Miracle-dz/UniFAR-FTUs huggingface dataset:
Nature and location of modifier alleles determine the resolution of intralocus sexual conflict

When selection favours different levels of expression for a shared trait in males and females, the population is said to be in Intralocus Sexual Conflict (IaSC). In a landmark study, Connallon and Clark (2010) showed that modifiers (alleles at a different locus that alter the expression of the trait under IaSC in a sex-specific manner), effectively resolve IaSC. Their model assumed that modifier alleles are “perfect”; i.e., they fully rescue the harmful effects of the deleterious allele while leaving the positive effects of the beneficial allele unaffected. In the present study, we relaxed this assumption to include more realistic “imperfect” modifier alleles. Imperfect modifiers are those that reduce the expressions of both detrimental allele and beneficial allele to different extents in a given sex. We also ask whether autosomes or X chromosomes are more conducive to resolution of IaSC. Our results suggest that the resolution of IaSC may not always be guaranteed when the modifier allele is “imperfect. ” Interestingly, IaSC gets resolved more easily on autosomes only when modifier alleles are “perfect” or near “perfect” in concordance with the assumption made by Connallon and Clark (2010). However, in general, X chromosomes are more conducive to the resolution of IaSC.
Dorsal peduncular cortex activity modulates affective behavior and fear extinction in mice

The medial prefrontal cortex (mPFC) is critical to cognitive and emotional function and underlies many neuropsychiatric disorders, including mood, fear and anxiety disorders. In rodents, disruption of mPFC activity affects anxiety- and depression-like behavior, with specialized contributions from its subdivisions. The rodent mPFC is divided into the dorsomedial prefrontal cortex (dmPFC), spanning the anterior cingulate cortex (ACC) and dorsal prelimbic cortex (PL), and the ventromedial prefrontal cortex (vmPFC), which includes the ventral PL, infralimbic cortex (IL), and in some studies the dorsal peduncular cortex (DP) and dorsal tenia tecta (DTT). The DP/DTT have recently been implicated in the regulation of stress- induced sympathetic responses via projections to the hypothalamus. While many studies implicate the PL and IL in anxiety-, depression-like and fear behavior, the contribution of the DP/DTT to affective and emotional behavior remains unknown. Here, we used chemogenetics and optogenetics to bidirectionally modulate DP/DTT activity and examine its effects on affective behaviors, fear and stress responses in C57BL/6J mice. Acute chemogenetic activation of DP/DTT significantly increased anxiety-like behavior in the open field and elevated plus maze tests, as well as passive coping in the tail suspension test. DP/DTT activation also led to an increase in serum corticosterone levels and facilitated auditory fear extinction learning and retrieval. Activation of DP/DTT projections to the dorsomedial hypothalamus (DMH) acutely decreased freezing at baseline and during extinction learning, but did not alter affective behavior. These findings point to the DP/DTT as a new regulator of affective behavior and fear extinction in mice.
Assessing the impact of 20th century internal migrations on the genetic structure of Estonia

Spatial genetic structure observed in many human populations is in large part attributed to past demographic events and isolation by distance. However, how intensifying migration affects this structure remains understudied. Here we harness a sample of more than 180 thousand individuals to explore the genetic correlates and consequences of contemporary migrations in Estonia. While we show that migration smoothens the genome-wide genetic structure, it intensifies inter-regional differences in polygenic scores (PGS) for certain traits, derived both from population as well as within-sibship studies. The strongest effect is observed for educational attainment which is consistent with previous observations in the UK and suggests this to be a general pattern. We explore those regional differences in PGS in terms of the driving forces behind them and from a temporal perspective, and suggest urbanisation as a major driver for this pattern in Estonia from at least the first half of the 20th century.
Lagged climate-driven range shifts at species’ leading, but not trailing, range edges revealed by multispecies seed addition experiment

