Reconstruction of 1,000 Projection Neurons Reveals New Cell Types and Organization of Long-Range Connectivity in the Mouse Brain.

Neuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons constitute more than 85 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.

SNT: a unifying toolbox for quantification of neuronal anatomy.

SNT is an end-to-end framework for neuronal morphometry and whole-brain connectomics that supports tracing, proof-editing, visualization, quantification and modeling of neuroanatomy. With an open architecture, a large user base, community-based documentation, support for complex imagery and several model organisms, SNT is a flexible resource for the broad neuroscience community. SNT is both a desktop application and multi-language scripting library, and it is available through the Fiji distribution of ImageJ.

Efficient delivery of carotenoids to adipocytes with albumin.

Carotenoids are very effectively delivered by albumin to adipocytes. The uptake of carotenoids to the cells occurs in the form of self-aggregates that localize in the vicinity of the adipocyte membrane, as shown by high spatial resolution Raman spectroscopy. The binding of carotenoids to albumin and the mechanism of their transport were elucidated with the help of chiroptical spectroscopies, in tandem with molecular docking and molecular dynamics simulations. In particular, apart from the recognized high affinity pocket of albumin that binds a carotenoid monomer in domain I, we have identified a hydrophobic periphery area in domain IIIB that loosely bounds the self-aggregated carotenoid in aqueous media and enables its easy detachment in hydrophobic environments. This explains the effectiveness of albumins as nanocarriers of carotenoids to adipocytes in vitro.

How do soil processes control the provision of ecosystem services in coastal wetlands?

Coastal wetlands are known for their diverse ecosystems, yet their soil characteristics are often misunderstood and thought to be monotonous. These soils are frequently subjected to saline water saturation, leading to unique soil processes. However, the combination and intensity of these processes can vary considerably across different ecosystems. In this study, we hypothesize that these diverse soil processes not only govern the geochemical conditions in coastal ecosystems but also influence their ability to deliver ecosystem services. To test this hypothesis, we conducted soil analyses in mangroves, seagrass meadows, and hypersaline tidal flats along the Brazilian coast. We used key soil properties as indicators of soil processes and developed a conceptual model linking soil processes and soil-related ecosystem services in these environments. Under more anoxic conditions, the intense soil organic matter accumulation and sulfidization processes in mangroves evidence their significance in terms of climate regulation through organic carbon sequestration and contaminants immobilization. Similarly, pronounced sulfidization in seagrasses underscores their ability to immobilize contaminants. In contrast, hypersaline tidal flats soils exhibit increased intensities of salinization and calcification processes, leading to a high capacity for accumulating inorganic carbon as secondary carbonates (CaCO3), underscoring their role in climate regulation through inorganic carbon sequestration. Our findings show that contrary to previously thought coastal wetlands are far from monotonous, exhibiting significant variations in the types and intensities of soil processes, which in turn influence their capacity to deliver ecosystem services. This understanding is pivotal for guiding effective management strategies to enhance ecosystem services in coastal wetlands.

Contrasting plant-induced changes in heavy metals dynamics: Implications for phytoremediation strategies in estuarine wetlands.

Wetland plants play a crucial role in regulating soil geochemistry, influencing heavy metal (HM) speciation, bioavailability, and uptake, thus impacting phytoremediation potential. We hypothesized that variations in HM biogeochemistry within estuarine soils are controlled by distinct estuarine plant species. We evaluated the soils (pH, redox potential, rhizosphere pH, HM total concentration, and geochemical fractionation), plant parts (shoot and root), and iron plaques of three plants growing in an estuary affected by Fe-rich mine tailings. Though the integration of multiple plant and soil analysis, this work emphasizes the importance of considering geochemical pools of HM for predicting their fate. Apart from the predominance of HM associated with Fe oxides, Typha domingensis accumulated the highest Cr and Ni contents in their shoots (> 100 mg kg-1). In contrast, Hibiscus tiliaceus accumulated more Cu and Pb in their roots (> 50 mg kg-1). The differences in rhizosphere soil conditions and root bioturbation explained the different potentials between the plants by altering the soil dynamics and HM's bioavailability, ultimately affecting their uptake. This study suggests that Eleocharis acutangula is not suitable for phytoextraction or phytostabilization, whereas Typha domingensis shows potential for Cr and Ni phytoextraction. In addition, we first showed Hibiscus tiliaceus as a promising wood species for Cu and Pb phytostabilization.

