bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of evolutionary constraint by genomic annotations improves prioritization of causal variants in maize
Authors: Ramstein Guillaume P. , Buckler Edward S. 
Published: September 2021

AbstractCrop improvement through cross-population genomic prediction and genome editing requires identification of causal variants at single-site resolution. Most genetic mapping studies have generally lacked such resolution. In contrast, evolutionary approaches can detect genetic effects at high resolution, but they are limited by shifting selection, missing data, and low depth of multiple-sequence alignments. Here we used genomic annotations to accurately predict nucleotide conservation across Angiosperms, as a proxy for fitness effect of mutations. Using only sequence analysis, we annotated non-synonymous mutations in 25,824 maize gene models, with information from bioinformatics (SIFT scores, GC content, transposon insertion, k-mer frequency) and deep learning (predicted effects of polymorphisms on protein representations by UniRep). Our predictions were validated by experimental information: within-species conservation, chromatin accessibility, gene expression and gene ontology enrichment. Importantly, they also improved genomic prediction for fitness-related traits (grain yield) in elite maize panels (+5% and +38% prediction accuracy within and across panels, respectively), by stringent prioritization of ≤ 1% of single-site variants (e.g., 104 sites and approximately 15deleterious alleles per haploid genome). Our results suggest that predicting nucleotide conservation across Angiosperms may effectively prioritize sites most likely to impact fitness-related traits in crops, without being limited by shifting selection, missing data, and low depth of multiple-sequence alignments. Our approach – Prediction of mutation Impact by Calibrated Nucleotide Conservation (PICNC) – could be useful to select polymorphisms for accurate genomic prediction, and candidate mutations for efficient base editing.
Inverse Problem Reveals Conditions for Characteristic Retinal Degeneration Patterns in Retinitis Pigmentosa under the Trophic Factor Hypothesis
Authors: Roberts Paul A. 
Published: September 2021

ABSTRACTRetinitis pigmentosa (RP) is the most common inherited retinal dystrophy with a prevalence of about 1 in 4000, affecting approximately 1.5 million people worldwide. Patients with RP experience progressive visual field loss as the retina degenerates, destroying light-sensitive photoreceptor cells (rods and cones), with rods affected earlier and more severely than cones. Spatio-temporal patterns of retinal degeneration in human RP have been well characterised; however, the mechanism(s) giving rise to these patterns have not been conclusively determined. One such mechanism, which has received a wealth of experimental support, is described by the trophic factor hypothesis. This hypothesis suggests that rods produce a trophic factor necessary for cone survival; the loss of rods depletes this factor, leading to cone degeneration. In this paper we formulate a partial differential equation mathematical model of RP in one spatial dimension, spanning the region between the retinal centre (fovea) and the retinal edge (ora serrata). Using this model we derive and solve an inverse problem, revealing for the first time experimentally testable conditions under which the trophic factor mechanism will qualitatively recapitulate the spatio-temporal patterns of retinal regeneration observed in human RP.
Generation of transducible version of a recombinant human HAND2 transcription factor from Escherichia coli
Authors: Haridhasapavalan Krishna Kumar , Sundaravadivelu Pradeep Kumar , Mohapatra Anshuman , Joshi Neha , Das Nayan Jyoti , Thummer Rajkumar P 
Published: September 2021

AbstractTranscription factor HAND2 has a significant role in vascularization, angiogenesis, and cardiac neural crest development. Also, it is one of the key cardiac factors crucial for the enhanced derivation of functional and mature myocytes from non-myocyte cells. Here, we report the generation of the recombinant human HAND2 fusion protein from the heterologous system. First, we cloned the full-length human HAND2 gene (only protein-coding sequence) after codon optimization along with the fusion tags (for cell penetration, nuclear translocation, and affinity purification) into the expression vector. We then transformed and expressed it in Escherichia coli (E. coli) strain, BL21(DE3). Next, the effect (in terms of expression) of tagging of fusion tags with this recombinant protein at two different terminals was also investigated. Notably, using affinity chromatography, we established the one-step homogeneous purification of human recombinant HAND2 protein; and through circular dichroism spectroscopy, we established that this purified protein had retained its secondary structure. Furthermore, we show that this purified human protein could transduce the human cells and translocate to its nucleus. Prospectively, the purified recombinant HAND2 protein can potentially be a safe and effective molecular tool in the direct cardiac reprogramming process and other biological applications.
Distinct inflammatory and transcriptomic profiles in dominant versus subordinate males in mouse social hierarchies
Authors: Lee Won , Milewski Tyler M. , Dwortz Madeleine F. , Young Rebecca L. , Gaudet Andrew D. , Fonken Laura K. , Champagne Frances A. , Curley James P. 
Published: September 2021

