Miracle-dz/UniFAR-FTUs huggingface dataset:
Failure to modulate reward prediction errors in declarative learning with theta (6 Hz) frequency transcranial alternating current stimulation

Recent evidence suggests that reward prediction errors (RPEs) play an important role in declarative learning, but its neurophysiological mechanism remains unclear. Here, we tested the hypothesis that RPEs modulate declarative learning via theta-frequency oscillations, which have been related to memory encoding in prior work. For that purpose, we examined the interaction between RPE and transcranial Alternating Current Stimulation (tACS) in declarative learning. Using a between-subject (real versus sham stimulation group), single-blind stimulation design, 76 participants learned 60 Dutch-Swahili word pairs, while theta-frequency (6 Hz) tACS was administered over the medial frontal cortex (MFC). Previous studies have implied MFC in memory encoding. We replicated our previous finding of signed RPEs (SRPEs) boosting declarative learning; with larger and more positive RPEs enhancing memory performance. However, tACS failed to modulate the SRPE effect in declarative learning and did not affect memory performance. Bayesian statistics supported evidence for an absence of effect. Our study confirms a role of RPE in declarative learning, but also calls for standardized procedures in transcranial electrical stimulation.
Physioxia stimulates extra-cellular matrix deposition and increases mechanical properties of human chondrocyte-derived tissue-engineered cartilage

Cartilage tissue has been recalcitrant to tissue engineering approaches. In this study, human chondrocytes were formed into self-assembled cartilage sheets, cultured in physiologic (5%) and atmospheric (20%) oxygen conditions and underwent biochemical, histological and biomechanical analysis at one- and two-months. The results indicated that sheets formed at physiological oxygen tension were thicker, contained greater amounts of glycosaminoglycans (GAGs) and type II collagen, and had greater compressive and tensile properties than those cultured in atmospheric oxygen. In all cases, cartilage sheets stained throughout for extracellular matrix components. Type II-IX-XI collagen heteropolymer formed in the neo-cartilage and fibrils were stabilized by trivalent pyridinoline cross-links. Collagen cross-links were not significantly affected by oxygen tension but increased with time in culture. Physiological oxygen tension and longer culture periods both served to increase extracellular matrix components. The foremost correlation was found between compressive stiffness and the GAG to collagen ratio. Summary Tissue-engineered cartilage formed from human articular chondrocytes produces thicker, stiffer, more extracellular-matrix rich cartilage tissue when grown under physiological (5%) vs. atmospheric oxygen (20%) tension.
Somatosensory versus cerebellar contributions to proprioceptive changes associated with motor skill learning: A theta burst stimulation study

Background It is well established that proprioception (position sense) is important for motor control, yet its role in motor learning and associated plasticity is not well understood. We previously demonstrated that motor skill learning is associated with enhanced proprioception and changes in sensorimotor neurophysiology. However, the neural substrates mediating these effects are unclear. Objective To determine whether suppressing activity in the cerebellum and somatosensory cortex (S1) affects proprioceptive changes associated with motor skill learning. Methods 54 healthy young adults practiced a skill involving visually-guided 2D reaching movements through an irregular-shaped track using a robotic manipulandum with their right hand. Proprioception was measured using a passive two-alternative choice task before and after motor practice. Continuous theta burst stimulation (cTBS), was delivered over S1 or the cerebellum (CB) at the end of training for two consecutive days. We compared group differences (S1, CB, Sham) in proprioception and motor skill, quantified by a speed-accuracy function, measured on a third consecutive day (retention). Results As shown previously, the Sham group demonstrated enhanced proprioceptive sensitivity after training and at retention. The S1 group had impaired proprioceptive function at retention through online changes during practice, whereas the CB group demonstrated offline decrements in proprioceptive function. All groups demonstrated motor skill learning, however, the magnitude of learning differed between the CB and Sham groups, consistent with a role for the cerebellum in motor learning. Conclusion Overall, these findings suggest that the cerebellum and S1 are important for distinct aspects of proprioceptive changes during skill learning.
Optimal policy for attention-modulated decisions explains human fixation behavior

