Joint efficacy of the three biomarkers SNCA,GYPB and HBG1 for atrial fibrillation and stroke: Analysis via the support vector machine neural network

Atrial fibrillation (AF) is the most common type of persistent arrhythmia. Although its incidence has been increasing, the pathogenesis of AF in stroke remains unclear. In this study, a total of 30 participants were recruited, including 10 controls, 10 patients with AF and 10 patients with AF and stroke (AF + STROKE). Differentially expressed genes (DEGs) were identified, and functional annotation of DEGs, comparative toxicogenomic database analysis associated with cardiovascular diseases, and predictions of miRNAs of hub genes were performed. Using RT‐qPCR, biological process and support vector machine neural networks, numerous DEGs were found to be related to AF. HBG1, SNCA and GYPB were found to be upregulated in the AF group. Higher expression of hub genes in AF and AF + STROKE groups was detected via RT‐PCR. Upon training the biological process neural network of SNCA and GYPB for HBG1, only small differences were detected. Based on the support vector machine, the predicted value of SNCA and GYPB for HBG1 was 0.9893. Expression of the hub genes of HBG1, SNCA and GYPB might therefore be significantly correlated to AF. These genes are involved in the incidence of AF complicated by stroke, and may serve as targets for early diagnosis and treatment.     

Conventional wisdom on roosting behavior of Australian flying‐foxes—A critical review,and evaluation using new data

1. Fruit bats (Family: Pteropodidae) are animals of great ecological and economic importance, yet their populations are threatened by ongoing habitat loss and human persecution. A lack of ecological knowledge for the vast majority of Pteropodid species presents additional challenges for their conservation and management.
2. In Australia, populations of flying‐fox species (Genus: Pteropus) are declining and management approaches are highly contentious. Australian flying‐fox roosts are exposed to management regimes involving habitat modification, through human–wildlife conflict management policies, or vegetation restoration programs. Details on the fine‐scale roosting ecology of flying‐foxes are not sufficiently known to provide evidence‐based guidance for these regimes, and the impact on flying‐foxes of these habitat modifications is poorly understood.
3. We seek to identify and test commonly held understandings about the roosting ecology of Australian flying‐foxes to inform practical recommendations and guide and refine management practices at flying‐fox roosts.
4. We identify 31 statements relevant to understanding of flying‐fox roosting structure and synthesize these in the context of existing literature. We then contribute a contemporary, fine‐scale dataset on within‐roost structure to further evaluate 11 of these statements. The new dataset encompasses 13‐monthly repeat measures from 2,522 spatially referenced roost trees across eight sites in southeastern Queensland and northeastern New South Wales.
5. We show evidence of sympatry and indirect competition between species, including spatial segregation of black and grey‐headed flying‐foxes within roosts and seasonal displacement of both species by little red flying‐foxes. We demonstrate roost‐specific annual trends in occupancy and abundance and provide updated demographic information including the spatial and temporal distributions of males and females within roosts.
6. Insights from our systematic and quantitative study will be important to guide evidence‐based recommendations on restoration and management and will be crucial for the implementation of priority recovery actions for the preservation of these species in the future.

     

Visitation of artificial watering points by the red fox (Vulpes vulpes) in semiarid Australia

The introduced red fox (Vulpes vulpes) now occupies most of the Australian continent outside the tropics, including arid and semiarid ecosystems. Information on the water requirements of foxes is scant, but free water is not thought to be required if adequate moisture‐containing food is available. The frequency and duration of visits by foxes fitted with GPS collars to known artificial watering points in semiarid Australia were recorded for 22 individual foxes across four austral seasons between October 2015 and November 2017, providing >93,000 location fixes. We modeled home range and the distance traveled by range‐resident foxes beyond their home range to reach known water sources. We used recurse analysis to determine the frequency of visitation and step‐selection functions to model the speed and directionality of movement inside and outside the home range. Our study demonstrates that some foxes in this semiarid environment utilize free‐standing water. The findings suggest that artificial watering points can be used as a focal point for conducting strategic fox control in arid and semiarid environments. Additionally, strategies that restrict access to water by foxes may reduce their duration of occupancy and/or long‐term abundance in parts of the landscape, thus providing benefits for conservation and agriculture.     

