Lizards combine stored energy and recently acquired nutrients flexibly to fuel reproduction

1. Energy allocation strategies for reproduction are viewed typically as a continuum between reliance on 'income' (recently acquired energy) vs. 'capital' (stored reserves) for fuelling reproduction. Because ectothermy facilitates long-term energy storage and often involves low feeding rates, traditional views suggest that many ectotherms rely heavily on stored reserves for egg production. 2. We explored the temporal relationship between energy intake and expenditure in a multi-clutching lizard (Amphibolurus muricatus) by evaluating the effect of maternal nutrition on reproductive output and by contrasting delta(13)C measurements of the maternal diet and endogenous energy stores with that of the eggs produced. 3. Our experiment revealed that females utilize both endogenous energy stores and recently acquired food to fuel reproduction; this pattern did not shift seasonally from first to second clutches produced. Importantly, however, egg lipid was derived primarily from capital, whereas egg protein was derived about equally from both income and capital. 4. Overall, these results suggest that the energy allocation strategy used for reproduction differs among egg components, and that the use of recently acquired energy for reproduction may be more widespread in ectotherms than thought previously.     

Alanine scanning of MS2 coat protein reveals protein-phosphate contacts involved in thermodynamic hot spots

The co-crystal structure of the MS2 coat protein dimer with its RNA operator reveals eight amino acid side-chains contacting seven of the RNA phosphates. These eight amino acids and five nearby control positions were individually changed to an alanine residue and the binding affinities of the mutant proteins to the RNA were determined. In general, the data agreed well with the crystal structure and previous RNA modification data. Interestingly, amino acid residues that are energetically most important for complex formation cluster in the middle of the RNA binding interface, forming thermodynamic hot spots, and are surrounded by energetically less relevant amino acids. In order to evaluate whether or not a given alanine mutation causes a global change in the RNA-protein interface, the affinities of the mutant proteins to RNAs containing one of 14 backbone modifications spanning the entire interface were determined. In three of six protein mutations tested, thermodynamic coupling between the site of the mutation and RNA groups that can be even more than 16 A away was detected. This suggests that, in some cases, the mutation may subtly alter the entire protein-RNA interface.     

Inhaled adenosine A(2A) receptor agonists for the treatment of chronic obstructive pulmonary disease

COPD is a major cause of mortality in the western world. A(2A) agonists are postulated to reduce the lung inflammation that causes COPD. The cardiovascular effects of A(2A) agonists dictate that a compound needs to be delivered by inhalation to be therapeutically useful. A strategy of minimizing side-effect liability by maximizing systemic clearance was followed and pharmacological and pharmacokinetic SAR of a series of inhaled A(2A) agonists described. A sevenfold improvement in potency and 150-fold reduction in side-effect liability over the lead compound CGS-21680, were obtained.     

Regional climate on the breeding grounds predicts variation in the natal origin of monarch butterflies overwintering in Mexico over 38 years

Addressing population declines of migratory insects requires linking populations across different portions of the annual cycle and understanding the effects of variation in weather and climate on productivity, recruitment, and patterns of long‐distance movement. We used stable H and C isotopes and geospatial modeling to estimate the natal origin of monarch butterflies (Danaus plexippus) in eastern North America using over 1000 monarchs collected over almost four decades at Mexican overwintering colonies. Multinomial regression was used to ascertain which climate‐related factors best‐predicted temporal variation in natal origin across six breeding regions. The region producing the largest proportion of overwintering monarchs was the US Midwest (mean annual proportion = 0.38; 95% CI: 0.36–0.41) followed by the north‐central (0.17; 0.14–0.18), northeast (0.15; 0.11–0.16), northwest (0.12; 0.12–0.16), southwest (0.11; 0.08–0.12), and southeast (0.08; 0.07–0.11) regions. There was no evidence of directional shifts in the relative contributions of different natal regions over time, which suggests these regions are comprising the same relative proportion of the overwintering population in recent years as in the mid‐1970s. Instead, interannual variation in the proportion of monarchs from each region covaried with climate, as measured by the Southern Oscillation Index and regional‐specific daily maximum temperature and precipitation, which together likely dictate larval development rates and food plant condition. Our results provide the first robust long‐term analysis of predictors of the natal origins of monarchs overwintering in Mexico. Conservation efforts on the breeding grounds focused on the Midwest region will likely have the greatest benefit to eastern North American migratory monarchs, but the population will likely remain sensitive to regional and stochastic weather patterns.     

