Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress

Relapse in cocaine seeking and intake is one of the main challenges when treating its addiction. Among the triggering factors for recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which are responsible for emotional and episodic memories. Besides, D3 receptor (D3R) antagonists have recently arisen as a potential treatment for preventing drug relapse. Thus, we have assessed the impact of D3R blockade in the expression of some dopaminergic markers and in the activity of the mTOR pathway, that is modulated by D3R, in the BLA and DG during the reinstatement of cocaine-induced CPP evoked by drug priming and social stress. Reinstatement of cocaine-CPP paralleled with a trend to increase of D3R and dopamine transporter (DAT) levels in the BLA. Social stress-but not drug-induced reactivation of cocaine memories was prevented by systemic administration of SB-277011-A (a selective D3R antagonist), that was able, however, to impede D3R and DAT up-regulation in the BLA during CPP reinstatement evoked by both stress and cocaine. Concomitantly with cocaine-CPP reactivation occurred a diminution of mTOR phosphorylation (activation) in the BLA and DG that was inhibited by D3R blockade in both nuclei before the social stress episode, and only in the BLA when CPP reinstatement was provoked by a cocaine prime. Our data, while support a main role for D3R signalling in the BLA in the reactivation of cocaine memories evoked by social stress, indicates that different neural circuits and signalling mechanisms might mediate in the reinstatement of cocaine-seeking behaviours depending upon the triggering stimuli.
Does land use matter? Carbon consequences of alternative land use futures in New England

Globally, forests play an important role in climate change mitigation. However, land-use impacts the ability of forests to sequester and store carbon. Here we quantify the impacts of five divergent future land-use scenarios on aboveground forest carbon stocks and fluxes throughout New England. These scenarios, four co-designed with stakeholders from throughout the region and the fifth a continuation of recent trends in land use, were simulated by coupling a land cover change model with a mechanistic forest growth model to produce estimates of aboveground carbon over 50 years. Future carbon removed through harvesting and development was tracked using a standard carbon accounting methodology, modified to fit our modeling framework. Of the simulated changes in land use, changes in harvesting had the most profound and immediate impacts on carbon stocks and fluxes. In one of the future land-use scenarios including a rapid expansion of harvesting for biomass energy, this changed New England’s forests from a net carbon sink to a net carbon source in 2060. Also in these simulations, relatively small reductions in harvest intensities (e.g., 10% reduction), coupled with an increased percent of wood going into longer-term storage, led to substantial reductions in net carbon emissions (909 MMtCO2eq) as compared to a continuation of recent trends in land use. However, these projected gains in carbon storage and reduction in emissions from less intense harvesting regimes can only be realized if it is paired with a reduction in the consumption of the timber products, and their replacements, that otherwise would result in additional emissions from leakage and substitution.
No evidence for general intelligence in a fish

Differences in human general intelligence or reasoning ability can be quantified with the psychometric factor g, because individual performance across cognitive tasks is positively correlated. g also emerges in mammals and birds, is correlated with brain size and may similarly reflect general reasoning ability and behavioural flexibility in these species. To exclude the alternative that these positive cross-correlations may merely reflect the general biological quality of an organism or an inevitable by-product of having brains it is paramount to provide solid evidence for the absence of g in at least some species. Here, we show that wild-caught cleaner fish Labroides dimidiatus, a fish species otherwise known for its highly sophisticated social behaviour, completely lacks g when tested on ecologically non-relevant tasks. Moreover, performance in these experiments was not or negatively correlated with an ecologically relevant task, and in none of the tasks did fish caught from a high population density site outperform fish from a low-density site. g is thus unlikely a default result of how brains are designed, and not an automatic consequence of variation in social complexity. Rather, the results may reflect that g requires a minimal brain size, and thus explain the conundrum why the average mammal or bird has a roughly 10 times larger brain relative to body size than ectotherms. Ectotherm brains and cognition may therefore be organized in fundamentally different ways compared to endotherms.
Dimerisation of the PICTS complex via LC8/Cut-up drives co-transcriptional transposon silencing in Drosophila

In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through the co-transcriptional gene silencing of transposon insertions. In Drosophila ovaries, piRNA-loaded Piwi detects nascent transposon transcripts and instructs heterochromatin formation through the Panoramix-induced co-transcriptional silencing (PICTS) complex, containing Panoramix, Nxf2 and Nxt1. Here, we report that the highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component of the PICTS complex. Loss of Ctp results in transposon de-repression and a reduction in repressive chromatin marks specifically at transposon loci. In turn, Ctp can enforce transcriptional silencing when artificially recruited to RNA and DNA reporters. We show that Ctp drives dimerisation of the PICTS complex through its interaction with conserved motifs within Panoramix. Artificial dimerisation of Panoramix bypasses the necessity for its interaction with Ctp, demonstrating that conscription of a protein from a ubiquitous cellular machinery has fulfilled a fundamental requirement for a transposon silencing complex.
More than expected: the abundance of yellow-legged gulls Larus michahellis breeding in the historic centre of Venice and the initial effects of the new waste collection policy on the population