AbstractSocial status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems. Particularly, changes in energetic investment in the immune system can have significant short and long-term effects on fitness and health. We have previously found that dominant alpha male mice living in social hierarchies have increased metabolic demands related to territorial defense. In this study, we tested the hypothesis that high-ranking male mice favor energetically inexpensive adaptive immunity, while subordinate mice show higher investment in innate immunity. We housed 12 groups of 10 outbred CD-1 male mice in a social housing system. All formed linear social hierarchies and subordinate mice had higher concentrations of plasma corticosterone (CORT) than alpha males. This difference was heightened in highly despotic hierarchies. Using flow cytometry, we found that dominant status was associated with a significant shift in immunophenotypes towards favoring adaptive versus innate immunity. Using Tag-Seq to profile hepatic and splenic transcriptomes of alpha and subordinate males, we identified genes that regulate metabolic and immune defense pathways that are associated with status and/or CORT concentration. In the liver, dominant animals showed an up-regulation of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed an up-regulation of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed up-regulation of genes facilitating oxidative phosphorylation and DNA repair and CORT was negatively associated with genes involved in lymphocyte proliferation and activation. Together, our findings suggest that dominant and subordinate animals adaptively shift energy investment in immune functioning and gene expression to match their contextual energetic demands.HighlightsImmunity is shaped by stress and energetic pressures associated with social statusDominant and subordinate mice favor adaptive and innate immunity, respectivelyDominants increase expression of genes involved in energy productionWound healing and DNA repair genes are upregulated in subordinatesGenes related to maintaining and signaling social status are upregulated in dominants
Entry to and exit from diapause arrest inCaenorhabditis elegansare both regulated by a steroid hormone pathway
Authors: Zhang Mark G , Sternberg Paul W 
Published: September 2021

AbstractDiapause arrest in animals such asCaenorhabditis elegansis tightly regulated so that animals make appropriate developmental decisions amidst environmental challenges. Fully understanding diapause requires mechanistic insight of both entry and exit from the arrested state. While a steroid hormone pathway regulates the entry decision intoCaenorhabditis elegansdauer diapause, its role in the exit decision is less clear. A complication to understanding steroid hormonal regulation of dauer has been the peculiar fact that steroid hormone mutants such asdaf-9form partial dauers under normal growth conditions. Here, we corroborate previous findings thatdaf-9mutants remain capable of forming full dauers under unfavorable growth conditions, and we establish that thedaf-9partial dauer state is likely a partially exited dauer that has initiated but cannot complete the dauer exit decision. We show that the steroid hormone pathway is both necessary for and promotes complete dauer exit, and that the spatiotemporal dynamics of steroid hormone regulation during dauer exit resembles that of dauer entry. Overall, dauer entry and dauer exit are distinct developmental decisions that are both controlled by steroid hormone signaling.Summary StatementIn animals such asCaenorhabditis elegans, a steroid hormone pathway controls both the entry and exit decisions into and out of the developmentally arrested dauer state in response to environmental signaling.
Free spermidine evokes superoxide radicals that manifest toxicity
Authors: Kumar Vineet , Mishra Rajesh Kumar , Ghose Debarghya , Kalita Arunima , Prakash Anand , Mitra Gopa , Arora Amit , Dutta Dipak 
Published: September 2021

AbstractSpermidine and other polyamines alleviate oxidative stress, yet excess spermidine seems toxic to Escherichia coli unless it is neutralized by SpeG, an enzyme for the spermidine N-acetyl transferase function. Besides, a specific mechanism of SpeG function conferring pathogenic fitness to Staphylococcus aureus USA300 strain is unknown. Here, we provide evidence that although spermidine mitigates oxidative stress by lowering hydroxyl radical and hydrogen peroxide levels, excess of it simultaneously triggers the production of superoxide radicals, thereby causing toxicity in the E. coli ΔspeG strain as well as naturally SpeG-deficient S. aureus RN4220 strain. However, wild-type E. coli and S. aureus USA300 with a horizontally-acquired speG gene tolerate applied exogenous spermidine stress. Furthermore, we demonstrate that while RNA-bound spermidine inhibits iron oxidation, free spermidine interacts and oxidizes the iron to evoke superoxide radicals directly. Superoxide radicals thus generated, further affects redox balance and iron homeostasis. Since iron acquisition and metabolism in the host tissues is a challenging task for S. aureus, the current findings helped us explain that the evolutionary gain of SpeG function by S. aureus USA300 strain allows it to neutralize exogenous spermidine- and spermine-mediated toxicity towards iron metabolism inside the host tissues.
Information processing dynamics in neural networks of macaque cerebral cortex reflect cognitive state and behavior
Authors: Varley Thomas F. , Sporns Olaf , Schaffelhofer Stefan , Scherberger Hansjörg , Dann Benjamin 
Published: September 2021