Climate change is causing many species’ ranges to shift upslope to higher elevations as species track their climatic requirements. However, many species have not shifted in pace with recent warming (i.e., ‘range stasis’), possibly due either to demographic lags or microclimatic buffering. The ‘lagged-response hypothesis’ posits that range stasis disguises an underlying climatic sensitivity if range shifts lag the velocity of climate change due to slow colonization or mortality. Alternatively, the ‘microclimatic buffering hypothesis’ proposes that small-scale variation within the landscape, such as canopy cover, creates patches of suitable habitat within otherwise unsuitable macroclimates that create climate refugia and buffer range contractions. To test these two hypotheses, we combined a large seed addition experiment of 25 plant species across macro- and micro-scale climate gradients with local herbaria records to compare patterns of seedling recruitment relative to adult ranges and microclimate in the North Cascades, USA. Despite high species-to-species variability in recruitment, community-level patterns supported the lagged response hypothesis, with a mismatch between where recruitment vs. adults occur. On average, the seedling recruitment optimum shifted from the adult climatic range centre to historically cooler, wetter regions and many species recruited beyond their cold (e.g., leading) range edge. Meanwhile, successful recruitment at warm and dry edges, despite recent climate change, suggests that macroclimatic effects on recruitment do not drive trailing range dynamics. By contrast, we were unable to detect evidence of microclimatic buffering due to canopy cover. Combined, our results suggest apparent range stasis in our system is a lagged response to climate change at the cool ends of species ranges, with range expansions likely to occur slowly or in a punctuated fashion.
Human ADA2 deficiency is characterized by the absence of an intracellular hypoglycosylated form of adenosine deaminase 2

Human deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease with a complex clinical phenotype of recurrent fever, vasculitis and stroke as well as immunodeficiency and bone marrow failure. It is caused by pathogenic variants in ADA2 that lead to impaired ADA2 protein secretion and reduced deaminase activity. However, the mechanisms driving the disease on a cellular level remain elusive. Here, we analyze protein expression of mutant ADA2 in human monocyte-derived macrophages from 10 DADA2 patients. We identify a low-molecular-weight (LMW) form of ADA2 expressed exclusively intracellularly in healthy control macrophages. This LMW-ADA2 is hypoglycosylated compared with secreted high-molecular-weight (HMW) ADA2 and it is absent in DADA2 patients’ monocyte-derived macrophages. We confirm the absence of LMW-ADA2 upon overexpression of 11 pathogenic ADA2 variants in HEK293T cells. By analyzing protein trafficking and glycan processing, we show that LMW-ADA2 is generated from wild-type HMW-ADA2 after transfer to the Golgi apparatus. In conclusion, we describe a previously unreported intracellular hypoglycosylated form of ADA2 and establish the absence of this LMW-ADA2 as a cellular characteristic of DADA2. Graphical abstract
A normalization method that controls for total RNA abundance affects the identification of differentially expressed genes, revealing bias toward morning-expressed responses

RNA-Sequencing is widely used to investigate changes in gene expression at the transcription level in plants. Most plant RNA-Seq analysis pipelines base the normalization approaches on the assumption that total transcript levels do not vary between samples. However, this assumption has not been demonstrated. In fact, many common experimental treatments and genetic alterations affect transcription efficiency or RNA stability, resulting in unequal transcript abundance. The addition of synthetic RNA controls is a simple correction that controls for variation in total mRNA levels. However, adding spike-ins appropriately is challenging with complex plant tissue, and carefully considering how they are added is essential to their successful use. We demonstrate that adding external RNA spike-ins as a normalization control produces differences in RNA-Seq analysis compared to traditional normalization methods, even between two times of day in untreated plants. We illustrate the use of RNA spike-ins with 3’ RNA-Seq and present a normalization pipeline that accounts for differences in total transcriptional levels. We evaluate the effect of normalization methods on identifying differentially expressed genes in the context of identifying the effect of the time of day on gene expression and response to chilling stress in sorghum.
Structural insight into rabies virus neutralization revealed by an engineered antibody scaffold

