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The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Romani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Midbrain dopamine neurons are thought to play key roles in learning by conveying the difference between expected and actual outcomes. Recent evidence suggests diversity in dopamine signaling, yet it remains poorly understood how heterogeneous signals might be organized to facilitate the role of downstream circuits mediating distinct aspects of behavior. Here, we investigated the organizational logic of dopaminergic signaling by recording and labeling individual midbrain dopamine neurons during associative behavior. Our findings show that reward information and behavioral parameters are not only heterogeneously encoded but also differentially distributed across populations of dopamine neurons. Retrograde tracing and fiber photometry suggest that populations of dopamine neurons projecting to different striatal regions convey distinct signals. These data, supported by computational modeling, indicate that such distributional coding can maximize dynamic range and tailor dopamine signals to facilitate specialized roles of different striatal regions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Floods have caused socio-economic and environmental damage globally and, thus, require research. Several factors influence flooding events, such as extreme rainfall, physical characteristics, and local anthropogenic factors; therefore, such factors are essential for mapping flood risk areas and enabling measures that mitigate the damage they cause. This study aimed to map and analyze regions susceptible to flood risk in three different study areas belonging to the same Atlantic Forest biome, in which flood disasters are recurrent. Due to the presence of numerous factors, a multicriteria analysis using the Analytical Hierarchical Process was conducted. First, a geospatial database was composed of layers of elevation, slope, drainage distance, soil drainage, soil hydrological group, precipitation, relief, and land use and cover. Flood risk maps for the study area were then generated, and patterns in the study areas were verified, with the greatest influence being exerted by intense precipitation on consecutive days, elevation at the edges of the channel with low altimetric variation and a flat combination, densely built areas close to the banks of the main river, and an expressive water mass in the main watercourse. The results demonstrate that these characteristics together can indicate the occurrence of flooding events., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thalamoreticular circuitry plays a key role in arousal, attention, cognition, and sleep spindles, and is linked to several brain disorders. A detailed computational model of mouse somatosensory thalamus and thalamic reticular nucleus has been developed to capture the properties of over 14,000 neurons connected by 6 million synapses. The model recreates the biological connectivity of these neurons, and simulations of the model reproduce multiple experimental findings in different brain states. The model shows that inhibitory rebound produces frequency-selective enhancement of thalamic responses during wakefulness. We find that thalamic interactions are responsible for the characteristic waxing and waning of spindle oscillations. In addition, we find that changes in thalamic excitability control spindle frequency and their incidence. The model is made openly available to provide a new tool for studying the function and dysfunction of the thalamoreticular circuitry in various brain states., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Managing water resources in regions with scarce data, like most developing countries, is still one of the major challenges around the world. Analysis of water quality parameters can provide important information for understanding the current status of water resources and their surroundings, including the changes that have occurred over time. This study aims to evaluate the influence of preservation areas on surface water quality in the Atlantic Forest biome. For this purpose, water quality monitoring sites with a greater number of parameters and longer monitoring time, located in six basins in the Atlantic Forest region of Brazil near preservation areas, were selected. This study employs seven statistical methods, such as cluster and principal component analysis (PCA), and promotes a robust analysis of the pollution of water resources in the Atlantic Forest. The most preserved basins, with more than 87% preservation area, have lower levels of pollution. The second most degraded basin, with 56% preservation area, presents intermediate pollution levels. The most degraded basin has the highest level of pollution. The basin with the lowest area of native vegetation is considered a degraded basin. Finally, non-point sources of pollution from agricultural activities were identified as the main sources of pollution in the region. The cophenetic correlation of 0.97 indicates a good performance of the cluster analysis. In addition, the pre-tests of PCA showed the suitability of the data for performing the test (Bartlett test, < 2.2e -16 and KMO, P= 0.7). The first principal component in the PCA, which accounts for 31.4% of the total variation, is associated with strong ammonia nitrogen and total Kjeldahl nitrogen loads, and moderate biological oxygen demand and nitrite loads. The second component, representing 13.6% of the total variation, indicates periods of self-cleaning of water resources after contamination. The results indicate the importance of maintaining preservation areas in the watershed contribution areas for the improvement of surface water quality in the Atlantic Forest., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The time of concentration (Tc) is the main hydrological parameter used to characterize the response of a given Hydrological Response Unit (HRU) to a precipitation event. Because of its importance, the determining Tc is an integral step in several studies involving runoff. Thus, this work presents an unprecedented review of the application of Tc in different lines of research involving water resources around the world. In this article, 1252 publications were listed, obtained from seven different databases, published by 2020, that presented the expressions "time of concentration," "runoff," and "watershed." The articles and conference papers obtained in this research were classified into 12 topics. The number of publications per topic and per country was measured and a cluster analysis was developed to verify the similarity of the distribution of topics per country. In addition, 125 equations applied in related publications for the estimation of Tc are also listed. Graphical abstract., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study evaluates the influence of physiographic characteristics on the peak flow to runoff volume ratio in watersheds belonging to the Cerrado and Atlantic Forest biomes, in the Center-South region of Brazil. Specifically, the peak flow and runoff volume values obtained in the outlet section are related to the physiographic characteristics of the watersheds. Using a geographic information system tool, 13 watersheds are delimited, and 38 variables are selected from each watershed. A recursive digital filter is used to separate the direct (surface) flow from base (groundwater) flow. Data are analyzed using multivariate statistics, which allows interpretation of the structure of a data set from the respective correlation matrices. The results indicate that the peak flow and runoff volume are strongly correlated with the physical characteristics of the watersheds and the types of anthropogenic activity in both biomes. Furthermore, the presence of woods and forests reduces the peak flow and runoff volume., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

