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The association of neurogenesis and gliogenesis with glioma remains unclear. By conducting single-cell RNA-seq analyses on 26 gliomas, we reported their classification into primitive oligodendrocyte precursor cell (pri-OPC)-like and radial glia (RG)-like tumors and validated it in a public cohort and TCGA glioma. The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations, and the pri-OPC-like ones were prone to carrying TP53 mutations. Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes, suggesting their distinct immune evasion programs. Furthermore, the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners. Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes. For example, glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes, respectively. Their expression was positively correlated with those of immune checkpoint genes (e.g., LGALS33) and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells. This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.
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Aim: A novel CD19xCD3xCD28 trispecific antibody with a tandem single-chain variable fragments (scFv) structure was developed for the treatment of B-cell malignancies. Methods: The trispecific antibody in inducing tumor-directed T-cell activation and cytotoxicity was evaluated in vitro and in vivo and compared with its bispecific counterpart BiTE-CD19xCD3 lacking a CD28-targeting domain. Results: The trispecific antibody with a co-stimulatory domain exhibited augmented T-cell activation and memory T-cell differentiation capability and it induced faster tumor cell lysis than the bispecific antibody. RNAseq analysis revealed that the trispecific antibody modulates CD3/TCR complex-derived signal and upregulates antiapoptotic factors to influence the survival of T cells. Conclusion: By CD3/CD28 co-engagement, the trispecific antibody demonstrated its advantages in T-cell immunity and potential use as a more powerful and long-lasting T-cell engager.
T-cell based immunotherapies are a type of treatment that stimulates the body's own immune system to fight cancer. They have grown in popularity in recent years and have had impressive results in cancer treatment. One type of T-cell immunotherapy is a T-cell engager antibody. This is a type of molecule that redirects the body's immune cells to recognise and kill cancer cells. In this study, we developed a new type of T-cell engager antibody to treat two types of blood and bone marrow cancer. The antibody works by joining immune cells and cancer cells close together, to help activate the immune cells for cancer killing. This new type of T-cell engager antibody worked better than previous versions. It helped the immune cells survive longer and kill cancer more effectively. This means the new antibody might be better at treating people who have these types of cancers, but more testing in humans needs to be done.
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Anticorpos Biespecíficos , Neoplasias , Humanos , Antígenos CD28 , Complexo CD3 , Linfócitos T , Anticorpos Biespecíficos/uso terapêutico , Ativação LinfocitáriaRESUMO
The exploitation pattern of the invertebrate resource (Oratosquilla oratoria) was investigated in the coastal waters of the Shandong Peninsula, along with the seasonal variation in body length structure, spatial distribution in abundance, and interannual stock status. Results showed that the model with only catch data suggested both stocks in the north and south were suffering from extreme fishing pressure without explicit recovery (North: B2019/BMSY = 0.468 and F2019/FMSY = 1.88 in CMSY. South: B2019/BMSY = 0.349 and F2019/FMSY = 2.59 in CMSY). However, the other two assessment models indicated that the northern stock began to gradually recover as the fishing pressure dropped to an appropriate level after the original overfished status (North: B2019/BMSY = 0.738 and F2019/FMSY = 0.882 in AMSY, B2019/BMSY = 0.831 and F2019/FMSY = 0.774 in BSM. South: B2019/BMSY = 0.164 and F2019/FMSY = 1.44 in AMSY, B2019/BMSY = 0.384 and F2019/FMSY = 1.76 in BSM). Overall, the stock status in the north was better than that in the south. This study suggested that spatial exploitation pattern and quarterly differences should be considered in fishery management process.
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Crustáceos , Pesqueiros , AnimaisRESUMO
Chelidonichthys spinosus, a secondary economic fish, is increasingly being exploited and valued in China. However, overfishing has led to it being recognized as one of the most depleted marine species in China. In this study, we generated a chromosome-level genome of C. spinosus using PacBio, Illumina, and Hi-C sequencing data. Ultimately, we assembled a 624.7 Mb genome of C. spinosus, with a contig N50 of 13.77 Mb and scaffold N50 of 28.11 Mb. We further anchored and oriented the assembled sequences onto 24 pseudo-chromosomes using Hi-C techniques. In total, 25,358 protein-coding genes were predicted, of which 24,072 (94.93%) genes were functionally annotated. The dot plot reveals a prominent co-linearity between C. spinosus and Cyclopterus lumpus, indicating a remarkably close phylogenetic relationship between these two species. The assembled genome sequences provide valuable information for elucidating the genetic adaptation and potential molecular basis of C. spinosus. They also have the potential to provide insight into the evolutionary investigation of teleost fish and vertebrates.
