Miracle-dz/UniFAR-FTUs huggingface dataset:
On the existence and sensitivity analysis of optimal catital accumulation paths in continuous time, infinite horizon models

Abstract In this paper we consider an infinite horizon, continuous time model of economic growth. We prove two theorems; one on the existence of optimal paths of capital accumulation and the other on the dependence of the set of optimal paths on the initial capital stock (sensitivity analysis). In the existence result the underlying technology set is nonconvex and only its “investment’ slices are convex. The proof is direct, without any use of necessary conditions. In the sensitivity analysis, the technology set is convex and so we have that the value function is concave. Then having that, we show that the set of optimal paths is an upper semicaontinuous multifunction of the initial capital stock.
Synthetically mannosylated antigens induce antigen-specific humoral tolerance and reduce anti-drug antibody responses to immunogenic biologics

Immunogenic biologics trigger an anti-drug antibody (ADA) response in patients, which reduces efficacy and increases adverse reactions. Our laboratory has previously shown that targeting protein antigen to the liver microenvironment can reduce antigen-specific T cell responses; herein, we present a strategy to increase delivery of otherwise immunogenic biologics to the liver via conjugation to a synthetic mannose polymer (p(Man)). This delivery leads to reduced antigen-specific T follicular helper cell and B cell responses resulting in diminished ADA production, which is maintained throughout subsequent administrations of the native biologic. We found that p(Man)-antigen treatment impairs the ADA response against recombinant uricase, a highly immunogenic biologic, without a dependence on hapten immunodominance or control by Tregs. We identify increased TCR signaling and increased apoptosis and exhaustion in T cells as effects of p(Man)-antigen treatment via transcriptomic analyses. This modular platform may enhance tolerance to biologics, enabling long-term solutions for an ever-increasing healthcare problem.
Building pangenome graphs

Pangenome graphs can represent all variation between multiple genomes, but existing methods for constructing them are biased due to reference-guided approaches. In response, we have developed PanGenome Graph Builder (PGGB), a reference-free pipeline for constructing unbi-ased pangenome graphs. PGGB uses all-to-all whole-genome alignments and learned graph embeddings to build and iteratively refine a model in which we can identify variation, measure conservation, detect recombination events, and infer phylogenetic relationships.
The shirker’s dilemma and the prospect of cooperation in large groups

Cooperation usually becomes harder to sustain as groups become larger because incentives to shirk increase with the number of potential contributors to collective action. But is this always the case? Here we study a binary-action cooperative dilemma where a public good is provided as long as not more than a given number of players shirk from a costly cooperative task. We find that at the stable polymorphic equilibrium, which exists when the cost of cooperation is low enough, the probability of cooperating increases with group size and reaches a limit of one when the group size tends to infinity. Nevertheless, increasing the group size may increase or decrease the probability that the public good is provided at such an equilibrium, depending on the cost value. We also prove that the expected payoff to individuals at the stable equilibrium (i.e., their fitness) decreases with group size. For low enough costs of cooperation, both the probability of provision of the public good and the expected payoff converge to positive values in the limit of large group sizes. However, we also find that the basin of attraction of the stable polymorphic equilibrium is a decreasing function of group size and shrinks to zero in the limit of very large groups. Overall, we demonstrate non-trivial comparative statics with respect to group size in an otherwise simple collective action problem.
Structured memory representations develop at multiple time scales in hippocampal-cortical networks

Influential views of systems memory consolidation posit that the hippocampus rapidly forms representations of specific events, while neocortical networks extract regularities across events, forming the basis of schemas and semantic knowledge. Neocortical extraction of schematic memory representations is thought to occur on a protracted timescale of months, especially for information that is unrelated to prior knowledge. However, this theorized evolution of memory representations across extended timescales, and differences in the temporal dynamics of consolidation across brain regions, lack reliable empirical support. To examine the temporal dynamics of memory representations, we repeatedly exposed human participants to structured information via sequences of fractals, while undergoing longitudinal fMRI for three months. Sequence-specific activation patterns emerged in the hippocampus during the first 1-2 weeks of learning, followed one week later by high-level visual cortex, and subsequently the medial prefrontal and parietal cortices. Schematic, sequence-general representations emerged in the prefrontal cortex after 3 weeks of learning, followed by the medial temporal lobe and anterior temporal cortex. Moreover, hippocampal and most neocortical representations showed sustained rather than time-limited dynamics, suggesting that representations tend to persist across learning. These results show that specific hippocampal representations emerge early, followed by both specific and schematic representations at a gradient of timescales across hippocampal-cortical networks as learning unfolds. Thus, memory representations do not exist only in specific brain regions at a given point in time, but are simultaneously present at multiple levels of abstraction across hippocampal-cortical networks.
Decoupling of evolutionary changes in mRNA and protein levels

