SINGLE SPECIES VERSUS MULTIPLE SPECIES MODELS: THE ECONOMIC IMPLICATIONS

Ecologists frequently note the importance of modelling entire ecosystems rather than single species, but most bioeconomic models in the current literature focus on a single species. While the mathematical difficulty of multiple species may quickly become overwhelming, sometimes making the single species option necessary, it is important to recognise the significance of the single species assumption to the model results. In this paper, the authors address the economic significance of this assumption through the development of a multiple species model and demonstrate the importance of interrelationships and economic values to the survival of endangered species.Resource /Energy Economics and Policy,

A novel method for RNA extraction from FFPE samples reveals significant differences in biomarker expression between orthotopic and subcutaneous pancreatic cancer patient-derived xenografts.

Next-generation sequencing (NGS) can identify and validate new biomarkers of cancer onset, progression and therapy resistance. Substantial archives of formalin-fixed, paraffin-embedded (FFPE) cancer samples from patients represent a rich resource for linking molecular signatures to clinical data. However, performing NGS on FFPE samples is limited by poor RNA purification methods. To address this hurdle, we developed an improved methodology for extracting high-quality RNA from FFPE samples. By briefly integrating a newly-designed micro-homogenizing (mH) tool with commercially available FFPE RNA extraction protocols, RNA recovery is increased by approximately 3-fold while maintaining standard A260/A280 ratios and RNA quality index (RQI) values. Furthermore, we demonstrate that the mH-purified FFPE RNAs are longer and of higher integrity. Previous studies have suggested that pancreatic ductal adenocarcinoma (PDAC) gene expression signatures vary significantly under in vitro versus in vivo and in vivo subcutaneous versus orthotopic conditions. By using our improved mH-based method, we were able to preserve established expression patterns of KRas-dependency genes within these three unique microenvironments. Finally, expression analysis of novel biomarkers in KRas mutant PDAC samples revealed that PEAK1 decreases and MST1R increases by over 100-fold in orthotopic versus subcutaneous microenvironments. Interestingly, however, only PEAK1 levels remain elevated in orthotopically grown KRas wild-type PDAC cells. These results demonstrate the critical nature of the orthotopic tumor microenvironment when evaluating the clinical relevance of new biomarkers in cells or patient-derived samples. Furthermore, this new mH-based FFPE RNA extraction method has the potential to enhance and expand future FFPE-RNA-NGS cancer biomarker studies

Lessons From the Pandemic: Engaging Wicked Problems With Transdisciplinary Deliberation

Some crises, such as those brought on or exposed by the COVID-19 pandemic, are wicked problems—large, complex problems with no immediate answer. As such, they make rich centerpieces for learning with respect to public deliberation and issue-based dialogue. This essay reflects on an experimental, transdisciplinary health and science communication course entitled Comprehending COVID-19. The course represents a collaborative effort among 14 faculty representing 10 different academic departments to create a resource for teaching students how to deliberate the pandemic, despite its attending, oversaturated, fake-news-infused, infodemic. We offer transdisciplinary deliberation as a pedagogical framework to expand communication repertoires in ways useful for sifting through the messiness of an infodemic while also developing key deliberation skills for productively engaging participatory decision-making with concern to wicked problems

Clebsch-Gordan Construction of Lattice Interpolating Fields for Excited Baryons

Large sets of baryon interpolating field operators are developed for use in lattice QCD studies of baryons with zero momentum. Operators are classified according to the double-valued irreducible representations of the octahedral group. At first, three-quark smeared, local operators are constructed for each isospin and strangeness and they are classified according to their symmetry with respect to exchange of Dirac indices. Nonlocal baryon operators are formulated in a second step as direct products of the spinor structures of smeared, local operators together with gauge-covariant lattice displacements of one or more of the smeared quark fields. Linear combinations of direct products of spinorial and spatial irreducible representations are then formed with appropriate Clebsch-Gordan coefficients of the octahedral group. The construction attempts to maintain maximal overlap with the continuum SU(2) group in order to provide a physically interpretable basis. Nonlocal operators provide direct couplings to states that have nonzero orbital angular momentum.Comment: This manuscript provides an anlytical construction of operators and is related to hep-lat/0506029, which provides a computational construction. This e-print version contains a full set of Clebsch-Gordan coefficients for the octahedral grou

Expression of iron-related genes in human brain and brain tumors

<p>Abstract</p> <p>Background</p> <p>Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (<it>HAMP</it>), HFE, neogenin (<it>NEO1</it>), transferrin receptor 1 (<it>TFRC</it>), transferrin receptor 2 (<it>TFR2</it>), and hemojuvelin (<it>HFE2</it>) in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines.</p> <p>Results</p> <p>Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens.</p> <p>Conclusion</p> <p>These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.</p

Metastatic recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model is inhibited by neoadjuvant chemotherapy in combination with fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore.

The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model. A PDOX model was established from a CA19-9-positive, CEA-negative tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS+NAC; FGS only; and FGS+NAC. An anti-CA19-9 or anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with the pancreatic cancer PDOX 24 hours before surgery. The PDOX was brightly labeled with fluorophore-conjugated anti-CA19-9, but not with a fluorophore-conjugated anti-CEA antibody. FGS was performed using the fluorophore-conjugated anti-CA19-9 antibody. FGS had no benefit over BLS to prevent metastatic recurrence. NAC in combination with BLS did not convey an advantage over BLS to prevent metastatic recurrence. However, FGS+NAC significantly reduced the metastatic recurrence frequency to one of 8 mice, compared to FGS only after which metastasis recurred in 6 out of 8 mice, and BLS+NAC with metastatic recurrence in 7 out of 8 mice (p = 0.041). Thus NAC in combination with FGS can reduce or even eliminate metastatic recurrence of pancreatic cancer sensitive to NAC. The present study further emphasizes the power of the PDOX model which enables metastasis to occur and thereby identify the efficacy of NAC in combination with FGS on metastatic recurrence

Analysis of striatal transcriptome in mice overexpressing human wild-type alpha-synuclein supports synaptic dysfunction and suggests mechanisms of neuroprotection for striatal neurons

Abstract Background Alpha synuclein (SNCA) has been linked to neurodegenerative diseases (synucleinopathies) that include Parkinson's disease (PD). Although the primary neurodegeneration in PD involves nigrostriatal dopaminergic neurons, more extensive yet regionally selective neurodegeneration is observed in other synucleinopathies. Furthermore, SNCA is ubiquitously expressed in neurons and numerous neuronal systems are dysfunctional in PD. Therefore it is of interest to understand how overexpression of SNCA affects neuronal function in regions not directly targeted for neurodegeneration in PD. Results The present study investigated the consequences of SNCA overexpression on cellular processes and functions in the striatum of mice overexpressing wild-type, human SNCA under the Thy1 promoter (Thy1-aSyn mice) by transcriptome analysis. The analysis revealed alterations in multiple biological processes in the striatum of Thy1-aSyn mice, including synaptic plasticity, signaling, transcription, apoptosis, and neurogenesis. Conclusion The results support a key role for SNCA in synaptic function and revealed an apoptotic signature in Thy1-aSyn mice, which together with specific alterations of neuroprotective genes suggest the activation of adaptive compensatory mechanisms that may protect striatal neurons in conditions of neuronal overexpression of SNCA

Mammary Extracellular Matrix Directs Differentiation of Testicular and Embryonic Stem Cells to Form Functional Mammary Glands In Vivo

Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived cells to produce normal mammary epithelial trees within epithelial divested mouse mammary fat-pads. Conversely, ECMs isolated from omental fat and lung did not redirect testicular cells to a MEC fate, indicating the necessity of tissue specific components of the mECM. mECM preparations also completely inhibited teratoma formation from ESC inoculations. Further, a phenotypically normal ductal outgrowth resulted from a single inoculation of ESCs and mECM. To the best of our knowledge, this is the first demonstration of a tissue specific ECM driving differentiation of cells to form a functional tissue in vivo