Modelling climatic suitability for myrtle rust with a widespread host species

Biological Invasions - Globalisation has resulted in the spread of infectious plant diseases to new regions and host species and the novel disease caused by myrtle rust poses a global threat to...     

C8- and C9-Alkylphenols and Ethoxylates: II. Assessment of Environmental Persistence and Bioaccumulation Potential

C8- and C9-alkylphenols and their ethoxylates (APE) are widely used commercial products mainly used in industrial applications, in the formulation of crop protection chemicals, and in industrial and household cleaners. Recent regulatory focus on these compounds has included an assessment of their potential to meet criteria for persistent, bioaccumulative, and toxic compounds (PBT). To fully evaluate either the relative persistence or bioaccumulation potential of any APE, degradation intermediates and metabolic by-products of these compounds should also be considered. To facilitate the evaluation of the ultimate fate of APE in the environment, a review of the degradation pathways and identification of degradation intermediates was performed (part I of a two-part series). In part II of this series, the relative persistence of APE as indicated by degradation half-lives was examined based on a review of abiotic and biological degradation data. To assess the bioaccumulation potential of APE, the relevant literature was also reviewed. The available data for C8- and C9-APE show that the commercial products and their degradation intermediates do not meet any national or international criteria for identifying these compounds as PBT substances.     

Structure at 2.5-A resolution of chemically synthesized human immunodeficiency virus type 1 protease complexed with a hydroxyethylene-based inhibitor

The crystal structure of a complex between chemically synthesized human immunodeficiency virus type 1 (HIV-1) protease and an octapeptide inhibitor has been refined to an R factor of 0.138 at 2.5-A resolution. The substrate-based inhibitor, H-Val-Ser-Gln-Asn-Leu psi [CH(OH)CH2]Val-Ile-Val-OH (U-85548e) contains a hydroxyethylene isostere replacement at the scissile bond that is believed to mimic the tetrahedral transition state of the proteolytic reaction. This potent inhibitor has Ki less than 1 nM and was developed as an active-site titrant of the HIV-1 protease. The inhibitor binds in an extended conformation and is involved in beta-sheet interactions with the active-site floor and flaps of the enzyme, which form the substrate/inhibitor cavity. The inhibitor diastereomer has the S configuration at the chiral carbon atom of the hydroxyethylene insert, and the hydroxyl group is within H-bonding distance of the two active-site carboxyl groups in the enzyme dimer. The two subunits of the enzyme are related by a pseudodyad, which superposes them at a 178 degrees rotation. The main difference between the subunits is in the beta turns of the flaps, which have different conformations in the two monomers. The inhibitor has a clear preferred orientation in the active site and the alternative conformation, if any, is a minor one (occupancy of less than 30%). A new model of the enzymatic mechanism is proposed in which the proteolytic reaction is viewed as a one-step process during which the nucleophile (water molecule) and electrophile (an acidic proton) attack the scissile bond in a concerted manner.     

Effect of Temperature on Argyrophil Impregnation: Development of A High Temperature Rapid Argyrophil Procedure

Out studies on the effects of temperature on the demonstration of neurosecretory granules using argyrophil stains indicate an inverse relationship between the time needed for staining and temperature of the silver and reducing solutions. Careful monitoring of the temperature of silver solutions during the Grimelius procedure and its modifications show long incubation times serve in large part only to bring the solutions to reaction temperature. Tissue sections added when this temperature has been reached will stain with the same intensity as sections impregnated for the entire incubation period. We have modified the argyrophil procedure so that double-impregnation with solutions preheated to 60-70 C and development in Bodian's reducer prepared with preheated water rapidly demonstrates secretory granules. Our method does not require a microwave oven and much shorter incubation periods are required than with usual procedures. It is not necessary to incubate sections in hot solutions for extended periods of time, which can lead to detachment of sections, nonspecific staining and decomposition of the silver solution. Rinsing after impregnation and before development greatly increases contrast of argyrophil cells by reducing background staining. Our procedure results in more reliable staining of argyrophil and argentaffin cells and takes only ten minutes.     

Function of the ski4p (Csl4p) and Ski7p proteins in 3'-to-5' degradation of mRNA

One of two general pathways of mRNA decay in the yeast Saccharomyces cerevisiae occurs by deadenylation followed by 3'-to-5' degradation of the mRNA body. Previous results have shown that this degradation requires components of the exosome and the Ski2p, Ski3p, and Ski8p proteins, which were originally identified due to their superkiller phenotype. In this work, we demonstrate that deletion of the SKI7 gene, which encodes a putative GTPase, also causes a defect in 3'-to-5' degradation of mRNA. Deletion of SKI7, like deletion of SKI2, SKI3, or SKI8, does not affect various RNA-processing reactions of the exosome. In addition, we show that a mutation in the SKI4 gene also causes a defect in 3'-to-5' mRNA degradation. We show that the SKI4 gene is identical to the CSL4 gene, which encodes a core component of the exosome. Interestingly, the ski4-1 allele contains a point mutation resulting in a mutation in the putative RNA binding domain of the Csl4p protein. This point mutation strongly affects mRNA degradation without affecting exosome function in rRNA or snRNA processing, 5' externally transcribed spacer (ETS) degradation, or viability. In contrast, the csl4-1 allele of the same gene affects rRNA processing but not 3'-to-5' mRNA degradation. We identify csl4-1 as resulting from a partial-loss-of-function mutation in the promoter of the CSL4 gene. These data indicate that the distinct functions of the exosome can be separated genetically and suggest that the RNA binding domain of Csl4p may have a specific function in mRNA degradation.     

