What can be learnt from analysing insect orientation flights using probabilistic SLAM?

In this paper, we provide an analysis of orientation flights in bumblebees, employing a novel technique based on simultaneous localisation and mapping (SLAM) a probabilistic approach from autonomous robotics. We use SLAM to determine what bumblebees might learn about the locations of objects in the world through the arcing behaviours that are typical of these flights. Our results indicate that while the bees are clearly influenced by the presence of a conspicuous landmark, there is little evidence that they structure their flights to specifically learn about the position of the landmark.     

Spirochete round bodies Syphilis, Lyme disease & AIDS: Resurgence of “the great imitator”?

We advocate investigation of spirochete cyclical symbioses (e.g.,Borrelia sp.,Leptospira sp., Treponema sp.) given the newly established verification of a developmental history in these gram-negative motile helical eubacteria, both in pure culture and in mammals. Symbiotic spirochetes can be compared to free-living relatives for their levels of integration (behavioral, metabolic, gene product or genetic levels), Detailed research that correlates life histories of symbiotic spirochetes to changes in the immune system of associated vertebrates is sorely needed. Genome analyses show that in necrotrophic symbioses (Borrelia andTreponema sp.) of humans and other primates, integration of the bionts occurs at the gene product and genetic level. Spirochete round bodies (also called cysts, L-forms and sphaeroplasts) can be induced by many types of unfavorable conditions (e.g., threats of starvation, desiccation, oxidation, penicillin and other antibiotics). Reversion to familiar helical, motile active swimmers by placement of pure cultures into favorable environments in some cases can be controlled. These observations are supported by a European literature, especially Russian, apparently unknown to American medicine and medical research.     

Distribution of modern salt-marsh foraminifera in the Albemarle–Pamlico estuarine system of North Carolina, USA: Implications for sea-level research

We described the distributions of foraminifera from ten physiographically distinct salt marshes in the Albemarle–Pamlico estuarine system, North Carolina using 193 surface samples. We defined elevation-dependent ecological zones at individual sites using cluster analysis and detrended correspondence analysis. Additionally, seven principal biozones of salt-marsh foraminifera were identified that have distinctive spatial distributions reflecting a pattern of salinity regimes caused by the current configuration of barrier-island inlets. High salinity sites along the southern Outer Banks are associated with sub-tidal calcareous assemblages, low marshes dominated by Miliammina fusca and high marsh environments defined by Haplophragmoides wilberti, Trochammina inflata and Arenoparrella mexicana. In contrast, lower salinity marshes have Ammobaculites spp. in sub-tidal settings, Miliammina fusca-dominated low marshes and high marsh settings characterized by Jadammina macrescens. Spatial variation of foraminiferal populations and the potential for biozones to migrate in response to changing inlet configuration and salinity, suggests that datasets of modern salt-marsh foraminifera from multiple environments would be appropriate for reconstructing Holocene relative sea level in North Carolina.     

DNA gyrase (GyrB)/topoisomerase IV (ParE) inhibitors: Synthesis and antibacterial activity

The synthesis and antibacterial activities of three chemotypes of DNA supercoiling inhibitors based on imidazolo[1,2-a]pyridine and [1,2,4]triazolo[1,5-a]pyridine scaffolds that target the ATPase subunits of DNA gyrase and topoisomerase IV (GyrB/ParE) is reported. The most potent scaffold was selected for optimization leading to a series with potent Gram-positive antibacterial activity and a low resistance frequency.     

5-Aminopyrimidin-2-ylnitriles as Cathepsin K inhibitors

A series of pyrimidine nitrile inhibitors of Cathepsin K with reduced glutathione reactivity has been identified and Molecular Core Matching (MoCoM) has been used to quantify the effect of an amino substituent at C5.     

Design and efficient synthesis of novel arylthiourea derivatives as potent hepatitis C virus inhibitors

A novel class of arylthiourea HCV inhibitors bearing various functionalities, such as cyclic urea, cyclic thiourea, urea, and thiourea, on the alkyl linker were designed and synthesized. Herein we report the synthesis and structure–activity relationships (SARs) of this novel class of arylthiourea derivatives that showed potent inhibitory activities against HCV in the cell-based subgenomic HCV replicon assay. Among compounds tested, the new carbazole derivative 64, which has an eight-carbon linkage between the phenyl and carbazole rings and a tolyl group at the N-9 position of carbazole, was found to possess strong anti-HCV activity (EC₅₀ = 0.031 μM), lower cytotoxicity (CC₅₀ >50 μM), and higher selectivity index (SI >1612) compared to its derivatives.     

Identification of potent pyrimidine inhibitors of phosphodiesterase 7 (PDE7) and their ability to inhibit T cell proliferation

A series of pyrimidine based inhibitors of PDE7 are discussed. The synthesis, structure–activity relationships (SAR) and selectivity against several other PDE family members as well as activity in T cells are presented. These compounds were found to have effects on T cell proliferation, however it is not clear whether the mechanism is related to PDE7 inhibition.     

Discovery of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine scaffold as a novel,potent and selective GABAA α5 inverse agonist series

Through iterative design cycles we have discovered a number of novel new classes where the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine was deemed the most promising GABA_A α5 inverse agonist class with potential for cognitive enhancement. This class combines a modest subtype binding selectivity with inverse agonism and has the most favourable molecular properties for further lead optimisation towards a central nervous system (CNS) acting medicine.