Design and chemical synthesis of a homogeneous polymer-modified erythropoiesis protein

We report the design and total chemical synthesis of "synthetic erythropoiesis protein" (SEP), a 51-kilodalton protein-polymer construct consisting of a 166-amino-acid polypeptide chain and two covalently attached, branched, and monodisperse polymer moieties that are negatively charged. The ability to control the chemistry allowed us to synthesize a macromolecule of precisely defined covalent structure. SEP was homogeneous as shown by high-resolution analytical techniques, with a mass of 50,825 +/-10 daltons by electrospray mass spectrometry, and with a pI of 5.0. In cell and animal assays for erythropoiesis, SEP displayed potent biological activity and had significantly prolonged duration of action in vivo. These chemical methods are a powerful tool in the rational design of protein constructs with potential therapeutic applications.     

Intra- and interobserver assessments of intestinal wall thickness and segmentations from transverse sections of feline abdominal ultrasound images

Measurements of intestinal wall thicknesses from ultrasound imaging (US) are routinely used to support diagnoses of intestinal disorders in cats, however published studies describing observer agreement are currently lacking. The aim of this retrospective, observer agreement study was to quantify inter- and intraobserver repeatability and agreement in the measurement of intestinal wall layer thicknesses and the segmentation of transverse sections of small intestines in US images of 20 cats. Intestinal wall layer thickness measurements of the mucosa, submucosa, muscularis, serosa layer, and total thickness of these layers were performed on five cats with small cell epitheliotropic lymphoma, five with inflammatory bowel disease, and 10 with other conditions. Thickness measurements and the segmentation encompassing the serosa layer were obtained from five observers four times non-sequentially. The average standard deviation in thickness measurements (95% confidence interval) in the mucosa, submucosa, muscularis, serosa, and total thickness were 0.35 (0.07–0.95), 0.24 (0.07-0.52), 0.22 (0.06-0.49), 0.20 (0.05-0.49), and 0.57 (0.11-1.60) mm, respectively. The average intraclass correlation coefficients, which estimates the degree of consistency in thickness measurements and segmentation areas for each observer, ranged from 0.355 to 0.870 and 0.850 to 0.993, respectively. The interclass correlation coefficient, which estimates the degree of consistency when measuring a thickness or segmentation area over all observers ranged from 0.115 to 0.753, and 0.811 to 0.902, respectively. The overall average Dice Coefficient, which estimates the extent of overlap of the segmentations for all observers was 0.957 (0.933 to 0.972). Our results suggest segmentations of small intestines have a higher interobserver agreement than measurements of intestinal wall thicknesses.     

Necrotizing Meningoencephalitis in Atypical Dog Breeds: A Case Series and Literature Review

Background

Canine necrotizing meningoencephalitis (NME) is a fatal, noninfectious inflammatory disease of unknown etiology. NME has been reported only in a small number of dog breeds, which has led to the presumption that it is a breed‐restricted disorder.

Hypothesis/Objectives

Our objective was to describe histopathologically confirmed NME in dog breeds in which the condition has not been reported previously and to provide preliminary evidence that NME affects a wider spectrum of dog breeds than previously reported.

Animals

Four dogs with NME.

Methods

Archives from 3 institutions and from 1 author''s (BS) collection were reviewed to identify histopathologically confirmed cases of NME in breeds in which the disease has not been reported previously. Age, sex, breed, survival from onset of clinical signs, and histopathologic findings were evaluated.

Results

Necrotizing meningoencephalitis was identified in 4 small dog breeds (Papillon, Shih Tzu, Coton de Tulear, and Brussels Griffon). Median age at clinical evaluation was 2.5 years. Histopathologic abnormalities included 2 or more of the following: lymphoplasmacytic or histiocytic meningoencephalitis or encephalitis, moderate‐to‐severe cerebrocortical necrosis, variable involvement of other anatomic locations within the brain (cerebellum, brainstem), and absence of detectable infectious agents.

Conclusions and Clinical Importance

Until now, NME has only been described in 5 small dog breeds. We document an additional 4 small breeds previously not shown to develop NME. Our cases further illustrate that NME is not a breed‐restricted disorder and should be considered in the differential diagnosis for dogs with signalment and clinical signs consistent with inflammatory brain disease.     

Presettlement and modern disturbance regimes in coast redwood forests: Implications for the conservation of old-growth stands

Coast redwood (Sequoia sempervirens), a western North American conifer of ancient lineage, has a paradoxical combination of late-successional characteristics and strong adaptations to disturbance. Despite its shade tolerance and heavy dominance of the canopy on many sites, redwood saplings are uncommon in upland old-growth stands. Information needed to ensure the conservation of old-growth redwood forests has been limited. In this review paper, we integrate evidence on redwood biology with data on the historic and modern disturbance regimes to help clarify the degree to which key attributes of redwood forests may have been dependent upon periodic disturbance. Available evidence suggests that episodes of fire, flooding, and slope failure prior to European settlement were frequent but predominantly of low to moderate severity and extent, resulting in broadly uneven-aged forests. The majority of fires prior to European settlement were apparently of human origin. Frequency and severity of the major disturbance agents have been radically changed in modern times. Fires have been largely excluded, and flooding has been altered in ways that have often been detrimental to old-growth redwoods on alluvial terraces. However, because of the apparent anthropogenic origin of most presettlement fires, the long-term evolutionary role of fire for coast redwood is ecologically ambiguous. With fire exclusion, redwood possibly could be displaced to some extent on upland sites by increasing abundance of fire-sensitive competitors. Alternatively, redwood may be able to maintain dominance by vegetative sprouting and new seedling establishment on root-wad mounds, fallen logs, and on soil exposed by slope failure. Future research priorities are suggested that will help resolve some of the current ambiguities.     

