Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineering Viral Vectors for Acoustically Targeted Gene Delivery

Targeted gene delivery to the brain is a critical tool for neuroscience research and has significant potential to treat human disease. However, the site-specific delivery of common gene vectors such as adeno-associated viruses (AAVs) is typically performed via invasive injections, limiting their scope of research and clinical applications. Alternatively, focused ultrasound blood-brain-barrier opening (FUS-BBBO), performed noninvasively, enables the site-specific entry of AAVs into the brain from systemic circulation. However, when used in conjunction with natural AAV serotypes, this approach has limited transduction efficiency, requires ultrasound parameters close to tissue damage limits, and results in undesirable transduction of peripheral organs. Here, we use high throughput in vivo selection to engineer new AAV vectors specifically designed for local neuronal transduction at the site of FUS-BBBO. The resulting vectors substantially enhance ultrasound-targeted gene delivery and neuronal tropism while reducing peripheral transduction, providing a more than ten-fold improvement in targeting specificity. In addition to enhancing the only known approach to noninvasively target gene delivery to specific brain regions, these results establish the ability of AAV vectors to be evolved for specific physical delivery mechanisms.
Endorsement and phylogenetic analysis of some Fabaceae plants based on DNA barcoding

Background DNA barcoding have been considered as a tool to facilitate species identification based on its simplicity and high-level accuracy in compression to the complexity and subjective biases linked to morphological identification of taxa. MaturaseK gene ( MatK gene) of the chloroplast is very vital in the plant system which is involved in the group II intron splicing. The main objective of this study is to determine the relative utility of the “ MatK ” chloroplast gene for barcoding in 15 legume as a tool to facilitate species identification based on their simplicity and high-level accuracy linked to morphological identification of taxa. Methods and Results MatK gene sequences were submitted to GenBank and the accession numbers were obtained with sequence length ranging from 730 to 1545 nucleotides. These DNA sequences were aligned with database sequence using PROMALS server , Clustal Omega server and Bioedit program. Maximum likelihood and neighbor-joining algorithms were employed for constructing phylogeny. Overall, these results indicated that the phylogenetic tree analysis and the evolutionary distances of an individual dataset of each species were agreed with a phylogenetic tree of all each other consisting of two clades, the first clade comprising (Enterolobium contortisiliquum, Albizia lebbek), Acacia saligna , Leucaena leucocephala, Dichrostachys Cinerea, (Delonix regia, Parkinsonia aculeata), (Senna surattensis, Cassia fistula, Cassia javanica) and Schotia brachypetala were more closely to each other, respectively. The remaining four species of Erythrina humeana, (Sophora secundiflora, Dalbergia Sissoo, Tipuana Tipu) constituted the second clade. Conclusion Moreover, their sequences could be successfully utilized in single nucleotide polymorphism or as part of the sequence as DNA fragment analysis utilizing polymerase chain reaction in plant systematic. Therefore, MatK gene is considered promising a candidate for DNA barcoding in the plant family Fabaceae and provides a clear relationship between the families.
Substitution Rate Variation in a Robust Procellariiform Seabird Phylogeny is not Solely Explained by Body Mass, Flight Efficiency, Population Size or Life History Traits

