Miracle-dz/UniFAR-FTUs huggingface dataset:
Body size is a better predictor of intra- than interspecific variation of animal stoichiometry across realms

Animal stoichiometry affects fundamental processes ranging from organismal physiology to global element cycles. However, it is unknown whether animal stoichiometry follows predictable scaling relationships with body mass and whether adaptation to life on land or water constrains patterns of elemental allocation. To test both interspecific and intraspecific body-size scaling relationships of the nitrogen (N), phosphorus (P), and N:P content of animals, we used a subset of the StoichLife database encompassing 9,933 individual animals (vertebrates and invertebrates) belonging to 1,543 species spanning 10 orders of magnitude of body size from terrestrial, freshwater, and marine realms. Across species, body mass did not explain much variation in %N and %P composition, although the %P of invertebrates decreased with size. The effects of body size on species elemental content were small in comparison to the effects of taxonomy. Body size was a better predictor of intraspecific than interspecific elemental patterns. Between 42 to 45% in intraspecific stoichiometric variation was explained by body size for 27% of vertebrate species and 35% of invertebrate species. Further, differences between organisms inhabiting aquatic and terrestrial realms were observed only in invertebrate interspecific %N, suggesting that the realm does not play an important role in determining elemental allocation of animals. Based on our analysis of the most comprehensive animal stoichiometry database, we conclude that (i) both body size and realm are relatively weak predictors of animal stoichiometry across taxa, and (ii) body size is a good predictor of intraspecific variation in animal elemental content, which is consistent with tissue-scaling relationships that hold broadly across large groups of animals. This research reveals a lack of general scaling patterns in the elemental content across animals and instead points to a large variation in scaling relationships within and among lineages.
Quantification of Energy Saving Potential for A Passenger Train Based on Inter-Run Variability in Speed Trajectories

Passenger train energy consumption is dependent on speed trajectories. The variability of passenger train energy consumption owing to the variability in speed trajectories can help identify ways to reduce train energy use via improved operations. Empirical fuel use data from a portable measurement emission measurement system (PEMS) and empirical speed trajectories measured using a global positioning system (GPS) receiver were used to verify and quantify real-world energy consumption variability and the variability in empirical speed trajectories, respectively. To identify potential realistic speed trajectories that can lead to energy saving (i.e., eco-driving), a Markov chain based speed trajectory simulator was used to simulate inter-run variability in speed trajectories. An energy index model (EIM) was used to compare energy consumption among different speed trajectories. The results show inter-run variability in fuel use associated with inter-run variability in the empirical speed trajectories. There is also inter-segment variability in fuel use related to the segment length and grade. The Markov chain based speed trajectory simulator can simulate realistic inter-run variability in speed trajectories based on calibration using empirical speed trajectories. The number of empirical speed trajectories used for simulator calibration affects the range of simulated inter-run variability. The EIM provides an accurate estimation of the empirical fuel use. Eco-driving, such as reducing the peak speed, can reduce energy consumption without compromising travel time. The methodology shown in this study is not system-specific and can be applied to other passenger train systems.
Extracellular ATP is a signalling molecule in bacteria

In animals and plants extracellular ATP (eATP) functions as signalling molecule and regulates the immune response. During inflammation intestinal bacteria are exposed to elevated eATP originating from the mucosa. Whether bacteria respond to eATP is unclear. Here we show that non-pathogenic Escherichia coli responds to eATP at physiologically relevant concentrations by modifying its transcriptional and metabolic landscape. The use of a promoter library showed that the response to eATP is time-, dose- and medium-dependent. Genes related to lipid, amino acid, or vitamin metabolism were regulated. Metabolomics showed that eATP triggers enrichment of molecules with bioactive properties on the host or bacteria. Combined genome-scale modelling highlighted the global metabolic modifications. Moreover, eATP altered the sensitivity to antibiotics and antimicrobial peptides. Finally, in pathogens eATP controls the expression of virulence and fitness factors. Our results indicate that eATP is a signalling molecule in prokaryotes which globally regulates physiology, antimicrobial resistance, and virulence.
Forecasting Lightning Using a Perfect Prog Technique Applied to Multiple Operational Models

