Miracle-dz/UniFAR-FTUs huggingface dataset:
Older age is associated with a shift from ventral to dorsal PCC in pathways connecting the DMN with visual and limbic areas and a directionality shift in pathways connecting the DMN with sensorimotor areas

Alterations in the default mode network (DMN) are known to associated with aging and with neurological and psychiatric diseases. We assessed age-dependent changes in interactions within the DMN and between the DMN with other brain areas, and correlations of these interactions with a battery of neuropsychological tests to formulate a macroscopic model of ageing. Using a novel multivariate analysis method, enabling determination of directed pathways, on resting-state functional MRI data from fifty young and thirty-one old healthy individuals, we identified directed intra- and inter-DMN directed pathways that differed between the groups and used their correlations with neuropsychological tests to infer their behavioral meaning. Pathways connecting the DMN with visual and limbic regions in old subjects engaged at BOLD low frequency and involved the dorsal PCC. In young subjects, they were at high frequency and involved the ventral PCC. Pathways combining the sensorimotor (SM) and the DMN, were efferent in young subjects (DMNSM). Most inter-DMN pathways in the old subjects, correlated with reduced speed and working memory and, were DMN efferent (DMN>). We suggest a macroscopic model of aging centered in the DMN. It suggests that the reduced sensorimotor efferent, probably brought about from reduced physical activity, and the increased need to control such activities by the mPFC, causes a higher dependency on external versus internal cues. This results in a shift from ventral to dorsal PCC of inter-DMN pathways. Consequently, the model combines physical activity with ageing.
Brain activation by a VR-based motor imagery and observation task: An fMRI study

Training motor imagery (MI) and motor observation (MO) tasks is being intensively exploited to promote brain plasticity in the context of post-stroke rehabilitation strategies. The desired brain plasticity mechanisms may benefit from the use of closed-loop neurofeedback, embedded in brain-computer interfaces (BCIs) to provide an alternative non-muscular channel. These can be further augmented through embodied feedback delivered through virtual reality (VR). Here, we used functional magnetic resonance imaging (fMRI) to map brain activation elicited by a VR-based MI-MO BCI task called NeuRow and compared with a conventional non-VR, and MI-only, task based on the Graz BCI paradigm. We found that, in healthy adults, NeuRow elicits stronger brain activation when compared to the Graz task, as well as to an overt motor execution task, recruiting large portions of the parietal and occipital cortices in addition to the motor and premotor cortices. In particular, NeuRow activates the mirror neuron system (MNS), associated with action observation, as well as visual areas related with visual attention and motion processing. We studied a cohort of healthy adults including younger and older subgroups, and found no significant age-related effects in the measured brain activity. Overall, our findings suggest that the virtual representation of the arms in a bimanual MI-MO task engage the brain beyond conventional MI tasks, even in older adults, which we propose could be explored for effective neurorehabilitation protocols.
iPSC-Derived PSEN2 (N141I) Astrocytes and Microglia Exhibit a Primed Inflammatory Phenotype

