Miracle-dz/UniFAR-FTUs huggingface dataset:
Most at‐risk individuals will not develop a mental disorder: the limited predictive strength of risk factors

World Psychiatry 20:2 June 2021 vehicle for indicated prevention of psychosis, one of the recent criticisms of the approach, echoed by Fusar-Poli et al, derives from the NEMESIS-2 cohort report that antecedent mood disorders account for more of the incidence of clinical psychosis than do psychotic-like symptoms. We see three important limitations of the NEMESIS-2 data that have received little attention. First, psychotic-like experiences gauged through questionnaires or non-clinical interviews in the general population are not comparable to clinician-assessed CHR syndromes. Second, the time-points in NEMESIS-2 were spaced three years apart. Partly-prospective data show that the average duration of CHR symptoms is two years or less in two-thirds of patients converting to psychosis, suggesting that the development of psychotic-like symptoms prior to psychosis may have been missed by the NEMESIS-2 design in as many as half the cases. Third and most crucially, the average age of cohort members at the second time point was 47.7 years, far older than the 12-to-early 30s range where CHR has been reported to predict psychosis and where the incidence of psychosis is known to be highest. As a consequence of these limitations, in our view the NEMESIS-2 data are only partially relevant to the value of CHR as a vehicle for indicated prevention. With regard to evidence for the success of preventive interventions for CHR, FusarPoli et al rightly point out that meta-analytic evidence so far is contradictory and that clinical trials featuring conversion to psychosis as their primary outcome require very large sample sizes. We do, however, see hope on the horizon. This past fall the US National Institute of Mental Health and the Foundation for the National Institutes of Health announced the Accelerated Medicines Partnership in Schizophrenia (AMP SCZ), a collaborative effort to advance early intervention for CHR individuals. This initiative seeks to identify parameters for future clinical trials on alternate outcomes of CHR such as social functioning or attenuated positive symptoms. These alternate endpoints can also potentially serve as surrogate outcomes for reducing the incidence of psychopathology, which can then be investigated directly after entry of the new treatments into clinical practice through epidemiologic methods. In conclusion, our view is not only that a combined universal and indicated approach is likely to be the best way to prevent psychosis in the future, but also that the CHR syndrome for psychosis continues to provide the most promising option for the indicated prevention component. We acknowledge a potential bias, working as we do in the CHR field, but we like to think we chose this field because it offers the best opportunities in psychiatry for improving public health rather than that we believe it offers the best opportunities for public health because we have chosen it.
Evaluation of Dietary Soluble Extract Hydrolysates with or without Supplementation of Inosine Monophosphate Based on Growth, Hematology, Non-Specific Immune Responses and Disease Resistance in Juvenile Nile Tilapia Oreochromis niloticus

Simple Summary This study was conducted to elucidate the effects of dietary soluble extract hydrolysates obtained from fishery by-products, such as shrimp soluble extract (SSE), tilapia soluble extract (TSE) and squid soluble extract (SQSE). Furthermore, we used a nucleotide, inosine monophosphate (IMP), as an additive in different concentrations along with shrimp soluble extract to understand their effects on growth, immunity and disease resistance in juvenile Nile tilapia. Our results demonstrated that dietary SSE could improve growth performance, non-specific immune responses and disease resistance against pathogenic bacteria Aeromonas hydrophila in juvenile Nile tilapia. Moreover, IMP did not add further benefits to the SSE diet. Further research is needed to better understand the effects of fishery by-products and IMP on fish diets. Abstract We performed an 8-week feeding trial to evaluate dietary soluble extract hydrolysates from fishery by-products, such as shrimp soluble extract (SSE) with or without inosine monophosphate (IMP), tilapia soluble extract (TSE) and squid soluble extract (SQSE), in juvenile Nile tilapia. A diet without feed additives was used as the control diet (CON); and five other experimental diets were formulated with 2% soluble extracts consisting of 100% SSE, 98% SSE + 2% IMP (SSEP2), 96% SSE + 4% IMP (SSEP4), 100% SQSE and 100% TSE. The diets were fed to 4.9 ± 0.07 g (mean ± SD) juvenile Nile tilapia in triplicate groups. The weight gain and specific growth rates of fish fed the SSE, SSEP2 and SSEP4 diets were significantly higher than those of fish fed the CON and SQSE diets. The superoxide dismutase activity levels of fish fed the SSE and SSEP4 diets were significantly higher than those of fish fed the CON, SSEP2, SQSE and TSE diets. Myeloperoxidase activity levels of fish fed the SSE and SSEP4 diets were significantly higher than those of fish fed the CON, SSEP2 and SQSE diets. Lysozyme activity levels of fish fed the SSEP4 and SQSE diets were significantly higher than those of fish fed the SSE and SSEP2 diets. Feed efficiency, protein efficiency ratio, survival rate, whole body proximate composition and hematological parameters were not significantly different among the groups. After ten days of challenge = against Aeromonas hydrophila, the cumulative survival rate of fish fed the SSE diet was significantly higher than those of fish fed the CON, SQSE and TSE diets. In conclusion, dietary shrimp soluble extract could improve the growth performance, non-specific immune responses and disease resistance in juvenile Nile tilapia, and inosine monophosphate did not add further benefits to this ingredient.
Modification of sodium bicarbonate and its effect on foaming behavior of polypropylene