Wintering areas predict age‐related breeding phenology in a migratory passerine bird

Understanding connections between breeding, stopover and wintering grounds for long‐distance migratory birds can provide important insight into factors influencing demography and the strength of carry‐over effects among various periods of the annual cycle. Using previously described, multi‐isotope (δ¹³C, δ¹⁵N, δ²H) feather isoscapes for Africa, we identified the most probable wintering areas for house martins Delichon urbica breeding at Badajoz in southwestern Spain. We identified two most‐probable wintering areas differing in isotopic signature in west Africa. We found that the probability to winter in the isotopic cluster two was related to age and sex of individuals. Specifically, experienced males (i.e. two years or older) winter in the isotopic cluster two with a greater probability than experienced females, whereas first‐year females winter in the isotopic cluster two with a greater probability than first‐year males. In addition, wintering area was correlated with breeding phenology, with individuals wintering in the isotopic cluster two initiating their clutches earlier than those wintering in the isotopic cluster one. For birds wintering in the isotopic cluster two, there was no relationship between age and clutch initiation date. In contrast, young birds wintering in the isotopic cluster one initiated their clutches earlier than experienced birds wintering in this area. There was no significant correlation between wintering area and clutch size or the number of fledglings produced. We hypothesize that the relationship among social status, population density and winter habitat quality should be the most important driver of the carry‐over effect we found for this population.     

VEGF increases endothelial permeability by separate signaling pathways involving ERK-1/2 and nitric oxide

We tested the hypothesis that VEGF regulates endothelial hyperpermeability to macromolecules by activating the ERK-1/2 MAPK pathway. We also tested whether PKC and nitric oxide (NO) mediate VEGF-induced increases in permeability via the ERK-1/2 pathway. FITC-Dextran 70 flux across human umbilical vein endothelial cell monolayers served as an index of permeability, whereas Western blots assessed the phosphorylation of ERK-1/2. VEGF-induced hyperpermeability was inhibited by antisense DNA oligonucleotides directed against ERK-1/2 and by blockade of MEK and Raf-1 activities (20 microM PD-98059 and 5 microM GW-5074). These blocking agents also reduced ERK-1/2 phosphorylation. The PKC inhibitor bisindolylmaleimide I (10 microM) blocked both VEGF-induced ERK-1/2 activation and hyperpermeability. The NO synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (200 microM) and the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidiazoline-1-oxyl-3-oxide (100 microM) abolished VEGF-induced hyperpermeability but did not block ERK-1/2 phosphorylation. These observations demonstrate VEGF-induced hyperpermeability involves activation of PKC and NOS as well as Raf-1, MEK, and ERK-1/2. Furthermore, our data suggest that ERK-1/2 and NOS are elements of different signaling pathways in VEGF-induced hyperpermeability.     

Effects of migration distance and sex on stopover timing and refueling by Wilson's Warblers

Migration distance and sex are integral to avian migration strategies, yet these intrinsic factors are understudied with respect to their effects on stopover ecology and behavior. We investigated how individual variation in migration distance and sex affected body condition, refueling performance, and stopover durations of Wilson's Warblers (Cardellina pusilla) during spring and fall 2006 at a stopover site in southern Arizona. Migration distance of individuals was inferred using the hydrogen stable isotope ratio of feathers (δ²H_f) as an index of breeding latitude, refueling rate was assessed using plasma triglyceride and β‐OH‐butyrate, and minimum length of stay was estimated by re‐sighting color‐banded birds. In the spring, migration distance and sex were strong determinants of the timing of migration by Wilson's Warblers, with males and shorter‐distance migrants passing through the site earlier than females and longer‐distance migrants. Later‐arriving migrants also had higher fat scores and refueling rates. However, neither migration distance nor sex independently affected body condition (fat score or size‐corrected mass), refueling rate, or minimum length of stay. In a smaller sample of fall migrants, we found that longer‐distance migrants and males had higher refueling rates than shorter‐distance migrants and females. Our results show that differences in migration distance can, under some circumstances, affect how birds use stopover sites. Stable isotope analysis and other methods can provide information on migration distance, and should be integrated with measurements of timing, fuel stores, refueling performance, and departure behavior to gain a deeper understanding of bird migration.     

Adenylate cyclase is required for chemotaxis to phosphotransferase system sugars by Escherichia coli.

We report that in Escherichia coli, chemotaxis to sugars transported by the phosphotransferase system is mediated by adenylate cyclase, the nucleotide cyclase linked to the phosphotransferase system. We conclude that adenylate cyclase is required in this chemotaxis pathway because mutations in the cyclase gene (cya) eliminate or impair the response to phosphotransferase system sugars, even though other components of the phosphotransferase system known to be required for the detection of these sugars are relatively unaffected by such mutations. Moreover, merely supplying the mutant bacteria with the products of this enzyme, cyclic AMP and cyclic GMP, does not restore the chemotactic response. Because a residual chemotactic response is observed in certain strains with residual cyclic GMP synthesis but no cyclic AMP synthesis, it appears that the guanylate cyclase activity rather than the adenylate cyclase activity of the enzyme may be required for chemotaxis to sugars transported by the phosphotransferase system. Mutations in the cyclic nucleotide phosphodiesterase gene, which increase the level of both cyclic AMP and cyclic GMP, also reduce chemotaxis to these sugars. Therefore, it appears that control of the level of a cyclic nucleotide is critical for the chemotactic response to phosphotransferase system sugars.