SARS-CoV-2 started spreading toward the end of 2019 causing COVID-19, a disease that reached pandemic proportions among the human population within months. The reasons for the spectrum of differences in the severity of the disease across the population, and in particular why the disease affects more severely the aging population and those with specific preconditions are unclear. We developed machine learning models to mine 240,000 scientific articles openly accessible in the CORD-19 database, and constructed knowledge graphs to synthesize the extracted information and navigate the collective knowledge in an attempt to search for a potential common underlying reason for disease severity. The machine-driven framework we developed repeatedly pointed to elevated blood glucose as a key facilitator in the progression of COVID-19. Indeed, when we systematically retraced the steps of the SARS-CoV-2 infection, we found evidence linking elevated glucose to each major step of the life-cycle of the virus, progression of the disease, and presentation of symptoms. Specifically, elevations of glucose provide ideal conditions for the virus to evade and weaken the first level of the immune defense system in the lungs, gain access to deep alveolar cells, bind to the ACE2 receptor and enter the pulmonary cells, accelerate replication of the virus within cells increasing cell death and inducing an pulmonary inflammatory response, which overwhelms an already weakened innate immune system to trigger an avalanche of systemic infections, inflammation and cell damage, a cytokine storm and thrombotic events. We tested the feasibility of the hypothesis by manually reviewing the literature referenced by the machine-generated synthesis, reconstructing atomistically the virus at the surface of the pulmonary airways, and performing quantitative computational modeling of the effects of glucose levels on the infection process. We conclude that elevation in glucose levels can facilitate the progression of the disease through multiple mechanisms and can explain much of the differences in disease severity seen across the population. The study provides diagnostic considerations, new areas of research and potential treatments, and cautions on treatment strategies and critical care conditions that induce elevations in blood glucose levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Logette, Lorin, Favreau, Oshurko, Coggan, Casalegno, Sy, Monney, Bertschy, Delattre, Fonta, Krepl, Schmidt, Keller, Kerrien, Scantamburlo, Kaufmann and Markram.)

Water quality models are quite complex to use even for scientists, requiring knowledge in different areas such as biology, chemistry, physics, and engineering. Hence, the use of these models by a non-specialist is quite complicated, demanding considerable time and research, particularly to choose which model is the most appropriate for a given situation. In this study, a comparative guide is suggested, which can help users select the appropriate water quality model for certain systems and variables. Five models were considered as follows: AQUATOX, CE-QUAL-W2, Spatially Referenced Regression Model on Watershed Attributes (SPARROW), Soil and Water Assessment Tool (SWAT), and Water Quality Analysis Simulation Program 7 (WASP7), which have been widely used during the last 5 years. All of these selected models are free and easily available. It was verified that each model has its particularities and applications; however, the AQUATOX model has several advantages compared with the other models analyzed. In addition, to illustrate the availability of the proposed comparative guide, a case study was carried out to demonstrating the selection process of the selected models.

