How antibiotic exposure affect predator-prey interactions by population dynamics in ciliates?

Biodiversity loss resulting from environmental pollution is a global concern. While interspecific interactions are central to ecology, the impact of environmental pollution on predator-prey interactions and its ecological consequences, such as extinction and biodiversity loss, remain unclear. To investigate the effects of antibiotic exposure on predation strength and the resulting ecological consequence, the Didinium-Paramecium was utilized as a predator-prey model and exposed to nitrofurazone or erythromycin, two common pollutants, respectively. Initially, we determined prey population growth dynamics, body size, and predator numerical-functional responses. Subsequently, these above parameters were integrated into a mathematical model of predator-prey predation. Then both the long time-series data and phase portraits obtained through model simulation were used to estimate interaction strength and to predict the outcome of predator-prey coexistence. Our results revealed that exposure to either antibiotic significantly reduced prey population growth parameters (e.g., µmax and K) while increasing individual body size. The combined effects of antibiotic exposure and predation pressure on population growth inhibition or body size promotion were variable, mostly additive, with a few cases of synergy and extremely rare antagonism, depending on antibiotic exposure concentration. As antibiotic exposure concentration increased, the predator rmax generally declined, while functional responses varied depending on specific parameters, implying a decrease in predator-prey interaction strength. Analyses of phase portrait features showed that the population oscillation amplitude decreased with increasing antibiotic exposure concentrations, the cycle length of adjacent peaks increased, and prey extinction occurred earlier. In conclusion, antibiotic exposure reduced both predator and prey fitness, underlying the reason antibiotics reduces the strength of predator-prey interaction. Despite the indirect benefits of prey gain from this, the presence of predators can expedite the process of prey extinction caused by antibiotic exposure.

GC-biased gene conversion drives accelerated evolution of ultraconserved elements in mammalian and avian genomes.

Ultraconserved elements (UCEs) are the most conserved regions among the genomes of evolutionarily distant species and are thought to play critical biological functions. However, some UCEs rapidly evolved in specific lineages, and whether they contributed to adaptive evolution is still controversial. Here, using an increased number of sequenced genomes with high taxonomic coverage, we identified 2191 mammalian UCEs and 5938 avian UCEs from 95 mammal and 94 bird genomes, respectively. Our results show that these UCEs are functionally constrained and that their adjacent genes are prone to widespread expression with low expression diversity across tissues. Functional enrichment of mammalian and avian UCEs shows different trends indicating that UCEs may contribute to adaptive evolution of taxa. Focusing on lineage-specific accelerated evolution, we discover that the proportion of fast-evolving UCEs in nine mammalian and 10 avian test lineages range from 0.19% to 13.2%. Notably, up to 62.1% of fast-evolving UCEs in test lineages are much more likely to result from GC-biased gene conversion (gBGC). A single cervid-specific gBGC region embracing the uc.359 allele significantly alters the expression of Nova1 and other neural-related genes in the rat brain. Combined with the altered regulatory activity of ancient gBGC-induced fast-evolving UCEs in eutherians, our results provide evidence that synergy between gBGC and selection shaped lineage-specific substitution patterns, even in the most constrained regulatory elements. In summary, our results show that gBGC played an important role in facilitating lineage-specific accelerated evolution of UCEs, and further support the idea that a combination of multiple evolutionary forces shapes adaptive evolution.

Intrahepatic biliary cystadenoma: Confusion, experience, and lessons learned from our center.

Background: Intrahepatic biliary cystadenoma (IBC) is a rare benign cystic tumor of the liver. So far, it has not been comprehensively understood, which causes incorrect diagnosis, treatment confusion, and even inappropriate treatment. Here, we reviewed clinical data of IBC patients in our center, shared our experiences and lessons learned, and improved the level of diagnosis and treatment. Methods: The clinical data of 10 patients with pathologically diagnosed IBC, admitted to the Department of Hepatobiliary Surgery of the Affiliated Hospital of Guangdong Medical University from January, 2007, to January, 2022 were retrospectively analyzed. Results: 10 patients underwent surgery and were discharged successfully. Cyst morphology: multiple cysts: 6 cases (6/10), monocular cyst: four cases(4/10). Six patients (6/10) were diagnosed as IBC preoperatively and received hepatectomy. Four patients with monocular cyst IBC underwent intraoperative frozen section examination, except one case showed IBC; the rest were misdiagnosed as simple liver cyst. In three misdiagnosed patients, one underwent open left hepatectomy seven days after the initial operation. The other patient refused to undergo reoperation and required follow-up observation. The last patient could not tolerate hepatectomy due to insufficient residual liver volume and chose follow-up observation. Conclusion: For IBC, especially monocular IBC, it is easy to be misdiagnosed as simple hepatic cyst, which brings great confusion to clinical treatment. We propose strengthening communication with pathologists to deepen understanding of IBC. Attention should be paid to the cyst wall's shape and the cyst fluid's properties during the operation to avoid the missed diagnosis, misdiagnosis, or even improper operation. For suspicious cases, directly choose hepatectomy to avoid reoperation after thoroughly evaluating the patient's condition.

