Miracle-dz/UniFAR-FTUs huggingface dataset:
Morphological trait evolution in Solanum (Solanaceae): evolutionary lability of key taxonomic characters

Solanum L. is one of the world’s largest and economically most important plant genera, including 1,245 currently accepted species and several major and minor crops (e.g., tomato, potato, brinjal eggplant, scarlet eggplant, Gboma eggplant, lulo, and pepino). Here we provide an overview of the evolution of 25 key morphological traits for the major and minor clades of this giant genus based on stochastic mapping using a well-sampled recently published phylogeny of Solanum. The most evolutionarily labile traits (showing >150 transitions across the genus) relate to plant structure (growth form and sympodial unit structure), herbivore defence (glandular trichomes), pollination (corolla shape and colour), and dispersal (fruit colour). Ten further traits show evolutionary lability with 50-100 transitions across the genus (e.g., specialised underground organs, trichome structure, leaf type, inflorescence position and branching, stamen heteromorphism). Our results reveal a number of highly convergent traits in Solanum, including tubers, rhizomes, simple leaves, yellow corollas, heteromorphic anthers, dioecy, and dry fruits, and some unexpected pathways of trait evolution that could be explored in future studies. We show that informally named clades of Solanum can be morphologically defined by trait combinations providing a tool for identification and enabling predictive phylogenetic placement of unsampled species.
Retro-miRs: Novel and functional miRNAs originated from mRNA retrotransposition

Background Reverse transcribed gene copies, or retrocopies, have emerged as a major source of evolutionary novelties. MicroRNAs (miRNAs) are small, highly conserved RNAs molecules among species that serve as key post-transcriptional regulators of gene expression. The birth and subsequent evolution of miRNAs have been addressed, but not fully. Results In this study, we carried out a comprehensive investigation of miRNAs origination through retroduplicated mRNA sequences (retrocopies). We identified 17 retroduplicated miRNAs (retro-miRs) that emerged from mRNAs retrocopies. Four of these retro-miRs had de novo origination within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and were duplicated along with their host mRNAs. We found that retro-miRs are primates specific, including 5 retro-miRs conserved among all primates and two human-specific retro-miRs. All of the retro-miRs were expressed and had predicted and experimentally validated target genes, with the exception of miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes, such as metabolic processes, cell signaling and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs have a potential oncogenic role in cancer, targeting key cancer genes and being overexpressed in several cancer types, including Liver Hepatocellular Carcinoma and Stomach Adenocarcinoma. Conclusion Our findings demonstrate that mRNAs retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play roles in cancer.
Antibody landscape of C57BL/6 mice cured of B78 melanoma via immunotherapy

Antibodies can play an important role in innate and adaptive immune responses against cancer, and in preventing infectious disease. Flow cytometry analysis of sera of immune mice that were previously cured of their melanoma through a combined immunotherapy regimen with long-term memory showed strong antibody-binding against melanoma tumor cell lines. Using a high-density whole-proteome peptide array, we assessed potential protein-targets for antibodies found in immune sera. Sera from 6 of these cured mice were analyzed with this high-density, whole-proteome peptide array to determine specific antibody-binding sites and their linear peptide sequence. We identified thousands of peptides that were targeted by 2 or more of these 6 mice and exhibited strong antibody binding only by immune, not naive sera. Confirmatory studies were done to validate these results using 2 separate ELISA-based systems. To the best of our knowledge, this is the first study of the “immunome” of protein-based epitopes that are recognized by immune sera from mice cured of cancer via immunotherapy. summary Hoefges et al. utilized a whole-proteome peptide array approach to show that C57BL/6 mice develop a large repertoire of antibodies against linear peptide sequences of their melanoma after receiving a curative immunotherapy regimen consisting of radiation and an immunocytokine.
Laminin-defined Mechanical Status Modulates Retinal Pigment Epithelium Functionality