Variation in gene expression across lineages is thought to explain much of the observed phenotypic variation and adaptation. The protein is closer to the target of natural selection but gene expression is typically measured as the amount of mRNA. The broad assumption that mRNA levels are good proxies for protein levels has been undermined by a number of studies reporting moderate or weak correlations between the two measures across species. One biological explanation for this discrepancy is that there has been compensatory evolution between the mRNA level and regulation of translation. However, we do not understand the evolutionary conditions necessary for this to occur nor the expected strength of the correlation between mRNA and protein levels. Here we develop a theoretical model for the coevolution of mRNA and protein levels and investigate the dynamics of the model over time. We find that compensatory evolution is widespread when there is stabilizing selection on the protein level, which is true across a variety of regulatory pathways. When the protein level is under directional selection, the mRNA level of a gene and its translation rate of the same gene were negatively correlated across lineages but positively correlated across genes. These findings help explain results from comparative studies of gene expression and potentially enable researchers to disentangle biological and statistical hypotheses for the mismatch between transcriptomic and proteomic studies.
Preoperative state anxiety predicts postoperative health-related quality of life: A prospective observational study on patients undergoing lung cancer surgery

Objective Improving quality of life (QOL) after surgery is very important. Recently, preoperative anxiety has been suggested to predict postoperative health-related (HR) QOL, however the accuracy of anxiety measurement remains problematic. We examined the relationship between preoperative anxiety level and postoperative HRQOL using qualitative and quantitative assessment of anxiety. Method We used a detailed anxiety assessment to quantitatively investigate preoperative anxiety as a predictor of postoperative HRQOL in lung cancer patients. Fifty one patients who underwent surgery for lung cancer were included. They were assessed four times: on admission, on discharge, 1 month after surgery, and 3 months after surgery. Anxiety was measured separately as “state anxiety” and “trait anxiety” using the State–Trait Anxiety Inventory, and HRQOL was measured using the EuroQol 5 dimension 5-level. Results The HRQOL decreased at discharge and gradually recovered over time, reaching the same level at 3 months after surgery as at admission. HRQOL score was lower at discharge than at pre-surgery and 3 months after the surgery (p < 0.0001 each), and the score at 1 month after the surgery was lower than at pre-surgery (p = 0.007). In addition, multiple regression analysis showed that HRQOL at discharge was associated with “state anxiety” rather than “trait anxiety” at admission (p = 0.004). Conclusion This study identifies the types of anxiety that affect postoperative HRQOL. We suggest that postoperative HRQOL on discharge may be improved by interventions such as psychological or medication treatment for preoperative state anxiety if identified preoperative state anxiety can be managed appropriately.
The role of quantitative ultrasound in diagnosing severe bone metabolic diseases in newborns

COPYRIGHT © 2023 Cerar, Paro-Panjan and SoltirovskaŠalamon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Comparative transcriptome analysis of Peromyscus leucopus and C3H mice infected with the Lyme disease pathogen

Lyme disease (LD), the most prevalent tick-borne disease of humans in the Northern Hemisphere, is caused by the spirochetal bacterium of Borreliella burgdorferi (Bb) sensu lato complex. In nature, Bb spirochetes are continuously transmitted between Ixodes ticks and mammalian or avian reservoir hosts. Peromyscus leucopus mice are considered the primary mammalian reservoir of Bb in the United States. Earlier studies demonstrated that experimentally infected P. leucopus mice do not develop disease. In contrast, C3H mice, a widely used laboratory strain of Mus musculus in the LD field, develop severe Lyme arthritis. To date, the exact tolerance mechanism of P. leucopus mice to Bb-induced infection remains unknown. To address this knowledge gap, the present study has compared spleen transcriptomes of P. leucopus and C3H/HeJ mice infected with Bb strain 297 with those of their respective uninfected controls. Overall, the data showed that the spleen transcriptome of Bb-infected P. leucopus mice was much more quiescent compared to that of the infected C3H mice. To date, the current investigation is one of the few that have examined the transcriptome response of natural reservoir hosts to Borreliella infection. Although the experimental design of this study significantly differed from those of two previous investigations, the collective results of the current and published studies have consistently demonstrated very limited transcriptomic responses of different reservoir hosts to the persistent infection of LD pathogens. Importance The bacterium Borreliella burgdorferi (Bb) causes Lyme disease, which is one of the emerging and highly debilitating human diseases in countries of the Northern Hemisphere. In nature, Bb spirochetes are maintained between hard ticks of Ixodes spp. and mammals or birds. In the United States, the white-footed mouse, Peromyscus leucopus, is one of the main Bb reservoirs. In contrast to humans and laboratory mice (e.g., C3H mice), white-footed mice rarely develop clinical signs (disease) despite being (persistently) infected with Bb. How the white-footed mouse tolerates Bb infection is the question that the present study has attempted to address. Comparisons of genetic responses between Bb-infected and uninfected mice demonstrated that, during a long-term Bb infection, C3H mice reacted much stronger, whereas P. leucopus mice were relatively unresponsive.
Effects of intra-annual precipitation patterns on grassland productivity moderated by the dominant species phenology

