Miracle-dz/UniFAR-FTUs huggingface dataset:
Syngap1 Dynamically Regulates the Fine-Scale Reorganization of Cortical Circuits in Response to Sensory Experience

Experience induces complex, neuron-specific changes in population activity within sensory cortex circuits. However, the mechanisms that enable neuron-specific changes within cortical populations remain unclear. To explore the idea that synapse strengthening is involved, we studied fine-scale cortical plasticity in Syngap1 mice, a neurodevelopmental disorder model useful for linking synapse biology to circuit functions. Repeated functional imaging of the same L2/3 somatosensory cortex neurons during single whisker experience revealed that Syngap1 selectively regulated the plasticity of a low-active, or “silent”, neuronal subpopulation. Syngap1 also regulated spike-timing-dependent synaptic potentiation and experience-mediated in vivo synapse bouton formation, but not synaptic depression or bouton elimination in L2/3. Adult re-expression of Syngap1 restored plasticity of “silent” neurons, demonstrating that this gene controls dynamic cellular processes required for population-specific changes to cortical circuits during experience. These findings suggest that abnormal experience-dependent redistribution of cortical population activity may contribute to the etiology of neurodevelopmental disorders.
Insect herbivory on urban trees: Complementary effects of tree neighbours and predation

Insect herbivory is an important component of forest ecosystems functioning and can affect tree growth and survival. Tree diversity is known to influence insect herbivory in natural forest, with most studies reporting a decrease in herbivory with increasing tree diversity. Urban ecosystems, on the other hand, differ in many ways from the forest ecosystem and the drivers of insect herbivory in cities are still debated. We monitored 48 urban trees from five species – three native and two exotic – in three parks of Montreal (Canada) for leaf insect herbivory and predator activity on artificial larvae, evaluated the relationships between herbivory, predation, and tree diversity in the vicinity of focal trees. Insect herbivory on leaves decreased with increasing tree diversity and with increasing predator attack rate. Our findings indicate that tree diversity is a key determinant of multitrophic interactions between trees, herbivores and predators in urban environments and that managing tree diversity could contribute to pest control in cities.
The relative densities of cell cytoplasm, nucleoplasm, and nucleoli are robustly conserved during cell cycle and drug perturbations

The cell nucleus is a compartment in which essential processes such as gene transcription and DNA replication occur. While the large amount of chromatin confined in the finite nuclear space could install the picture of a particularly dense organelle surrounded by less dense cytoplasm, recent studies have begun to report the opposite. However, the generality of this newly emerging, opposite picture has so far not been tested. Here, we used combined optical diffraction tomography (ODT) and epi-fluorescence microscopy to systematically quantify the mass densities of cytoplasm, nucleoplasm, and nucleoli of human cell lines, challenged by various perturbations. We found that the nucleoplasm maintains a lower mass density than cytoplasm during cell cycle progression by scaling its volume to match the increase of dry mass during cell growth. At the same time, nucleoli exhibited a significantly higher mass density than the cytoplasm. Moreover, actin and microtubule depolymerization and changing chromatin condensation altered volume, shape, and dry mass of those compartments, while the relative distribution of mass densities was generally unchanged. Our findings suggest that the relative mass densities across membrane-bound and membraneless compartments are robustly conserved, likely by different as of yet unknown mechanisms, which hints at an underlying functional relevance. This surprising robustness of mass densities contributes to an increasing recognition of the importance of physico-chemical properties in determining cellular characteristics and compartments.
A separable neural code in monkey IT enables perfect CAPTCHA decoding

Reading distorted letters is easy for us but so challenging for machine vision that it is used on websites as CAPTCHAs (Completely Automated Public Turing test to tell Computers and Humans Apart). How does our brain solve this problem? One solution is to have neurons invariant to letter distortions but selective for letter combinations. Another is for neurons to separately encode letter distortions and combinations. Here, we provide evidence for the latter using neural recordings in the monkey inferior temporal (IT) cortex. Neurons encoded letter distortions as a product of letter and distortion tuning, and letter combinations as a sum of letters. These rules were sufficient for perfect CAPTCHA decoding and were also present in neural networks trained for word recognition. Taken together, our findings suggest that a separable neural code enables efficient letter recognition.
Genetic Signatures of Evolution of the Pluripotency Gene Regulating Network across Mammals

