Domain loss enabled evolution of novel functions in the snake three-finger toxin gene superfamily.

Three-finger toxins (3FTXs) are a functionally diverse family of toxins, apparently unique to venoms of caenophidian snakes. Although the ancestral function of 3FTXs is antagonism of nicotinic acetylcholine receptors, redundancy conferred by the accumulation of duplicate genes has facilitated extensive neofunctionalization, such that derived members of the family interact with a range of targets. 3FTXs are members of the LY6/UPAR family, but their non-toxin ancestor remains unknown.

Single-cell reference mapping to construct and extend cell-type hierarchies.

Single-cell genomics is now producing an ever-increasing amount of datasets that, when integrated, could provide large-scale reference atlases of tissue in health and disease. Such large-scale atlases increase the scale and generalizability of analyses and enable combining knowledge generated by individual studies. Specifically, individual studies often differ regarding cell annotation terminology and depth, with different groups specializing in different cell type compartments, often using distinct terminology.

Abrupt height growth setbacks show overbrowsing of tree saplings, which can be reduced by raising deer harvest.

Intensive ungulate browsing significantly impacts forests worldwide. However, it is usually not single browsing events that lead to sapling mortality, but the little-researched interactions of browsed saplings with their biotic and abiotic environment. (I) Our objective was to assess the impact of ungulate browsing on the growth of young saplings relative to other environmental factors by utilizing their height increment as a sensitive measure of vitality to indicate their status.

Synchrotron radiation-based microcomputed tomography for three-dimensional growth analysis of Aspergillus niger pellets.

Filamentous fungi produce a wide range of relevant biotechnological compounds. The close relationship between fungal morphology and productivity has led to a variety of analytical methods to quantify their macromorphology. Nevertheless, only a µ-computed tomography (µ-CT) based method allows a detailed analysis of the 3D micromorphology of fungal pellets.

DeepdlncUD: Predicting regulation types of small molecule inhibitors on modulating lncRNA expression by deep learning.

Targeting lncRNAs by small molecules (SM-lncR) to alter their expression levels has emerged as an important therapeutic modality for disease treatment. To date, no computational tools have been dedicated to predicting small molecule-mediated upregulation or downregulation of lncRNA expression. Here, we introduce DeepdlncUD, which integrates predictions of nine deep learning algorithms together, to infer the regulation types of small molecules on modulating lncRNA expression.

A Comparative Study on the Roll-to-Roll Processing of a Silicate-Polyvinyl Alcohol Composite Barrier Lacquer Using Slot-Die and Reverse Gravure Coating Techniques.

The integration of platelet-shaped montmorillonite particles to improve the oxygen barrier of polyvinyl-alcohol-based barrier layers is state-of-the-art, but research on roll-to-roll coatings of such composite barrier lacquers has not been widely published. In this study, two different coating techniques, slot-die and reverse gravure, were used on a roll-to-roll scale to apply barrier lacquers comprising polyvinyl alcohol and montmorillonite. The lacquers were analyzed regarding viscosity at certain shear rates and surface energy and the dried coating layers regarding oxygen barrier, surface morphology, and particle orientation.

Plant traits poorly predict winner and loser shrub species in a warming tundra biome.

Climate change is leading to species redistributions. In the tundra biome, shrubs are generally expanding, but not all tundra shrub species will benefit from warming. Winner and loser species, and the characteristics that may determine success or failure, have not yet been fully identified.

Climatic water availability modifies tree functional diversity effects on soil organic carbon storage in European forests.

Forest stand and environmental factors influence soil organic carbon (SOC) storage, but little is known about their relative impacts in different soil layers. Moreover, how environmental factors modulate the impact of stand factors, particularly species mixing, on SOC storage, is largely unexplored. In this study, conducted in 21 forest triplets (two monocultures of different species and their mixture on the same site) distributed in Europe, we tested the hypothesis that stand factors (functional identity and diversity) have stronger effects on topsoil (FF + 0-10 cm) C storage than environmental factors (climatic water availability, clay + silt content, oxalate-extractable Al-Al) but that the opposite occurs in the subsoil (10-40 cm).

Genome analyses reveal population structure and a purple stigma color gene candidate in finger millet.

Finger millet is a key food security crop widely grown in eastern Africa, India and Nepal. Long considered a 'poor man's crop', finger millet has regained attention over the past decade for its climate resilience and the nutritional qualities of its grain. To bring finger millet breeding into the 21 century, here we present the assembly and annotation of a chromosome-scale reference genome.

Unlocking complex soil systems as carbon sinks: multi-pool management as the key.

Much research focuses on increasing carbon storage in mineral-associated organic matter (MAOM), in which carbon may persist for centuries to millennia. However, MAOM-targeted management is insufficient because the formation pathways of persistent soil organic matter are diverse and vary with environmental conditions. Effective management must also consider particulate organic matter (POM).

Auxin transport at the endoplasmic reticulum: roles and structural similarity of PIN-FORMED and PIN-LIKES.

Auxin is a crucial plant hormone that controls a multitude of developmental processes. The directional movement of auxin between cells is largely facilitated by canonical PIN-FORMED proteins in the plasma membrane. In contrast, non-canonical PIN-FORMED proteins and PIN-LIKES proteins appear to reside mainly in the endoplasmic reticulum.