Traditional accumulation-to-bound decision-making models assume that all choice options are processed simultaneously with equal attention. In real life decisions, however, humans tend to alternate their visual fixation between individual items in order to efficiently gather relevant information [46, 23, 21, 12, 15]. These fixations also causally affect one’s choices, biasing them toward the longer-fixated item [38, 2, 25]. We derive a normative decision-making model in which fixating a choice item boosts information about that item. In contrast to previous models [25, 39], we assume that attention enhances the reliability of information rather than its magnitude, consistent with neurophysiological findings [3, 13, 29, 45]. Furthermore, our model actively controls fixation changes to optimize information gathering. We show that the optimal model reproduces fixation patterns and fixation-related choice biases seen in human decision-makers, and provides a Bayesian computational rationale for the fixation bias. This insight led to additional behavioral predictions that we confirmed in human behavioral data. Finally, we explore the consequences of changing the relative allocation of cognitive resources to the attended versus the unattended item, and show that decision performance is benefited by a more balanced spread of cognitive resources.
Light Stimuli and Circadian Clock Affect Neural Development in Drosophila melanogaster

Endogenous clocks enable organisms to adapt their physiology and behavior to daily variation in environmental conditions. Metabolic processes in cyanobacteria to humans are effected by the circadian clock, and its dysregulation causes metabolic disorders. In mouse and Drosophila were shown that the circadian clock directs translation of factors involved in ribosome biogenesis and synchronizes protein synthesis. However, the role of clocks in Drosophila neurogenesis and the potential impact of clock impairment on neural circuit formation and function is less understood. Here we demonstrate that light stimuli or circadian clock causes a defect in neural stem cell growth and proliferation accompanied by reduced nucleolar size. Further, we define that light and clock independently affect the InR/TOR growth regulatory pathway due to the effect on regulators of protein biosynthesis. Altogether, these data suggest that alterations in growth regulatory pathways induced by light and clock are associated with impaired neural development.
Dynamic correlations help prefrontal ensembles transmit 1 information about social behavior

How neurons encode behavior is a fundamental question. Neuronal ensembles increase or 16 decrease activity during specific behaviors. However, it is unclear whether ensembles encode 17 information solely via changes in activity levels, or whether changes in correlations between 18 neurons carry additional information. We used microendoscopic GCaMP imaging to measure 19 prefrontal activity while mice were either alone or engaged in social interaction. Using neural 20 network classifiers to measure how well prefrontal neurons transmit information about social 21 behavior to downstream neurons, we find that surrogate datasets which preserve dynamic 22 correlations outperform those which preserve ensemble activity but not correlations. Notably, 23 this ability of correlations to enhance the information transmitted by neuronal ensembles is lost 24 in mice lacking the autism-associated gene Shank3. These results show that dynamically 25 modulated correlations create patterns of coactive neurons which are behaviorally-specific and 26 enhance the information transmitted by neuronal ensembles. Furthermore, this process can be 27 disrupted in pathological states. 28
Macrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFβ1 after myocardial infarction

Macrophages produce factors that participate in cardiac repair and remodeling after myocardial infarction (MI); however, how these factors crosstalk with other cell types mediating repair is not fully understood. In this study, we demonstrated that cardiac macrophages increased expression of Mmp14 (MT1-MMP) 7 days post-MI. Specific macrophage-targeting of MT1-MMP (MT1-MMPΔLysM mice) attenuates post-MI cardiac dysfunction, reduces fibrosis, and preserves the cardiac capillary network. Mechanistically, we showed that MT1-MMP activates latent TGFβ1 in macrophages, leading to paracrine SMAD2-mediated signaling in endothelial cells and endothelial-to-mesenchymal transition (EndMT). Post-MI MT1-MMPΔLysM hearts contained fewer cells undergoing EndMT than their wild-type counterparts, and MT1-MMP-deficient macrophages showed a reduced ability to induce EndMT in co-cultures with endothelial cells. Our results demonstrate the contribution of EndMT to cardiac fibrosis and adverse remodeling post-MI and identify macrophage MT1-MMP as a key regulator of this process. The identified mechanism has potential as a therapeutic target in ischemic heart disease.
The DNA mimic protein BCAS0292 is involved in the regulation of virulence of Burkholderia cenocepacia