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Genoma , Perciformes , Animais , Cromossomos/genética , Conservação dos Recursos Naturais , Perciformes/genética , FilogeniaRESUMO
The Formosa Ridge, also named Site F, is an active cold seep marine ecosystem site that has been studied since it was discovered on the continental slope of the northeast South China Sea (SCS). However, few studies have focused on the eukaryotic diversity at Site F. Environmental DNA (eDNA) technology is a non-invasive method applied in biodiversity surveys with a high species detection probability. In the present study, we identified multi-trophic biodiversity using eDNA metabarcoding combined with multiple ribosomal RNA gene (rDNA) markers. We detected 142 phytoplankton, 90 invertebrates, and 64 fish species by amplifying the 18S rRNA gene V4 region, the 18S rRNA gene V9 region, and the 12S rRNA gene. The results elucidated dissimilar trends of different assemblages with depth. The diversity of phytoplankton and invertebrate assemblages markedly decreased with depth, whereas little change was observed within the fish assemblage. We comprehensively assessed the relationship between the three assemblages and environmental factors (temperature, salinity, depth, dissolved oxygen, and chlorophyll a). These factors strongly impacted on phytoplankton and invertebrates, but only slightly on fish. We inferred the finding might be due to fish having a strong migration capacity and wide distribution. This study indicates that eDNA metabarcoding with multiple markers is a powerful tool for marine biodiversity research that is able to provide technical support and knowledge for resource management and biodiversity protection efforts.
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DNA Ambiental , Ecossistema , Animais , Clorofila A , Taiwan , Código de Barras de DNA Taxonômico , Biodiversidade , Peixes/genética , Fitoplâncton , RNA Ribossômico 18S/genética , Monitoramento Ambiental/métodosRESUMO
The big-head schizothorcin (Aspiorhynchus laticeps) is an endemic and near-extinction freshwater fish in Xinjiang, China. In this study, a chromosome-scale genome assembly of A. laticeps was generated using PacBio and Hi-C techniques. The PacBio sequencing data resulted in a 1.58 Gb assembly with a contig N50 of 1.27 Mb. Using Hi-C scaffolding approach, 88.38% of the initial assembled sequences were anchored and oriented into a chromosomal-scale assembly. The final assembly consisted of 25 pseudo-chromosomes that yielded 1.37 Gb of sequence, with a scaffold N50 of 44.02 Mb. BUSCO analysis showed a completeness score of 93.7%. The genome contained 48,537 predicted protein-coding genes and 58.31% of the assembly was annotated as repetitive sequences. Whole genome duplication events were further confirmed using 4dTv analysis. The genome assembly of A. laticeps should be valuable and important to understand the genetic adaptation and endangerment process of this species, which could lead to more effective management and conservation of the big-head schizothorcin and related freshwater fish species.
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Cyprinidae , Animais , China , Cromossomos/genética , Cyprinidae/genética , Água Doce , Análise de Sequência de DNARESUMO
The prevailing determinant of maturation in fishes is thought to be a redirection of energy from growth to reproduction. Instead, the Gill Oxygen Limitation Theory predicts that maturation, and thus reproduction, is induced when a fish reaches a critical ratio of oxygen supply to demand (Qm /Qmaint ). The consistency of this critical ratio has been previously documented in many fishes, but a broader test was lacking. In this study, the authors assess if this critical ratio is consistent across 132 unique fish species, as measured by the slope of the relationship between Lmax D and Lm D , where Lmax is the maximum length reached in a given population, Lm is the mean size at first maturity in that population and D is a gill-related exponent which renders the Lmax D /Lm D ratio equivalent to the Qm /Qmaint ratio. The authors found that across all species, the Lmax D /Lm D ratio was 1.40 (95% c.i. 1.38-1.42), which was not significantly different from that previously estimated across other species groups (1.35, 95% c.i. 1.22-1.53), especially when phylogenetic relationships were considered (1.25, 95% Bayesian credible interval 1.09-1.40). The consistency of the Lmax D /Lm D ratio across taxa, which expresses the difference in metabolic rate at maturity and maximum size, suggests that the scaling of gill surface area is the factor that underlies this ratio, and which triggers the maturation in fishes.