Low-Load High Volume Resistance Exercise Stimulates Muscle Protein Synthesis More Than High-Load Low Volume Resistance Exercise in Young Men

Background

We aimed to determine the effect of resistance exercise intensity (% 1 repetition maximum—1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression.

Methodology/Principal Findings

Fifteen men (21±1 years; BMI = 24.1±0.8 kg/m²) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of [ring-¹³C₆] phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in Akt^Ser473 at 24h in all conditions (P = 0.023) and mTOR^Ser2448 phosphorylation at 4 h post-exercise (P = 0.025). Phosporylation of Erk1/2^Tyr202/204, p70S6K^Thr389, and 4E-BP1^Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1^Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P = 0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition.

Conclusions/Significance

These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes.     

Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes

Background

Obesity and type 2 diabetes (T2DM) are associated with increased circulating free fatty acids and triacylglycerols. However, very little is known about specific molecular lipid species associated with these diseases. In order to gain further insight into this, we performed plasma lipidomic analysis in a rodent model of obesity and insulin resistance as well as in lean, obese and obese individuals with T2DM.

Methodology/Principal Findings

Lipidomic analysis using liquid chromatography coupled to mass spectrometry revealed marked changes in the plasma of 12 week high fat fed mice. Although a number of triacylglycerol and diacylglycerol species were elevated along with of a number of sphingolipids, a particularly interesting finding was the high fat diet (HFD)-induced reduction in lysophosphatidylcholine (LPC) levels. As liver, skeletal muscle and adipose tissue play an important role in metabolism, we next determined whether the HFD altered LPCs in these tissues. In contrast to our findings in plasma, only very modest changes in tissue LPCs were noted. To determine when the change in plasma LPCs occurred in response to the HFD, mice were studied after 1, 3 and 6 weeks of HFD. The HFD caused rapid alterations in plasma LPCs with most changes occurring within the first week. Consistent with our rodent model, data from our small human cohort showed a reduction in a number of LPC species in obese and obese individuals with T2DM. Interestingly, no differences were found between the obese otherwise healthy individuals and the obese T2DM patients.

Conclusion

Irrespective of species, our lipidomic profiling revealed a generalized decrease in circulating LPC species in states of obesity. Moreover, our data indicate that diet and adiposity, rather than insulin resistance or diabetes per se, play an important role in altering the plasma LPC profile.     

Substrate-specific changes in mitochondrial respiration in skeletal and cardiac muscle of hibernating thirteen-lined ground squirrels

During torpor, the metabolic rate (MR) of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) is considerably lower relative to euthermia, resulting in part from temperature-independent mitochondrial metabolic suppression in liver and skeletal muscle, which together account for ~40 % of basal MR. Although heart accounts for very little (<0.5 %) of basal MR, in the present study, we showed that respiration rates were decreased up to 60 % during torpor in both subsarcolemmal (SS) and intermyofibrillar (IM) mitochondria from cardiac muscle. We further demonstrated pronounced seasonal (summer vs. winter [i.e., interbout] euthermia) changes in respiration rates in both mitochondrial subpopulations in this tissue, consistent with a shift in fuel use away from carbohydrates and proteins and towards fatty acids and ketones. By contrast, these seasonal changes in respiration rates were not observed in either SS or IM mitochondria isolated from hind limb skeletal muscle. Both populations of skeletal muscle mitochondria, however, did exhibit metabolic suppression during torpor, and this suppression was 2- to 3-fold greater in IM mitochondria, which provide ATP for Ca²⁺- and myosin ATPases, the activities of which are likely quite low in skeletal muscle during torpor because animals are immobile. Finally, these changes in mitochondrial respiration rates were still evident when standardized to citrate synthase activity rather than to total mitochondrial protein.     

Mating senescence and male reproductive organ size in the Mexican fruit fly

Ageing can reduce the probability that individuals reproduce. The present study investigates whether ageing influences the mating frequency of mass‐reared fertile and sterile Mexican fruit flies Anastrepha ludens (Loew). The ability of males of different ages to inhibit female remating is also determined, and the growth of male reproductive organs is measured as they age. Young males (6 days old) have a lower mating frequency than older males, and also have a lower capacity to inhibit female remating than older males. However, 7‐day‐old males are as likely to inhibit female remating as older males. Young males also have smaller reproductive organs than middle‐aged (21‐day‐old) or senescent males (57‐day‐old). These results have implications for the sterile insect technique because sterilized males of A. ludens are released in the field 6 days after emergence. The highest mating frequency, the lowest mating latency and the largest size of testes are observed at 21 days of age. Older males (57 days old) have more sperm in their seminal vesicles than young males (6 and 9 days old). Accessory glands take longer to grow to their complete size compared with testes, and mating frequency is more closely associated with accessory gland size than testes size. Furthermore, there are more sperm in the seminal vesicles during the afternoon period of peak sexual activity than during the morning when sexual activity is absent. These results indicate that, even at the onset of reproductive senescence, mass‐reared males of A. ludens are still capable of mating, as well as inhibiting remating in females.