Abstract As a potential physical blowing agent, sodium bicarbonate (SB) is environmentally friendly and low in cost, but its low decomposition temperature cannot meet the requirements of polyolefin foam materials. Herein, for enhancing the thermal properties of SB, a modified way was offered to fabricate various SB-based capsules via suspension polymerization. As the modified SB-based capsules, epoxy resin (EP) accompanied with several organic acids was successfully coated on the surface of SB, serving as heat-insulation layer of SB. Various physicochemical characterizations provided reliable evidences for the good coating effect, and the thermal performance of the modified SB was improved. Further, the composite SB capsules were applied for the foaming of polypropylene (PP), and the foaming behavior of the SB-based capsules in PP was significantly improved, with more uniform distribution, smaller cell diameter, and higher cell density. In all, this work fully proved that the coated shells enhanced the thermal properties of SB, and the modified SB capsules significantly improved the foaming quality of foamed PP.
Effect of Fertilization on Photosynthetic Physiology and Growth Characteristics of Phoebe zhennan Seedlings

A pot experiment was conducted to study the effects of application of four fertilizers,nitrogen fertilizer(NF),compound fertilizer(CF),organic fertilizer(OF)and mixed fertilizer(MF),on 1-year-old Phoebe zhennan seedlings.Each fertilizer was applied at three levels based on the annual nitrigen application rate,namely,low(L,0.3g/pail),medium(M,0.6g/pail)and high(H,0.9g/pail),which was divided into three equal parts and applied into pail in the middle of May,July and September,respectively.The morphological and photosynthetic indicators of P.zhennanseedlings were measured after a month of fertilization to explore the effects of fertilizer application on photosynthetic and growth characteristics of the seedlings.The results showed that:(1)The medium nitrogen application rate showed the greatest promoting effects on the growth of P.zhennan seedlings for the 3 types of fertilizers,and when comparison was conducted between fertilizer types,CF acted the worst,NF acted well only at early stage(May-June),MF application reflected a relative lack of nutrient in the late phase(September-October),while OF was able to provide nutrients for the seedlings more continuously;(2)Fertilization functioned well in promotingchlorophyll synthesis,extending the functional period of green leaves,and enhancing net photosynthetic rate of P.zhennanseedlings,wherein OF and MF performed more effectively,coupled with the photosynthetic capacity of seedlings improved under an environment of strong light,high CO2 concentration;(3)In addition to CF,application of other three kinds of fertilizers has increased the height and diameter growth of P.zhennanseedlings to varying degrees,with the greatest stimulation observed in OF at medium application rate(MOF),which displaying an increment twice as much as that of CK.As can be seen,MOFis the best choice in the fertilizer management of P.zhennanseedlings.
Insularity forcing on plant persistence strategies in edaphic island systems

