Ribosomal RNA sequence phylogeny is not congruent with ascospore morphology among species in Ceratocystis sensu stricto

The genus Ceratocystis sensu stricto includes important fungal pathogens of woody and herbaceous plants. This genus is distinguished from species in Ceratocystis sensu lato by the presence of Chalara anamorphs. Ascospore shape has been used extensively in delineating Ceratocystis taxa, which show a large variety of ascospore shapes. Sequence analysis of one region of he 18S ribosomal RNA subunit and two regions of the 28S ribosomal RNA subunit showed that there was a majority of multiple substitutions at nucleotide sites and that there was a low transition/transversion ratio, T = 0.72. Both of these results suggest that these are well established, old species. Ascospore morphology, for the most part, was not congruent with the molecular phylogeny, and the use of morphological characters may be misleading in the taxonomy of these species.      

SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation

Notch receptors and their ligands play important roles in both normal animal development and pathogenesis. We show here that the F-box/WD40 repeat protein SEL-10 negatively regulates Notch receptor activity by targeting the intracellular domain of Notch receptors for ubiquitin-mediated protein degradation. Blocking of endogenous SEL-10 activity was done by expression of a dominant-negative form containing only the WD40 repeats. In the case of Notch1, this block leads to an increase in Notch signaling stimulated by either an activated form of the Notch1 receptor or Jagged1-induced signaling through Notch1. Expression of dominant-negative SEL-10 leads to stabilization of the intracellular domain of Notch1. The Notch4 intracellular domain bound to SEL-10, but its activity was not increased as a result of dominant-negative SEL-10 expression. SEL-10 bound Notch4 via the WD40 repeats and bound preferentially to a phosphorylated form of Notch4 in cells. We mapped the region of Notch4 essential for SEL-10 binding to the C-terminal region downstream of the ankyrin repeats. When this C-terminal fragment of Notch4 was expressed in cells, it was highly labile but could be stabilized by the expression of dominant-negative SEL-10. Ubiquitination of Notch1 and Notch4 intracellular domains in vitro was dependent on SEL-10. Although SEL-10 interacts with the intracellular domains of both Notch1 and Notch4, these proteins respond differently to interference with SEL-10 function. Thus, SEL-10 functions to promote the ubiquitination of Notch proteins; however, the fates of these proteins may differ.     

Simulation of stent deployment in a realistic human coronary artery

Background  

The process of restenosis after a stenting procedure is related to local biomechanical environment. Arterial wall stresses caused by the interaction of the stent with the vascular wall and possibly stress induced stent strut fracture are two important parameters. The knowledge of these parameters after stent deployment in a patient derived 3D reconstruction of a diseased coronary artery might give insights in the understanding of the process of restenosis.     

