ER Stress-Induced eIF2-alpha Phosphorylation Underlies Sensitivity of Striatal Neurons to Pathogenic Huntingtin

A hallmark of Huntington's disease is the pronounced sensitivity of striatal neurons to polyglutamine-expanded huntingtin expression. Here we show that cultured striatal cells and murine brain striatum have remarkably low levels of phosphorylation of translation initiation factor eIF2 alpha, a stress-induced process that interferes with general protein synthesis and also induces differential translation of pro-apoptotic factors. EIF2 alpha phosphorylation was elevated in a striatal cell line stably expressing pathogenic huntingtin, as well as in brain sections of Huntington's disease model mice. Pathogenic huntingtin caused endoplasmic reticulum (ER) stress and increased eIF2 alpha phosphorylation by increasing the activity of PKR-like ER-localized eIF2 alpha kinase (PERK). Importantly, striatal neurons exhibited special sensitivity to ER stress-inducing agents, which was potentiated by pathogenic huntingtin. We could strongly reduce huntingtin toxicity by inhibiting PERK. Therefore, alteration of protein homeostasis and eIF2 alpha phosphorylation status by pathogenic huntingtin appears to be an important cause of striatal cell death. A dephosphorylated state of eIF2 alpha has been linked to cognition, which suggests that the effect of pathogenic huntingtin might also be a source of the early cognitive impairment seen in patients

Challenges and lessons learned from digitizing small Brazilian herbaria.

The digital era provides new opportunities for taxonomists, as well as for everyone that studies biodiversity. Many herbaria have been able to digitize their collections, a process that started with the typing of label data, moving more recently towards the digitization of each sample with the simultaneous acquisition of high-resolution images. Here we discuss some of the challenges we faced in digitizing samples and provide a series of suggestions to avoid common mistakes for herbaria that have yet to start the process. We used a professional camera, database management software, and a barcode scanner to digitize the collections of herbaria CRI, ECT, FURB, LUSC, and UFRN. Pre-revision of samples with prior restoration when needed, barcode fixation, and a good database allowed faster digitization of samples. Good database software and the formation of a network among small herbaria accelerated digitization and increased the number of images available of Brazilian biodiversity. Thus far, our joint efforts made 118,000 specimen images available online with the purpose of accelerating botanical research

Delayed Senescence in Soybean: Terminology, Research Update, and Survey Results from Growers

The terms used to describe symptoms of delayed senescence in soybean often are used inconsistently or interchangeably and do not adequately distinguish the observed symptoms in the field. Various causes have been proposed to explain the development of delayed senescence symptoms. In this article, we review published reports on delayed senescence symptoms in soybean, summarize current research findings, provide examples of terms related to specific symptoms, and present an overview of the results of a multi-state survey directed to soybean growers to understand their concerns about delayed soybean senescence. Some of these terms, such as green bean syndrome and green stem syndrome, describe symptoms induced by biotic factors, while other terms describe symptoms associated with abiotic factors. Some delayed senescence terms involve the whole plant remaining green while other terms include just the stem and other plant parts such as pods. In the grower survey, 77% reported observing soybean plants or plant parts that remained green after most plants in the field were fully mature with ripe seed. Most respondents attributed these symptoms to changes in breeding and choice of cultivars. At the end of this article, we standardized the terms used to describe delayed senescence in soybean

Right ventricular dysfunction in patients with Brugada-like electrocardiography: a two dimensional strain imaging study

<p>Abstract</p> <p>Background</p> <p>Sodium channel blockers augment ST-segment elevation in the right precordial leads in patients undergoing Brugada-type electrocardiography (ECG). However, their effect on echocardiographic features is not known. We address this by assessing global and regional ventricular function using conventional Doppler and two- dimensional (2D) speckle tracking techniques.</p> <p>Methods</p> <p>Thirty-one patients with Brugada-type ECG were studied. A pure sodium channel blocker, pilsicainide, was used to provoke an ECG response. The percentage longitudinal systolic myocardial strain at the base of both the right ventricular (RV) free wall and the interventricular septum wall was measured using 2D speckle tracking. Left ventricular (LV) and RV myocardial performance (TEI) indices were also measured.</p> <p>Results</p> <p>The pilsicainide challenge provoked a positive ECG response in 13 patients (inducible group). In the inducible group, longitudinal strain was significantly reduced only at the RV (-27.3 ± 5.4% vs -22.1 ± 3.6%, <it>P </it>< 0.01), and both RV and LV TEI indices increased (RV: 0.19 ± 0.09 vs 0.27 ± 0.11, <it>P </it>< 0.05; LV: 0.30 ± 0.10 vs 0.45 ± 0.10, <it>P </it>< 0.01) after pilsicainide administration.</p> <p>Conclusions</p> <p>Temporal and spatial analysis using the TEI index and 2D strain imaging revealed the deterioration of global ventricular function associated with conduction disturbance and RV regional function in patients with Brugada-type ECG and coved type ST elevation due to administration of a sodium channel blocker.</p

A selected bibliography on parameter optimization methods suitable for hybrid computation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68333/2/10.1177_003754976700800610.pd

Geologic controls on the recent evolution of oyster reefs in Apalachicola Bay and St. George Sound, Florida

This paper is not subject to U.S. copyright. The definitive version was published in Estuarine, Coastal and Shelf Science 88 (2010): 385-394, doi:10.1016/j.ecss.2010.04.019.Apalachicola Bay and St. George Sound contain the largest oyster fishery in Florida, and the growth and distribution of the numerous oyster reefs here are the combined product of modern estuarine conditions in the bay and its late Holocene evolution. Sidescan-sonar imagery, bathymetry, high-resolution seismic profiles, and sediment cores show that oyster beds occupy the crests of a series of shoals that range from 1 to 7 km in length, trend roughly north-south perpendicular to the long axes of the bay and sound, and are asymmetrical with steeper sides facing to the west. Surface sediment samples show that the oyster beds consist of shelly sand, while much of the remainder of the bay floor is covered by mud delivered by the Apalachicola River. The present oyster reefs rest on sandy delta systems that advanced southward across the region between 6400 and 4400 yr BP when sea level was 4–6 m lower than present. Oysters started to colonize the region around 5100 yr BP and became extensive by 1200 and 2400 yr BP. Since 1200 yr BP, their aerial extent has decreased due to burial of the edges of the reefs by the prodelta mud that continues to be supplied by the Apalachicola River. Oyster reefs that are still active are narrower than the original beds, have grown vertically, and become asymmetrical in cross-section. Their internal bedding indicates they have migrated westward, suggesting a net westerly transport of sediment in the bay.Funding for this research was provided by the NOAA Coastal Services Center

Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

BACKGROUND Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, −3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute–National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.