Small molecule-mediated targeting of microRNAs for drug discovery: Experiments, computational techniques, and disease implications.

Small molecules have been providing medical breakthroughs for human diseases for more than a century. Recently, identifying small molecule inhibitors that target microRNAs (miRNAs) has gained importance, despite the challenges posed by labour-intensive screening experiments and the significant efforts required for medicinal chemistry optimization. Numerous experimentally-verified cases have demonstrated the potential of miRNA-targeted small molecule inhibitors for disease treatment.

Learning consistent subcellular landmarks to quantify changes in multiplexed protein maps.

Highly multiplexed imaging holds enormous promise for understanding how spatial context shapes the activity of the genome and its products at multiple length scales. Here, we introduce a deep learning framework called CAMPA (Conditional Autoencoder for Multiplexed Pixel Analysis), which uses a conditional variational autoencoder to learn representations of molecular pixel profiles that are consistent across heterogeneous cell populations and experimental perturbations. Clustering these pixel-level representations identifies consistent subcellular landmarks, which can be quantitatively compared in terms of their size, shape, molecular composition and relative spatial organization.

Multimodal characterization of murine gastruloid development.

Gastruloids are 3D structures generated from pluripotent stem cells recapitulating fundamental principles of embryonic pattern formation. Using single-cell genomic analysis, we provide a resource mapping cell states and types during gastruloid development and compare them with the in vivo embryo. We developed a high-throughput handling and imaging pipeline to spatially monitor symmetry breaking during gastruloid development and report an early spatial variability in pluripotency determining a binary response to Wnt activation.

Bispecific antibodies redirect synthetic agonistic receptor modified T cells against melanoma.

Background: Melanoma is an immune sensitive disease, as demonstrated by the activity of immune check point blockade (ICB), but many patients will either not respond or relapse. More recently, tumor infiltrating lymphocyte (TIL) therapy has shown promising efficacy in melanoma treatment after ICB failure, indicating the potential of cellular therapies. However, TIL treatment comes with manufacturing limitations, product heterogeneity, as well as toxicity problems, due to the transfer of a large number of phenotypically diverse T cells.

Skin substitutes based on gellan gum with mechanical and penetration compatibility to native human skin.

The study reports on a simple system to fabricate skin substitutes consisting of a naturally occurring bacterial polysaccharide gellan gum. Gelation was driven by the addition of a culture medium whose cations induced gellan gum crosslinking at physiological temperature, resulting in hydrogels. Human dermal fibroblasts were incorporated in these hydrogels and their mechanical, morphological, and penetration characteristics were studied.

Predicting cellular responses to complex perturbations in high-throughput screens.

Recent advances in multiplexed single-cell transcriptomics experiments facilitate the high-throughput study of drug and genetic perturbations. However, an exhaustive exploration of the combinatorial perturbation space is experimentally unfeasible. Therefore, computational methods are needed to predict, interpret, and prioritize perturbations.

Genetic knockout of porcine GGTA1 or CMAH/GGTA1 is associated with the emergence of neo-glycans.

Background: Pig-derived tissues could overcome the shortage of human donor organs in transplantation. However, the glycans with terminal α-Gal and Neu5Gc, which are synthesized by enzymes, encoded by the genes GGTA1 and CMAH, are known to play a major role in immunogenicity of porcine tissue, ultimately leading to xenograft rejection.

Methods: The N-glycome and glycosphingolipidome of native and decellularized porcine pericardia from wildtype (WT), GGTA1-KO and GGTA1/CMAH-KO pigs were analyzed by multiplexed capillary gel electrophoresis coupled to laser-induced fluorescence detection.

In Vitro Investigation of the Interaction of Avian Metapneumovirus and Newcastle Disease Virus with Turkey Respiratory and Reproductive Tissue.

In poultry, several respiratory viral infections lead to a drop in egg production associated with high economic losses. While the virus-host interactions at the respiratory epithelium are well studied, less is known about these interactions in the oviduct. To investigate possible differences between virus infections at these epithelial structures, we compared the interactions of two important poultry viruses on turkey organ cultures.

The Mechanism of Resistance of EUROPEAN Plum to Mediated by Hypersensitive Response Is Linked to VIRAL NIa and Its Protease Activity.

(PPV) infects trees across the globe, causing the serious Sharka disease. Breeding programs in the past 20 years have been successful, generating plum varieties hypersensitive to PPV that show resistance in the field. Recently, a single tree displaying typical PPV symptoms was detected in an orchard of resistant plums.

Multi-scale systems genomics analysis predicts pathways, cell types, and drug targets involved in normative variation in peri-adolescent human cognition.

An open challenge in human genetics is to better understand the systems-level impact of genotype variation on developmental cognition. To characterize the genetic underpinnings of peri-adolescent cognition, we performed genotype-phenotype and systems analysis for binarized accuracy in nine cognitive tasks from the Philadelphia Neurodevelopmental Cohort (~2,200 individuals of European continental ancestry aged 8-21 years). We report a region of genome-wide significance within the 3' end of the Fibulin-1 gene (P = 4.