Epithelial cells are highly interconnected, whereby they acquire mesoscale mechanical properties to accomplish specific tissue functions. In homeostasis, this mechanical status can be summarised as mechanical homeostasis, regulated by the balance of intercellular tension and extracellular matrix adhesion forces. In the outer retina, the significance of this force balance and its consequences for vision remains poorly understood. The retinal pigmented epithelium (RPE) is located at the base of the retina and supports vision by ensuring the light sensitivity and lifespan of photoreceptor cells. Given the varying photoreceptor densities along the visual angle, the functional demand on the RPE varies from the most illuminated macula to the retinal periphery and corresponds to a significant difference in RPE homeostatic state. In this work, we hypothesised that extracellular matrix (ECM) cues define the relation between RPE mechanical status and functional capacity. We found that the density of basement membrane laminins modulates the level of RPE contractility, which directly controls the efficiency of the epithelium in phagocytosing photoreceptor outer segments. In vivo, the density gradient of laminin α5 and 332 follows retinal functional demand, supporting the physiological role of laminins in controlling RPE mechanical homeostasis. Our data suggest that laminin density and isoforms can differentially engage integrins β1 and β4, the ratio of which determines the contribution of actin vs keratin cytoskeleton in balancing tissue mechanics. With this work, we suggest that the ECM-defined mechanical status of RPE is a novel parameter for visual function, opening new paths of investigation and treatment for sight-threatening diseases such as high myopia and age-related macular degeneration.
Insights into a viral motor: the structure of the HK97 packaging termination assembly

Double-stranded DNA viruses utilise machinery, made of terminase proteins, to package viral DNA into the capsid. For cos bacteriophage, a defined signal, recognised by small terminase, flanks each genome unit. Here we present the first structural data for a cos virus DNA packaging motor, assembled from the bacteriophage HK97 terminase proteins, procapsids encompassing the portal protein, and DNA containing a cos site. The cryo-EM structure is consistent with the packaging termination state adopted after DNA cleavage, with DNA density within the large terminase assembly ending abruptly at the portal protein entrance. Retention of the large terminase complex after cleavage of the short DNA substrate suggests that motor dissociation from the capsid requires headful pressure, in common with pac viruses. Interestingly, the clip domain of the 12-subunit portal protein does not adhere to C12 symmetry, indicating asymmetry induced by binding of the large terminase/DNA. The motor assembly is also highly asymmetric, showing a ring of 5 large terminase monomers, tilted against the portal. Variable degrees of extension between N- and C-terminal domains of individual subunits suggest a mechanism of DNA translocation driven by inter-domain contraction and relaxation.
Cross-species proteomic and microRNA comparison of extracellular vesicles in human milk, cow’s milk, and infant formula products: moving towards next generation infant formula products

Milk and milk products such as infant formula (IF) play a fundamental role in serving the nutritional needs of the developing infant. Extracellular vesicles (EVs) in human (HM) and cow’s milk (CM) contain molecular cargo such as proteins and micro(mi)RNA that serve as functional messengers between cells and may be of importance to infant health. Here, we have developed a pipeline using advanced proteomics and transcriptomics to enable cross-species comparison of milk and IF EVs. EVs from HM, CM and IF were subjected to data-independent acquisition mass spectrometry and RNA-seq. Differentially abundant proteins (143) and miRNAs (514) were identified in HM and CM EVs, and CM EV proteins and miRNAs were preserved in IF EVs (∼20% protein; ∼90% miRNA). We foresee this work to be used in large scale studies to determine biologically relevant species-specific differences in milk EVs that could be leveraged to improve IF products.
Community diversity affects functionality and species sorting during propagation of a natural microbial community

