Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of cold compressed coconut oil on cognition and behavior among patients with Alzheimer's disease - A pilot intervention study

Background: Alzheimerâ€™s disease (AD)â€™s pharmacotherapy is limited, with anecdotal reports claiming some usefulness of cold pressed coconut oil. Aims and Objectives: To study the effect of cold pressed coconut oil on cognition and behavior of AD patients who are treatment naA¯ve or stabilized on cholinesterase inhibitors or memantine for at least 3 months with a mini-mental state examination (MMSE) score of 10-24. Materials and Methods: An investigator initiated pilot randomized controlled trial studied the effect of cold pressed coconut oil on cognition and behavior of AD patients. Minimum sample size was calculated assuming an increase of 30% in MMSE scores in the experimental group with 95% confidence interval and 80% power to be 20 at each experimental and control groups. Efficacy was measured using MMSE, clock drawing test (CDT), neuropsychiatric inventory questionnaire at baseline, 3 and 6 months, with safety profile monitored by electrocardiogram, and laboratory investigations at baseline and at 6 months. Results: 40 individuals out of 99 screened were enrolled, with no significant differences in cognitive level between the intervention and control group at baseline. At 6 months, the control group showed significant (P = 0.035) improvement in CDT. Diarrhea, the most common adverse event caused high dropout in intervention group. Conclusion: Cold pressed coconut oil did not improve cognition or behavior in AD patients.
Distant homologies and domain conservation of the Hereditary Spastic Paraplegia protein SPG11/ALS5/spatacsin

Loss-of-function mutations in SPG11 protein (spatacsin) are a common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. To identify regions of the protein that may have functions that are disrupted in disease, we carried out bioinformatic analyses of its conserved regions. An N-terminal region of around 650 amino-acid residues, present in SPG11 across a wide range of metazoan animals, was missing from many insect lineages. Evolutionary loss of this domain correlated with loss of its binding partner, the AP-5 adaptor complex, suggesting that its main function is interaction with AP-5 in intracellular trafficking, and that the remainder of SPG11 carries out AP-5-independent functions. At the C-terminus of SPG11, a spatacsin_C domain showed sequence similarity and predicted structural homology to the Vps16_C domain of the HOPS complex protein Vps16. It localized to acidic compartments, consistent with a role in endolysosomal or autolysosomal transport, like Vps16. Mass spectrometry analysis of binding partners of this domain identified membrane trafficking proteins, some SM proteins, and several aminoacyl-tRNA synthetases. Since mutations affecting SPG11 or aminoacyl-tRNA synthetases can both cause Charcot-Marie-Tooth neuropathy (CMT) type 2, we suggest autolysosomal trafficking as a target process in CMT type 2.
Adaptation supports short-term memory in a visual change detection task

The maintenance of short-term memories is critical for survival in a dynamically changing world. Previous studies suggest that this memory can be stored in the form of persistent neural activity or using a synaptic mechanism, such as with short-term plasticity. Here, we compare the predictions of these two mechanisms to neural and behavioral measurements in a visual change detection task. Mice were trained to respond to changes in a repeated sequence of natural images while neural activity was recorded using two-photon calcium imaging. We also trained two types of artificial neural networks on the same change detection task as the mice. Following fixed pre-processing using a pretrained convolutional neural network, either a recurrent neural network (RNN) or a feedforward neural network with short-term synaptic depression (STPNet) was trained to the same level of performance as the mice. While both networks are able to learn the task, the STPNet model contains units whose activity are more similar to the in vivo data and produces errors which are more similar to the mice. When images are omitted, an unexpected perturbation which was absent during training, mice often do not respond to the omission but are more likely to respond to the subsequent image. Unlike the RNN model, STPNet also produces a similar pattern of behavior. These results suggest that simple neural adaptation mechanisms may serve as an important bottom-up memory signal in this task, which can be used by downstream areas in the decision-making process. Author Summary Animals have to adapt to environments with rich dynamics and maintain multiple types of memories. In this study, we focus on a visual change detection task in mice which requires short-term memory. Learning which features need to be maintained in short-term memory can be realized in a recurrent neural network by changing connections in the network, resulting in memory maintenance through persistent activity. However, in biological networks, a large diversity of time-dependent intrinsic mechanisms are also available. As an alternative to persistent neural activity, we find that learning to make use of internal adapting dynamics better matches both the observed neural activity and behavior of animals in this simple task. The presence of a large diversity of temporal traces could be one of the reasons for the diversity of cells observed. We believe that both learning to keep representations of relevant stimuli in persistent activity and learning to make use of intrinsic time-dependent mechanisms exist, and their relative use will be dependent on the exact task.
The Gliopeptide ODN, a Ligand for the Benzodiazepine Site of GABAA Receptors, Boosts Functional Recovery after Stroke

