Transient Interphase Microtubules Appear in Differentiating Sponge Cells.

Microtubules are an indispensable component of all eukaryotic cells due to their role in mitotic spindle formation, yet their organization and number can vary greatly in the interphase. The last common ancestor of all eukaryotes already had microtubules and microtubule motor proteins moving along them. Sponges are traditionally regarded as the oldest animal phylum. Their body does not have a clear differentiation into tissues, but it contains several distinguishable cell types. The choanocytes stand out among them and are responsible for creating a flow of water with their flagella and increasing the filtering and feeding efficiency of the sponge. Choanocyte flagella contain microtubules, but thus far, observing a developed system of cytoplasmic microtubules in non-flagellated interphase sponge cells has been mostly unsuccessful. In this work, we combine transcriptomic analysis, immunofluorescence, and electron microscopy with time-lapse recording to demonstrate that microtubules appear in the cytoplasm of sponge cells only when transdifferentiation processes are activated. We conclude that dynamic cytoplasmic microtubules in the cells of sponges are not a persistent but rather a transient structure, associated with cellular plasticity.

Giant honeybees (Apis dorsata) trade off defensiveness against periodic mass flight activity.

The giant honeybee Apis dorsata (Fabricius, 1793) is an evolutionarily ancient species that builds its nests in the open. The nest consists of a single honeycomb covered with the bee curtain which are several layers of worker bees that remain almost motionless with their heads up and abdomens down on the nest surface, except for the mouth area, the hub between inner- and outer-nest activities. A colony may change this semi-quiescence several times a day, depending on its reproductive state and ambient temperature, to enter the state of mass flight activity (MFA), in which nest organisation is restructured and defense ability is likely to be suppressed (predicted by the mass-flight-suspend-defensiveness hypothesis). For this study, three episode of MFA (mfa1-3) of a selected experimental nest were analysed in a case study with sequences of >60 000 images at 50 Hz, each comprise a short pre-MFA session, the MFA and the post-MFA phase of further 10 min. To test colony defensiveness under normative conditions, a dummy wasp was cyclically presented with a standardised motion programme (Pd) with intervening sessions without such a presentation (nPd). Motion activity at five selected surveillance zones (sz1-5) on the nest were analysed. In contrast to mfa1,2, in mfa3 the experimental regime started with the cyclic presentation of the dummy wasp only after the MFA had subsided. As a result, the MFA intensity in mfa3 was significantly lower than in mfa1-2, suggesting that a colony is able to perceive external threats during the MFA. Characteristic ripples appear in the motion profiles, which can be interpreted as a start signal for the transition to MFA. Because they are strongest in the mouth zone and shift to higher frequencies on their way to the nest periphery, it can be concluded that MFA starts earlier in the mouth zone than in the peripheral zones, also suggesting that the mouth zone is a control centre for the scheduling of MFA. In Pd phases of pre- and postMFA, the histogram-based motion spectra are biphasic, suggesting two cohorts in the process, one remaining at quiescence and the other involved in shimmering. Under MFA, nPd and Pd spectra were typically Gaussian, suggesting that the nest mates with a uniform workload shifted to higher motion activity. At the end of the MFA, the spectra shift back to the lower motion activities and the Pd spectra form a biphasic again. This happens a few minutes earlier in the peripheral zones than in the mouth zone. Using time profiles of the skewness of the Pd motion spectra, the mass-flight-suspend-defensiveness hypothesis is confirmed, whereby the inhibition of defense ability was found to increase progressively during the MFA. These sawtooth-like time profiles of skewness during MFA show that defense capability is recovered again quite quickly at the end of MFA. Finally, with the help of the Pd motion spectra, clear indications can be obtained that the giant honeybees engage in a decision in the sense of a tradeoff between MFA and collective defensiveness, especially in the regions in the periphery to the mouth zone.

Recent Advances in the Synthesis of the Marine-Derived Alkaloid Fascaplysin and Its Metabolites Homofascaplysins A-C.

