Miracle-dz/UniFAR-FTUs huggingface dataset:
Cerebellar Purkinje cells can differentially modulate coherence between sensory and motor cortex depending on region and behavior

Significance Coordinated activity of sensory and motor cortices is essential for adjusting movements based on sensory feedback. Sensory and motor cortices communicate directly as well as via the thalamus and also receive indirect input from the cerebellum. We show here that cerebellar activity can affect the amplitude and coherence of fast sensorimotor responses in the primary somatosensory and motor cortices upon whisker stimulation. The cerebellum can differentially alter sensory-induced theta- and gamma-band cortical coherences via a fast ascending pathway. In line with the functional heterogeneity of its modular organization, cerebellar impact is region-specific and tuned to ongoing motor responses. Our data highlight site-specific and context-dependent cerebello-cerebral interactions that can come into play during a plethora of sensorimotor functions. Activity of sensory and motor cortices is essential for sensorimotor integration. In particular, coherence between these areas may indicate binding of critical functions like perception, motor planning, action, or sleep. Evidence is accumulating that cerebellar output modulates cortical activity and coherence, but how, when, and where it does so is unclear. We studied activity in and coherence between S1 and M1 cortices during whisker stimulation in the absence and presence of optogenetic Purkinje cell stimulation in crus 1 and 2 of awake mice, eliciting strong simple spike rate modulation. Without Purkinje cell stimulation, whisker stimulation triggers fast responses in S1 and M1 involving transient coherence in a broad spectrum. Simultaneous stimulation of Purkinje cells and whiskers affects amplitude and kinetics of sensory responses in S1 and M1 and alters the estimated S1–M1 coherence in theta and gamma bands, allowing bidirectional control dependent on behavioral context. These effects are absent when Purkinje cell activation is delayed by 20 ms. Focal stimulation of Purkinje cells revealed site specificity, with cells in medial crus 2 showing the most prominent and selective impact on estimated coherence, i.e., a strong suppression in the gamma but not the theta band. Granger causality analyses and computational modeling of the involved networks suggest that Purkinje cells control S1–M1 phase consistency predominantly via ventrolateral thalamus and M1. Our results indicate that activity of sensorimotor cortices can be dynamically and functionally modulated by specific cerebellar inputs, highlighting a widespread role of the cerebellum in coordinating sensorimotor behavior.
Characterization of Salix nigra floral insect community and activity of three native Andrena bees

Salix nigra (black willow) is a widespread tree that hosts many species of polylectic hymenopterans and oligolectic bees of the genus Andrena. The early flowering time of S. nigra makes it an important nutritive resource for arthropods emerging from hibernation. However, since S. nigra is dioecious, not all insect visits will lead to successful pollination. Using both visual observation and pan-trapping we characterized the community of arthropods that visited S. nigra flowers and assessed the differences among male and female trees as well as the chemical and visual drivers that influenced community composition across three years. We found that male trees consistently supported higher diversity of insects than female trees and only three insect species, all Andrena spp. , consistently visited both sexes. Additionally, A. nigrae, which was the only insect that occurred more on female than male flowers, correlated strongly to volatile cues. This suggests that cross-pollinators cue into specific aspects of floral scent, but diversity of floral visitors is driven strongly by visual cues. Through time the floral activity of two Andrena species remained stable, but A. nigrae visited less in 2017 when flowers bloomed earlier than other years. When native bee emergence does not synchronize with bloom, activity appears to be greatly diminished which could threaten species that only subsist on a single host. Despite the community diversity of S. nigra flowers, its productivity depends on a small fraction of species that are not threatened by competition, but rather rapidly changing conditions that lead to host-insect asynchrony.
Combining mass spectrometric platforms for lipidome investigation - Application to the characterisation of disruptions in the lipid profile of pig serum upon β-agonist treatment