How do replanted mangroves affect phosphorus dynamics in their soils?

Phosphorus is a limiting element for the productivity of mangroves, which in turn are important ecosystems in regulating nutrients cycle and climate change by sequestering carbon (C). Despite this, there is an intense process of degradation in these environments. In addition to providing socio-environmental services, mangrove replanting can also alter the dynamics of nutrients in soils. Therefore, this study aims to understand the changes in soil phosphorus (P) fractions after a mangrove restoration. Soil samples from an unvegetated area (NV), a mature mangrove (R) and 7 and 9 year old replanted mangroves at SE-Brazil (APA Guapi-mirim, Rio de Janeiro state) were collected and analyzed to characterize the redox conditions (Eh), pH, and iron (Fe) fractionation, Total Organic Carbon (TOC) contents and P fractionation (exchangeable P; P associated with reducible Fe and Mn oxyhydroxides; associated with Al silicates and hydroxides; associated with humic acids; associated with Ca and Mg; associated with humin). The results indicate an increase in TOC as the age of the mangrove restoration increases (from 8.6 to 17.9%). The pH values were significantly lower, reaching very acidic values, associated with an increase in Eh. Both parameters also showed strong seasonal variation, with a drop in Eh during the wet period (from 165% to -46%) and an increase in pH in the same period (from 6.0 to 6.7). Regarding P fractionation, the main P pool was organic P forms, which showed the highest concentrations in all studied sites. Unvegetated areas showed higher organic P forms (NV: 108.8 µg g-1) than vegetated areas (M7: 55.7 µg g-1, M9: 83.6 µg g-1, R: 87.3 µg g-1). Vegetated sites also showed lower levels of the PEx, PFeMn and Papatite fractions (total forest mean: 2.4 µg g-1, 5.8 µg g-1, 3.0 µg g-1, respectively). Besides no clear trend on P fractionation through seasons and forest age, pseudo-total P increased following the forest recovery (e.g. M7

Rocking motion in solid proteins studied by the 15N proton-decoupled R1ρ relaxometry.

Recently it has been revealed that proteins in solid samples undergo slow overall rocking. The parameters of this motion depend on intermolecular interactions. Therefore, the characterization of the rocking motion enables one to investigate protein-protein interactions. NMR R1ρ relaxometry is the most suitable tool to study slow molecular motions. However, the time scale of the rocking motion is on the edge of the dynamics window of the standard R1ρ experiment, precluding the R1ρ data analysis from being precise and reliable. In this work, we apply a modified R1ρ relaxation method to characterize the slow motion in solids with much higher precision and reliability. The modification is the simultaneous use of a strong 1H-CW pulse and a weak/moderate 15N spin-lock pulse. We demonstrate theoretically and experimentally that under this condition, R1ρ decays have a significantly better signal-to-noise ratio and a much shorter "dead time" caused by the initial oscillations compared to the conventional R1ρ experiment. Moreover, the proton-decoupled R1ρ's can be measured at a much smaller difference between the spin-lock and MAS frequencies; thus, much slower molecular motions can be sampled. The proton decoupling during the 15N spin-lock pulse also suppresses the interfering coherent spin-spin relaxation pathway at low spin-lock fields, which overlaps the Bloch-McConnell (chemical exchange) range of R1ρ dispersions. The proton-decoupled and standard R1ρ experiments were used to study the rocking motion of 15N,2H-enriched protein GB1 in two solid forms, microcrystals and lyophilized amorphous powder. The most striking finding is that the correlation function of this motion consists of two components with very different correlation times, 2-20 µs and a few hundred µs. The rocking motion parameters in microcrystals and powder are quite different, revealing the distinct nature of inter-protein interactions in these two samples.

Emotional Dysregulation Mediates the Association Between Unsupportive Maternal Socialization Strategies of Overjoy and Psychopathological Symptoms in Adolescent Boys but not Girls.