Mammalian pluripotent stem cells (PSCs) have distinct molecular and biological characteristics, but we lack a comprehensive understanding of regulatory network evolution in mammals. Here, we applied a comparative genetic analysis of 134 genes constituting the pluripotency gene regulatory network across 48 mammalian species covering all the major taxonomic groups. We found evolutionary conservation in JAK-STAT and PI3K-Akt signaling pathways, suggesting equivalent capabilities in self-renewal and proliferation of mammalian PSCs. On the other hand, we discovered rapid evolution of the downstream targets of the core regulatory circuit, providing insights into variations of characteristics. Our data indicate that the variations in the PSCs characteristics may be due to positive selections in the downstream targets of the core regulatory circuit. We further reveal that positively selected genes can be associated with species unique adaptation that is not dedicated to regulation of PSCs. These results provide important insight into the evolution of the pluripotency gene regulatory network underlying variations in characteristics of mammalian PSCs.
Doxycycline Significantly Enhances Induction of iPSCs to Endoderm by Enhancing survival via AKT Phosphorylation

Induced pluripotent stem cells (iPSCs) provide an important tool for the generation patient-derived cells including hepatocyte-like cells via developmental cues through an endoderm intermediate. However, most iPSCs fail to differentiate into endoderm, with induction resulting in apoptosis. To address this issue, we built upon published methods to develop an improved protocol with our discovery that doxycycline dramatically enhances the iPSC to endoderm differentiation efficiency by inhibiting apoptosis and promoting proliferation via the AKT pathway. We tested this new protocol in more than 70 iPSC lines with consistent formation of complete sheets of endoderm in 90%. Endoderm generated by our method achieves similar transcriptomic profiles, including FOXA2, HNF1β, CXCR4, and SOX17 positive cells, and the ability to be further differentiated. Furthermore this method achieves a four-fold increase in endoderm cell number and will accelerate studies of human diseases in vitro and facilitate the expansion of iPSC-derived cells for transplantation studies.
Stability of β-lactam antibiotics in bacterial growth media

Laboratory assays such as MIC tests assume that antibiotic molecules are stable in the chosen growth medium - but rapid degradation has been observed for antibiotics including β-lactams under some conditions in aqueous solution. Degradation rates in bacterial growth medium are less well known. Here, we develop a ‘delay time bioassay’ that provides a simple way to estimate antibiotic stability in bacterial growth media. We use the bioassay to measure degradation half-lives of the β-lactam antibiotics mecillinam, aztreonam and cefotaxime in widely-used bacterial growth media based on MOPS and Luria-Bertani (LB) broth. We find that mecillinam degradation can occur rapidly, with a half-life as short as 2 hours in MOPS medium at 37°C and pH 7.4, and 4-5 hours in LB, but that adjusting the pH and temperature can increase its stability to a half-life around 6 hours without excessively perturbing growth. Aztreonam and cefotaxime were found to have half-lives longer than 6 hours in MOPS medium at 37°C and pH 7.4, but still shorter than the timescale of a typical minimum inhibitory concentration (MIC) assay. Taken together, our results suggest that care is needed in interpreting MIC tests and other laboratory growth assays for β-lactam antibiotics, since there may be significant degradation of the antibiotic during the assay.
Complex dynamics of choice during operant extinction and a simple associative learning account