The influence of community diversity on community function has long been a central question in ecology. Particularly, the dynamics over time of this relationship as a function of levels of diversity remains unclear. Natural populations may vary in levels of species diversity, for instance after they experience disturbances that remove significant amounts of their genetic and species variation, including rare but functionally unique guilds. We investigated the influence of diversity on associated community function by propagating natural microbial communities from a traditionally fermented milk beverage diluted to various levels. Specifically, we assessed the influence of less abundant microbial types such as yeast and rarer bacterial types on community functionality and species sorting trajectories over approximately 100 generations. We observed repeatable changes in bacterial community compositions, metabolic profiles, and acidity related to starting diversity levels. The influence of a single ecological guild, yeast in our study, played a dramatic role on function, but interestingly not on long-term species sorting trajectories of the remaining bacterial community. Our results together evidence ecological selection on the microbial communities in our system and suggest an unexpected niche division between yeast and bacterial communities.
Repeated footshock stress induces an escalation of cocaine self-administration in male and female rats: Role of the cannabinoid receptor 1

Stress is a significant contributor to the development and progression of substance use disorders (SUDs) and is problematic as it is unavoidable in daily life. Therefore, it is important to understand the neurobiological mechanisms that underlie the influence of stress on drug use. We have previously developed a model to examine the contribution of stress to drug-related behavior by administering a stressor, electric footshock stress, daily at the time of cocaine self-administration in rats resulting in an escalation of cocaine intake. This stress-induced escalation of cocaine intake involves neurobiological mediators of stress and reward such as cannabinoid signaling. However, all of this work has been conducted in male rats. Here we test the hypothesis that repeated daily stress can produce an escalation of cocaine in both male and female rats. We further hypothesize that cannabinoid receptor 1 (CB1R) signaling is recruited by repeated stress to influence cocaine intake in both male and female rats. Male and female Sprague-Dawley rats self-administered cocaine (0.5 mg/kg/inf, i.v.) during a modified short-access paradigm wherein the 2-hr access was separated into 4-30 min self-administration blocks separated by 4-5 min drug free period. Footshock stress produced a significant escalation of cocaine intake similarly in both male and female rats. Female stress-escalated rats did display greater time-out non-reinforced responding and greater “front-loading” behavior. In males, systemic administration of a CB1R inverse agonist/antagonist Rimonabant only attenuated cocaine intake in rats with a history of combined repeated stress and cocaine self-administration. However, in females, Rimonabant attenuated cocaine intake in the no stress control group but only at the highest dose of Rimonabant (3 mg/kg, i.p.) suggesting that females show a greater sensitivity to CB1R antagonism. However, female rats with a history of stress showed even greater sensitivity to CB1R antagonism as both doses of Rimonabant (1, 3 mg/kg) attenuated cocaine intake in stress-escalated rats similar to males. Altogether these data demonstrate that stress can produce significant changes in cocaine self-administration and suggests that repeated stress at the time of cocaine self-administration recruits CB1Rs to regulate cocaine-taking behavior across sexes.
Dynamical modeling reveals RNA decay mediates the effect of matrix stiffness on aged muscle stem cell fate

Loss of muscle stem cell (MuSC) self-renewal with aging reflects a combination of influences from the intracellular (e.g., post-transcriptional modifications) and extracellular (e.g., matrix stiffness) environment. Whereas conventional single cell analyses have revealed valuable insights into factors contributing to impaired self-renewal with age, most are limited by static measurements that fail to capture nonlinear dynamics. Using bioengineered matrices mimicking the stiffness of young and old muscle, we showed that while young MuSCs were unaffected by aged matrices, old MuSCs were phenotypically rejuvenated by young matrices. Dynamical modeling of RNA velocity vector fields in silico revealed that soft matrices promoted a self-renewing state in old MuSCs by attenuating RNA decay. Vector field perturbations demonstrated that the effects of matrix stiffness on MuSC self-renewal could be circumvented by fine-tuning the expression of the RNA decay machinery. These results demonstrate that post-transcriptional dynamics dictate the negative effect of aged matrices on MuSC self-renewal. Graphical Abstract Graphical abstract description: The balance of self-renewal and differentiation in young muscle stem cells (MuSCs) is robust to perturbations of the biophysical microenvironment. In contrast, aged MuSCs are highly sensitive to extrinsic perturbations, and exposure to a youthful microenvironment rejuvenates the self-renewing potential of aged MuSCs by modulating post-transcriptional RNA dynamics.
Predicting S. aureus antimicrobial resistance with interpretable genomic space maps

