The marine gastropod Conomurex luhuanus (Strombidae) has high-resolution spatial vision and eyes with complex retinas

All species within the conch snail family Strombidae possess large camera-type eyes that are surprisingly well-developed compared to those found in most other gastropods. Although these eyes are known to be structurally complex, very little research on their visual function has been conducted. Here, we use isoluminant expanding visual stimuli to measure the spatial resolution and contrast sensitivity of a strombid, Conomurex luhuanus. Using these stimuli, we show that this species responds to objects as small as 1.06° in its visual field. We also show that C. luhuanus responds to Michelson contrasts of 0.07, a low contrast sensitivity between object and background. The defensive withdrawal response elicited by visual stimuli of such small angular size and low contrast suggests that conch snails may use spatial vision for the early detection of potential predators. We support these findings with morphological estimations of spatial resolution of 1.04 ± 0.14°. These anatomical data therefore agree with the behavioural measures and highlight the benefits of integrating morphological and behavioural approaches in animal vision studies. Furthermore, using contemporary imaging techniques including serial block-face scanning electron microscopy (SBF-SEM), in conjunction with transmission electron microscopy (TEM), we found that C. luhuanus have more complex retinas, in terms of cell type diversity, than previous studies of the group have discovered using TEM alone. We found the C. luhuanus retina is comprised of six cell types, including a newly identified ganglion cell and accessory photoreceptor, rather than the previously described four cell types.

A new Diancta species of the family Diplommatinidae (Cyclophoroidea) from Vanua Levu Island, Fiji

A new species of Diancta of the staircase snail family Diplommatinidae is described from Mt. Savusavu, Vanua Levu Island, Fiji. Due to its left coiling shell and a constriction before the last whorl, it is placed in the genus Diancta. Micro-CT imaging reveals two apertural teeth and an inner lamella that is situated at the zone of constriction. The shell abruptly changes coiling direction by 45 degrees before the last whorl. Up to now, this coiling modus had not yet been documented for any species of Diplommatinidae from the Fiji Islands.

Dynamin 3 Inhibits the Proliferation of Non-small-Cell Lung Cancer Cells by Suppressing c-MET–GBR2–STAT3 Complex Formation

Dynamin 3 (DNM3) has gained increased attention ever since its potential as a tumor suppressor was reported. However, its action in lung cancer (LC) is undefined. In this study, the role of DNM3 in LC development was investigated. DNM3 expression was found to be downregulated in tumors of patients with LC, especially those with metastasis. The DNM3 downregulation enhanced the proliferative and metastatic ability of LC cells, whereas its upregulation had the opposite effects. In vivo xenograft experiments confirmed that lung tumors with lower DNM3 expression had higher growth and metastatic abilities. Mechanistic studies revealed that DNM3 interacts with growth factor receptor-bound protein 2 (GBR2), thereby interrupting tyrosine-protein kinase Met (c-MET)–GBR2–signal transducer and activator of transcription 3 (STAT3) complex formation, which suppressed STAT3 activation. Therefore, the absence of DNM3 frees GBR2 to activate STAT3, which regulates the expression of genes related to LC proliferation and metastasis (e.g., cyclin D1 and Snail family transcriptional repressor 1). Additionally, the c-MET inhibitor crizotinib effectively suppressed LC cell proliferation and migration in vitro and in vivo, even with DNM3 depleted. Therefore, our study has demonstrated the antitumor effect of DNM3 in LC and suggests that the inhibition of c-MET might be a promising strategy for treating those LC patients with low DNM3 expression.

SNAI2-Induced CircMTO1 Promotes Cell Proliferation and Inhibits Apoptosis Through the miR-320b/MCL1 Axis in Human Granulosa-Like Tumor Cells

Polycystic ovary syndrome (PCOS), one of the most common types of endocrine diseases, is characterized by a high prevalence among women of reproductive-age. However, its pathogenesis and molecular mechanisms remain unclear. CircMTO1 has been reported to participate in numerous biological processes, but, its role in PCOS progression remains unknown. In the current study, we elucidated the expression and circRNA characterization of circMTO1 in human granulosa-like tumor cells. We found that circMTO1 knockdown promoted human granulosa-like tumor cell proliferation and inhibited its apoptosis rate. Next, we explored the underlying molecular mechanisms by using a series of experiments. Our results revealed the effect of the novel circMTO1/miR-320b/MCL1 axis in human granulosa-like tumor cells. Furthermore, we found that the expression of circMTO1 was induced by Snail family transcriptional repressor 2 (SNAI2) in human granulosa-like tumor cells. Our results may provide potential targets for PCOS research and a novel direction for the diagnosis and treatment of PCOS.

Snail-Family Proteins: Role in Carcinogenesis and Prospects for Antitumor Therapy

The review analyzes Snail family proteins, which are transcription factors involved in the regulation of the epithelial-mesenchymal transition (EMT) of tumor cells. We describe the structure of these proteins, their post-translational modification, and the mechanisms of Snail-dependent regulation of genes. The role of Snail proteins in carcinogenesis, invasion, and metastasis is analyzed. Furthermore, we focus on EMT signaling mechanisms involving Snail proteins. Next, we dissect Snail signaling in hypoxia, a condition that complicates anticancer treatment. Finally, we offer classes of chemical compounds capable of down-regulating the transcriptional activity of Snails. Given the important role of Snail proteins in cancer biology and the potential for pharmacological inhibition, Snail family proteins may be considered promising as therapeutic targets.

