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Ventral hippocampal CA1 (vCA1) projections to the amygdala are necessary for contextual fear memory. Here we used in vivo Ca 2+ imaging in mice to assess the temporal dynamics by which ensembles of vCA1 neurons mediate encoding and retrieval of contextual fear memories. We found that a subset of vCA1 neurons were responsive to the aversive shock during context conditioning, their activity was necessary for memory encoding, and these shock-responsive neurons were enriched in the vCA1 projection to the amygdala. During memory retrieval, a population of vCA1 neurons became correlated with shock-encoding neurons, and the magnitude of synchronized activity within this population was proportional to memory strength. The emergence of these correlated networks was disrupted by inhibiting vCA1 shock responses during memory encoding. Thus, our findings suggest that networks of cells that become correlated with shock-responsive neurons in vCA1 are essential components of contextual fear memory ensembles. The vCA1-BA projection is enriched in shock responsive neurons, which are necessary for fear memory encoding and become correlated with a network of neurons during retrieval. Here the authors show that the magnitude of vCA1 correlated activity is proportional to memory strength and requires the shock response during encoding.

Resorting to a One Strain Many Compounds (OSMAC) approach, the marine Streptomyces sp. BRB081 strain was grown in six different media settings over 1, 2, 3 or 7 days. Extractions of mycelium and broth were conducted separately for each media and cultivation period by sonication using methanol/acetone 1:1 and agitation with ethyl acetate, respectively. All methanol/acetone and ethyl acetate crude extracts were analysed by HPLC-MS/MS and data treatment was performed through GNPS platform using MZmine 2 software. In parallel, the genome was sequenced, assembled and mined to search for biosynthetic gene clusters (BGC) of secondary metabolites using the AntiSMASH 5.0 software. Spectral library search tool allowed the annotation of desferrioxamines, fatty acid amides, diketopiperazines, xanthurenic acid and, remarkably, the cyclic octapeptides surugamides. Molecular network analysis allowed the observation of the surugamides cluster, where surugamide A and the protonated molecule corresponding to the B-E isomers, as well as two potentially new analogues, were detected. Data treatment through MZmine 2 software allowed to distinguish that the largest amount of surugamides was obtained by cultivating BRB081 in SCB medium during 7 days and extraction of culture broth. Using the same data treatment, a chemical barcode was created for easy visualization and comparison of the metabolites produced overtime in all media. By genome mining of BRB081 four regions of biosynthetic gene clusters of secondary metabolites were detected supporting the metabolic data. Cytotoxic evaluation of all crude extracts using MTT assay revealed the highest bioactivity was also observed for extracts obtained in the optimal conditions as those for surugamides production, suggesting these to be the main active compounds herein. This method allowed the identification of compounds in the crude extracts and guided the selection of best conditions for production of bioactive compounds.

Single-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for the comprehensive analysis of the nuclear transcriptome from frozen tissues, allowing the dissection of all cell types present in the liver, regardless of cell size or cellular fragility. We use this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that ploidy states are associated with different metabolic potential, and gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobule. Our work reveals a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes.

In neuroscience, empathy is often conceived as relatively automatic. The voluntary control that people can exert on brain mechanisms that map the emotions of others onto our own emotions has received comparatively less attention. Here, we therefore measured brain activity while participants watched emotional Hollywood movies under two different instructions: to rate the main characters’ emotions by empathizing with them, or to do so while keeping a detached perspective. We found that participants yielded highly consistent and similar ratings of emotions under both conditions. Using intersubject correlation-based analyses we found that, when encouraged to empathize, participants’ brain activity in limbic (including cingulate and putamen) and somatomotor regions (including premotor, SI and SII) synchronized more during the movie than when encouraged to detach. Using intersubject functional connectivity we found that comparing the empathic and detached perspectives revealed widespread increases in functional connectivity between large scale networks. Our findings contribute to the increasing awareness that we have voluntary control over the neural mechanisms through which we process the emotions of others. •People are highly consistent in their rating of characters’ emotions in movies.•Voluntarily empathizing increases recruitment of empathy related brain regions.•Voluntarily empathizing increases functional connectivity across networks.•Voluntarily empathizing increases perceived intensity of other people’s emotions.