Background Widescale evidence points to the involvement of glia and immune pathways in the progression of Alzheimer’s disease (AD). AD-associated iPSC-derived glial cells show a diverse range of AD-related phenotypic states encompassing cytokine/chemokine release, phagocytosis and morphological profiles, but to date studies are limited to cells derived from PSEN1, APOE and APP mutations or sporadic patients. The aim of the current study was to successfully differentiate iPSC-derived microglia and astrocytes from patients harbouring an AD-causative PSEN2 (N141I) mutation and characterise the inflammatory and morphological profile of these cells. Methods iPSCs from three healthy control individuals and three familial AD patients harbouring a heterozygous PSEN2 (N141I) mutation were used to derive astrocytes and microglia-like cells and cell identity and morphology were characterised through immunofluorescent microscopy. Cellular characterisation involved the stimulation of these cells by LPS and Aβ42 and analysis of cytokine/chemokine release was conducted through ELISAs and multi-cytokine arrays. The phagocytic capacity of these cells was then indexed by the uptake of fluorescently labelled fibrillar Aβ42. Results AD-derived astrocytes and microglia-like cells exhibited an atrophied and less complex morphological appearance than healthy controls. AD-derived astrocytes showed increased basal expression of GFAP, S100β and increased secretion and phagocytosis of Aβ42 while AD-derived microglia-like cells showed decreased IL-8 secretion compared to healthy controls. Upon immunological challenge AD-derived astrocytes and microglia-like cells show exaggerated secretion of the pro-inflammatory IL-6, CXCL1, ICAM-1 and IL-8 from astrocytes and IL-18 and MIF from microglia. Conclusion Our study showed, for the first time, the differentiation and characterisation of iPSC-derived astrocytes and microglia-like cells harbouring a PSEN2 (N141I) mutation. PSEN2 (N141I)-mutant astrocytes and microglia-like cells presented with a ‘primed’ phenotype characterised by reduced morphological complexity, exaggerated pro-inflammatory cytokine secretion and altered Aβ42 production and phagocytosis.
Molecular basis of interactions between CaMKII and α-actinin-2 that underlie dendritic spine enlargement

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is essential for long-term potentiation (LTP) of excitatory synapses that is linked to learning and memory. In this study, we focused on understanding how interactions between CaMKIIα and the actin crosslinking protein α-actinin-2 underlie long-lasting changes in dendritic spine architecture. We found that association of the two proteins was unexpectedly elevated following stimulation of NMDA receptors to trigger structural LTP in primary hippocampal neurons. Furthermore, disruption of interactions between the two proteins prevented the accumulation of enlarged mushroom-type dendritic spines following NMDA receptor activation. α-actinin-2 binds to the regulatory segment of CaMKII. Calorimetry experiments, and a crystal structure of α-actinin-2 EF hands 3 and 4 in complex with the CaMKII regulatory segment, indicate that the regulatory segment of autoinhibited CaMKII is not fully accessible to α-actinin-2. Pull-down experiments show that occupation of the CaMKII substrate binding groove by GluN2B markedly increases α-actinin-2 access to the CaMKII regulatory segment. Overall, our study provides new mechanistic insight into the molecular basis of structural LTP and reveals an added layer of sophistication to the function of CaMKII.
The thermal, arched filaments of the radio Arc near the Galactic center: magnetohydrodynamic-induced ionization?

This paper presents a detailed observational study of the most prominent thermal component of the radio Arc located near the Galactic center, the 'arched filaments'. Images produced from data gathered at 6 and 20 cm reveal that the arched filaments have a wispy, flocculent character that is quite different from the uniform, continuous, and almost straight filaments of the nonthermal portion of the Arc. The two systems of filaments show clear signs of interaction at their intersection. There is no evidence from the radio maps that the arched filaments are linked to the Galactic nucleus. Various ideas for the ionization mechanism of the arched filaments are considered. It is suggested that the ionization is caused by a magnetohydrodynamic interaction between a molecular cloud with a large peculiar velocity and an ambient poloidal magnetic field of milligauss strength. 50 refs.
Dynamic organization of cerebellar climbing fiber response and synchrony in multiple functional components reduces dimensions for reinforcement learning

Daynamic functional organization by synchronization is theorized to be essential for dimension reduction of the cerebellar learning space. We analyzed a large amount of coordinate-localized, two-photon imaging data from cerebellar Crus II in mice undergoing “Go/No-go” reinforcement learning. Tensor component analysis revealed that a majority of climbing fiber inputs to Purkinje cells were reduced to only four functional components, corresponding to accurate timing control of motor initiation related to a Go cue, cognitive error-based learning, reward processing, and inhibition of erroneous behaviors after a No-go cue. Spatial distribution of these components coincided well with the boundaries of Aldolase-C/zebrin II expression in Purkinje cells, whereas several components are mixed in single neurons. Synchronization within individual components was bidirectionally regulated according to specific task contexts and learning stages. These findings suggest that the cerebellum, based on anatomical compartments, reduces dimensions by self-organization of components, a feature that may inspire new-generation AI designs.
Predicting distributed working memory activity in a large-scale mouse brain: the importance of the cell type-specific connectome