Water quality models are important tools used in the management of water resources. The models are usually developed for specific regions, with particular climates and physical characteristics. Thus, applying these models in regions other than those they were designed for can generate large simulation errors. With consideration to these discrepancies, the goal of this study is to identify the models employed in different countries and assist researchers in the selection of the most appropriate models for management purposes. Published studies from the last 21 years (1997-2017) that discuss the application of water quality models were selected from three engineering databases: SpringerLink, Web of Science, and Scopus. Seven models for water quality simulations have been widely applied around the world: AQUATOX, CE-QUAL-W2, EFDC, QUALs, SWAT, SPARROW, and WASP. The countries most frequently applying water quality models are the USA, followed by China, and South Korea. SWAT was the most used model, followed by the QUAL group and CE-QUAL-W2. This study provides the opportunity for researchers, who wish to study countries with fewer cases of applied water quality models, to easily identify the work from that region. Furthermore, this work collated central themes of interest and the most simulated parameters for the seven countries that most frequently employed the water quality models.

Unlabelled: Galvanic vestibular stimulation (GVS) uses modulated currents to evoke neuronal activity in vestibular endorgans in the absence of head motion. GVS is typically used for a characterization of vestibular pathologies; for studies on the vestibular influence of gaze, posture, and locomotion; and for deciphering the sensory-motor transformation underlying these behaviors. At variance with the widespread use of this method, basic aspects such as the activated cellular substrate at the sensory periphery or the comparability to motion-induced neuronal activity patterns are still disputed. Using semi-intact preparations of Xenopus laevis tadpoles, we determined the cellular substrate and the spatiotemporal specificity of GVS-evoked responses and compared sinusoidal GVS-induced activity patterns with motion-induced responses in all neuronal elements along the vestibulo-ocular pathway. As main result, we found that, despite the pharmacological block of glutamatergic hair cell transmission by combined bath-application of NMDA (7-chloro-kynurenic acid) and AMPA (CNQX) receptor blockers, GVS-induced afferent spike activity persisted. However, the amplitude modulation was reduced by ∼30%, suggesting that both hair cells and vestibular afferent fibers are normally recruited by GVS. Systematic alterations of electrode placement with respect to bilateral semicircular canal pairs or alterations of the bipolar stimulus phase timing yielded unique activity patterns in extraocular motor nerves, compatible with a spatially and temporally specific activation of vestibulo-ocular reflexes in distinct planes. Despite the different GVS electrode placement in semi-intact X. laevis preparations and humans and the more global activation of vestibular endorgans by the latter approach, this method is suitable to imitate head/body motion in both circumstances., Significance Statement: Galvanic vestibular stimulation is used frequently in clinical practice to test the functionality of the sense of balance. The outcome of the test that relies on the activation of eye movements by electrical stimulation of vestibular organs in the inner ear helps to dissociate vestibular impairments that cause vertigo and imbalance in patients. This study uses an amphibian model to investigate at the cellular level the underlying mechanism on which this method depends. The outcome of this translational research unequivocally revealed the cellular substrate at the vestibular sensory periphery that is activated by electrical currents, as well as the spatiotemporal specificity of the evoked eye movements, thus facilitating the interpretation of clinical test results., (Copyright © 2016 the authors 0270-6474/16/369097-14$15.00/0.)

Mutations in leucine-rich repeat kinase 2 (LRRK2) lead to late-onset, autosomal dominant Parkinson's disease, characterized by the degeneration of dopamine neurons of the substantia nigra pars compacta, a deficit in dopamine neurotransmission and the development of motor and non-motor symptoms. The most prevalent Parkinson's disease LRRK2 mutations are located in the kinase (G2019S) and GTPase (R1441C) encoding domains of LRRK2. To better understand the sequence of events that lead to progressive neurophysiological deficits in vulnerable neurons and circuits in Parkinson's disease, we have generated LRRK2 bacterial artificial chromosome transgenic rats expressing either G2019S or R1441C mutant, or wild-type LRRK2, from the complete human LRRK2 genomic locus, including endogenous promoter and regulatory regions. Aged (18-21 months) G2019S and R1441C mutant transgenic rats exhibit L-DOPA-responsive motor dysfunction, impaired striatal dopamine release as determined by fast-scan cyclic voltammetry, and cognitive deficits. In addition, in vivo recordings of identified substantia nigra pars compacta dopamine neurons in R1441C LRRK2 transgenic rats reveal an age-dependent reduction in burst firing, which likely results in further reductions to striatal dopamine release. These alterations to dopamine circuit function occur in the absence of neurodegeneration or abnormal protein accumulation within the substantia nigra pars compacta, suggesting that nigrostriatal dopamine dysfunction precedes detectable protein aggregation and cell death in the development of Parkinson's disease. In conclusion, our longitudinal deep-phenotyping provides novel insights into how the genetic burden arising from human mutant LRRK2 manifests as early pathophysiological changes to dopamine circuit function and highlights a potential model for testing Parkinson's therapeutics., (© The Author 2016. Published by Oxford University Press.)