Several large-scale drivers of both anthropogenic and natural environmental changes are interacting nonlinearly in the transition zone between eastern Amazonia and the adjacent Cerrado, considered to be another Brazilian agricultural frontier. Land-use change for agrobusiness expansion together with climate change in the transition zone between eastern Amazonia and the adjacent Cerrado may have induced a worsening of severe drought conditions over the last decade. Here we show that the largest warming and drying trends over tropical South America during the last four decades are observed to be precisely in the eastern Amazonia-Cerrado transition region, where they induce delayed wetseason and worsen severe drought conditions over the last decade. Our results evidence an increase in temperature, vapor pressure deficit, subsidence, dry-day frequency, and a decrease in precipitation, humidity, and evaporation, plus a delay in the onset of the wet season, inducing a higher risk of fire during the dry-to-wet transition season. These findings provide observational evidence of the increasing climatic pressure in this area, which is sensitive for global food security, and the need to reconcile agricultural expansion and protection of natural tropical biomes.

In vivo calcium imaging through microendoscopic lenses enables imaging of previously inaccessible neuronal populations deep within the brains of freely moving animals. However, it is computationally challenging to extract single-neuronal activity from microendoscopic data, because of the very large background fluctuations and high spatial overlaps intrinsic to this recording modality. Here, we describe a new constrained matrix factorization approach to accurately separate the background and then demix and denoise the neuronal signals of interest. We compared the proposed method against previous independent components analysis and constrained nonnegative matrix factorization approaches. On both simulated and experimental data recorded from mice, our method substantially improved the quality of extracted cellular signals and detected more well-isolated neural signals, especially in noisy data regimes. These advances can in turn significantly enhance the statistical power of downstream analyses, and ultimately improve scientific conclusions derived from microendoscopic data.

Streptococcus pyogenes (Group A Streptococcus, GAS) is an important human commensal that occasionally causes localized infections and less frequently causes severe invasive disease with high mortality rates. How GAS regulates expression of factors used to colonize the host and avoid immune responses remains poorly understood. Intercellular communication is an important means by which bacteria coordinate gene expression to defend against host assaults and competing bacteria, yet no conserved cell-to-cell signaling system has been elucidated in GAS. Encoded within the GAS genome are four rgg-like genes, two of which (rgg2 and rgg3) have no previously described function. We tested the hypothesis that rgg2 or rgg3 rely on extracellular peptides to control target-gene regulation. We found that Rgg2 and Rgg3 together tightly regulate two linked genes encoding new peptide pheromones. Rgg2 activates transcription of and is required for full induction of the pheromone genes, while Rgg3 plays an antagonistic role and represses pheromone expression. The active pheromone signals, termed SHP2 and SHP3, are short and hydrophobic (DI[I/L]IIVGG), and, though highly similar in sequence, their ability to disrupt Rgg3-DNA complexes were observed to be different, indicating that specificity and differential activation of promoters are characteristics of the Rgg2/3 regulatory circuit. SHP-pheromone signaling requires an intact oligopeptide permease (opp) and a metalloprotease (eep), supporting the model that pro-peptides are secreted, processed to the mature form, and subsequently imported to the cytoplasm to interact directly with the Rgg receptors. At least one consequence of pheromone stimulation of the Rgg2/3 pathway is increased biogenesis of biofilms, which counteracts negative regulation of biofilms by RopB (Rgg1). These data provide the first demonstration that Rgg-dependent quorum sensing functions in GAS and substantiate the role that Rggs play as peptide receptors across the Firmicute phylum.