Mothers play an important role in the emotion socialization of their teenage children, with implications for psychological adjustment. However, studies on maternal socialization of positive emotions in adolescence are still scarce and inconclusive. In this study, we aim to deepen our understanding on the association between unsupportive maternal socialization strategies of overjoy and internalization but also externalization symptoms as mediated by emotion dysregulation, and moderated by adolescents' gender. The study was conducted with 418 adolescents (M age = 14.75; 57.7% girls). Moderated mediation analysis indicated the effect of punishment and override of overjoy on internalization (punishment: b = 1.38, 95% CI [0.63, 2.31]; override: b = 1.36, 95% CI [0.59, 2.31]) and externalization (punishment: b = 0.71, 95% CI [0.20, 1.34]; override: b = 0.77, 95% CI [0.26, 1.46]) was mediated by emotional dysregulation in the case of boys. Contrary to expectations, for girls this effect was not found, indicating that further analysis are required.

Stability and Change in Adolescents' Sense of Agency: Contributions of Sex, Multiple Risk, Pandemic Stress, and Attachment to Parents.

Although literature states that individual, relational, and contextual factors contribute to adolescents' sense of agency, more research is needed to clarify and understand how adolescents develop this belief over time. The current study examined the stability/change trajectories of the sense of agency during adolescence, specifically across high school, analyzing whether attachment to parents over time, adolescents' sex, cumulative risk in baseline, and pandemic-related stress explained these trajectories. The sample included 467 Portuguese adolescents (40.7% were males; Mage = 15.58 years, SD = 0.80), evaluated three times across 18 months. This work yielded three significant findings. First, adolescents' sense of agency significantly increased over time, with significant between-subject variance at the initial levels but not at the growth rate. Second, attachment to parents consistently links to adolescents' sense of agency across time, despite the differential contributions from attachment to mothers and fathers. Third, boys reported greater growth in the sense of agency than girls. Adolescents' cumulative risk at T1 predicted lower initial levels of sense of agency, whereas higher pandemic-related stress predicted less growth of the sense of agency. These findings emphasize the contributions of individual and family characteristics and the role of the broader social context in shaping the development of adolescents' sense of agency. The findings underline the need to consider further the differential influences of adolescents' relationships with mothers and fathers to understand changes in adolescents' sense of agency.

Forecasting Commodity Market Synchronization with Commodity Currencies: A Network-Based Approach.

This paper shows that some commodity currencies (from Chile, Iceland, Norway, South Africa, Australia, Canada, and New Zealand) predict the synchronization of metals and energy commodities. This relationship links the present-value theory for exchange rates and its connection with commodity export economies' fundamentals, where prospective commodity price fluctuations affect exchange rates. Predicting commodity market return synchronization is critical for dealing with systemic risk, market efficiency, and financial stability since synchronization reduces the benefits of diversification and increases the probability of contagion in financial markets during economic and financial crises. Using network methods coupled with in-sample and out-of-sample econometrics models, we find evidence that a fall in the return of commodity-currencies (dollar appreciation) predicts an increase in commodity market synchronization and, consequently, in commodity market systemic risk. This discovery is consistent with a transitive capacity phenomenon, suggesting that commodity currencies have a predictive ability over commodities that extend beyond the commodity bundle that a country produces. The latter behavior would be exacerbated by the high financialization of commodities and strong co-movement of commodity markets. Our paper is part of a vigorously growing literature that has recently measured and predicted systemic risk caused by synchronization, combining a complex systems perspective and financial network analysis.

Extracting Rules via Markov Chains for Cryptocurrencies Returns Forecasting.

With the growing popularity of digital currencies known as cryptocurrencies, there is a need to develop models capable of robustly analyzing and predicting the value of future returns in these markets. In this article, we extract behavior rules to predict the values of future returns in the Bitcoin, Ethereum, Litecoin, and Ripple closing series. We used categorical data in the analyses and Markov chain models from the first to the tenth order to propose a new way of establishing possible future scenarios, in which we analyze the dependence of memory on the dynamics of the process. We used the measurements of accuracy Mean Quadratic Error, Absolute Error Mean Percentage, and Absolute Standard Deviation for the choice of the best models. Our findings reveal that cryptocurrencies have long-range memory. Bitcoin, Ethereum, and Ripple exposed seven steps of memory, while Litecoin displayed nine memory steps. From the transitions between states that happened the most, we defined decision rules that assisted in the definition of future returns in the series. Our results can support the decisions of traders, investors, crypto-traders, and policy-makers.