Using a multi-year period of observed cloud-to-ground (CG) lightning flashes over Alaska and the contiguous U.S. (CONUS), a climatology of lightning has been developed and is used along with NARR analyses to create prediction equations for lightning. The method uses a perfect prog(nosis) technique and logistic regression to build equations for predicting lightning within 10-km grids in Alaska and 40-km grids for the CONUS. These equations can be applied to a number of NCEP model forecasts including the GFS, NAM, RAP and SREF in real time. One of the primary applications of the lightning guidance is for predicting lightning-started wildfires. Since lightning often strikes in remote areas with rugged terrain, the fires that result from those ignitions often consume the most acreage with catastrophic results. Prediction of lightning, days in advance, allows for better planning and positioning of fire-fighting resources to attack fires while they are still small and more easily controlled. Probabilistic lightning forecasts for 1, 3, and 10 or more CG flashes are made for Alaska (10 x 10 km grid box) while probabilistic forecasts for 1, 10, and 100 or more CG flashes are made for the CONUS (40 x 40 km grid box). The ability to produce forecasts from a variety of models offers several unique benefits. Hourly forecasts for the short term (0 to 18 hours) can be produced using the RAP model. At the other end of the spectrum, 3-hour forecasts can be produced using the GFS model out to 7.5 days. In addition, the same equations can be applied to an ensemble (e.g., SREF) to produce a range, or envelope, of probabilities for each 3 hour time period.
Growth characterization and biostimulant potential of Coelastrella sp. D14 a green microalga isolated from a solar panel

Extremophile environments are an important source for finding microorganisms with a potential for biotechnological applications. Among these microorganisms, microalgae contribute to several sustainable processes such as wastewater treatments or nutrition. In this work it was characterized a microalga isolated from a solar panel. The morphological and phylogenetic analysis revealed that the isolate collected was a Coelastrella strain. Cultivation and stress experiments has shown that Coelastrella sp. D14 can resist a long period of desiccation and it can grow on cheap sources such as piggery wastewaters (PWW). This work reports that a Coelastrella strain displays biostimulant properties with a germination index of 123% on Lepidium sativum when D14 biomass grown at 10% piggery effluent was used. Altogether, these results suggest that this novel strain could be a good chassis for further biotechnological applications. Highlights Coelastrella sp. D14, a xero-tolerant strain, has been isolated from a solar panel This strain can grow on piggery wastewater Coelastrella sp. D14 can promote germination of Lepidium sativum
Heparan sulfate modified proteins affect cellular processes central to neurodegeneration and modulate presenilin function

Mutations in presenilin-1 (PSEN1) are the most common cause of familial, early-onset Alzheimer’s disease (AD), typically producing cognitive deficits in the fourth decade. A variant of APOE, APOE3 Christchurch (APOE3ch), was found associated with protection from both cognitive decline and Tau accumulation in a 70-year-old bearing the disease-causing PSEN1-E280A mutation. The amino acid change in ApoE3ch is within the heparan sulfate (HS) binding domain of APOE, and purified APOEch showed dramatically reduced affinity for heparin, a highly sulfated form of HS. The physiological significance of ApoE3ch is supported by studies of a mouse bearing a knock-in of this human variant and its effects on microglia reactivity and Aβ-induced Tau deposition. The studies reported here examine the function of heparan sulfate-modified proteoglycans (HSPGs) in cellular and molecular pathways affecting AD-related cell pathology in human cell lines and mouse astrocytes. The mechanisms of HSPG influences on presenilin-dependent cell loss and pathology were evaluated in Drosophila using knockdown of the presenilin homolog, Psn, together with partial loss of function of sulfateless (sfl), a homolog of NDST1, a gene specifically affecting HS sulfation. HSPG modulation of autophagy, mitochondrial function, and lipid metabolism were shown to be conserved in cultured human cell lines, Drosophila, and mouse astrocytes. RNAi of Ndst1 reduced intracellular lipid levels in wild-type mouse astrocytes or those expressing humanized variants of APOE, APOE3, and APOE4. RNA-sequence analysis of human cells deficient in HS synthesis demonstrated effects on the transcriptome governing lipid metabolism, autophagy, and mitochondrial biogenesis and showed significant enrichment in AD susceptibility genes identified by GWAS. Neuron-directed knockdown of Psn in Drosophila produced cell loss in the brain and behavioral phenotypes, both suppressed by simultaneous reductions in sfl mRNA levels. Abnormalities in mitochondria, liposome morphology, and autophagosome-derived structures in animals with Psn knockdown were also rescued by simultaneous reduction of sfl. sfl knockdown reversed Psn-dependent transcript changes in genes affecting lipid transport, metabolism, and monocarboxylate carriers. These findings support the direct involvement of HSPGs in AD pathogenesis.
Metabolomic Profiles and Pathways in Osteoarthritic Human Cartilage: A Comparative Analysis with Healthy Cartilage

