Miracle-dz/UniFAR-FTUs huggingface dataset:
Female reproductive fluid composition differs based on mating system in Peromyscus mice

Post-copulatory sexual selection is theorized to favor female traits that allow them to control sperm use and fertilization, leading to the prediction that female reproductive traits that influence sperm migration should differ between polyandrous and monogamous species. Here we exploit natural variation in the female mating strategies of closely related Peromyscus mice to compare female traits that influence sperm motility – the viscosity, pH, and calcium concentration of fluids in the reproductive tract – between polyandrous and monogamous species. We find that the viscosity and pH, but not calcium concentration, of fluids collected from both the uterus and the oviduct significantly differ between species based on mating system. Our results demonstrate the existence of a viscosity gradient within the female reproductive tract that increases in monogamous species but decreases in polyandrous species. Both species have a more alkaline environment in the uterus than oviduct, but only in the polyandrous species did we observe a decrease in calcium in the distal end of the tract. These results suggest that fluid viscosity and pH in the female reproductive tracts of these mice may be influenced by post-copulatory sexual selection and provide a promising potential mechanism for female sperm control given their importance in modulating sperm behavior.
Temporal integration of rod signals in luminance and chromatic pathways

We assessed how rod excitation (R) affects luminance (L+M+S) and chromatic [L/(L+M)] reaction times (RTs). A four-primary display based on the overlapped images of two spectrally-modified monitors, which allowed specific or combined [L+M+S+R, L/(L+M) + R] photoreceptor stimulation, was used to present a C-target stimulus differing from the background only by the selected stimulation. For the luminance pathway, rod input increased RTs, suggesting a suppressive rod-cone interaction. The responses of the chromatic pathway were faster when rods were involved, suggesting a major role of rods in mesopic color perception.
Rethinking the nature of intraspecific variability and its consequences on species coexistence

Context Intraspecific variability (IV) has been proposed to explain species coexistence in diverse communities. Assuming, sometimes implicitly, that conspecific individuals can perform differently in the same environment and that IV blurs species differences, previous studies have found contrasting results regarding the effect of IV on species coexistence. Objective We aim at showing that the large IV observed in data does not mean that conspecific individuals are necessarily different in their response to the environment and that the role of high-dimensional environmental variation in determining IV has been largely underestimated in forest plant communities. Methods and Results We first used a simulation experiment where an individual attribute is derived from a high-dimensional model, representing “perfect knowledge” of individual response to the environment, to illustrate how a large observed IV can result from “imperfect knowledge” of the environment. Second, using growth data from clonal Eucalyptus plantations in Brazil, we estimated a major contribution of the environment in determining individual growth. Third, using tree growth data from long-term tropical forest inventories in French Guiana, Panama and India, we showed that tree growth in tropical forests is structured spatially and that despite a large observed IV at the population level, conspecific individuals perform more similarly locally than compared with heterospecific individuals. Synthesis As the number of environmental dimensions that are typically quantified is generally much lower than the actual number of environmental dimensions influencing individual attributes, a great part of observed IV might be misinterpreted as random variation across individuals when in fact it is environmentally-driven. This mis-representation has important consequences for inference about community dynamics. We emphasize that observed IV does not necessarily impact species coexistence per se but can reveal species response to high-dimensional environment, which is consistent with niche theory and the observation of the many differences between species in nature.
Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function

Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis. NETs selectively impact the expression of tight junction genes claudins 4, 8 and 11. Bronchial epithelia exposed to NETs demonstrate visible gaps in E-cadherin staining, a decrease in full-length E-cadherin protein and the appearance of cleaved E-cadherin peptides. Pretreatment of NETs with alpha-1 antitrypsin (A1AT) inhibits NET serine protease activity, limits E-cadherin cleavage, decreases bronchial cell apoptosis and preserves epithelial integrity. In conclusion, NETs disrupt human airway epithelial barrier function through bronchial cell death and degradation of E-cadherin, which are limited by exogenous A1AT.
Novel diversity panel facilitates genomic dissection of lodging in tef (Eragrostis tef)

6 Underutilized species that are not widely cultivated (known as orphan crops) present opportunities 7 to increase crop diversity and food security. Tef [Eragrostis tef (Zucc.) Trotter] is known for its 8 high-quality grain and forage. Root-borne lodging is a devastating problem in tef cultivation, 9 leading to large economic losses and limiting its widespread adoption. The aim of this study was 10 to identify genomic regions that are associated with tef lodging. A diversity panel comprised of 11 297 lines (TDP-300) was assembled, genotyped, and phenotyped across 4 field environments. 12 Genome-wide association study identified 29 genomic regions associated with lodging; in all 13 cases with a minor allele conferring reduced lodging. The eleven most prominent sites were 14 located in or near genes, 5 of them with a putative role, of which 3 were to be associated with root 15 development. The identification of lodging-related sites in the current study may advance 16 understanding of the mechanisms underlying tef lodging and crop improvement. To the best of 17 our knowledge, this is the first diversity panel developed for tef. This platform is expected to be 18 useful for detecting genomic regions and markers associated with traits of interest in tef, as well 19 as for breeding and molecular investigations. 20
Plasma iron controls neutrophil production and function