Adaptation of opportunistic pathogens to their host environment requires reprogramming of a vast array of genes to facilitate survival in the host. Burkholderia cenocepacia, a Gram-negative bacterium that colonizes environmental niches, is exquisitely adaptable to the hypoxic environment of the cystic fibrosis lung and survives in macrophages. B. cenocepacia possesses a large genome encoding multiple virulence systems, stress response proteins and a large locus that responds to low oxygen. We previously identified BCAS0292, an acidic protein encoded on replicon 3. Deletion of the BCAS0292 gene resulted in altered abundance of >1000 proteins; 46 proteins became undetectable while 556 proteins showed ≥1.5-fold reduced abundance, suggesting BCAS0292 is a global regulator. Moreover, the ΔBCAS0292 mutant showed a range of pleiotropic effects: virulence, host-cell attachment and motility were reduced, antibiotic susceptibility was altered and biofilm formation enhanced. Its growth and survival were impaired in 6% oxygen. Structural analysis revealed BCAS0292 presents a dimeric β-structure with a negative electrostatic surface. Further, the ΔBCAS0292 mutant displayed altered DNA supercoiling, implicated in global regulation of gene expression. We propose that BCAS0292 acts as a DNA-mimic, altering DNA topology and regulating the expression of multiple genes, thereby enabling the adaptation of B. cenocepacia to highly diverse environments.
Astroglia in lateral habenula is essential for antidepressant efficacy of light

Successful antidepressant (AD) treatments are still difficult to achieve. Recently, bright light stimulation (BLS) was shown effective in non-seasonal depression but its mode of action remains elusive. We demonstrate here, using a new mouse model of depression resistant to ADs including ketamine, that chemogenetic activation of lateral habenula (LHb) astroglia prevented the potentiating effect of BLS on the AD response. Additionally, the beneficial action of BLS was associated with upregulation of a specific part of the prefrontal cortex opioid system. These results show that improved behavioral outcome produced by BLS requires habenular astroglia and endogenous opioids as crucial buffer systems.
Rhesus Cytomegalovirus-Specific CD8+ Cytotoxic T Lymphocytes Do Not Become Functionally Exhausted in Chronic SIVmac239 Infection

CD8+ cytotoxic T lymphocytes (CTLs) exert potent antiviral activity after HIV/SIV infection. However, efforts to harness the antiviral efficacy of CTLs for HIV/SIV prophylaxis and therapy have been severely hindered by two major problems: viral escape and exhaustion. By contrast, CTLs directed against human cytomegalovirus (HCMV), a ubiquitous chronic herpesvirus, seldom select for escape mutations and remain functional and refractory to exhaustion during chronic HCMV and HIV infection. Recently, attempts have been made to retarget HCMV-specific CTLs for cancer immunotherapy. We speculate that such a strategy may also be beneficial in the context of HIV/SIV infection, facilitating CTL-mediated control of HIV/SIV replication. As a preliminary assessment of the validity of this approach, we investigated the phenotypes and functionality of rhesus CMV (RhCMV)-specific CTLs in SIVmac239-infected Indian rhesus macaques (RMs), a crucial HIV animal model system. We recently identified two immunodominant, Mamu-A∗02-restricted CTL epitopes derived from RhCMV proteins and sought to evaluate the phenotypic and functional characteristics of these CTL populations in chronic SIVmac239 infection. We analyzed and directly compared RhCMV- and SIVmac239-specific CTLs during SIVmac239 infection in a cohort of Mamu-A∗01+ and Mamu-A∗02+ RMs. CTL populations specific for at least one of the RhCMV-derived CTL epitopes were detected in ten of eleven Mamu-A∗02+ animals tested, and both populations were detected in five of these animals. Neither RhCMV-specific CTL population exhibited significant changes in frequency, memory phenotype, granzyme B expression, exhaustion marker (PD-1 and CTLA-4) expression, or polyfunctionality between pre- and chronic SIVmac239 infection timepoints. In chronic SIVmac239 infection, RhCMV-specific CTLs exhibited higher levels of granzyme B expression and polyfunctionality, and lower levels of exhaustion marker expression, than SIVmac239-specific CTLs. Additionally, compared to SIVmac239-specific CTLs, greater proportions of RhCMV-specific CTLs were of the terminally differentiated effector memory phenotype (CD28– CCR7–) during chronic SIVmac239 infection. These results suggest that, in contrast to SIVmac239-specific CTLs, RhCMV-specific CTLs maintain their phenotypes and cytolytic effector functions during chronic SIVmac239 infection, and that retargeting RhCMV-specific CTLs might be a promising SIV immunotherapeutic strategy.
Metabolic potential and survival strategies of microbial communities across extreme temperature gradients on Deception Island volcano, Antarctica