Extinction learning, the process of ceasing an acquired behavior in response to altered reinforcement contingencies, is essential for survival in a changing environment. So far, research has mostly neglected the learning dynamics and variability of behavior during extinction learning and instead focused on a few response types that were studied by population averages. Here, we take a different approach by analyzing the trial-by-trial dynamics of operant extinction learning in both pigeons and a computational model. The task involved discriminant operant conditioning in context A, extinction in context B, and a return to context A to test the context-dependent return of the conditioned response (ABA renewal). By studying single learning curves across animals under repeated sessions of this paradigm, we uncovered a rich variability of behavior during extinction learning: (1) Pigeons prefer the unrewarded alternative choice in one-third of the sessions, predominantly during the very first extinction session an animal encountered. (2) In later sessions, abrupt transitions of behavior at the onset of context B emerge, and (3) the renewal effect decays as sessions progress. While these results could be interpreted in terms of rule learning mechanisms, we show that they can be parsimoniously accounted for by a computational model based only on associative learning between stimuli and actions. Our work thus demonstrates the critical importance of studying the trial-by-trial dynamics of learning in individual sessions, and the unexpected power of simple associative learning processes.
Midkine-a functions as a universal regulator of proliferation during epimorphic regeneration in adult zebrafish

Zebrafish have the ability to regenerate damaged cells and tissues by activating quiescent stem and progenitor cells or reprogramming differentiated cells into regeneration-competent precursors. Proliferation among the cells that will functionally restore injured tissues is a fundamental biological process underlying regeneration. Midkine-a is a cytokine growth factor, whose expression is strongly induced by injury in a variety of tissues across a range of vertebrate classes. Using a zebrafish Midkine-a loss of function mutant, we evaluated regeneration of caudal fin, extraocular muscle and retinal neurons to investigate the function of Midkine-a during epimorphic regeneration. In wildtype zebrafish, injury among these tissues induces robust proliferation and rapid regeneration. In Midkine-a mutants, the initial proliferation in each of these tissues is significantly diminished or absent. Regeneration of the caudal fin and extraocular muscle is delayed; regeneration of the retina is nearly completely absent. These data demonstrate that Midkine-a is universally required in the signaling pathways that convert tissue injury into the initial burst of cell proliferation. Further, these data highlight differences in the molecular mechanisms that regulate epimorphic regeneration in zebrafish.
A Hierarchy of Functional States in Working Memory

Extensive research has examined how information is maintained in working memory (WM), but it remains unknown how WM is used to guide behavior. We addressed this question by combining human electrophysiology (50 subjects, male and female) with pattern analyses, cognitive modeling, and a task requiring the prolonged maintenance of two WM items and priority shifts between them. This enabled us to discern neural states coding for memories that were selected to guide the next decision from states coding for concurrently held memories that were maintained for later use, and to examine how these states contribute to WM-based decisions. Selected memories were encoded in a functionally active state. This state was reflected in spontaneous brain activity during the delay period, closely tracked moment-to-moment fluctuations in the quality of evidence integration, and also predicted when memories would interfere with each other. In contrast, concurrently held memories were encoded in a functionally latent state. This state was reflected only in stimulus-evoked brain activity, tracked memory precision at longer timescales, but did not engage with ongoing decision dynamics. Intriguingly, the two functional states were highly flexible, as priority could be dynamically shifted back and forth between memories without degrading their precision. These results delineate a hierarchy of functional states, whereby latent memories supporting general maintenance are transformed into active decision circuits to guide flexible behavior. SIGNIFICANCE STATEMENT Working memory enables maintenance of information that is no longer available in the environment. Abundant neuroscientific work has examined where in the brain working memories are stored, but it remains unknown how they are represented and used to guide behavior. Our study shows that working memories are represented in qualitatively different formats, depending on behavioral priorities. Memories that are selected for guiding behavior are encoded in an active state that transforms sensory input into decision variables, whereas other concurrently held memories are encoded in a latent state that supports precise maintenance without affecting ongoing cognition. These results dissociate mechanisms supporting memory storage and usage, and open the door to reveal not only where memories are stored but also how.
Inner Experience – Direct Access to Reality: A Complementarist Ontology and Dual Aspect Monism Support a Broader Epistemology