Recent advances in connectomic and neurophysiological tools make it possible to probe whole-brain mechanisms in the mouse that underlie cognition and behavior. Based on experimental data, we developed a large-scale model of the mouse brain for a cardinal cognitive function called working memory, the brain’s ability to internally hold and process information without sensory input. In the model, interregional connectivity is constrained by mesoscopic connectome data. The density of parvalbumin-expressing interneurons in the model varies systematically across the cortex. We found that the long-range cell type-specific targeting and density of cell classes define working memory representations. A core cortical subnetwork and the thalamus produce distributed persistent activity, and the network exhibits numerous attractor states. Novel cell type-specific graph theory measures predicted the activity patterns and core subnetwork. This work highlights the need for cell type-specific connectomics, and provides a theory and tools to interpret large-scale recordings of brain activity during cognition.
The priming effect of rewarding brain stimulation depends on both the cost and strength of reward

Receipt of an intense reward boosts motivation to work for more of that reward. This phenomenon is called the priming effect of rewards . Using a novel measurement method, we show that the priming effect depends on the cost, as well as on the strength, of the anticipated reward. Previous research on the priming effect of electrical brain stimulation utilized a runway paradigm in which running speed serves as the measure of motivation. In the present study, the speed with which a two-lever response chain was executed in a standard operant-conditioning chamber served as the measure of motivation. In a second experiment, we introduced a modification of our measurement method that entails self-administered priming stimulation and alternating blocks of primed and unprimed trials. Reliable, consistent priming effects of substantial magnitude were obtained in the modified paradigm, which is closely analogous to the runway paradigm.
Efficacy of a between-session homework component delivered digitally for the treatment of adjustment disorders: Results from a pilot randomized clinical trial

Background: Adjustment Disorder (AjD) is one of the most frequently diagnosed mental disorders worldwide. However, there is still no treatment of choice for this problem. One of the first treatment programs specifically designed for AjD is the one presented in this study, a CBT protocol that uses Virtual Reality (VR) to improve patients’ adherence. Another key aspect to improve treatment outcomes is the use of between-sessions homework. However, little is known about how to increase patient engagement with these tasks. The use of Information and Communication Technologies (ICTs) can help patients to see homework as less demanding and provides greater flexibility. A previous study tested the feasibility of TEO (Online Emotional Therapy), a program to implement online homework during treatment. The aim of this study is to present session-to-session efficacy data from the homework assignment component and the patients’ preferences and opinions about this component in both formats (Traditional vs. TEO). Methods: A two-arm pilot randomised clinical trial (RCT) was conducted with 57 patients with AjD. The two groups received the same CBT intervention with VR support, but one group completed homework in the traditional way and the other using TEO. Mood, self-efficacy and positive and negative emotions were measured to test the effect of the homework component in each treatment session. Preferences about the homework format were also assessed before and after treatment. Results: Both types of administration produced significant improvements in mood, self-efficacy and emotional variables after completion of the homework component and before and after each homework session. Effect sizes ranged from small to large, with no differences between groups. Regarding the acceptability of the program, most participants preferred the TEO condition both before starting the treatment and after completing the homework assignment. Overall, participants were satisfied with all homework sessions and found them useful. Again, no significant differences were found between groups. Conclusion: This is the first time that the effect of an online homework program during AjD treatment has been tested. It is proposed that this way of implementing homework could be as effective as the traditional format, but would be preferred by patients. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02452411
Cooperation between cGAS and RIG-I sensing pathways enables improved innate recognition of HIV-1 by myeloid dendritic cells in elite controllers

