8-Mercaptoguanine-based inhibitors of Mycobacterium tuberculosis dihydroneopterin aldolase: synthesis,in vitro inhibition and docking studies

The dihydroneopterin aldolase (DHNA, EC 4.1.2.25) activity of FolB protein is required for the conversion of 7,8-dihydroneopterin (DHNP) to 6-hydroxymethyl-7,8-dihydropterin (HP) and glycolaldehyde (GA) in the folate pathway. FolB protein from Mycobacterium tuberculosis (MtFolB) is essential for bacilli survival and represents an important molecular target for drug development. S8-functionalized 8-mercaptoguanine derivatives were synthesised and evaluated for inhibitory activity against MtFolB. The compounds showed IC₅₀ values in the submicromolar range. The inhibition mode and inhibition constants were determined for compounds that exhibited the strongest inhibition. Additionally, molecular docking analyses were performed to suggest enzyme-inhibitor interactions and ligand conformations. To the best of our knowledge, this study describes the first class of MtFolB inhibitors.     

Island shape,size, and isolation affect nest‐site selection by Little Terns

ABSTRACT Populations of many seabirds and other species that nest along coasts are declining due to habitat degradation and loss. An improved understanding of the species‐specific factors that determine nest density across a landscape is therefore critical for conservation efforts. We examined factors that affected the density (number per hectare) and abundance (number at a sampling site) of nests of Little Terns (Sternula albifrons) on the Sinai Peninsula, Egypt. Terns preferred to nest on islands rather than the mainland, with islands constituting 64% of the area surveyed, but containing 99% of the 439 tern nests we found. Nest densities were highest on islands that were small, located at moderate distances from the mainland, and irregularly shaped or elongated. Most nests (69%) were on islands with areas < 3 ha, although these islands represented < 5% of total island area, and islands with the highest nest densities were 80–300 m from the mainland. Terrestrial predators were more likely to occur on larger islands, visiting three of the largest four islands. Most tern nests were within 1 m of shorelines, causing island perimeter to be a strong influence on nest density. Island shape was the only factor that significantly affected nest abundance, with more nests on islands with relatively long perimeters for their size. Our results suggest that protection or creation of relatively small, slender islands at moderate distances from shore may be an effective means of increasing the number of breeding sites for Little Terns. Although not generally considered a potential determinant of nest site preferences for seabirds, island shape is likely to be important for species that prefer sites adjacent to water, including species that nest on beaches and seaside cliffs.     

Conspecifics and Their Posture Influence Site Choice and Oviposition in the Damselfly Argia moesta

Finding a suitable oviposition site can be costly because of energy and time requirements, and ovipositioning can be dangerous because of the risk of predation and harassment by males. The damselfly Argia moesta oviposits, contact-guarded by her mate, on vegetation in streams. Oviposition aggregations are commonly observed in this species, despite their territorial nature during other behaviors. We conducted experiments in the field to test the hypothesis that aggregations are the result of conspecific attraction. In the first experiment, two oviposition sites (sycamore leaves) were provided, one with models of ovipositing pairs, and one without. In the second experiment, one leaf again had ovipositing models, while the other had models of uncoupled males and females in a resting posture. In both experiments, damselfly pairs preferred the site with ovipositing models. In general, they visited the ovipositing models first more often than expected by chance, stayed longer there, were more likely to oviposit there, and laid a greater total number of eggs there. These results support the hypothesis that conspecific attraction is responsible for ovipositing aggregations in A. moesta and that posture is an important cue for attraction. Using conspecific cues could be a beneficial strategy to save in search costs while taking advantage of the presence of ovipositing conspecifics to dilute the effects of harassment and predation.     

On Lithobiidae from the Seychelles with descriptions of two new species of the subgenus Australobius, genus Lithobius (Chilopoda: Lithobiomorpha)

Three species of Lithobius, L. sechellarum Brölemann, L. inflatitarsis sp. nov. and L. abbreviate sp. nov., are described from the Seychelles. All belong to the oriental subgenus Australobius which is reviewed. The species are believed to be endemic and thus support the view that the Seychellean fauna is akin to that of the Oriental Region.     

The lived experience of depression: a bottom-up review co-written by experts by experience and academics

We provide here the first bottom-up review of the lived experience of depression, co-written by experts by experience and academics. First-person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of depression, family members and carers, representing a global network of organizations. The material was enriched by phenomenologically informed perspectives and shared with all collaborators in a cloud-based system. The subjective world of depression was characterized by an altered experience of emotions and body (feeling overwhelmed by negative emotions, unable to experience positive emotions, stuck in a heavy aching body drained of energy, detached from the mind, the body and the world); an altered experience of the self (losing sense of purpose and existential hope, mismatch between the past and the depressed self, feeling painfully incarcerated, losing control over one's thoughts, losing the capacity to act on the world; feeling numb, empty, non-existent, dead, and dreaming of death as a possible escape route); and an altered experience of time (experiencing an alteration of vital biorhythms, an overwhelming past, a stagnation of the present, and the impossibility of the future). The experience of depression in the social and cultural context was characterized by altered interpersonal experiences (struggling with communication, feeling loneliness and estrangement, perceiving stigma and stereotypes), and varied across different cultures, ethnic or racial minorities, and genders. The subjective perception of recovery varied (feeling contrasting attitudes towards recovery, recognizing recovery as a journey, recognizing one's vulnerability and the need for professional help), as did the experience of receiving pharmacotherapy, psychotherapy, and social as well as physical health interventions. These findings can inform clinical practice, research and education. This journey in the lived experience of depression can also help us to understand the nature of our own emotions and feelings, what is to believe in something, what is to hope, and what is to be a living human being.