Wnt/β-catenin signaling is required for development of the exocrine pancreas

Background  

β-catenin is an essential mediator of canonical Wnt signaling and a central component of the cadherin-catenin epithelial adhesion complex. Dysregulation of β-catenin expression has been described in pancreatic neoplasia. Newly published studies have suggested that β-catenin is critical for normal pancreatic development although these reports reached somewhat different conclusions. In addition, the molecular mechanisms by which loss of β-catenin affects pancreas development are not well understood. The goals of this study then were; 1] to further investigate the role of β-catenin in pancreatic development using a conditional knockout approach and 2] to identify possible mechanisms by which loss of β-catenin disrupts pancreatic development. A Pdx1-cre mouse line was used to delete a floxed β-catenin allele specifically in the developing pancreas, and embryonic pancreata were studied by immunohistochemistry and microarray analysis.     

Gene expression profiling and its practice in drug development

The availability of sequenced genomes of human and many experimental animals necessitated the development of new technologies and powerful computational tools that are capable of exploiting these genomic data and ask intriguing questions about complex nature of biological processes. This gave impetus for developing whole genome approaches that can produce functional information of genes in the form of expression profiles and unscramble the relationships between variation in gene expression and the resulting physiological outcome. These profiles represent genetic fingerprints or catalogue of genes that characterize the cell or tissue being studied and provide a basis from which to begin an investigation of the underlying biology. Among the most powerful and versatile tools are high-density DNA microarrays to analyze the expression patterns of large numbers of genes across different tissues or within the same tissue under a variety of experimental conditions or even between species. The wide spread use of microarray technologies is generating large sets of data that is stimulating the development of better analytical tools so that functions can be predicted for novel genes. In this review, the authors discuss how these profiles are being used at various stages of the drug discovery process and help in the identification of new drug targets, predict the function of novel genes, and understand individual variability in response to drugs.     

Hyperspectral Remote Sensing of Canopy Biodiversity in Hawaiian Lowland Rainforests

Mapping biological diversity is a high priority for conservation research, management and policy development, but few studies have provided diversity data at high spatial resolution from remote sensing. We used airborne imaging spectroscopy to map woody vascular plant species richness in lowland tropical forest ecosystems in Hawai’i. Hyperspectral signatures spanning the 400–2,500 nm wavelength range acquired by the NASA Airborne Visible and Infrared Imaging Spectrometer (AVIRIS) were analyzed at 17 forest sites with species richness values ranging from 1 to 17 species per 0.1–0.3 ha. Spatial variation (range) in the shape of the AVIRIS spectra (derivative reflectance) in wavelength regions associated with upper-canopy pigments, water, and nitrogen content were well correlated with species richness across field sites. An analysis of leaf chlorophyll, water, and nitrogen content within and across species suggested that increasing spectral diversity was linked to increasing species richness by way of increasing biochemical diversity. A linear regression analysis showed that species richness was predicted by a combination of four biochemically-distinct wavelength observations centered at 530, 720, 1,201, and 1,523 nm (r ² = 0.85, p < 0.01). This relationship was used to map species richness at approximately 0.1 ha resolution in lowland forest reserves throughout the study region. Future remote sensing studies of biodiversity will benefit from explicitly connecting chemical and physical properties of the organisms to remotely sensed data.     

Home-based exercise rehabilitation in addition to specialist heart failure nurse care: design, rationale and recruitment to the Birmingham Rehabilitation Uptake Maximisation study for patients with congestive heart failure (BRUM-CHF): a randomised controlled trial

Background

We aimed to assess whether we could identify a graded association between increasing number of components of the metabolic syndrome and cardiac structural and functional abnormalities independently of predicted risk of coronary heart disease by the Framingham risk score.

Methods

We conducted a cross-sectional study on a random sample of the urban population of Porto aged 45 years or over. Six hundred and eighty-four participants were included. Data were collected by a structured clinical interview with a physician, ECG and a transthoracic M-mode and 2D echocardiogram. The metabolic syndrome was defined according to ATPIII-NCEP. The association between the number of features of the metabolic syndrome and the cardiac structural and functional abnormalities was assessed by 3 multivariate regression models: adjusting for age and gender, adjusting for the 10-year predicted risk of coronary heart disease by Framingham risk score and adjusting for age, gender and systolic blood pressure.

Results

There was a positive association between the number of features of metabolic syndrome and parameters of cardiac structure and function, with a consistent and statistically significant trend for all cardiac variables considered when adjusting for age and gender. Parameters of left ventricular geometry patterns, left atrial diameter and diastolic dysfunction maintained this trend when taking into account the 10-year predicted risk of coronary heart disease by the Framingham score as an independent variable, while left ventricular systolic dysfunction did not. The prevalence of left ventricular diastolic dysfunction, and the mean left ventricular mass, left ventricular diameter and left atrial diameter increased significantly with the number of features of the metabolic syndrome when additionally adjusting for systolic blood pressure as a continuous variable.