Active volcanoes in Antarctica, in contrast to the rest of the icy landscape, have remarkable temperature and geochemical gradients that could select for a wide variety of microbial adaptive mechanisms and metabolic pathways. Deception Island is a stratovolcano flooded by the sea, resulting in contrasting ecosystems such as permanent glaciers (<0 °C) and active fumaroles (up to 100 °C). Steep gradients in temperature, salinity and geochemistry over very short distances have been reported for Deception Island, and have been shown to effect microbial community structure and diversity. However, little is known regarding how these gradients affect ecosystem functioning, for example due to inhibition of key metabolic enzymes or pathways. In this study, we used shotgun metagenomics and metagenome-assembled genomes to explore how microbial functional diversity is shaped by extreme geochemical, salinity and temperature gradients in fumarole and glacier sediments. We observed that microbial communities from a 98 °C fumarole harbor specific hyperthermophilic molecular strategies, as well as reductive and autotrophic pathways, while those from <80 °C fumaroles possess more diverse metabolic and survival strategies capable of responding to fluctuating redox and temperature conditions. In contrast, glacier communities showed less diverse metabolic potentials, comprising mainly heterotrophic and carbon pathways. Through the reconstruction of genomes, we were able to clarify putative novel lifestyles of underrepresented taxonomic groups, especially those related to Nanoarchaeota and thermophilic ammonia-oxidizing archaeal lineages. Our results enhance understanding of the metabolic and survival capabilities of different extremophilic lineages of Bacteria and Archaea.
Genetic signatures of human brain structure: A comparison between GWAS and relatedness-based regression

Identifying the genetic variations impacting human brain structure and their further effects on cognitive functions, is important for our understanding of the fundamental bases of cognition. In this study, we take two different approaches to this issue: classical genome-wide association analysis (GWAS) and a relatedness-based regression approach (REL) to search for associations between genotype and brain structural measures of gray matter and white matter. Instead of searching genetic variants by testing the association between a phenotype trait and the genotype of each single-nucleotide polymorphism (SNP) as in GWAS, REL takes advantage of multiple SNPs within a genomic window as a single measure, which potentially find associations wherever the functional SNP is in linkage disequilibrium (LD) with SNPs that have been sampled. We also conducted a simulation analysis to systemically compare GWAS and REL with respect to different levels of LD. Both methods succeed in identifying genetic variations associated with regional and global brain structural measures and tend to give complementary results due to the different aspects of genetic properties used. Simulation results suggest that GWAS outperforms REL when the signal is relatively weak. However, the collective effects due to local LD boost the performance of REL with increasing signal strength, resulting in better performance than GWAS. Our study suggests that the optimal approach may vary across the genome and that pre-testing for LD could allow GWAS to be preferred where LD is high and REL to be used where LD is low, or the local pattern of LD is complex.
Polymicrobial Sepsis Impairs Antigen-Specific Memory CD4 T Cell-Mediated Immunity

