Miracle-dz/UniFAR-FTUs huggingface dataset:
Prelimbic and Infralimbic Prefrontal Regulation of Active and Inhibitory Avoidance and Reward-Seeking

Flexible initiation or suppression of actions to avoid aversive events is crucial for survival. The prelimbic (PL) and infralimbic (IL) regions of the medial prefrontal cortex (mPFC) have been implicated in different aspects of avoidance and reward-seeking, but their respective contribution in instigating versus suppressing actions in aversive contexts remains to be clarified. We examined mPFC involvement in different forms of avoidance in rats well trained on different cued lever-press avoidance tasks. Active/inhibitory avoidance required flexible discrimination between auditory cues signaling foot-shock could be avoided by making or withholding instrumental responses. On a simpler active avoidance task, a single cue signaled when a lever press would avoid shock. PL inactivation disrupted active but not inhibitory avoidance on the discriminative task while having no effect on single-cued avoidance. In comparison, IL inactivation broadly impaired active and inhibitory avoidance. Conversely, on a cued appetitive go/no-go task, both IL and PL inactivation impaired inhibitory but not active reward-seeking, the latter effect being diametrically opposite to that observed on the avoidance task. These findings highlight the complex manner in which different mPFC regions aid in initiating or inhibiting actions in the service of avoiding aversive outcomes or obtaining rewarding ones. IL facilitates active avoidance but suppress inappropriate actions in appetitive and aversive contexts. In contrast, contextual valence plays a critical role in how the PL is recruited in initiating or suppressing actions, which may relate to the degree of cognitive control required to flexibly negotiate response or motivational conflicts and override prepotent behaviors. SIGNIFICANCE STATEMENT Choosing to make or withhold actions in a context-appropriate manner to avoid aversive events or obtain other goals is a critical survival skill. Different medial prefrontal cortex (mPFC) regions have been implicated in certain aspects of avoidance, but their contributions to instigating or suppressing actions remains to be clarified. Here, we show that the dorsal, prelimbic (PL) region of the medial PFC aids active avoidance in situations requiring flexible mitigation of response conflicts, but also aids in withholding responses to obtain rewards. In comparison the ventral infralimbic (IL) cortex plays a broader role in active and inhibitory avoidance as well as suppressing actions to obtain rewards. These findings provide insight into mechanisms underlying normal and maladaptive avoidance behaviors and response inhibition.
Niche conservatism promotes speciation in cycads: the case of Dioon merolae (Zamiaceae) in Mexico.

Niche conservatism is the tendency of lineages to retain the same niche of their ancestors. It constrains biological groups and prevents ecological divergence. However, theory predicts that niche conservatism can hinder gene flow, strengthen drift and increase local adaptation: does it mean that it also can facilitate speciation? Why does this happen? We aim to answer these questions. We examined the variation of chloroplast DNA, genome-wide single nucleotide polymorphisms, morphological traits, and environmental variables across the Dioon merolae cycad populations. We tested geographic structure, scenarios of demographic history, and niche conservatism between population groups. Lineage divergence is associated with the presence of a geographic barrier consisting of unsuitable habitats for cycads. There is a clear genetic and morphological distinction between the geographic groups, suggesting allopatric divergence. However, even in contrasting available environmental conditions, groups retain their ancestral niche, evidencing niche conservatism. Niche conservatism is a process that can promote speciation. In D. merolae, lineage divergence occurred because unsuitable habitats represented a barrier against gene flow, incurring populations to experience isolated demographic histories and disparate environmental conditions. This study explains why cycads, despite their ancient lineage origin and biological stasis, have been able to diversify into modern ecosystems worldwide.
The Neurobiology of an Insect Brain

Preface 1. Biology of locusts and grasshoppers 2. Anatomy of the nervous system 3. Components of the nervous system 4. Development of the nervous system 5. Neurotransmitters, neuromodulators and neurohormones 6. Actions of neuromodulators 7. Controlling local movements of the legs 8. Walking 9. Jumping 10. Escape movements 11. Flying 12. Breathing Glossary References
A Mechanistic High-Content Analysis Assay Using a Chimeric Androgen Receptor That Rapidly Characterizes Androgenic Chemicals

