Ultrashort Cell-Penetrating Peptides for Enhanced Sonophoresis-Mediated Transdermal Transport.

The skin is a key site for drug administration because of its large surface area and noninvasive accessibility. However, the dermal architecture serves as an excellent barrier, protecting from external mechanical, chemical, microbial, and physical perturbations. Most drugs display poor permeability through this barrier, thus making dermal and subdermal delivery challenging. Cell-penetrating peptides (CPPs), a diverse group of relatively short cationic and amphipathic membrane-interacting peptides, are fast becoming an important class of drug carriers and could potentially be developed for the dermal delivery of active molecules. However, the mechanism of CPP transdermal delivery is not fully understood, and there is a genuine need for a minimal model to understand this important phenomenon. Here, we demonstrate the potent membrane interactions of a minimal four-amino-acid-long CPP as well as the significance of guanidinium patterning and cationic nature of this palindromic peptide on its bioactivity. Furthermore, we demonstrate the biocompatibility of this peptide as well as its rapid cellular uptake and endosomal distribution. Finally, by utilizing a porcine full-thickness skin model, we demonstrate the substantial independent dermal and sonophoresis-based transdermal penetration of this minimal model. These results provide a minimal model for CPPs which can be easily manipulated for further biophysical and biochemical evaluations as well as a potent functional CPP with excellent skin permeability, which can be utilized for a wide variety of cosmetic and medical applications.

Reproductive strategies of the coral Turbinaria reniformis in the northern Gulf of Aqaba (Red Sea).

Here we describe for the first time the reproductive biology of the scleractinian coral Turbinaria reniformis studied during three years at the coral reefs of Eilat and Aqaba. We also investigated the possibility of sex change in individually tagged colonies followed over a period of 12 years. T. reniformis was found to be a stable gonochorist (no detected sex change) that reproduces by broadcast spawning 5-6 nights after the full moon of June and July. Spawning was highly synchronized between individuals in the field and in the lab. Reproduction of T. reniformis is temporally isolated from the times at which most other corals reproduce in Eilat. Its relatively long reproductive cycle compared to other hermaphroditic corals may be due to the high reproductive effort associated with the production of eggs by gonochoristic females. Sex ratio in both the Aqaba and Eilat coral populations deviated significantly from a 1:1 ratio. The larger number of males than of females may provide a compensation for sperm limitation due to its dilution in the water column. We posit that such sex allocation would facilitate adaptation within gonochoristic species by increasing fertilization success in low density populations, constituting a phenomenon possibly regulated by chemical communication.

Fast neurotransmission related genes are expressed in non nervous endoderm in the sea anemone Nematostella vectensis.

Cnidarian nervous systems utilize chemical transmission to transfer signals through synapses and neurons. To date, ample evidence has been accumulated for the participation of neuropeptides, primarily RFamides, in neurotransmission. Yet, it is still not clear if this is the case for the classical fast neurotransmitters such as GABA, Glutamate, Acetylcholine and Monoamines. A large repertoire of cnidarian Fast Neurotransmitter related Genes (FNGs) has been recently identified in the genome of the sea anemone, Nematostella vectensis. In order to test whether FNGs are localized in cnidarian neurons, we characterized the expression patterns of eight Nematostella genes that are closely or distantly related to human central and peripheral nervous systems genes, in adult Nematostella and compared them to the RFamide localization. Our results show common expression patterns for all tested genes, in a single endodermal cell layer. These expressions did not correspond with the RFamide expressing nerve cell network. Following these results we suggest that the tested Nematostella genes may not be directly involved in vertebrate-like fast neurotransmission.

Macroalgae in the coral reefs of Eilat (Gulf of Aqaba, Red Sea) as a possible indicator of reef degradation.

