c-di-GMP-mediated regulation of virulence and biofilm formation

It is now apparent that the signaling molecule 3',5'-cyclic diguanylic acid (c-di-GMP) is a central regulator of the prokaryote biofilm lifestyle and recent evidence also links this molecule to virulence. Environmentally responsive signal transduction systems that control expression and/or activity of the enzymes (GGDEF and EAL domain containing proteins) that are responsible for synthesis and degradation of c-di-GMP have recently been identified. Members of the phosphorelay family feature prominently amongst these systems, which include several with hybrid polydomain sensors and one that is similar to well-characterized chemotaxis-controlling pathways. These findings support the hypothesis that c-di-GMP levels are tightly controlled in response to a broad range, in terms of both diversity and intensity, of extracellular signals. Insight into how c-di-GMP affects changes in gene expression and/or protein activity has come from the demonstration that proteins containing the PilZ domain can bind c-di-GMP and control phenotypes involved in biofilm formation and virulence. These recent developments should pave the way for researchers to answer the important question of how a vast array of extracellular signals that are sensed by multiple sensory transduction pathways which all lead to the production or destruction of c-di-GMP are coordinated such that the appropriate phenotypic response is produced.     

Patterns and predictors of condition indices in a critically endangered fish

Hydrobiologia - Condition indices are key predictors of health and fitness in wild fish populations. Variation in body condition, therefore, can be used to identify stressful conditions that may...     

Foraging habits in a generalist predator: Sex and age influence habitat selection and resource use among bottlenose dolphins (Tursiops truncatus)

This study examines resource use (diet, habitat use, and trophic level) within and among demographic groups (males, females, and juveniles) of bottlenose dolphins (Tursiops truncatus). We analyzed the δ¹³C and δ¹⁵N values of 15 prey species constituting 84% of the species found in stomach contents. We used these data to establish a trophic enrichment factor (TEF) to inform dietary analysis using a Bayesian isotope mixing model. We document a TEF of 0‰ and 2.0‰ for δ¹³C and δ¹⁵N, respectively. The dietary results showed that all demographic groups relied heavily on low trophic level seagrass‐associated prey. Bayesian standard ellipse areas (SEA_b) were calculated to assess diversity in resource use. The SEA_b of females was nearly four times larger than that of males indicating varied resource use, likely a consequence of small home ranges and habitat specialization. Juveniles possessed an intermediate SEA_b, generally feeding at a lower trophic level compared to females, potentially an effect of natal philopatry and immature foraging skills. The small SEA_b of males reflects a high degree of specialization on seagrass associated prey. Patterns in resource use by the demographic groups are likely linked to differences in the relative importance of social and ecological factors.     

Ecological dynamics of emerging bat virus spillover

Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.     

Combining tree-ring analyses on stems and coarse roots to study the growth dynamics of forest trees: a case study on Norway spruce (Picea abies [L.] H. Karst)

We show the potential of a new method combining tree-ring analyses on stems and on coarse roots of individual trees in order to advance the understanding of growth dynamics in forest trees. To this end, we studied the root–shoot allometry of trees and its dependence on site conditions. Along a gradient in water supply in Southern Germany from dry to moist sites we selected 43 Norway spruce trees (Picea abies [L.] H. Karst.) aged 65–100 years. Increment cores were taken from stem and main roots revealing aboveground and belowground growth course over the last 34 years. Annual growth rates in roots and stems and their allometric relationships were applied as surrogate variables for tree resource allocation to aboveground and belowground organs. The mean sensitivities of both stem and root chronologies were found to be site-specific, and increased from the moist through the dry sites. No temporal offset between aboveground and belowground growth reactions to climate conditions was found in Norway spruce at any of the sites. These results suggest that the root–shoot allometry depends on the specific site conditions only at the driest site, following the optimal biomass partitioning theory (the more restricted the water supply, the more organic matter allocation into the belowground organs).     

Discovery of INCB10820/PF-4178903, a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist

We report the discovery of a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist (3S,4S)-N-[(1R,3S)-3-isopropyl-3-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}carbonyl)cyclopentyl]-3-methoxytetrahydro-2H-pyran-4-amine (19). After evaluation in 28-day toxicology studies, compound 19 (INCB10820/PF-4178903) was selected as a clinical candidate.