Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome assembly of the maize inbred line A188 provides a new reference genome for functional genomics

Heretofore, little is known about the mechanism underlying the genotype-dependence of embryonic callus (EC) induction, which has severely inhibited the development of maize genetic engineering. Here, we report the genome sequence and annotation of a maize inbred line with high EC induction ratio, A188, which is assembled from single-molecule sequencing and optical genome mapping. We assembled a 2,210 Mb genome with a scaffold N50 size of 11.61 million bases (Mb), compared to those of 9.73 Mb for B73 and 10.2 Mb for Mo17. Comparative analysis revealed that ∼30% of the predicted A188 genes had large structural variations to B73, Mo17 and W22 genomes, which caused considerable protein divergence and might lead to phenotypic variations between the four inbred lines. Combining our new A188 genome, previously reported QTLs and RNA sequencing data, we reveal 8 large structural variation genes and 4 differentially expressed genes playing potential roles in EC induction. Highlight Our manuscript presents a high-quality reference genome of the inbred line A188, and provides new insights into candidate genes underlying maize embryonic callus induction and other maize agronomic traits.
Paired Feed-Forward Excitation With Delayed Inhibition Allows High Frequency Computations Across Brain Regions

The transmission of high-frequency temporal information across brain regions is critical to perception, but the mechanisms underlying such transmission remain unclear. Long-range projection patterns across brain areas are often comprised of paired feedforward excitation followed closely by delayed inhibition, including the thalamic triad synapse, thalamic projections to cortex, and projections within hippocampus. Previous studies have shown that these joint projections produce a shortened period of depolarization, sharpening the timing window over which the postsynaptic neuron can fire. Here we show that these projections can facilitate the transmission of high-frequency computations even at frequencies that are highly filtered by neuronal membranes. Further, they can coordinate computations across multiple brain areas, even amid ongoing local activity. We suggest that paired feedforward excitation and inhibition provides a hybrid signal – carrying both a value and a clock-like trigger – to allow circuits to be responsive to input whenever it arrives.
A signature of Neanderthal introgression on molecular mechanisms of environmental responses

Ancient human migrations led to the settlement of population groups in varied environmental contexts worldwide. The extent to which adaptation to local environments has shaped human genetic diversity is a longstanding question in human evolution. Recent studies have suggested that introgression of archaic alleles in the genome of modern humans may have contributed to adaptation to environmental pressures such as pathogen exposure. Functional genomic studies have demonstrated that variation in gene expression across individuals and in response to environmental perturbations is a main mechanism underlying complex trait variation. We considered gene expression response to in vitro treatments as a molecular phenotype to identify genes and regulatory variants that may have played an important role in adaptations to local environments. We investigated if Neanderthal introgression in the human genome may contribute to the transcriptional response to environmental perturbations. To this end we used eQTLs for genes differentially expressed in a panel of 52 cellular environments, resulting from 5 cell types and 26 treatments, including hormones, vitamins, drugs, and environmental contaminants. We found that SNPs with introgressed Neanderthal alleles (N-SNPs) disrupt binding of transcription factors important for environmental responses, including ionizing radiation and hypoxia, and for glucose metabolism. We identified an enrichment for N-SNPs among eQTLs for genes differentially expressed in response to 8 treatments, including glucocorticoids, caffeine, and vitamin D. Using Massively Parallel Reporter Assays (MPRA) data, we validated the regulatory function of 21 introgressed Neanderthal variants in the human genome, corresponding to 8 eQTLs regulating 15 genes that respond to environmental perturbations. These findings expand the set of environments where archaic introgression may have contributed to adaptations to local environments in modern humans and provide experimental validation for the regulatory function of introgressed variants.
Insights into the drivers of radiating diversification in biodiversity hotspots using Saussurea (Asteraceae) as a case

The Qinghai-Tibet Plateau (QTP) encompasses areas with a remarkably high degree of biodiversity, harboring exceptional species-rich radiations. How these radiations formed by interacting with geology, climate and ecology remains seldom examined. We investigate the roles of abiotic (environmental) and biotic (species-intrinsic) factors in driving radiating diversification of Saussurea (Asteraceae) by deploying a number of time-dependent, paleoenvironment-dependent and trait-dependent models, as well as ecological distribution data. We show that three main clades of Saussurea begin to diversify in the Miocene almost simultaneously, with increasing diversification rates toward the present and negative dependence to paleotemperature. Acceleration in diversification rates are correlated with adaptive traits, as well climate lability, niche breadth and species range. We conclude that fluctuation of paleoclimate along with complex QTP environments provided opportunities for increased diversification rates of Saussurea with diverse adaptive traits, highlighting the importance of combinations of clade-specific traits and ecological niches in driving rapid radiation.
Rediscovering the musician’s brain: a systematic review and meta-analysis