Salt-avoidance tropism in Arabidopsis thaliana

The orientation of plant root growth is modulated by developmental as well as environmental cues. Among the environmental factors, gravity has been extensively studied because of its overpowering effects in modulating root growth direction. However, our knowledge of the effects of other abiotic signals that influence root growth direction is largely unknown. Recently, we have shown that high salinity can modify root growth direction by inducing rapid amyloplast degradation in root columella cells of Arabidopsis thaliana. By exploiting salt overly sensitive (sos) mutants and PIN2 expression analyses, we have shown that the altered root growth direction in response to salt is mediated by ion disequilibrium and is correlated with PIN2 mRNA abundance and expression and localization of the protein. Our study demonstrates that the SOS pathway may mediate this process. Here we discuss our data from broader perspectives. We propose that salt-induced modification of root growth direction is a salt-avoidance behavior, which is an active adaptive mechanism for plants grown under saline conditions. Furthermore, high salinity also stimulates alteration of gravitropic growth of shoots. These findings illustrate that plants have a fine and sophisticated sensory and communication system that enable plants to dynamically and efficiently cope with rapidly changing environment.Key words: abidopsis, adaptation, avoidance, root, salt stress, tropic growthOwing to their sessile nature, plant roots are constantly bombarded with various environmental stimuli from the soil, such as gravity, physical obstacles and imbalanced distribution of water and/or nutrients and high salinity. Where to grow is an important developmental decision in the life cycle of a plant that is crucial for its adaptation and the subsequent reproductive success. The proper orientation of root growth is shaped by both the developmental inputs and external signals.^1,2 The overwhelming environmental factor that modulates root growth direction is gravity, and plant primary roots grow downward toward the gravity vector. This directed growth of root in response to gravity is named as tropic growth to gravity or gravitropism. Studies of gravity perception and signaling pathway of the root cap at the primary root of Arabidopsis strongly support the starch statolith hypothesis.³ In this hypothesis, the columella cells in the root cap, which contain sedimentable amyloplasts, are the gravity-perceptive site in roots. The inner columella cells of the second tier have been proposed as making the greatest contribution to root gravitropism.⁴ Upon gravity stimulation, cytosolic ions such as Ca²⁺ and rapid cytoplasmic alkalization may be involved in gravity signal transduction.^5–7 Asymmetric distribution of auxin in roots caused by basipetal transport mainly through the auxin efflux carrier PIN-FORMED2 (PIN2), which is distributed asymmetrically within the cells, results in gravitropic root response of the root elongation zone.^8,9In contrast to our understanding of gravitropism of root, our knowledge of tropistic responses of root to other major environmental stimuli, such as water availability, imbalanced nutrient distribution and high salinity, and the interplay between these stimuli in determining the directional growth of root remains enigmatic. Recent studies have confirmed the existence of hydrotropism and the molecular genetic basis of the tropistic growth of root to water in determining the final direction of root growth starts to be deciphered.^10–12 Hydrotropic growth of roots is an important trait for plants to actively find water and to optimize their fitness under drought condition. Salinity is another major constraint to root system development, and limits the productivity of agricultural crops and the distribution of plant species.^13–15 It is known that salt stress-induced disturbed balance of ions is the primary cause for inhibition of plant growth and subsequent yield reduction. How does root minimize entrance of harmful ions and subsequently avoid salt injury? Does plant have capacity to sense salt signal, and prevent potentially harmful ions reaching root and shoot?Previous studies have shown that plant use different strategies to avoid salt injury at various levels. After Na⁺ enters the root cells, the Casparian strip can restrict the movements of the harmful ion into the xylem.¹⁶ Root cells also avoid salt injury by extruding Na⁺ actively back to the outside solution. This energy-dependent ion efflux from cytosol across the plasma membrane is mediated by SOS1 gene, a Na⁺-H⁺ antiporter, which is regulated by at least other genes, SOS3 (calcium binding protein) and SOS2 (serine/threonine kinase). This is the well characterized SOS (Salt Overly Sensitive) signaling pathway.^17,18 Another way for plant root cells to avoid ion injury is to accumulate Na⁺ into vacuole. Vacuolar compartmentation of Na⁺ is also in part regulated by Na⁺-H⁺ antiporters, such as AtNHX1.¹⁹ These findings reveal mechanisms of how plants avoid Na⁺ injury after passive entrance of sodium ions into root cells. We questioned whether a plant is capable of actively preventing the harmful ions from reaching root cells or escape from high salinity in the environment, and how plant roots respond to changing salt conditions, because salt distribution is unbalanced under natural saline conditions, especially after rain and irrigation. With a new assay that allows us to specifically address how plant roots respond to changing salt levels, we discovered an alternative adaptive mechanism for plant root to avoid salt injury.²⁰We set up a two-layer medium assay in which a sodium ion gradient would be generated. A normal nutrient agar medium is at the top of the growth bottle and an agar with salt-stressed medium is in the bottom of the bottle. This simple assay allows us to monitor root growth and orientation. The roots of the wild type seedlings penetrated the interface of the layers and grew straight downwards exhibiting gravitropism, when both layers were MS media. In contrast, when the bottom medium contained NaCl, roots of seedlings grew downward first, and then curved and grew upward toward the lower levels of salt. Roots started to bend upward at an early stage even before contacting high-salt medium (250 mM NaCl) on the bottom. The results indicate that roots can sense ion gradients in the growing environment and transduce the signal, combine with internal signals to make decisions that enable roots to stay away from high salt.^21,22 Here, we would like to propose this salt-induced tropic growth as a salt-avoidance tropism, which is an important adaptive behavior for plant roots to avoid salt injury and direct them toward their goal of optimal fitness.²³ Because salt stress inhibits root elongation, we tested impact of salt-induced negative gravitropism on the root growth. The results showed that inhibitory effect of salt on root growth was largely alleviated with this tropic curve (Fig. 1), further verifying our hypothesis that the salt-induced developmental plasticity is a salt-avoidance behavior (Fig. 2).Open in a separate windowFigure 1Effects of salt on root elongation of Arabidopsis thaliana seedlings from different salt treatments. The inhibitory effect of salt stress on root growth was greatly alleviated in the wild type (Col-0) when root growth of the seedlings was analyzed using a two-layer medium assay (black bars). The MS nutrient medium is on the top, and NaCl concentrations in the media on the bottom are 0, 150 and 250 mM. More severe inhibition of root growth of the seedlings by various levels of NaCl in a root bending assay (white bars) was observed. Data represents means of measurements from >40 individuals from three independent experiments. Bars represent standard error.Open in a separate windowFigure 2An illustrative model of the sensing and response by the plant root when grown under different saline conditions. This model proposes two major mechanisms of salt responses by plants, where salt tolerance is the ability to function while stressed; Salt avoidance is the capacity to stay away from salt stress when growing in changing saline conditions.Another important point that we would like to bring out based on our observation in this work is that salinity also stimulated shoot positive gravitropism or negative phototropism. The observation implicates long-distance communication from root to shoot during plant salt response in the stressed plants. The exact biological function of shoot tropic growth, the signals in this long-distance communication, and underlying molecular mechanism still remains unknown.In conclusion, our study has revealed a novel complex adaptive mechanism that provides plants a capacity for avoiding injury from salt. The hypothesis we have proposed here should provide novel insights into plant stress avoidance. Further analysis using a combinatorial approach, mutant analysis and genomics, is required to decipher the molecular network underlying this salt-avoidance behavior.     