Conclusion

Increasing severity of metabolic syndrome was associated with increasingly compromised structure and function of the heart. This association was independent of Framingham risk score for indirect indices of diastolic dysfunction but not systolic dysfunction, and was not explained by blood pressure level.     

High-capacity purification of His-tagged proteins by affinity membranes containing functionalized polymer brushes

Porous membrane absorbers are attractive for increasing the rate of protein purification, but their binding capacity is low relative to porous beads. Modification of membranes with functionalized polymer brushes, however, can greatly enhance capacity. This work demonstrates that membrane modification with poly(2-hydroxyethyl methacrylate) (PHEMA) brushes derivatized with nitrilotriacetate-Ni2+ (NTA-Ni2+) complexes allows purification of polyhistidine-tagged ubiquitin (HisU) in less than 30 min with a binding capacity of 120 mg of HisU/cm3 of porous alumina membrane. Adsorption isotherms show that saturation of the brushes occurs at HisU concentrations as low as 0.04 mg/mL and that these brushes can bind up to 23 monolayers of HisU. Gel electrophoresis reveals that the purity of eluted HisU is more than 99%, even when the initial feed solution contains 10% bovine serum or a 20-fold excess of BSA. Thus, reusable porous membranes modified by PHEMA-NTA-Ni2+ brushes are attractive candidates for rapid purification of polyhistidine-tagged proteins.     

Imaging mass spectrometry of neuropeptides in decapod crustacean neuronal tissues

Imaging mass spectrometry (IMS) of neuropeptides in crustacean neuronal tissues was performed on a MALDI-TOF/TOF instrument. Sample preparation protocols were developed for the sensitive detection of these highly complex endogenous signaling molecules. The neuromodulatory complements of the pericardial organ (PO) and brain of the Jonah crab, Cancer borealis, were mapped. Distributions of peptide isoforms belonging to 10 neuropeptide families were investigated using the IMS technique. Often, neuropeptides of high sequence homology were similarly located. However, two RFamide-family peptides and a truncated orcokinin peptide were mapped to locations distinct from other members of their respective families. Over 30 previously sequenced neuropeptides were identified based on mass measurement. For increased confidence of identification, select peptides were fragmented by post-source decay (PSD) and collisional-induced dissociation (CID). Collectively, this organ-level IMS study elucidates the spatial relationships between multiple neuropeptide isoforms of the same family as well as the relative distributions of neuropeptide families.     

Mitoproteome plasticity of rat brown adipocytes in response to cold acclimation

Cold acclimation induces an adaptative increase in respiration in brown adipose tissue (BAT). A comparative analysis by two-dimensional differential in-gel electrophoresis of mitochondrial protein patterns found in rat control and cold-acclimated BAT was performed. A total of 58 proteins exhibiting significant differences in their abundance was unambiguously identified. Proteins implicated in the major catabolic pathways were up-regulated as were ATP synthase and mitofilin. Moreover, these results support the fact that adipocytes can balance their ATP synthesis and their heat production linked to UCP1-sustained uncoupling.     

Effects of helicopter net-gunning on survival of bighorn sheep

Wildlife capture, and the data collection associated with it, has led to major advancements in ecology that are integral to decision making pertaining to wildlife conservation. Capturing wildlife, however, can cause lethal and non-lethal risks to animals. Understanding the factors that contribute to the level of risk involved in wildlife capture is therefore important for the development and implementation of the safest and most effective methodologies. We used data from 736 animal captures of 389 individuals for 2 subspecies of female bighorn sheep (Rocky Mountain bighorn [Ovis canadensis canadensis], Sierra Nevada bighorn sheep [O. c. sierrae]) in Wyoming and California, USA, in 2002–2020 to evaluate the degree and extent of time that capture via helicopter net-gunning affects survival. We compared pre- and post-capture survival during a 10-week window centered on a capture event, and post-capture survival between captured animals and animals that were monitored but not captured during the 10-week window. Additionally, we evaluated the effects of handling techniques (number of times captured, season of capture event, handling time, chase time, and body temp) and biological factors (age and nutritional condition) on probability of capture mortality. Mean daily survival was 0.9992 during a 5-week pre-capture window, dropped to 0.9864 on the day of capture, and rebounded within 3 days of capture to pre-capture levels and that of sheep that were not captured. Overall, direct mortality resulting from capture was 1.36%, with 0.54% mortality occurring within the 3 days following a capture event for an overall 1.90% capture-related mortality. The only handling and biological metrics that influenced the probability of capture mortality were rectal temperature and nutritional condition; high initial rectal temperatures and poor body condition were associated with increased risk of mortality in the days following capture. Overall, helicopter net-gunning imposed low and short-term risk to survival of female bighorn sheep. To reduce bias in survival estimates, we recommend using a 3-day censorship window for post-capture mortalities as opposed to the common practice of a 2–5-week censor window. Helicopter net-gunning, including annual or seasonal recaptures, remains an effective and comparatively safe technique for capture and associated data collection of bighorn sheep.