Inter and Intra Varietal Variation in Textural Characteristics of Carrots: a Standard Food in Chewing Studies

Carrots have been widely used as a model food in chewing studies yet inter and intra varietal variation have not been considered, treating them as a standard material whose rheological and breakdown characteristics are constant. Using a texture analyzer, we determined small strain compression (Young’s) moduli of carrot cores. We also undertook high speed, high strain compression tests to mimic the type of forces involved in chewing studies. Results suggest that for fresh carrots there is no significant difference between the textural characteristics of carrot varieties studied. Moreover, no difference exists in textural characteristics of sample cores obtained from different locations within the same carrot. As carrots are stored at temperatures between 10 and 30 °C the Young’s modulus declines exponentially with time, while the breaking stress gradually increases. Our data does suggest that the many researchers who have used carrots as consistent model food is justified in doing so as long as the produce is fresh

The Influence Of Wood Moisture Content On The Fungitoxicity Of Methylisothiocyanate In Douglas-Fir Heartwood

High concentrations of the fumigant methylisothiocyanate (MITC) will effectively control decay fungi in large wood structures, but the fungitoxicity of low MITC concentrations and the influence of wood moisture content (MC) on its performance are not well understood. The MC of Douglas-fir heartwood greatly influenced the susceptibility of the decay fungus Poria carbonica to MITC vapors and the amount of MITC adsorbed by the wood. At constant, low MITC vapor concentrations (less than 1μg/cc air), wood at 10% MC adsorbed 5 times more MITC, but required 4 times the exposure period to control P. carbonica, than wood above the fiber saturation point. Adsorption of MITC to wood was not substantially influenced by the amount of wood decay. When wood MC was raised from 10% to 30% during fumigation, previously adsorbed MITC rapidly volatilized and fumigant fungitoxicity increased

New-England or A Briefe Enarration of the Ayre, Earth, Water, Fish and Fowles of That Country. With a Description of the Natures, Orders, Habits, and Religion of the Natives; in Latine and English Verse

This text, a Latin poem in dactylic hexameter with an accompanying English translation in heroic verse stands as the earliest surviving work of poetry about New England and the second oldest poem whose origins can be traced directly to the British American colonies. Only two copies of the original 1625 edition are known to survive; one is held at the Huntington Library in San Marino, California, and the other is housed at the British Museum. The Latin portion comprises 309 lines and praises the geographic features, flora and fauna of New England, and spends a majority of its verses describing the Native Americans with awe and curiosity. The English version contains 366 lines, frequently uses obscure terminology, and departs too drastically from the original to be of any assistance for discerning the Latin. The author is William Morrell, (ca. 1590-after 1626) who received his Bachelors of Arts from Magdalene College, Cambridge in 1615. On May 23 and 24, 1619 Morrell was ordained as a deacon and priest respectively at Peterborough. Several years later in 1623, after receiving a commission by the ecclesiastical court to oversee and administer any churches which were already or might be instituted in the new colonies, Morrell accompanied English navy Captain Robert Gorges to New England, who was tasked with assisting the establishment of the short-lived Wessagusset Colony in present-day Weymouth. The colony was abandoned in the spring of 1624 due to financial difficulties and tensions with the Natives. Robert Gorges served as Governor-General of New England between 1623 and 1624. Gorges returned to England in 1624, but Morrell remained behind in Plymouth for one year to learn more about New England. These two poems are the fruits of his observations. They were published in 1625 in London by John Dawson. These writings make it clear that Morrell was an able classical scholar. He frequently peppers his English with Latin maxims reminiscent of Virgil and Apuleius and he employs numerous references to classical mythological figures and events

Optical Discovery of Probable Stellar Tidal Disruption Flares

Using archival Sloan Digital Sky Survey (SDSS) multi-epoch imaging data (Stripe 82), we have searched for the tidal disruption of stars by supermassive black holes in non-active galaxies. Two candidate tidal disruption events (TDEs) are identified. The TDE flares have optical blackbody temperatures of 2 × 10^4 K and observed peak luminosities of M_g = –18.3 and –20.4 (νL_ν = 5 × 10^(42), 4 × 10^(43) erg s^(–1), in the rest frame); their cooling rates are very low, qualitatively consistent with expectations for tidal disruption flares. The properties of the TDE candidates are examined using (1) SDSS imaging to compare them to other flares observed in the search, (2) UV emission measured by GALEX, and (3) spectra of the hosts and of one of the flares. Our pipeline excludes optically identifiable AGN hosts, and our variability monitoring over nine years provides strong evidence that these are not flares in hidden AGNs. The spectra and color evolution of the flares are unlike any SN observed to date, their strong late-time UV emission is particularly distinctive, and they are nuclear at high resolution arguing against these being first cases of a previously unobserved class of SNe or more extreme examples of known SN types. Taken together, the observed properties are difficult to reconcile with an SN or an AGN-flare explanation, although an entirely new process specific to the inner few hundred parsecs of non-active galaxies cannot be excluded. Based on our observed rate, we infer that hundreds or thousands of TDEs will be present in current and next-generation optical synoptic surveys. Using the approach outlined here, a TDE candidate sample with O(1) purity can be selected using geometric resolution and host and flare color alone, demonstrating that a campaign to create a large sample of TDEs, with immediate and detailed multi-wavelength follow-up, is feasible. A by-product of this work is quantification of the power spectrum of extreme flares in AGNs

Disrupted Endothelial Cell Layer and Exposed Extracellular Matrix Proteins Promote Capture of Late Outgrowth Endothelial Progenitor Cells.

