Miracle-dz/UniFAR-FTUs huggingface dataset:
Divergent sensory processing converges in frontal cortex for a planned motor response

Purposeful behavior requires planning of actions based on external information. However, neuronal mechanisms converting sensory input into a motor plan remain elusive. Here, we combined wide-field calcium imaging, multi-area single-neuron recordings and focal optogenetic inactivation to reveal the precise sequence of cortical activity transforming sensory information into motor planning in mice trained to respond to a brief whisker stimulus by licking after a delay. We found that upon learning, the sensory information, initially highly-localized, rapidly spreads to diverse motor and higher-order areas, together with transient deactivation of orofacial regions, converging during the delay period to a focalized region of the frontal cortex. The secondary whisker motor cortex (wM2) appears as a key relay of this sensorimotor transformation, showing the earliest learning-enhanced response to the whisker stimulus. Our results suggest a specific cortical circuit with wM2 acquiring a pivotal role in transforming whisker information into preparatory activity for goal-directed motor planning. Highlights Cortex-wide, task-epoch specific causal neuronal dynamics of sensorimotor learning Sensory information converges to a focal frontal region critical for delay-response Orofacial cortex acquired an inhibitory response with delayed lick learning Secondary whisker motor cortex is a key node converting whisker input to lick plan
NAP-CNB: Bioinformatic pipeline to predict MHC-I-restricted T cell epitopes in mice

Motivation Lack of a dedicated integrated pipeline for neoantigen discovery in mice hinders cancer immunotherapy research. Novel sequential approaches through recurrent neural networks can improve the accuracy of T-cell epitope immunogenicity predictions in mice and a simplified variant selection process can reduce operational requirements. Results We have developed a web server tool (NAP-CNB) for a full and automatic pipeline, based on recurrent neural networks, able to predict putative neoantigens from tumoral RNA sequencing reads. The developed software is able to estimate H-2 peptide ligands, with an AUC of 0.95, directly from tumor samples. As a proof-of-concept, we used the B16 melanoma model to test the predictive capabilities of the system and we report its putative neoantigens. Availability and implementation NAP-CNB web server is freely available at http://biocomp.cnb. csic.es/NeoantigensApp/ with scripts and datasets accessible through the download section.
Forest Fire Severity Patterns of Resource Objective Wildfires in the Southern Sierra Nevada

Distinguishing favorable versus undesirable outcomes of wildland fires in coniferous forest ecosystems is challenging and requires a clear and objective approach. I applied the natural range of variation (NRV) concept and used fire severity indicators to evaluate the possible effects of wildfires managed for resource benefits (hereafter “resource objective wildfires”) in four national forests of the southern Sierra Nevada, California. Results indicated that resource objective wildfires in coniferous forests were overwhelmingly within the NRV with respect to fire severity proportions and mean and maximum high-severity patch size. These results suggest that the continued and expanded use of resource objective wildfires, including the establishment of “demonstration firesheds” within and across administrative boundaries, has the potential to vastly increase the scale of regional forest restoration efforts in the western United States.
The Effects of Social Stress on Memory: If, How and When

Physical stress, such as from the cold-pressor test, has been robustly associated with altered memory retrieval, but it is not yet clear whether the same happens following psychosocial stress. Studies using psychosocial stressors report mixed effects on memory, leading to uncertainty about the common cognitive impact of both forms of stress. The current study uses a stepped replication design, with four near-identical experiments, each differing by a single critical factor. In three experiments we induced psychosocial stress after participants encoded word stimuli, then assessed retrieval after a prolonged delay. These experiments found no group level influence of postencoding stress on recognition of neutral words or cued recall of word-pairs, but a small effect on recollection of semantically-related words. There was, however, some indication of positive relationships within the stress group between measures of stress (cortisol in experiment 1 and self-reported-anxiety in experiment 3) and recollection of single word stimuli. In the fourth experiment, we found that psychosocial stress immediately before retrieval did not influence word recognition. Overall, our findings demonstrate that psychosocial stress has a typically modest impact on memory, lower than previously claimed, but that individual differences in stress responsivity, particularly for tasks that tap recollection, may help to explain variability in previous findings.
Dynamic and reversible remapping of network representations in an unchanging environment

In response to environmental changes, the medial entorhinal cortex alters its single-cell firing properties. This flexibility in neural coding is hypothesized to support navigation and memory by dividing sensory experience into unique contextual episodes. However, it is unknown how the entorhinal circuit transitions between different representations, particularly when sensory information is not delineated into discrete contexts. Here, we describe spontaneous and abrupt transitions between multiple spatial maps of an unchanging task and environment. These remapping events were synchronized across hundreds of medial entorhinal neurons and correlated with changes in running speed. While remapping altered spatial coding in individual neurons, we show that features of the environment were statistically preserved at the population-level, enabling simple decoding strategies. These findings provoke a reconsideration of how medial entorhinal cortex dynamically represents space and broadly suggest a remarkable capacity for higher-order cortical circuits to rapidly and substantially reorganize their neural representations.
Phenotypic Differences in Adult and Fetal Dermal Fibroblast Responses to Mechanical Tension