Exome sequencing of deer mice on two California Channel Islands identifies potential adaptation to strongly contrasting ecological conditions

Understanding the forces that drive genotypic and phenotypic change in wild populations is a central goal of evolutionary biology. We examined exome variation in populations of deer mice from two of the California Channel Islands: Peromyscus maniculatus elusus from Santa Barbara Island and P. m. santacruzae from Santa Cruz Island exhibit significant differences in olfactory predator recognition, activity timing, aggressive behavior, morphology, prevalence of Sin Nombre virus, and population densities. We characterized variation in protein‐coding regions using exome capture and sequencing of 25 mice from Santa Barbara Island and 22 mice from Santa Cruz Island. We identified and examined 386,256 SNPs using three complementary methods (BayeScan, pcadapt, and LFMM). We found strong differences in molecular variation between the two populations and 710 outlier SNPs in protein‐coding genes that were detected by all three methods. We identified 35 candidate genes from this outlier set that were related to differences in phenotypes between island populations. Enrichment analyses demonstrated that patterns of molecular variation were associated with biological processes related to response to chemical stimuli and regulation of immune processes. Candidate genes associated with olfaction (Gfy, Tlr2, Vmn13r2, numerous olfactory receptor genes), circadian activity (Cry1), anxiety (Brca1), immunity (Cd28, Eif2ak4, Il12a, Syne1), aggression (Cyp19a, Lama2), and body size (Bc16, Syne1) exhibited non‐synonymous mutations predicted to have moderate to large effects. Variation in olfaction‐related genes, including a stop codon in the Santa Barbara Island population, suggests loss of predator‐recognition traits at the molecular level, consistent with a lack of behavioral aversion to fox feces. These findings also suggest that divergent pathogen prevalence and population density may have influenced adaptive immunity and behavioral phenotypes, such as reduced aggression. Overall, our study indicates that ecological differences between islands are associated with signatures of selection in protein‐coding genes underlying phenotypes that promote success in those environments.     

Chromosome‐level genome assembly for the horned‐gall aphid provides insights into interactions between gall‐making insect and its host plant

The aphid Schlechtendalia chinensis is an economically important insect that can induce horned galls, which are valuable for the medicinal and chemical industries. Up to now, more than twenty aphid genomes have been reported. Most of the sequenced genomes are derived from free‐living aphids. Here, we generated a high‐quality genome assembly from a galling aphid. The final genome assembly is 271.52 Mb, representing one of the smallest sequenced genomes of aphids. The genome assembly is based on contig and scaffold N50 values of the genome sequence are 3.77 Mb and 20.41 Mb, respectively. Nine‐seven percent of the assembled sequences was anchored onto 13 chromosomes. Based on BUSCO analysis, the assembly involved 96.9% of conserved arthropod and 98.5% of the conserved Hemiptera single‐copy orthologous genes. A total of 14,089 protein‐coding genes were predicted. Phylogenetic analysis revealed that S. chinensis diverged from the common ancestor of Eriosoma lanigerum approximately 57 million years ago (MYA). In addition, 35 genes encoding salivary gland proteins showed differentially when S. chinensis forms a gall, suggesting they have potential roles in gall formation and plant defense suppression. Taken together, this high‐quality S. chinensis genome assembly and annotation provide a solid genetic foundation for future research to reveal the mechanism of gall formation and to explore the interaction between aphids and their host plants.     