Following stroke, the survival of neurons and their ability to reestablish connections is critical to functional recovery. This is strongly influenced by the balance between neuronal excitation and inhibition. In the acute phase of experimental stroke, lethal hyperexcitability can be attenuated by positive allosteric modulation of GABAA receptors (GABAARs). Conversely, in the late phase, negative allosteric modulation of GABAAR can correct the suboptimal excitability and improves both sensory and motor recovery. Here, we hypothesized that octadecaneuropeptide (ODN), an endogenous allosteric modulator of the GABAAR synthesized by astrocytes, influences the outcome of ischemic brain tissue and subsequent functional recovery. We show that ODN boosts the excitability of cortical neurons, which makes it deleterious in the acute phase of stroke. However, if delivered after day 3, ODN is safe and improves motor recovery over the following month in two different paradigms of experimental stroke in mice. Furthermore, we bring evidence that, during the subacute period after stroke, the repairing cortex can be treated with ODN by means of a single hydrogel deposit into the stroke cavity. SIGNIFICANCE STATEMENT Stroke remains a devastating clinical challenge because there is no efficient therapy to either minimize neuronal death with neuroprotective drugs or to enhance spontaneous recovery with neurorepair drugs. Around the brain damage, the peri-infarct cortex can be viewed as a reservoir of plasticity. However, the potential of wiring new circuits in these areas is restrained by a chronic excess of GABAergic inhibition. Here we show that an astrocyte-derived peptide, can be used as a delayed treatment, to safely correct cortical excitability and facilitate sensorimotor recovery after stroke.
Evolutionary Distance of Gene-Gene Interactions: Estimation under Statistical Uncertainty

Consider the functional interaction of gene A to an interaction subject X; for instance, it is the gene-gene interaction if X represents for a gene, or gene-tissue interaction (expression status) if X for a tissue. In the simplest case, the status of this A-X interaction is r=1 if they are interacted, or r=0 otherwise. A fundamental problem in molecular evolution is, given two homologous (orthologous or paralogous) genes A and B, to what extent their functional overlapping could be by the means of interaction networks. Given a set of interaction subjects (X1, … XN), it is straightforward to calculate the interaction distance (IAB) between genes A and B, by a Markov-chain model. However, since the high throughput interaction data always involve a high level of noises, reliable inference of r=1 or r=0 for each gene remains a big challenge. Consequently, the estimated interaction distance (IAB) is highly sensitive to the cutoff of interaction inference which is subject to some arbitrary. In this paper we will address this issue by developing a statistical method for estimating IAB based on the p-values (significant levels). Computer simulations are carried out to evaluate the performance of different p-value transformations against the uncertainty of interaction networks.
Anatomically precise relationship between specific amygdala connections and selective markers of mental well-being in humans

There has been increasing interest in using neuroimaging measures to predict psychiatric disorders. However, predictions usually rely on large numbers of brain connections and large disorder heterogeneity, thus lacking both anatomical and behavioural specificity, preventing the advancement of targeted interventions. Here, we address both challenges. First, using resting-state functional MRI, we parcellated the amygdala, a region implicated in mood disorders but difficult to image with high fidelity, into seven nuclei. Next, a questionnaire factor analysis provided four sub-clinical latent behaviours frequently found in anxious-depressive individuals, such as negative emotions and sleep problems. Finally, for each latent behaviour, we identified the most predictive connections between individual amygdala nuclei and highly specific regions of interest e.g. dorsal raphe nucleus in the brainstem or medial prefrontal cortical regions. A small number of distinct connections predicted behaviours, providing unprecedented levels of specificity, in humans, for relating mental well-being to precise anatomical connections.
Phosphorylation barcode-dependent signal bias of the dopamine D1 receptor