Yellow-legged gull, Larus michahellis, has undergone widespread colonization of the urban environment in recent past. Starting in 2000 this affected the historical centre of Venice, 24 roof-nesting pairs being recorded in 2005, with this number increasing significantly in the last decade. In 2016, the waste management company of Venice established a new door to door garbage collection system to prevent the accumulation of rubbish in the streets and limit the trophic resources available for the species. The study provides an up-to-date estimate of the urban population of yellow-legged gulls, using Distance Sampling method. We also studied the effect of the new system on the species by comparing the population estimate before and after the change and by analysing the trend of individuals collected in the old town by the service of wildlife recovery during 2010-2018. Results estimate 440 breeding pairs (95s% confidence interval: 326-593) in June 2018 and show a 34% decrease of breeding pairs in 2018 with respect to 2017, as well as a decrease in number of 1-year birds and pulli collected by wildlife recovery service starting from 2016, year of the policy implementation. Our data did not show a significant decrease in the overall number of individuals, suggesting the new policy has a stronger effect on the breeding success of the species than on adult survival. This study emphasizes the importance of preventing rubbish accumulation in the streets as factor for reducing the abundance of urban yellow-legged gulls.
Protist and Fungal Metaxin-like Proteins: Relationship to Vertebrate Metaxins that Function in Protein Import into Mitochondria

Metaxin-like proteins are shown to be encoded in the genomes of a wide range of protists and fungi. The metaxin proteins were originally described in humans and mice, and were experimentally demonstrated to have a role in the import of nascent proteins into mitochondria. In this study, metaxin-like proteins of protists and fungi predicted from genome sequences were identified by criteria including their sequence homology with vertebrate metaxin proteins and the existence of distinctive metaxin protein domains. Protists of diverse taxa, including amoebae, protozoa, phytoplankton, downy mildews, water molds, and algae, were found to possess genes for metaxin-like proteins. With fungi, the important taxonomic divisions (phyla) of Ascomycota, Basidiomycota, Chytridiomycota, Mucoromycota, and Zoopagomycota had species with metaxin-like protein genes. The presence of distinctive GST_N_Metaxin, GST_C_Metaxin, and Tom37 domains in the predicted proteins indicates that the protist and fungal proteins are related to the vertebrate metaxins. However, the metaxin-like proteins are not direct homologs of vertebrate metaxins 1, 2, or 3, but have similarity to each of the three. The alignment of the metaxin-like proteins of a variety of protists with vertebrate metaxins 1 and 2 showed about 26% and 19% amino acid identities, respectively, while for fungal metaxin-like proteins, the identities were about 29% and 23%. The different percentages with the two vertebrate metaxins indicates that the metaxin-like proteins are both metaxin 1-like and, to a lesser degree, metaxin 2-like. The secondary structures of protist and fungal metaxin-like proteins both consist of nine α-helical segments, the same as for the vertebrate metaxins, with a negligible contribution from β-strand. Phylogenetic analysis demonstrated that the protist and fungal metaxin-like proteins and the vertebrate metaxins form distinct and separate groups, but that the groups are derived from a common ancestral protein sequence.
Synaptojanin1 deficiency upregulates basal level autophagosome formation in astrocytes

Macroautophagy (hereafter, autophagy) dysregulation is implicated in multiple neurological disorders. While the autophagy pathways are heavily investigated in heterologous cells and neurons, how autophagy is regulated in the astrocyte, the most abundant cell type in the mammalian brain, is less understood. Here we report that Synaptojanin1 (Synj1), a neuron enriched lipid phosphatase, is expressed in low levels in astrocytes and represses autophagy at the basal level. Synj1 is encoded by the Synj1 gene, whose missense mutations are linked to Parkinsonism with seizure. While the best-known role of Synj1 is to facilitate synaptic vesicle recycling, recent studies suggest that Synj1 also regulates autophagy. Our previous study using the Synj1 haploinsufficient (Synj1+/−) mouse demonstrated that Synj1 deficiency was associated with an age-dependent autophagy impairment in multiple brain regions. We now use cultured astrocytes from Synj1 deficient mice to investigate its role in astrocyte autophagy. We demonstrate that Synj1 deficient astrocytes exhibit increased LC3 puncta, which is more pronounced when lysosomal acidification is blocked. The increased autophagosome formation is accompanied by reduced autophagy substrate, p62, but an insensitivity to starvation induced autophagy clearance. Moreover, we show, for the first time, that the Parkinsonism associated R839C mutation impacts astrocyte autophagy. The profound impact of this mutation on Synj1’s phosphatase functions results in elevated basal level autophagosome formation and clearance that mimics Synj1 deletion. We find that energy sensing molecules, including mTOR and AMPK, are altered in Synj1 deficient astrocytes, which may contribute to the enhanced basal level autophagy.
Pan-genome Analysis in Sorghum Highlights the Extent of Genomic Variation and Sugarcane Aphid Resistance Genes

