A Synthetic Peptide Fragment Derived from RANTES is a Potent Inhibitor of HIV-1 Infectivity Despite a Surprising Lack of CCR5 Receptor Affinity

Summary CCR5 (CC-chemokine receptor 5) is a key co-receptor, in concert with CD4, for infectivity of HIV-1 (human immunodeficiency virus type-1) into healthy human cells, and RANTES, an endogenous ligand for CCR5, is a potent inhibitor of HIV-1 infectivity. In this structure-activity relationship (SAR) study, peptide fragments derived from RANTES were designed, synthesized and evaluated for their ability to inhibit HIV-1 infectivity. The goal was to determine the effect of peptide length on anti-HIV activity and to obtain an optimally sized RANTES peptide probe for further SAR studies. The analogue Ac[Ala^10,11]RANTES-(1–14)NH₂, AA14, was identified as an effective inhibitor of HIV-1 infectivity at 10 nM but despite the functional activity, surprisingly it did not exhibit any notable affinity for the CCR5 chemokine receptor. Further, increasing peptide size enhanced neither the inhibition of HIV-1 infectivity nor CCR5 receptor affinity. As a potent inhibitor of HIV-1 infectivity, the lead analogue most likely utilizes a different (and currently unknown) mechanism than interaction with CCR5 for anti-HIV activity.     

Ontogeny of the Alimentary Canal and Respiratory Physiology of Larval Hoplosternum littorale (Hancock, 1828): an Intestinal Air-Breathing Teleost

Synopsis Newly hatched larval Hoplosternum littorale do not exhibit bimodal respiration upon hatching but depend initially on branchial respiration. As the respiratory intestine develops, its increasing length leads to an increasing dependence on aerial respiration. The respiratory intestine first appears when the fish is 9 days old but is microscopic at this age and becomes detectable by gross morphological examination at 13 days old. Development of the gut for the remainder of the juvenile period (up to 32 days old) consists of increasing length, mucosal folding, concentration of taste buds, gastric glands, mucous glands and goblet cells. Stage 1 commenced with newly hatched larvae until the larval fish were 11 days old. During this stage the fish did not have the capacity to air-breathe and thus behaved as oxygen conformers. Stage 2 extended from day 12 to day 23 and the fish had the capacity to air-breathe although the respiratory intestine was still developing. Stage 3 began from day 24 to day 32 and at this point the respiratory intestine was well-developed and functioned efficiently. The rate of oxygen consumption of the larval fish was found to be related to dissolved oxygen concentration, age of the larval fish and various interactions of these two factors.     

Trade-off between digestion and respiration in two airbreathing callichthyid catfishes Holposternum littorale (Hancock) and Corydoras aeneus (Gill)

In callichthyid catfishes, the posterior intestine is modified to function as an air breathing organ by being air-filled, thin-walled and highly vascularized. These modifications make it unsuitable for digestive functions and digesta has to be transported quickly through this region to minimize disruption of vital respiratory functions. However, the weak muscles of the wall of the respiratory intestine make this problematic. It is hypothesized that the unidirectional ventilatory air current within the respiratory intestine is responsible for the quick transport of digesta through the respiratory intestine. To verify this, movement of digesta through the alimentary tract was examined in Hoplosternum littorale and Corydoras aeneus that were either allowed to breathe air or prevented from air breathing. When air breathing was prevented, digesta was not transported to the rectum in H. littorale and there was a 94% reduction in the amount of digesta in the rectum of C. aeneus. This study suggests that the anterior digestive intestine facilitates the passage of air although it is filled with digesta. The anterior digestive intestine packages digesta into a string of slightly compressed boluses, creating an air channel in the digestive intestine thus allowing air to pass unimpeded.