The current state of health of the coral reefs in the northern Gulf of Aqaba (Red Sea), notably the Eilat reefs, is under debate regarding both their exact condition and the causes of degradation. A dearth of earlier data and unequivocal reliable indices are the major problems hinder a clear understanding of the reef state. Our research objective was to examine coral-algal dynamics as a potential cause and an indication of reef degradation. The community structure of stony corals and algae along the northern Gulf of Aqaba reveal non-seasonal turf algae dominancy in the shallow Eilat reefs (up to 72%), while the proximate Aqaba reefs present negligible turf cover (<6%). We believe that turf dominancy can indicate degradation in these reefs, based on the reduction in essential reef components followed by proliferation of perennial turf algae. Our findings provide further evidence for the severe state of the Eilat coral reefs.

Photoreactivation is the main repair pathway for UV-induced DNA damage in coral planulae.

The larvae of most coral species spend some time in the plankton, floating just below the surface and hence exposed to high levels of ultraviolet radiation (UVR). The high levels of UVR are potentially stressful and damaging to DNA and other cellular components, such as proteins, reducing survivorship. Consequently, mechanisms to either shade (prevent) or repair damage potentially play an important role. In this study, the role of photoreactivation in the survival of coral planulae was examined. Photoreactivation is a light-stimulated response to UV-damaged DNA in which photolyase proteins repair damaged DNA. Photoreactivation rates, as well as the localization of photolyase, were explored in planulae under conditions where photoreactivation was or was not inhibited. The results indicate that photoreactivation is the main DNA repair pathway in coral planulae, repairing UV-induced DNA damage swiftly (K=1.75 h(-1) and a half-life of repair of 23 min), with no evidence of any light-independent DNA repair mechanisms, such as nucleotide excision repair (NER), at work. Photolyase mRNA was localized to both the ectoderm and endoderm of the larvae. The amount of cell death in the coral planulae increased significantly when photoreactivation was inhibited, by blocking photoreactivating light. We found that photoreactivation, along with additional UV shielding in the form of five mycosporine-like amino acids, are sufficient for survival in surface tropical waters and that planulae do not accumulate DNA damage despite being exposed to high UVR.

Energy integration between the solitary polyps of the clonal coral Lobophyllia corymbosa.

Clonal integration in the coral Lobophyllia corymbosa was studied from two perspectives: transfer of carbon among clonemates and allorecognition. This coral forms colonies in the early post-metamorphic stages. In later ontogeny, the tissues interconnecting polyps die, transforming the colony into a clone of solitary polyps. These polyps continue to live in close proximity but without tissue continuity. Isolated polyps labeled with radioactive carbon in the light showed oriented transfer of assimilates towards adjacent, injured polyps. No significant transfer of carbon was observed towards intact, isogeneic polyps or allogeneic polyps. Grafting of coral tissues resulted in intra-clonal fusion, but only when polyps were previously sectioned. Allogeneic sectioned grafts were always rejected. Intact polyps were unresponsive towards isogeneic and allogeneic counterparts when grafted. Our results show that isolated Lobophyllia polyps not only recognize their clonemates as such, but also help them when necessary, although no tissue continuity exists between them.

The effect of gravity on coral morphology.

Coral morphological variability reflects either genetic differences or environmentally induced phenotypic plasticity. We present two coral species that sense gravity and accordingly alter their morphology, as characterized by their slenderness (height to diameter) ratio (SR). We experimentally altered the direction (and intensity) of the gravitational resultant force acting along or perpendicular to the main body axis of coral polyps. We also manipulated light direction, in order to uncouple gravity and light effects on coral development. In the experiments, vertically growing polyps had significantly higher SR than their horizontal siblings even when grown in a centrifuge (experiencing different resultant gravitational forces in proximal and distal positions). Lowest SR was in horizontal side-illuminated polyps, and highest in vertical top-illuminated polyps. Adult colonies in situ showed the same pattern. Gravitational intensity also affected polyp growth form. However, polyp volume, dry skeleton weight and density in the various centrifuge positions, and in aquaria experiments, did not differ significantly. This reflects the coral's ability to sense altered gravity direction and intensity, and to react by changing the development pattern of their body morphology, but not the amount of skeleton deposited.