Aim Trait-based approaches are increasingly implemented in island biogeography, providing key insights into the eco-evolutionary dynamics of insular systems. However, what determines persistence of plant species once they have arrived and established in an island remains largely unexplored. Here, we examined links between non-acquisitive persistence strategies and insularity across three terrestrial edaphic island systems, hypothesising that insularity promotes strategies for local persistence. Location Europe: Western Carpathians, Moravia, and Cantabrian Range. Time period Present. Major taxa studied Vascular plants. Methods For each system, we used linear models at the island scale to test whether persistence-related plant trait patterns (average trait values and diversity) depend on three insularity metrics (island size, isolation and target effect). We focused on patterns of edaphic island specialists because, in contrast to matrix-derived species, their presence is confined to the edaphic islands. Results We found that insularity metrics explained large proportions in the variation of the average and diversity of persistence-related traits of edaphic island specialists. Insularity was associated with a decline in the proportion of island specialists that have clonal abilities, yet it affected trait values of specialists towards enhanced abilities to persist locally (e.g. more extensive lateral spread) while reducing trait variability. Higher degrees of insularity within the systems were translated to stronger effects on functional trait patterns. Main conclusions Insularity affects plant species diversity, distribution and forms in terrestrial island-like systems, similarly as it is assumed for true islands. Insularity – measured using a single (island size, isolation) or combined (target effect) predictors – may operate selecting for enhanced and less diverse persistence strategies. Ultimately, this process, which we call insularity forcing, operates as a selective process to promote species ability to avoid local extinction and to persist on terrestrial islands.
Reversal of the adipostat control of torpor during migration in hummingbirds

Many small endotherms use torpor to reduce metabolic rate and manage daily energy balance. However, the physiological “rules” that govern torpor use are unclear. We tracked torpor use and body composition in ruby-throated hummingbirds (Archilochus colubris), a long-distance migrant, throughout the summer using respirometry and quantitative magnetic resonance. During the mid-summer, birds entered torpor at consistently low fat stores (∼5% of body mass), and torpor duration was negatively related to evening fat load. Remarkably, this energy-emergency strategy was abandoned in the late summer when birds accumulated fat for migration. Migrating birds were more likely to enter torpor on nights when they had higher fat stores, and fat gain was positively correlated with the amount of torpor used. These findings demonstrate the versatility of torpor throughout the annual cycle and suggest a fundamental change in physiological feedback between adiposity and torpor during migration. Moreover, this study highlights the underappreciated importance of facultative heterothermy in migratory ecology.
Genetic diversity at putatively adaptive but not neutral loci in Primula 1 veris responds to recent habitat change in semi-natural grasslands 2

Genetic diversity at putatively adaptive but not neutral loci in Primula 1 veris responds to recent habitat change in semi-natural grasslands 2 S. Träger*1,2, C. Rellstab3, I. Reinula1, N. Zemp4, A. Helm1, R. Holderegger3,5, T. Aavik1 3 1Department of Botany, Institute of Ecology and Earth Sciences, University of Tartu, Lai 40, 4 51005 Tartu, Estonia 5 2Institute of Biology/Geobotany and Botanical Garden, Martin-Luther-University Halle6 Wittenberg, Große Steinstr. 79/80, 06108 Halle (Saale), Germany 7 3WSL Swiss Federal Research Institute, Zürcherstrasse 111, 8903 Birmensdorf, Switzerland 8 4Genetic Diversity Centre (GDC), ETH Zurich, Universitätstrasse 16, 8092 Zürich, Switzerland 9 5Institute of Integrative Biology (IBZ), ETH Zurich, Universitätstrasse 16, 8092 Zürich, 10 Switzerland 11
Histone acetyltransferases and deacetylases are required for virulence, conidiation, DNA damage repair, and multiple stresses resistance of Alternaria alternata

