Regulatory mechanisms to control tissue alpha-tocopherol

To test the hypothesis that hepatic regulation of alpha-tocopherol metabolism would be sufficient to prevent overaccumulation of alpha-tocopherol in extrahepatic tissues and that administration of high doses of alpha-tocopherol would up-regulate extrahepatic xenobiotic pathways, rats received daily subcutaneous injections of either vehicle or 0.5, 1, 2, or 10 mg alpha-tocopherol/100 g body wt for 9 days. Liver alpha-tocopherol increased 15-fold in rats given 10 mg alpha-tocopherol/100 g body wt (mg/100 g) compared with controls. Hepatic alpha-tocopherol metabolites increased with increasing alpha-tocopherol doses, reaching 40-fold in rats given the highest dose. In rats injected with 10 mg/100 g, lung and duodenum alpha-tocopherol concentrations increased 3-fold, whereas alpha-tocopherol concentrations of other extrahepatic tissues increased 2-fold or less. With the exception of muscle, daily administration of less than 2 mg/100 g failed to increase alpha-tocopherol concentrations in extrahepatic tissues. Lung cytochrome P450 3A and 1A levels were unchanged by administration of alpha-tocopherol at any dose. In contrast, lung P-glycoprotein (MDR1) levels increased dose dependently and expression of this xenobiotic transport protein was correlated with lung alpha-tocopherol concentrations (R(2)=0.88, p<0.05). Increased lung MDR1 may provide protection from exposure to environmental toxins by increasing alveolar space alpha-tocopherol.     

Isolation and characterisation of endophytic actinobacteria and their effect on the growth and nodulation of chickpea (Cicer arietinum)

Plant and Soil - Phyllostachys praecox is one of the bamboo species that cultivated extensively in southern China. An organic material mulching technique is commonly adopted in winter to increase...     

Rapid Proteasomal Degradation of Posttranscriptional Regulators of the TIS11/Tristetraprolin Family Is Induced by an Intrinsically Unstructured Region Independently of Ubiquitination

The TIS11/tristetraprolin (TTP) CCCH tandem zinc finger proteins are major effectors in the destabilization of mRNAs bearing AU-rich elements (ARE) in their 3′ untranslated regions. In this report, we demonstrate that the Drosophila melanogaster dTIS11 protein is short-lived due to its rapid ubiquitin-independent degradation by the proteasome. Our data indicate that this mechanism is tightly associated with the intrinsically unstructured, disordered N- and C-terminal domains of the protein. Furthermore, we show that TTP, the mammalian TIS11/TTP protein prototype, shares the same three-dimensional characteristics and is degraded by the same proteolytic pathway as dTIS11, thereby indicating that this mechanism has been conserved across evolution. Finally, we observed a phosphorylation-dependent inhibition of dTIS11 and TTP degradation by the proteasome in vitro, raising the possibility that such modifications directly affect proteasomal recognition for these proteins. As a group, RNA-binding proteins (RNA-BPs) have been described as enriched in intrinsically disordered regions, thus raising the possibility that the mechanism that we uncovered for TIS11/TTP turnover is widespread among other RNA-BPs.     

Dimethyl Fumarate Protects Pancreatic Islet Cells and Non-Endocrine Tissue in L-Arginine-Induced Chronic Pancreatitis

Background

Chronic pancreatitis (CP) is a progressive disorder resulting in the destruction and fibrosis of the pancreatic parenchyma which ultimately leads to impairment of the endocrine and exocrine functions. Dimethyl Fumarate (DMF) was recently approved by FDA for treatment of patients with multiple sclerosis. DMF''s unique anti-oxidant and anti-inflammatory properties make it an interesting drug to test on other inflammatory conditions. This study was undertaken to determine the effects of DMF on islet cells and non-endocrine tissue in a rodent model of L-Arginine-induced CP.