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Peixes , Brânquias , Animais , Teorema de Bayes , Água Doce , Brânquias/metabolismo , Oxigênio/metabolismo , FilogeniaRESUMO
The South China Sea (SCS) is an important part of the Indo-Pacific convergence zone, with high biodiversity and abundant marine resources. Traditional methods are primarily used to monitor biodiversity. However, a few studies have used environmental DNA (eDNA) metabarcoding to research the assemblage structure of the SCS. This study used eDNA metabarcoding to survey the SCS assemblage and its relationship with environmental factors over a month-long time-series (August 30th to September 30th, 2020) of seawater samples from the central part of the SCS (9°-20°86' N, 113°-118°47' E). 32 stations were divided into six groups (A, B, C, D, E, F) according to longitude. We collected water samples, extracted eDNA, and amplified 18S rRNA gene V4 region (18S V4), 18S rRNA gene V9 region (18S V9), and 12S rRNA gene (12S). Krona diagrams were used to show species composition. We identified 192 phytoplankton, 104 invertebrate, and 61 fish species from 18S V4, 18S V9, and 12S, respectively. Generally, the three assemblage structures exhibited an increase in species diversity with increasing longitude. Group E had the highest fish diversity. Groups F and C had the highest phytoplankton and invertebrate diversity, respectively. Canonical correspondence analysis showed that four factors (chlorophyll a, depth, salinity, and temperature) were correlated with assemblage structure. Chlorophyll a was the main environmental factor that affected fish, phytoplankton, and invertebrate assemblage structures; salinity was strongly correlated with fish and invertebrate assemblage structures; temperature was a key factor that impacted fish and invertebrate assemblage structures; and depth was strongly correlated with invertebrate assemblage structure. Our results revealed that eDNA metabarcoding is a powerful tool for improving detection rate and using multiple markers is an effective approach for monitoring biodiversity. This study provided information that can be used to enhance biodiversity protection efforts in the SCS.
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DNA Ambiental , Animais , Biodiversidade , Clorofila A/análise , Código de Barras de DNA Taxonômico , DNA Ambiental/genética , Monitoramento Ambiental/métodosRESUMO
Patients with monoallelic bromodomain and PHD finger-containing protein 1 (BRPF1) mutations showed intellectual disability. The hippocampus has essential roles in learning and memory. Our previous work indicated that Brpf1 was specifically and strongly expressed in the hippocampus from the perinatal period to adulthood. We hypothesized that mouse Brpf1 plays critical roles in the morphology and function of hippocampal neurons, and its deficiency leads to learning and memory deficits. To test this, we performed immunofluorescence, whole-cell patch clamp, and mRNA-Seq on shBrpf1-infected primary cultured hippocampal neurons to study the effect of Brpf1 knockdown on neuronal morphology, electrophysiological characteristics, and gene regulation. In addition, we performed stereotactic injection into adult mouse hippocampus to knock down Brpf1 in vivo and examined the learning and memory ability by Morris water maze. We found that mild knockdown of Brpf1 reduced mEPSC frequency of cultured hippocampal neurons, before any significant changes of dendritic morphology showed. We also found that Brpf1 mild knockdown in the hippocampus showed a decreasing trend on the spatial learning and memory ability of mice. Finally, mRNA-Seq analyses showed that genes related to learning, memory, and synaptic transmission (such as C1ql1, Gpr17, Htr1d, Glra1, Cxcl10, and Grin2a) were dysregulated upon Brpf1 knockdown. Our results showed that Brpf1 mild knockdown attenuated hippocampal excitatory synaptic transmission and reduced spatial learning and memory ability, which helps explain the symptoms of patients with BRPF1 mutations.
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The complete mitochondrial genome of the half-fin anchovy, Setipinna tenuifilis collected from Yellow and Bohai Seas was determined by next-generation sequencing. The mitogenome is a circular molecule 16,668 bp in length, including the typical structure of 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a control region. The termination-associated sequence (TAS), central conserved sequence block (CSB) and CSB are detected in the control region. The gene contents of the mitogenome are identical to those observed in most bony fishes.
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The spiny red gurnard, Chelidonichthys spinosus is a common marine economic fish species along the coast of China. In the present study, the complete mitochondrial genome of spiny red gurnard collected from the Yangtze Estuary was determined by next-generation sequencing (NGS). The mitogenome is a circular nucleotide 16,466 bp in length and has the typical vertebrate genome structure of 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and two control regions (Origin of Heavy chain and Origin of Light chain). The termination associated sequence (TAS), the central conserved sequence block (central CSB), and the conserved sequence block (CSB) were detected in the control region. Phylogenetic analysis of C. spinosus places in a fully supported clade with C. kumu in a sister position to Eutrigla gurnardus. The complete mitochondrial genome sequence of the spiny red gurnard provides baseline genetic information for future studies on the molecular systematics and phylogeny of bony fishes in the Triglidae.
