OPT3 is a component of the iron-signaling network between leaves and roots and misregulation of OPT3 leads to an over-accumulation of cadmium in seeds.

Plants and seeds are the main dietary sources of zinc, iron, manganese, and copper, but are also the main entry point for toxic elements such as cadmium into the food chain. We report here that an Arabidopsis oligopeptide transporter mutant, opt3-2, over-accumulates cadmium (Cd) in seeds and roots but, unexpectedly, under-accumulates Cd in leaves. The cadmium distribution in opt3-2 differs from iron, zinc, and manganese, suggesting a metal-specific mechanism for metal partitioning within the plant. The opt3-2 mutant constitutively up-regulates the Fe/Zn/Cd transporter IRT1 and FRO2 in roots, indicative of an iron-deficiency response. No genetic mutants that impair the shoot-to-root signaling of iron status in leaves have been identified. Interestingly, shoot-specific expression of OPT3 rescues the Cd sensitivity and complements the aberrant expression of IRT1 in opt3-2 roots, suggesting that OPT3 is required to relay the iron status from leaves to roots. OPT3 expression was found in the vasculature with preferential expression in the phloem at the plasma membrane. Using radioisotope experiments, we found that mobilization of Fe from leaves is severely affected in opt3-2, suggesting that Fe mobilization out of leaves is required for proper trace-metal homeostasis. When expressed in yeast, OPT3 does not localize to the plasma membrane, precluding the identification of the OPT3 substrate. Our in planta results show that OPT3 is important for leaf phloem-loading of iron and plays a key role regulating Fe, Zn, and Cd distribution within the plant. Furthermore, ferric chelate reductase activity analyses provide evidence that iron is not the sole signal transferred from leaves to roots in leaf iron status signaling

Azithromycin in the extremely low birth weight infant for the prevention of Bronchopulmonary Dysplasia: a pilot study

<p>Abstract</p> <p>Background</p> <p>Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis. Bronchopulmonary dysplasia (BPD) is a pulmonary disorder which causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis and impaired alveolar development. The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight (≤ 1000 grams) population.</p> <p>Methods</p> <p>Infants ≤ 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level III, regional referral center) from 9/1/02-6/30/03 were eligible for this pilot study. The pilot study was double-blinded, randomized, and placebo-controlled. Infants were randomized to treatment or placebo within 12 hours of beginning mechanical ventilation (IMV) and within 72 hours of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study. Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed by intention to treat using Chi-square and ANOVA.</p> <p>Results</p> <p>A total of 43 extremely premature infants were enrolled in this pilot study. Mean gestational age and birth weight were similar between groups. Mortality, incidence of BPD, days of IMV, and other morbidities were not significantly different between groups. Post-natal steroid use was significantly less in the treatment group [31% (6/19)] vs. placebo group [62% (10/16)] (p = 0.05). Duration of mechanical ventilation was significantly less in treatment survivors, with a median of 13 days (1–47 days) vs. 35 days (1–112 days)(p = 0.02).</p> <p>Conclusion</p> <p>Our study suggests that azithromycin prophylaxis in extremely low birth weight infants may effectively reduce post-natal steroid use for infants. Further studies are needed to assess the effects of azithromycin on the incidence of BPD and possible less common side effects, before any recommendations regarding routine clinical use can be made.</p

The Next Linear Collider machine protection system

The Next Linear Collider (NLC) electron and positron beams are capable of damaging the linac accelerating structure and beamline vacuum chambers during an individual aberrant accelerator pulse. Machine protection system (MPS) considerations, outlined in this paper, have an impact on the engineering and design of most machine components downstream of the damping ring injector complex. The MPS consists of two functional levels. The first is a system that provides a benign, single bunch, low intensity, high emittance beam that will be used for commissioning and at any time that the integrity or the settings of the downstream component are in doubt. This level also provides for the smooth transition back and forth between high power operation and the benign diagnostic pilot bunch operation. The pilot bunch parameters in the main linac are estimated on the basis of the expected stress in the accelerator structure copper. Beam tests have been done at the SLAC linac to examine the behaviour of the copper at the damage stress threshold. Typical pilot beam parameters (compared with nominal) are: 10 times reduced intensity, 10 times increased horizontal emittance and 1000 times increased vertical emittance, resulting in a reduction in charge density of 105. The second level is the primary protection against a single aberrant pulse. It’s goal is to reduce the possibility that a substantial transverse field changes the trajectory of the high power beam from one pulse to the next. All devices that could produce such a field are 1) monitored by a fast response network and 2) have deliberately slowed response times. A ‘maximum allowable interpulse difference ’ is evaluated for each such device as well as the beam trajectory monitors in each interpulse period.

The burden of non-TB lung disease presenting to TB clinics in The Gambia: preliminary data in the Xpert® MTB/Rif era

In some low and middle-income countries, 10-20% of patients presenting with a persistent cough have tuberculosis (TB). Once TB is excluded, health service provision for alternative diagnoses is limited. We prospectively studied patients with two Xpert-negative sputum results presenting to a TB clinic in The Gambia. Of 239 patients, 108 did not have TB; 65/102 (6 were lost to follow-up) had alternative diagnoses, 24.6% of which were non-respiratory; 37/102 had no diagnosis, 27.0% of whom were HIV-1-positive; 37.8% had a history of TB and 24.3% smoked. We highlight the need for general health service integration with TB platforms and exploration of non-TB patients with chronic respiratory symptoms

Platelet CD36 Signaling Through ERK5 Promotes Caspase-Dependent Procoagulant Activity and Fibrin Deposition In Vivo

Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer exposure and, subsequently, recruitment of the prothrombinase complex, resulting in the generation of fibrin from the activation of thrombin. Caspase activity was observed when platelets were stimulated with oxLDL. This was prevented by inhibiting CD36 and ERK5. Furthermore, oxLDL potentiates convulxin/glycoprotein VI–mediated fibrin formation by platelets, which was prevented when CD36, ERK5, and caspases were inhibited. Using 2 in vivo arterial thrombosis models in apoE-null hyperlipidemic mice demonstrated enhanced arterial fibrin accumulation upon vessel injury. Importantly, absence of ERK5 in platelets or mice lacking CD36 displayed decreased fibrin accumulation in high-fat diet–fed conditions comparable to that seen in chow diet–fed animals. These findings suggest that platelet signaling through CD36 and ERK5 induces a procoagulant phenotype in the hyperlipidemic environment by enhancing caspase-mediated PSer exposure

The Grizzly, September 18, 2008

How Safe do You Feel?: Campus Discussion About Safety • Jersey in July: Not Just Another Day at the Beach for Some • Studies Suggest Nicotine Addiction Linked to Gene Mutation • Harry Potter: The Boy Who Brought Lawsuits? • Motion with Emotion: Professional Dancer Ruth Andrian Arrives at UC • Ursinus Kicks Off This Year\u27s International Film Festival • Opinions: Democrat\u27s Perspective on Potential VP Sarah Palin; Barack Obama: The Only Right Choice for U.S. President • Volleyball Vamps Up for First Victorious Season in Years • UC Field Hockey Prepares to Restore Remarkable Reputationhttps://digitalcommons.ursinus.edu/grizzlynews/1768/thumbnail.jp