Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the ...world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that 'obesity' might be an indicator of good health for cetaceans.
Primary sclerosing cholangitis (PSC) is an idiopathic and heterogenous cholestatic liver disease characterized by chronic inflammation and fibrosis of the biliary tree. Currently, no effective ...therapies are available for this condition, whose incidence is rising. At present, specificity and sensitivity of current serum markers used to diagnose PSC are limited and often unreliable. In this study, we characterize circulating extracellular vesicles and provide supporting data on their potential use as novel surrogate biomarkers for PSC. EVs are membrane surrounded structures, 100-1000 nm in size, released by cells under various conditions and which carry a variety of bioactive molecules, including small non-coding RNAs, lipids and proteins. In recent years, a large body of evidence has pointed to diagnostic implications of EVs and relative cargo in various human diseases. We isolated EVs from serum of well-characterized patients with PSC or control subjects by differential centrifugation and size-exclusion chromatography. A complete characterization identified elevated levels of circulating EVs in PSC patients compared to healthy control subjects (2000 vs. 500 Calcein-FITC + EVs/μL). Tissue and cell specificity of circulating EVs was assessed by identification of liver-specific markers and cholangiocyte marker CK-19. Further molecular characterization identified 282 proteins that were differentially regulated in PSC-derived compared to healthy control-EVs. Among those, IL-13Ra1 was the most significantly and differentially expressed protein in PSC-derived EVs and correlated with the degree of liver fibrosis. In addition to protein profiling, we performed a miRNA-sequencing analysis which identified 11 among established, liver-specific (e.g., miR-122 and miR-192) and novel miRNAs. One of the newly identified miRNAs, miR-4645-3p, was significantly up-regulated fourfold in PSC-derived EVs compared to circulating EVs isolated from healthy controls. This study provides supporting evidence of the potential role of circulating EVs and associated protein and miRNA cargo as surrogate noninvasive and reliable biomarker for PSC.
Cetaceans (whales, dolphins, and porpoises) are a group of mammals adapted to various aquatic habitats, from oceans to freshwater rivers. We report the sequencing, de novo assembly and analysis of a ...finless porpoise genome, and the re-sequencing of an additional 48 finless porpoise individuals. We use these data to reconstruct the demographic history of finless porpoises from their origin to the occupation into the Yangtze River. Analyses of selection between marine and freshwater porpoises identify genes associated with renal water homeostasis and urea cycle, such as urea transporter 2 and angiotensin I-converting enzyme 2, which are likely adaptations associated with the difference in osmotic stress between ocean and rivers. Our results strongly suggest that the critically endangered Yangtze finless porpoises are reproductively isolated from other porpoise populations and harbor unique genetic adaptations, supporting that they should be considered a unique incipient species.
Cetaceans, having experienced prolonged adaptation to aquatic environments, have undergone evolutionary changes in their respiratory systems. This process of evolution has resulted in the emergence ...of distinctive phenotypic traits, notably the abundance of elastic fibers and thickened alveolar walls in their lungs, which may facilitate alveolar collapse during diving. This structure helps selective exchange of oxygen and carbon dioxide, while minimizing nitrogen exchange, thereby reducing the risk of DCS. Nevertheless, the scientific inquiry into the mechanisms through which these unique phenotypic characteristics govern the diving behavior of marine mammals, including cetaceans, remains unresolved.
This study entails an evolutionary analysis of 42 genes associated with pulmonary fibrosis across 45 mammalian species. Twenty-one genes in cetaceans exhibited accelerated evolution, featuring specific amino acid substitutions in 14 of them. Primarily linked to the development of the respiratory system and lung morphological construction, these genes play a crucial role. Moreover, among marine mammals, we identified eight genes undergoing positive selection, and the evolutionary rates of three genes significantly correlated with diving depth. Specifically, the SFTPC gene exhibited convergent amino acid substitutions. Through in vitro cellular experiments, we illustrated that convergent amino acid site mutations in SFTPC contribute positively to pulmonary fibrosis in marine mammals, and the presence of this phenotype can induce deep alveolar collapse during diving, thereby reducing the risk of DCS during diving.
