We have synthesized 50 benzimidazole (BMZ) derivatives with 1,2‐phenylenediamines and aromatic aldehydes under mild oxidation conditions by using inexpensive, nontoxic inorganic salt sodium metabisulfite in a one‐pot condensation reaction and screened their ability to interfere with Zika virus (ZIKV) infection utilizing a cell‐based phenotypic assay. Seven BMZs inhibited an African ZIKV strain with a selectivity index (SI=CC50/EC50) of 9–37. Structure‐activity relationship analysis demonstrated that substitution at the C‐2, N‐1, and C‐5 positions of the BMZ ring were important for anti‐ZIKV activity. The hybrid structure of BMZ and naphthalene rings was a structural feature responsible for the high anti‐ZIKV activity. Importantly, BMZs inhibited ZIKV in human neural stem cells, a physiologically relevant system considering the severe congenital anomalies, like microcephaly, caused by ZIKV infection. Compound 39 displayed the highest antiviral efficacy against the African ZIKV strain in Huh‐7 (SI>37) and neural stem cells (SI=12). Compound 35 possessed the highest activity in Vero cells (SI=115). Together, our data indicate that BMZs derivatives have to be considered for the development of ZIKV therapeutic interventions.

Although fishes by nature are aquatic, many species reproduce in such a way that their embryos are exposed to air either occasionally or constantly during incubation. We examine the ecological context and review specific examples of reproduction by fishes at the air-water interface, including fishes that do and do not breathe air. Four modes of reproduction at the air-water interface are described across 18 teleost Orders, from fresh water, estuaries and sea water. Mode 1, the most common type of reproduction by fishes at the air-water interface, includes 21 Families of mostly marine teleosts that spawn in water onto a substrate surface, on vegetation, or into hollow objects such as shells that will later be continuously or occasionally exposed to air. Although the eggs are emerged into air, many of these species do not emerge into air as adults, and only about half of them breathe air. Mode 2 involves six Families of freshwater fishes setting up and guarding a nest and guarding on the water surface, either with bubbles or in vegetation. Most of these species breathe air. In Mode 3, annual killifishes in at least two Families in seasonally dry habitats bury eggs in mud in temporary pools, then die before the next generation emerges. These species neither guard nests nor breathe air. Mudskippers (Gobiidae) breathe air and use Mode 4, excavating burrows in a soft substrate and then storing air in a subterranean chamber. In a variation of Mode 4, eggs are placed on bubbles within a nesting burrow by swamp eels (Synbranchidae). No fishes from basal taxa are known to place their embryos where they will be exposed to air, although most of these species breathe air as adults. The widespread but still rare, diverse forms of fish reproduction at the air-water interface across a broad taxonomic spectrum suggest repeated independent evolutionary events and strong selection pressure for adult fishes to protect their embryos from hypoxic waters, aquatic predators, pathogens, and UV radiation. Air-breathing by adult fishes appears to be de-coupled from air exposure of developing embryos or aerial emersion of adults during spawning.

BackgroundMudskippers are amphibious fishes that use their pectoral fins to move on land. Their pectoral fins are specifically modified for terrestrial locomotion. Studies of the anatomy and kinematics of adult mudskippers suggest that modifications of the pectoral fins, such as their protrusion and elongation of the proximal radials, may provide greater control and flexibility in pectoral fin–based locomotion. However, it is unknown when and how the unique features of these pectoral fins form during the development of mudskippers, which begin life as a planktonic organism.ResultsHere we examined the developmental process of the pectoral fins of the mudskipper Periophthalmus modestus to address these questions. We also observed other developmental characteristics to provide clarified descriptions, including indicative morphological changes that occur during metamorphosis.ConclusionOur results show that the localized cell division of the proximal part of the endoskeletal disc—the primordium of the proximal radials—and subsequent cell division along the proximal-distal axis, which is restricted to the distal part of the disc during the larva-to-juvenile transition (metamorphosis), lead to the elongation of the proximal radials.Electronic supplementary materialThe online version of this article (10.1186/s40851-018-0105-z) contains supplementary material, which is available to authorized users.

No abstract

There has been a long-standing controversy about whether vertebrates emerged in the Paleozoic from marine or freshwater environments. Several hypotheses have proposed coastal, estuarine and riparian areas as sites of the transition. Here, we report the ecology of an amphibious fish Periophthalmodon septemradiatus, which we presume is in the process of niche expansion into terrestrial habitats from estuarine to freshwater environments along the Mekong River, Vietnam. Adult fish are highly terrestrial and have not been observed to venture into water during our survey. Courtship behaviour was observed, and fertilised eggs were recovered from burrows in both brackish and freshwater environments. The smallest fish collected at 12, 96, and 148 km from the river mouth were juveniles shortly after starting an amphibious life. These findings suggest reproduction in both brackish and freshwater environments. In contrast, otolith Sr:Ca ratio indicates larval hatching only in brackish water. Analysis of a 940-base pair (bp) segment of the mitochondrial cytochrome c oxidase subunit II and a 934-bp segment of the mitochondrial D-loop demonstrated no genetic segregation between populations. The fish may provide a unique opportunity to study how ambient salinity affects the biology and ecology of a living vertebrate during transition from water to land.