The fascaplysin and homofascaplysin class of marine natural products has a characteristic 12H-pyrido[1,2-a:3,4-b']diindole pentacyclic structure. Fascaplysin was isolated in 1988 from the marine sponge Fascaplysinopsis bergquist sp. The analogs of fascaplysin, such as homofascaplysins A, B, and C, were discovered late in the Fijian sponge F. reticulate, and also have potent antimicrobial activity and strong cytotoxicity against L-1210 mouse leukemia. In this review, the total synthesis of fascaplysin and its analogs, such as homofascaplysins A, B, and C, will be reviewed, which will offer useful information for medicinal chemistry researchers who are interested in the exploration of marine alkaloids.

Acremosides A-G, Sugar Alcohol-Conjugated Acyclic Sesquiterpenes from a Sponge-Derived Acremonium Species.

Seven new sugar alcohol-conjugated acyclic sesquiterpenes, acremosides A-G (1-7), were isolated from the cultures of the sponge-associated fungus Acremonium sp. IMB18-086 cultivated with heat-killed Pseudomonas aeruginosa. The structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data. The relative configurations were established by J-based configuration analysis and acetonide derivatization. The absolute configurations were elucidated by the Mosher ester method and ECD calculations. The structures of acremosides E-G (5-7) featured the linear sesquiterpene skeleton with a tetrahydrofuran moiety attached to a sugar alcohol. Acremosides A (1) and C-E (3-5) showed significant inhibitory activities against hepatitis C virus (EC50 values of 4.8-8.8 µM) with no cytotoxicity (CC50 of >200 µM).

Aurantoside L, a New Tetramic Acid Glycoside with Anti-Leishmanial Activity Isolated from the Marine Sponge Siliquariaspongia japonica.

A new tetramic acid glycoside, aurantoside L (1), was isolated from the sponge Siliquariaspongia japonica collected at Tsushima Is., Nagasaki Prefecture, Japan. The structure of aurantoside L (1) composed of a tetramic acid bearing a chlorinated polyene system and a trisaccharide part was elucidated using spectral analysis. Aurantoside L (1) showed anti-parasitic activity against L. amazonensis with an IC50 value of 0.74 µM.

Meroterpenoids from Marine Sponge Hyrtios sp. and Their Anticancer Activity against Human Colorectal Cancer Cells.

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.

The Discovery of Weddellamycin, a Tricyclic Polyene Macrolactam Antibiotic from an Antarctic Deep-Sea-Derived Streptomyces sp. DSS69, by Heterologous Expression.

Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a cryptic gene cluster for the biosynthesis of putative macrolactams was disclosed from a sponge-associated bacterium, Streptomyces sp. DSS69, by genome mining. Cloning and heterologous expression of the whole biosynthetic gene cluster led to the discovery of weddellamycin, a polyene macrolactam bearing a 23/5/6 ring skeleton. A negative regulator, WdlO, and two positive regulators, WdlA and WdlB, involved in the regulation of weddellamycin production were unraveled. The fermentation titer of weddellamycin was significantly improved by overexpression of wdlA and wdlB and deletion of wdlO. Notably, weddellamycin showed remarkable antibacterial activity against various Gram-positive bacteria including MRSA, with MIC values of 0.10-0.83 µg/mL, and antifungal activity against Candida albicans, with an MIC value of 3.33 µg/mL. Weddellamycin also displayed cytotoxicity against several cancer cell lines, with IC50 values ranging from 2.07 to 11.50 µM.

Structural Insights into the Marine Alkaloid Discorhabdin G as a Scaffold towards New Acetylcholinesterase Inhibitors.