Ontology, the ideas we have about the nature of reality, and epistemology, our concepts about how to gain knowledge about the world, are interdependent. Currently, the dominant ontology in science is a materialist model, and associated with it an empiricist epistemology. Historically speaking, there was a more comprehensive notion at the cradle of modern science in the middle ages. Then “experience” meant both inner, or first person, and outer, or third person, experience. With the historical development, experience has come to mean only sense experience of outer reality. This has become associated with the ontology that matter is the most important substance in the universe, everything else—consciousness, mind, values, etc., —being derived thereof or reducible to it. This ontology is insufficient to explain the phenomena we are living with—consciousness, as a precondition of this idea, or anomalous cognitions. These have a robust empirical grounding, although we do not understand them sufficiently. The phenomenology, though, demands some sort of non-local model of the world and one in which consciousness is not derivative of, but coprimary with matter. I propose such a complementarist dual aspect model of consciousness and brain, or mind and matter. This then also entails a different epistemology. For if consciousness is coprimary with matter, then we can also use a deeper exploration of consciousness as happens in contemplative practice to reach an understanding of the deep structure of the world, for instance in mathematical or theoretical intuition, and perhaps also in other areas such as in ethics. This would entail a kind of contemplative science that would also complement our current experiential mode that is exclusively directed to the outside aspect of our world. Such an epistemology might help us with various issues, such as good theoretical and other intuitions.
Tree Root Zone Microbiome: Exploring the Magnitude of Environmental Conditions and Host Tree Impact

Tree roots attract their associated microbial partners from the local soil community. Accordingly, tree root-associated microbial communities are shaped by both the host tree and local environmental variables. To rationally compare the magnitude of environmental conditions and host tree impact, the “PhytOakmeter” project planted clonal oak saplings (Quercus robur L., clone DF159) as phytometers into different field sites that are within a close geographic space across the Central German lowland region. The PhytOakmeters were produced via micro-propagation to maintain their genetic identity. The current study analyzed the microbial communities in the PhytOakmeter root zone vs. the tree root-free zone of soil two years after out-planting the trees. Soil DNA was extracted, 16S and ITS2 genes were respectively amplified for bacteria and fungi, and sequenced using Illumina MiSeq technology. The obtained microbial communities were analyzed in relation to soil chemistry and weather data as environmental conditions, and the host tree growth. Although microbial diversity in soils of the tree root zone was similar among the field sites, the community structure was site-specific. Likewise, within respective sites, the microbial diversity between PhytOakmeter root and root-free zones was comparable. The number of microbial species exclusive to either zone, however, was higher in the host tree root zone than in the tree root-free zone. PhytOakmeter “core” and “site-specific” microbiomes were identified and attributed to the host tree selection effect and/or to the ambient conditions of the sites, respectively. The identified PhytOakmeter root zone-associated microbiome predominantly included ectomycorrhizal fungi, yeasts and saprotrophs. Soil pH, soil organic matter, and soil temperature were significantly correlated with the microbial diversity and/or community structure. Although the host tree contributed to shape the soil microbial communities, its effect was surpassed by the impact of environmental factors. The current study helps to understand site-specific microbe recruitment processes by young host trees.
Selection of the Better Dual-Timed Up and Go Cognitive Task to Be Used in Patients With Stroke Characterized by Subtraction Operation Difficulties