Inhibition of endoplasmic reticulum stress prevents high‐fat diet mediated atrial fibrosis and fibrillation

Obesity is a significant risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia with increased mortality and morbidity. High‐fat diet (HFD)‐induced obesity is associated with the activation of endoplasmic reticulum stress (ERS). However, the role of ERS in HFD‐induced AF remains elusive. Human atrium samples were examined for the ERS activation test. C57BL/6J mice were divided into four groups, including the control group, the HFD group, the 4‐phenylbutyric acid (4‐PBA) group, and the HFD + 4‐PBA group. At the age of 4 weeks, the HFD group and the HFD + 4‐PBA group were given HFD to construct the obesity model, while the other two groups were given a normal diet (ND). Transesophageal programmed electrical stimulation was conducted to evaluate the AF inducibility and duration. Atrial fibrosis and ERS activation were also investigated.We found that CHOP and GRP‐78 protein were significantly higher in overweight patients than the controls (both P < 0.05). AF inducibility and duration of the HFD group were significantly higher than the other groups (both P < 0.05), while there was no difference between those groups (P > 0.05). The mice of the HFD group had significantly higher collagen volume fraction (CVF%) than the other groups (P < 0.05). ERS marker protein of GRP78, p‐PERK, ATF6 and CHOP protein expression level was increased in the HFD group, which were significantly mitigated in the HFD + 4‐PBA group. In summary, HFD‐induced ERS activation facilitates atrial fibrosis and AF. The inhibition of ERS might alleviate atrial fibrosis and reduce the incidence of AF‐associated obesity.     

Are British urban foxes (Vulpes vulpes) “bold”? The importance of understanding human–wildlife interactions in urban areas

Human–wildlife interactions are believed to be increasing in urban areas. In Britain, numerous media reports have stated that urban foxes (Vulpes vulpes) are becoming “bolder,” thereby posing a risk to public safety. However, such claims overlook how an individual''s personality might influence urban fox behavior. Personality determines multiple aspects of an animal''s interactions with both conspecifics and its environment, and can have a significant impact on how people perceive wildlife. Furthermore, describing urban foxes as “bold” confounds two different but inter‐related behaviors, both of which influence an animal''s propensity to take risks. Neophobia affects an animal''s reaction to novelty, wariness its reaction to potential threats. Since urban wildlife frequently encounters both novel and threatening stimuli, a highly adaptable species such as the red fox might be predicted to exhibit reduced neophobia and wariness. We investigated how social status influenced both behaviors in Bristol''s fox population. Dominant foxes were significantly more neophobic and warier than subordinates, which adopt a more exploratory and risk‐taking lifestyle to meet their energetic and other needs. We found no seasonal effect on neophobia and wariness, although this may be due to sample size. The presence of conspecifics decreased neophobia for dominants, and wariness for both dominants and subordinates. We highlight the importance of considering animal social status and personality when planning management protocols, since interventions that destabilize fox social groups are likely to increase the number of subordinate foxes in the population, thereby increasing rather than decreasing the number of interactions between humans and urban foxes.     

Detection of farm fox and hybrid genotypes among wild arctic foxes in Scandinavia

In Scandinavia, farmed arctic foxes frequently escape from farms, raising concern about hybridization with the endangered wild population. This study was performed to find a genetic marker to distinguish escaped farm foxes from wild Scandinavian foxes. Microsatellite and mitochondrial control region variation were analyzed in 41 farm foxes. The results were compared with mitochondrial and microsatellite data from the wild population in Scandinavia. The farm foxes were genetically distinct from the wild foxes (F _ST=0.254, P < 0.00001) and all farm foxes had a single control region haplotype different from those observed in the wild population. We developed a method based on Restriction Fragment Length Polymorphism (RFLP) on the mitochondrial control region to differentiate between farmed and wild arctic foxes. This test was subsequently successfully used on 25 samples from free-ranging foxes, of which four had a suspected farm origin. All four of the suspected foxes, and none of the others, carried the farm fox haplotype. Three of these were successfully genotyped for all eleven microsatellite loci. A population assignment test and a Bayesian Markov Chain Monte Carlo analysis indicated that two of these individuals were escaped farm foxes, and that the third possibly was a hybrid between a farmed and a wild arctic fox.     