Histone acetylation, which is critical for transcriptional regulation and various biological processes in eukaryotes, is a reversible dynamic process regulated by HATs and HDACs. This study determined the function of 6 histone acetyltransferases (HATs) (Gcn5, RTT109, Elp3, Sas3, Sas2, Nat3) and 6 histone deacetylases (HDACs) (Hos2, Rpd3, Hda1, Hos3, Hst2, Sir2) in the phytopathogenic fungus Alternaria alternata by analyzing targeted gene deletion mutants. Our data provide evidence that HATs and HDACs are both required for mycelium growth, cell development and pathogenicity as many gene deletion mutants (ΔGcn5, ΔRTT109, ΔElp3, ΔSas3, ΔNat3, ΔHos2, and ΔRpd3) displayed reduced growth, conidiation or virulence at varying degrees. In addition, HATs and HDACs are involved in the resistance to multiple stresses such as oxidative stress (Sas3, Gcn5, Elp3, RTT109, Hos2), osmotic stress (Sas3, Gcn5, RTT109, Hos2), cell wall-targeting agents (Sas3, Gcn5, Hos2), and fungicide (Gcn5, Hos2). ΔGcn5, ΔSas3 and ΔHos2 displayed severe growth defects on sole carbon source medium suggesting a vital role of HATs and HDACs in carbon source utilization. More SNPs were generated in ΔGcn5 in comparison to wild-type when they were exposed to ultraviolet ray. Moreover, ΔRTT109, ΔGcn5 and ΔHos2 showed severe defects in resistance to DNA-damaging agents, indicating the critical role of HATs and HDACs in DNA damage repair. These phenotypes correlated well with the differentially expressed genes in ΔGcn5 and ΔHos2 that are essential for carbon sources metabolism, DNA damage repair, ROS detoxification, and asexual development. Furthermore, Gcn5 is required for the acetylation of H3K4. Overall, our study provides genetic evidence to define the central role of HATs and HDACs in the pathological and biological functions of A. alternata. Importance In filamentous fungi, HATs and HDACs have been found to be involved in growth, development, virulence, synthesis of secondary metabolites and multi-stress resistance. However, the role of all HATs and HDACs in the same fungal pathogen has not been systematically explored. Our study revealed that HATs and HDACs are required for the vegetative growth, conidiation, pathogenicity, multiple stresses resistance, DNA damage repair, and carbon source utilization in A. alternata. Moreover, HATs and HDACs identified in A. alternata are highly conserved in many notorious pathogenic fungi, such as Magnaporthe grisea and Candida albicans. Therefore, this study not only systematically reveals the biological functions of twelve histone acetylation-required enzymes for the first time, but also provides a foundation for future investigations in A. alternata or other pathogenic fungi.
Distinct developmental mechanisms influence sexual dimorphisms in the milkweed bug Oncopeltus fasciatus

Sexual dimorphism is common in animals. The most complete model of sex determination comes from Drosophila melanogaster, where the relative dosage of autosomes and X chromosomes leads indirectly to sex-specific transcripts of doublesex. Female Dsx interacts with a mediator complex protein encoded by intersex to activate female development. In males the transcription factor encoded by fruitless promotes male-specific behavior. The genetics of sex determination have been examined in a small number of other insects, yet several questions remain about the pleisomorphic state. Is doublesex required for female and male development? Is fruitless conserved in male behavior or morphology? Are other components such as intersex functionally conserved? To address these questions, we report expression and functional tests of doublesex, intersex and fruitless in the hemipteran Oncopeltus fasciatus, characterizing three sexual dimorphisms. doublesex prevents intersex phenotypes in all sexes and dimorphic traits in the milkweed bug. intersex and fruitless are expressed across the body, in females and males. fruitless and intersex also affect the genitalia of both sexes, but have effects limited to different dimorphic structures in different sexes. These results reveal roles for intersex and fruitless distinct from other insects, and demonstrate distinct development mechanisms in different sexually dimorphic structures.
Direct Reconstruction of Gene Regulatory Networks underlying Cellular state Transitions without Pseudo-time Inference