In this study, Antarctic Latrunculia sponge-derived discorhabdin G was considered a hit for developing potential lead compounds acting as cholinesterase inhibitors. The hypothesis on the pharmacophore moiety suggested through molecular docking allowed us to simplify the structure of the metabolite. ADME prediction and drug-likeness consideration provided valuable support in selecting 5-methyl-2H-benzo[h]imidazo[1,5,4-de]quinoxalin-7(3H)-one as a candidate molecule. It was synthesized in a four-step sequence starting from 2,3-dichloronaphthalene-1,4-dione and evaluated as an inhibitor of electric eel acetylcholinesterase (eeAChE), human recombinant AChE (hAChE), and horse serum butyrylcholinesterase (BChE), together with other analogs obtained by the same synthesis. The candidate molecule showed a slightly lower inhibitory potential against eeAChE but better inhibitory activity against hAChE than discorhabdin G, with a higher selectivity for AChEs than for BChE. It acted as a reversible competitive inhibitor, as previously observed for the natural alkaloid. The findings from the in vitro assay were relatively consistent with the data available from the AutoDock Vina and Protein-Ligand ANTSystem (PLANTS) calculations.

Attenuation of Nicotine Effects on A549 Lung Cancer Cells by Synthetic α7 nAChR Antagonists APS7-2 and APS8-2.

Nicotine binds to nicotinic acetylcholine receptors (nAChRs) that are overexpressed in different cancer cells, promoting tumor growth and resistance to chemotherapy. In this study, we aimed to investigate the potential of APS7-2 and APS8-2, synthetic analogs of a marine sponge toxin, to inhibit nicotine-mediated effects on A549 human lung cancer cells. Our electrophysiological measurements confirmed that APS7-2 and APS8-2 act as α7 nAChR antagonists. APS8-2 showed no cytotoxicity in A549 cells, while APS7-2 showed concentration-dependent cytotoxicity in A549 cells. The different cytotoxic responses of APS7-2 and APS8-2 emphasize the importance of the chemical structure in determining their cytotoxicity on cancer cells. Nicotine-mediated effects include increased cell viability and proliferation, elevated intracellular calcium levels, and reduced cisplatin-induced cytotoxicity and reactive oxygen species production (ROS) in A549 cells. These effects of nicotine were effectively attenuated by APS8-2, whereas APS7-2 was less effective. Our results suggest that APS8-2 is a promising new therapeutic agent in the chemotherapy of lung cancer.

Growth, filtration and respiration characteristics of small single-osculum demosponge Halichondria panicea explants.

Filter-feeding demosponges are modular organisms that consist of modules each with one water-exit osculum. Once a mature module has been formed, the weight-specific filtration and respiration rates do not change. Sponge modules only grow to a certain size and for a sponge to increase in size, new modules must be formed. However, the growth characteristics of a small single-osculum module sponge are fundamentally different from those of multi-modular sponges, and a theoretically derived volume-specific filtration rate scales as F/V=V-1/3, indicating a decrease with increasing total module volume (V, cm3). Here, we studied filtration rate (F, l h-1), respiration rate (R, ml O2 h-1), volume-specific (F/V) and weight-specific (F/W) filtration rates, and the ratios F/R and F/W along with growth rates of small single-osculum demosponge Halichondria panicea explants of various sizes exposed to various concentrations of algal cells. The following relationships were found: F/V=7.08V-0.24, F=a1W1.05, and R=a2W0.68 where W is the dry weight (mg). The F/R and F/W ratios were constant and essentially independent of W, and other data indicate exponential growth. It is concluded that the experimental data support the theoretical F/V∝V-1/3.

Psammaplin A and Its Analogs Attenuate Oxidative Stress in Neuronal Cells through Peroxisome Proliferator-Activated Receptor γ Activation.

