity resulting in effective membrane clearance of the target receptor at varying levels. In addition, we designed E3 Ligase self-degrading molecules, ‘fratricide’ REULRs (RNF128, RNF130, RENF167, RNF43, ZNRF3), that allow downregulation of one or several E3 Ligases from the cell surface and consequently modulate receptor signaling strength. REULR molecules represent a VHH-based, modular and versatile “mix and match” targeting strategy for facile modulation of cell surface proteins by induced proximity to transmembrane PA-TM-RING E3 ligases.
Platelets favor the outgrowth of established metastases

Despite abundant evidence demonstrating that platelets foster metastasis, a therapeutic approach based on anti-platelet agents is not an option due to the risk of hemorrhages. In addition, whether platelets can regulate metastasis at the late stages of the disease remains unknown. In this study, we subjected syngeneic models of metastasis to various thrombocytopenic regimes to show that platelets provide a biphasic contribution to metastasis. While potent intravascular binding of platelets to tumor cells efficiently promotes metastasis, platelets further support the outgrowth of established metastases. Genetic depletion and pharmacological targeting of the platelet-specific receptor GPVI in humanized mouse models efficiently reduced the growth of established metastases, independently of active platelet binding to tumor cells in the bloodstream. Our study is the first to demonstrate therapeutic efficacy when targeting animals carrying growing metastases. It further identifies GPVI as the first molecular target whose inhibition can impair metastasis without inducing collateral hemostatic perturbations.
Deep model predictive control of gene expression in thousands of single cells

Gene expression is inherently dynamic, due to complex regulation and stochastic biochemical events. However, the effects of these dynamics on cell phenotypes can be difficult to determine. Researchers have historically been limited to passive observations of natural dynamics, which can preclude studies of elusive and noisy cellular events where large amounts of data are required to reveal statistically significant effects. Here, using recent advances in the fields of machine learning and control theory, we train a deep neural network to accurately predict the response of an optogenetic system in Escherichia coli cells. We then use the network in a deep model predictive control framework to impose arbitrary and cell-specific gene expression dynamics on thousands of single cells in real time, applying the framework to generate complex time-varying patterns. We also showcase the framework’s ability to link expression patterns to dynamic functional outcomes by controlling expression of the tetA antibiotic resistance gene. This study highlights how deep learning-enabled feedback control can be used to tailor distributions of gene expression dynamics with high accuracy and throughput.
Resting mitochondrial complex I from Drosophila melanogaster adopts a helix-locked state

Respiratory complex I is a proton-pumping oxidoreductase key to bioenergetic metabolism. Biochemical studies have found a divide in the behavior of complex I in metazoans that aligns with the evolutionary split between Protostomia and Deuterostomia. Complex I from Deuterostomia including mammals can adopt an off-pathway “deactive” state, whereas complex I from Protostomia cannot. The presence of off-pathway states complicates the interpretation of structural results and has led to considerable mechanistic debate. Here we report the structure of mitochondrial complex I from the thoracic muscles of the model protostomian Drosophila melanogaster. We show that, although D. melanogaster complex I (Dm-CI) does not deactivate the resting state of Dm-CI adopts multiple conformations. We identify a new helix-locked open state in which an N-terminal α-helix on the NDUFS4 subunit wedges between the peripheral and membrane arms. Comparison of the Dm-CI structure and conformational states to those observed in bacteria, yeast and mammals provides insight into the roles of subunits across organisms, explains why Dm-CI does not deactivate and reveals incompatibilities with current mechanistic models of complex I turnover. Additionally, the Dm-CI structure and novel regulatory mechanism will allow for the development of more selective pesticides for agriculture and human disease.
Engineering transmembrane signal transduction in synthetic membranes using two-component systems

Cells use signal transduction across their membranes to sense and respond to a wide array of chemical and physical signals. Creating synthetic systems which can harness cellular signaling modalities promises to provide a powerful platform for biosensing and therapeutic applications. As a first step towards this goal, we investigated how bacterial two-component systems can be leveraged to enable transmembrane-signaling with synthetic membranes. Specifically, we demonstrate that a bacterial two-component nitrate-sensing system (NarX-NarL) can be reproduced outside of a cell using synthetic membranes and cell-free protein expression systems. We find that performance and sensitivity of the two-component system can be tuned by altering the biophysical properties of the membrane in which the histidine kinase (NarX) is integrated. Through protein engineering efforts, we modify the sensing domain of NarX to generate sensors capable of detecting an array of ligands. Finally, we demonstrate that these systems can sense ligands in relevant sample environments. By leveraging membrane and protein design, this work helps reveal how transmembrane sensing can be recapitulated outside of the cell, adding to the arsenal of deployable cell-free systems primed for real world biosensing. Significance Statement Cells detect and respond to environmental and chemical information by using a combination of membrane proteins and genetic polymers. Recapitulation of this behavior in synthetic systems holds promise for engineering biosensors and therapeutics. Using the nitrate-sensing bacterial two-component system as a model, we demonstrate methods to reproduce and tune transmembrane signaling in synthetic lipid membranes, leading to the synthesis of genetically programmed proteins. Through this study, we gain insight into how membrane augmented cell-free systems can be used as a platform to characterize membrane-receptor interactions and engineer new biosensors.
TRPA1 activation in non-sensory supporting cells contributes to regulation of cochlear sensitivity after acoustic trauma