The study unveils pivotal genetic signals in cetaceans and other marine mammals, arising through evolution. These genetic signals may influence lung characteristics in marine mammals and have been linked to a reduced risk of developing DCS. Moreover, the research serves as a valuable reference for delving deeper into human diving physiology.
Mammals have wide variations in testicular position, with scrotal testes in some species and ascrotal testes in others. Although cryptorchidism is hazardous to human health, some mammalian taxa are ...natural cryptorchids. However, the evolution of testicular position and the molecular mechanisms underlying the maintenance of health, including reproductive health, in ascrotal mammals are not clear. In the present study, comparative genomics and evolutionary analyses revealed that genes associated with the extracellular matrix and muscle, contributing to the development of the gubernaculum, were involved in the evolution of testicular position in mammals. Moreover, genes related to testicular position were significantly associated with spermatogenesis and sperm fertility. These genes showed rapid evolution and the signature of positive selection, with specific substitutions in ascrotal mammals. Genes associated with testicular position were significantly enriched in functions and pathways related to cancer, DNA repair, DNA replication, and autophagy. Our results revealed that alterations in gubernaculum development contributed to the evolution of testicular position in mammals and provided the first support for two hypotheses for variation in testicular position in mammals, the "cooling hypothesis", which proposes that the scrotum provides a cool environment for acutely heat-sensitive sperm and the "training hypothesis", which proposes that the scrotum develops the sperm by exposing them to an exterior environment. Further, we identified cancer resistance and DNA repair as potential protective mechanisms in natural cryptorchids. These findings provide general insights into cryptorchidism and have implications for health and infertility both in humans and domestic mammals.
There is an increasing demand for data with the development of the world, and various fiber optic multiplexing techniques have become an important research direction to improve transmission capacity. ...However, the transmitted signals are subject to great interference due to mode coupling and mode dispersion, which require multiple-input multiple-output (MIMO) digital signal processing techniques to restore the quality of the transmitted signals. In this paper, a novel MIMO detector is designed using an adaptive learning recurrent neural network and successfully implemented in a mixed wavelength-division-mode-division-multiplexing (WDM-MDM) optical transmission system, and its performance is compared with that of the forced-zero detector and the minimum-mean-square-error detector. The results show that the introduction of an adaptive machine learning model in MIMO detection for WDM-MDM optical transmission systems can significantly improve the quality of the transmitted signals and achieve better performance than other MIMO detection algorithms while maintaining a faster computational speed and a lower number of parameters.
Cetacean hindlimbs were lost and their forelimb changed into flippers characterized by webbed digits and hyperphalangy, thus allowing them to adapt to a completely aquatic environment. However, the ...underlying molecular mechanism behind cetacean limb development remains poorly understood. In the present study, we explored the evolution of 16 limb-related genes and their cis-regulatory elements in cetaceans and compared them with that of other mammals. TBX5, a forelimb specific expression gene, was identified to have been under accelerated evolution in the ancestral branches of cetaceans. In addition, 32 cetacean-specific changes were examined in the SHH signaling network (SHH, PTCH1, TBX5, BMPs and SMO), within which mutations could yield webbed digits or an additional phalange. These findings thus suggest that the SHH signaling network regulates cetacean flipper formation. By contrast, the regulatory activity of the SHH gene enhancer--ZRS in cetaceans--was significantly lower than in mice, which is consistent with the cessation of SHH gene expression in the hindlimb bud during cetacean embryonic development. It was suggested that the decreased SHH activity regulated by enhancer ZRS might be one of the reasons for hindlimb degeneration in cetaceans. Interestingly, a parallel / convergent site (D42G) and a rapidly evolving CNE were identified in marine mammals in FGF10 and GREM1, respectively, and shown to be essential to restrict limb bud size; this is molecular evidence explaining the convergence of flipper-forelimb and shortening or degeneration of hindlimbs in marine mammals. We did evolutionary analyses of 16 limb-related genes and their cis-regulatory elements in cetaceans and compared them with those of other mammals to provide novel insights into the molecular basis of flipper forelimb and hindlimb loss in cetaceans.