GABAergic activity is thought to influence developing neocortical sensory circuits. Yet the late postnatal maturation of local layer (L)4 circuits suggests alternate sources of GABAergic control in nascent thalamocortical networks. We show that a population of L5b, somatostatin (SST)-positive interneuron receives early thalamic synaptic input and, using laser-scanning photostimulation, identify an early transient circuit between these cells and L4 spiny stellates (SSNs) that disappears by the end of the L4 critical period. Sensory perturbation disrupts the transition to a local GABAergic circuit, suggesting a link between translaminar and local control of SSNs. Conditional silencing of SST+ interneurons or conversely biasing the circuit toward local inhibition by overexpression of neuregulin-1 type 1 results in an absence of early L5b GABAergic input in mutants and delayed thalamic innervation of SSNs. These data identify a role for L5b SST+ interneurons in the control of SSNs in the early postnatal neocortex., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Midbrain dopaminergic (mDA) neurons are implicated in cognitive functions, neuropsychiatric disorders, and pathological conditions; hence understanding genes regulating their homeostasis has medical relevance. Transcription factors FOXA1 and FOXA2 (FOXA1/2) are key determinants of mDA neuronal identity during development, but their roles in adult mDA neurons are unknown. We used a conditional knockout strategy to specifically ablate FOXA1/2 in mDA neurons of adult mice. We show that deletion of Foxa1/2 results in down-regulation of tyrosine hydroxylase, the rate-limiting enzyme of dopamine (DA) biosynthesis, specifically in dopaminergic neurons of the substantia nigra pars compacta (SNc). In addition, DA synthesis and striatal DA transmission were reduced after Foxa1/2 deletion. Furthermore, the burst-firing activity characteristic of SNc mDA neurons was drastically reduced in the absence of FOXA1/2. These molecular and functional alterations lead to a severe feeding deficit in adult Foxa1/2 mutant mice, independently of motor control, which could be rescued by L-DOPA treatment. FOXA1/2 therefore control the maintenance of molecular and physiological properties of SNc mDA neurons and impact on feeding behavior in adult mice.

Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle-specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist prazosin to the drinking water of Sprague-Dawley rats (n = 33), whereas 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-wk prazosin treatment, which ensured that prazosin was cleared from the blood stream. Whole body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue-specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]glucose during the plateau phase of the clamp. Whole body insulin sensitivity increased by ∼24%, and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]glucose disposal increased by ∼30% concomitant with an ∼20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes., (Copyright © 2014 the American Physiological Society.)

Objective: To propose a measure (index) of expected risks to evaluate and follow up the performance analysis of research projects involving financial and adequate structure parameters for its development., Methods: A ranking of acceptable results regarding research projects with complex variables was used as an index to gauge a project performance. In order to implement this method the ulcer index as the basic model to accommodate the following variables was applied: costs, high impact publication, fund raising, and patent registry. The proposed structured analysis, named here as RoSI (Return on Scientific Investment) comprises a pipeline of analysis to characterize the risk based on a modeling tool that comprises multiple variables interacting in semi-quantitatively environments., Results: This method was tested with data from three different projects in our Institution (projects A, B and C). Different curves reflected the ulcer indexes identifying the project that may have a minor risk (project C) related to development and expected results according to initial or full investment., Conclusion: The results showed that this model contributes significantly to the analysis of risk and planning as well as to the definition of necessary investments that consider contingency actions with benefits to the different stakeholders: the investor or donor, the project manager and the researchers.