In the last decade, many mass spectrometric fingerprinting methods dedicated to lipidomics have been proposed: either non-targeted approaches, coupled with annotation methods, or targeted strategies, aiming at specifically monitoring a limited number of substances. In a general public health perspective and through a strategy combining non-targeted and targeted lipidomics MS-based approaches, this study aims at identifying disrupted patterns in serum lipidome upon growth promoter treatment in pig and evaluating the relative contributions of the three platforms involved. Pig serum samples collected during an animal experiment involving control and treated animals, whose food had been supplemented with ractopamine, were extracted and characterised using three MS strategies: Non-targeted RP LC-HRMS; the targeted Lipidyzer™ platform (differential ion mobility associated with shotgun lipidomics) and a homemade LC-HRMS triglyceride platform. The three different platforms showed complementarity insight into lipid characterisation, which, applied to a selected set of samples, enabled highlighting specific lipid profile patterns involving various lipid classes, mainly in relation with cholesterol esters, sphingomyelins, lactosylceramide, phosphatidylcholines and triglycerides. Thanks to the combination of both non-targeted and targeted MS approaches, the exploration of various compartments of the pig serum lipidome could be performed, including commonly characterised lipids (Lipidyzer™), triglyceride isomers (Triglyceride platform) -whose accurate analysis was considered an analytical challenge, and unique lipid features (non-targeted LC-HRMS). Thanks to their respective characteristics, the complementarity of the three tools could be demonstrated for public health purposes, with enhanced lipidome coverage, level of characterisation and applicability.
Childhood urbanization affects prefrontal cortical responses to trait anxiety and interacts with polygenic risk for depression

Global increases in urbanization have brought dramatic economic, environmental and social changes. However, less is understood about how these may influence disease-related brain mechanisms underlying epidemiological observations that urban birth and childhoods may increase the risk for neuropsychiatric disorders, including increased social stress and depression. In a genetically homogeneous Han Chinese adult population with divergent urban and rural birth and childhoods, we examined the structural and functional MRI neural correlates of childhood urbanicity, focusing on behavioral traits responding to social status threats, and polygenic risk for depression. Subjects with divergent rural and urban childhoods were similar in adult socioeconomic status and were genetically homogeneous. Urban childhoods, however, were associated with higher trait anxiety-depression. On structural MRI, urban childhoods were associated with relatively reduced medial prefrontal gray matter volumes. Functional medial prefrontal engagement under social status threat during working memory correlated with trait anxiety-depression in subjects with urban childhoods, to a significantly greater extent than in their rural counterparts, implicating an exaggerated physiological response to the threat context. Stress-associated medial prefrontal engagement also interacted with polygenic risk for depression, significantly predicting a differential response in individuals with urban but not rural childhoods. Developmental urbanicity thus differentially influenced medial prefrontal structure and function, at least in part through mechanisms associated with the neural processing of social status threat, trait anxiety, and genetic risk for depression, which may be factors in the association of urbanicity with adult psychopathology. Significance Statement Urban living has been associated with social inequalities and stress. However, less is understood about the neural underpinnings by which these stressors affect disease risk, and in particular, genetic risk for depression. Leveraging urbanization in China, we studied adults with diverse urban and rural upbringings, who were genetically homogeneous and with similar current socioeconomic status, to isolate the effects of childhood urbanicity. At medial prefrontal cortex, a region critical for processing emotional stressors and social status, genetic risk for depression resulted in more deleterious function under stress in individuals with urban, but not rural childhoods. This implicates medial prefrontal cortex’s critical role in brain development, integrating genetic mechanisms of stress and depression with the childhood environment.
The Effect of Self-Loading on the Mechano-Stability and Stalk Lodging Resistance of Plant Stems