TRPA1 channels are expressed in nociceptive neurons, where they detect noxious stimuli, and in the mammalian cochlea, where their function is unknown. Here we show that TRPA1 activation in the supporting non-sensory Hensen’s cells causes prolonged Ca2+ responses, which propagate across the organ of Corti and cause long-lasting contractions of pillar and Deiters’ cells. Caged Ca2+ experiments demonstrated that, similar to Deiters’ cells, pillar cells also possess Ca2+-dependent contractile machinery. TRPA1 channels are activated by endogenous products of oxidative stress and by extracellular ATP. Since both these stimuli are present in vivo after acoustic trauma, TRPA1 activation after noise may affect cochlear sensitivity through supporting cell contractions. Consistently, TRPA1 deficiency results in larger but less prolonged noise-induced temporary shift of hearing thresholds, accompanied by permanent changes of latency and shape of the auditory brainstem responses. We conclude that TRPA1 contributes to the regulation of cochlear sensitivity after acoustic trauma.
Evaluation of stability and adaptability for new spring safflower lines in different environmental conditions of Iran.

The stability of seven spring safflower cultivars and lines were evaluated in five different environmental conditions of Karaj, Isfahan, Eslamabad, and Zargan, in Iran, for two years (20022004). Simple analysis of variances of grain and oil yields from each experiment showed significant differences among the genotypes. After having homogeneity test for error variances combined analysis of variance was performed. F.test of different sources of variation revealed that the effect of genotype x year x location interaction was significant (P<1%). Analysis of the grain and oil yields using Eberhart and Russell method showed significant difference for the main effects of genotype and genotype x environment (linear) interactions and nonsignificant difference for deviation from regression for some genotypes. According to the classification of genotypes based on the mean of grain and oil yields, coefficient of regression and deviation from regression, the new line I.L. 111 with its high grain and oil yields and stability was selected as a desirable genotype.
Fabrication of Micro Glass Spherical Resonator by Chemical Foaming Process (CFP)

Background and Objectives: The Hemispherical Resonator Gyroscope (HRG) is an inertial sensor which is a good choice for space missions and inertial navigation due to their low noise, low energy consumption, long life, and excellent accuracy and sensitivity. It consists of three main parts: the shell, the excitation and detection system, and the control circuits. In recent years, with using MEMS technology in the construction of HRG, vibrating shells with low volume and low price are made. Methods: The hemispherical shell is the main part and the beating heart of hemispherical resonator gyroscopes and is responsible for sensing. An optimized shell is required to implement the excitation and detection system and operate the gyroscope properly. In this research, the structure of a spherical shell with an environmental base that does not need to release the shell from its environment for its excitation and detection system is selected and the relationships governing this type of shell to improve the parameters of the glass blowing method will be investigated. Also, all sub-processes of this type method of fabrication to optimize the glass-blown spherical shell are implemented. Results: The process of making spherical shell by glass blowing using the chemical foaming process is used to obtain shells with height to radius ratio greater than 1, and finally, a glass shell with an etched cavity with a radius of 562 μm and depth of 524 μm created by the CNC process, with height to radius ratio of approximately 1.8 has been achieved. In this method, using direct transfer of calcium carbonate to the etched cavity, before anodic bonding, the glass shell volume has been increased from 0.602 nL to 1.04 nL. Conclusion: The result is that to achieve a glass shell with a height to radius ratio of more than 1, in addition to improving the fabrication process, it is necessary to transfer the solid foaming agent to the etched cavity. Finally, in the fabrication of the glass-blown spherical shell, we have used the chemical foaming process (CFP) to obtain shells with a height to radius ratio greater than 1.
Global existence and blow-up of solutions to some quasilinear wave equation in one space dimension

