Miracle-dz/UniFAR-FTUs huggingface dataset:
Zfp503/Nlz2 Is Required for RPE Differentiation and Optic Fissure Closure

Purpose Uveal coloboma is a congenital eye malformation caused by failure of the optic fissure to close in early human development. Despite significant progress in identifying genes whose regulation is important for executing this closure, mutations are detected in a minority of cases using known gene panels, implying additional genetic complexity. We have previously shown knock down of znf503 (the ortholog of mouse Zfp503) in zebrafish causes coloboma. Here we characterize Zfp503 knock out (KO) mice and evaluate transcriptomic profiling of mutant vs. wild-type (WT) retinal pigment epithelium (RPE)/Choroid. Methods Zfp503 KO mice were generated by gene targeting using homologous recombination. Embryos were characterized grossly and histologically. Patterns and level of developmentally relevant proteins/genes were examined with immunostaining/in situ hybridization. The transcriptomic profile of E11.5 KO RPE/choroid was compared to that of WT. Results Zfp503 is dynamically expressed in developing mouse eyes and that loss of its expression results in uveal coloboma. KO embryos exhibit altered mRNA levels and expression patterns of several key transcription factors involved in eye development, including Otx2, Mitf, Pax6, Pax2, Vax1 and Vax2, resulting in reduced melanin pigmentation in the presumptive RPE and its differentiation into neural-retina-like lineages. Comparison of RNA-Seq data from wild type and KO E11.5 embryos demonstrated reduced expression of melanin-related genes and significant overlap with genes known to be dynamically regulated at the optic fissure. Conclusions These results demonstrate a critical role of Zfp503 in RPE differentiation and in optic fissure closure.
Telomere-to-telomere human DNA replication timing profiles

The spatiotemporal organization of DNA replication produces a highly robust and reproducible replication timing profile. Sequencing-based methods for assaying replication timing genome-wide have become commonplace, but regions of high repeat content in the human genome have remained refractory to analysis. Here, we report the first nearly-gapless telomere-to-telomere replication timing profiles in human, using the T2T-CHM13 genome assembly and sequencing data for five cell lines. We find that replication timing can be successfully assayed in centromeres and large blocks of heterochromatin. Centromeric regions replicate in mid-to-late S-phase and contain replication-timing peaks at a similar density to other genomic regions, while distinct families of heterochromatic satellite DNA differ in their bias for replicating in late S-phase. The high degree of consistency in centromeric replication timing across chromosomes within each cell line prompts further investigation into the mechanisms dictating that some cell lines replicate their centromeres earlier than others, and what the consequences of this variation are.
Transcriptional control of nucleus accumbens neuronal excitability by retinoid X receptor alpha tunes sensitivity to drug rewards

The complex nature of the transcriptional networks underlying addictive behaviors suggests intricate cooperation between diverse gene regulation mechanisms that go beyond canonical activity-dependent pathways. Here we implicate in this process a novel nuclear receptor transcription factor, Retinoid X Receptor Alpha (RXRα), which we identified bioinformatically as associated with addiction-like behaviors. In the nucleus accumbens (NAc) of male and female mice, we show that, while its own expression remains unaltered after cocaine exposure, RXRα controls plasticity- and addiction-relevant transcriptional programs in both dopamine receptor D1- and D2-expressing medium spiny neurons, which in turn modulate intrinsic excitability and synaptic activity of these NAc cell types. Behaviorally, bidirectional viral and pharmacological manipulation of RXRα regulates drug reward sensitivity in both non-operant and operant paradigms. Together, this study demonstrates a key role for NAc RXRα in promoting drug addiction, and paves the way for future studies of rexinoid signaling in psychiatric disease states.
Action sequence dynamics rely on accessory hyperdirect pathway-related targets in the striatum

We found that M1 hyperdirect pathway projections to the STN also send dense axonal collaterals to external globus pallidus and dorsal striatum, with the highest synaptic volumes found in the DLS. Speciﬁc interruption of the M1 → DLS circuit reduced the proportion of successful sequences while speeding-up and reducing action timing-variabil-ity, revealing a role for M1 → DLS circuitry in setting the exploration/exploitation balance that is required for adaptively guiding the timing and success of instrumental action.
Stability and learning in excitatory synapses by nonlinear inhibitory plasticity