Substitution rate variation among branches can lead to inaccurate reconstructions of evolutionary relationships and obscure the true phylogeny of affected clades. Body mass is often assumed to have a major influence on substitution rate, though other factors such as population size, life history traits, and flight demands are also thought to have an influence. Birds of the order Procellariiformes—which encompasses petrels, storm-petrels and albatrosses—show a striking 900-fold difference in body mass between the smallest and largest members, divergent life history traits, and substantial heterogeneity in mitochondrial substitution rates. Here, we used genome-scale nuclear DNA sequence data from 4365 ultraconserved element loci (UCEs) in 51 procellariiform species to examine whether phylogenetic reconstruction using genome-wide datasets is robust to the presence of rate heterogeneity, and to identify predictors of substitution rate variation. Our results provide a backbone phylogeny for procellariiform seabirds and resolve several controversies about the evolutionary history of the order, demonstrating that albatrosses are basal, storm-petrels are paraphyletic and diving petrels nestled within the Procellariidae. We find evidence of rate variation; however, all phylogenetic analyses using both concatenation and multispecies coalescent approaches recovered the same branching topology, including analyses implementing different clock models, and analyses of the most and least clock-like loci. Overall, we find that rate heterogeneity is little impacted by body mass, population size, age at first breeding, and longevity but moderately correlated with hand-wing index, a proxy for wing shape and flight efficiency. Given our results and the context of the broader literature perhaps it is time that we begin to question the prevailing paradigm that one or a few traits largely explain rate variation and accept instead that substitution rate may be the product of weak interactions among many, potentially taxon-specific, variables.
Contribution of 3D genome topological domains to genetic risk of cancers: a genome-wide computational study

Genome-wide association studies have identified statistical associations between various diseases, including cancers, and a large number of single-nucleotide polymorphisms (SNPs). However, they provide no direct explanation of the mechanisms underlying the association. Based on the recent discovery that changes in three-dimensional genome organization may have functional consequences on gene regulation favoring diseases, we investigated systematically the genome-wide distribution of disease-associated SNPs with respect to a specific feature of 3D genome organization: topologically associating domains (TADs) and their borders. For each of 449 diseases, we tested whether the associated SNPs are present in TAD borders more often than observed by chance, where chance (i.e., the null model in statistical terms) corresponds to the same number of pointwise loci drawn at random either in the entire genome, or in the entire set of disease-associated SNPs listed in the GWAS catalog. Our analysis shows that a fraction of diseases displays such a preferential localization of their risk loci. Moreover, cancers are relatively more frequent among these diseases, and this predominance is generally enhanced when considering only intergenic SNPs. The structure of SNP-based diseasome networks confirms that localization of risk loci in TAD borders differs between cancers and non-cancer diseases. Furthermore, different TAD border enrichments are observed in embryonic stem cells and differentiated cells, consistent with changes in topological domains along embryogenesis and delineating their contribution to disease risk. Our results suggest that, for certain diseases, part of the genetic risk lies in a local genetic variation affecting the genome partitioning in topologically insulated domains. Investigating this possible contribution to genetic risk is particularly relevant in cancers. This study thus opens a way of interpreting genome-wide association studies, by distinguishing two types of disease-associated SNPs: one with an effect on an individual gene, the other acting in interplay with 3D genome organization.
Selection and evaluation of qPCR reference genes for expression analysis in the tiny egg parasitoid wasp, Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae)

The egg parasitoid Trichogramma spp. is an important biological control agent used against multiple species of Lepidopteran pest in forestry and agriculture. Due to the importance of Trichogramma spp. in biocontrol programs, its biological characteristics have been studied in detail, and current investigations should focus on the molecular biology of these tiny parasitoids. Real-time quantitative PCR (qPCR) is considered as the standard method for quantifying the gene expression of organisms. Surprisingly, the appropriate reference genes to ensure robust qPCR have not been documented at all for the Trichogramma genus. This study aimed to identify suitable reference genes for use in qPCR procedure of Trichogramma dendrolimi. Nine candidate housekeeping genes, namely glyceraldehyde-3-phosphate dehydrogenase (GAPDH), forkhead box O (FOXO), superoxide dismutase (SOD), beta-actin (ACTIN), ribosomal protein L10a (RPL10a), L18 (RPL18), L28 (RPL28), S13 (RPS13), and S15 (RPS15), were tested for their suitability as reference genes for developmental stage (3rd, 4th, 5th, 6th, 7th, 8th, 9th, and 10th day after parasitization), tissue (head, thorax, and abdomen of adults), sex of adults (male and female), and temperature (17 °C, 25 °C, and 32 °C). According to the GeNorm analysis, robust analysis should involve using an appropriate combination of reference genes, namely, at least three genes for different development stages, two genes for different tissues, two genes for different sex, and two genes for different temperature, respectively. According to the RelFinder method and by assessing the integrated values from using the ΔCt method, GeNorm, NormFinder, and BestKeeper, we identified the developmental stage-specific reference genes SOD, GAPDH, and ACTIN; tissue-specific reference genes RPL18 and RPS15; sex-specific reference genes SOD and RPL18; and temperature-specific reference genes RPL18 and RPL10. When testing the use of stable vs. unstable reference genes, the substantial differences were observed in the estimation expression of a hypothetical target gene, HSP90, in response to temperature. The present study provides a robust method for the measurement of gene expression in T. dendrolimi and will be helpful for future biological control programs using Trichogramma wasps.
Bridging length-scales from molecules to tissues using mouse genetics, cryoCLEM, and cryoET