Increasing antimicrobial resistance (AMR) represents a global healthcare threat. Methods for rapid selection of optimal antibiotic treatment are urgently needed to decrease the spread of AMR and associated mortality. The use of machine learning (ML) techniques based on genomic data to predict resistance phenotypes serves as a solution for the acceleration of the clinical response prior to phenotypic testing. Nonetheless, many existing ML methods lack interpretability and do not implicitly incorporate visualization of the sequence space that can be useful for extracting insightful patterns from genomic data. Herein, we present a methodology for AMR prediction and visualization of sequence space based on the non-linear dimensionality reduction method □ generative topographic mapping (GTM). This approach applied to data on AMR of >5000 S. aureus isolates retrieved from the PATRIC database yielded GTM models with reasonable accuracy for all drugs (balanced accuracy values ≥0.75). The GTMs represent data in the form of illustrative 2D maps of the genomic space and allow for antibiotic-wise comparison of resistance phenotypes. In addition to that, the maps were found to be useful for the analysis of genetic determinants responsible for drug resistance based on the data from the PATRIC database. Overall, the GTM-based methodology is a useful tool for the illustrative exploration of the genomic sequence space and modelling AMR and can be used as a tool complementary to the existing ML methods for AMR prediction. Availability https://doi.org/10.5281/zenodo.7101559
Comprehensive interrogation of human skeletal muscle reveals a dissociation between insulin resistance and mitochondrial capacity

Aims/Hypothesis Insulin resistance and blunted mitochondrial capacity in skeletal muscle are often synonymous; however, this association remains controversial. The aim of this study was to perform an in-depth multi-factorial comparison of skeletal muscle mitochondrial capacity between individuals who were lean and active (Active), individuals with obesity (Obese) and individuals with Obesity, insulin resistance and type 2 diabetes (T2D). Methods Skeletal muscle biopsies were obtained from the Vastus Lateralis of individuals who were lean and active (Active- n = 9), individuals with obesity (Obese- n = 9) and individuals with obesity insulin resistance and T2D (T2D- n =22) in this cross-sectional design. Mitochondrial capacity was assessed by ex vivo mitochondrial respiration with fatty-acid and glycolytic supported protocols adjusted for mitochondrial content (mtDNA and citrate synthase activity). Supercomplex assembly was measured by BN-PAGE and immunoblot. TCA cycle intermediates were assessed with targeted metabolomics. Exploratory transcriptomics and DNA methylation analyses were performed to uncover molecular differences affecting mitochondrial function among the three groups. Results Active had greater mitochondrial capacity compared to both Obese and T2D for ex vivo mitochondrial respiration with fatty-acid and glycolytic supported protocols adjusted for mitochondrial content (P < 0.05). Complex IV supercomplex assembley was greater in Active compared to Obese and T2D (P < 0.05) whereas Complex I and III supercomplex assembly was greater in Active compared to T2D only (P < 0.05). TCA cycle intermediates; citrate, succinate, fumarate and malate were all significantly greater in Active compared to Obese and T2D (P < 0.05). Strikingly, Obese and T2D do not differ in any of the skeletal muscle mitochondrial measurements. Active had an upregulation of genes related to respiration/mitochondrial capacity compared to both Obese and T2D. Transcriptional differences between Obese and T2D were not driven by mitochondrial related process. Active had reduced methylation correlated with increased gene expression for important mitochondrial-related genes, including ATP5PD and MFN2. Conclusions/Interpretations We reveal no discernable differences in skeletal muscle mitochondrial content, mitochondrial capacity and mitochondrial molecular profiles between obese individuals with and without T2D that had comparable levels of confounding factors (BMI, age, aerobic capacity) that affect mitochondrial capacity. We highlight that lean, active individuals have enhanced skeletal muscle mitochondrial capacity that is also reflected at the level of DNA methylation and gene transcription. The collective observation of comparable muscle mitochondrial capacity in individuals with obesity and T2D (vs. individuals without T2D) underscores a dissociation from skeletal muscle insulin resistance. Clinical trial number NCT0191110
Observations of Multiple X Lines Collisionless Reconnection in the Near Earth‐Tail