Transgenic nonhuman primates for neurodegenerative diseases

Animal models that represent human diseases constitute an important tool in understanding the pathogenesis of the diseases, and in developing effective therapies. Neurodegenerative diseases are complex disorders involving neuropathologic and psychiatric alterations. Although transgenic and knock-in mouse models of Alzheimer's disease, (AD), Parkinson's disease (PD) and Huntington's disease (HD) have been created, limited representation in clinical aspects has been recognized and the rodent models lack true neurodegeneration. Chemical induction of HD and PD in nonhuman primates (NHP) has been reported, however, the role of intrinsic genetic factors in the development of the diseases is indeterminable. Nonhuman primates closely parallel humans with regard to genetic, neuroanatomic, and cognitive/behavioral characteristics. Accordingly, the development of NHP models for neurodegenerative diseases holds greater promise for success in the discovery of diagnoses, treatments, and cures than approaches using other animal species. Therefore, a transgenic NHP carrying a mutant gene similar to that of patients will help to clarify our understanding of disease onset and progression. Additionally, monitoring disease onset and development in the transgenic NHP by high resolution brain imaging technology such as MRI, and behavioral and cognitive testing can all be carried out simultaneously in the NHP but not in other animal models. Moreover, because of the similarity in motor repertoire between NHPs and humans, it will also be possible to compare the neurologic syndrome observed in the NHP model to that in patients. Understanding the correlation between genetic defects and physiologic changes (e.g. oxidative damage) will lead to a better understanding of disease progression and the development of patient treatments, medications and preventive approaches for high risk individuals. The impact of the transgenic NHP model in understanding the role which genetic disorders play in the development of efficacious interventions and medications is foreseeable.     