Rotational decoupling between the hydrophilic and hydrophobic regions in lipid membranes.

Cells use homeostatic mechanisms to ensure an optimal composition of distinct types of lipids in cellular membranes. The hydrophilic region of biological lipid membranes is mainly composed of several types of phospholipid headgroups that interact with incoming molecules, nanoparticles, and viruses, whereas the hydrophobic region consists of a distribution of acyl chains and sterols affecting membrane fluidity/rigidity related properties and forming an environment for membrane-bound molecules such as transmembrane proteins. A fundamental open question is to what extent the motions of these regions are coupled and, consequently, how strongly the interactions of phospholipid headgroups with other molecules depend on the properties and composition of the membrane hydrophobic core. We combine advanced solid-state nuclear magnetic resonance spectroscopy with high-fidelity molecular dynamics simulations to demonstrate how the rotational dynamics of choline headgroups remain nearly unchanged (slightly faster) with incorporation of cholesterol into a phospholipid membrane, contrasting the well-known extreme slowdown of the other phospholipid segments. Notably, our results suggest a new paradigm in which phospholipid dipole headgroups interact as quasi-freely rotating flexible dipoles at the interface, independent of the properties in the hydrophobic region.

Filling the Gap with Long n-Alkanes: Incorporation of C20 and C30 into Phospholipid Membranes.

Investigating how hydrophobic molecules mix with phospholipid bilayers and how they affect membrane properties is commonplace in biophysics. Despite this, a molecular-level empirical description of a membrane model as simple as a phospholipid bilayer with long linear hydrophobic chains incorporated is still missing. Here, we present an unprecedented molecular characterization of the incorporation of two long n-alkanes, n-eicosane (C20) and n-triacontane (C30) with 20 and 30 carbons, respectively, in phosphatidylcholine (PC) bilayers using a combination of experimental techniques (2H NMR, 31P NMR, 1H-13C dipolar recoupling solid-state NMR, X-ray scattering, and cryogenic electron microscopy) and atomistic molecular dynamics (MD) simulations. At low hydration, deuterated C20 and C30 yield 2H NMR spectra evidencing anisotropic-motion, which demonstrates their miscibility in PC membranes up to a critical alkane-to-acyl-chain volume fraction, ϕc. The acquired 2H NMR spectra of C20 and C30 have notably different lineshapes. At low alkane volume fractions below ϕc, CHARMM36 MD simulations predict such 2H NMR spectra qualitatively and thus enable an atomistic-level interpretation of the spectra. Above ϕc, the 2H NMR lineshapes become characteristic of motions in the intermediate-regime that, together with the MD simulation results, suggest the onset of immiscibility between the alkane molecules and the acyl chains. For all the systems investigated, the phospholipid molecular structure is unperturbed by the presence of the alkanes. However, at conditions of excess hydration and at surprisingly low alkane fractions below ϕc, a peak characteristic of isotropic motion is observed in both the 2H spectra of the alkanes and 31P spectra of the phospholipids, strongly indicating that the incorporation of the alkanes induces a reduction on the average radius of the lipid vesicles.

Mutant p53 reactivator SLMP53-2 hinders ultraviolet B radiation-induced skin carcinogenesis.