Psammaplins are sulfur containing bromotyrosine alkaloids that have shown antitumor activity through the inhibition of class I histone deacetylases (HDACs). The cytotoxic properties of psammaplin A (1), the parent compound, are related to peroxisome proliferator-activated receptor γ (PPARγ) activation, but the mechanism of action of its analogs psammaplin K (2) and bisaprasin (3) has not been elucidated. In this study, the protective effects against oxidative stress of compounds 1-3, isolated from the sponge Aplysinella rhax, were evaluated in SH-SY5Y cells. The compounds improved cell survival, recovered glutathione (GSH) content, and reduced reactive oxygen species (ROS) release at nanomolar concentrations. Psammaplins restored mitochondrial membrane potential by blocking mitochondrial permeability transition pore opening and reducing cyclophilin D expression. This effect was mediated by the capacity of 1-3 to activate PPARγ, enhancing gene expression of the antioxidant enzymes catalase, nuclear factor E2-related factor 2 (Nrf2), and glutathione peroxidase. Finally, HDAC3 activity was reduced by 1-3 under oxidative stress conditions. This work is the first description of the neuroprotective activity of 1 at low concentrations and the mechanism of action of 2 and 3. Moreover, it links for the first time the previously described effects of 1 in HDAC3 and PPARγ signaling, opening a new research field for the therapeutic potential of this compound family.

Bactericidal effect of bacteria isolated from the marine sponges Hymeniacidon perlevis and Halichondria panicea against carbapenem-resistant Acinetobacter baumannii.

In this study, we evaluated the antimicrobial activity of bacteria isolated from the marine sponges Hymeniacidon perlevis and Halichondria panicea against seven Acinetobacter baumannii strains, the majority of which were clinically relevant carbapenem-resistant A. baumannii strains. We observed the inhibitory activity of 18 (out of 114) sponge-isolated bacterial strains against all A. baumanii strains using medium-throughput solid agar overlay assays. These inhibitory strains belonged to the genera Lactococcus, Pseudomonas, and Vagococcus. In addition, this antimicrobial activity was validated through a liquid co-cultivation challenge using an inhibitory strain of each genus and a green fluorescent protein-tagged A. baumanii strain. Fluorescence measurements indicated that the growth of A. baumanii was inhibited by the sponge isolates. In addition, the inability of A. baumanii to grow after spreading the co-cultures on solid medium allowed us to characterize the activity of the sponge isolates as bactericidal. In conclusion, this study demonstrates that marine sponges are a reservoir of bacteria that deserves to be tapped for antibiotic discovery against A. baumanii.

Heavy metal accumulation analysis using bivalve, sponge, sea urchin, and gastropod species as bioindicators.

A comparative assessment of heavy metal accumulation potential in four distinct marine benthic bioindicators: the bivalve Perna perna, the sponge Callyspongia fibrosa, the sea urchin Tripneustes gratilla, and the gastropod Purpura bufo were conducted. These organisms were collected from the same location, and the concentration of ten heavy metals was analyzed in water, sediment and various body parts of the organisms. The bioaccumulation potential was evaluated using the bio-water accumulation factor and bio-sediment accumulation factor. There was significant variation in the bioaccumulation potential of each organism with respect to different metals. The sponge proved to be a reliable indicator of Cd with a highest concentration of 2.60 µg/g. Sea urchin accumulated high concentrations of Cr (16.98 µg/g) and Pb (4.80 µg/g), whereas Cu was predominant (21.05 µg/g) in gastropod, followed by bivalve (17.67 µg/g). The concentration of metals in hard parts was found to be lower than in the tissues.

Prokaryotic communities of the French Polynesian sponge Dactylospongia metachromia display a site-specific and stable diversity during an aquaculture trial.

Dynamics of microbiomes through time are fundamental regarding survival and resilience of their hosts when facing environmental alterations. As for marine species with commercial applications, such as marine sponges, assessing the temporal change of prokaryotic communities allows us to better consider the adaptation of sponges to aquaculture designs. The present study aims to investigate the factors shaping the microbiome of the sponge Dactylospongia metachromia, in a context of aquaculture development in French Polynesia, Rangiroa, Tuamotu archipelago. A temporal approach targeting explants collected during farming trials revealed a relative high stability of the prokaryotic diversity, meanwhile a complementary biogeographical study confirmed a spatial specificity amongst samples at different longitudinal scales. Results from this additional spatial analysis confirmed that differences in prokaryotic communities might first be explained by environmental changes (mainly temperature and salinity), while no significant effect of the host phylogeny was observed. The core community of D. metachromia is thus characterized by a high spatiotemporal constancy, which is a good prospect for the sustainable exploitation of this species towards drug development. Indeed, a microbiome stability across locations and throughout the farming process, as evidenced by our results, should go against a negative influence of sponge translocation during in situ aquaculture.