Methods

Male Wistar rats fed daily DMF (25 mg/kg) or vehicle by oral gavage were given 5 IP injections of L-Arginine (250 mg/100 g×2, 1 hr apart). Rats were assessed with weights and intra-peritoneal glucose tolerance tests (IPGTT, 2 g/kg). Islets were isolated and assessed for islet mass and viability with flow cytometry. Non-endocrine tissue was assessed for histology, myeloperoxidase (MPO), and lipid peroxidation level (MDA). In vitro assessments included determination of heme oxygenase (HO-1) protein expression by Western blot.

Results

Weight gain was significantly reduced in untreated CP group at 6 weeks. IPGTT revealed significant impairment in untreated CP group and its restoration with DMF therapy (P <0.05). Untreated CP rats had pancreatic atrophy, severe acinar architectural damage, edema, and fatty infiltration as well as elevated MDA and MPO levels, which were significantly improved by DMF treatment. After islet isolation, the volume of non-endocrine tissue was significantly smaller in untreated CP group. Although islet counts were similar in the two groups, islet viability was significantly reduced in untreated CP group and improved with DMF treatment. In vitro incubation of human pancreatic tissue with DMF significantly increased HO-1 expression.

Conclusion

Administration of DMF attenuated L-Arginine-induced CP and islet function in rats. DMF treatment could be a possible strategy to improve clinical outcome in patients with CP.     

Non-Invasive Bedside Assessment of Central Venous Pressure: Scanning into the Future

Background

Noninvasive evaluation of central venous pressure (CVP) can be achieved by assessing the Jugular Venous Pressure (JVP), Peripheral Venous Collapse (PVC), and ultrasound visualization of the inferior vena cava. The relative accuracy of these techniques compared to one another and their application by trainees of varying experience remains uncertain. We compare the application and utility of the JVP, PVC, and handheld Mini Echo amongst trainees of varying experience including a medical student, internal medicine resident, and cardiology fellow. We also introduce and validate a new physical exam technique to assess central venous pressures, the Anthem sign.

Methods

Patients presenting for their regularly scheduled echocardiograms at the hospital echo department had clinical evaluations of their CVP using these non-invasive bedside techniques. The examiners were blinded to the echo results, each other''s assessments, and patient history; their CVP estimates were compared to the gold standard level 3 echo-cardiographer''s estimates at the completion of the study.

Results

325 patients combined were examined (mean age 65, s.d. 16 years). When compared to the gold standard of central venous pressure by a level 3 echocardiographer, the JVP was the most sensitive at 86%, improving with clinical experience (p<0.01). The classic PVC technique and Anthem sign had better specificity compared to the JVP. Mini Echo estimates were comparable to physical exam assessments.

Conclusions

JVP evaluation is the most sensitive physical examination technique in CVP assessments. The PVC techniques along with the newly described Anthem sign may be of value for the early learner who still has not mastered the art of JVP assessment and in obese patients in whom JVP evaluation is problematic. Mini Echo estimates of CVPs are comparable to physical examination by trained clinicians and require less instruction. The use of Mini Echo in medical training should be further evaluated and encouraged.     

Wolbachia do not live by reproductive manipulation alone: infection polymorphism in Drosophila suzukii and D. subpulchrella

Drosophila suzukii recently invaded North America and Europe. Populations in Hawaii, California, New York and Nova Scotia are polymorphic for Wolbachia, typically with <20% infection frequency. The Wolbachia in D. suzukii, denoted wSuz, is closely related to wRi, the variant prevalent in continental populations of D. simulans. wSuz is also nearly identical to Wolbachia found in D. subpulchrella, plausibly D. suzukii's sister species. This suggests vertical Wolbachia transmission through cladogenesis (‘cladogenic transmission’). The widespread occurrence of 7–20% infection frequencies indicates a stable polymorphism. wSuz is imperfectly maternally transmitted, with wild infected females producing on average 5–10% uninfected progeny. As expected from its low frequency, wSuz produces no cytoplasmic incompatibility (CI), that is, no increased embryo mortality when infected males mate with uninfected females, and no appreciable sex‐ratio distortion. The persistence of wSuz despite imperfect maternal transmission suggests positive fitness effects. Assuming a balance between selection and imperfect transmission, we expect a fitness advantage on the order of 20%. Unexpectedly, Wolbachia‐infected females produce fewer progeny than do uninfected females. We do not yet understand the maintenance of wSuz in D. suzukii. The absence of detectable CI in D. suzukii and D. subpulchrella makes it unlikely that CI‐based mechanisms could be used to control this species without transinfection using novel Wolbachia. Contrary to their reputation as horizontally transmitted reproductive parasites, many Wolbachia infections are acquired through introgression or cladogenesis and many cause no appreciable reproductive manipulation. Such infections, likely to be mutualistic, may be central to understanding the pervasiveness of Wolbachia among arthropods.     