Background Stalk lodging (breaking of agricultural plant stalks prior to harvest) is a multi-billion dollar a year problem. Stalk lodging occurs when bending moments induced by a combination of external loading (e.g. wind) and self-loading (e.g. the plant’s own weight) exceed the bending strength of plant stems. Previous biomechanical plant stem models have investigated both external loading and self-loading of plants, but have evaluated them as separate and independent phenomena. However, these two types of loading are highly interconnected and mutually dependent. The purpose of this paper is twofold: (1) to investigate the combined effect of external loads and plant weight on the displacement and stress state of plant stems / stalks, and (2) to provide a generalized framework for accounting for self-weight during mechanical phenotyping experiments used to predict stalk lodging resistance. Results A method of properly accounting for the interconnected relationship between self-loading and external loading of plants stems is presented. The interconnected set of equations are used to produce user-friendly applications by presenting (1) simplified self-loading correction factors for a number of common external loading configurations of plants, and (2) a generalized Microsoft Excel framework that calculates the influence of self-loading on crop stems. The effect of self-loading on the structural integrity of wheat is examined in detail. A survey of several other plants is conducted and the influence of self-loading on their structural integrity is also presented. Conclusions The self-loading of plants plays a potentially critical role on the structural integrity of plant stems. Equations and tools provided herein enable researchers to account for the plant’s weight when investigating the flexural rigidity and bending strength of plant stems.
Axial skeleton anterior-posterior patterning is regulated through feedback regulation between Meis transcription factors and retinoic acid

ABSTRACT Vertebrate axial skeletal patterning is controlled by co-linear expression of Hox genes and axial level-dependent activity of HOX protein combinations. MEIS transcription factors act as co-factors of HOX proteins and profusely bind to Hox complex DNA; however, their roles in mammalian axial patterning remain unknown. Retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors; however, whether this role is related to MEIS/HOX activity remains unknown. Here, we study the role of Meis in axial skeleton formation and its relationship to the RA pathway in mice. Meis elimination in the paraxial mesoderm produces anterior homeotic transformations and rib mis-patterning associated to alterations of the hypaxial myotome. Although Raldh2 and Meis positively regulate each other, Raldh2 elimination largely recapitulates the defects associated with Meis deficiency, and Meis overexpression rescues the axial skeletal defects in Raldh2 mutants. We propose a Meis-RA-positive feedback loop, the output of which is Meis levels, that is essential to establish anterior-posterior identities and patterning of the vertebrate axial skeleton. Summary: Positive feedback between Meis and retinoic acid regulates axial skeleton patterning in the mouse embryo.
Hippocampal inputs engage CCK+ interneurons to mediate endocannabinoid-modulated feed-forward inhibition in the prefrontal cortex

Connections from the ventral hippocampus (vHPC) to the prefrontal cortex (PFC) regulate cognition, emotion and memory. These functions are also tightly regulated by inhibitory networks in the PFC, whose disruption is thought to contribute to mental health disorders. However, relatively little is known about how the vHPC engages different populations of interneurons in the PFC. Here we use slice physiology and optogenetics to study vHPC-evoked feed-forward inhibition in the mouse PFC. We first show that cholecystokinin (CCK+), parvalbumin (PV+), and somatostatin (SOM+) interneurons are prominent in layer 5 (L5) of infralimbic PFC. We then show that vHPC inputs primarily activate CCK+ and PV+ interneurons, with weaker connections onto SOM+ interneurons. CCK+ interneurons make stronger synapses onto pyramidal tract (PT) cells over nearby intratelencephalic (IT) cells. However, CCK+ inputs undergo depolarization-induced suppression of inhibition (DSI) and CB1 receptor modulation only at IT cells. Moreover, vHPC-evoked feed-forward inhibition undergoes DSI only at IT cells, confirming a central role for CCK+ interneurons. Together, our findings show how vHPC directly engages multiple populations of inhibitory cells in deep layers of the infralimbic PFC, highlighting unexpected roles for both CCK+ interneurons and endocannabinoid modulation in hippocampal-prefrontal communication.
Entorhinal cortex minimises uncertainty for optimal behaviour