Talaromides A-C, Bioactive Cyclic Heptapeptides from Talaromyces siglerae Isolated from a Marine Sponge.

Three new cyclic heptapeptides, talaromides A-C (1-3), were isolated from cultures produced by the fungus Talaromyces siglerae (Ascomycota), isolated from an unidentified sponge. The structures, featuring an unusual proline-anthranilic moiety, were elucidated by analysis of spectroscopic data and chemical transformations, including the advanced Marfey's method and GITC derivatization. Talaromides A and B inhibited migration activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.

Neopetromin, a Cyclic Tripeptide with a C-N Cross-Link, from the Marine Sponge Neopetrosia sp., That Causes Vacuole Fragmentation in Tobacco BY-2 Cells.

HPLC-MS analysis revealed the presence of an unreported peptide in the extract of the marine sponge Neopetrosia sp. Its structure was determined as a tripeptide, named neopetromin (1), composed of two tyrosine and one tryptophan residues with a heteroaromatic C-N cross-link between side chains. The absolute configuration of amino acids was determined using Marfey's method after ozonolysis and hydrolysis of 1. Compound 1 promoted vacuole fragmentation in an actin-independent manner in tobacco BY-2 cells.

Taxonomy of Placospongia Gray, 1867 from Northern and Northeastern Brazil, with description of two new species (Porifera: Demospongiae: Clionaida).

The demosponge genus Placospongia includes 13 valid species, of which six occur in the Brazilian Exclusive Economic Zone. In the present study, we describe two new species of Placospongia from Northern (off the Amazon River mouth) and Northeastern Brazilian continental shelf and oceanic islands (i.e., Fernando de Noronha Archipelago), viz., Placospongia beatrizae sp. nov. and Placospongia amphinolastra sp. nov., and redescribe the holotype of Placospongia cristata Boury-Esnault, 1973, a poorly known species. In addition, we revise the Brazilian records of the allegedly cosmopolitan species P. carinata, P. melobesioides and P. intermedia, and provide new records of P. colombiensis and P. ruetzleri from Brazil. We demonstrate that P. carinata sensu Coelho & Mello-Leito and P. intermedia sensu Muricy & Moraes and Jimenez et al. belong in fact to P. ruetzleri, and that P. melobesioides sensu Mothes et al. and Gonzlez-Faras is a new species, described here as Placospongia beatrizae sp. nov. With the description of the two new species and synonymyzation of previous records, six species of Placospongia are currently known in Brazilian waters, two of which are endemic. A key to Placospongia species is also provided.

A new Acanthotetilla sponge from the Southwest Atlantic (Tetillidae, Spirophorina, Tetractinellida, Demospongiae), with an updated discussion on the diversity, distribution and morphologic characters of Acanthotetilla spp.