Molecular phylogeny of the limacoid snail family Dyakiidae in Southeast Asia, with the description of a new genus and species

Members of the terrestrial snail family Dyakiidae from Southeast Asia show a distinct geographical distribution pattern and possess different degrees of complexity in their amatorial organ gland. This study is the first molecular phylogeny of ten of the 12 genera in this family, performed to provide insights into the origin of Dyakiidae and the evolution of their shells and amatorial organ gland structure. A new genus and new species, Pseudoquantula lenticularis Jirapatrasilp & Panha gen. & sp. nov., was uncovered based on its distinct morphological characters and molecular divergence. All other genera were retrieved as monophyletic except for Dyakia. Mainland Southeast Asia was inferred to be the ancestral range of the Dyakiidae, and the lineages then dispersed to and diversified in Borneo. Cladistic analysis showed that all 14 morphological characters used in this study were homoplastic. These results disagree with the previous amatorial organ transformation series, in which neither Pseudoplecta nor Quantula was ancestral to the other genera. The enigmatic genus Pseudoplecta, which lacks an amatorial organ gland, exhibited secondary loss.

miRNA-153 Targets Snail Family Transcriptional Repressor 1 and Inhibits the Cell Apoptosis in the Model of MPP+-Induced Parkinson?s Disease

Rationale: Parkinson?s disease (PD) is a heterogeneous neurodegenerative disorder in which microRNAs are significantly involved. Previous studies have reported that MiR-153 might inhibit the progression of PD. However, the biological roles of MiR-153 and its underlying molecular mechanism in PD remain unclear. Methods: In the present study, MES23.5 cells were treated with gradient concentration of neurotoxin 1-Methyl-4-Phenyl-Pyridinium (MPP+) to construct the PD model. Quantitative real-time PCR (qRT-PCR) was performed to detect the expressions of MiR-153 and SNAI1. Western blotting (WB) measured the expressions of SNAI1, Nrf2 and HO-1. The relationship between MiR-153 and SNAI1 was analyzed by luciferase reporter assay. In addition, cell proliferation and apoptosis were examined using cell counting kit-8 (CCK-8) and TUNEL assays. Results: MiR-153 expression was decreased after MPP+ treatment in neurons cells and overexpression of MiR-153 significantly inhibited MPP+-inhibited viability. Moreover, dual-luciferase reporter assays showed that SNAI1 was a target of MiR-153 and there was a negative correlation between them. Overexpression of SNAI1 attenuated the inhibitory effect of MiR-153 overexpression on MPP+-induced apoptosis. In addition, overexpression of MiR-153 significantly increased the expression levels of Nrf2 and HO-1. Conclusion: In summary, the results suggest that MiR-153 inhibits MPP+-induced apoptosis via activating Nrf2/HO-1 pathway by targeting SNAI1 in PD, indicating that MiR-153 is a potential molecular target for PD treatment.

Slug regulates the Dll4-Notch-VEGFR2 axis to control endothelial cell activation and angiogenesis

Slug (SNAI2), a member of the well-conserved Snail family of transcription factors, has multiple developmental roles, including in epithelial-to-mesenchymal transition (EMT). Here, we show that Slug is critical for the pathological angiogenesis needed to sustain tumor growth, and transiently necessary for normal developmental angiogenesis. We find that Slug upregulation in angiogenic endothelial cells (EC) regulates an EMT-like suite of target genes, and suppresses Dll4-Notch signaling thereby promoting VEGFR2 expression. Both EC-specific Slug re-expression and reduced Notch signaling, either by γ-secretase inhibition or loss of Dll4, rescue retinal angiogenesis in SlugKO mice. Conversely, inhibition of VEGF signaling prevents excessive angiogenic sprouting of Slug overexpressing EC. Finally, endothelial Slug (but not Snail) is activated by the pro-angiogenic factor SDF1α via its canonical receptor CXCR4 and the MAP kinase ERK5. Altogether, our data support a critical role for Slug in determining the angiogenic response during development and disease.

The New Model of Snail Expression Regulation: The Role of MRTFs in Fast and Slow Endothelial–Mesenchymal Transition

Endothelial–mesenchymal transition (EndMT) is a crucial phenomenon in regulating the development of diseases, including cancer metastasis and fibrotic disorders. The primary regulators of disease development are zinc-finger transcription factors belonging to the Snail family. In this study, we characterized the myocardin-related transcription factor (MRTF)-dependent mechanisms of a human snail promoter regulation in TGF-β-stimulated human endothelial cells. Although in silico analysis revealed that the snail promoter’s regulatory fragment contains one GCCG and two SP1 motifs that could be occupied by MRTFs, the genetic study confirmed that MRTF binds only to SP1 sites to promote snail expression. The more accurate studies revealed that MRTF-A binds to both SP1 elements, whereas MRTF-B to only one (SP1near). Although we found that each MRTF alone is capable of inducing snail expression, the direct cooperation of these proteins is required to reinforce snail expression and promote the late stages of EndMT within 48 hours. Furthermore, genetic and biochemical analysis revealed that MRTF-B alone could induce the late stage of EndMT. However, it requires a prolonged time. Therefore, we concluded that MRTFs might cause EndMT in a fast- and slow-dependent manner. Based on MRTF-dependent Snail upregulation, we recognized that TGF-β1, as an MRTF-B regulator, is involved in slow EndMT induction, whereas TGF-β2, which altered both MRTF-A and MRTF-B expression, promotes a fast EndMT process.