Background: The Timed Up and Go Test (TUG) with serial subtraction is commonly used to assess cognitive-dual task performance during walking for fall prediction. Some stroke patients cannot perform number subtraction and it is unclear which cognitive task can be used to substitute for the subtraction task in the TUG test. The aim of this study was to determine the type of cognitive task that produced the highest decrease on both motor and cognitive performances during TUG-dual in stroke patients. Methods: A total of 23 persons with stroke but capable of completing subtraction (ST) and 19 persons with subtraction operation difficulties (SOD) participated. Both groups have a similar age range (ST: 59.3 ± 10.4 years and SOD: 62.0 ± 6.8 years) and stroke onset duration (ST: 44.13 ± 62.29 months and SOD: 42.34 ± 39.69 months). The participants performed TUG without a cognitive task (TUG-single) followed by a cognitive task when seated (cognitive-single). In addition, TUG with a cognitive task (TUG-dual) was performed, with the activity randomly selected from four cognitive tasks, including alternate reciting, auditory working memory, clock task, and phonologic fluency. The main outcome variables—TUG duration measured by OPAL accelerometer and cognitive-dual task effect (DTE)—were analyzed using repeated-measures analyses of variance (ANOVA). Results: The number of correct responses when seated were significantly lower in the SOD as compared to the ST (p < 0.05) during all cognitive tasks, except the phonologic fluency. During TUG-cognitive, TUG duration in the ST was significantly longer for all cognitive tasks compared with TUG-single (p < 0.0001), whereas TUG duration in the SOD was significantly increased only during the phonologic fluency task (p < 0.01). In the ST, there was a significant difference in cognitive DTE between the subtraction and the phonologic fluency tasks (p < 0.01). The highest cognitive cost was found in the subtraction task, whereas the highest cognitive benefit was shown in the phonologic fluency task. No significant cognitive DTE was found among the cognitive tasks in the SOD. Conclusion: For stroke persons with SOD, phonologic fluency is suitable to be used in the TUG-cognitive assessment. In contrast, subtraction (by 3s) is recommended for the assessment of TUG-cognitive in stroke persons who can perform subtraction.
Hepatoprotective and Anti-Oxidative Effects of Total Flavonoids From Qu Zhi Qiao (Fruit of Citrus Paradisi cv.Changshanhuyou) on Nonalcoholic Steatohepatitis In Vivo and In Vitro Through Nrf2-ARE Signaling Pathway

Nonalcoholic steatohepatitis (NASH) is a liver disease defined as the dynamic condition of hepatocellular injury during the progress of nonalcoholic fatty liver disease (NAFLD). Total flavonoids from the dry and immature fruits of Citrus Paradisi cv.Changshanhuyou (accepted species name: Citrus × aurantium L) (Qu Zhi Qiao, QZQ) are purified and named TFCH. This study was purposed to investigate and analyze the effect of TFCH on NASH model through Nuclear factor erythroid 2-related factor 2 (Nrf2)- antioxidant response elements pathway in vivo and in vitro. In vivo study was performed using male C57BL/6 mice fed with high fat diet 16 weeks for NASH model. After 7-week modeling, mice in TFCH-treated group were daily treated with intragastric administration of TFCH at 25 mg/kg, 50 mg/kg, 200 mg/kg, respectively, for successive 8 weeks. Histopathological and immunohistochemical analyses were conducted for evaluating severity of NASH-mice model and the effect of TFCH treatment. In vitro experiment was performed by using human LX-2 cells and cultured with Free fatty acid (FFA) (Oleic acid: palmitic: l: 0.5 mmol/L) for 24 h and then treated with TFCH at different concentrations (0, 25, 50, 100, 200 mg/ml) for 6 h,12 h, and 24 h. Anti-apoptosis effect of TFCH on LX-2 cells cultured with FFA was revealed by the CCK-8 assay. Lipid parameters and oxidative stress markers were measured in vivo and in vitro, results showed that TFCH dose-dependently and greatly increased the antioxidant ability and reduced the oxidative damage in NASH model. The protein expression of Nrf2 and the downstream target genes in mice liver and human LX-2 cells were tested by Western blot analysis to investigate the possible molecular mechanisms of TFCH. Our results indicated that TFCH up-regulated protein expression of these genes and have the significant influence in activating the Nrf2-ARE signaling pathway. This study shows Nrf2-ARE signaling pathway may provide novel therapeutic opportunities for NASH therapy in the future.