Expression of normal and mutant avian integrin subunits in rodent cells [published erratum appears in J Cell Biol 1989 Oct;109(4 Pt 1):1187]

We describe the expression of the beta 1 subunit of avian integrin in rodent cells with the purpose of examining the structure-function relationships of various domains within this subunit. The exogenous subunit is efficiently and stably expressed in 3T3 cells, and it forms hybrid heterodimers with endogenous murine alpha subunits, including alpha 3 and alpha 5. These heterodimers are exported to the cell surface and localize in focal contacts where both extracellular matrix and cytoskeleton associate with the plasma membrane. Hybrid heterodimers consisting of exogenous beta 1 and endogenous alpha subunits bind effectively and specifically to columns of cell-binding fragments of fibronectin. The exogenous avian beta 1 subunit appears to function as well as its endogenous murine equivalent, consistent with the high degree of conservation noted previously for integrins. In contrast, expression of a mutant form of avian integrin beta 1 subunit lacking the cytoplasmic domain produces hybrid heterodimers which, while efficiently exported to the cell surface and still capable of binding fibronectin, do not localize efficiently in focal contacts. This further implicates the cytoplasmic domain of the beta 1 subunit in interactions required for cytoskeletal organization.     

Synthesis and biological evaluation of azobicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes

A series of novel azobicyclo[3.3.0]octane derivatives were synthesized and evaluated as dipeptidyl peptidase 4 (DPP-4) inhibitors. The effort resulted in the discovery of inhibitor 2a, which exhibited excellent efficacies in an oral glucose tolerance test. Introduction of methyl group (2j) could prolong the inhibition of serum DPP-4 activity.     

Expected future plague levels in a wildlife host under different scenarios of climate change

We predicted future plague and black-tailed prairie dog dynamics in the North American prairies under different scenarios of climate change. A climate-driven model for the joint dynamic of the host–parasite system was used. Projections for the regional climate were obtained through empirical–statistical downscaling of global climate scenarios generated by an ensemble of global climate models for the recent Fourth Assessment Report by the IPCC. The study shows the uncertainties involved in predicting future regional climate and climate-driven population dynamics, but reveals that unchanged or lower levels of plague, leading to increased black-tailed prairie dog colonies, can be expected. Less plague is particularly expected for scenarios that assume the highest emission of greenhouse gases associated with the greatest projected future warming. Moreover, under high-emission scenarios, decreased probabilities of extremely high numbers of infected colonies are expected, along with decreased probabilities of extremely low total numbers of colonies. The assumed main underlying mechanism is an inhibiting effect of high temperatures on fleas (dispersal vector) and on flea-mediated transmission of the disease-causing bacterium. Our study highlights the importance of using dynamic ecological (here host–parasite) models together with ensembles of climate projections to investigate the responses of populations and parasites to a changed climate.     

Comparative transcriptome analysis reveals molecular regulators underlying pluripotent cell induction and callus formation in Anthurium andraeanum “Alabama”

In Vitro Cellular & Developmental Biology - Plant - Shoot regeneration from pluripotent cell masses is an important process for genetic improvement of Anthurium andraeanum through...     

Adiponectin Upregulates MiR-133a in Cardiac Hypertrophy through AMPK Activation and Reduced ERK1/2 Phosphorylation