The growing incidence of skin cancer (SC) has prompted the search for additional preventive strategies to counteract this global health concern. Mutant p53 (mutp53), particularly with ultraviolet radiation (UVR) signature, has emerged as a promising target for SC prevention based on its key role in skin carcinogenesis. Herein, the preventive activity of our previously disclosed mutp53 reactivator SLMP53-2 against UVR-induced SC was investigated. The pre-treatment of keratinocyte HaCaT cells with SLMP53-2, before UVB exposure, depleted mutp53 protein levels with restoration of wild-type-like p53 DNA-binding ability and subsequent transcriptional activity. SLMP53-2 increased cell survival by promoting G1-phase cell cycle arrest, while reducing UVB-induced apoptosis through inhibition of c-Jun N-terminal kinase (JNK) activity. SLMP53-2 also protected cells from reactive oxygen species and oxidative damage induced by UVB. Moreover, it enhanced DNA repair through upregulation of nucleotide excision repair pathway and depletion of UVB-induced DNA damage, as evidenced by a reduction of DNA in comet tails, γH2AX staining and cyclobutane pyrimidine dimers (CPD) levels. SLMP53-2 further suppressed UVB-induced inflammation by inhibiting the nuclear translocation and DNA-binding ability of NF-κB, and promoted the expression of key players involved in keratinocytes differentiation. Consistently, the topical application of SLMP53-2 in mice skin, prior to UVB irradiation, reduced cell death and DNA damage. It also decreased the expression of inflammatory-related proteins and promoted cell differentiation, in UVB-exposed mice skin. Notably, SLMP53-2 did not show signs of skin toxicity for cumulative topical use. Overall, these results support a promising protective activity of SLMP53-2 against UVB-induced SC.

Relations between child self-control, maternal relational frustration, and teacher-child conflict: a longitudinal study with children from dual-earner families.

This longitudinal study follows children from dual-earner families in 4 time-points, covering the early childhood period. We examined the influence of work-family conflict (WFC) on maternal relational frustration (RF) towards the child, and investigated the reciprocal relations among maternal RF, children's self-control (SC), and teacher-child (TC) conflict over time. Participants were 214 children (97 girls; M age = 4.00 years), their mothers, and teachers. Mothers reported their own WFC and RF, whereas teachers reported child SC and T-C conflict. Results from a cross-lagged panel model indicated the experience of WFC positively predicted maternal RF. Maternal RF and T-C conflict were negatively related to the child later SC abilities. Conversely, children who displayed SC difficulties were more likely to experience later maternal RF and T-C conflict. There was evidence supporting the bidirectional effects of child SC and T-C conflict across time. Moreover, maternal RF and T-C conflict were indirectly linked, via child SC. The findings are consistent with a transactional view of development, stressing the importance of contextual factors to the quality of caregiving relationships and highlighting the complex and reciprocal relations between child regulatory competence and the quality of relationships with distinct caregivers.

PRMT7 regulates RNA-binding capacity and protein stability in Leishmania parasites.

RNA binding proteins (RBPs) are the primary gene regulators in kinetoplastids as transcriptional control is nearly absent, making Leishmania an exceptional model for investigating methylation of non-histone substrates. Arginine methylation is an evolutionarily conserved protein modification catalyzed by Protein aRginine Methyl Transferases (PRMTs). The chromatin modifier PRMT7 is the only Type III PRMT found in higher eukaryotes and a restricted number of unicellular eukaryotes. In Leishmania major, PRMT7 is a cytoplasmic protein implicit in pathogenesis with unknown substrates. Using comparative methyl-SILAC proteomics for the first time in protozoa, we identified 40 putative targets, including 17 RBPs hypomethylated upon PRMT7 knockout. PRMT7 can modify Alba3 and RBP16 trans-regulators (mammalian RPP25 and YBX2 homologs, respectively) as direct substrates in vitro. The absence of PRMT7 levels in vivo selectively reduces Alba3 mRNA-binding capacity to specific target transcripts and can impact the relative stability of RBP16 in the cytoplasm. RNA immunoprecipitation analyses demonstrate PRMT7-dependent methylation promotes Alba3 association with select target transcripts and thus indirectly stabilizes mRNA of a known virulence factor, δ-amastin surface antigen. These results highlight a novel role for PRMT7-mediated arginine methylation of RBP substrates, suggesting a regulatory pathway controlling gene expression and virulence in Leishmania. This work introduces Leishmania PRMTs as epigenetic regulators of mRNA metabolism with mechanistic insight into the functional manipulation of RBPs by methylation.

The nosographic structure of posttraumatic stress symptoms across trauma types: An exploratory network analysis approach.