Influence of CYP3A5, IL-10 polymorphisms and metabolism rate on tacrolimus exposure in renal post-transplant recipients.

Aim: To investigate the influence of CYP3A5 and IL-10 polymorphisms on tarcolimus metabolism and renal function for renal transplantation recipients at a stable period. Methods: CYP3A5 and IL-10 polymorphisms, together with other clinical factors, were collected for 149 renal transplantation patients at postoperative stable period. Statistics analysis was performed to explore key factors affecting tarcolimus metabolism. Results: CYP3A5 6986A >G and IL-10 -819C >T significantly impacted tacrolimus metabolism (p < 0.001). CYP3A5 6986A >G G allele and IL-10 -819C >T T allele were associated with poorer tacrolimus metabolic capability. Patients with various tacrolimus metabolism rates presented little difference in renal functions at stable period. Conclusion: Genotyping of CYP3A5 and IL-10 might benefit the precision dosage of tacrolimus for renal transplantation recipients.

Applying machine learning to the pharmacokinetic modeling of cyclosporine in adult renal transplant recipients: a multi-method comparison.

Objective: The aim of this study was to identify the important factors affecting cyclosporine (CsA) blood concentration and estimate CsA concentration using seven different machine learning (ML) algorithms. We also assessed the predictability of established ML models and previously built population pharmacokinetic (popPK) model. Finally, the most suitable ML model and popPK model to guide precision dosing were determined. Methods: In total, 3,407 whole-blood trough and peak concentrations of CsA were obtained from 183 patients who underwent initial renal transplantation. These samples were divided into model-building and evaluation sets. The model-building set was analyzed using seven different ML algorithms. The effects of potential covariates were evaluated using the least absolute shrinkage and selection operator algorithms. A separate evaluation set was used to assess the ability of all models to predict CsA blood concentration. R squared (R 2) scores, median prediction error (MDPE), median absolute prediction error (MAPE), and the percentages of PE within 20% (F20) and 30% (F30) were calculated to assess the predictive performance of these models. In addition, previously built popPK model was included for comparison. Results: Sixteen variables were selected as important covariates. Among ML models, the predictive performance of nonlinear-based ML models was superior to that of linear regression (MDPE: 3.27%, MAPE: 34.21%, F20: 30.63%, F30: 45.03%, R 2 score: 0.68). The ML model built with the artificial neural network algorithm was considered the most suitable (MDPE: -0.039%, MAPE: 25.60%, F20: 39.35%, F30: 56.46%, R 2 score: 0.75). Its performance was superior to that of the previously built popPK model (MDPE: 5.26%, MAPE: 29.22%, F20: 33.94%, F30: 51.22%, R 2 score: 0.68). Furthermore, the application of the most suitable model and the popPK model in clinic showed that most dose regimen recommendations were reasonable. Conclusion: The performance of these ML models indicate that a nonlinear relationship for covariates may help to improve model predictability. These results might facilitate the application of ML models in clinic, especially for patients with unstable status or during initial dose optimization.

Increased detection of circulating tumor DNA by short fragment enrichment.

BACKGROUND: Circulating cell-free DNA (cfDNA) detection for non-invasive diagnosis requires higher sensitivity and accuracy due to the low circulating tumor DNA (ctDNA) content. Many methods have been developed to improve detection of ctDNA, including ultra-deep sequencing or enrichment of shorter cfDNA fragments, such as those in the range of 90-150 bp. METHODS: Here, we developed a method for single-stranded DNA (ssDNA) library preparation with a large proportion of magnetic beads to enrich the shorter cfDNA fragments. We aimed to determine if this could increase the ctDNA content and thus improve the sensitivity of ctDNA detection by testing the method in blood samples from patients with advanced cancers (non-small cell lung cancers, esophageal squamous cell carcinoma, cholangiocarcinoma, colorectal cancer and liver cancer). RESULTS: This method was able to obtain shorter cfDNA both in commercial cfDNA references and real world clinical cfDNA samples. Plasmid simulation experiments showed that using a large proportion of magnetic beads to construct the library could obtain more ctDNA derived from shorter-fragment plasmids, which could significantly improve the detection of ctDNA especially in the low-variant allele frequency sample. In real-world clinical samples, this method may be able to increase the opportunity to obtain alteration reads from short fragments, which was important to low frequency detection. CONCLUSIONS: The ssDNA library preparation with large proportion of magnetic beads could increase the opportunity to obtain alteration reads from short fragments, which is crucial for low variant allele frequency detection.

EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses.

High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole altitudinal range across China to uncover the genetic basis for adaptation to high-altitude hypoxia. Our genome data set includes 65 lowland animals across ten Chinese native breeds, 61 horses living at least 3,300 m above sea level across seven locations along Qinghai-Tibetan Plateau, as well as 7 Thoroughbred and 5 Przewalski's horses added for comparison. We find that Tibetan horses do not descend from Przewalski's horses but were most likely introduced from a distinct horse lineage, following the emergence of pastoral nomadism in Northwestern China ∼3,700 years ago. We identify that the endothelial PAS domain protein 1 gene (EPAS1, also HIF2A) shows the strongest signature for positive selection in the Tibetan horse genome. Two missense mutations at this locus appear strongly associated with blood physiological parameters facilitating blood circulation as well as oxygen transportation and consumption in hypoxic conditions. Functional validation through protein mutagenesis shows that these mutations increase EPAS1 stability and its hetero dimerization affinity to ARNT (HIF1B). Our study demonstrates that missense mutations in the EPAS1 gene provided key evolutionary molecular adaptation to Tibetan horses living in high-altitude hypoxic environments. It reveals possible targets for genomic selection programs aimed at increasing hypoxia tolerance in livestock and provides a textbook example of evolutionary convergence across independent mammal lineages.

Allele-specific expression and alternative splicing in horse×donkey and cattle×yak hybrids.

Divergence of gene expression and alternative splicing is a crucial driving force in the evolution of species; to date, however the molecular mechanism remains unclear. Hybrids of closely related species provide a suitable model to analyze allele-specific expression (ASE) and allele-specific alternative splicing (ASS). Analysis of ASE and ASS can uncover the differences in cis-regulatory elements between closely related species, while eliminating interference of trans-regulatory elements. Here, we provide a detailed characterization of ASE and ASS from 19 and 10 transcriptome datasets across five tissues from reciprocal-cross hybrids of horse×donkey (mule/hinny) and cattle×yak (dzo), respectively. Results showed that 4.8%-8.7% and 10.8%-16.7% of genes exhibited ASE and ASS, respectively. Notably, lncRNAs and pseudogenes were more likely to show ASE than protein-coding genes. In addition, genes showing ASE and ASS in mule/hinny were found to be involved in the regulation of muscle strength, whereas those of dzo were involved in high-altitude adaptation. In conclusion, our study demonstrated that exploration of genes showing ASE and ASS in hybrids of closely related species is feasible for species evolution research.

Author Correction: An intercross population study reveals genes associated with body size and plumage color in ducks.

In the original version of this Article, there was an error in the legend for Figure 2, whereby the descriptions of panels a, b and c were presented in a different order to the corresponding figure panels. The text 'a GWAS of duck plumage color, including 76 colored ducks and 30 white Pekin ducks. The gray horizontal dashed lines indicate the Bonferroni significance threshold of the GWAS (1 × 10-9). b Fixation index (FST) of all SNPs along chromosome 13 between mallards and Pekin ducks. Red dots indicate fixed SNPs. c The nucleotide diversity (π) of mallards (blue line) and Pekin ducks (red line) from 16.0 to 17.0 Mb on chromosome 13.' should have read 'a Fixation index (FST) of all SNPs along chromosome 13 between mallards and Pekin ducks. Red dots indicate fixed SNPs. b The nucleotide diversity (π) of mallards (blue line) and Pekin ducks (red line) from 16.0 to 17.0 Mb on chromosome 13. c GWAS of duck plumage color, including 76 colored ducks and 30 white Pekin ducks. The gray horizontal dashed lines indicate the Bonferroni significance threshold of the GWAS (1 × 10-9).' This has been corrected in both the PDF and HTML versions of the Article.

An intercross population study reveals genes associated with body size and plumage color in ducks.

Comparative population genomics offers an opportunity to discover the signatures of artificial selection during animal domestication, however, their function cannot be directly revealed. We discover the selection signatures using genome-wide comparisons among 40 mallards, 36 indigenous-breed ducks, and 30 Pekin ducks. Then, the phenotypes are fine-mapped based on resequencing of 1026 ducks from an F2 segregating population generated by wild × domestic crosses. Interestingly, the two key economic traits of Pekin duck are associated with two selective sweeps with fixed mutations. A novel intronic insertion most possibly leads to a splicing change in MITF accounted for white duck down feathers. And a putative long-distance regulatory mutation causes continuous expression of the IGF2BP1 gene after birth which increases body size by 15% and feed efficiency by 6%. This study provides new insights into genotype-phenotype associations in animal research and constitutes a promising resource on economically important genes in fowl.