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Intellectual disability is closely related to impaired GABA neurotransmission. Brpf1 was specifically expressed in medial ganglionic eminence (MGE), a developmental niche of GABAergic interneurons, and patients with BRPF1 mutations showed intellectual disability. To test its role in the development and function of MGE-derived GABAergic interneurons, we performed immunofluorescence staining, whole-cell patch-clamp, MGE transplantation, and mRNA-Seq to understand its effect on neuronal differentiation, dendritic morphology, electrophysiology, migration, and gene regulation, using mouse MGE-derived GABAergic interneurons infected with AAV-shBrpf1. The results showed that Brpf1 knockdown had a decreasing trend, although not significant, on the differentiation of GABAergic interneurons into parvalbumin+ interneurons. Moreover, increased firing threshold, decreased number of evoked action potentials, and a reduced amplitude of miniature inhibitory postsynaptic currents were observed before any significant change of MAP2+ dendritic morphology and in vivo migration ability appeared. Finally, mRNA-Seq analysis revealed that genes related to neurodevelopment and synaptic transmission such as Map2k7 were dysregulated. Our results demonstrated a key role of Brpf1 in inhibitory neurotransmission and related gene expression of GABAergic interneurons.
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Deficiência Intelectual , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas de Ligação a DNA , Humanos , Deficiência Intelectual/genética , Interneurônios , Eminência Mediana , Camundongos , Transmissão SinápticaRESUMO
The complete mitochondrial genome of Dictyosoma burgeri collected from Yellow and Bohai Seas was determined by next-generation sequencing. The mitogenome is a circular molecule 16,513 bp in length, including the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region. The TAS, central CSB, and CSB were detected in the control region. The gene contents of the mitogenome are identical to those observed in most bony fishes.
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The ecological niche is a key concept for elucidating patterns of species distributions and developing strategies for conserving biodiversity. However, recent times are seeing a widespread debate whether species niches are conserved across space and time (niche conservatism hypothesis). Biological invasions represent a unique opportunity to test this hypothesis in a short time frame at the global scale. We synthesized empirical findings for 434 invasive species from 86 studies to assess whether invasive species conserve their climatic niche between native and introduced ranges. Although the niche conservatism hypothesis was rejected in most studies, highly contrasting conclusions for the same species between and within studies suggest that the dichotomous conclusions of these studies were sensitive to techniques, assessment criteria, or author preferences. We performed a consistent quantitative analysis of the dynamics between native and introduced climatic niches reported by previous studies. Our results show there is very limited niche expansion between native and introduced ranges, and introduced niches occupy a position similar to native niches in the environmental space. These findings support the niche conservatism hypothesis overall. In particular, introduced niches were narrower for terrestrial animals, species introduced more recently, or species with more native occurrences. Niche similarity was lower for aquatic species, species introduced only intentionally or more recently, or species with fewer introduced occurrences. Climatic niche conservatism for invasive species not only increases our confidence in transferring ecological niche models to new ranges but also supports the use of niche models for forecasting species responses to changing climates.
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Ecossistema , Espécies Introduzidas/estatística & dados numéricos , Modelos Biológicos , Distribuição Animal , Animais , Teorema de Bayes , Clima , Plantas , Dinâmica PopulacionalRESUMO
The reliability of transferring species distribution models (SDMs) to new ranges and future climates has been widely debated. Biological invasions offer the unique opportunity to evaluate model transferability, as distribution data between species' native and introduced ranges are geographically independent of each other. Here, we performed the first global quantitative synthesis of the spatial transferability of SDMs for 235 invasive species and assessed the association of model transferability with the focal invader, model choice and parameterisation. We found that SDMs had limited spatial transferability overall. However, model transferability was higher for terrestrial endotherms, species introduced from or to the Southern Hemisphere, and species introduced more recently. Model transferability was also positively associated with the number of presences for model calibration and evaluation, respectively, but negatively with the number of predictors. These findings highlight the importance of considering the characteristics of the focal invader, environment and modelling in the application and assessment of SDMs.