Synapses are specialized, submicron-sized cell-cell contacts that wire-up neuronal circuits and mediate the storage of information. Most synaptic communication is via chemical neurotransmitters, of which glutamate is the major excitatory neurotransmitter in the mammalian brain. Glutamate is packaged and released from the presynaptic terminal and detected by glutamate receptors in the postsynaptic membrane. The functional output of synapses is determined directly by the molecular composition and structure of the postsynaptic compartment, which is thought to be responsible for the acquisition of memory. fixed, dehydrated, and heavy metal-stained tissues identification of glutamatergic Glutamatergic synapses in these samples are characterized by an extraordinary of proteins with postsynaptic called the postsynaptic To obtain structural insights into the native 3D molecular architecture of fresh glutamatergic synapses in the adult mouse brain we developed workflows combining mouse genetics, cryogenic correlated light and electron microscopy (cryoCLEM) and cryo-electron tomography. To locate mature glutamatergic synapses within the brain we generated a Psd95 EGFP
The effect of NAA (1-naphthalene acetic acid) and AVG (aminoethoxyvinylglycine) on physical, chemical, colour and mechanical properties of Braeburn apple

Abstract Recently, plant growth regulators have been used for multiple purposes in tree fruits. NAA (1-naphthalene acetic acid) and AVG (aminoethoxyvinylglycine) have been widely used in apple fruit. NAA and AVG have been used to control preharvest fruit drop and improve the quality of fruit. In this study, the effects NAA (20 mgL–1), AVG (500 mgL–1) and control (non treatment) treatments on physical, chemical, colour characteristics and mechanical properties of apple (cv. Braeburn) were investigated. The higher length, width, thickness, geometric mean diameter, fruit mass, surface area, projected area, volume, fruit and bulk densities were obtained in AVG treatment. Total acidity, total soluble solid content and starch starch index were higher in control as compared to NAA and AVG treatments. Total phenolic content of the flesh apple was higher than the other treatments. While total antioxidant activities of skin and flesh fruit were higher in AVG according to FRAP method, total monomeric anthocyanin was lower in AVG as compared to the other treatments. AVG treatment generally had positive impacts on fruit removal force, skin and flesh firmnesses because retarding the fruit ripening.
Bayesian Approaches to Finding the Needles in the Microscopy Haystack

normally distributed. The approach is postulated to be particularly effective when using EDS measurements to determine the number of elementally distinct clusters in manufactured materials, as manufacturing variability and EDS measurement uncertainty can be reasonably modeled as Gaussian distributions and the calculated covariance matrices carry meaningful information on the intra-cluster composition variation. The authors present an application case study herein on a novel Oak Ridge National Laboratory developed FeNiCr alloy. Early results indicate that certain heat treatments may result in up to six elementally unique metallic and precipitate phases in the alloy, resulting in a rich exploratory dataset. A representative Backscatter Electron micrograph of the alloy is provided in Figure 2 for reference. The Bayesian machine learning approach outlined above is compared to both traditional multi-scale characterization and alternative machine learning methods including Principal Components Analysis with respect to determining the number of feature clusters.
How much can inelastically scattered electrons contribute to electron cryotomography of biological specimens?