Synaptic changes underlie learning and memory formation in the brain. But synaptic plasticity of excitatory synapses on its own is unstable, leading to unlimited growth of synaptic strengths without additional homeostatic mechanisms. To control excitatory synaptic strengths we propose a novel form of synaptic plasticity at inhibitory synapses. We identify two key features of inhibitory plasticity, dominance of inhibition over excitation and a nonlinear dependence on the firing rate of postsynaptic excitatory neurons whereby inhibitory synaptic strengths change in the same direction as excitatory synaptic strengths. We demonstrate that the stable synaptic strengths realized by this novel inhibitory plasticity achieve a fixed excitatory/inhibitory set-point in agreement with experimental results. Applying a disinhibitory signal can gate plasticity and lead to the generation of receptive fields and strong bidirectional connectivity in a recurrent network. Hence, a novel form of nonlinear inhibitory plasticity can simultaneously stabilize excitatory synaptic strengths and enable learning upon disinhibition.
Histone marks retained during epigenetic reprogramming and their roles essential for fish early development

Reprograming of epigenetic modifications after fertilization is required for proper embryonic development and cell differentiation. However, histone modifications that escape reprogramming in non-mammalian vertebrates and their potential functional roles are poorly understood. Here, we quantitatively analyzed histone modification dynamics during reprogramming in Japanese Killifish, medaka (Oryzias latipes) embryos, and revealed that H3K27ac, H3K27me3 and H3K9me3 are retained, while H3K4 methylation is completely erased. Furthermore, we experimentally demonstrated the functional roles of such retained modifications at early stages; H3K27ac at promoters is required for proper patterning of H3K4 and H3K27 methylation at zygotic genome activation (ZGA) and specific retention of H3K9me3 at telomeric regions maintains genomic stability during cleavage stage. These results expand the understanding of diversity and conservation of reprogramming in vertebrates and unveil previously uncharacterized functions of histone modifications retained during epigenetic reprogramming.
Natural variation identifies new effectors of water-use efficiency in Arabidopsis

Water use efficiency (WUE) is the ratio of biomass gained per unit of water consumed; thus, it can be altered by genetic factors that affect either side of the ratio. In the present study, we exploited natural variation for WUE as an unbiased approach to discover loci affecting either biomass accumulation or water use as factors affecting WUE. Genome-wide association (GWAS) analysis using integrated WUE measured through carbon isotope discrimination (δ13C) of Arabidopsis thaliana accessions identified genomic regions associated with WUE. Reverse genetic analysis of 70 candidate genes selected based on the GWAS results and transcriptome data identified 25 genes affecting WUE as measured by gravimetric and δ13C analyses. Mutants of four genes had higher WUE than wild type, while mutants of the other 21 genes had lower WUE. The differences in WUE were caused by either altered biomass or water consumption (or both). Stomatal density was not a primary cause of altered WUE in these mutants. Leaf surface temperatures indicated that transpiration differed for mutants of 16 genes, but generally biomass accumulation had greater effect on WUE. The genes we identified are involved in diverse cellular processes including hormone and calcium signaling, meristematic activity, photosynthesis, flowering time, leaf/vasculature development, and cell wall composition; however, none of them had been previously linked to WUE or traits related to plant water relations. Thus, our study successfully identified new effectors of WUE that can be used to understand the genetic basis of WUE and improve crop productivity.
Age‐related differences in functional network segregation in the context of sex and reproductive stage

Age is accompanied by differences in the organization of functional brain networks, which impact behavior in adulthood. Functional networks tend to become less segregated and more integrated with age. However, sex differences in network segregation declines with age are not well-understood. Further, network segregation in the context of female reproductive stage is relatively understudied, though unmasking such relationships would be informative for elucidating biological mechanisms that contribute to sex-specific differences in aging. In the current work, we used data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) repository to evaluate differences in resting-state network segregation as a product of sex and reproductive stage. Reproductive stage was categorized using the Stages of Reproductive Aging Workshop (STRAW+10) criteria. Replicating prior work, we investigated the following functional networks: auditory, cerebellar-basal ganglia, cingulo-opercular task control, default mode, dorsal attention, fronto-parietal task control, salience, sensory somatomotor mouth, sensory somatomotor hand, ventral attention, and visual. First, our results mirror findings from previous work indicating that network segregation is lower with increasing age. Second, when analyzing associations between network segregation and age within each sex separately, we find differences between females and males. Finally, we report significant effects of reproductive stage on network segregation, though these findings are likely driven by age. Broadly, our results suggest that impacts of sex are important to evaluate when investigating network segregation differences across adulthood, though further work is needed to determine the unique role of menopause and sex hormones on the organization of functional brain networks within aging females. Key Points Segregation of functional brain networks declines with increasing age Age-segregation relationships are modified by biological sex Reproductive stage may impact sex differences in brain network organization
Distinct regulation of Hox genes by Polycomb Group genes in a crustacean