Phenology and productivity are important functional indicators of grassland ecosystems. However, our understanding of how intra-annual precipitation patterns affect plant phenology and productivity in grasslands is still limited. Here, we conducted a two-year precipitation manipulation experiment to explore the responses of plant phenology and productivity to intra-annual precipitation patterns at the community and dominant species levels in a temperate grassland. We found that increased early growing season precipitation enhanced the above-ground biomass of the dominant rhizome grass, Leymus chinensis, by advancing its flowering date, while increased late growing season precipitation increased the above-ground biomass of the dominant bunchgrass, Stipa grandis, by delaying senescence. The complementary effects in phenology and biomass of the dominant species, L. chinensis and S. grandis, maintained stable dynamics of the community above-ground biomass under intra-annual precipitation pattern variations. Our results highlight the critical role that intra-annual precipitation and soil moisture patterns play in the phenology of temperate grasslands. By understanding the response of phenology to intra-annual precipitation patterns, we can more accurately predict the productivity of temperate grasslands under future climate change.
Adaptive immune receptor genotyping using the corecount program

We present a new Rep-Seq analysis tool called corecount, for analyzing genotypic variation in immunoglobulin (IG) and T cell receptor (TCR) genes. corecount is highly efficient at identifying V alleles, including those that are infrequently used in expressed repertoires and those that contain 3’ end variation that are otherwise refractory to reliable identification during germline inference from expressed libraries. Furthermore, corecount facilitates accurate D and J gene genotyping. The output is highly reproducible and facilitates the comparison of genotypes from multiple individuals, such as those from clinical cohorts. Here, we applied corecount to the genotypic analysis of IgM libraries from 16 individuals. To demonstrate the accuracy of corecount, we Sanger sequenced all the heavy chain IG alleles (65 IGHV, 27 IGHD and 7 IGHJ) from one individual from whom we also produced two independent IgM Rep-seq datasets. Genomic analysis revealed that 5 known IGHV and 2 IGHJ sequences are truncated in current reference databases. This dataset of genomically validated alleles and IgM libraries from the same individual provides a useful resource for benchmarking other bioinformatic programs that involve V, D and J assignments and germline inference, and may facilitate the development of AIRR-Seq analysis tools that can take benefit from the availability of more comprehensive reference databases.
Engaging distributed cortical and cerebellar networks through motor execution, observation, and imagery

When we interact with the environment around us, we are sometimes active participants, making directed physical motor movements and other times only mentally engaging with our environment, taking in sensory information and internally planning our next move without directed physical movement. Traditionally, cortical motor regions and key subcortical structures such as the cerebellum have been tightly linked to motor initiation, coordination, and directed motor behavior. However, recent neuroimaging studies have noted the activation of the cerebellum and wider cortical networks specifically during various forms of motor processing, including the observations of actions and mental rehearsal of movements through motor imagery. This phenomenon of cognitive engagement of traditional motor networks raises the question of how these brain regions are involved in the initiation of movement without physical motor output. Here, we will review evidence for distributed brain network activation during motor execution, observation, and imagery in human neuroimaging studies as well as the potential for cerebellar involvement specifically in motor-related cognition. Converging evidence suggests that a common global brain network is involved in both movement execution and motor observation or imagery, with specific task-dependent shifts in these global activation patterns. We will further discuss underlying cross-species anatomical support for these cognitive motor-related functions as well as the role of cerebrocerebellar communication during action observation and motor imagery.
Effect of replacing whole wheat with broken rye as a sustainable grain in diets of fattening turkeys on growth performance, litter quality, and foot pad health

Introduction Rye is one of the most important cereal crops in Central Europe, thus attempts have been made to include it in the diets of birds to reduce production costs, since the cost of feed accounts for as much as 50 %−70 % thereof. Nevertheless, the use of rye has been limited to date, particularly in turkeys. This study aimed to test the effects of rye inclusion up to 10 % on growth, excreta, and/or litter dry matter, and foot pad health. Methods Four trials were performed with a total of 4,322, 4,307, 4,256, and 4,280 female turkeys (BUT BIG 6, Aviagen) for trials 1, 2, 3, and 4, respectively. All birds were fed commercial starter diets for the dietary phases 1 and 2 (up to d 35 of life). Thereafter, at the start of the study, the control group received commercial supplementary feed with 5 % or 10 % wheat until the end of the fattening period. The experimental group was offered supplementary feed to which instead of wheat increasing levels of rye were added stepwise from 5 % to 10 %. Results Using supplementary feed with rye showed no significant differences in the final body weight between the control and experimental groups (10.9 vs. 10.8 kg). The dry matter content of fresh excreta for turkeys during the experimental period did not show significant differences between both groups, except at weeks 10 and 14 of life. The feed type (either control diet or experimental diet) did not significantly affect litter dry matter content between the groups throughout the experimental period. No significant differences were noted in food pad dermatitis scoring between both groups throughout the experimental period, except at weeks 11 and 16 of life. Overall, this study showed that including proportions of rye up to 10% could replace conventional ingredients and may increase sustainability in poultry production regardless of the addition of supplementary feed.
Aneuploidy enables cross-tolerance to unrelated antifungal drugs in Candida parapsilosis