Electron cryotomography (cryoET) is an application of transmission electron cryomicroscopy (cryoEM) used to determine three-dimensional structures of cells and macromolecules [1]. The samples used for cryoET are often thicker than 1000 Å, meaning many 300 keV electrons suffer at least one inelastic scattering event in transit through the specimen (Figure 1). Electrons that inelastically scatter have, by definition, lost significant energy and are thus incorrectly focused in the image due to the chromatic aberration ( C c ) in the objective lens. As a result, elastically scattered electrons that have also inelastically scattered do not provide high resolution information in phase contrast images and will instead contribute noise. The current practice is to remove these electrons with an electron energy filter to reduce the noise. Given the advent of practical chromatic aberration correction [2], there is a potential improvement in signal by incorporating these inelastically scattered electrons in the image in the context of an achromatic objective lens. Unfortunately, inelastic scattering not only changes the energy but also the direction of electrons, which can be thought of as reducing their spatial coherence. The aim of this study is to evaluate the conditions necessary to best use inelastically scattered electrons for biological imaging and determine the potential improvement in signal afforded by achromatic imaging of the
Investigations of magneto-elastic coupling in a multiferroic ferrite by in-situ precession diffraction

Imitate couplings among charge, lattice, and spin degrees of freedom are widely considered to breed rich emergent physical properties, like multiferroics and colossal magnetoresistance Deciphering the intertwined interplay among these degrees of freedom is one of the major themes at the core of condensed matter physics. Such an interplay is generally complex and can be further complicated especially at phase transitions, where delicate changes in different kinds of energy can induce prominent changes in different degrees of freedom and introduce emergent physical properties. A typical example is multiferroics, where atomic displacements
In-situ NiO nanostructure growth during heating in water vapor atmosphere

Oxidation behavior of bulk nickel in water vapor atmosphere was previously documented with the formation of different surface features including whiskers and pits [1]. However, transition metal nanoparticles possess unique physical and chemical properties compared to bulk due to their high surface-to-volume ratio. Anisotropic growth of NiO from nickel nanoparticles due to rapid thermal annealing in oxygen was reported [2]. The growth of NiO exhibits either nanocube or nanorod morphologies depending on the oxidation condition and particle size [2]. In this study, in-situ heating experiments were carried out for nickel nanoparticles with a nominal diameter of 300 nm using a Thermofisher Quattro Environmental Scanning Electron Microscope (ESEM). Isothermal heating experiments were performed at 800 °C in atmospheres of dry nitrogen or water vapor pressures ranging between 250 and 400 Pa. A Bruker Quantax 400 XFlash 6 solid-state detector was used to acquire Energy dispersive x-ray spectroscopy (EDXS) data before and after in-situ heating. Figure 1(a) and (c) show the as-received nickel particles acquired at room temperature before ESEM heating. The particles show round geometry and smooth surfaces. EDXS data demonstrates a nickel to oxygen atomic concentration ratio of around 95:5, which indicates a native nickel oxide layer present on the nickel particle surface [3,4].
Photocathode Investigation for Ultrafast Electron Microscopy