Sorghum bicolor, one of the most important grass crops around the world, harbors a high degree of genetic diversity. We constructed chromosome-level genome assemblies for two important sorghum inbred lines, Tx2783 and RTx436. The final high-quality reference assemblies consist of 19 and 18 scaffolds, respectively, with contig N50 values of 25.6 and 20.3 Mb. Genes were annotated using evidence-based and de novo gene predictors, and RAMPAGE data demonstrate that transcription start sites were effectively captured. Together with other public sorghum genomes, BTx623, RTx430, and Rio, extensive structural variations (SVs) of various sizes were characterized using Tx2783 as a reference. Genome-wide scanning for disease resistance (R) genes revealed high levels of diversity among these five sorghum accessions. To characterize sugarcane aphid (SCA) resistance in Tx2783, we mapped the resistance region on chromosome 6 using a recombinant inbred line (RIL) population and found a SV of 191 kb containing a cluster of R genes in Tx2783. Using Tx2783 as a backbone, along with the SVs, we constructed a pan-genome to support alignment of resequencing data from 62 sorghum accessions, and then identified core and dispensable genes using this population. This study provides the first overview of the extent of genomic structural variations and R genes in the sorghum population, and reveals potential targets for breeding of SCA resistance.
Semi-supervised Calibration of Risk with Noisy Event Times (SCORNET) Using Electronic Health Record Data

Leveraging large-scale electronic health record (EHR) data to estimate survival curves for clinical events can enable more powerful risk estimation and comparative effectiveness research. However, use of EHR data is hindered by a lack of direct event times observations. Occurrence times of relevant diagnostic codes or target disease mentions in clinical notes are at best a good approximation of the true disease onset time. On the other hand, extracting precise information on the exact event time requires laborious manual chart review and is sometimes altogether infeasible due to a lack of detailed documentation. Current status labels – binary indicators of phenotype status during follow up – are significantly more efficient and feasible to compile, enabling more precise survival curve estimation given limited resources. Existing survival analysis methods using current status labels focus almost entirely on supervised estimation, and naive incorporation of unlabeled data into these methods may lead to biased results. In this paper we propose Semi-supervised Calibration of Risk with Noisy Event Times (SCORNET), which yields a consistent and efficient survival curve estimator by leveraging a small size of current status labels and a large size of imperfect surrogate features. In addition to providing theoretical justification of SCORNET, we demonstrate in both simulation and real-world EHR settings that SCORNET achieves efficiency akin to the parametric Weibull regression model, while also exhibiting non-parametric flexibility and relatively low empirical bias in a variety of generative settings.
From adverse to beneficial – contrasting dietary effects of freshwater mixotrophs on zooplankton

The importance of mixotrophic algae as key bacterivores in microbial food webs is increasingly acknowledged, but their effects on the next trophic level remain poorly understood. Their high stoichiometric food quality is contrasted by anti-grazing strategies. We tested the quality of freshwater mixotrophs as prey for zooplankton, using four non-colonial chrysophyte species and a cryptophyte as a high quality reference food. We (1) analyzed the stoichiometric and biochemical (fatty acid) composition of the mixotrophs, and (2) quantified their dietary effects on Daphnia longispina survival. Survival of D. longispina significantly depended on the identity of species provided as food, ranging from higher to lower as compared to starvation. This was not reflected in differences in cellular stoichiometry or fatty acid profiles of the mixotrophs. We suggest that toxicity may be the driver for the observed differences. Generalization of the dietary effects of mixotrophic chrysophytes does not appear straightforward. Besides fundamental species-specific differences, potential toxic effects may vary depending on environmental cues or physiological strategies. Notably in our study, Ochromonas tuberculata, a species previously reported to be deleterious turned out to be a beneficial food source, in terms of enabling high survival of D. longispina. We challenge the generality of the assumption that chrysophytes are of low value as food for zooplankton. We recommend that future studies test how environmental conditions and physiological strategies shape the quality of mixotrophs as food for consumers at higher trophic levels, specifically focusing on effects of dietary toxicity.
Structural basis for Potassium transport by KdpFABC