Non-insect crustaceans exhibit tremendous body plan diversity. The evolution of diverse patterns of Hox gene expression has been implicated as a primary driver of body plan evolution between crustacean groups, but the mechanisms underlying Hox regulatory evolution remain unknown. We identify Polycomb and Trithorax Group proteins, crucial for proper Hox regulation across bilaterians, in the genome of the amphipod crustacean Parhyale hawaiensis, and demonstrate their essential functions in crustacean Hox regulation and embryonic development using CRISPR-Cas9 mutagenesis. Examination of Hox misexpression patterns between individual Hox genes with respect to timing, tissue, and PcG mutant gene in mutant embryos reveals that each crustacean Hox gene follows its own idiosyncratic regulatory mechanism. These results suggest a distinct regulation of Hox genes that may have enabled crustacean body plan evolution. Primary Findings - The genome of the amphipod crustacean Parhyale hawaiensis contains all core Polycomb Group (PcG) and Trithorax Group (TrxG) proteins - CRISPR-Cas9 mutagenesis of PcG proteins induces homeotic transformations and misexpression of Hox genes that differ from similar experiments in insects - PcG knockout embryos show proper initiation of Hox expression boundaries at early developmental stages - Each of the three posterior Hox genes in Parhyale displays distinct patterns of misexpression in response to PcG knockout - Hox regulation appears to occur via different mechanisms in the nervous system vs. limbs - PcG phenotypes reveal the potential for distinct layers of Hox regulation in crustaceans
Neuron-specific transcriptomic signatures indicate neuroinflammation and altered neuronal activity in ASD temporal cortex

Autism spectrum disorder (ASD) is a highly heterogeneous disorder, yet transcriptomic profiling of bulk brain tissue has identified substantial convergence among dysregulated genes and pathways in ASD. However, this approach lacks cell-specific resolution. We performed comprehensive transcriptomic analyses on bulk tissue and laser-capture microdissected (LCM) neurons of 59 postmortem human brains (27 ASD and 32 matched controls) in the superior temporal gyrus (STG) ranging from 2-73 years of age. In bulk tissue, synaptic signaling, heat shock protein-related pathways and RNA splicing were significantly altered in ASD. There was age-dependent dysregulation of genes involved in GABA (GAD1 and GAD2) and glutamate (SLC38A1) signaling pathways. In LCM neurons, AP-1 mediated neuroinflammation and insulin/IGF-1 signaling pathways were upregulated in ASD, while mitochondrial function, ribosome and spliceosome components were downregulated. GABA synthesizing enzymes GAD1 and GAD2 were both downregulated in ASD neurons. Alterations in small nucleolar RNAs (snoRNAs) associated with splicing events suggested interplay between snoRNA dysregulation and splicing disruption in neurons of individuals with ASD. Our findings supported the fundamental hypothesis of altered neuronal communication in ASD, demonstrated that inflammation was elevated at least in part in ASD neurons, and may reveal windows of opportunity for biotherapeutics to target the trajectory of gene expression and clinical manifestation of ASD throughout the human lifespan.
Estimating interaction matrices from performance data for diverse systems

Network theory allows us to understand complex systems by evaluating how their constituent elements interact with one another. Such networks are built from matrices which describe the effect of each element on all others. Quantifying the strength of these interactions from empirical data can be difficult, however, because the number of potential interactions increases non-linearly as more elements are included in the system, and not all interactions may be empirically observable when some elements are rare. We present a novel modelling framework which estimates the strength of pairwise interactions in diverse horizontal systems, using measures of species performance in the presence of varying densities of their potential interaction partners. Our method allows us to directly estimate pairwise effects when they are statistically identifiable and approximate pairwise effects when they would otherwise be statistically unidentifiable. The resulting interaction matrices can include positive and negative effects, the effect of a species on itself, and are non-symmetrical. The advantages of these features are illustrated with a case study on an annual wildflower community of 22 focal and 52 neighbouring species, and a discussion of potential applications of this framework extending well beyond plant community ecology.
Job vacancies and personnel policy in establishments - A supplementary survey on applicant selection: survey design, survey process and data quality analyses

"The online survey 'Job Vacancies and Personnel Policy in Establishments - A Supplementary Survey on Applicant Selection' aims to investigate how a company's decision to fill vacancies is influenced by the applicants' individual characteristics on the one hand and by how the significance of these individual characteristics differs between professions on the other. The factorial survey design (vignette survey) was used for this purpose. It is particularly well suited for analyses set to determine the significance of individual determinants and their interactions. Below, we will first detail the online survey design including the selection of the dimensions at the vignette level and at the professional level. The focus is on the technical implementation of the vignette module in the questionnaire. Afterwards, the sampling of the companies and the surveying procedure are documented. Subsequently, we describe analyses of the sample response rate and selectivity of the participants as well as the calculation of the resulting weighting factors. This is followed by data quality analyses. The Appendix giving a detailed specification of the materials used is provided only in the German version of this documentation. The questionnaire in German language is part of a separate Appendix" (Author's abstract, IAB-Doku) ((en)) Additional Information Questionnaire in German language
Mobile Learning in Higher Education: Adoption and Discussion Criteria