Adiponectin and miR-133a are key regulators in cardiac hypertrophy. However, whether APN has a potential effect on miR-133a remains unclear. In this study, we aimed to investigate whether APN could regulate miR-133a expression in Angiotensin II (Ang II) induced cardiac hypertrophy in vivo and in vitro. Lentiviral-mediated adiponectin treatment attenuated cardiac hypertrophy induced by Ang II infusion in male wistar rats as determined by reduced cell surface area and mRNA levels of atrial natriuretic peptide (ANF) and brain natriuretic peptide (BNP), also the reduced left ventricular end-diastolic posterior wall thickness (LVPWd) and end-diastolic interventricular septal thickness (IVSd). Meanwhile, APN elevated miR-133a level which was downregulated by Ang II. To further investigate the underlying molecular mechanisms, we treated neonatal rat ventricular myocytes (NRVMs) with recombinant rat APN before Ang II stimulation. Pretreating cells with recombinant APN promoted AMP-activated protein kinase (AMPK) phosphorylation and inhibited ERK activation. By using the inhibitor of AMPK or a lentiviral vector expressing AMPK short hairpin RNA (shRNA) cancelled the positive effect of APN on miR-133a. The ERK inhibitor PD98059 reversed the downregulation of miR-133a induced by Ang II. These results indicated that the AMPK activation and ERK inhibition were responsible for the positive effect of APN on miR-133a. Furthermore, adiponectin receptor 1 (AdipoR1) mRNA expression was inhibited by Ang II stimulation. The positive effects of APN on AMPK activation and miR-133a, and the inhibitory effect on ERK phosphorylation were inhibited in NRVMs transfected with lentiviral AdipoR1shRNA. In addition, APN depressed the elevated expression of connective tissue growth factor (CTGF), a direct target of miR-133a, through the AMPK pathway. Taken together, our data indicated that APN reversed miR-133a levels through AMPK activation, reduced ERK1/2 phosphorylation in cardiomyocytes stimulated with Ang II, revealing a previously undemonstrated and important link between APN and miR-133a.     

Effects of experimental warming on arctic willows (Salix spp.): a comparison of responses from the Canadian High Arctic, Alaskan Arctic, and Swedish Subarctic

Three species of dwarf, prostrate willow ( Salix arctica , S. rotundifolia and S. herbacea ) were subjected to experimental summer warming in high arctic Canada, arctic Alaska, and subarctic Sweden, respectively, as part of the International Tundra Experiment. Phenological and growth responses of these species were compared for the second season of the experiment. Stigmas became receptive and pollen dispersal occurred significantly earlier for S. rotundifolia and S. herbacea in the ITEX open-top chambers, but not for S. arctica . Warming had no effect on the timing of seed dispersal, leaf yellowing, or leaf senescence. The length and dry weight of the largest leaves were greater for warmed plants, and was significant for S. rotundifolia . The number of catkins/plot did not differ among species or treatments, but the fruit : flower ratio was reduced in the experimental plots.     

Multiple Modes of Cell Death Discovered in a Prokaryotic (Cyanobacterial) Endosymbiont

Programmed cell death (PCD) is a genetically-based cell death mechanism with vital roles in eukaryotes. Although there is limited consensus on similar death mode programs in prokaryotes, emerging evidence suggest that PCD events are operative. Here we present cell death events in a cyanobacterium living endophytically in the fern Azolla microphylla, suggestive of PCD. This symbiosis is characterized by some unique traits such as a synchronized development, a vertical transfer of the cyanobacterium between plant generations, and a highly eroding cyanobacterial genome. A combination of methods was used to identify cell death modes in the cyanobacterium. Light- and electron microscopy analyses showed that the proportion of cells undergoing cell death peaked at 53.6% (average 20%) of the total cell population, depending on the cell type and host developmental stage. Biochemical markers used for early and late programmed cell death events related to apoptosis (Annexin V-EGFP and TUNEL staining assays), together with visualization of cytoskeleton alterations (FITC-phalloidin staining), showed that all cyanobacterial cell categories were affected by cell death. Transmission electron microscopy revealed four modes of cell death: apoptotic-like, autophagic-like, necrotic-like and autolytic-like. Abiotic stresses further enhanced cell death in a dose and time dependent manner. The data also suggest that dynamic changes in the peptidoglycan cell wall layer and in the cytoskeleton distribution patterns may act as markers for the various cell death modes. The presence of a metacaspase homolog (domain p20) further suggests that the death modes are genetically programmed. It is therefore concluded that multiple, likely genetically programmed, cell death modes exist in cyanobacteria, a finding that may be connected with the evolution of cell death in the plant kingdom.