Fused-in-Sarcoma ( FUS ) gene encodes an RNA/DNA binding protein whose mutations are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). This study shows that FUS functions in the neuronal DNA damage response by its recruitment to the site of DNA double-stranded breaks and by its interaction with histone deacetylase 1. The study also shows ALS/FTLD-associated mutant FUS is defective in DNA repair mechanism and that ALS/FTLD patients with FUS mutations have greater DNA damage. Defects in DNA repair have been extensively linked to neurodegenerative diseases, but the exact mechanisms remain poorly understood. We found that FUS, an RNA/DNA-binding protein that has been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, is important for the DNA damage response (DDR). The function of FUS in DDR involved a direct interaction with histone deacetylase 1 (HDAC1), and the recruitment of FUS to double-stranded break sites was important for proper DDR signaling. Notably, FUS proteins carrying familial ALS mutations were defective in DDR and DNA repair and showed a diminished interaction with HDAC1. Moreover, we observed increased DNA damage in human ALS patients harboring FUS mutations. Our findings suggest that an impaired DDR and DNA repair may contribute to the pathogenesis of neurodegenerative diseases linked to FUS mutations.

Land surface waters play a primary role in the global water cycle and climate. As a consequence, there is a widespread demand for accurate and long‐term quantitative observations of their distribution over the whole globe. This study presents the first global data set that quantifies the monthly distribution of surface water extent at ∼25 km sampling intervals over 12 years (1993–2004). These estimates, generated from complementary multiple‐satellite observations, including passive (Special Sensor Microwave Imager) and active (ERS scatterometer) microwaves along with visible and near‐infrared imagery (advanced very high‐resolution radiometer; AVHRR), were first developed over 1993–2000. The ERS encountered technical problems in 2001 and the processing scheme had to be adapted to extend the time series. Here we investigate and discuss the adjustments of the methodology, compare the various options, and show that the data set can be extended with good confidence beyond 2000, using ERS and AVHRR mean monthly climatologies. In addition to a large seasonal and interannual variability, the new results show a slight overall decrease in global inundated area between 1993 and 2004, representing an ∼5.7% reduction of the mean annual maximum in 12 years. The decrease is mainly observed in the tropics during the 1990s. Over inland water bodies and large river basins, we assess the variability of the surface water extent against related variables such as in situ river discharges, altimeter‐derived and in situ river/floodplain water level heights, and precipitation estimates. This new 12 year data set of global surface water extent represents an unprecedented source of information for future hydrological or methane modeling.

The WAter Cycle Multi-mission Observation Strategy – EvapoTranspiration (WACMOS-ET) project aims to advance the development of land evaporation estimates on global and regional scales. Its main objective is the derivation, validation, and intercomparison of a group of existing evaporation retrieval algorithms driven by a common forcing data set. Three commonly used process-based evaporation methodologies are evaluated: the Penman–Monteith algorithm behind the official Moderate Resolution Imaging Spectroradiometer (MODIS) evaporation product (PM-MOD), the Global Land Evaporation Amsterdam Model (GLEAM), and the Priestley–Taylor Jet Propulsion Laboratory model (PT-JPL). The resulting global spatiotemporal variability of evaporation, the closure of regional water budgets, and the discrete estimation of land evaporation components or sources (i.e. transpiration, interception loss, and direct soil evaporation) are investigated using river discharge data, independent global evaporation data sets and results from previous studies. In a companion article (Part 1), Michel et al. (2016) inspect the performance of these three models at local scales using measurements from eddy-covariance towers and include in the assessment the Surface Energy Balance System (SEBS) model. In agreement with Part 1, our results indicate that the Priestley and Taylor products (PT-JPL and GLEAM) perform best overall for most ecosystems and climate regimes. While all three evaporation products adequately represent the expected average geographical patterns and seasonality, there is a tendency in PM-MOD to underestimate the flux in the tropics and subtropics. Overall, results from GLEAM and PT-JPL appear more realistic when compared to surface water balances from 837 globally distributed catchments and to separate evaporation estimates from ERA-Interim and the model tree ensemble (MTE). Nonetheless, all products show large dissimilarities during conditions of water stress and drought and deficiencies in the way evaporation is partitioned into its different components. This observed inter-product variability, even when common forcing is used, suggests that caution is necessary in applying a single data set for large-scale studies in isolation. A general finding that different models perform better under different conditions highlights the potential for considering biome- or climate-specific composites of models. Nevertheless, the generation of a multi-product ensemble, with weighting based on validation analyses and uncertainty assessments, is proposed as the best way forward in our long-term goal to develop a robust observational benchmark data set of continental evaporation.