Observations of the Earth's magnetotail made by the Cluster II during 09:42~09:50 UT on October 1 2001 are presented. Two tailward magnetic flux ropes bounded by earthward and tailward convective high speed flows were observed. We directly detected the source of tailward high flow and the outflow region of earthward flow. Combining the observations, we provided important experimental evidence of multiple X lines reconnection. The time interval between two magnetic flux ropes was about 26 s.
Escherichia coli B-Strains Are Intrinsically Resistant to Colistin and Not Suitable for Characterization and Identification of mcr Genes

Given the rise in multidrug, extensive drug, and pandrug resistance in bacteria and the increasing use of colistin to treat human infections, occurrence of mcr genes threatens human health, and characterization of these resistance genes becomes more important. We show that three commonly used heterologous expression strains are intrinsically resistant to colistin. ABSTRACT Antimicrobial resistance is an increasing threat to human and animal health. Due to the rise of multi-, extensive, and pandrug resistance, last resort antibiotics, such as colistin, are extremely important in human medicine. While the distribution of colistin resistance genes can be tracked through sequencing methods, phenotypic characterization of putative antimicrobial resistance (AMR) genes is still important to confirm the phenotype conferred by different genes. While heterologous expression of AMR genes (e.g., in Escherichia coli) is a common approach, so far, no standard methods for heterologous expression and characterization of mcr genes exist. E. coli B-strains, designed for optimum protein expression, are frequently utilized. Here, we report that four E. coli B-strains are intrinsically resistant to colistin (MIC 8–16 μg/mL). The three tested B-strains that encode T7 RNA polymerase show growth defects when transformed with empty or mcr-expressing pET17b plasmids and grown in the presence of IPTG; K-12 or B-strains without T7 RNA polymerase do not show these growth defects. E. coli SHuffle T7 express carrying empty pET17b also skips wells in colistin MIC assays in the presence of IPTG. These phenotypes could explain why B-strains were erroneously reported as colistin susceptible. Analysis of existing genome data identified one nonsynonymous change in each pmrA and pmrB in all four E. coli B-strains; the E121K change in PmrB has previously been linked to intrinsic colistin resistance. We conclude that E. coli B-strains are not appropriate heterologous expression hosts for identification and characterization of mcr genes. IMPORTANCE Given the rise in multidrug, extensive drug, and pandrug resistance in bacteria and the increasing use of colistin to treat human infections, occurrence of mcr genes threatens human health, and characterization of these resistance genes becomes more important. We show that three commonly used heterologous expression strains are intrinsically resistant to colistin. This is important because these strains have previously been used to characterize and identify new mobile colistin resistance (mcr) genes. We also show that expression plasmids (i.e., pET17b) without inserts cause cell viability defects when carried by B-strains with T7 RNA polymerase and grown in the presence of IPTG. Our findings are important as they will facilitate improved selection of heterologous strains and plasmid combinations for characterizing AMR genes, which will be particularly important with a shift to Culture-independent diagnostic tests where bacterial isolates become increasingly less available for characterization.
On the Complete Eigenvalue Solution of Ridged Waveguide

The complete solution of the ridged waveguide eigen-value problem is presented. The solution is obtained by the formulation of an integral eigenvalue equation which is subsequently solved numerically by application of the Ritz-Galerkin method. The significance of the eigenvalue spectrum is discussed and the modes are classified as either hybrid or trough modes. Equations are given for the electric and magnetic fields and a brief discussion of the edge singularity is presented. The theory is illustrated by computing the dominant eigenvalues and characteristic impedances of various unsymmetrical ridged waveguides.