Identification of A Novel Class of Benzofuran Oxoacetic Acid-Derived Ligands that Selectively Activate Cellular EPAC1

Cyclic AMP promotes EPAC1 and EPAC2 activation through direct binding to a specific cyclic nucleotide-binding domain (CNBD) within each protein, leading to activation of Rap GTPases, which control multiple cell responses, including cell proliferation, adhesion, morphology, exocytosis, and gene expression. As a result, it has become apparent that directed activation of EPAC1 and EPAC2 with synthetic agonists may also be useful for the future treatment of diabetes and cardiovascular diseases. To identify new EPAC agonists we have developed a fluorescent-based, ultra-high-throughput screening (uHTS) assay that measures the displacement of binding of the fluorescent cAMP analogue, 8-NBD-cAMP to the EPAC1 CNBD. Triage of the output of an approximately 350,000 compound screens using this assay identified a benzofuran oxaloacetic acid EPAC1 binder (SY000) that displayed moderate potency using orthogonal assays (competition binding and microscale thermophoresis). We next generated a limited library of 91 analogues of SY000 and identified SY009, with modifications to the benzofuran ring associated with a 10-fold increase in potency towards EPAC1 over SY000 in binding assays. In vitro EPAC1 activity assays confirmed the agonist potential of these molecules in comparison with the known EPAC1 non-cyclic nucleotide (NCN) partial agonist, I942. Rap1 GTPase activation assays further demonstrated that SY009 selectively activates EPAC1 over EPAC2 in cells. SY009 therefore represents a novel class of NCN EPAC1 activators that selectively activate EPAC1 in cellulae

Plant-dwelling spider communities of three developmental phases in primeval oak-lime-hornbeam forest in the Białowieża National Park, Poland

The Białowieża Forest is the only place in Europe where the full development cycle of temperate forest can be observed on a large scale, starting from the regeneration phase until the terminal (decay) phase. At present, the terminal phase is not observed in most forests in Europe due to management practices such as logging and removal of dead trees. In this study, we analysed plant-dwelling spider communities in three developmental phases (optimal, terminal and regeneration) of a primeval oak-lime-hornbeam stand in the Białowieża National Park. Spiders were sampled from May to October in 1998 and 1999 using a sweep net. A total of 3693 spider individuals from 13 families were collected, of which 2278 were identified at the species level. In total, 63 spider species were recorded (including species identified based only on juvenile individuals): 33 in the optimal phase, 36 in the terminal phase, and 41 in the regeneration phase. The composition of plant-dwelling spider communities in three developmental phases was similar. Among adult individuals, Linyphia triangularis (Clerck, 1757) was the most numerous species on the plot in the optimal phase, whereas Bathyphantes nigrinus (Westring, 1851) was the most abundant species on the plots in the terminal and regeneration phases of the stand development. Significantly higher species diversity (calculated for the whole study period) was found in the regeneration and optimal phases compared to the terminal phase. We revealed no difference in the abundance, species richness, and species diversity (calculated per sample) between the analysed plots. On the other hand, each of the developmental stages was characterised by a significant proportion of exclusive species, even though they were represented by a few individuals. This suggests that the presence of different forest stages in a given area favours higher species diversity

An assessment of weed flora and orthopteran diversity in winter cereals cultivated in organic and conventional systems

W pracy przeanalizowano różnorodność gatunkową oraz liczebność flory segetalnej i owadów z rzędu prostoskrzydłych, występujących w zbożach ozimych uprawianych w systemie ekologicznym i konwencjonalnym. Badania przeprowadzono w 2012 r., na wybranych gruntach, użytkowanych zgodnie z zasadami rolnictwa ekologicznego oraz na działkach użytkowanych konwencjonalnie, zlokalizowanych na terenie województwa lubelskiego. Nie stwierdzono istotnych różnic w liczbie gatunków chwastów w uprawach ekologicznych i konwencjonalnych, ale zbiorowiska różniły się pod względem jakościowym. Spośród 95 wykazanych gatunków chwastów, 17 wystąpiło tylko w systemie ekologicznym, a 15 – wyłącznie w uprawach konwencjonalnych. Liczebność chwastów w uprawach zbóż ozimych w systemie ekologicznym była istotnie większa (o 45%) niż w uprawach konwencjonalnych. Nie stwierdzono istotnych różnic w bogactwie gatunkowym i liczebności owadów prostoskrzydłych, występujących w uprawach ekologicznych i konwencjonalnych, ale wystąpiły różnice w liczebności poszczególnych rodzin.The diversity of weed flora and Orthoptera insects in winter cereals cultivated in organic and conventional system was analyzed. The study was carried out in 2012 on selected organic and conventional fields in the Lublin voivodeship. There were no statistical differences in the number of weed species between organic and conventional fields, but there were qualitative differences between weed communities. From among 95 weed species, 17 occurred only on organic fields and 15 were found exclusively on conventional fields. The number of weeds in winter cereals cultivated in organic system was significantly higher (by 45%) than in conventional system. There were no significant differences in species richness and the number of Orthoptera insects between organic and conventional fields, but there were some differences in the number of individuals representing particular families of Orthoptera

Tourism disassembles patterns of co-occurrence and weakens responses to environmental conditions of spider communities on small lake islands

The impact of disturbance on animal and plant assemblages has been described mainly in terms of aggregate community properties like species richness, abundance, or productivity. However, the question how disturbance acts on species interactions, particularly on patterns of co-occurrence, has received much less attention. Here we use a large pitfall trap sample of spiders from two complexes of lake islands in Northern Poland to show how disturbance by tourist visits affects species richness, composition and co-occurrence. On the pristine and protected islands of Lake Wigry, species co-occurrence was significantly segregated. Further, island species richness and abundances could be predicted from environmental correlates, particularly from island area, soil fertility and humidity. In turn, on the lake islands that are frequently visited by tourists, species co-occurrences were random and environmental correlates other than island area failed to predict species richness and abundances. However, species composition, α-, β-, and γ-diversities, as well as average local spider abundances did not significantly differ between both island complexes. Our results show that disturbance disassembles the structure of spider communities prior to visible richness and abundance effects. This result has implications for biological conservation. The detection of community disassembly might be an early sign for factors that act negatively on ecosystem functioning