Human health is at risk from environmental exposures to a wide range of chemical toxicants and endocrine-disrupting chemicals (EDCs). As part of understanding this risk, the U.S. Environmental Protection Agency (EPA) has been pursuing new high-throughput in vitro assays and computational models to characterize EDCs. EPA models have incorporated our high-content analysis–based green fluorescent protein estrogen receptor (GFP-ER): PRL-HeLa assay, which allows direct visualization of ER binding to DNA regulatory elements. Here, we characterize a modified functional assay based on the stable expression of a chimeric androgen receptor (ARER), wherein a region containing the native AR DNA-binding domain (DBD) was replaced with the ERα DBD (amino acids 183–254). We demonstrate that the AR agonist dihydrotestosterone induces GFP-ARER nuclear translocation, PRL promoter binding, and transcriptional activity at physiologically relevant concentrations (<1 nM). In contrast, the AR antagonist bicalutamide induces only nuclear translocation of the GFP-ARER receptor (at μM concentrations). Estradiol also fails to induce visible chromatin binding, indicating androgen specificity. In a screen of reference chemicals from the EPA and the Agency for Toxic Substances and Disease Registry, the GFP-ARER cell model identified and mechanistically grouped activity by known (anti-)androgens based on the ability to induce nuclear translocation and/or chromatin binding. Finally, the cell model was used to identify potential (anti-)androgens in environmental samples in collaboration with the Houston Ship Channel/Galveston Bay Texas A&M University EPA Superfund Research Program. Based on these data, the chromatin-binding, in vitro assay–based GFP-ARER model represents a selective tool for rapidly identifying androgenic activity associated with drugs, chemicals, and environmental samples.
The expression of microRNAs and exposure to environmental contaminants related to human health: a review

ABSTRACT Environmental contaminants exposure may lead to detrimental changes to the microRNAs (miRNAs) expression resulting in several health effects. miRNAs, small non-coding RNAs that regulate gene expression, have multiple transcript targets and thereby regulate several signalling molecules. Even a minor alteration in the abundance of one miRNA can have deep effects on global gene expression. Altered patterns of miRNAs can be responsible for changes linked to various health outcomes, suggesting that specific miRNAs are activated in pathophysiological processes. In this review, we provide an overview of studies investigating the impact of air pollution, organic chemicals, and heavy metals on miRNA expression and the potential biologic effects on humans. Abbreviations: AHRR, aryl-hydrocarbon receptor repressor; AHR, aryl-hydrocarbon receptor; As, arsenic; BCL2, B-cell lymphoma 2; BCL2L11, B-cell lymphoma 2 like 11; BCL6, B-cell lymphoma 6; BPA, bisphenol A; CVD, cardiovascular diseases; CD40, cluster of differentiation 40; CCND1, Cyclin D1; CDKN1A, cyclin-dependent kinase inhibitor 1A; Cr, chromium; CTBP1, C-terminal binding protein 1; CXCL12, C-X-C motif chemokine ligand 12; DAZAP1, deleted in azoospermia associated protein 1; DEP, diesel exhaust particles; EGFR, epidermal growth factor receptor; eNOS, endothelial nitric oxide synthase; EVs, extracellular vesicles; FAK, focal adhesion kinase; FAS, fas cell surface death receptor; FOXO, forkhead box O; HbA1c, glycated hemoglobin; Hg, mercury; HLA-A, human leukocyte antigen A; HMGB, high-mobility group protein B; IFNAR2, interferon alpha receptor subunit 2; IL-6, interleukin-6; IRAK1, interleukin 1 receptor associated kinase 1; JAK/STAT, janus kinase/signal transducers and activators of transcription; MAPK, mitogen-activated protein kinase; miRNAs, microRNAs; MVs, microvesicles; NCDs, noncommunicable diseases; NFAT, nuclear factor of activated T cells; NFkB, nuclear factor kappa B; NRF2, nuclear factor, erythroid-derived 2; NRG3, neuregulin 3; O3, ozone; OP, organophosphorus pesticides; PAHs, polycyclic aromatic hydrocarbons; Pb, lead; PCBs, polychlorinated biphenyls; PDCD4, programmed cell death 4; PDGFB, platelet derived growth factor subunit beta; PDGFR, platelet-derived growth factor receptor; PI3K/Akt, phosphoinositide-3-kinase/protein kinase B; PKA, protein kinase A; PM, particulate matter; PRKCQ, protein kinase C theta; PTEN, phosphatase and tensin homolog; SORT1, sortilin 1; TGFβ, transforming growth factor-β; TLR, toll-like receptor; TNF, tumor necrosis factors; TRAF1, tumor necrosis factors-receptor associated factors 1; TRAP, traffic-related air pollution; TREM1, triggering receptor expressed on myeloid cells 1; TRIAP1, TP53 regulated inhibitor of apoptosis 1; VCAM-1, vascular cell adhesion molecule 1; VEGFA, vascular endothelial growth factor A; XRCC2, X-ray repair cross complementing 2; YBX2, Y-box-binding protein 2; ZEB1, zinc finger E-box-binding homeobox 1; ZEB2, zinc finger E-box-binding homeobox 2; 8-OH-dG, 8-hydroxy-guanine.
Health Impacts of Ambient Biomass Smoke in Tasmania, Australia