Minimizing spatial uncertainty is essential for navigation but the neural mechanisms remain elusive. First, we show that polarising cues produce an anisotropy in the information available to movement trajectories. Secondly, we simulate entorhinal grid cells in an environment with anisotropic information and show that self-location is decoded best when grid-patterns are aligned with the axis of greatest information. Thirdly, we expose human participants to polarised virtual reality environments and confirm the predicted anisotropy in navigation performance and eye movements. Finally, using fMRI we find that the orientation of grid-like hexadirectional activity in entorhinal cortex is aligned with the environmental axis of greatest information; and that this alignment predicted the anisotropy of participants’ spatial memory. In sum, we demonstrate a crucial role of the entorhinal grid system in reducing uncertainty in the neural representation of self-location and find evidence for adaptive spatial computations underlying entorhinal representations in service of optimising behaviour.
Oxytocin increases the pleasantness of affective touch and orbitofrontal cortex activity independent of valence

Touch plays a crucial role in affiliative behavior and social communication. The neuropeptide oxytocin is released in response to touch and may act to facilitate the rewarding effects of social touch. However, no studies to date have determined whether oxytocin facilitates behavioral or neural responses to non-socially administered affective touch and possible differential effects of touch valence. In a functional MRI experiment using a randomized placebo-controlled, within-subject design in 40 male subjects we investigated the effects of intranasal oxytocin (24IU) on behavioral and neural responses to positive, neutral and negative valence touch administered to the arm via different types of materials at a frequency aimed to optimally stimulate C-fibers. Results showed that oxytocin significantly increased both the perceived pleasantness of touch and activation of the orbitofrontal cortex independent of touch valence. The effects of OT on touch-evoked orbitofrontal activation were also positively associated with basal oxytocin concentrations in blood. Additionally, anterior insula activity and the functional connectivity between the amygdala and right anterior insula were enhanced only in response to negative valence touch. Overall, the present study provides the first evidence that oxytocin may facilitate the rewarding effects of all types of touch, irrespective of valence.
Patterns of gene-body-methylation conservation and its divergent association with gene expression in Pigeonpea and Soybean

Pigeonpea and Soybean are closely related agronomically important legumes that diverged ∼23 million years ago followed by a whole genome duplication event in Soybean. However, the impact of divergence on their epigenomes is not known. Comparative epigenomics is a powerful tool to understand shaping of epigenomes and its functional consequences during evolution. In this study, we investigated the conservation and divergence of Gene body methylation (GbM) and gene-expression patterns between the two species. We compared their genome-wide DNA methylation landscape at single-base resolution and studied the influence of GbM on duplicate gene retention. Our results indicate that during the divergence of Pigeonpea and Soybean, the effects of methylation on gene expression evolved in a heterogeneous manner. GbM features-slow evolution rate and increased length remained conserved in Pigeonpea and Soybean. We also found that contrary to high CG-methylation conservation, non-CG methylated genes remained diverged during evolution due to transposons insertion in adjacent sequences. The methylation differences in paralogs were associated with expression divergence. Notably, we found that variably methylated marks are less likely to target evolutionary conserved sequences. Finally, our findings identify conservation of nitrogen-related genes during evolution, which are promising candidates for epi-alleles for crop improvement.
Genome-wide Screens Identify Lineage- and Tumor Specific-Genes Modulating MHC-I and MHC-II Immunosurveillance in Human Lymphomas

Tumors frequently subvert MHC class I (MHC-I) peptide presentation to evade CD8+ T cell immunosurveillance. To better define the regulatory networks controlling antigen presentation, we employed genome-wide screening in human diffuse large B cell lymphomas (DLBCLs). This approach revealed dozens of novel genes that positively and negatively modulate MHC-I cell surface levels. Identified genes cluster in multiple pathways including cytokine signaling, mRNA processing, endosomal trafficking, and protein metabolism. Many genes exhibit lymphoma subtype- or tumor-specific MHC-I regulation, and a majority of primary DLBCL tumors display genetic alterations in multiple regulators. We establish that the HSP90 co-chaperone SUGT1 is a major positive regulator of both MHC-I and MHC-II cell surface expression. Further, pharmacological inhibition of two negative regulators of antigen presentation, EZH2 and thymidylate synthase, enhances DLBCL MHC-I presentation. These and other genes represent potential targets for manipulating MHC-I immunosurveillance in cancers, infectious diseases, and autoimmunity.
Hormonal regulation of the BRC1-dependent strigolactone transcriptome involved in shoot branching responses