Objective Osteoarthritis (OA) is a chronic joint disease with heterogenous metabolic pathology. To gain insight into OA-related metabolism, healthy and end-stage osteoarthritic cartilage were compared metabolically to uncover disease-associated profiles, classify OA-specific metabolic endotypes, and identify targets for intervention for the diverse populations of individuals affected by OA. Design Femoral head cartilage (n=35) from osteoarthritis patients were collected post-total joint arthroplasty. Healthy cartilage (n=11) was obtained from a tissue bank. Metabolites from all cartilage samples were extracted and analyzed using liquid chromatography-mass spectrometry metabolomic profiling. Additionally, cartilage extracts were pooled and underwent fragmentation analysis for biochemical identification of metabolites. Results Specific metabolites and metabolic pathways, including lipid- and amino acid pathways, were differentially regulated between osteoarthritis-derived and healthy cartilage. The detected alterations of amino acids and lipids highlight key differences in bioenergetic resources, matrix homeostasis, and mitochondrial alterations in osteoarthritis-derived cartilage compared to healthy. Moreover, metabolomic profiles of osteoarthritic cartilage separated into four distinct endotypes highlighting the heterogenous nature of OA metabolism and diverse landscape within the joint between patients. Conclusions The results of this study demonstrate that human cartilage has distinct metabolomic profiles between healthy and end-stage osteoarthritis patients. By taking a comprehensive approach to assess metabolic differences between healthy and osteoarthritic cartilage, and within osteoarthritic cartilage alone, several metabolic pathways with distinct regulation patterns were detected. Additional investigation may lead to the identification of metabolites that may serve as valuable indicators of disease status or potential therapeutic targets.
Selection of different parameters to study epistatic effect between heat shock and slightly deleterious mutations in the most fragile stage of embryogenesis Cyprinus carpio L

The primary genetic challenge encountered in artificial populations lies in the strong genetic drift, which leads to the accumulation of numerous slightly deleterious mutations across the genome. Such mutations diminish the adaptability of the entire population. The objective of this project involves the investigation and implementation of genetic selection methods within cultivated fish populations such Cyprinus carpio L. In order to maintain a high level of genome quality in productive species, we conducted a proof-of-principle experiment employing stress-induced strong purifying selection. This selection process is based on negative epistasis and effectively eliminates organisms carrying an excess of deleterious variants. The first step involves the creation of mutant and intact groups of fish. To obtain mutant groups, we treated male gametes with the ENU mutagen, which primarily induces single-nucleotide substitutions uniformly throughout the genome, thereby imitating natural mutations. This methodology is paramount for the accurate interpretation of experimental outcomes. Notably, temperature stands as a pivotal factor influencing the embryonic development of fish. Therefore, we subjected the embryos to a diverse range of temperatures and varied the duration of exposure during critical stages of embryogenesis. Through meticulous examination, we ascertained that the stage most susceptible to screening purposes is the 22-somite pair stage, occurring at a temperature of 38°C, with a 40-minute exposure period. We suppose, this comprehensive approach can be applied to improve the quality of the gene pool within domestic fish populations, ultimately enhancing the economic efficacy of fish farms. The future prospects of this method encompass its potential application to various species.
Single-Cell Local Stress Analysis in Tumoroids