Physiology during smoltification in Atlantic salmon: effect of melatonin implants

Melatonin implants were used to override natural melatonin rhythm in groups of juvenile Atlantic salmon, Salmo salar, raised at simulated natural photoperiod (SNP) and constant light (LL) from mid-March until end of August. The experiment contained also both sham control (with non-melatonin implants) and control (no implants). No differences were found in the experimental variables between these two control groups. Growth and food intake were negatively affected by melatonin implantation. Overall, higher GH levels were observed in the SNP melatonin-implanted group, whereas no differences in GH levels were seen between the SNP control, LL control, or the LL melatonin-implanted groups. Highest food intake was seen in the LL control group. No differences in food intake were recorded between the LL melatonin-implanted and SNP control groups. Gill Na⁺, K⁺, ATPase (NKA) activity was influenced by time as well as the interaction between photoperiod and time. No differences in gill NKA activity or plasma chloride levels following transfer to seawater were seen between the groups with melatonin implants and their controls. Based on the present results, it seems apparent that melatonin does play a role in regulating food intake and growth in Atlantic salmon smolts.     

RISK ASSESSMENT IN OPEN-OCEAN AQUACULTURE: A FIRM-LEVEL INVESTMENT-PRODUCTION MODEL

ABSTRACT

We develop a framework for risk assessment in open-ocean aquaculture. The framework consists of three components: a firm-level investment-production model simulates a specific grow-out project and estimates the project's benefit-cost values, a second model calculates the risk premium for a risk-averse investor, and a third model quantifies the option value for a risk-neutral investor. We show that under uncertainty, the traditional NPV rule for making an investment should be modified. We illustrate our models using a case study of open-ocean aquaculture of Atlantic cod (Gadus morhua) in New England.     

Critical Loads of Acidity to Protect and Restore Acid-Sensitive Streams in Virginia and West Virginia

The purpose of the research described here is to apply a new approach for generating aquatic critical load (CL) and exceedance calculations for an important acid-sensitive region of the eastern USA. A widespread problem in regional aquatic acidification CL modeling for US ecosystems has been the lack of site-specific weathering data needed to derive accurate model CL estimates. A modified version of the steady-state water chemistry CL model was applied here to estimate CL and exceedances for streams throughout acid-sensitive portions of Virginia and West Virginia. A novel approach for estimating weathering across the regional landscape was applied, based on weathering estimates extracted from a well-tested, process-based watershed model of drainage water acid?Cbase chemistry and features of the landscape that are available as regional spatial data coverages. This process allowed extrapolation of site-specific weathering data from 92 stream watersheds to the regional context in three ecoregions for supporting CL calculations. Calculated CL values were frequently low, especially in the Blue Ridge ecoregion where one-third of the stream length had CL?<?50?meq/m²/year to maintain stream ANC at 50???eq/L under steady-state conditions. About half or more of the stream length in the study region was in exceedance of the CL for long-term aquatic resource protection under assumed nitrogen saturation at steady state. Land managers and air quality policy makers will need this information to better understand responses to air pollution emissions reductions and to develop ecoregion-specific air pollution targets.     

Mainestay: A high-yielding, round white potato variety for fresh market

The Mainestay potato variety is high-yielding and late-maturing producing attractive, round, white-skinned, white-fleshed tubers with medium-shallow eyes. Its major use is expected to be as a maincrop tablestock variety. Mainestay appearance ratings are similar to those of Katahdin, and greening in Mainestay tubers is less than in Kennebec. Most boil and bake qualities were rated equal to Katahdin in at least half of the tests, and Mainestay usually has a low incidence of internal defects. However, purple streak, heat necrosis, vascular discoloration, and heat sprouts have been seen on occasion. Mainestay tubers do not show the net necrosis caused by potato leafroll virus, and have shown very little hollow heart or blackspot bruising. Mainestay is susceptible to common scab and acid scab, but moderately resistant to verticillium wilt (Verticillium, albo-atrum andV. dahliae), early blight (Alternaria solani), rhizoctonia (Rhizoctonia solani), dry rot (Fusarium sambucinum), and pink rot (Phytophthora erythroseptica). It is moderately susceptible to the common race of late blight (Phytophthora infestans). Mainestay tubers are slow to mature after vine kill, and additional time is required prior to harvest in order to allow for proper periderm development and to reduce storage losses.