The nosographic structure of posttraumatic stress disorder (PTSD) remains unclear, and attempts to determine its symptomatic organization have been unsatisfactory. Several explanations have been suggested, and the impact of trauma type is receiving increasing attention. As little is known about the differential impact trauma type in the nosographic structure of PTSD, we explored the nosology of PTSD and the effect of trauma type on its symptomatic organization. We reanalyzed five cross-sectional psychopathological networks involving different trauma types, encompassing a broad range of traumatic events in veterans, war-related trauma in veterans, sexual abuse, terrorist attacks, and various traumatic events in refugees. The weighted topological overlap was used to estimate the networks and attribute weights to their links. Coexpression differential network analysis was used to identify the common and specific network structures of the connections across different trauma types and to determine the importance of symptoms across the networks. We found a set of symptoms with more common connections with other symptoms, suggesting that these might constitute the prototypical nosographic structure of PTSD. We also found a set of symptoms that had a high number of specific connections with other symptoms; these connections varied according to trauma type. The importance of symptoms across the common and specific networks was ascertained. The present findings offer new insights into the symptomatic organization of PTSD and support previous research on the impact of trauma type on the nosology of this disorder.

Host foraging behavior and nest type influence prevalence of avian haemosporidian parasites in the Pantanal.

Avian haemosporidians from the genera Plasmodium and Haemoproteus are vector transmitted parasites. A growing body of evidence suggests that variation in their prevalence within avian communities is correlated with a variety of avian ecological traits. Here, we examine the relationship between infection probability and diversity of haemosporidian lineages and avian host ecological traits (average body mass, foraging stratum, migratory behavior, and nest type). We used molecular methods to detect haemosporidian parasites in blood samples from 642 individual birds of 149 species surveyed at four localities in the Brazilian Pantanal. Based on cytochrome b sequences, we recovered 28 lineages of Plasmodium and 17 of Haemoproteus from 31 infected avian species. Variation in lineage diversity among bird species was not explained by avian ecological traits. Prevalence was heterogenous across avian hosts. Bird species that forage near the ground were less likely to be infected by Haemoproteus, whereas birds that build open cup nests were more likely infected by Haemoproteus. Furthermore, birds foraging in multiple strata were more likely to be infected by Plasmodium. Two other ecological traits, often related to host resistance (body mass and migratory behavior), did not predict infection probability among birds sampled in the Pantanal. Our results suggest that avian host traits are less important determinants of haemosporidian diversity in Pantanal than in other regions, but reinforces that host attributes, related to vector exposure, are to some extent important in modulating infection probability within an avian host assemblage.

Diagnostic Classification of Cases of Canine Leishmaniasis Using Machine Learning.

Proposal techniques that reduce financial costs in the diagnosis and treatment of animal diseases are welcome. This work uses some machine learning techniques to classify whether or not cases of canine visceral leishmaniasis are present by physical examinations. For validation of the method, four machine learning models were chosen: K-nearest neighbor, Naïve Bayes, support vector machine and logistic regression models. The tests were performed on three hundred and forty dogs, using eighteen characteristics of the animal and the ELISA (enzyme-linked immunosorbent assay) serological test as validation. Logistic regression achieved the best metrics: Accuracy of 75%, sensitivity of 84%, specificity of 67%, a positive likelihood ratio of 2.53 and a negative likelihood ratio of 0.23, showing a positive relationship in the evaluation between the true positives and rejecting the cases of false negatives.

Facial edema as an adverse drug reaction to olanzapine in a patient with cancer receiving palliative care.

OBJECTIVE: Atypical neuroleptics such as olanzapine are indicated for the treatment of various psychiatric disorders and have been used in the palliative care setting also for several clinical indications. Peripheral and facial edema are a rare side effect of the treatment with olanzapine. We report a case of an advanced cancer patient cared receiving palliative care who developed severe facial edema after initiating a low dose of olanzapine in monotherapy. METHOD: A patient with advanced cancer who presented with severe facial edema after initiating olanzapine for the treatment of her opioid use disorder. RESULTS: After excluding other differential diagnosis for facial edema, olanzapine was discontinued with complete resolution of the edema. SIGNIFICANCE OF RESULTS: To the best of our knowledge, this is the first case reporting facial edema due to olanzapine treatment in a patient with advanced cancer. Our report will help clinicians recognize the possible role of olanzapine in cases of rapid onset of facial edema, allowing its rapid resolution.