Objective Fetal regenerative wound healing is characterized by hyaluronan(HA)-rich microenvironment and fibroblasts that produce pericellular matrices(PCM) abundant in high molecular weight HA. Recent studies showed that while small wounds in fetal skin heal regeneratively, large wounds heal with fibrosis. We posit large wounds generate higher mechanical tension which alters HA metabolism in the fetal fibroblasts and lead to a pro-fibrotic phenotype. Approach C57BL/6J murine fetal (FFB; E14.5) and adult (AFB; 8wk) dermal fibroblasts were subjected to +/-10% tonic strain. Changes in PCM, HA enzymes and molecular weight, and fibrotic gene expression were measured. Results FFB pericellular matrix reduced upon exposure to increased tension, and the HA profile shifted from high to lower molecular weight. Under static conditions, AFB had higher expression of HA synthases (HAS) 1 and 2 and degradation enzymes KIAA1199, HYAL1, and TMEM2 than FFB, suggesting more HA turnover in AFB. Tension resulted in an increase in HAS1, HAS3, KIAA1199, and HYAL2 expression and a decrease in HAS2 and TMEM2 expression in FFB. CD26, a marker associated with scar production, increased in FFB under tension, along with altered fibrotic gene expression profile and reorganized cytoskeletal f-actin and increased α-SMA that resembled AFB. Innovation This study elucidates the differences in how biomechanical tension alters HA metabolism and fibrotic phenotype of FFB vs AFB, providing further understanding of the fetal regenerative wound healing phenotype. Conclusion Understanding the intrinsic differences in HA metabolism and fibrotic phenotype among FFB and AFB in response to wound mechanical stimuli may yield new insights to promote regenerative wound healing.
Involvement of the Postrhinal and Perirhinal Cortices in Microscale and Macroscale Visuospatial Information Encoding

Whereas the postrhinal cortex (POR) is a critical center for the integration of egocentric and allocentric spatial information, the perirhinal cortex (PRC) plays an important role in the encoding of objects that supports spatial learning. The POR and PRC send afferents to the hippocampus, a structure that builds complex associative memories from the spatial experience. Hippocampal encoding of item-place experience is accompanied by the nuclear expression of immediate early gene (IEGs). Subfields of the Cornus ammonius and subregions of the hippocampus exhibit differentiated and distinct encoding responses, depending on whether the spatial location and relationships of large highly visible items (macroscale encoding) or small partially concealed items (microscale encoding), is learned. But to what extent the PRC and POR support hippocampal processing of different kinds of item-place representations is unclear. Using fluorescence in situ hybridization (FISH), we examined the effect of macroscale (overt, landmark) and microscale (subtle, discrete) item-place learning on the nuclear expression of the IEG, Arc. We observed an increase in Arc mRNA in the caudal part of PRC area 35 and the caudal part of the POR after macroscale, but not microscale item-place learning. The caudal part of PRC area 36, the rostral and middle parts of PRC areas 35 and 36, as well as the middle part of the POR responded to neither type of item. These results suggest that macroscale items may contain a strong identity component that is processed by specific compartments of the PRC and POR. In contrast small, microscale items are not encoded by the POR or PRC, indicating that item dimensions may play a role in the involvement of these structures in item processing.
Structural Brain Imaging Predicts Individual-Level Task Activation Maps Using Deep Learning

Accurate individual functional mapping of task activations is a potential tool for biomarker discovery and is critically important for clinical care. While structural imaging does not directly map task activation, we hypothesized that structural imaging contains information that can accurately predict variations in task activation between individuals. To this end, we trained a convolutional neural network to use structural imaging (T1-weighted, T2-weighted, and diffusion tensor imaging) to predict 47 different functional MRI task activation volumes across seven task domains. The U-Net model was trained on 654 subjects and then subsequently tested on 122 unrelated subjects. The predicted activation maps correlated more strongly with their actual maps than with the maps of the other test subjects. An ablation study revealed that a model using the shape of the cortex alone or the shape of the subcortical matter alone was sufficient to predict individual-level differences in task activation maps, but a model using the shape of the whole brain resulted in markedly decreased performance. The ablation study also showed that the additional information provided by the T2-weighted and diffusion tensor imaging strengthened the predictions as compared to using the T1-weighted imaging alone. These results indicate that structural imaging contains information that is predictive of inter-subject variability in task activation mapping and cortical folding patterns as well as microstructural features may be a key component to linking brain structure to brain function.
A new crocodylid from the middle Miocene of Kenya and the timing of crocodylian faunal change in the late Cenozoic of Africa

