GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress

Perturbation of endoplasmic reticulum (ER) homeostasis impairs insulin biosynthesis, beta cell survival, and glucose homeostasis. We show that a murine model of diabetes is associated with the development of ER stress in beta cells and that treatment with the GLP-1R agonist exendin-4 significantly reduced biochemical markers of islet ER stress in vivo. Exendin-4 attenuated translational downregulation of insulin and improved cell survival in purified rat beta cells and in INS-1 cells following induction of ER stress in vitro. GLP-1R agonists significantly potentiated the induction of ATF-4 by ER stress and accelerated recovery from ER stress-mediated translational repression in INS-1 beta cells in a PKA-dependent manner. The effects of exendin-4 on the induction of ATF-4 were mediated via enhancement of ER stress-stimulated ATF-4 translation. Moreover, exendin-4 reduced ER stress-associated beta cell death in a PKA-dependent manner. These findings demonstrate that GLP-1R signaling directly modulates the ER stress response leading to promotion of beta cell adaptation and survival.     

A before–after control–impact assessment to understand the potential impacts of highway construction noise and activity on an endangered songbird

Anthropogenic noise associated with highway construction and operation can have individual‐ and population‐level consequences for wildlife (e.g., reduced densities, decreased reproductive success, behavioral changes). We used a before–after control–impact study design to examine the potential impacts of highway construction and traffic noise on endangered golden‐cheeked warblers (Setophaga chrysoparia; hereafter warbler) in urban Texas. We mapped and monitored warbler territories before (2009–2011), during (2012–2013), and after (2014) highway construction at three study sites: a treatment site exposed to highway construction and traffic noise, a control site exposed only to traffic noise, and a second control site exposed to neither highway construction or traffic noise. We measured noise levels at varying distances from the highway at sites exposed to construction and traffic noise. We examined how highway construction and traffic noise influenced warbler territory density, territory placement, productivity, and song characteristics. In addition, we conducted a playback experiment within study sites to evaluate acute behavioral responses to highway construction noises. Noise decreased with increasing distance from the highways. However, noise did not differ between the construction and traffic noise sites or across time. Warbler territory density increased over time at all study sites, and we found no differences in warbler territory placement, productivity, behavior, or song characteristics that we can attribute to highway construction or traffic noise. As such, we found no evidence to suggest that highway construction or traffic noise had a negative effect on warblers during our study. Because human population growth will require recurring improvements to transportation infrastructure, understanding wildlife responses to anthropogenic noise associated with the construction and operation of roads is essential for effective management and recovery of prioritized species.     

Measurement of grey parrot (Psittacus erithacus) trachea via magnetic resonance imaging,dissection, and electron beam computed tomography

To produce a model to explain the acoustic properties of human speech sounds produced by Grey parrots (Psittacus erithacus) and to compare these properties across species (e.g., with humans, other psittacine and nonpsittacine mimics), researchers need adequate measurements of the chambers that constitute the parrot vocal tract. Various methods can provide such data. Here we compare results for tracheal measurements provided by a) magnetic resonance imaging (MRI) of a live bird, b) caliper measurements of four preserved specimens, and c) electron beam computed tomography (EBCT) of three of these preserved specimens. We find that EBCT scans provide data that correspond to the inner area of the dissected trachea, whereas MRI results correspond to area measurements that include tracheal ring thickness. We briefly discuss how these data may predict formant values for Grey parrot reproduction of human vowels. Our results suggest how noninvasive techniques can be used for cross-species comparisons, including the coevolution of structure and function in avian mimicry. J. Morphol. 238:81–91, 1998. © 1998 Wiley-Liss, Inc.     