The reciprocal interplay between cancer cells and their local environment, mediated by mechanical forces, necessitates a deeper experimental understanding. This requires precise quantitative measurements of cellular forces within the intricate three-dimensional context of the extracellular matrix. While methods such as traction-force microscopy and micropillar-array technology have effectively reported on cellular forces in two-dimensional cell culture, extending these techniques to three dimensions has proven exceedingly challenging. In the current study, we introduced a novel approach utilizing soft, elastic hydrogel microparticles, resembling the size of cells, to serve as specific and sensitive traction probes in three-dimensional cell culture of collagen-embedded tumoroids. Our methodology relies on high-resolution detection of microparticle deformations. These deformations are translated into spatially resolved traction fields, reaching a spatial resolution down to 1 μm and thereby detecting traction forces as low as 30 Pa. By integrating this high-resolution traction analysis with three-dimensional cell segmentation, we reconstructed the traction fields originating from individual cells. Our methodology enables us to explore the relationships between cellular characteristics, extracellular traction fields, and cellular responses. We observed that cellular stresses ranged from 10 to 100 Pa, integrating to cellular forces from 0.1 to 100 nN, which correlated with the localization of the cells actin skeleton, and the interaction area that cells developed towards the microparticles. Interestingly, the interaction of cells with inert microparticles appeared to be governed by contact mechanics resembling that two soft particles. The methodology presented here not only addresses the challenges of extending traditional stress-probe techniques to three dimensions, but also opens a strategy for the study of specific interactions between cells and the local tumoroid environment in a strive to fully understand cell-matrix reciprocity in tissue.
MRCK-1 activates non-muscle myosin for outgrowth of a unicellular tube in Caenorhabditis elegans

The formation and patterning of unicellular biological tubes is essential for metazoan development. It is well established that vascular tubes and neurons use similar guidance cues to direct their development, but the downstream mechanisms that promote the outgrowth of biological tubes are not well characterized. We show that the conserved kinase MRCK-1 and its substrate the regulatory light chain of non-muscle myosin, MLC-4, are required for outgrowth of the unicellular excretory canal in C. elegans. Structure-function analysis of MRCK-1 indicates that the kinase domain, but not the small GTPase-binding CRIB domain, is required for canal outgrowth. Expression of a phosphomimetic form of MLC-4 rescues canal truncations in mrck-1 mutants and shows enrichment at the growing canal tip. Specific depletion of MRCK-1 or MLC-4 in the canal causes severe truncations, with unlumenized projections of the basal membrane. Moreover, our work reveals a novel function for non-muscle myosin downstream of MRCK-1 in excretory canal outgrowth that may be conserved in the development of seamless tubes in other organisms.
Gelatinous matrix, an original convergent evolution to cope with oligotrophy in Nassellaria (Radiolaria)

Radiolaria are heterotrophic protists abundant in the world’s oceans playing important roles in oceanic biogeochemical cycles. Some species can host photosynthetic algae thus contributing to primary production. Such mixotrophic behaviour is believed to explain their ecological success in oligotrophic waters, notably Collodaria, a group of exclusively mixotrophic radiolarians embedded in a gelatinous matrix. Sampling oligotrophic California Current communities revealed an abundant, rarely observed population of Nassellaria of the genus Phlebarachnium, characterized to live within a gelatinous matrix along with Collodaria and Orodaria. Phylogenetic reconstruction of the ribosomal DNA suggests that these distantly related lineages within Nassellaria independently developed the ability to produce a gelatinous matrix ∼120 million years ago. Molecular analyses identify photosynthetic symbionts as Scrippsiella sp. , a common dinoflagellate symbiont of other planktonic groups. By matching our physical samples with their genetic signature, we identified these rarely observed organisms in global metabarcoding datasets, revealing a strong biogeographic affinity to oligotrophic water masses. Our results suggest that the gelatinous matrix is an exclusive adaptation to oligotrophic waters although further research is required to evaluate the similarities between the gelatinous matrices of Collodaria, Orodaria and Phlebarachnium. We hypothesize that such an original convergent evolution could increase the effective volume to weight ratio favoring prey contact and capture and provide an advantageous microenvironment for symbionts, enhancing ecological success in nutrient-depleted waters. This study advances our understanding of the evolution of eukaryotic diversity and highlights the specific advantages of certain adaptations, specifically when evolution occurs independently among various lineages.
scMeFormer: a transformer-based deep learning model for imputing DNA methylation states in single cells enhances the detection of epigenetic alterations in schizophrenia