Candida parapsilosis is an emerging major human fungal pathogen. Echinocandins are first-line antifungal drugs for the treatment of invasive Candida infections. In clinical isolates, tolerance to echinocandins in Candida species is mostly due to point mutations of FKS genes, which encode the target protein of echinocandins. However, here, we found chromosome 5 trisomy was the major mechanism of adaptation to the echinocandin drug caspofungin, and FKS mutations were rare events. Chromosome 5 trisomy conferred tolerance to echinocandin drugs caspofungin and micafungin and cross-tolerance to 5-flucytosine, another class of antifungal drugs. The inherent instability of aneuploidy caused unstable drug tolerance. Tolerance to echinocandins might be due to increased copy number and expression of CHS7, which encodes chitin synthase. Although copy number of chitinase genes CHT3 and CHT4 was also increased to the trisomic level, the expression was buffered to the disomic level. Tolerance to 5-flucytosine might be due to the decreased expression of FUR1. Therefore, the pleiotropic effect of aneuploidy on antifungal tolerance was due to the simultaneous regulation of genes on the aneuploid chromosome and genes on euploid chromosomes. In summary, aneuploidy provides a rapid and reversible mechanism of drug tolerance and cross-tolerance in C. parapsilosis.
Heat stress inhibits the proliferation and differentiation of myoblasts and is associated with damage to mitochondria

Introduction: Heat stress is harmful to the health of humans and animals, more and more common, as a consequence of global warming, while the mechanism that heat stress modulates skeletal development remains unknown. Hence, we conducted a model of heat stress in vitro. Methods: We used Hu sheep myoblasts as the research object, real-time quantitative PCR (RT-qPCR) and western blot (WB) were conducted to detect the expression of mRNA and protein in heat-stressed myoblasts. The would-healing assay was used to detect the migration of myoblasts. The mitochondria were observed by a transmission electron microscope. Results: mRNA and protein expression of HSP60 was significantly enriched in the heat-stressed myoblasts during proliferation and differentiation (p < 0.05). In our study, we indicated that heat stress enriched the intracellular ROS of the myoblasts (p < 0.001), leading to an increase in autophagy in the myoblasts to induce apoptosis. The results demonstrated that the protein expression of LC3B-1 and BCL-2 was significantly increased in myoblasts under heat stress during proliferation and differentiation (p < 0.05). Additionally, heat stress inhibited mitochondrial biogenesis and function and reduced the mitochondrial membrane potential and downregulated the expression of mtCo2, mtNd1 and DNM1L (p < 0.05) in myoblasts during proliferation and differentiation. Consequently, heat stress inhibited the proliferation and differentiation of the myoblasts, in accordance with the downregulation of the expression of PAX7, MYOD, MYF5, MYOG and MYHC (p < 0.05). Moreover, heat stress also inhibited the cell migration of the myoblasts. Discussion: This work demonstrates that heat stress inhibits proliferation and differentiation, and accelerates apoptosis by impairing mitochondrial function and promoting autophagy, which provides a mechanism to understand heat stress affects the development of the skeletal muscle.
Deciphering mechanisms of action of ACE inhibitors in neurodegeneration using Drosophila models of Alzheimer’s disease

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder for which there is no cure. Recently, several studies have reported a significant reduction in the incidence and progression of dementia among some patients receiving antihypertensive medications such as angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs). Why these drugs are beneficial in some AD patients and not others is unclear although it has been shown to be independent of their role in regulating blood pressure. Given the enormous and immediate potential of ACE-Is and ARBs for AD therapeutics it is imperative that we understand how they function. Recently, studies have shown that ACE-Is and ARBs, which target the renin angiotensin system in mammals, are also effective in suppressing neuronal cell death and memory defects in Drosophila models of AD despite the fact that this pathway is not conserved in flies. This suggests that the beneficial effects of these drugs may be mediated by distinct and as yet, identified mechanisms. Here, we discuss how the short lifespan and ease of genetic manipulations available in Drosophila provide us with a unique and unparalleled opportunity to rapidly identify the targets of ACE-Is and ARBs and evaluate their therapeutic effectiveness in robust models of AD.