Low plasma iron (hypoferremia) induced by hepcidin is a conserved inflammatory response that protects against infections but inhibits erythropoiesis. How hypoferremia influences leukocytogenesis is unclear. Using proteomic data, we predicted that neutrophil production would be profoundly more iron-demanding than generation of other white blood cell types. Accordingly in mice, hepcidin-mediated hypoferremia substantially reduced numbers of granulocytes but not monocytes, lymphocytes or dendritic cells. Neutrophil rebound after anti-GR1-induced neutropenia was blunted during hypoferremia, but was rescued by supplemental iron. Similarly, hypoferremia markedly inhibited pharmacologically-stimulated granulopoiesis mediated by GCSF and inflammation-induced accumulation of neutrophils in the spleen and peritoneal cavity. Furthermore, hypoferremia specifically altered neutrophil effector functions, suppressing antibacterial mechanisms but enhancing mitochondrial ROS-dependent NETosis associated with chronic inflammation. Notably, antagonising endogenous hepcidin during acute inflammation enhanced production of neutrophils. We propose plasma iron modulates the profile of innate immunity by controlling monocyte-to-neutrophil ratio and neutrophil activity in a therapeutically targetable system.
GBScleanR: robust genotyping error correction using a hidden Markov model with error pattern recognition

Reduced-representation sequencing (RRS) provides cost-effective and time-saving genotyping platforms. Although the outstanding advantage of RRS in throughput, the obtained genotype data usually contains a large number of errors. Several error correction methods employing hidden Morkov model (HMM) have been developed to overcome these issues. Those methods assume that markers have a uniform error rate with no bias in the allele read ratio. However, bias does occur because of uneven amplification of genomic fragments and read mismapping. In this paper we introduce an error correction tool, GBScleanR, which enables robust and precise error correction for noisy RRS-based genotype data by incorporating marker-specific error rates into the HMM. The results indicate that GBScleanR improves the accuracy by more than 25 percentage points at maximum as compared to the existing tools in simulation datasets and achieves the most reliable genotype estimation in real data even with error prone markers.
Zhx2 Is a Candidate Gene Underlying Oxymorphone Metabolite Brain Concentration Associated with State-Dependent Oxycodone Reward

Understanding the pharmacogenomics of opioid metabolism and behavior is vital to therapeutic success, as mutations can dramatically alter therapeutic efficacy and addiction liability. We found robust, sex-dependent BALB/c substrain differences in oxycodone behaviors and whole brain concentration of oxycodone metabolites. BALB/cJ females showed robust state-dependent oxycodone reward learning as measured via conditioned place preference when compared with the closely related BALB/cByJ substrain. Accordingly, BALB/cJ females also showed a robust increase in brain concentration of the inactive metabolite noroxycodone and the active metabolite oxymorphone compared with BALB/cByJ mice. Oxymorphone is a highly potent, full agonist at the mu opioid receptor that could enhance drug-induced interoception and state-dependent oxycodone reward learning. Quantitative trait locus (QTL) mapping in a BALB/c F2 reduced complexity cross revealed one major QTL on chromosome 15 underlying brain oxymorphone concentration that explained 32% of the female variance. BALB/cJ and BALB/cByJ differ by fewer than 10,000 variants, which can greatly facilitate candidate gene/variant identification. Hippocampal and striatal cis-expression QTL (eQTL) and exon-level eQTL analysis identified Zhx2, a candidate gene coding for a transcriptional repressor with a private BALB/cJ retroviral insertion that reduces Zhx2 expression and sex-dependent dysregulation of cytochrome P450 enzymes. Whole brain proteomics corroborated the Zhx2 eQTL and identified upregulated CYP2D11 that could increase brain oxymorphone in BALB/cJ females. To summarize, Zhx2 is a highly promising candidate gene underlying brain oxycodone metabolite levels. Future studies will validate Zhx2 and its site of action using reciprocal gene editing and tissue-specific viral manipulations in BALB/c substrains. SIGNIFICANCE STATEMENT Our findings show that genetic variation can result in sex-specific alterations in whole brain concentration of a bioactive opioid metabolite after oxycodone administration, reinforcing the need for sex as a biological factor in pharmacogenomic studies. The cooccurrence of female-specific increased oxymorphone and state-dependent reward learning suggests that this minor yet potent and efficacious metabolite of oxycodone could increase opioid interoception and drug-cue associative learning of opioid reward, which has implications for cue-induced relapse of drug-seeking behavior and for precision pharmacogenetics.
Antimicrobial peptide secretion protects endosymbionts from bacteriome autoimmunity in insects