The island state of Tasmania has marked seasonal variations of fine particulate matter (PM2.5) concentrations related to wood heating during winter, planned forest fires during autumn and spring, and bushfires during summer. Biomass smoke causes considerable health harms and associated costs. We estimated the historical health burden from PM2.5 attributable to wood heater smoke (WHS) and landscape fire smoke (LFS) in Tasmania between 2010 and 2019. We calculated the daily population level exposure to WHS- and LFS-related PM2.5 and estimated the number of cases and health costs due to premature mortality, cardiorespiratory hospital admissions, and asthma emergency department (ED) visits. We estimated 69 deaths, 86 hospital admissions, and 15 asthma ED visits, each year, with over 74% of impacts attributed to WHS. Average yearly costs associated with WHS were of AUD$ 293 million and AUD$ 16 million for LFS. The latter increased up to more than AUD$ 34 million during extreme bushfire seasons. This is the first study to quantify the health impacts attributable to biomass smoke for Tasmania. We estimated substantial impacts, which could be reduced through replacing heating technologies, improving fire management, and possibly implementing integrated strategies. This would most likely produce important and cost-effective health benefits.
Determining Free-Energy Differences Through Variationally Derived Intermediates

Free-energy calculations based on atomistic Hamiltonians and sampling are key to a first-principles understanding of biomolecular processes, material properties, and macromolecular chemistry. Here, we generalize the free-energy perturbation method and derive nonlinear Hamiltonian transformation sequences yielding free-energy estimates with minimal mean squared error with respect to the exact values. Our variational approach applies to finite sampling and holds for any finite number of intermediate states. We show that our sequences are also optimal for the Bennett acceptance ratio (BAR) method, thereby generalizing BAR to small sampling sizes and non-Gaussian error distributions.
Adaptive social networks promote the wisdom of crowds

Significance Under what conditions do groups outperform their individual members? This question is of paramount importance and has spurred many studies in management and organizational science, psychology, sociology, complex systems, and computer science. Here, we investigate the conditions under which the interaction network within a group can adapt to leverage the dispersion of individual abilities and promote collective intelligence. We find that network plasticity and feedback provide fundamental mechanisms for both improving individual judgments and inducing the collective “wisdom of the network,” allowing groups to outperform their best individuals working in isolation. Social networks continuously change as new ties are created and existing ones fade. It is widely acknowledged that our social embedding has a substantial impact on what information we receive and how we form beliefs and make decisions. However, most empirical studies on the role of social networks in collective intelligence have overlooked the dynamic nature of social networks and its role in fostering adaptive collective intelligence. Therefore, little is known about how groups of individuals dynamically modify their local connections and, accordingly, the topology of the network of interactions to respond to changing environmental conditions. In this paper, we address this question through a series of behavioral experiments and supporting simulations. Our results reveal that, in the presence of plasticity and feedback, social networks can adapt to biased and changing information environments and produce collective estimates that are more accurate than their best-performing member. To explain these results, we explore two mechanisms: 1) a global-adaptation mechanism where the structural connectivity of the network itself changes such that it amplifies the estimates of high-performing members within the group (i.e., the network “edges” encode the computation); and 2) a local-adaptation mechanism where accurate individuals are more resistant to social influence (i.e., adjustments to the attributes of the “node” in the network); therefore, their initial belief is disproportionately weighted in the collective estimate. Our findings substantiate the role of social-network plasticity and feedback as key adaptive mechanisms for refining individual and collective judgments.
De Novo Synthesized Estradiol: A Role in Modulating the Cerebellar Function

