2023 Vol. 44, No. 2
Although 9.4 T magnetic resonance imaging (MRI) has been tested in healthy volunteers, its safety in diabetic patients is unclear. Furthermore, the effects of high static magnetic fields (SMFs), especially gradient vs. uniform fields, have not been investigated in diabetics. Here, we investigated the consequences of exposure to 1.0–9.4 T high SMFs of different gradients (>10 T/m vs. 0–10 T/m) on type 1 diabetic (T1D) and type 2 diabetic (T2D) mice. We found that 14 h of prolonged treatment of gradient (as high as 55.5 T/m) high SMFs (1.0–8.6 T) had negative effects on T1D and T2D mice, including spleen, hepatic, and renal tissue impairment and elevated glycosylated serum protein, blood glucose, inflammation, and anxiety, while 9.4 T quasi-uniform SMFs at 0–10 T/m did not induce the same effects. In regular T1D mice (blood glucose ≥16.7 mmol/L), the >10 T/m gradient high SMFs increased malondialdehyde (P<0.01) and decreased superoxide dismutase (P<0.05). However, in the severe T1D mice (blood glucose ≥30.0 mmol/L), the >10 T/m gradient high SMFs significantly increased tissue damage and reduced survival rate. In vitro cellular studies showed that gradient high SMFs increased cellular reactive oxygen species and apoptosis and reduced MS-1 cell number and proliferation. Therefore, this study showed that prolonged exposure to high-field (1.0–8.6 T) >10 T/m gradient SMFs (35–1 380 times higher than that of current clinical MRI) can have negative effects on diabetic mice, especially mice with severe T1D, whereas 9.4 T high SMFs at 0–10 T/m did not produce the same effects, providing important information for the future development and clinical application of SMFs, especially high-field MRI.
Reproductive strategies and spawning habits play key roles in the evolution of endemic East Asian cyprinids. However, the molecular mechanisms underlying the regulation of spawning habits are not well understood. We recently identified zona pellucida (Zp) as the top differentially expressed protein between East Asian cyprinids that produce adhesive and semi-buoyant eggs, suggesting that Zp protein may play important roles in the regulation of egg type. In this work, we generated transgenic zebrafish in which oocyte-specific expression of zp genes from rare minnow (Gobiocypris rarus), an East Asian cyprinid laying adhesive eggs, was driven by a zebrafish zp3.2 gene promoter. We found that the transgenic eggs obtained partial adhesiveness and exhibited alteration in hydration and buoyancy. Abnormal metabolism of vitellogenin (VTG) may contribute to enhanced hydration and/or buoyancy. Our work shows that expression of the exogenous zp3a gene from an adhesive-egg producing fish is sufficient to induce changes in both egg adhesiveness and buoyancy in zebrafish, emphasizing the important role of zp genes in the regulation of spawning habits. Our results thus provide new insights into how endemic East Asian cyprinids may have adapted to the Yangtze river-lake system via changes in spawning habits.
Common carp are among the oldest domesticated fish in the world. As such, there are many food and ornamental carp strains with abundant phenotypic variations due to natural and artificial selection. Hebao red carp (HB, Cyprinus carpio wuyuanensis), an indigenous strain in China, is renowned for its unique body morphology and reddish skin. To reveal the genetic basis underlying the distinct skin color of HB, we constructed an improved high-fidelity (HiFi) HB genome with good contiguity, completeness, and correctness. Genome structure comparison was conducted between HB and a representative wild strain, Yellow River carp (YR, C. carpio haematopterus), to identify structural variants and genes under positive selection. Signatures of artificial selection during domestication were identified in HB and YR populations, while phenotype mapping was performed in a segregating population generated by HB×YR crosses. Body color in HB was associated with regions with fixed mutations. The simultaneous mutation and superposition of a pair of homologous genes (mitfa) in chromosomes A06 and B06 conferred the reddish color in domesticated HB. Transcriptome analysis of common carp with different alleles of the mitfa mutation confirmed that gene duplication can buffer the deleterious effects of mutation in allotetraploids. This study provides new insights into genotype-phenotype associations in allotetraploid species and lays a foundation for future breeding of common carp.