Abstract. Brochuchus is a small crocodylid originally based on specimens from the early Miocene of Rusinga Island, Lake Victoria, Kenya. Here, we report occurrences of Brochuchus from several early and middle Miocene sites. Some are from the Lake Victoria region, and others are in the Lake Turkana Basin. Specimens from the middle Miocene Maboko locality form the basis of a new species, Brochuchus parvidens, which has comparatively smaller maxillary alveoli. Because of the smaller alveoli, the teeth appear to be more widely spaced in the new species. We also provide a revised diagnosis for Brochuchus and its type species, B. pigotti. A phylogenetic analysis supports a close relationship between Brochuchus and tube-snouted Euthecodon, but although relationships among crocodylids appear poorly resolved in the set of optimal trees, this is because Brochuchus and Euthecodon, along with early Miocene “Crocodylus” gariepensis from the early Miocene of Namibia, jointly adopt two distinct positions—either closely related to the living sharp-nosed crocodile (Mecistops) or to a group including the living dwarf crocodiles (Osteolaemus). Character support for a close relationship with Mecistops is problematic, and we suspect a closer relationship to Osteolaemus will be recovered with improved sampling, but the results here are ambiguous. In either case, Brochuchus is more closely related to living groups not currently found in East Africa. This material helps constrain the timing of crocodylian faunal turnover in the East African Rift Valley System, with endemic lineages largely being replaced by Crocodylus in the middle or late Miocene possibly in response to regional xerification and the replacement of continuous rainforest cover with open grasslands and savannas.
Whose Data? Which Rights? Whose Power? A Policy Discourse Analysis of Student Privacy Policy Documents

ABSTRACT The proliferation of information technology tools in higher education has resulted in an explosion of data about students and their contexts. Yet, current policies governing these data are limited in their usefulness for informing students, instructors, and administrators of their rights and responsibilities related to data use because they are based on antiquated conceptions of data and data systems. To understand how data privacy policies conceptualize and represent data, privacy, student agency, and institutional power, we conducted a policy discourse analysis of 151 university policy statements related to student information privacy and the responsible use of student data from 78 public and private post-secondary institutions in the U.S. Three common discourses emerged: educational records are static artifacts, privacy solutions are predicated upon institutional responsibility and student agency, and legitimate educational interest in data are institutionally defined and broadly applied. We explore the assumptions, biases, silences, and consequences of these discourses and offer counter- discourses to begin a foundation for the development of privacy policies in a new data age.
Joint estimation of neural sources and their functional connections from MEG data

Current techniques to estimate directed functional connectivity from magnetoencephalography (MEG) signals involve two sequential steps; 1) Estimation of the sources and their amplitude time series from the MEG data by solving the inverse problem, and 2) fitting a multivariate autoregressive (MVAR) model to these time series for the estimation of AR coefficients, which reflect the directed interactions between the sources. However, such a sequential approach is not optimal since i) source estimation algorithms typically assume that the sources are independent, ii) the information provided by the connectivity structure is not used to inform the estimation of source amplitudes, and iii) the limited spatial resolution of source estimates often leads to spurious connectivity due to spatial leakage. Here, we present an algorithm to jointly estimate the source and connectivity parameters using Bayesian filtering, which does not require anatomical constraints in form of structural connectivity or a-priori specified regions-of-interest. By formulating a state-space model for the locations and amplitudes of a given number of sources, we show that estimation of functional connectivity can be reduced to a system identification problem. We derive a solution to this problem using a variant of the expectation–maximization (EM) algorithm known as stochastic approximation EM (SAEM). Compared to the traditional two-step approach, the joint approach using the SAEM algorithm provides a more accurate reconstruction of connectivity parameters, which we show with a connectivity benchmark simulation as well as with an electrocorticography-based simulation of MEG data. Using real MEG responses to visually presented faces in 16 subjects, we also demonstrate that our method gives source and connectivity estimates that are both physiologically plausible and largely consistent across subjects. In conclusion, the proposed joint-estimation approach based on the SAEM algorithm outperforms the traditional two-step approach in determining functional connectivity structure in MEG data.
Depauperate Fish Faunas of Sinking Creeks near Mammoth Cave, Kentucky