AbstractOne of the essential functions biological neural networks is the processing of information. This comprises processing sensory information to perceive the environment, up to processing motor information to interact with the environment. Due to methodological concerns, it has been historically unclear how information processing changes during different cognitive or behavioral states, and to what extent information is processed within or between the network of neurons in different brain areas. In this study, we leverage recent advances in the calculation of information dynamics to explore neural-level processing within and between the fronto-parietal areas AIP, F5 and M1 during a delayed grasping task performed by three macaque monkeys. While information processing was high within all areas during all cognitive and behavioral states of the task, inter-areal processing varied widely: during visuo-motor transformation, AIP and F5 formed a reciprocally connected processing unit, while no processing was present between areas during the memory period. Movement execution was processed globally across all areas with a predominance of processing in the feedback direction. Additionally, the fine-scale network structure re-configured at the neuron-level in response to different grasping conditions, despite of no differences in the overall amount of information present. These results suggest that areas dynamically form higher-order processing units according to the cognitive or behavioral demand, and that the information processing network is hierarchically organized at the neuron-level, with the coarse network structure determining the behavioral state and finer changes reflecting different conditions.Significance StatementWhat does it mean to say that the brain “processes information?” Scientists often discuss the brain in terms of information processing – animals take in information from their environment through their senses, and use it to make decisions about how to act in the world. In this work, we use a mathematical framework called information theory to explore how signals from the environment influence brain activity, and how brain activity in turn informs on behaviors. We found that different brain regions processed information in dynamic and flexible ways, with signals flowing up and down the hierarchy of sensory-motor depending on the demands of the moment. This shows how “computation” in the brain can reflect complex behaviors and cognitive states.
Post-pandemic residential environment in Amman
Authors: Abed Amal 
Published: September 2021

PurposeThe fundamental lifestyle changes, economic concerns, property price increase and construction cost can explain the transformation of traditional housing layouts to massive indoor planes by prioritizing indoor over outdoor spaces. That is, overlooking the effect of outdoor spaces, on life quality, to compensate for indoor spaces expansion. As a result, this study highlighted outdoor spaces and their impact on psychological wellbeing, especially through the enforcement of quarantine conditions and social distance.Design/methodology/approachTo achieve that, a spatial analysis for (70) apartments, in Amman, was undertaken to understand outdoor space in terms of spatial configuration, size, adjacent spaces and usage. An assessment for outdoor space based on both users' and professionals' perspectives to discuss the current situation condition in terms of physical layout, activities, area, spaces' treatment and associated incentives. (125) responses were collected from the head of household living in an apartment through using a structured questionnaire. In addition, feedback in terms of dynamics home components, home buyers' market trends and local regulations were collected from (22) professionals.FindingsStudy results have shown that apartments' buildings in Amman are deficient, quantitatively and qualitatively, in both apartments with outdoor spaces in general and units on typical floors without outdoor space in specific. While, quantitative deficiency is associated with the poor layout in terms of area, functionality and variety. Qualitative is related to the absence of nature inspiration that incorporates five senses. As a result, this underlines the need for formulation design guidelines and strategies considering psychological wellbeing to improve outdoor spaces as a hub for activities.Originality/valueHighlight the value of introducing post-pandemic multi-family housing that could lead to changes in building codes and design strategies to enhance psychological wellbeing of residents.
Design-led events in collaborative planning: improving post-event planning and delivery
Authors: AlWaer Husam , Rintoul Susan , Cooper Ian 
Published: September 2021