Mobile and wireless technology has permeated into many aspects of life, and will continue to do so both through choice and requirement. In the case of education, the adoption of the technology can be seen as adding value to key processes and information systems supporting the delivery services where ultimately it is the students that benefit. The demands of a modern Higher Education systems and expectations of students will, no doubt, continue to fuel its take up. This paper presents an outline of reference points with which to align adoption discussions for mobile learning in a higher educational system
A Critical Study of Class Ten Our English Book

A textbook holds an important place in ELT programme, particularly in an EFL setting where most teachers depend totally on the approved books, and don't bother to prepare tailor-made teaching materials. Objectives: The main objective is to critically examine the current English textbook for class ten used by all the government as well as English-medium private schools across Nepal. Methodology: A descriptive qualitative research design was adopted to evaluate the quality of the book on mainly two criteria: what to teach and how to teach, At the same time, many other things have been taken into consideration, for example, what is the quality of the input in the book from the viewpoints of four elements of language and four macro skills as well as their constituent micro skills, what is the learning outcome of the book, and so on. Result: There seems to be serious loopholes in the organization of the presentation and practice materials of the book from both viewpoints: knowledge transmission and communicative ability development. Conclusion: The book needs to be adapted and rewritten.
SECURE AND PRIVACY PRESERVING SMARTPHONE BASED TRAFFIC INFORMATION SYSTEM

The main reason for such systems would be to alleviate traffic congestion that is available in each and every major city. This project is for solving the problem by collecting traffic data, producing traffic estimates, and providing drivers with location-specific information. The Present methods designed for getting the present location through GPS. But no possibility of route map to other place from present place. Moving to desired place has become difficulty to the driver and also the traffic density in that route. The proposed method using the smart phone based traffic information system. Here TIS information is collected based on the IR Sensors that are connected with each other based on the distance which make us to know the information that number of vehicles moving on road with that information we can change the direction of route based on the number vehicles moving. This task that can’t be accomplished only by depending around the security from the mobile-to-cellular infrastructure communication. But also as TISs require fine-grained location information, the privacy from the adding participants must be protected. We have to ensure their security and privacy as well as their effectiveness (e.g., precision). This paper used the condition of the available facilities like Road maps, path ways and available telecommunication infrastructure. Growing smart phone transmission combined with the wide coverage of cellular infrastructures, renders smart phone based traffic human resources (TISs) this is an extensive solution for smart phone-based traffic estimation that is known as secure and privacy protecting. We provide a complete-blown implementation on actual smart phones, along with a comprehensive assessment of their precision and efficiency. Our results make sure smart phone-based TISs can provide accurate traffic condition estimation while being secure and privacy protecting.
Integrating Social-Ecological and Political-Ecological Models of Agrobiodiversity With Nutrient Management of Keystone Food Spaces to Support SDG 2

Agrobiodiversity—the biodiversity of food, agriculture, and land use—is essential to U.N. Sustainable Development Goal 2 by providing crucial food and nutritional quality of diets combined with strengthening agroecological sustainability. Focusing on the agrobiodiversity nexus to SDG 2, the current study utilized the interdisciplinary Agrobiodiversity Knowledge Framework (AKF), household-level surveys, and biodiversity sampling of crop fields and home gardens in a case study in Huánuco, Peru, in 2017. Statistical measures estimated agrobiodiversity of crop fields (n = 268 households) and home gardens (n=159 households) based on species richness (3.7 and 10.2 species/household, in fields and gardens, respectively) and evenness (Shannon diversity index; 0.70 and 1.83 in fields and gardens, respectively). Robust results of Poisson and OLS regression models identified several AKF-guided determinants of agrobiodiversity. Estimated species richness and evenness were significantly associated with 12 social-ecological and political-ecological factors from the four AKF thematic axes: farm characteristics and agroecology; diets and nutrition; markets, governance and sociocultural practices; and global change. This study's AKF approach, agrobiodiversity modeling, agroecological characterization, and field-based case study advanced a series of useful research insights, comparisons, and conceptual innovations to address SDG 2. Characterization of nutrient management through soil- and plant-focused cultural practices and livelihood roles distinguished the “keystone agrobiodiversity-and-food space” of multi-species maize fields (maizales) identified in AKF regression and characterization results. This key space furnished crucial food-nutrition and agroecological benefits that can be expanded by overcoming identified barriers. AKF-guided models incorporating key agrobiodiversity-and-food spaces and ecological nutrient management are needed to strengthen SDG 2 strategies.