Spatial and temporal variation in prey color patterns for background matching across a continuous heterogeneous environment

In heterogeneous habitats, camouflage via background matching can be challenging because visual characteristics can vary dramatically across small spatial scales. Additionally, temporal variation in signaling functions of coloration can affect crypsis, especially when animals use coloration seasonally for intraspecific signaling (e.g., mate selection). We currently have a poor understanding of how wild prey optimize background matching within continuously heterogeneous habitats, and whether this is affected by requirements of intraspecific signaling across biological seasons. Here, we quantified color patterns of a wild population of shore skink (Oligosoma smithi), a variably colored lizard endemic to New Zealand, to (a) investigate whether background matching varies across a vegetation gradient; (b) assess potential signaling functions of color; and (c) to determine whether there is a trade‐off between requirements for crypsis and intraspecific signaling in coloration across seasons. Although all pattern types occurred throughout the vegetation gradient, we found evidence for background matching in skinks across the vegetation gradient, where dorsal brightness and pattern complexity corresponded with the proportion of vegetation cover. There was also a significant disparity between ventral color (saturation) of juveniles and adults, and also between sexes, suggestive of sex recognition. However, there was little indication that color was condition‐dependent in adults. Despite some evidence for a potential role in signaling, crypsis did not greatly differ across seasons. Our study suggests that selection favors a mix of generalist and specialist background matching strategies across continuously heterogeneous habitats.     

The role of hopanoids in fortifying rhizobia against a changing climate

Bacteria are a globally sustainable source of fixed nitrogen, which is essential for life and crucial for modern agriculture. Many nitrogen-fixing bacteria are agriculturally important, including bacteria known as rhizobia that participate in growth-promoting symbioses with legume plants throughout the world. To be effective symbionts, rhizobia must overcome multiple environmental challenges: from surviving in the soil, to transitioning to the plant environment, to maintaining high metabolic activity within root nodules. Climate change threatens to exacerbate these challenges, especially through fluctuations in soil water potential. Understanding how rhizobia cope with environmental stress is crucial for maintaining agricultural yields in the coming century. The bacterial outer membrane is the first line of defence against physical and chemical environmental stresses, and lipids play a crucial role in determining the robustness of the outer membrane. In particular, structural remodelling of lipid A and sterol-analogues known as hopanoids are instrumental in stress acclimation. Here, we discuss how the unique outer membrane lipid composition of rhizobia may underpin their resilience in the face of increasing osmotic stress expected due to climate change, illustrating the importance of studying microbial membranes and highlighting potential avenues towards more sustainable soil additives.     

Bistratene A Causes Phosphorylation of Talin and Redistribution of Actin Microfilaments in Fibroblasts: Possible Role for PKC-δ

Bistratene A is a marine toxin which induces phosphorylation of cellular proteins. Our current evidence indicates that this occurs through activation of protein kinase C-δ. In fibroblasts bistratene A causes rounding up of the cells and a rapid disappearance of vinculin staining and actin stress fibers as detected by fluorescence immunohistochemistry. Phosphorylation of the focal adhesion protein, talin, is increased after bistratene A treatment and this is inhibited by calphostin C, a specific inhibitor of PKC. No changes in the phosphorylation status of vinculin, tubulin, or vimentin were observed in the presence of the toxin. Treatment with bistratene A caused a redistribution of PKC-δ from cytosolic and membrane compartments to the nuclear fraction. There was no effect on the subcellular distribution of any other PKC isoform. These results demonstrate that phosphorylation of talin is implicated in the disruption of actin microfilaments in fibroblasts by bistratene A and that this is most likely mediated by PKC-δ.     

Dissimilatory arsenate and sulfate reduction in Desulfotomaculum auripigmentum sp. nov.