Many insects house symbiotic intracellular bacteria (endosymbionts) that provide them with essential nutrients, thus promoting usage of nutrient-poor habitats. Endosymbiont seclusion within host specialized cells, called bacteriocytes, often organized in a dedicated organ, the bacteriome, is crucial in protecting them from host immune defenses while avoiding chronic host immune activation. Previous evidence obtained in the cereal weevil Sitophilus oryzae has shown that bacteriome immunity is activated against invading pathogens, suggesting endosymbionts might be targeted and impacted by immune effectors during an immune challenge. To pinpoint any molecular determinants associated with such challenges, we conducted a dual transcriptomic analysis of S. oryzae's bacteriome subjected to immunogenic peptidoglycan fragments. We show that upon immune challenge the bacteriome actively participates in the innate immune response via a burst of antimicrobial peptides (AMPs). Surprisingly, endosymbionts do not undergo any transcriptomic changes, indicating that this potential threat goes unnoticed. Immunohistochemistry of selected AMPs show that these are secreted outside the bacteriome, excluding direct contact with the endosymbionts. This work demonstrates that endosymbiont protection during an immune challenge is mainly achieved by efficient confinement within bacteriomes, which provides physical separation between host systemic response and endosymbionts.
A novel class of long small RNAs associates with Argonaute1 and is up-regulated by nutrient deprivation in the alga Chlamydomonas

Small RNAs (sRNAs) associate with Argonaute (AGO) proteins forming effector complexes with key roles in gene regulation and defense responses against molecular parasites. In multicellular eukaryotes, extensive duplication and diversification of RNA interference (RNAi) components have resulted in intricate pathways for epigenetic control of gene expression. The unicellular alga Chlamydomonas reinhardtii also has a complex RNAi machinery, including three AGOs and three Dicer-like (DCL) proteins. However, little is known about the biogenesis and function of most endogenous sRNAs. We demonstrate here that Chlamydomonas contains uncommonly long sRNAs (>26 nt), which associate preferentially with AGO1. Somewhat reminiscent of animal PIWI-interacting RNAs, these long sRNAs are derived from moderately repetitive genomic clusters and their biogenesis appears to be Dicer-independent. Interestingly, long sRNA encoding sequences have been conserved and amplified in phylogenetically related Chlamydomonas species. Additionally, expression of several long sRNAs increases substantially under nutrient deprivation, correlating with the downregulation of predicted target transcripts. We hypothesize that the transposon-like sequences encoding long sRNAs might have been ancestrally targeted for silencing by the RNAi machinery but, during evolution, some long sRNAs might have fortuitously acquired endogenous target genes and become integrated into gene regulatory networks.
A murine model of hnRNPH2-related neurodevelopmental disorder recapitulates clinical features of human disease and reveals a mechanism for genetic compensation of HNRNPH2

Mutations in HNRNPH2 cause an X-linked neurodevelopmental disorder with a phenotypic spectrum that includes developmental delay, intellectual disability, language impairment, motor function deficits, and seizures. More than 90% of patients with this disorder have a missense mutation within or adjacent to the nuclear localization signal (NLS) of hnRNPH2, although the specific pathogenic consequences of these mutations have not been examined. Here we found that hnRNPH2 NLS mutations result in reduced interaction with the nuclear transport receptor Kapβ2 in vitro and in cultured human cells. These mutations also cause modest accumulation of hnRNPH2 in the cytoplasm, suggesting that mislocalization of the protein might contribute to pathogenesis. We generated two knock-in mouse models with human-equivalent mutations in the endogenous mouse gene Hnrnph2, as well as Hnrnph2 knockout (KO) mice, and subjected them to extensive phenotyping. Mutant knock-in mice displayed a spectrum of phenotypes that recapitulated aspects of the human disorder, including reduced survival in males, craniofacial abnormalities, impaired motor and cognitive functions, and increased susceptibility to audiogenic seizures. Mutant knock-in male mice developed more severe phenotypes than female mice, likely due to differences in X-chromosome gene dosage. In contrast, two independent lines of Hnrnph2 KO mice showed no detectable phenotypes. Notably, KO mice had upregulated expression of Hnrnph1, a close paralog of Hnrnph2, whereas mutant Hnrnph2 knock-in mice failed to upregulate Hnrnph1. Thus, genetic compensation by Hnrnph1 might be sufficient to counteract the loss of hnRNPH2. These findings suggest that the pathogenesis of HNRNPH2-related disorder in humans may be driven by a toxic gain of function or a complex loss of HNRNPH2 function with impaired compensation by HNRNPH1. The mutant knock-in mice described here are an important resource for preclinical studies to assess the potential benefit of either gene replacement or therapeutic knockdown of mutant hnRNPH2.
Technology applications in bovine gait analysis: A scoping review