Host-cell entry of the highly pathogenic rabies virus (RABV) is mediated by trimeric glycoprotein (G) spikes, which also represent the primary target for the humoral immune response. RABV-G displays several antigenic sites targeted by neutralizing antibodies, including monoclonal antibodies (mAbs) which have been proposed as quality-controlled alternatives to traditional polyclonal rabies immunoglobulin treatment. In this study, we determine the epitope of a potently neutralizing human anti-rabies mAb, CR57, which we engineered into a diabody to facilitate crystallization. We report the crystal structure of the CR57 diabody alone at 2.38 Å resolution, and in complex with RABV-G domain III at 3.15 Å resolution. CR57 is demonstrated to bind RABV through a predominantly hydrophobic interface, with essential interactions targeting a conserved six-residue peptide sequence ’KLCGVL’ on the RABV-G. Further, our structural analysis suggests that CR57 sterically hinders receptor recognition and the fusogenic transitions of the spike protein that are required for host-cell entry. Altogether, this investigation provides a structural perspective on rabies inhibition by a potent antibody and delineates a functionally significant region in the spike. This understanding could pave the way for the development of prophylactic antibodies and other therapeutic strategies. Author summary Rabies virus (RABV) and many other lyssaviruses possess the ability to invade the central nervous system, leading to fatal encephalitis in mammals. Initiation of the infectious cycle depends on host cell recognition and entry, which is mediated by viral surface glycoprotein (G) spikes and can be inhibited by spike-targeting neutralizing antibodies. In our study, we elucidated the crystal structure of an antigenic domain from RABV-G in complex with a diabody derived from the potently neutralizing antibody CR57. This investigation revealed the molecular interactions by which CR57 binds to RABV-G and outlined a site of vulnerability comprising a conserved peptide in RABV-G domain III, where antibody binding is likely to inhibit RABV by obstructing host cell entry. Insights into the binding modalities of antibodies like CR57 deepen our understanding of how RABV and other lyssaviruses are neutralized, aiding the development of potential therapeutics. Furthermore, our study showcases the utility of engineering antibodies into diabodies to obtain crystal structures of antibody-antigen complexes.
Negative density dependence promotes persistence of a globally rare yet locally abundant plant species (Oenothera coloradensis)

Identifying the mechanisms underlying the persistence of rare species has long been a motivating question for ecologists. Classical theory implies that community dynamics should be driven by common species, and that natural selection should not allow small populations of rare species to persist. Yet, a majority of the species found on Earth are rare. Consequently, several mechanisms have been proposed to explain their persistence, including negative density dependence, demographic compensation, vital rate buffering, asynchronous responses of sub-populations to environmental heterogeneity, and fine-scale source-sink dynamics. Persistence of seeds in a seed bank, which is often ignored in models of population dynamics, can also buffer small populations against collapse. We used integral projection models (IPMs) to examine the population dynamics of Oenothera coloradensis, a rare, monocarpic perennial forb, and determine whether any of five proposed demographic mechanisms for rare species persistence contribute to the long-term viability of two populations. We also evaluated how including a discrete seed bank stage changed population models for this species. Including a seed bank stage in population models had a significant positive impact on modeled O. coloradensis population growth rate. Using IPMs that included a discrete seedbank state, we found that negative density-dependence was the only supported mechanism for the persistence of this rare species. Synthesis: IPMs of two populations of the rare species O. coloradensis emphasize the importance of including cryptic life stages such as seed banks in demographic models, but fail to provide strong support for most of the proposed mechanisms of rare species persistence. We propose that high micro-site abundance in a spatially heterogeneous environment enables this species to persist, allowing it to sidestep the demographic and genetic challenges of small population size that rare species typically face. These results emphasize that globally rare species can employ many different strategies for persistence, including the somewhat counter-intuitive phenomenon of local abundance. This reinforces the need for customized management and conservation strategies that mirror the diversity of mechanisms that allow rare species persistence.
Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum

Clinical outcomes for total-pancreatectomy followed by intraportal islet autotransplantation (TP-IAT) to treat chronic pancreatitis (CP) patients are suboptimal due to the inflammatory state of the patient’s pancreas, oxidative tissue damage during the isolation process, and the harsh engraftment conditions in the liver’s vasculature, which include ischemia-reperfusion injury, and instant blood–mediated inflammatory reactions. We describe the use of the thermoresponsive, antioxidant macromolecule poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN) to protect islet redox status and function in vitro and in vivo and to create a viable extrahepatic islet engraftment site in the abdomen. PPCN in aqueous media transitions from a liquid to an elastic hydrogel when exposed to body temperature via temperature-induced macromolecular self-assembly. Islets entrapped in the PPCN hydrogel and exposed to oxidative stress remain functional and support long-term euglycemia, in contrast to islets entrapped in a biologic scaffold (BS). When applied to the omentum of non-human primates (NHPs), PPCN is well-tolerated, safe, and mostly resorbed without fibrosis at 3 months post-implantation. To obtain autologous islets, a partial pancreatectomy was performed, followed by STZ administration to induce diabetes and destroy any remaining endogenous islets. Application of the autologous islets to the momentum using PPCN restored normoglycemia with minimal insulin requirements for over 100 days. These results support the use of PPCN as a scaffold for minimally invasive delivery of islets to the omentum of pancreatitis patients and highlight the importance of scaffold antioxidant properties as a new mechanism to protect islet function and maximize long-term autologous graft performance. One Sentence Summary Omentum islet transplantation using a thermoresponsive, antioxidative polymer supports autologous islet viability and function in nonhuman primates.
Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion, and drug screening

Brain organoids offer unprecedented insights into brain development and disease modeling and hold promise for drug screening. Significant hindrances, however, are morphological and cellular heterogeneity, inter-organoid size differences, cellular stress, and poor reproducibility. Here, we describe a method that reproducibly generates thousands of organoids across multiple iPSC lines. These High Quantity brain organoids (Hi-Q brain organoids) exhibit reproducible cytoarchitecture, cell diversity, and functionality, are free from ectopically active cellular stress pathways, and allow cryopreservation and re-culturing. Using patient-derived Hi-Q brain organoids, we recapitulated distinct forms of microcephaly pathogenesis: primary microcephaly due to a mutation in centrosomal CDK5RAP2 and progeria-associated microcephaly in Cockayne syndrome. When modeling glioma invasion, hi-Q brain organoids displayed a similar invasion pattern for a given patient-derived glioma cell line. This enabled a medium-throughput screen to identify Selumetinib and Fulvestrant, which also perturbed glioma invasion in vivo. Thus, the Hi-Q approach can easily be adapted to reliably harness brain organoids’ utility for personalized disease modeling and drug discovery.
A calibration protocol for soil-crop models

Process-based soil-crop models are widely used in agronomic research. They are major tools for evaluating climate change impact on crop production. Multi-model simulation studies show a wide diversity of results among models, implying that simulation results are very uncertain. A major path to improving simulation results is to propose improved calibration practices that are widely applicable. This study proposes an innovative generic calibration protocol. The two major innovations concern the treatment of multiple output variables and the choice of parameters to estimate, both of which are based on standard statistical procedure adapted to the particularities of soil-crop models. The protocol performed well in a challenging artificial-data test. The protocol is formulated so as to be applicable to a wide range of models and data sets. If widely adopted, it could substantially reduce model error and inter-model variability, and thus increase confidence in soil-crop model simulations.
Tower and Aircraft Eddy Covariance Measurements of Water Vapor, Energy, and Carbon Dioxide Fluxes during SMACEX