The estrogen estradiol is a potent neuroactive steroid that may regulate brain structure and function. Although the effects of estradiol have been historically associated with gonadal secretion, the discovery that this steroid may be synthesized within the brain has expanded this traditional concept. Indeed, it is accepted that de novo synthesized estradiol in the nervous system (nE2) may modulate several aspects of neuronal physiology, including synaptic transmission and plasticity, thereby influencing a variety of behaviors. These modulations may be on a time scale of minutes via non-classical and often membrane-initiated mechanisms or hours and days by classical actions on gene transcription. Besides the high level, recent investigations in the cerebellum indicate that even a low aromatase expression can be related to the fast nE2 effect on brain functioning. These pieces of evidence point to the importance of an on-demand and localized nE2 synthesis to rapidly contribute to regulating the synaptic transmission. This review is geared at exploring a new scenario for the impact of estradiol on brain processes as it emerges from the nE2 action on cerebellar neurotransmission and cerebellum-dependent learning.
Muscular Fatigue and Mortality in Troll-Caught Chinook Salmon (Oncorhynchus tshawytscha)

Blood samples were analyzed for lactic acid from 66 troll caught chinook salmon after from zero to 103/4 hours of rest. Fish were held in a live box aboard a trolling vessel. During the course of the experiment 22 individuals died. Analysis of these data indicate a general response of blood lactic acid comparable with results of other experiments. The typical response is a gradual increase of blood lactic acid to high levels in the third and fourth hours, followed by a general decline. Death is strongly associated with high blood lactic acid. The level of lactic acid response is not significantly increased with more than 10 minutes of vigorous exercise nor is it significantly affected by the size of the fish within the ranges sampled in this experiment. Mortality rate is estimated at 71% with 95 percent binomial confidence limits of 40% and 86%.
Heat or cold chronic stress affects organ weights and Hsp70 levels in chicken embryos

This study was carried out with the objective of evaluating the effect of heat (38.8°C) or cold (35.8°C) stress on chicken embryo development and tissues Hsp70 levels, after the 13th day of incubation. Embryo weight (percent egg weight), organ weight (percent embryo weight) and Hsp70 levels (ng Hsp70 mg–1 total protein) in different tissues (liver, breast muscle, heart, lungs, brain and kidney) were studied at the end of incubation. Cold stress induced a lower embryo weight and lower kidney and lungs weights, whereas heart and liver were lighter in heat-stressed embryos. An interaction between temperature and age was obtained only for Hsp70 levels in kidney and heart. Cold-stressed embryos showed higher Hsp70 levels in the brain, lungs and liver; a decrease in brain and breast muscle Hsp70 levels was seen from the 19th to 20th days in control embryos. Hsp70 levels increased with age in kidneys of control embryos and in heart of heat- and cold-stressed embryos. In conclusion, this study showed that chicken.
Histone variant H2A.Z regulates nucleosome unwrapping and CTCF binding in mouse ES cells

Abstract Nucleosome is the basic structural unit of chromatin, and its dynamics plays critical roles in the regulation of genome functions. However, how the nucleosome structure is regulated by histone variants in vivo is still largely uncharacterized. Here, by employing Micrococcal nuclease (MNase) digestion of crosslinked chromatin followed by chromatin immunoprecipitation (ChIP) and paired-end sequencing (MNase-X-ChIP-seq), we mapped unwrapping states of nucleosomes containing histone variant H2A.Z in mouse embryonic stem (ES) cells. We found that H2A.Z nucleosomes are more enriched with unwrapping states compared with canonical nucleosomes. Interestingly, +1 H2A.Z nucleosomes with 30–80 bp DNA is correlated with less active genes compared with +1 H2A.Z nucleosomes with 120–140 bp DNA. We confirmed the unwrapping of H2A.Z nucleosomes under native condition by re-ChIP of H2A.Z and H2A after CTCF CUT&RUN in mouse ES cells. Importantly, we found that depletion of H2A.Z results in decreased unwrapping of H3.3 nucleosomes and increased CTCF binding. Taken together, through MNase-X-ChIP-seq, we showed that histone variant H2A.Z regulates nucleosome unwrapping in vivo and that its function in regulating transcription or CTCF binding is correlated with unwrapping states of H2A.Z nucleosomes.
Occurrence and stability of lone pair-π and OH–π interactions between water and nucleobases in functional RNAs