Quantitative bovine gait analysis using technology has evolved significantly over the last two decades. However, subjective methods of gait assessment using visual locomotion scoring remain the primary on-farm and experimental approach. The objective of this review is to map research trends in quantitative bovine gait analysis and to explore the technologies that have been utilized to measure biomechanical parameters of gait. A scoping literature review was conducted according to PRISMA guidelines. A search algorithm based on PICO framework generated three components – bovine, gait, and technology – to address our objectives. Three online databases were searched for original work published from January 2000 to June 2020. A two-step screening process was then conducted, starting with the review of article titles and abstracts based on inclusion criteria. A remaining 125 articles then underwent a full-text assessment, resulting in 82 final articles. Thematic analysis of research aims resulted in four major themes among the studies: gait/claw biomechanics, lameness detection, intervention/comparison, and system development. Lameness detection (55 % of studies) was the most common reason for technology use. Studies in the field of bovine gait analysis used three main technologies: force and pressure platforms (FPP), vision-based systems (VB), and accelerometers. FPP were the first and most popular technologies to evaluate bovine gait and were used in 58.5 % of studies. They include force platforms, pressure mapping systems, and weight distribution platforms. The second most applied technology was VB (34.1 % of studies), which predominately consists of video analysis and image processing systems. Accelerometers, another technological method to measure gait characteristics, were used in 14.6 % of studies. A strong demand for automatic lameness detection influences the path of development for quantitative gait analysis technologies. Although progress has been made, more research is needed to achieve more accurate, practical, and user-friendly technologies.
Protein degradation sets the fraction of active ribosomes at vanishing growth

Growing cells adopt common basic strategies to achieve optimal resource allocation under limited resource availability. Our current understanding of such “growth laws” neglects degradation, assuming that it occurs slowly compared to the cell cycle duration. Here we argue that this assumption cannot hold at slow growth, leading to important consequences. We propose a simple framework showing that at slow growth protein degradation is balanced by a fraction of “maintenance” ribosomes. Consequently, active ribosomes do not drop to zero at vanishing growth, but as growth rate diminishes, an increasing fraction of active ribosomes performs maintenance. Through a detailed analysis of compiled data, we show that the predictions of this model agree with data from E. coli and S. cerevisiae. Intriguingly, we also find that protein degradation increases at slow growth, which we interpret as a consequence of active waste management and/or recycling. Our results highlight protein turnover as an underrated factor for our understanding of growth laws across kingdoms. Author summary The idea that simple quantitative relationships relate cell physiology to cellular composition dates back to the 1950s, but the recent years saw a leap in our understanding of such “growth laws”, with relevant implications regarding the interdependence between growth, metabolism and biochemical networks. However, recent works on nutrient-limited growth mainly focused on laboratory conditions that are favourable to growth. Thus, our current mathematical understanding of the growth laws neglects protein degradation, under the argument that it occurs slowly compared to the timescale of the cell cycle. Instead, at slow growth the timescales of mass loss from protein degradation and dilution become comparable. In this work, we propose that protein degradation shapes the quantitative relationships between ribosome allocation and growth rate, and determines a fraction of ribosomes that do not contribute to growth and need to remain active to balance degradation.
Towards Fair Multiparty Computation in Scriptless Distributed Ledger Systems

—Fairness is one of the fundamental properties for multiparty computation (MPC) protocols. Although fair MPC protocols for general functions is shown to be impossible with a dishonest majority, a variant of fairness called “fairness with penalty” has been explored recently. A MPC protocol provides fairness with penalty if either all participants can get the output, or the dishonest parties who break the protocol after getting the output will be financially penalized. Fairness with penalty is enabled by previous works leveraging the emerging distributed ledger systems (DLS), e.g. Bitcoin and Ethereum. They utilize the scripting functionality provided by the DLSs to make automatic penalty practical without relying on any trusted third party. However, there is also a significant number of DLSs that do not provide the scripting functionality. In this paper, we propose the ROSE protocol which enables fairness with penalty while only requiring the underlying DLS can verify and broadcast digital signatures on transactions. This requirement can be fulfilled by almost all DLSs, including the scriptless DLSs. To the best of our knowledge, it is still unknown how to realize fairness with penalty on scriptless DLSs before our work. We also provide a implementation of ROSE. The experimental results show that applying ROSE only brings little computation and