Focus Issue on Roots: Branching Out in Roots: Uncovering Form,Function, and Regulation

Root branching is critical for plants to secure anchorage and ensure the supply of water, minerals, and nutrients. To date, research on root branching has focused on lateral root development in young seedlings. However, many other programs of postembryonic root organogenesis exist in angiosperms. In cereal crops, the majority of the mature root system is composed of several classes of adventitious roots that include crown roots and brace roots. In this Update, we initially describe the diversity of postembryonic root forms. Next, we review recent advances in our understanding of the genes, signals, and mechanisms regulating lateral root and adventitious root branching in the plant models Arabidopsis (Arabidopsis thaliana), maize (Zea mays), and rice (Oryza sativa). While many common signals, regulatory components, and mechanisms have been identified that control the initiation, morphogenesis, and emergence of new lateral and adventitious root organs, much more remains to be done. We conclude by discussing the challenges and opportunities facing root branching research.Branching through lateral and adventitious root formation represents an important element of the adaptability of the root system to its environment. Both are regulated by nutrient and hormonal signals (Bellini et al., 2014; Giehl and von Wirén, 2014), which act locally to induce or inhibit root branching. The net effect of these adaptive responses is to increase the surface area of the plant root system in the most important region of the soil matrix for resource capture (e.g. surface layers for phosphorus uptake and deeper layers for nitrate uptake) or to secure anchorage. Different species use different combinations of lateral or adventitious roots to achieve this, with lateral roots dominating the root system of eudicots while adventitious (crown and brace) roots dominate the root system of monocots, including in cereal crops.Our understanding of the mechanisms controlling lateral and adventitious root development has accelerated in recent years, primarily through research on model plants. The simple anatomy and the wealth of genetic resources in Arabidopsis (Arabidopsis thaliana) have greatly aided embryonic and postembryonic root developmental studies (De Smet et al., 2007; Péret et al., 2009a; Fig. 1, A and E). Nevertheless, impressive recent progress has been made studying root branching in other crop species, notably cereals such as maize (Zea mays) and rice (Oryza sativa).Open in a separate windowFigure 1.A to D, Schematics showing diversity in root system architecture at both seedling (left) and mature (right) stages in eudicots (A and C) and monocots (B and D). A, Arabidopsis root system. B, Maize root system. C, Tomato root system (for clarity, stem-derived adventitious roots are only shown in the labeled region). D, Wheat root system. E and F, Cross sections of emerging lateral root primordia in Arabidopsis (E) and rice (F). E and F are adapted from Péret et al. (2009b).In this Update, we initially describe the diversity of postembryonic root forms in eudicots and monocots (Fig. 1). Next, we highlight recent advances in our understanding of the genes, signals, and mechanisms regulating lateral root and adventitious root branching in Arabidopsis, rice, and maize. Due to space limits, we cannot provide an exhaustive review of this subject area, focusing instead on recent research advances. However, we direct readers to several recent in-depth reviews on lateral root (Lavenus et al., 2013; Orman-Ligeza et al., 2013) and adventitious root development (Bellini et al., 2014).     

Synthesis of the C1-phosphonate analog of UDP-GlcNAc

We describe the first synthesis of the C1-phosphonate analog of UDP-GlcNAc, based on a new preparation of the corresponding glycosyl phosphonate. This C-glycosyl analog is shown to be a very weak inhibitor (Ki>10 mM) of fungal chitin synthase, indicating that at least in this case the replacement of the anomeric oxygen with a methylene group is not an innocent substitution.