Patients who survive sepsis display prolonged immune dysfunction and heightened risk of secondary infection. CD4 T cells support a variety of cells required for protective immunity, and perturbations to the CD4 T cell compartment can decrease overall immune system fitness. Using the cecal ligation and puncture (CLP) mouse model of sepsis, we investigated the impact of sepsis on endogenous Ag-specific memory CD4 T cells generated in C57BL/6 (B6) mice infected with attenuated Listeria monocytogenes (Lm) expressing the I-Ab-restricted 2W1S epitope (Lm-2W). The number of 2W1S-specific memory CD4 T cells was significantly reduced on day 2 after sepsis induction, but recovered by day 14. In contrast to the transient numerical change, the 2W1S-specific memory CD4 T cells displayed prolonged functional impairment after sepsis, evidenced by a reduced recall response (proliferation and effector cytokine production) after restimulation with cognate Ag. To define the extent to which the observed functional impairments in the memory CD4 T cells impacts protection to secondary infection, B6 mice were infected with attenuated Salmonella enterica-2W (Se-2W) 30 days before sham or CLP surgery, and then challenged with virulent Se-2W after surgery. Pathogen burden was significantly higher in the CLP-treated mice compared to shams. Similar reductions in functional capacity and protection were noted for the endogenous OVA323-specific memory CD4 T cell population in sepsis survivors upon Lm-OVA challenge. Our data collectively show CLP-induced sepsis alters the number and function of Ag-specific memory CD4 T cells, which contributes (in part) to the characteristic long-lasting immunoparalysis seen after sepsis.
Therapeutic Effects and Mechanisms of Herbal Medicines for Treating Polycystic Ovary Syndrome: A Review

Background Polycystic ovary syndrome (PCOS) is one of the most common disorders of endocrinology in reproductive-age women. In this study, we reviewed data on the effects and underlying mechanisms of herbal medicines used in the treatment of PCOS in laboratory studies. Methods Articles published in English up to June 30, 2018 were searched in Medline and EMBASE. We extracted data regarding herbal intervention; target cell (or animal model) usage; method of herbal extraction; route of administration; dosage and periods; and outcomes of the compounds isolated from herbs, individual herbal extracts, and herbal formula decoctions. We summarized the actions and the mechanisms underlying the beneficial effects of herbal medicines on PCOS. Results A total of 27 studies involving 22 herbal medicines reported their efficacy on PCOS. The herbal interventions in the 27 studies comprised four compounds isolated from herbs (6 studies), nine individual herbal extracts (11 studies), and nine herbal formula decoctions (10 studies). Herbal medicines normalized female hormones, diminished male hormones, recovered the estrous cycle, ameliorated insulin resistance, and improved lipid metabolism in PCOS. The mechanisms underlying the beneficial effects of herbal medicines on PCOS were found to be associated with anti-inflammation, anti-oxidative stress, inhibition of autophagy and/or apoptosis, and ovarian nerve growth factor reduction. Conclusions Herbal medicines are thought to be promising resources in the development of effective therapeutic agents for PCOS. Further studies that include methodological quality assessment and quantitative synthesis of outcomes are recommended.
Co-posting Author Assortativity in Reddit

In the context of social networks, a renowned paper of New-man introduced the notion of “assortativity”, also known as “assortative mixing”. Strictly akin to the concept of homophily, it shows how much a node tends to associate with other nodes somewhat similar to it. Degree centrality is the most used similarity metrics for evaluating assortativity between nodes, but several more could be dealt with. Assortativity was deeply investigated in many past researches, given diﬀerent social platforms. However, Reddit was not one of the social networks taken into account, even if it is a really popular social medium. In this paper, we want to ﬁnd out the possible presence of a form of assortativity in Reddit; in particular, we focus our analysis on co-posters, i.e. authors posting contents on the same subreddit.