Introduction Spontaneous control of HIV-1 replication in the absence of anti-retroviral therapy (ART) naturally occurs in a small proportion of HIV-1-infected individuals known as elite controllers (EC), likely as a result of improved innate and adaptive immune mechanisms. Previous studies suggest that enhanced cytosolic immune recognition of HIV-1 reverse transcripts in conventional dendritic cells (mDC) from EC enables effective induction of antiviral effector T cell responses. However, the specific molecular circuits responsible for such improved innate recognition of HIV-1 in mDC from these individuals remain unknown. Results and methods Here, we identified a subpopulation of EC whose mDC displayed higher baseline abilities to respond to intracellular HIV-1 dsDNA stimulation. A computational analysis of transcriptional signatures from such high responder EC, combined with functional studies, suggested cytosolic recognition of HIV-1 dsDNA by cGAS, combined with sensing of viral mRNA by RIG-I after polymerase III-mediated HIV-1 DNA transcription. Discussion Together, our work identifies collaborative networks of innate sensing pathways that enhance cell-intrinsic abilities of mDC to induce antiviral innate responses against HIV-1; these observations might be useful for the therapeutic induction of effective antiviral immune responses.
Motoric performance variation from morning to evening: 80% intensity post-activation potentiation protocol impacts performance and its diurnal amplitude in basketball players

Introduction Post-activation potentiation (PAP) can be defined as the acute enhancement in muscle performance after preload stimulation that occurs during strength exercises or warm-up protocols, and the contractile history of any muscle group can directly influence the presented performance. The purpose of this study was to compare the results of motoric performance tests carried out at two different times of the day using three different PAP protocols. Methods Thirty-two male basketball players with at least 2 years of training experience and who competed at the national level were recruited for this study [age: 21.80 ± 1.91 years; body height: 178.40 ± 6.85 cm; body mass: 72.50 ± 7.16 kg; body mass index (BMI): 22.81 ± 2.28]. After control and experimental-specific warm-up (SWU) sessions, participants completed a countermovement jump (CMJ) and seated medicine ball throw (SMBT). The SWU protocol was developed based on the athlete’s typical warm-up routine. The experimental warm-ups included the same exercises as the SWU, with one set of bench presses for five repetitions at 80% (80% PAP) and one repetition at 100% of 1 RM (100% PAP). Each of the protocols consists of 15 min. The SWU and experimental warm-up sessions were completed in a random, counterbalanced order, completed in a period of 3-weeks. Results According to the research findings, carrying out the protocols in the evening led to a larger improvement in SMBT than in the morning (F = 35.94, p < 0.001, η2p = 0.537). Additionally, the SMBT results were statistically more significant in the group that received 80% PAP compared to the SWU (p = 0.034), and the SMBT results were also higher in the group that received 100% PAP compared to the SWU (p = 0.002). Furthermore, the interaction effect (time × PAP) was statistically significant in SMBT (F = 6.39, p = 0.003, η2p = 0.17). Discussion These results may provide more particular recommendations than previously thought to basketball coaches for the planning of basketball-specific PAP exercises prior to the start of training programs.
The effect of malaria on childhood anemia in a quasi-experimental study of 7,384 twins from 23 Sub-Saharan African countries

Background Young children in Sub-Saharan Africa (SSA), particularly those from resource-limited settings, are heavily burdened by anemia and malaria. While malaria infected children frequently become anemic (hemoglobin < 110 g/L), anemia is a strongly multifactorial disease with many other risk factors than malaria. Due to the complex and often overlapping contributors to anemia, it remains challenging to isolate the true impact of malaria on population level hemoglobin concentrations. Methods We quantified the malaria-induced effect on hemoglobin levels in children under 5 years of age, leveraging data from 7,384 twins and other multiples, aged 6 to 59 months, from 57 nationally representative Demographic and Health Surveys (DHSs) from 23 SSA countries from 2006 to 2019. The quasi-experimental twin fixed-effect design let us minimize the impact of potential confounders that do not vary between twins. Results Our analyses of twins revealed a malaria-induced hemoglobin decrease in infected twins of 9 g/L (95% CI -10; -7, p<0.001). The relative risk of severe anemia was higher (RR = 3.01, 95% CI 1.79; 5.1, p<0.001) among malaria positive children, compared to malaria negative children. Conversely, malaria positive children are only half as likely to be non-anemic (RR = 0.51, 95% CI 0.43; 0.61, p<0.001). Conclusion Even after rigorous control for confounding through a twin fixed-effects study design, malaria substantially decreased hemoglobin levels among SSA twins, rendering them much more susceptible to severe anemia. This effect reflects the population-level effect of malaria on anemia.
Fault-Tolerant Tracking Control of Spacecraft with Attitude-Only Measurement Under Actuator Failures