A newly discovered arsenate-reducing bacterium, strain OREX-4, differed significantly from strains MIT-13 and SES-3, the previously described arsenate-reducing isolates, which grew on nitrate but not on sulfate. In contrast, strain OREX-4 did not respire nitrate but grew on lactate, with either arsenate or sulfate serving as the electron acceptor, and even preferred arsenate. Both arsenate and sulfate reduction were inhibited by molybdate. Strain OREX-4, a gram-positive bacterium with a hexagonal S-layer on its cell wall, metabolized compounds commonly used by sulfate reducers. Scorodite (FeAsO₄2· H₂O) an arsenate-containing mineral, provided micromolar concentrations of arsenate that supported cell growth. Physiologically and phylogenetically, strain OREX-4 was far-removed from strains MIT-13 and SES-3: strain OREX-4 grew on different electron donors and electron acceptors, and fell within the gram-positive group of the Bacteria, whereas MIT-13 and SES-3 fell together in the ɛ-subdivision of the Proteobacteria. Together, these results suggest that organisms spread among diverse bacterial phyla can use arsenate as a terminal electron acceptor, and that dissimilatory arsenate reduction might occur in the sulfidogenic zone at arsenate concentrations of environmental interest. 16S rRNA sequence analysis indicated that strain OREX-4 is a new species of the genus Desulfotomaculum, and accordingly, the name Desulfotomaculum auripigmentum is proposed. Received: 22 October 1997 / Accepted: 16 June 1997     

Cellular degeneration in the production of some mutant phenotypes in Drosophila melanogaster

Summary A number of mutants of Drosophila melanogaster are characterized by the absence of structures present in the wild type. Imaginal discs from the wing mutants vestigial, apterous-Xasta, Beadex and cut and from the eye mutants Bar, eyeless and lozenge were examined by light and electron microscopy. In all these mutants, with the exception of lozenge, clear evidence of degeneration was found. The onset and duration of degeneration and the number and distribution of dying cells were specific characteristics of each mutant. In most cases the degenerate areas of the disc could be correlated with the missing parts of the adult wing or eye. In contrast, in wild type wing and eye discs and in wing discs from the mutant miniature, which has a wing reduced in size but fully formed, extensive cell death was not observed.The ultrastructural features of the degenerating areas weresimilar in all the mutants studied. Conspicuous aspects of the cytolytic process included condensation and fragmentation of the dying cells followed by phagocytosis of the cell fragments by neighboring disc cells.The results indicate that localized cell death during development is a widespread occurrence among Drosophila mutants which exhibit structural deficiències.     

The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient''s propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum.A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI.These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.     

Vegetation differentiation in the patterned landscape of the central Everglades: importance of local and landscape drivers

Aim We present a model to account for self‐assembly of the slough–ridge–tree island patterned landscape of the central Everglades in southern Florida via feedbacks among landforms, hydrology, vegetation and biogeochemistry. We test aspects of this model by analysing vegetation composition in relation to local and landscape‐level drivers. Location We quantified vegetation composition and environmental characteristics in central Water Conservation Area (WCA) 3A, southern WCA‐3A and southern WCA‐3B in southern Florida, based on their divergence in water management and flow regimes over the past 50 years. Methods In 562 quadrats, we estimated species coverages and quantified maximum, minimum and average water depth, soil depth to bedrock, normalized difference vegetation index (NDVI) and proximity to the nearest tree island. We used non‐metric multi‐dimensional scaling (NMS) to relate compositional variation to local and landscape‐level factors, and evaluated environmental differences among eight a priori vegetation types via anova . Results Water depth and hydroperiod decreased from sloughs to ridges to tree islands, but regions also differed significantly in the abundance of several community types and the hydroregimes characterizing them. NMS revealed two significant axes of compositional variation, tied to local gradients of water depth and correlated factors, and to a landscape‐scale gradient of proximity to tall tree islands. Sawgrass height and soil thickness increased toward higher ridges, and NDVI was greatest on tree islands. Main conclusions This study supports four components of our model: positive feedback of local substrate height on itself, woody plant invasion and subsequent P transport and concentration by top predators nesting on taller tree islands, compositional shifts in sites close to tree islands due to nutrient leakage, and flow‐induced feedback against total raised area. Regional divergence in the relationship of community types to current hydroregimes appears to reflect a lag of a few years after shifts in water management; a longer lag would be expected for shifts in landscape patterning. Both local and landscape‐level drivers appear to shape vegetation composition and soil thickness in the central Everglades.