Peripheral inflammatory responses are suggested to play a major role in the pathophysiology of Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a new recognized biomarker, can ...reflect peripheral inflammation in PD. However, the association between the NLR and dopaminergic degeneration in PD remains unclear.
In this retrospective study, 101 enrolled PD patients were categorized into early-stage and advanced-stage PD based on the Hoehn and Yahr (HY) scale. We evaluated the clinical characteristics, peripheral immune profile, and 11C-CFT striatal dopamine transporter (DAT) binding levels. Linear regression analyses were employed to assess the associations between NLR and striatal DAT levels at different stages in PD patients.
Covariate-controlled regression analysis revealed that higher NLR was significantly associated with lower DAT levels in the caudate (β = -0.27,
= 0.003) and the putamen (β = -0.27,
= 0.011). Moreover, in the early-stage PD subgroup, a similar association was observed (caudate: β = -0.37,
= 0.013; putamen: β = -0.45,
= 0.005). The lymphocytes count was correlated positively with the striatal DAT levels in the Spearman correlation analysis whether in total patients (caudate: ρ = 0.25,
= 0.013; putamen: ρ = 0.22,
= 0.026) or in the early-stage subgroup (caudate: ρ = 0.31,
= 0.023, putamen: ρ = 0.34,
= 0.011).
Dopaminergic degeneration is associated with peripheral inflammation in PD. The NLR, a widely used inflammatory marker, may have the potential to reflect the degree of dopaminergic degeneration in individuals with early-stage PD.
In this paper, the mode selective coupler (MSC) is analyzed using the supermode theory. It is shown that all characteristic parameters of the MSC can be obtained using the propagation constants of ...the supermodes supported by the MSC structure. Simulation results show that the characteristic parameters calculated by the supermode theory match well with those calculated by the traditional coupled mode theory (CMT) near the phase matching point of the MSC structure. In practice, the propagation constants of the supermodes can be obtained using common finite element software directly, avoiding the complex double integral in the traditional CMT. This analysis based on the supermode theory gives a deeper insight into the characteristics of the MSC, providing a fast and accurate method for the analysis of MSCs, which is helpful for their design, fabrication and applications.
Recently diverged taxa are often characterized by high rates of hybridization, which can complicate phylogenetic reconstruction. For this reason, the phylogenetic relationships and evolutionary ...history of dolphins are still not very well resolved; the question of whether the genera
Tursiops
and
Stenella
are monophyletic is especially controversial. Here, we performed re-sequencing of six dolphin genomes and combined them with eight previously published dolphin SRA datasets and six whole-genome datasets to investigate the phylogenetic relationships of dolphins and test the monophyly hypothesis of
Tursiops
and
Stenella
. Phylogenetic reconstruction with the maximum likelihood and Bayesian methods of concatenated loci, as well as with coalescence analyses of sliding window trees, produced a concordant and well-supported tree. Our studies support the non-monophyletic status of
Tursiops
and
Stenella
because the species referred these genera do not form exclusive monophyletic clades. This suggests that the current taxonomy of both genera might not reflect their evolutionary history and may underestimate their diversity. A four-taxon
D
-statistic (ABBA-BABA) test, five-taxon
D
FOIL
test, and tree-based PhyloNet analyses all showed extensive gene flow across dolphin species, which could explain the instability in resolving phylogenetic relationship of oceanic dolphins with different and limited markers
.
This study could be a good case to demonstrate how genomic data can reveal complex speciation and phylogeny in rapidly radiating animal groups.
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