Significance The functional importance of receptor phosphorylation in GPCR regulation has been demonstrated. Over the past decade, the phospho-barcode concept was developed to explain the multidimensional nature of the arrestin-dependent signaling network downstream of GPCRs. Here, we used the dopamine-1 receptor (D1R) to explore the effect of receptor phosphorylation on G protein-dependent and arrestin-dependent ERK and Src activation. Our studies suggest that D1R intracellular loop-3 phosphorylation affects both G proteins and arrestins. Differential D1R phosphorylation can direct signaling toward ERK or Src activation. This implies that phosphorylation induces different conformations of receptor and/or bound arrestin to initiate or select different cellular signaling pathways. Agonist-activated G protein-coupled receptors (GPCRs) must correctly select from hundreds of potential downstream signaling cascades and effectors. To accomplish this, GPCRs first bind to an intermediary signaling protein, such as G protein or arrestin. These intermediaries initiate signaling cascades that promote the activity of different effectors, including several protein kinases. The relative roles of G proteins versus arrestins in initiating and directing signaling is hotly debated, and it remains unclear how the correct final signaling pathway is chosen given the ready availability of protein partners. Here, we begin to deconvolute the process of signal bias from the dopamine D1 receptor (D1R) by exploring factors that promote the activation of ERK1/2 or Src, the kinases that lead to cell growth and proliferation. We found that ERK1/2 activation involves both arrestin and Gαs, while Src activation depends solely on arrestin. Interestingly, we found that the phosphorylation pattern influences both arrestin and Gαs coupling, suggesting an additional way the cells regulate G protein signaling. The phosphorylation sites in the D1R intracellular loop 3 are particularly important for directing the binding of G protein versus arrestin and for selecting between the activation of ERK1/2 and Src. Collectively, these studies correlate functional outcomes with a physical basis for signaling bias and provide fundamental information on how GPCR signaling is directed.
Beyond a single patch: local and regional processes explain diversity patterns in a seagrass epifaunal metacommunity

Ecological communities are jointly structured by dispersal, density-independent responses to environmental conditions, and density-dependent biotic interactions. Metacommunity ecology provides a framework for understanding how these processes combine to determine community seagrass meadows along the British Columbia coast. We tested the hypothesis that eelgrass Zostera marina L. epifaunal invertebrate assemblages are influenced by local environmental conditions but that high dispersal rates at larger spatial scales dampen the effects of environmental differences. We used hierarchical joint species distribution modelling to understand the contribution of environmental conditions, spatial distance between meadows, and species co-occurrences to epifaunal invertebrate abundance and distribution across the region. We found that patterns of taxonomic compositional similarity among meadows were inconsistent with dispersal limitation, and meadows in the same region were often no more similar to each other than meadows over 1000 km away. Abiotic environmental conditions (temperature, dissolved oxygen) explained a small fraction of variation in taxonomic abundance patterns across the region. We found novel co-occurrence patterns among taxa that could not be explained by shared responses to environmental gradients, suggesting the possibility that interspecific interactions influence seagrass invertebrate abundance and distribution. Our results suggest that biodiversity and ecosystem functions provided by seagrass meadows reflect ecological processes occurring both within meadows and across seascapes and that management of eelgrass habitat for biodiversity may be most effective when both local and regional processes are considered.
Genome Regulation and Gene Interaction Networks Inferred From Muscle Transcriptome Underlying Feed Efficiency in Pigs

Improvement of feed efficiency (FE) is key for sustainability and cost reduction in pig production. Our aim was to characterize the muscle transcriptomic profiles in Danbred Duroc (Duroc) and Danbred Landrace (Landrace), in relation to FE for identifying potential biomarkers. RNA-seq data was analyzed employing differential gene expression methods, gene-gene interaction and network analysis, including pathway and functional analysis. We compared the results with genome regulation in human exercise data. In the differential expression analysis, 13 genes were differentially expressed, including: MRPS11, MTRF1, TRIM63, MGAT4A, KLH30. Based on a novel gene selection method, the divergent count, we performed pathway enrichment analysis. We found 5 significantly enriched pathways related to feed conversion ratio (FCR). These pathways were mainly mitochondrial, and summarized in the mitochondrial translation elongation (MTR) pathway. In the gene interaction analysis, highlights include the mitochondrial genes: PPIF, MRPL35, NDUFS4and the fat metabolism and obesity genes: AACS, SMPDL3B, CTNNBL1, NDUFS4 and LIMD2. In the network analysis, we identified two modules significantly correlated with FCR. Pathway enrichment of modules identified MTR, electron transport chain and DNA repair as enriched pathways. In the network analysis, the mitochondrial gene group NDUF was a key hub group, showing potential as biomarkers. Comparing with human transcriptomic exercise studies, genes related to exercise displayed enrichment in our FCR related genes. We conclude that mitochondrial activity is a driver for FCR in muscle tissue, and mitochondrial genes could be potential biomarkers for FCR in pigs. We hypothesize that increased FE mimics processes triggered in exercised muscle.
StPOPA, encoding an anionic peroxidase in Solanum tuberosum, enhances resistance against Phytophthora infestans