Prevalent intron retention fine‐tunes gene expression and contributes to cellular senescence

Intron retention (IR) is the least well‐understood alternative splicing type in animals, and its prevalence and function in physiological and pathological processes have long been underestimated. Cellular senescence contributes to individual aging and age‐related diseases and can also serve as an important cancer prevention mechanism. Dynamic IR events have been observed in senescence models and aged tissues; however, whether and how IR impacts senescence remain unclear. Through analyzing polyA⁺ RNA‐seq data from human replicative senescence models, we found IR was prevalent and dynamically regulated during senescence and IR changes negatively correlated with expression alteration of corresponding genes. We discovered that knocking down (KD) splicing factor U2AF1, which showed higher binding density to retained introns and decreased expression during senescence, led to senescence‐associated phenotypes and global IR changes. Intriguingly, U2AF1‐KD‐induced IR changes also negatively correlated with gene expression. Furthermore, we demonstrated that U2AF1‐mediated IR of specific gene (CPNE1 as an example) contributed to cellular senescence. Decreased expression of U2AF1, higher IR of CPNE1, and reduced expression of CPNE1 were also discovered in dermal fibroblasts with age. We discovered prevalent IR could fine‐tune gene expression and contribute to senescence‐associated phenotypes, largely extending the biological significance of IR.     

Genetic analysis of potential biomarkers and therapeutic targets in ferroptosis from coronary artery disease

Ferroptosis plays a key role in the death of cells including cardiomyocytes, and it is related to a variety of cardiac diseases. However, the role of ferroptosis‐related genes (FRGs) in coronary artery disease (CAD) is not well characterized. We downloaded CAD‐related information and FRGs from the gene expression omnibus (GEO) database and Ferroptosis Database (FerrDb) respectively. A total of 10 CAD‐related DE‐FRGs were obtained, which were closely linked to autophagy regulation and immune response. Subsequently, CA9, CBS, CEBPG, HSPB1, SLC1A4, STMN1 and TRIB3 among the 10 DE‐FRGs were identified as marker genes by LASSO and SVM‐RFE algorithms, which had tolerable diagnostic capabilities. Subsequent functional enrichment analysis showed that these marker genes may play a corresponding role in CAD by participating in the regulation of immune response, amino acid metabolism, cell cycle and multiple pathways related to the pathogenesis of CAD. Furthermore, a total of 58 drugs targeting 7 marker genes had been obtained. On the contrary, the ceRNA network revealed a complex regulatory relationship based on the marker genes. Also, CIBERSORT analysis showed that the changes in the immune microenvironment of CAD patients may be related to CBS, HSPB1 and CEBPG. We developed a diagnostic potency and provided an insight for exploring the mechanism for CAD. Before clinical application, further research is needed to test its diagnostic value for CAD.     

Stress Triangle: Do Introduced Predators Exert Indirect Costs on Native Predators and Prey?

Non-consumptive effects of predators on each other and on prey populations often exceed the effects of direct predation. These effects can arise from fear responses elevating glucocorticoid (GC) hormone levels (predator stress hypothesis) or from increased vigilance that reduces foraging efficiency and body condition (predator sensitive foraging hypothesis); both responses can lead to immunosuppression and increased parasite loads. Non-consumptive effects of invasive predators have been little studied, even though their direct impacts on local species are usually greater than those of their native counterparts. To address this issue, we explored the non-consumptive effects of the invasive red fox Vulpes vulpes on two native species in eastern Australia: a reptilian predator, the lace monitor Varanus varius and a marsupial, the ringtail possum Pseudocheirus peregrinus. In particular, we tested predictions derived from the above two hypotheses by comparing the basal glucocorticoid levels, foraging behaviour, body condition and haemoparasite loads of both native species in areas with and without fox suppression. Lace monitors showed no GC response or differences in haemoparasite loads but were more likely to trade safety for higher food rewards, and had higher body condition, in areas of fox suppression than in areas where foxes remained abundant. In contrast, ringtails showed no physiological or behavioural differences between fox-suppressed and control areas. Predator sensitive foraging is a non-consumptive cost for lace monitors in the presence of the fox and most likely represents a response to competition. The ringtail’s lack of response to the fox potentially represents complete naiveté or strong and rapid selection to the invasive predator. We suggest evolutionary responses are often overlooked in interactions between native and introduced species, but must be incorporated if we are to understand the suite of forces that shape community assembly and function in the wake of biological invasions.     