KdpFABC is an oligomeric K+ transport complex in prokaryotes that maintains ionic homeostasis under stress conditions. The complex comprises a channel-like subunit (KdpA) from the Superfamily of K+ Transporters and a pump-like subunit (KdpB) from the superfamily of P-type ATPases. Recent structural work has defined the architecture and generated contradictory hypotheses for the transport mechanism. Here, we use substrate analogs to stabilize four key intermediates in the reaction cycle and determine the corresponding structures by cryo-EM. We find that KdpB undergoes conformational changes consistent with other representatives from the P-type superfamily, whereas KdpA, KdpC and KdpF remain static. We observe a series of spherical densities that we assign as K+ or water and which define a pathway for K+ transport. This pathway runs through an intramembrane tunnel in KdpA and delivers ions to sites in the membrane domain of KdpB. Our structures suggest a mechanism where ATP hydrolysis is coupled to K+ transfer between alternative sites in the membrane domain of KdpB, ultimately reaching a low-affinity site where a water-filled pathway allows release of K+ to the cytoplasm.
A Self-Supervised Machine Learning Approach for Objective Live Cell Segmentation and Analysis

Machine learning algorithms hold the promise of greatly improving live cell image analysis by way of (1) analyzing far more imagery than can be achieved by more traditional manual approaches and (2) by eliminating the subjective nature of researchers and diagnosticians selecting the cells or cell features to be included in the analyzed data set. Currently, however, even the most sophisticated model based or machine learning algorithms require user supervision, meaning the subjectivity problem is not removed but rather incorporated into the algorithm’s initial training steps and then repeatedly applied to the imagery. To address this roadblock, we have developed a self-supervised machine learning algorithm that recursively trains itself directly from the live cell imagery data, thus providing objective segmentation and quantification. The approach incorporates an optical flow algorithm component to self-label cell and background pixels for training, followed by the extraction of additional feature vectors for the automated generation of a cell/background classification model. Because it is self-trained, the software has no user-adjustable parameters and does not require curated training imagery. The algorithm was applied to automatically segment cells from their background for a variety of cell types and five commonly used imaging modalities - fluorescence, phase contrast, differential interference contrast (DIC), transmitted light and interference reflection microscopy (IRM). The approach is broadly applicable in that it enables completely automated cell segmentation for long-term live cell phenotyping applications, regardless of the input imagery’s optical modality, magnification or cell type.
Microglial Neuropilin-1 trans-regulates oligodendrocyte expansion during development and remyelination

NG2 glia or oligodendrocyte precursor cells (OPCs) are distributed throughout the gray and white matter and generate myelinating cells. OPCs in white matter proliferate more than those in gray matter in response to platelet-derived growth factor AA (PDGF AA), despite similar levels of its alpha receptor (PDGFRα) on their surface. Here we show that the type 1 integral membrane protein Neuropilin-1 (Nrp1) is expressed not on OPCs but on amoeboid and activated microglia in white but not gray matter in an age- and activity-dependent manner. Microglia-specific deletion of Nrp1 compromised developmental OPC proliferation in white matter as well as OPC expansion and subsequent myelin repair after acute demyelination. Exogenous Nrp1 increased PDGF AA-induced OPC proliferation and PDGFRα phosphorylation on dissociated OPCs, most prominently in the presence of suboptimum concentrations of PDGF AA. These findings uncover a novel mechanism of regulating oligodendrocyte lineage cell density that involves trans-activation of PDGFRα on OPCs via Nrp1 expressed by adjacent microglia.
Extracellular endosulfatase Sulf-2 harbours a chondroitin/dermatan sulfate chain that modulates its enzyme activity

Sulfs represent a class of unconventional sulfatases, which differ from all other members of the sulfatase family by their structures, catalytic features and biological functions. Through their specific endosulfatase activity in extracellular milieu, Sulfs provide an original post-synthetic regulatory mechanism for heparan sulfate complex polysaccharides and have been involved in multiple physiopathological processes, including cancer. However, Sulfs remain poorly characterized enzymes, with major discrepancies regarding their in vivo functions. Here we show that human Sulf-2 (HSulf-2) features a unique polysaccharide post-translational modification. We identified a chondroitin/dermatan sulfate glycosaminoglycan (GAG) chain, attached to the enzyme substrate binding domain. We found that this GAG chain affects enzyme/substrate recognition and tunes HSulf-2 activity in vitro and in vivo using a mouse model of tumorigenesis and metastasis. In addition, we showed that mammalian hyaluronidase acted as a promoter of HSulf-2 activity by digesting its GAG chain. In conclusion, our results highlight HSulf-2 as a unique proteoglycan enzyme and its newly-identified GAG chain as a critical non-catalytic modulator of the enzyme activity. These findings contribute in clarifying the conflicting data on the activities of the Sulfs and introduce a new paradigm into the study of these enzymes.