Musical expertise is a model of neuroplasticity associated with pervasive, long-lasting training effects. Indeed, decades of cognitive neuroscience widely investigated brain functional and structural changes associated with musical training, providing a widespread and variegated set of findings. However, several controversial results emerged, leading the neuroscientific community to lack a well-defined neuro-functional-anatomy of musical expertise. Here, we performed a systematic review and meta-analysis of publications investigating brain functional and structural differences between musicians and non-musicians. Eighty-four publications were included in the qualitative synthesis. Coordinate-based meta-analyses were conducted using the anatomic/activation likelihood estimation (ALE) method implemented in GingerALE, with a total of 675 foci, 79 experiments and 2780 participants. Results showed a widespread and complex array of functional and structural changes in musicians’ brains, revealing for the first time a comprehensive picture of the brain plasticity associated with musical training.
Allele frequency divergence reveals ubiquitous influence of positive selection in Drosophila

Resolving the role of natural selection is a basic objective of evolutionary biology. It is generally difficult to detect the influence of selection because ubiquitous non-selective stochastic change in allele frequencies (genetic drift) degrades evidence of selection. As a result, selection scans typically only identify genomic regions that have undergone episodes of intense selection. Yet it seems likely such episodes are the exception; the norm is more likely to involve subtle, concurrent selective changes at a large number of loci. We develop a new theoretical approach that uncovers a previously undocumented genome-wide signature of selection in the collective divergence of allele frequencies over time. Applying our approach to temporally resolved allele frequency measurements from laboratory and wild Drosophila populations, we quantify the selective contribution to allele frequency divergence and find that selection has substantial effects on much of the genome. We further quantify the magnitude of the total selection coefficient (a measure of the combined effects of direct and linked selection) at a typical polymorphic locus, and find this to be large (of order 1%) even though most mutations are not directly under selection. We find that selective allele frequency divergence is substantial at intermediate allele frequencies, which we argue is most parsimoniously explained by positive — not purifying — selection. Thus, in these populations most mutations are far from evolving neutrally in the short term (tens of generations), including mutations with neutral fitness effects, and the result cannot be explained simply as a purging of deleterious mutations. Author summary Natural selection is the process fundamentally driving evolutionary adaptation; yet the specifics of how natural selection molds the genome are contentious. A prevailing neutralist view holds that the evolution of most mutations is essentially random. Here, we develop new theory that looks past the stochasticity of individual mutations and instead analyzes the behavior of mutations across the genome as a collective. We find that selection has a strong non-random influence on most of the Drosophila genome over short timescales (tens of generations), including the bulk of mutations that are not themselves directly targeted by selection. We show that this likely involves ongoing positive selection.
Histone H3 clipping is a novel signature of human neutrophil extracellular traps

Neutrophils are critical to host defence, executing diverse strategies to perform their antimicrobial and regulatory functions. One tactic is the production of neutrophil extracellular traps (NETs). In response to certain stimuli neutrophils decondense their lobulated nucleus and release chromatin into the extracellular space through a process called NETosis. However, NETosis, and the subsequent degradation of NETs, can become dysregulated. NETs are proposed to play a role in infectious as well as many non-infection related diseases including cancer, thrombosis, autoimmunity and neurological disease. Consequently, there is a need to develop specific tools for the study of these structures in disease contexts. In this study, we identified a NET-specific histone H3 cleavage event and harnessed this to develop a cleavage site-specific antibody for the detection of human NETs. By microscopy, this antibody distinguishes NETs from chromatin in purified and mixed cell samples. It also detects NETs in tissue sections. We propose this antibody as a new tool to detect and quantify NETs.
Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance

Alteration of antibiotic binding sites through modification of ribosomal RNA (rRNA) is a common form of resistance to ribosome-targeting antibiotics. The rRNA-modifying enzyme Cfr methylates an adenosine nucleotide within the peptidyl transferase center, resulting in the C-8 methylation of A2503 (m8A2503). Acquisition of cfr results in resistance to eight classes of ribosome-targeting antibiotics. Despite the prevalence of this resistance mechanism, it is poorly understood whether and how bacteria modulate Cfr methylation to adapt to antibiotic pressure. Moreover, direct evidence for how m8A2503 alters antibiotic binding sites within the ribosome is lacking. In this study, we performed directed evolution of Cfr under antibiotic selection to generate Cfr variants that confer increased resistance by enhancing methylation of A2503 in cells. Increased rRNA methylation is achieved by improved expression and stability of Cfr through transcriptional and post-transcriptional mechanisms, which may be exploited by pathogens under antibiotic stress as suggested by natural isolates. Using a variant which achieves near-stoichiometric methylation of rRNA, we determined a 2.2 Å cryo-EM structure of the Cfr-modified ribosome. Our structure reveals the molecular basis for broad resistance to antibiotics and will inform the design of new antibiotics that overcome resistance mediated by Cfr.
Decoding the information structure underlying the neural representation of concepts