Genome‐wide transcriptome signatures of ant‐farmed Squamellaria epiphytes reveal key functions in a unique symbiosis

Farming of fungi by ants, termites, or beetles has led to ecologically successful societies fueled by industrial‐scale food production. Another type of obligate insect agriculture in Fiji involves the symbiosis between the ant Philidris nagasau and epiphytes in the genus Squamellaria (Rubiaceae) that the ants fertilize, defend, harvest, and depend on for nesting. All farmed Squamellaria form tubers (domatia) with preformed entrance holes and complex cavity networks occupied by P. nagasau. The inner surface of the domatia consists of smooth‐surfaced walls where the ants nest and rear their brood, and warty‐surfaced walls where they fertilize their crop by defecation. Here, we use RNA sequencing to identify gene expression patterns associated with the smooth versus warty wall types. Since wall differentiation occurred in the most recent common ancestor of all farmed species of Squamellaria, our study also identifies genetic pathways co‐opted following the emergence of agriculture. Warty‐surfaced walls show many upregulated genes linked to auxin transport, root development, and nitrogen transport consistent with their root‐like function; their defense‐related genes are also upregulated, probably to protect these permeable areas from pathogen entry. In smooth‐surfaced walls, genes functioning in suberin and wax biosynthesis are upregulated, contributing to the formation of an impermeable ant‐nesting area in the domatium. This study throws light on a number of functional characteristics of plant farming by ants and illustrates the power of genomic studies of symbiosis.     

Genetic associations for two biological age measures point to distinct aging phenotypes

Biological age measures outperform chronological age in predicting various aging outcomes, yet little is known regarding genetic predisposition. We performed genome‐wide association scans of two age‐adjusted biological age measures (PhenoAgeAcceleration and BioAgeAcceleration), estimated from clinical biochemistry markers (Levine et al., 2018; Levine, 2013) in European‐descent participants from UK Biobank. The strongest signals were found in the APOE gene, tagged by the two major protein‐coding SNPs, PhenoAgeAccel—rs429358 (APOE e4 determinant) (p = 1.50 × 10⁻⁷²); BioAgeAccel—rs7412 (APOE e2 determinant) (p = 3.16 × 10⁻⁶⁰). Interestingly, we observed inverse APOE e2 and e4 associations and unique pathway enrichments when comparing the two biological age measures. Genes associated with BioAgeAccel were enriched in lipid related pathways, while genes associated with PhenoAgeAccel showed enrichment for immune system, cell function, and carbohydrate homeostasis pathways, suggesting the two measures capture different aging domains. Our study reaffirms that aging patterns are heterogeneous across individuals, and the manner in which a person ages may be partly attributed to genetic predisposition.     

Comparative nutrient digestibility of arctic foxes (Alopex lagopus) on Svalbard and farm-raised blue foxes (Alopex lagopus)

Arctic foxes from Svalbard (n=4) and farmed blue foxes (n=4) was used in a digestibility experiment with a high-carbohydrate feed to add more information to the nutritional physiology of the arctic fox, and to compare its digestive capacity with that of the farmed blue fox. The arctic fox has a diet containing mainly protein and fat from mammals and birds, while farmed blue foxes have been exposed to an omnivorous dietary regime for more than 80 generations. The experiment showed in general no difference in digestive capacity for protein and fat between the foxes (P>0.05), but for carbohydrates, including starch and glucose, the blue fox revealed higher digestibility values. The superior digestive capacity for carbohydrates in blue fox might be a result of a long-term selection of animals digesting dietary carbohydrates more efficiently, or that an early age exposition to dietary carbohydrates has given permanent improvement of the carbohydrate digestion in the gut.