DNA methylation (DNAm), a crucial epigenetic mark, plays a key role in gene regulation, mammalian development, and various human diseases. Single-cell technologies enable the profiling of DNAm states at cytosines within the DNA sequence of individual cells, but they often suffer from limited coverage of CpG sites. In this study, we introduce scMeFormer, a transformer-based deep learning model designed to impute DNAm states for each CpG site in single cells. Through comprehensive evaluations, we demonstrate the superior performance of scMeFormer compared to alternative models across four single-nucleus DNAm datasets generated by distinct technologies. Remarkably, scMeFormer exhibits high-fidelity imputation, even when dealing with significantly reduced coverage, as low as 10% of the original CpG sites. Furthermore, we applied scMeFormer to a single-nucleus DNAm dataset generated from the prefrontal cortex of four schizophrenia patients and four neurotypical controls. This enabled the identification of thousands of differentially methylated regions associated with schizophrenia that would have remained undetectable without imputation and added granularity to our understanding of epigenetic alterations in schizophrenia within specific cell types. Our study highlights the power of deep learning in imputing DNAm states in single cells, and we expect scMeFormer to be a valuable tool for single-cell DNAm studies.
The Search for Neutrinoless Double Beta Decay with 130Te with CUORE-0

Author(s): Ouellet, Jonathan, L | Abstract: This thesis describes the design, operation and results of an experimental search for neutrinoless double beta decay (0$\nu\beta\beta$) of $^{130}$Te using the CUORE-0 detector. The discovery of 0$\nu\beta\beta$ would have profound implications for particle physics and our understanding of the Universe. Its discovery would demonstrate the violation of lepton number and imply that neutrinos are Majorana fermions and therefore their own anti-particles. Combined with other experimental results, the discovery of 0$\nu\beta\beta$ could also have implications for understanding the absolute neutrino mass scale as well as the presently unknown neutrino mass hierarchy. The CUORE experiment is a ton-scale search for 0$\nu\beta\beta$ in $^{130}$Te expected to begin operation in late 2015. The first stage of this experiment is a smaller 39-kg active-mass detector called CUORE-0. This detector contains 11~kg of $^{130}$Te and operates in the Laboratori Nazionali del Gran Sasso lab in Italy from 2013 -- 2015. The results presented here are based on a $^\text{nat}$TeO$_2$ exposure of 35.2~kg$\cdot$yr, or 9.8~kg$\cdot$yr exposure of $^{130}$Te collected between 2013 -- 2015. We see no evidence of 0$\nu\beta\beta$ and place an upper limit on the 0$\nu\beta\beta$ decay rate of $\Gamma_\text{0$\nu\beta\beta$}l0.25\times10^{-24}$~yr$^{-1}$ (90\% C.L.), corresponding to a lower limit on the half-life of $T^{0\nu}_{1/2}g2.8\times10^{24}$~yr (90\% C.L.). We combine the present result with the results of previous searches in $^{130}$Te. Combining it with the 1.2~kg$\cdot$yr $^{130}$Te exposure from the Three Towers Test run we place a half-life limit of $T_{1/2}^{0\nu}g3.3\times10^{24}$~yr (90\% C.L.). And combining these results with the 19.75~kg$\cdot$yr $^{130}$Te exposure from CUORE-0ino, we place the strongest limit on the 0$\nu\beta\beta$ half-life of $^{130}$Te to date, at $T^{0\nu}_{1/2}g4.5\times10^{24}$~yr (90\% C.L.). Using the present nuclear matrix element calculations for $^{130}$Te, this result corresponds to a 90\% upper limit range on the effective Majorana mass of $m_{\beta\beta}l250-710$~meV.