Abstract We identified over 1000 instances of water-nucleobase stacking contacts in a variety of RNA molecules from a non-redundant set of crystal structures with resolution ≤3.0 Å. Such contacts may be of either the lone pair-π (lp–π) or the OH–π type, in nature. The distribution of the distances of the water oxygen from the nucleobase plane peaks at 3.5 Å for A, G and C, and approximately at 3.1–3.2 Å for U. Quantum mechanics (QM) calculations confirm, as expected, that the optimal energy is reached at a shorter distance for the lp–π interaction as compared to the OH–π one (3.0 versus 3.5 Å). The preference of each nucleobase for either type of interaction closely correlates with its electrostatic potential map. Furthermore, QM calculations show that for all the nucleobases a favorable interaction, of either the lp–π or the OH–π type, can be established at virtually any position of the water molecule above the nucleobase skeleton, which is consistent with the uniform projection of the OW atoms over the nucleobases ring we observed in the experimental occurrences. Finally, molecular dynamics simulations of a model system for the characterization of water-nucleobase stacking contacts confirm the stability of these interactions also under dynamic conditions.
Sulfur cycling and sulfide intrusion in mixed Southeast Asian tropical seagrass meadows

Abstract Seagrass distribution and sediment biogeochemical conditions were measured around Libong Island in the Andaman Sea, Thailand. Seagrass diversity was moderate for a tropical site (four species found: Cymodocea rotundata, Enhalus acoroides, Halophila ovalis and Thalassia hemprichii), with the diminutive species H. ovalis particularly abundant and perhaps serving as important food for dugongs present in the area. Although the sediment organic matter content was low in the seagrass meadows, the sulfate reduction rates were high (48–138 mmol m-2 d-1). A significant positive relationship between belowground biomass and sulfate reduction rates across the seagrass species examined indicates that stimulation of microbial activity in the rhizosphere sediments is controlled by the biomass of roots and rhizomes, rather than by specific seagrass characteristics (e.g., morphology, plant activity). The low iron contents in the seagrass tissues were within the range suggested for nutrient limitation. Sediment sulfur pools, in particular pyrite pools, were high and most of the available iron was bound in sulfides, which may cause iron limitation in seagrass tissues. High sediment sulfide production and sulfide accumulation in concert exert sulfide stress on the seagrasses, as indicated by an accumulation of elemental sulfur in the plants examined, suggesting that tropical seagrasses are prone to sulfide intrusion, similar to findings for temperate seagrasses.
Power Distribution and Relationship Quality in Long-Term Heterosexual Couples

Abstract Power imbalance in romantic couples is associated with lower relationship quality. Reasons underlying this phenomenon remain, however, unclear. In 192 Czech and Slovak long-term heterosexual couples, we measured relationship quality (Dyadic Adjustment Scale) and assessed its link with perceived relationship power, control, decision making, and personality dominance. Decreased relationship quality was found in power-imbalanced couples, and power distribution affected perceived relationship quality especially in men. In women, lower perceived relationship quality was associated with their partners’ control and personality dominance. Results are discussed in the context of interdependence and approach/inhibition theories of power, and some culturally specific explanations are provided.
Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration

Exosomes are nano-sized vesicles that serve as mediators for cell-to-cell communication. With their unique nucleic acids, proteins, and lipids cargo compositions that reflect the characteristics of producer cells, exosomes can be utilized as cell-free therapeutics. Among exosomes derived from various cellular origins, mesenchymal stem cell-derived exosomes (MSC-exosomes) have gained great attention due to their immunomodulatory and regenerative functions. Indeed, many studies have shown anti-inflammatory, anti-aging and wound healing effects of MSC-exosomes in various in vitro and in vivo models. In addition, recent advances in the field of exosome biology have enabled development of specific guidelines and quality control methods, which will ultimately lead to clinical application of exosomes. This review highlights recent studies that investigate therapeutic potential of MSC-exosomes and relevant mode of actions for skin diseases, as well as quality control measures required for development of exosome-derived therapeutics.