Acanthotetilla is a genus of tetillid sponges diagnosed by the presence of medium-sized, heavily spined oxeas, which are known as megacanthoxeas (or simply acanthoxeas). Currently, seven species are known worldwide: three from the Western Atlantic (A. gorgonosclera, A. rocasensis and A. walteri), three from the Western Indian (A. hemisphaerica, A. enigmatica and A. seychellensis) and one from the Western Pacific (A. celebensis). A megacanthoxea-bearing specimen was obtained from the Fernando de Noronha Archipelago, Southwest Atlantic, in 2016. It is described here as a new Acanthotetilla, namely, A. noronhensis sp. nov. This new species has two categories of megacanthoxeas, like A. celebensis from Celebes/Sulawesi Sea, Indonesia. However, the former differs from the latter, as well as from other congeners, by the combination of endolithic habit and spiculation. Acanthotetilla noronhensis sp. nov. is known on the basis of a single specimen from a large collection of sponges from Fernando de Noronha. Besides, the species was not found in other sponge collections from different areas of Brazil, including oceanic areas. Thus, the new species has probably a low abundance and restricted distribution, alike all other known Acanthotetilla species, aside A. celebensis, which (regardless its low abundance) occurs in a large sector of the western Pacific. Despite A. noronhensis sp. nov. and A. celebensis being separated by a wide geographic distance, the unique occurrence of two categories of megacanthoxeas might suggest closer phylogenetic relationship and biogeographic history as well. A wider discussion on the diversity, distribution and morphologic characters of Acanthotetilla spp. is supplied in this study. A comparative taxonomic table and a taxonomic identification key to Acanthotetilla spp. is supplied as well.

New records of demosponges (Porifera) from the South Orkney Islands (Antarctica) with a checklist for the region.

The South Orkney Islands (SOI) is a poorly studied Antarctic archipelago located in the Scotia Arc. In this study, we added 25 Demospongiae species to the SOI known sponge richness, which was previously represented by only 16 species. Of these, 22 species represent new records for SOI region, although they were previously recorded from other Antarctic sectors. Samples were collected during two Argentinean Antarctic Research Cruises onboard RV Puerto Deseado. The most frequently collected species were Artemisina apollinis, Iophon gaussi, I. unicorne, Lissodendoryx (E.) ramilobosa, Myxodoryx hanitschi and Tedania (T.) tantula. Data and illustrations of some rare or uncommon species are provided: Iophon gaussi, Lissodendoryx (E.) anacantha, Microxina charcoti, Raspailia (H.) hentscheli, Haliclona spongiosissima, Haliclona (G.) cf. cucurbitiformis. Although the present results increase substantially the previously known information on sponge species, this is still an underestimation of total richness because certain orders (Tetractinellida, Suberitida, Biemnida, Polymastiida) and classes were not studied during the current investigation, although previous records were included.

Causal effect of porphyria biomarkers on alcohol-related hepatocellular carcinoma through Mendelian Randomization.

PURPOSE: According to some cohort studies, an association exists between acute intermittent porphyria (AIP) and liver cancer. However, establishing a definitive causal relationship between porphyria and hepatocellular carcinoma (HCC) remains challenging. Prexisting studies regarding porphyria biomarkers and alcohol-related hepatocellular carcinoma (AR-HCC) make possible an entry point. In this study, we aimed to investigate the causal relationships between biomarkers of two types of porphyria, AIP and congenital erythropoietic porphyria (CEP), and AR-HCC. METHODS: Single-nucleotide polymorphisms (SNPs) associated with porphobilinogen deaminase (PBGD) and uroporphyrinogen-III synthase (UROS), along with outcome data on AR-HCC, were extracted from public genome-wide association studies (GWAS). The GWAS data were then used to explore the potential causal relationships via a two-sample Mendelian randomization (MR) analysis. The effect estimates were calculated using the random-effect inverse-variance-weighted (IVW) method. Additionally, the Cochrane's Q test, MR-Egger test, and leave-one-out analysis were conducted to detect heterogeneity and pleiotropy in the MR results. RESULTS: Using the IVW method as the primary causal effects model in the MR analyses, we found that both PBGD (effect estimate = 1.51; 95% CI, from 1.08 to 2.11, p = 0.016) and UROS (effect estimate = 1.53; 95% CI, from 1.08 to 2.18, p = 0.018) have a significant causal effect on AR-HCC. CONCLUSION: Our findings revealed a causal effect of both PBGD and UROS on AR-HCC, suggesting that both AIP and CEP have a causal association with AR-HCC.