Significance The ability to identify individual objects or events as members of a kind (e.g., “knife,” “dog,” or “party”) is a fundamental aspect of human cognition. It allows us to quickly access a wealth of information pertaining to a newly encountered object or event and use it to guide our behavior. How is this information represented in the brain? We used functional MRI to analyze patterns of brain activity corresponding to hundreds of familiar concepts and quantitatively characterized the informational structure of these patterns. Our results indicate that conceptual knowledge is stored as patterns of neural activity that encode sensory-motor and affective information about each concept, contrary to the long-held idea that concept representations are independent of sensory-motor experience. The nature of the representational code underlying conceptual knowledge remains a major unsolved problem in cognitive neuroscience. We assessed the extent to which different representational systems contribute to the instantiation of lexical concepts in high-level, heteromodal cortical areas previously associated with semantic cognition. We found that lexical semantic information can be reliably decoded from a wide range of heteromodal cortical areas in the frontal, parietal, and temporal cortex. In most of these areas, we found a striking advantage for experience-based representational structures (i.e., encoding information about sensory-motor, affective, and other features of phenomenal experience), with little evidence for independent taxonomic or distributional organization. These results were found independently for object and event concepts. Our findings indicate that concept representations in the heteromodal cortex are based, at least in part, on experiential information. They also reveal that, in most heteromodal areas, event concepts have more heterogeneous representations (i.e., they are more easily decodable) than object concepts and that other areas beyond the traditional “semantic hubs” contribute to semantic cognition, particularly the posterior cingulate gyrus and the precuneus.
A biomechanical comparison of the jerk, back jerk, vertical jump and jump squat

Although weightlifting exercises and their pulling and catching derivatives have been well studied, less is known about the group of weightlifting overhead pressing derivatives (WOPDs). There were two purposes of the present study. Above all, it was to compare WOPDs (i.e. jerk and back jerk) with jump squat in enhancing sport performance such as vertical jump in the perspective of biomechanics. Furthermore, it was to gain a better understanding of the biomechanical difference between jerk and back jerk. The study compared the kinetics, kinematics, and muscle activation of the jerk, back jerk, vertical jump and jump squat. Ground reaction forces, joint angle data and electromyography were collected from 20 track and field athletes while they performed the four movements. The joint coordination pattern and EMG characters of the jump squat were more similar to those of the vertical jump. WOPDs, especially jerk, exhibited less similarity with vertical jump in joint coordination, as well as the subsequent peak activation. The electromyography data demonstrated significant differences in rectus femoris and gluteus maximus in the relative timing of peak activations and the maximum activation. Jump squat was greater in peak force (2211N) than jerk (P < .005), greater peak power (4749W) than jerk and back jerk (P < .001) and no significant difference with WOPDs in rate of force development. Back jerk produced a greater peak force (2223 N), peak power (3767W) and eccentric RFD (15965 N·s−1) than jerk (2061N)(P < .001) (3364W)(P < .05) (12280 N·s−1)(P < .01)and the opposite in concentric RFD that jerk (7702 N·s−1) was greater than back jerk (5972 N·s−1)(P < .05). We can conclude that for runner and jumpers, jump squat was better for improving vertical jump than WOPDs and back jerk is better than jerk in power training.
Changes in coffee brews in relation to storage temperature

Coffee beverage bottled aseptically was tested in order to evaluate the more evident chemical and sensory changes occurring during storage. The decline in pH and the quality score correlated well at several storage temperatures. The sensory analysis permitted definition of a lower limit of pH at which the product's shelf-life ended. The original panel scores were assessed by response surface methodology to obtain estimated scores for the different time/ temperature storage conditions. Knowledge of the kinetic rate constants of the decline in pH at different temperatures permitted correlation of the shelf-life of the product with its storage temperature.
Single cell RNA sequencing of the Strongylocentrotus purpuratus larva reveals the blueprint of major cell types and nervous system of a non-chordate deuterostome