We consider the global existence and blow up of solutions of the Cauchy problem of the quasilinear wave equation: $\partial_{t}^2 u = \partial_x(c(u)^2 \partial_x u)$, which has richly physical backgrounds. Under the assumption that $c(u(0,x))\geq \delta$ for some $\delta>0$, we give sufficient conditions for the existence of global smooth solutions and the occurrence of two types of blow-up respectively. One of the two types is that $L^{\infty}$-norm of $\partial_t u$ or $\partial_x u$ goes up to the infinity. The other type is that $c(u)$ vanishes, that is, the equation degenerates.
The Most Important Election of Our Lifetime: Focalism and Political Participation

This paper argues that a psychological bias called focalism contributes to an overestimation of the diﬀerences between political candidates, which in turn increases participation and polarization. Focalism causes people to confuse the allocation of attention to things with the importance of those things. Because attention to politics typically centers on conﬂict, the result is an exaggeration of diﬀerences across the partisan di-vide. I test this intuition using an experimental design that provides all respondents with all of the information they need to estimate how much Joe Biden and Donald Trump objectively disagreed on policy positions just before the 2020 election. I ﬁnd that shifting attention – towards either those positions the candidates agreed or disagreed with each other on – inﬂuences beliefs about the diﬀerences between candidates. The eﬀect exceeds that of identifying as a Democrat or as a Republican. Beyond those perceptions, focalism increases turnout intentions, perceptions of election importance, negative feelings towards the out-candidate, and aﬀective polarization.
listener of function

The present study investigated “the” reduction in phrase-medial Verb- the -Noun sequences elicited from 2 five-year-old children and college-aged adults. Several measures of reduction were calculated based on 3 acoustic measurement of these sequences. Analyses on the measures indicated that the determiner vowel 4 was reduced in both child and adult speech relative to content word vowels, but it was reduced less in 5 children’s speech compared to adults’ speech. Listener ratings on the sequences indicated a preference for 6 adult speech over children's speech. Acoustic measures of reduction also predicted goodness ratings. 7 Listeners preferred sequences with shorter and lower amplitude determiner vowels relative to content 8 word vowels. They also preferred a more neutral schwa over more coarticulated versions. In sequences 9 where ratings differed by age group, the effect of coarticulation was limited to adult speech and the effect 10 of relative schwa duration was limited to children’s speech. The results are discussed with reference to 11 communicative pressures on function word production in speech, including the rhythmic and semantic 12 pressure towards reduction versus the pressure to convey adequate information in the acoustic signal. It is 13 argued that competing pressures on production may delay the acquisition of adult-like function word 14 reduction.
Optical validation and characterisation of Planck PSZ1 sources at the Canary Islands observatories

We report new galaxy clusters previously unknown included in the first Planck Sunyaev–Zeldovich (SZ) sources catalogue, the PSZ1. The results presented here were achieved during the second year of a two-year observational programme, the ITP13, developed at the Roque de los Muchachos Observatory (La Palma, Spain). Using the 2.5 m Isaac Newton telescope, the 3.5 m Telescopio Nazionale Galileo, the 4.2 m William Herschel telescope and the 10.4 m Gran Telescopio Canarias we characterised 75 SZ sources with low SZ significance, SZ S/N < 5.32. We performed deep optical imaging and spectroscopy in order to associate actual galaxy clusters with the SZ Planck source. We adopted robust criteria, based on the 2D spatial distribution, richness, and velocity dispersions to confirm actual optical counterparts up to z < 0.85. The selected systems are confirmed only if they are well aligned with respect to the PSZ1 coordinate and show high richness and high velocity dispersion. In addition, we also inspected the Compton y-maps and SZ significance in order to identify unrealistic detections. Following this procedure, we identify 26 cluster counterparts associated with the SZ emission, which means that only about 35% of the clusters considered in this low S/N PSZ1 subsample are validated. Forty-nine SZ sources (∼65% of this PSZ1 subset) remain unconfirmed. At the end of the ITP13 observational programme, we have studied 256 SZ sources with Dec ≥ −15° (212 of them completely unknown), finding optical counterparts for 152 SZ sources. The ITP13 validation programme has allowed us to update the PSZ1 purity, which is now more refined, increasing from 72% to 83% in the low SZ S/N regime. Our results are consistent with the predicted purity curve for the full PSZ1 catalogue and with the expected fraction of false detections caused by the non-Gaussian noise of foreground signals. We find a strong correlation between the number of unconfirmed sources and the thermal emission of diffuse galactic dust at 857 GHz, thus increasing the fraction of false Planck SZ detections at low galactic latitudes.