Abstract A network of eddy covariance (EC) and micrometeorological flux (METFLUX) stations over corn (Zea mays L.) and soybean [Glycine max (L.) Merr. ] canopies was established as part of the Soil Moisture–Atmosphere Coupling Experiment (SMACEX) in central Iowa during the summer of 2002 to measure fluxes of heat, water vapor, and carbon dioxide (CO2) during the growing season. Additionally, EC measurements of water vapor and CO2 fluxes from an aircraft platform complemented the tower-based measurements. Sensible heat, water vapor, and CO2 fluxes showed the greatest spatial and temporal variability during the early crop growth stage. Differences in all of the energy balance components were detectable between corn and soybean as well as within similar crops throughout the study period. Tower network–averaged fluxes of sensible heat, water vapor, and CO2 were observed to be in good agreement with area-averaged aircraft flux measurements.
Human DDX6 regulates translation and decay of inefficiently translated mRNAs

Recent findings indicate that the translation elongation rate influences mRNA stability. One of the factors that has been implicated in this link between mRNA decay and translation speed is the yeast DEAD-box helicase Dhh1p. Here, we demonstrate that the human ortholog of Dhh1p, DDX6, triggers deadenylation-dependent decay of inefficiently translated mRNAs in human cells. DDX6 interacts with the ribosome through the Phe-Asp-Phe (FDF) motif in its RecA2 domain. Furthermore, RecA2-mediated interactions and ATPase activity are both required for DDX6 to destabilize inefficiently translated mRNAs. Using ribosome profiling and RNA sequencing, we identified two classes of endogenous mRNAs that are regulated in a DDX6-dependent manner. The identified targets are either translationally regulated or regulated at the steady-state-level and either exhibit signatures of poor overall translation or of locally reduced ribosome translocation rates. Transferring the identified sequence stretches into a reporter mRNA caused translation-and DDX6-dependent degradation of the reporter mRNA. In summary, these results identify DDX6 as a crucial regulator of mRNA translation and decay triggered by slow ribosome movement and provide insights into the mechanism by which DDX6 destabilizes inefficiently translated mRNAs.
SOLAR RADIATION FORECAST USING ARTIFICAL NEURAL NETWORKS IN SOUTH BRAZIL

Forecasts from Eta/CPTEC model, expressing the future atmospheric conditions, are used as inputs in Artificial Neural Networks (ANNs), in order to achieve more reliable short-term forecasts for the incident solar radiation. Global solar radiation measurements performed by two stations of the SONDA project located in south Brazil (Florianopolis and Sao Martinho da Serra) are used as the targets during ANNs training and for forecasts evaluation. Solar radiation forecasts from ANNs present higher correlation coefficients and lower errors than the Eta model output for shortwave radiation on ground. The well-know bias observed in solar radiation forecasts by the Eta model was removed by the use of ANNs. The improvement in RMSE obtained with ANNs over the Eta model was higher than 30%, estimated with a skillscore. This improvement is a response to a constant demand from the energy sector for more accurate ways of forecasting the solar energy power, so as to support the management of the national generation and distribution systems of electricity.
Uplink Grant-free PDMA Transmission Scheme by Exploiting Poly Complementary Sequence

Non-orthogonal multiple access (NOMA) technology is a key technology of the future cellular mobile communication system. It provides services for users under diﬀerent channel conditions through signal superposition transmission and spectrum multiplexing. Pattern division multiple access (PDMA) is a new NOMA technology based on the overall optimization of multi-user communication system. Since the performance of PDMA mainly depends on the gain of the pattern matrix, we propose a design scheme of uplink PDMA pattern matrix for ultra-reliable low latency communication (uRLLC). For the interference between users is a common problem in NOMA system, ﬁrst, we use poly complementary sequence (PCS) as the spread code-book to spread the PDMA transmission signal and reduce interference. Meanwhile, an uplink power control scheme is proposed. It allocates wireless resources reasonably by jointly considering the interference between users and resource blocks within users (JUR), the corresponding outage probability formula is also derived. Simulation results show that compared with the previous researches, the pattern matrix design scheme and JUR power control scheme proposed in this paper have greatly improved the transmission performance. The addition of PCS spread spectrum technology can signiﬁcantly reduce the block error rate and outage probability.