Due to the difficulty in accurately identifying structural variants (SVs) across genomes, their impact on cis-regulatory divergence of closely related species, especially fish, remains to be explored. Recently identified broad H3K4me3 domains are essential for the regulation of genes involved in several biological processes. However, the role of broad H3K4me3 domains in phenotypic divergence remains poorly understood. Siniperca chuatsi and S. scherzeri are closely related but divergent in several phenotypic traits, making them an ideal model to study cis-regulatory evolution in sister species. Here, we generated chromosome-level genomes of S. chuatsi and S. scherzeri, with assembled genome sizes of 716.35 and 740.54 Mb, respectively. The evolutionary histories of S. chuatsi and S. scherzeri were studied by inferring dynamic changes in ancestral population sizes. To explore the genetic basis of adaptation in S. chuatsi and S. scherzeri, we performed gene family expansion and contraction analysis and identified positively selected genes (PSGs). To investigate the role of SVs in cis-regulatory divergence of closely related fish species, we identified high-quality SVs as well as divergent H3K27ac and H3K4me3 domains in the genomes of S. chuatsi and S. scherzeri. Integrated analysis revealed that cis-regulatory divergence caused by SVs played an essential role in phenotypic divergence between S. chuatsi and S. scherzeri. Additionally, divergent broad H3K4me3 domains were mostly associated with cancer-related genes in S. chuatsi and S. scherzeri and contributed to their phenotypic divergence.
The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance. However, the genetic basis of muscle development in the Boer goat remains obscure. In this study, we identified specific structural variants in the Boer goat based on genome-wide selection signals and analyzed the basis of the molecular heredity of related candidate genes in muscle development. A total of 9 959 autosomal copy number variations (CNVs) were identified through selection signal analysis in 127 goat genomes. Specifically, we confirmed that the highest signal CNV (HSV) was a chromosomal arrangement containing an approximately 1.11 Mb (CHIR17: 60062304–61171840 bp) duplicated fragment inserted in reverse orientation and a 5 362 bp deleted region (CHIR17:60145940–60151302 bp) with overlapping genes (e.g., ARHGAP10, NR3C2, EDNRA, PRMT9, and TMEM184C). The homozygous duplicated HSV genotype (+/+) was found in 96% of Boer goats but was not detected in Eurasian goats and was only detected in 4% of indigenous African goats. The expression network of three candidate genes (ARHGAP10, NR3C2, and EDNRA) regulating dose transcription was constructed by RNA sequencing. Results indicated that these genes were involved in the proliferation and differentiation of skeletal muscle satellite cells (SMSCs) and their overexpression significantly increased the expression of SAA3. The HSV of the Boer goat contributed to superior skeletal muscle growth via the dose effects of overlapping genes.
Adult hippocampal neurogenesis (AHN) is crucial for learning, memory, and emotion. Deficits of AHN may lead to reduced cognitive abilities and neurodegenerative disorders, such as Alzheimer's disease. Extensive studies on rodent AHN have clarified the developmental and maturation processes of adult neural stem/progenitor cells. However, to what extent these findings apply to primates remains controversial. Recent advances in next-generation sequencing technologies have enabled in-depth investigation of the transcriptome of AHN-related populations at single-cell resolution. Here, we summarize studies of AHN in primates. Results suggest that neurogenesis is largely shared across species, but substantial differences also exist. Marker gene expression patterns in primates differ from those of rodents. Compared with rodents, the primate hippocampus has a higher proportion of immature dentate granule cells and a longer maturation period of newly generated granule cells. Future research on species divergence may deepen our understanding of the mechanisms underlying adult neurogenesis in primates.
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent years not only caused a global pandemic but resulted in enormous social, economic, and health burdens worldwide. Despite considerable efforts to combat coronavirus disease 2019 (COVID-19), various SARS-CoV-2 variants have emerged, and their underlying mechanisms of pathogenicity remain largely unknown. Furthermore, effective therapeutic drugs are still under development. Thus, an ideal animal model is crucial for studying the pathogenesis of COVID-19 and for the preclinical evaluation of vaccines and antivirals against SARS-CoV-2 and variant infections. Currently, several animal models, including mice, hamsters, ferrets, and non-human primates (NHPs), have been established to study COVID-19. Among them, ferrets are naturally susceptible to SARS-CoV-2 infection and are considered suitable for COVID-19 study. Here, we summarize recent developments and application of SARS-CoV-2 ferret models in studies on pathogenesis, therapeutic agents, and vaccines, and provide a perspective on the role of these models in preventing COVID-19 spread.
Amyotrophic lateral sclerosis (ALS) is a devastating motoneuron disease, in which lower motoneurons lose control of skeletal muscles. Degeneration of neuromuscular junctions (NMJs) occurs at the initial stage of ALS. Dipeptide repeat proteins (DPRs) from G4C2 repeat-associated non-ATG (RAN) translation are known to cause C9orf72-associated ALS (C9-ALS). However, DPR inclusion burdens are weakly correlated with neurodegenerative areas in C9-ALS patients, indicating that DPRs may exert cell non-autonomous effects, in addition to the known intracellular pathological mechanisms. Here, we report that poly-GA, the most abundant form of DPR in C9-ALS, is released from cells. Local administration of poly-GA proteins in peripheral synaptic regions causes muscle weakness and impaired neuromuscular transmission in vivo. The NMJ structure cannot be maintained, as evidenced by the fragmentation of postsynaptic acetylcholine receptor (AChR) clusters and distortion of presynaptic nerve terminals. Mechanistic study demonstrated that extracellular poly-GA sequesters soluble Agrin ligands and inhibits Agrin-MuSK signaling. Our findings provide a novel cell non-autonomous mechanism by which poly-GA impairs NMJs in C9-ALS. Thus, targeting NMJs could be an early therapeutic intervention for C9-ALS.