Nowadays the advanced technology for single-cell transcriptional profiling enables people to routinely generate thousands of single-cell expression data, in which data from different cell states or time points are derived from different samples. Without transferring such time-stamped cross-sectional data into pseudo-time series, we propose COSLIR (COvariance restricted Sparse LInear Regression) for directly reconstructing the gene regulatory networks (GRN) that drives the cell-state transition. The differential gene expression between adjacent cell states is modeled as a linear combination of gene expressions in the previous cell state, and the GRN is reconstructed through solving an optimization problem only based on the first and second moments of the sample distributions. We apply the bootstrap strategy as well as the clip threshold method to increase the precision and stability of the estimation. Simulations indicate the perfect accuracy of COSLIR in the oracle case as well as its good performance and stability in the sample case. We apply COSLIR separately to two cell lineages in a published single-cell qPCR dataset during mouse early embryo development. Nearly half of the inferred gene-gene interactions have already been experimentally reported and some of them were even discovered during the past decade after the dataset was published, indicating the power of COSLIR. Furthermore, COSLIR is also evaluated on several single-cell RNA-seq datasets, and the performance is comparable with other methods relying on the pseudo-time reconstruction.
A large majority of awake hippocampal sharp-wave ripples feature spatial trajectories with momentum

During periods of rest, hippocampal place cells feature bursts of activity called sharp-wave ripples (SWRs). Heuristic approaches to their analysis have revealed that a small fraction of SWRs appear to “simulate” trajectories through the environment—called awake hippocampal replay—while the functional role of a majority of these SWRs remains unclear. Applying a novel probabilistic approach to characterize the spatio-temporal dynamics embedded in SWRs, we instead show that almost all SWRs of foraging rodents simulate such trajectories through the environment. Furthermore, these trajectories feature momentum, that is, inertia in their velocities, that mirrors the animals’ natural movement. This stands in contrast to replay events during sleep which seem to follow Brownian motion without such momentum. Lastly, interpreting the replay trajectories in the context of navigational planning revealed that similar past analyses were biased by the heuristic SWR sub-selection. Overall, our approach provides a more complete characterization of the spatio-temporal dynamics within SWRs, highlights qualitative differences between sleep and awake replay, and ought to support future, more detailed, and less biased analysis of the role of awake replay in navigational planning.
Differential receptor crosstalk in DRD1-DRD2 heterodimer upon phasic and tonic dopamine signals

In response to phasic and tonic release, dopamine neurotransmission is regulated by its receptor subtypes, mainly dopamine receptor type 1 and 2 (DRD1 and DRD2). These dopamine receptors are known to form a heterodimer, however the receptor crosstalk between DRD1 and DRD2 was only suspected by measuring their downstream signaling products, due to the lack of methodology for selectively detecting individual activity of different dopamine receptors. Here, we develop red DRD1 sensor (R-DRD1) and green DRD2 sensor (G-DRD2) which can specifically monitor the real-time activity of DRD1 and DRD2, and apply these multicolor sensors to directly measure the receptor crosstalk in the DRD1-DRD2 heterodimer. Surprisingly, we discover that DRD1 activation in the heterodimer is inhibited only at micromolar phasic concentration of dopamine, while DRD2 activation is selectively inhibited at nanomolar tonic dopamine level. Differential receptor crosstalk in the DRD1-DRD2 heterodimer further modulates their downstream cAMP level. These data imply a novel function of the DRD1-DRD2 heterodimer at physiological dopamine levels of phasic and tonic release. Our approach utilizing multicolor receptor sensors will be useful to discover novel function of GPCR heterodimers.
Wnt signaling mediates acquisition of blood-brain barrier properties in naïve endothelium derived from human pluripotent stem cells

Endothelial cells (ECs) in the central nervous system (CNS) acquire their specialized blood-brain barrier (BBB) properties in response to extrinsic signals, with Wnt/β-catenin signaling coordinating multiple aspects of this process. Our knowledge of CNS EC development has been advanced largely by animal models, and human pluripotent stem cells (hPSCs) offer the opportunity to examine BBB development in an in vitro human system. Here we show that activation of Wnt signaling in hPSC-derived naïve endothelial progenitors, but not in matured ECs, leads to robust acquisition of canonical BBB phenotypes including expression of GLUT-1, increased claudin-5, and decreased PLVAP. RNA-seq revealed a transcriptome profile resembling ECs with CNS-like characteristics, including Wnt-upregulated expression of LEF1, APCDD1, and ZIC3. Together, our work defines effects of Wnt activation in naïve ECs and establishes an improved hPSC-based model for interrogation of CNS barriergenesis.