This paper investigates the velocity-measurement-free feedback control problem associated with attitude tracking for a rigid spacecraft in the presence of both actuator failures and actuator saturation. The decreased reaction torque fault and the increased bias torque fault in the reaction wheel are handled. By using only the measurable attitude, a terminal sliding-mode-based observer is developed to reconstruct all the states of the attitude system in finite time. With the reconstructed information, a novel attitude tracking controller is developed. A Lyapunov analysis shows that the desired attitude trajectories are followed even in the presence of external disturbances. The key features of the proposed control approach are that it is independent from the knowledge of actuator faults and fault-tolerant control is achieved without the need of angular velocity. The attitude tracking performance using the proposed strategy is evaluated through a numerical example.
Development and function of natural TCR+ CD8αα+ intraepithelial lymphocytes

The complexity of intestinal homeostasis results from the ability of the intestinal epithelium to absorb nutrients, harbor multiple external and internal antigens, and accommodate diverse immune cells. Intestinal intraepithelial lymphocytes (IELs) are a unique cell population embedded within the intestinal epithelial layer, contributing to the formation of the mucosal epithelial barrier and serving as a first-line defense against microbial invasion. TCRαβ+ CD4- CD8αα+ CD8αβ- and TCRγδ+ CD4- CD8αα+ CD8αβ- IELs are the two predominant subsets of natural IELs. These cells play an essential role in various intestinal diseases, such as infections and inflammatory diseases, and act as immune regulators in the gut. However, their developmental and functional patterns are extremely distinct, and the mechanisms underlying their development and migration to the intestine are not fully understood. One example is that Bcl-2 promotes the survival of thymic precursors of IELs. Mature TCRαβ+ CD4- CD8αα+ CD8αβ- IELs seem to be involved in immune regulation, while TCRγδ+ CD4- CD8αα+ CD8αβ- IELs might be involved in immune surveillance by promoting homeostasis of host microbiota, protecting and restoring the integrity of mucosal epithelium, inhibiting microbiota invasion, and limiting excessive inflammation. In this review, we elucidated and organized effectively the functions and development of these cells to guide future studies in this field. We also discussed key scientific questions that need to be addressed in this area.
Post-transplant lymphoproliferative disease after pediatric kidney transplant

Post-transplant lymphoproliferative disease (PTLD) is the most common malignancy complicating solid organ transplantation (SOT) in adults and children. PTLD encompasses a spectrum of histopathologic features and organ involvement, ranging from benign lymphoproliferation and infectious-mononucleosis like presentation to invasive neoplastic processes such as classical Hodgkin lymphoma. The predominant risk factors for PTLD are Epstein-Barr virus (EBV) serostatus at the time of transplant and the intensity of immunosuppression following transplantation; with EBV-negative recipients of EBV-positive donor organs at the highest risk. In children, PTLD commonly presents in the first two years after transplant, with 80% of cases in the first year, and over 90% of cases associated with EBV-positive B-cell proliferation. Though pediatric kidney transplant recipients are at lower risk (1–3%) for PTLD compared to their other SOT counterparts, there is still a significant risk of morbidity, allograft failure, and an estimated 5-year mortality rate of up to 50%. In spite of this, there is no consensus for monitoring of at-risk patients or optimal management strategies for pediatric patients with PTLD. Here we review pathogenesis and risk factors for the development of PTLD, with current practices for prevention, diagnosis, and management of PTLD in pediatric kidney transplant recipients. We also highlight emerging concepts, current research gaps and potential future developments to improve clinical outcomes and longevity in these patients.