A critical function of animal movement is to maximize access to essential resources in temporally fluctuating and spatially heterogeneous environments. Seasonally mediated resource fluctuations may influence animal movements, enabling them to track changing resource distributions, resulting in annual migration patterns. The conservation-dependent giant panda (Ailuropoda melanoleuca) displays seasonal movement patterns; however, the key factor driving these seasonal migration patterns remains poorly understood. Here, we used GPS tracking collars to monitor the movements of six giant pandas over a 12-year period across different elevations, and performed statistical analysis of seasonal migration directions, routes, habitat revisitation, home range overlap, first arrival events, and stability. Our results revealed a compelling pattern of seasonal migrations that facilitated the ability of the pandas to forage at the appropriate time and place to maximize nutritional intake. Our results indicated that pandas utilize spatial memory to locate reliable food resources, as evidenced by their annual return to the same or similar winter and summer home ranges and the consistently maintained percentage of home range overlap. These novel insights into giant panda foraging and movement ecology not only enhance our understanding of its ability to adapt to nutritionally poor dietary resources but also provide important information for the development of resource utilization-based protection and management strategies.
We report on a new species, Zhangixalus melanoleucus sp. nov. , from Phou Samsoum Mountain (PSM) in Xiengkhouang Province, northeastern Laos, based on an integrative taxonomic approach, including morphological, molecular, and bioacoustic lines of evidence. Morphologically, the new species can be distinguished from its congeners by a combination of the following diagnostic characters: medium body size (SVL 34.4–36.3 mm in males, 53.7 mm in a single female); dorsum smooth and green; chest and belly lacking spots; ﬂanks, axillae, ventral surfaces of forearms, inguinal, anterior and posterior surfaces of thighs white, covered with irregular black pattern; finger webbing formula I 2½–3 II 2–3 III 2¼–2 IV; toe webbing formula I 2–2½ II 1–2 III 1–2 IV 2–1 V; toe webbing cream with small black blotches; outer margin of forearms and feet with weak dermal ridges; supracloacal fold and pointed projection at tibiotarsal articulation absent; and iris reddish-orange. The new species is divergent from all other members of Zhangixalus based on 16S rRNA gene sequences (P=3.4%–8.8%) and is reconstructed as the sister species of Z. nigropunctatus. The advertisement call of the new species consists of clicking sounds and includes a series of notes, each 0.28 s in duration and consisting of 2–3 pulses with a dominant frequency of ca. 3.14 kHz. To date, Zhangixalus melanoleucus sp. nov. is known only from the montane evergreen forests of PSM at elevations of 2 000–2 200 m a.s.l. We preliminary suggest the new species should be considered as Data Deficient (DD) following the IUCN’s Red List categories.
The subfamily Megophryinae, as a representative batrachian group of the Oriental Realm and one of the most diverse groups of amphibians, has attracted considerable attention due to continued conjecture regarding its generic classification and failure to reach a satisfactory consensus. China boasts the richest diversity of Asian horned toads, containing some two thirds of the total species cataloged. However, most species have a complicated taxonomic history, resulting in multiple misidentifications. As such, an overall clarification of historical records and regional checklists is required. In the current investigation, we established the phylogeny of the Asian horned toads and performed detailed examinations with redefinitions of several important morphological traits. Based on the phylogenetic relationships and morphological differences, we propose a new ten-genus classification for the Asian horned toad subfamily Megophryinae: i.e., Brachytarsophrys, Atympanophrys, Grillitschia, Sarawakiphrys gen. nov. , Jingophrys gen. nov. , Xenophrys, Megophrys, Pelobatrachus, Ophryophryne, and Boulenophrys. Revisions on the diagnosability, distribution, and content of each genus are provided. Furthermore, we present a careful review of the taxonomic history of Asian horned toad species from China and provide a monograph of congeners, including six species of Brachytarsophrys, four species of Atympanophrys, five species of Jingophrys gen. nov. , 10 species of Xenophrys, two species of Ophryophryne, and 60 species of Boulenophrys. Finally, we discuss the importance of traditional morphological traits based on multiple populations in taxonomic work as well as taxonomic inflation caused by the genetic species delimitation.