The plant hormone strigolactone (SL) inhibits shoot branching by suppressing the growth of axillary buds. This is thought to occur largely via regulation of the transcription factor BRANCHED1 (BRC1). Here, we clarify the central role of BRC1 and identify additional transcriptional responses by which SL might regulate axillary bud outgrowth in garden pea (Pisum sativum). We used a transcriptomic approach to identify differentially expressed transcripts in pea axillary buds in response to a synthetic SL, rac-GR24. Changes in transcript abundance were confirmed by measuring their response to GR245DS. BRC1 was required for the regulation of over half of the fourteen GR245DS-regulated genes, confirming its role as a mediator of SL transcriptional responses in axillary buds. All, but one, of the BRC1-dependent GR245DS-regulated genes were also regulated by branch-promoting treatments cytokinin (CK) and/or decapitation in an opposing manner to SL. This suggests that SL, CK, and decapitation regulate shoot branching via a common pathway. We used correlational analyses of gene co-expression data to infer a gene regulatory network consisting of nine key co-expression modules correlated with rac-GR24 treatment. Enrichment of GO terms such as cell proliferation, carbohydrate responses, and abscisic acid and jasmonic acid hormone pathways suggest a role for these in SL-mediated inhibition of shoot branching. In summary, we have shown that BRC1 is indeed a key transcriptional regulator of the SL signalling pathway in pea buds as well as a focal point of the SL, CK and decapitation signalling pathways to coordinate shoot branching in pea buds. One Sentence Summary Identification of genes that are strigolactone-responsive and BRC1-dependent in pea buds reveals a high degree of overlap among strigolactone, cytokinin and decapitation response pathways.
Mechanism of BceAB-type transporter: Resistance by lipid II flipping

Treatment of bacterial infections are the great challenge of our era due to the evolved resistance mechanisms against antibiotics. The Achilles heel of bacteria is the cell wall especially during the needs of its synthesis and cell division. Here lipid II is an essential cell wall precursor component synthesized in the cytosol and flipped into the outer leaflet of the membrane prior to its incorporation into the cell wall. Compounds targeting the cell wall or its biosynthesis precursors have been around for decades and have been used as antibiotics against bacterial infections like meningitis, pneumonia and endocarditis. Antimicrobial peptides (AMPs) have proven to be a promising weapon against multiresistant bacteria. However, the Bacitracin efflux (BceAB)-type ATP binding cassette transporters expressed in the membrane of human pathogenic bacteria have been shown to confer resistance to these alternative antibiotics, thereby hampering their medical development. In Streptococcus agalactiae COH1 the BceAB-type transporter NsrFP (SaNsrFP) confers high-level resistance against the antimicrobial peptide nisin, a member of the lantibiotic subfamily. We showed that SaNsrFP provides a novel resistance mechanism by flipping lipid II back into the cytosol, thereby preventing the binding of nisin as well as other lipid II targeting compounds. This is intriguing since a relatively simple reaction mediates resistance to human pathogenic bacteria to lipid II targeting antibiotics, regardless of their structure. Significance Statement The ABC-transporter NsrFP from Streptococcus agalactiae (SaNsrFP) belongs to the BceAB-type transporters. Several BceAB-type transporters are known to confer resistance against multiple antimicrobial peptides. In this study a new resistance mechanism was identified, which is based on the reduction of the number of cell wall precursor lipid II molecules on the cell surface mediated by SaNsrFP. SaNsrFP flips lipid II, which are considered to be the target for many antibiotics, back into the cytoplasm. With this newly gained knowledge about the resistance mechanism of BceAB-type transporters, novel strategies can be established to overcome or bypass this resistance in human pathogenic bacteria.