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Espécies Introduzidas , Modelos Biológicos , Clima , Ecossistema , Reprodutibilidade dos TestesRESUMO
Seasonal variations of the ichthyoplankton assemblage and its relationship with the environment were analyzed based on four seasonal surveys during 2012. Historical data was collected to be compared with results from previous years in order to indicate the seasonal and inter-annual variation of the ichthyoplankton assemblage in the Yangtze Estuary and the adjacent waters. A total of 3,688 individuals belonging to 5 orders, 9 families, and 15 species were collected. No samples were collected in the winter cruise. In 2012, all samples were separated into four ecotypes, which is comparable with the historical data from previous years. The Engraulis japonicus was the most abundant species of all teleost fishes. The E. japonicus was captured in every season and contributed the most to the abundance of ichthyoplankton, which was greater than that of previous years. This result may be due to the periodic fluctuations of E. japonicus or from the displacement of spawning grounds offshore for environmental reasons. The diversity indices of the assemblage were significantly different among seasons, with the number and abundance of the species peaking in the spring, while richness, evenness and diversity indices peaked in the autumn. The species richness of the ichthyoplankton varied from 0.74 to 1.62, the Pielou evenness index varied from 0.10 to 0.49 and the Shannon-Wiener index varied from 0.19 to 1.04. The results of CCA analysis showed that the major factors affecting the ichthyoplankton assemblage differed throughout the seasons. Chla was the key factor affecting the ichthyoplankton in 2012. These seasonal and inter-annual variations likely resulted from migrations associated with fish spawning as well as the environment. Compared with data from previous studies, the relationship between the assemblage structure of ichthyoplankton and corresponding environmental variables have undergone a decline.
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The rearrangement and expression of immunoglobulin genes are regulated by enhancers and their binding transcriptional factors that activate or suppress the activities of the enhancers. The immunoglobulin κ (Igκ) gene locus has three important enhancers: the intrinsic enhancer (Ei), 3' enhancer (E3'), and distal enhancer (Ed). Ei and E3' are both required for Igκ gene rearrangement during early stages of B-cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3' and Ed. The transcription factor YY1 affects the expression of many genes involved in B-cell development, probably by mediating interactions between their enhancers and promoters. Herein, we found that YY1 binds to the E3' enhancer and suppresses Igκ expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Igκ expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3' enhancer. Moreover, in germinal centre B cells and plasma cells, YY1 expression was reversely associated with Igκ levels, implying that YY1 might facilitate antibody affinity maturation in germinal centre B cells through the transient attenuation of Igκ expression.
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Linfócitos B/imunologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Elementos Facilitadores Genéticos/genética , Cadeias kappa de Imunoglobulina/biossíntese , Linfoma de Células B/imunologia , Fator de Transcrição YY1/metabolismo , Linfócitos B/citologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Linhagem Celular Tumoral , Centro Germinativo/imunologia , Células HEK293 , Humanos , Cadeias kappa de Imunoglobulina/genética , Linfoma de Células B/patologia , Regiões Promotoras Genéticas/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Transcrição Gênica/genética , Fator de Transcrição YY1/genéticaRESUMO
Resources of Japanese anchovy (Engraulis japonicus Temminck & Schlegel, 1846) are undergoing dramatic recessions in China as the consequence of intensifying anthropogenic activities. Elucidating the influences of local-scale environmental factors on early life history traits is of great importance to design strategies conserving and restoring the declining anchovy resources. In this research, we studied hatching date and early growth of anchovy in the Yangtze River Estuary (YRE) using information obtained from otolith microstructure. Onset of hatching season and growth rates of anchovy was compared to populations in Japan and Taiwan. In YRE, the hatching date of anchovy ranged from February 26th to April 6th and mean growth rate ranged from 0.27 to 0.77 mm/d. Anchovies hatching later had higher growth rates than individuals hatching earlier before the 25th day. Among populations, hatching onsets of anchovy from the higher latitude were later than populations in the lower latitude, and growth rates of anchovy in YRE were much lower than populations in Japan and Taiwan. Variations in hatching onsets and early growth patterns of anchovy thus provide important knowledge on understanding the adaptation of anchovy in YRE and designing management strategies on conserving China's anchovy resources.
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The complete mitochondrial genome of the larval Syngnathus schlegeli collected from Yangtze estuary was determined by next-generation sequencing. The mitogenome is a circular molecule 16,465 bp in length, including 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a control region. The TAS, central CSB and CSB were detected in the control region. The gene contents of the mitogenome are identical to those observed in most marine bony fishes. The NJ phylogenetic tree showed that S. schlegeli clustered in a branch close to the species from the same genus.