Potato late blight, caused by Phytophthora infestans, is one of the major threats affecting the quality and output of potato all over the world. Reactive oxygen species (ROS) acted as a signal molecule to transmit signals in plants at the early stage of disease infection, and it could induce disease resistance of the plant, including potato late blight. Anionic peroxidases in many plants were reported to be involved in defense to disease. However, limited information about anionic peroxidase genes is available for the potato. Here, we reported that the expression of the StPOPA, a gene encoding a suberization-associated anionic peroxidase, was associated with resistance in potato against P. infestans. The StPOPA gene was induced by P. infestans infection, mechanical damage, jasmonic acid and ethylene treatment. Overexpression of the StPOPA gene in potato enhanced the resistance against P. infestans via promoting the accumulation of callose in the cell wall and ROS in the cytoplasm, which restricted the infection and spreading of the disease possibly by purposeful programmed cell death. Taken together, our results suggested that the StPOPA gene contributed to potato immunity against P. infestans and this gene could be used for the genetic improvement of resistance against potato late blight.
A critical assessment of single-cell transcriptomes sampled following patch-clamp electrophysiology

Patch-seq, combining patch-clamp electrophysiology with single-cell RNA-sequencing (scRNAseq), enables unprecedented single-cell access to a neuron’s transcriptomic, electrophysiological, and morphological features. Here, we present a systematic review and re-analysis of scRNAseq profiles from 4 recent patch-seq datasets, benchmarking these against analogous profiles from cellular-dissociation based scRNAseq. We found an increased likelihood for off-target cell-type mRNA contamination in patch-seq, likely due to the passage of the patch-pipette through the processes of adjacent cells. We also observed that patch-seq samples varied considerably in the amount of mRNA that could be extracted from each cell, strongly biasing the numbers of detectable genes. We present a straightforward marker gene-based approach for controlling for these artifacts and show that our method improves the correspondence between gene expression and electrophysiological features. Our analysis suggests that these technical confounds likely limit the interpretability of patch-seq based single-cell transcriptomes. However, we provide concrete recommendations for quality control steps that can be performed prior to costly RNA-sequencing to optimize the yield of high quality samples.
Evidence for Elton’s diversity-invasibility hypothesis from belowground

Sixty year ago, Elton proposed that diverse communities are more resistant to biological invasion. However, still little is known about which processes could drive this diversity-invasibility relationship. Here we examined whether plant-soil feedback on alien invaders is more negative when the soil originates from multiple native species. We trained soils with five individually grown native species, and used amplicon sequencing to analyze the resulting bacterial and fungal soil communities. We mixed the soils to create trained soils from one, two or four native species. We then grew four alien species separately on these differently trained soils. In the soil-conditioning phase, the five native species built species-specific bacterial and fungal communities in their rhizospheres. In the test phase, it did not matter whether the soil had been trained by one or two native species. However, the alien species achieved 11.7% less aboveground biomass when grown on soils trained by four native species than on soils trained by two native species. Our results showed for the first time, that plant-soil feedback could be a process that contributes to the negative relationship between diversity and invasibility.
Geological degassing enhances microbial metabolism in the continental subsurface

Mantle degassing provides a substantial amount of reduced and oxidized gases shaping microbial metabolism at volcanic sites across the globe, yet little is known about its impact on microbial life under non-thermal conditions. Here, we characterized deep subsurface fluids from a cold-water geyser driven by mantle degassing using genome-resolved metagenomics to investigate how the gases impact the metabolism and activity of indigenous microbes compared to non-impacted sites. While species-specific analyses of Altiarchaeota suggest site-specific adaptations and a particular biogeographic pattern, chemolithoautotrophic core features of the communities appeared to be conserved across 17 groundwater ecosystems between 5 and 3200 m depth. We identified a significant negative correlation between ecosystem depth and bacterial replication, except for samples impacted by high amounts of subsurface gases, which exhibited near-surface activity. Our results suggest that geological degassing leads to higher nutrient flows and microbial activity in the deep subsurface than previously estimated.
A Tgfbr1/Snai1-dependent developmental module at the core of vertebrate axial elongation

Formation of the vertebrate postcranial body axis follows two sequential but distinct phases. The first phase generates pre-sacral structures (the so-called primary body) through the activity of the primitive streak on axial progenitors within the epiblast. The embryo then switches to generate the secondary body (post-sacral structures), which depends on axial progenitors in the tail bud. Here we show that the mammalian tail bud is generated through an independent functional developmental module, concurrent but functionally different from that generating the primary body. This module is triggered by convergent Tgfbr1 and Snai1 activities that promote an incomplete epithelial to mesenchymal transition on a subset of epiblast axial progenitors. This EMT is functionally different from that coordinated by the primitive streak, as it does not lead to mesodermal differentiation but brings axial progenitors into a transitory state, keeping their progenitor activity to drive further axial body extension.