Sinking creeks south of Mammoth Cave, Kentucky contain reduced numbers of fish species compared to similar normal streams. Several headwater species remain and some human introductions are present. However, shiner minnows (Notropis), suckers (Catostomidae), and darters (Etheostomatini), are absent, though common in nearby normal streams. As in normal streams, species numbers increase with rising stream order, but the total fish fauna is only 13 species. Most fishes seen in the large subterranean streams in Mammoth Cave probably enter from the nearby Green River. However, the creek chub, Semotilus atromaculatus, could be brought into these streams from tributary sinking creeks. Northern swamp fish, Chologaster agassizii, found in Mammoth Cave are considered to be strays from the sinking creeks and Sinkhole Plain regions, because of inadequacies of the local habitat for supporting breeding populations.
A triresidue motif in the GLUTAMATE RECEPTOR-LIKE 3.3 C-tail interacts with IMPAIRED SUCROSE INDUCTION 1 and controls long distance wound signaling

Arabidopsis Clade 3 GLUTAMATE RECEPTOR-LIKE (GLRs) genes are primary players in wound-induced electrical signaling and jasmonate-activated defense responses. As cation-permeable ion channels, previous studies have focused on resolving their gating properties and structures. However, little is known regarding to the regulatory mechanism of these channel proteins. Here, we report that the C-tail of GLR3.3 contains key elements that control its function in long distance wound signaling. GLR3.3 without its C-tail failed to rescue the glr3.3a mutant. To further investigate the underlying mechanism, we performed a yeast two-hybrid screen. IMPAIRED SUCROSE INDUCTION 1 (ISI1) was identified as an interactor with both the C-tail and the full-length GLR3.3 in planta. Reduced function isi1 mutants had enhanced electrical activity and jasmonate-regulated defense responses. Furthermore, we found that a triresidue motif RFL (R884, F885 and L886) in the GLR3.3 C-tail is essential for interacting with ISI1. RFL mutation abolished GLR3.3 function in electrical signaling and jasmonate-mediated defense gene activation. Our study shows the importance of the C-tail in GLR3.3 function, and reveals parallels with the ipnotropic glutamate receptor regulation in animal cells.
Lipid anchoring and electrostatic interactions target the phospholipase NOT-LIKE-DAD to pollen endo-plasma membrane

Phospholipases are ubiquitous enzymes that cleave phospholipids, one major constituent of membranes. They are thus essential for many developmental processes, including male gamete development. In flowering plants, mutation of phospholipase NOT-LIKE-DAD (NLD) leads to peculiar defects in sexual reproduction. Indeed, pollination of a wild-type female with mutant pollen generates haploid embryos containing solely maternal genetic information. Contrary to previous reports NLD does not localize to cytosol and plasma membrane (PM) of sperm cells but to the pollen endo-plasma membrane (endo-PM), a specific membrane derived from the PM of the pollen vegetative cell that encircles the two sperm cells. Pharmacological approaches coupled with targeted mutagenesis revealed that lipid anchoring together with electrostatic interactions between membrane and NLD are involved in the attachment of NLD to this atypical endo-PM. Membrane surface-charge and anionic lipid bio-sensors indicated that phosphatidylinositol-4,5-bisphosphate (PIP(4,5)P2) is enriched in the endo-PM as compared to the PM. Our results uncover a unique example of how membrane electrostatic properties can specify a unique polar domain (i.e. endo-PM), which is critical for plant reproduction and gamete formation.
GABA quantification in human anterior cingulate cortex

γ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the human brain. It has been shown that altered GABA concentration plays an important role in a variety of psychiatric and neurological disorders. The main purpose of this study was to propose a combination of PRESS and MEGA-PRESS acquisitions for absolute GABA quantification and to compare GABA estimations obtained using total choline (tCho), total creatine (tCr), and total N-acetyl aspartate (tNAA) as the internal concentration references with water referenced quantification. The second aim was to demonstrate the fitting approach of MEGA-PRESS spectra with QuasarX algorithm using a basis set of GABA, glutamate, glutamine, and NAA in vitro spectra. Thirteen volunteers were scanned with the MEGA-PRESS sequence at 3T. Interleaved water referencing was used for quantification, B0 drift correction and to update the carrier frequency of RF pulses in real time. Reference metabolite concentrations were acquired using a PRESS sequence with short TE (30 ms) and long TR (5000 ms). Absolute concentration were corrected for cerebrospinal fluid, gray and white matter water fractions and relaxation effects. Water referenced GABA estimations were significantly higher compared to the values obtained by metabolite references. We conclude that QuasarX algorithm together with the basis set of in vitro spectra improves reliability of GABA+ fitting. The proposed GABA quantification method with PRESS and MEGA-PRESS acquisitions enables the utilization of tCho, tCr, and tNAA as internal concentration references. The use of different concentration references have a good potential to improve the reliability of GABA estimation.
Sex differences in lifespan trajectories and variability of human sulcal and gyral morphology

Sex differences in development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants two scans, 104 three scans, age range: 16-70 years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40 years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. While hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and thickness and lower variability for sulcal width. Across sexes, variability decreased with age for all measures except for cortical volume and thickness. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions.