A Man For All Seasons : A Tribute to Dean J. Martin Burke

A Man For All Seasons : A tribute to Dean J. Martin Burk

Leveraging Attitudes, Motivations, and Values from Farmers’ Market Managers in Florida: An Opportunity to Improve Nutritional Outcomes Through Extension

Increasingly, farmers’ markets in the United States offer nutrition incentives to help limited-resource shoppers afford fresh fruits and vegetables and support local farmers. Despite increased attention to these efforts, there has been less focus on the market managers and staff members responsible for implementing and administering incentive programs. Using qualitative data collected from semi-structured phone interviews, we explore the attitudes, motivations, and values of farmers’ market managers in relation to their efforts to administer and promote a nutrition incentive program at their respective markets in Florida. Results demonstrate that program adopting managers: 1) express concern for inclusivity, social justice, and equity; 2) sympathize with the economic pressures their produce grower-vendors face; 3) are motivated to provide locally grown foods to all shoppers; 4) take pride in ethical standards and transparency protocols; and 5) value loyalty between themselves, their vendors and their customers. We believe Extension professionals can leverage prevailing attitudes among market managers to improve manager engagement with nutrition incentive programs and ensure expanded nutritional access outcomes at farmers’ markets for limited-resource shoppers

Three-year outcomes after acute kidney injury: results of a prospective parallel group cohort study

Objectives Using a prospective study design, we aimed to characterise the effect of acute kidney injury (AKI) on long-term changes in renal function in a general hospital population. Participants Hospitalised patients with AKI (exposed) and hospitalised patients without AKI (non-exposed), recruited at 3 months after hospital admission. Design Prospective, matched parallel group cohort study, in which renal function and proteinuria were measured at 3 months, 1 year and 3 years. Setting Single UK centre. Clinical end points Clinical end points at 3 years were comparison of the following variables between exposed and non-exposed groups: renal function, prevalence of proteinuria and albuminuria and chronic kidney disease (CKD) progression/development at each time point. CKD progression was defined as a decrease in the estimated glomerular filtration rate (eGFR) of ≥25% associated with a decline in eGFR stage. Results 300 exposed and non-exposed patients were successfully matched 1:1 for age and baseline renal function; 70% of the exposed group had AKI stage 1. During follow-up, the AKI group had lower eGFR than non-exposed patients at each time point. At 3 years, the mean eGFR was 60.7±21 mL/min/1.73 m2 in the AKI group compared with 68.4±21 mL/min/1.73 m2 in the non-exposed group, p=0.003. CKD development or progression at 3 years occurred in 30 (24.6%) of the AKI group compared with 10 (7.5%) of the non-exposed group, p<0.001. Albuminuria was more common in the AKI group, and increased with AKI severity. Factors independently associated with CKD development/progression after AKI were non-recovery at 90 days, male gender, diabetes and recurrent AKI. Conclusions AKI is associated with deterioration in renal function to 3 years, even in an unselected population with predominantly AKI stage 1. Non-recovery from AKI is an important factor determining long-term outcome

A systems view of epithelial–mesenchymal transition signaling states

Epithelial–mesenchymal transition (EMT) is an important contributor to the invasion and metastasis of epithelial-derived cancers. While considerable effort has focused in the regulators involved in the transition process, we have focused on consequences of EMT to prosurvival signaling. Changes in distinct metastable and ‘epigentically-fixed’ EMT states were measured by correlation of protein, phosphoprotein, phosphopeptide and RNA transcript abundance. The assembly of 1167 modulated components into functional systems or machines simplified biological understanding and increased prediction confidence highlighting four functional groups: cell adhesion and migration, metabolism, transcription nodes and proliferation/survival networks. A coordinate metabolic reduction in a cluster of 17 free-radical stress pathway components was observed and correlated with reduced glycolytic and increased oxidative phosphorylation enzyme capacity, consistent with reduced cell cycling and reduced need for macromolecular biosynthesis in the mesenchymal state. An attenuation of EGFR autophosphorylation and a switch from autocrine to paracrine-competent EGFR signaling was implicated in the enablement of tumor cell chemotaxis. A similar attenuation of IGF1R, MET and RON signaling with EMT was observed. In contrast, EMT increased prosurvival autocrine IL11/IL6-JAK2-STAT signaling, autocrine fibronectin-integrin α5β1 activation, autocrine Axl/Tyro3/PDGFR/FGFR RTK signaling and autocrine TGFβR signaling. A relatively uniform loss of polarity and cell–cell junction linkages to actin cytoskeleton and intermediate filaments was measured at a systems level. A more heterogeneous gain of ECM remodeling and associated with invasion and migration was observed. Correlation to stem cell, EMT, invasion and metastasis datasets revealed the greatest similarity with normal and cancerous breast stem cell populations, CD49f(hi)/EpCAM(-/lo) and CD44(hi)/CD24(lo), respectively. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10585-010-9367-3) contains supplementary material, which is available to authorized users

Histological and global gene expression analysis of the 'lactating' pigeon crop

Background: Both male and female pigeons have the ability to produce a nutrient solution in their crop for the nourishment of their young. The production of the nutrient solution has been likened to lactation in mammals, and hence the product has been called pigeon &lsquo;milk&rsquo;. It has been shown that pigeon &lsquo;milk&rsquo; is essential for growth and development of the pigeon squab, and without it they fail to thrive. Studies have investigated the nutritional value of pigeon &lsquo;milk&rsquo; but very little else is known about what it is or how it is produced. This study aimed to gain insight into the process by studying gene expression in the &lsquo;lactating&rsquo; crop.Results: Macroscopic comparison of &lsquo;lactating&rsquo; and non-&rsquo;lactating&rsquo; crop reveals that the &lsquo;lactating&rsquo; crop is enlarged and thickened with two very obvious lateral lobes that contain discrete rice-shaped pellets of pigeon &lsquo;milk&rsquo;. This was characterised histologically by an increase in the number and depth of rete pegs extending from the basal layer of the epithelium to the lamina propria, and extensive proliferation and folding of the germinal layer into the superficial epithelium. A global gene expression profile comparison between &lsquo;lactating&rsquo; crop and non-&rsquo;lactating&rsquo; crop showed that 542 genes are up-regulated in the &lsquo;lactating&rsquo; crop, and 639 genes are down-regulated. Pathway analysis revealed that genes up-regulated in &lsquo;lactating&rsquo; crop were involved in the proliferation of melanocytes, extracellular matrix-receptor interaction, the adherens junction and the wingless (wnt) signalling pathway. Gene ontology analysis showed that antioxidant response and microtubule transport were enriched in &lsquo;lactating&rsquo; crop.Conclusions: There is a hyperplastic response in the pigeon crop epithelium during &lsquo;lactation&rsquo; that leads to localised cellular stress and expression of antioxidant protein-encoding genes. The differentiated, cornified cells that form the pigeon &lsquo;milk&rsquo; are of keratinocyte lineage and contain triglycerides that are likely endocytosed as very low density lipoprotein (VLDL) and repackaged as triglyceride in vesicles that are transported intracellularly by microtubules. This mechanism is an interesting example of the evolution of a system with analogies to mammalian lactation, as pigeon &lsquo;milk&rsquo; fulfils a similar function to mammalian milk, but is produced by a different mechanism.<br /

Transcriptome analysis of pigeon milk production - role of cornification and triglyceride synthesis genes

BACKGROUND : The pigeon crop is specially adapted to produce milk that is fed to newly hatched young. The process of pigeon milk production begins when the germinal cell layer of the crop rapidly proliferates in response to prolactin, which results in a mass of epithelial cells that are sloughed from the crop and regurgitated to the young. We proposed that the evolution of pigeon milk built upon the ability of avian keratinocytes to accumulate intracellular neutral lipids during the cornification of the epidermis. However, this cornification process in the pigeon crop has not been characterised. RESULTS: We identified the epidermal differentiation complex in the draft pigeon genome scaffold and found that, like the chicken, it contained beta-keratin genes. These beta-keratin genes can be classified, based on sequence similarity, into several clusters including feather, scale and claw keratins. The cornified cells of the pigeon crop express several cornification-associated genes including cornulin, S100-A9 and A16-like, transglutaminase 6-like and the pigeon \u27lactating\u27 crop-specific annexin cp35. Beta-keratins play an important role in \u27lactating\u27 crop, with several claw and scale keratins up-regulated. Additionally, transglutaminase 5 and differential splice variants of transglutaminase 4 are up-regulated along with S100-A10. CONCLUSIONS: This study of global gene expression in the crop has expanded our knowledge of pigeon milk production, in particular, the mechanism of cornification and lipid production. It is a highly specialised process that utilises the normal keratinocyte cellular processes to produce a targeted nutrient solution for the young at a very high turnover

Genome-wide transcript profiling reveals novel breast cancer-associated intronic sense RNAs

Non-coding RNAs (ncRNAs) play major roles in development and cancer progression. To identify novel ncRNAs that may identify key pathways in breast cancer development, we performed high-throughput transcript profiling of tumor and normal matched-pair tissue samples. Initial transcriptome profiling using high-density genome-wide tiling arrays revealed changes in over 200 novel candidate genomic regions that map to intronic regions. Sixteen genomic loci were identified that map to the long introns of five key protein-coding genes, CRIM1, EPAS1, ZEB2, RBMS1, and RFX2. Consistent with the known role of the tumor suppressor ZEB2 in the cancer-associated epithelial to mesenchymal transition (EMT), in situ hybridization reveals that the intronic regions deriving from ZEB2 as well as those from RFX2 and EPAS1 are down-regulated in cells of epithelial morphology, suggesting that these regions may be important for maintaining normal epithelial cell morphology. Paired-end deep sequencing analysis reveals a large number of distinct genomic clusters with no coding potential within the introns of these genes. These novel transcripts are only transcribed from the coding strand. A comprehensive search for breast cancer associated genes reveals enrichment for transcribed intronic regions from these loci, pointing to an underappreciated role of introns or mechanisms relating to their biology in EMT and breast cancer

From Biomedicine to Natural History Research: EST Resources for Ambystomatid Aalamanders

BACKGROUND: Establishing genomic resources for closely related species will provide comparative insights that are crucial for understanding diversity and variability at multiple levels of biological organization. We developed ESTs for Mexican axolotl (Ambystoma mexicanum) and Eastern tiger salamander (A. tigrinum tigrinum), species with deep and diverse research histories. RESULTS: Approximately 40,000 quality cDNA sequences were isolated for these species from various tissues, including regenerating limb and tail. These sequences and an existing set of 16,030 cDNA sequences for A. mexicanum were processed to yield 35,413 and 20,599 high quality ESTs for A. mexicanum and A. t. tigrinum, respectively. Because the A. t. tigrinum ESTs were obtained primarily from a normalized library, an approximately equal number of contigs were obtained for each species, with 21,091 unique contigs identified overall. The 10,592 contigs that showed significant similarity to sequences from the human RefSeq database reflected a diverse array of molecular functions and biological processes, with many corresponding to genes expressed during spinal cord injury in rat and fin regeneration in zebrafish. To demonstrate the utility of these EST resources, we searched databases to identify probes for regeneration research, characterized intra- and interspecific nucleotide polymorphism, saturated a human - Ambystoma synteny group with marker loci, and extended PCR primer sets designed for A. mexicanum / A. t. tigrinum orthologues to a related tiger salamander species. CONCLUSIONS: Our study highlights the value of developing resources in traditional model systems where the likelihood of information transfer to multiple, closely related taxa is high, thus simultaneously enabling both laboratory and natural history research

Setting clinical performance specifications to develop and evaluate biomarkers for clinical use

Background: Biomarker discovery studies often claim ‘promising’ findings, motivating further studies and marketing as medical tests. Unfortunately, the patient benefits promised are often inadequately explained to guide further evaluation, and few biomarkers have translated to improved patient care. We present a practical guide for setting minimum clinical performance specifications to strengthen clinical performance study design and interpretation. Methods: We developed a step-by-step approach using test evaluation and decision-analytic frameworks and present with illustrative examples. Results: We define clinical performance specifications as a set of criteria that quantify the clinical performance a new test must attain to allow better health outcomes than current practice. We classify the proposed patient benefits of a new test into three broad groups and describe how to set minimum clinical performance at the level where the potential harm of false-positive and false-negative results does not outweigh the benefits. (1) For add-on tests proposed to improve disease outcomes by improving detection, define an acceptable trade-off for false-positive versus true-positive results; (2) for triage tests proposed to reduce unnecessary tests and treatment by ruling out disease, define an acceptable risk of false-negatives as a safety threshold; (3) for replacement tests proposed to provide other benefits, or reduce costs, without compromising accuracy, use existing tests to benchmark minimum accuracy levels. Conclusions: Researchers can follow these guidelines to focus their study objectives and to define statistical hypotheses and sample size requirements. This way, clinical performance studies will allow conclusions about whether test performance is sufficient for intended use

Measurement of the Target-Normal Single-Spin Asymmetry in Quasi-Elastic Scattering from the Reaction 3^3He↑(e,e′)^\uparrow(e,e^\prime)

We report the first measurement of the target single-spin asymmetry, $A_y$, in quasi-elastic scattering from the inclusive reaction $^3$He$^{\uparrow}(e,e^\prime)$ on a $^3$He gas target polarized normal to the lepton scattering plane. Assuming time-reversal invariance, this asymmetry is strictly zero for one-photon exchange. A non-zero $A_y$ can arise from the interference between the one- and two-photon exchange processes which is sensitive to the details of the sub-structure of the nucleon. An experiment recently completed at Jefferson Lab yielded asymmetries with high statistical precision at $Q^{2}=$ 0.13, 0.46 and 0.97 GeV$^{2}$. These measurements demonstrate, for the first time, that the $^3$He asymmetry is clearly non-zero and negative with a statistical significance of (8-10)$\sigma$. Using measured proton-to-$^{3}$He cross-section ratios and the effective polarization approximation, neutron asymmetries of $-$(1-3)% were obtained. The neutron asymmetry at high $Q^2$ is related to moments of the Generalized Parton Distributions (GPDs). Our measured neutron asymmetry at $Q^2=0.97$ GeV$^2$ agrees well with a prediction based on two-photon exchange using a GPD model and thus provides a new, independent constraint on these distributions