Forced expression of murine IL-17E induces growth retardation, jaundice, a Th2-biased response, and multiorgan inflammation in mice.

IL-17 is a proinflammatory cytokine, and its in vivo expression induces neutrophilia in mice. IL-17E is a recently described member of an emerging family of IL-17-related cytokines. IL-17E has been shown to bind IL-17Rh1, a protein distantly related to the IL-17R, suggesting that IL-17E probably possesses unique biological functions. In this study, we have identified the murine ortholog of IL-17E and developed transgenic mice to characterize its actions in vivo. Biological consequences of overexpression of murine (m)IL-17E, both unique to IL-17E and similar to IL-17, were revealed. Exposure to mIL-17E resulted in a Th2-biased response, characterized by eosinophilia, increased serum IgE and IgG1, and a Th2 cytokine profile including elevated serum levels of IL-13 and IL-5 and elevated gene expression of IL-4, IL-5, IL-10, and IL-13 was observed in many tissues. Increased gene expression of IFN-gamma in several tissues and elevated serum TNF-alpha were also noted. In addition, IL-17E induces G-CSF production in vitro and mIL-17E-transgenic mice had increased serum G-CSF and exhibit neutrophilia, a property shared by IL-17. Moreover, exposure to mIL-17E elicited pathological changes in multiple tissues, particularly liver, heart, and lungs, characterized by mixed inflammatory cell infiltration, epithelial hyperplasia, and hypertrophy. Taken together, these findings suggest that IL-17E is a unique pleiotropic cytokine and may be an important mediator of inflammatory and immune responses.     

The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog.

The Caenorhabditis elegans sel-10 protein is structurally similar to E3 ubiquitin ligases and is a negative regulator of Notch (lin-12) and presenilin signaling. In this report, we characterize the mammalian Sel-10 homolog (mSel-10) and analyze its effects on Notch signaling. We find that mSel-10 localizes to the cell nucleus, and that it physically interacts with the Notch 1 intracellular domain (IC) and reduces Notch 1 IC-mediated activation of the HES 1 promoter. Notch 1 IC is ubiquitinated by mSel-10, and ubiquitination requires the presence of the most carboxyl-terminal region of the Notch IC, including the PEST domain. In the presence of the proteasome inhibitor MG132, the amount of Notch 1 IC and its level of ubiquitination are increased. Interestingly, this accumulation of Notch 1 IC in the presence of MG132 is accompanied by decreased activation of the HES 1 promoter, suggesting that ubiquitinated Notch 1 IC is a less potent transactivator. Finally, we show that mSel-10 itself is ubiquitinated and degraded by the proteasome. In conclusion, these data reveal the importance of ubiquitination and proteasome-mediated degradation for the activity and turnover of Notch ICs, and demonstrate that mSel-10 plays a key role in this process.     

Prevalence of Vitamin D Deficiency in Sickle Cell Disease: A Systematic Review

Vitamin D deficiency has emerged as a public health focus in recent years and patients with sickle cell disease (SCD) reportedly have a high prevalence of the condition. Our objectives were to summarize definitions of vitamin D deficiency and insufficiency used in the literature, and to determine the prevalence and magnitude of each in patients with SCD through a systematic review conducted according to PRISMA guidelines. From a PubMed search, 34 potential articles were identified and 15 met eligibility criteria for inclusion. Definitions of deficiency and insufficiency varied greatly across studies making direct comparisons difficult. This review provides evidence to suggest that suboptimal vitamin D levels are highly prevalent among those with SCD, far more so than in comparable non-SCD patients or matched control populations. Defining deficiency as vitamin D <20ng/mL, prevalence estimates in SCD populations range from 56.4% to 96.4%. When compared with results from the population-based National Health and Nutrition Examination Survey, however, the general African American population appeared to have a similarly high prevalence of vitamin D deficiency. African American patients with and without SCD were both substantially higher than that of Caucasians. What remains to be determined is whether there are adverse health effects for patients with SCD because of concurrent vitamin D deficiency.