Ultrafast transmission electron microscopes (UEM) have provided scientists the ability to investigate materials dynamics on the nanometer femtosecond spatiotemporal scale, leading to many new scientific discoveries. After starting as highly specialized tools, these instruments are becoming more and more common throughout the world as companies work to make them commercially available and institutions recognize their value. While new operating concepts are being developed [1], typical UEMs in operation utilize a photocathode to produce short bursts of electrons. The community has not coalesced around a single photocathode design, with a variety of geometries and materials being employed [2-4]. While this is partly due to differing needs in terms of coherence, number of electrons per pulse, etc., there is an active field of research trying to determine the best design for photocathodes in UEM, the performance of which is generally the limiting factor in the instruments’ resolutions. Here we investigate one such photocathode design, the “guard ring” cathode. The UEM at the Center for Nanoscale Materials at Argonne is a modified JEOL 2100 plus with a Gatan continuum GIF and a K2 IS detector installed at the end of the spectrometer. The guard ring cathode demonstrated here has a 10μm diameter LaB6 crystal embedded in a 500μm graphite cylinder. This geometry helps to suppress side emission from the LaB6 and create a more uniform electric field caused by the wehnelt bias [5]. While the cathode behaved as expected upon installation, after a few months of normal operation, emission was also observed from the graphite region, as shown in Figure 1a. After optimization of temporal resolution, it was observed that two separate electron pulses were being emitted from the photocathode, separated by ~2.5ps as shown in Figure 1b. We hypothesize
In Situ Thermomechanical Loading for TEM Studies of Nanocrystalline Alloys

In situ microscopy methods enable the qualitative and quantitative assessment of a material’s nano/microstructure evolution under different stimuli. These stimuli include annealing, mechanical loading, electrical bias, gas reactions and even electro-chemical reactions in a liquid environment. To achieve these conditions, many of these in situ devices leverage microelectromechanical systems (MEMS) to provide the stimuli [1]. In this work, the development and assessment of an in situ thermomechanical loading chip for use in transmission electron microscopy (TEM) is presented. In this work, we replicated a MEMS chip design based on the comb-drive based system devised by Zhu [2] to address nanocrystalline stability. This chip, like the one similarly reported by Pierron [3], uses an electro-static drive system and is shown in Fig. 1(a). Here, an electrical voltage is applied across the combs which provides an electrostatic force between each comb-line, Fig. 1(b). As the voltage is increased, the combs close together resulting in further separation at the specimen mount position, or shuttle, shown in Fig. 1(c). The extent of the force applied is given by:
Multi-Energy X-Ray Computed Tomography for Source Rock Characterization

Source rocks are composed of inorganic minerals and organic matter that were compacted during burial and exposed to heat in the subsurface where the organic matter was cracked to light hydrocarbons [1-2]. The inorganic phase of carbonate source rocks is predominantly composed of calcite (CaCO 3 ) but may also contain dolomite (CaMg(CO 3 ) 2 ), clays (aluminum phyllosilicates), and others such as quartz (SiO 2 ). The organic matter type also varies and may be kerogen, bitumen, and/or pyrobitumen where the molecular composition diverges with thermal maturity during hydrocarbon generation [2-4]. The texture of these rocks is a result of burial conditions and varies at the submillimeter scale where, in addition to the organic and inorganic components, void space can also exist in the form of pores and fractures. Core analysis techniques are used characterize hydrocarbon reservoirs during exploration prior to field development by measuring rock properties such as porosity, permeability, density, and mineralogy. The measured properties are used to calibrate well logs and to develop empirical equations for log interpretation. Single Energy X-Ray Computed Tomography (CT) is commonly used to determine porosity and image fluid displacements in conventional sandstones and carbonates where the rocks are composed mainly of a single inorganic phase and relatively large pores. Other CT applications include identifying fractures and determining lithology and mineralogy transitions from whole core as well as local heterogeneity in core plugs.
Structural and chemical analysis of mixed cation antiferromagnetic layered metal chalcophosphate FeCoP2S6

chalcophosphate FeCoP2S6 Matthew Cheng, Yea-Shine Lee, Roberto dos Reis, Abishek Iyer, Daniel Chica, Mercouri Kanatzidis and Vinayak Dravid Department of Materials Science and Engineering, Northwestern University, EVANSTON, Illinois, United States, Department of Materials Science and Engineering, Northwestern University, United States, Department of Chemistry, Northwestern University, United States