PurposeDesign-led events are known under a range of different titles such charrettes, participatory placemaking, co-design and enquiry by design. Rather than being standalone, such events form one single step in a multi-stage collaborative planning process. What comes after them has to be acknowledged as important to their effective contribution to collaborative planning. To date, no coherent body of empirical evidence on the aftermath of events has been published demonstrating critical factors that contribute to their success.Design/methodology/approachThe paper’s significance resides in identifying an extended framework for the stages in the collaborative planning process and in highlighting critical issues for ensuring that the aspirations and concerns expressed by stakeholders throughout the process are acted on and delivered, namely, subsequent decision-making and delivery; follow-on support, resourcing and funding; the legal status of events and related governance issues; and appropriate monitoring and evaluation practices.FindingsThe paper provides guidance for professional and local stakeholders who are expected to carry the burden of acting on the outputs arising from such events. To be successful, collaborative planning has to be based on longitudinal stakeholder engagement – both long before but also after such events. It is here that the significance of the results reported here lie.Originality/valueThe originality of this paper lies in its attempt to broaden understanding of what happens in collaborative planning following design-led events, drawing on interviews with professional and lay participants in events held across Scotland over the past decade.
Consolidation of off-balance sheet entities and investment efficiency
Authors: Zhao Fang , Barua Abhijit , Kim Jung Hoon 
Published: September 2021

PurposeThe purpose of this study is to examine the effect of consolidating off-balance sheet entities on firm-level investment efficiency. Financial Accounting Standards Board Interpretation No. 46, consolidation of variable interest entities – an Interpretation of ARB No. 51 (FIN 46) is used as a quasi-exogenous shock to financial reporting in this study.Design/methodology/approachThe authors empirically test the change of investment efficiency for a sample of firms affected by FIN 46 in the post-FIN 46 periods. In the regression, a group of matched pairs selected from unaffected firms is used as the control sample and firm characteristics are used as control variables.FindingsThe authors find that firms affected by FIN 46 experience improvement in investment efficiency after adopting the standard compared to unaffected firms. The authors also document that FIN 46 firms’ level of investment decreases after FIN 46 compared to unaffected firms. These empirical results suggest that the improvement in investment efficiency is likely to be achieved by the reduction in over-investment. Further analyses show that amongst the affected firms, firms consolidating off-balance sheet special purpose entities (SPEs) improve investment efficiency mainly by reducing over-investment, whereas firms avoiding the consolidation of SPEs do not display such tendency.Originality/valueThis study contributes to the literature on the relation between financial reporting and investment efficiency, as well as the literature on the impact of FIN 46. To the best of the authors’ knowledge, this study is the first to examine the relation between the consolidation of off-balance sheet entities and investment efficiency.
Cooking fuel choices of households in urban areas in Uganda: a multinomial probit regression analysis
Authors: Elasu Joseph , Kimuli Bright Richard , Adaramola Muyiwa S. 
Published: September 2021

PurposeThis study explores the economic and sociodemographic factors that influence households' decisions on the type of fuel used for cooking in urban areas in Uganda.Design/methodology/approachIn total, two cross-section data surveyed by the Uganda Bureau of Statistics (UBOS) in 2012/13 and 2016/17 were used to analyze consumption of energy for cooking purposes in urban areas of Uganda. This paper employed a multinomial probit regression model and the corresponding marginal effects to analyze cooking fuel choices, which are biomass, electricity and gas and kerosene combined.FindingsThe results showed that household expenditure was statistically significant for the choice of cooking fuel chosen. Furthermore, kitchen type, dwelling type and apartment tenure type are found to be significantly influence the choice of household cooking fuel decisions.Originality/valueThis study takes into consideration the combined influence of the kitchen type, dwelling and tenure type as explanatory variables for the choice of cooking fuel for households in urban areas in Uganda. These factors have not been considered in previous studies done in Uganda, especially within the context of urban households when making choices for cooking fuel.
The impact of training on productivity and wages in Tunisia
Authors: Ben Jemaa Cherif Naouel 
Published: September 2021

PurposeThe purpose of this paper is to investigate the impact of training on labor productivity and wages in order to examine how the benefits from training are shared between employers and employees.Design/methodology/approachThis study analyzes an industry panel covering all sectors of the Tunisian economy for the period 2000–2014. The panel structure of the data allows controlling for the endogeneity of training by using different panel data techniques.FindingsResults show that both employers and workers benefit from training since it has a positive and significant effect on productivity and wages. However, the effect of training on productivity is substantially higher than on wages, suggesting that employers obtain the largest part of the returns to training. This result is consistent with theories that explain firm-sponsored training by a compressed wage structure in imperfect labor markets.Originality/valueThis study, particularly showcasing the labor market in Tunisia, is one of the first to provide estimates for a developing country to assess the effects of training for both employer and employee. It is also among the few empirical works that analyzed the impact of training on labor productivity and wages simultaneously.