Identifying the molecular fingerprint of organismal cell types is key for understanding their function and evolution. Here, we use single cell RNA sequencing (scRNA-seq) to survey the cell types of the sea urchin early pluteus larva, representing an important developmental transition from non-feeding to feeding larva. We identify 21 distinct cell clusters, representing cells of the digestive, skeletal, immune, and nervous systems. Further subclustering of these reveal a highly detailed portrait of cell diversity across the larva, including the identification of neuronal cell types. We then validate important gene regulatory networks driving sea urchin development and reveal new domains of activity within the larval body. Focusing on neurons that co-express Pdx-1 and Brn1/2/4, we identify an unprecedented number of genes shared by this population of neurons in sea urchin and vertebrate endocrine pancreatic cells. Using differential expression results from Pdx-1 knockdown experiments, we show that Pdx1 is necessary for the acquisition of the neuronal identity of these cells. We hypothesize that a network similar to the one orchestrated by Pdx1 in the sea urchin neurons was active in an ancestral cell type and then inherited by neuronal and pancreatic developmental lineages in sea urchins and vertebrates.
A graph-based cell tracking algorithm with few manually tunable parameters and automated segmentation error correction

Automatic cell segmentation and tracking enables to gain quantitative insights into the processes driving cell migration. To investigate new data with minimal manual effort, cell tracking algorithms should be easy to apply and reduce manual curation time by providing automatic correction of segmentation errors. Current cell tracking algorithms, however, are either easy to apply to new data sets but lack automatic segmentation error correction, or have a vast set of parameters that needs either manual tuning or annotated data for parameter tuning. In this work, we propose a tracking algorithm with only few manually tunable parameters and automatic segmentation error correction. Moreover, no training data is needed. We investigate the performance of our approach by simulating erroneous segmentation data, including false negatives, over- and under-segmentation errors, on 2D and 3D cell data sets. We compare our approach against three well-performing tracking algorithms from the Cell Tracking Challenge. Our tracking algorithm can correct false negatives, over- and under-segmentation errors as well as a mixture of the aforementioned segmentation errors. Furthermore, in case of under-segmentation or a combination of segmentation errors our approach outperforms the other tracking approaches.
Co-variation between glucocorticoids, behaviour and immunity supports the pace-of-life syndrome hypothesis: an experimental approach

The biomedical literature has consistently highlighted that long-term elevation of glucocorticoids might impair immune functions. In wild animals, patterns are less clear. Here, we re-explored the stress-immunity relationship considering the potential effects of behavioural profiles. Thirteen captive roe deer (Capreolus capreolus) were monitored over an eight-week period encompassing two capture events. We assessed how changes in baseline faecal cortisol metabolite (FCM) concentrations following a standardised capture protocol and vaccination affected changes in thirteen immune parameters of the innate and adaptive immunity, and whether behavioural profiles were linked to changes in baseline FCM levels and immune parameters. We found that individuals showing an increase in baseline FCM levels also exhibited an increase in immunity and were characterised by more reactive behavioural profiles (low activity levels, docility to manipulation and neophilia). Our results suggest that immunity of large mammals may be influenced by glucocorticoids, but also behavioural profiles, as it is predicted by the pace-of-life syndrome hypothesis. Our results highlight the need to consider co-variations between behaviour, immunity and glucocorticoids in order to improve our understanding of the among-individual variability in the stress-immunity relationships observed in wildlife, as they may be underpinned by different life-history strategies.
BEdeepon: an in silico tool for prediction of base editor efficiencies and outcomes

Base editors enable direct conversion of one target base into another in a programmable manner, but conversion efficiencies vary dramatically among different targets. Here, we performed a high-throughput gRNA-target library screening to measure conversion efficiencies and outcome product frequencies at integrated genomic targets and obtained datasets of 60,615 and 73,303 targets for ABE and CBE, respectively. We used the datasets to train deep learning models, resulting in ABEdeepon and CBEdeepon which can predict on-target efficiencies and outcome sequence frequencies. The software is freely accessible via online web server http://www.deephf. com/#/bedeep.
Endomitosis controls tissue-specific gene expression during development

Polyploid cells contain more than two copies of the genome and are found in many plant and animal tissues. Different types of polyploidy exist, in which the genome is confined to either one nucleus (mononucleation) or two or more nuclei (multinucleation). Despite the widespread occurrence of polyploidy, the functional significance of different types of polyploidy are largely unknown. Here, we assess the function of multinucleation in C. elegans intestinal cells through specific inhibition of binucleation without altering genome ploidy. Through single worm RNA sequencing, we find that binucleation is important for tissuespecific gene expression, most prominently for genes that show a rapid upregulation at the transition from larval development to adulthood. Regulated genes include vitellogenins, which encode yolk proteins that facilitate nutrient transport to the germline. We find that reduced expression of vitellogenins in mononucleated intestinal cells leads to progeny with developmental delays and reduced fitness. Together, our results show that binucleation facilitates rapid upregulation of intestine-specific gene expression during development, independently of genome ploidy, underscoring the importance of spatial genome organization for polyploid cell function.