Late outgrowth endothelial progenitor cells (LO-EPC) possess a high proliferative potential, differentiate into vascular endothelial cells (EC), and form networks, suggesting they play a role in vascular repair. However, due to their scarcity in the circulation there is a requirement for ex vivo expansion before they could provide a practical cell therapy and it is currently unclear if they would home and engraft to an injury site. Using an in vitro flow system we studied LO-EPC under simulated injury conditions including EC activation, ischaemia, disrupted EC integrity, and exposed basement membrane. Perfused LO-EPC adhered to discontinuous EC paracellularly at junctional regions between adjacent cells under shear stress 0.7 dyn/cm2. The interaction was not adhesion molecule-dependent and not enhanced by EC activation. LO-EPC expressed high levels of the VE-Cadherin which may explain these findings. Ischaemia reperfusion injury decreased the interaction with LO-EPC due to cell retraction. LO-EPC interacted with exposed extracellular matrix (ECM) proteins, fibronectin and vitronectin. The interaction was mediated by integrins α5β3, αvβ1, and αvβ3. This study has demonstrated that an injured local environment presents sufficient adhesive signals to capture flow perfused LO-EPC in vitro and that LO-EPC have properties consistent with their potential role in vascular repair

Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline

<b>Objective</b>: MicroRNAs (miRNAs) are small noncoding RNAs that have the capacity to control protein production through binding "seed" sequences within a target mRNA. Each miRNA is capable of potentially controlling hundreds of genes. The regulation of miRNAs in the lung during the development of pulmonary arterial hypertension (PAH) is unknown.<p></p> <b>Methods and Results</b>: We screened lung miRNA profiles in a longitudinal and crossover design during the development of PAH caused by chronic hypoxia or monocrotaline in rats. We identified reduced expression of Dicer, involved in miRNA processing, during the onset of PAH after hypoxia. MiR-22, miR-30, and let-7f were downregulated, whereas miR-322 and miR-451 were upregulated significantly during the development of PAH in both models. Differences were observed between monocrotaline and chronic hypoxia. For example, miR-21 and let-7a were significantly reduced only in monocrotaline-treated rats. MiRNAs that were significantly regulated were validated by quantitative polymerase chain reaction. By using in vitro studies, we demonstrated that hypoxia and growth factors implicated in PAH induced similar changes in miRNA expression. Furthermore, we confirmed miR-21 downregulation in human lung tissue and serum from patients with idiopathic PAH.<p></p> <b>Conclusion</b>: Defined miRNAs are regulated during the development of PAH in rats. Therefore, miRNAs may contribute to the pathogenesis of PAH and represent a novel opportunity for therapeutic intervention.<p></p&gt

Estrogen metabolites in a small cohort of patients with idiopathic pulmonary arterial hypertension.

Increased risk and severity of idiopathic pulmonary arterial hypertension (iPAH) is associated with elevated estradiol in men and postmenopausal women. Pulmonary arteries synthesise estradiol via aromatase and metabolise it via CYP1B1 to mitogenic metabolites; SNPs in aromatase and CYP1B1 have been associated with PAH. This suggests that estradiol metabolism could be altered in iPAH. This proof-of-concept study profiles estradiol and several metabolites of estradiol simultaneously in serum from iPAH patients and controls. We show that the estradiol and metabolite profile is altered in iPAH and that 16-hydroxyestrone and 16-hydroxyestradiol accumulate in iPAH patients with 16-hydroxyestrone levels relating to disease severity

MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension

Rationale: The pathogenesis of PAH remains unclear. The four microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. Objective: To elucidate the transcriptional regulation of the miR-143/145 cluster, and the role of miR-143 in PAH. Methods and Results: We identified the promoter region that regulates miR-143/145 miRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signalling pathways, including estrogens receptor (ER), liver X factor/retinoic X receptor (LXR/RXR), TGF-β (Smads), and hypoxia (HRE) that regulated levels of all pri-miR stem loop transcription and resulting miRNA expression. We observed that miR-143-3p is selectively upregulated compared to miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMCs-derived exosomes. Using assays with pulmonary arterial endothelial cells (PAECs) we demonstrated a paracrine pro-migratory and pro-angiogenic effect of miR-143-3p enriched exosomes from PASMC. Quantitative PCR and in situ hybridisation showed elevated expression of miR-143 in calf models of PAH as well as in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role for miR-143 in experimental PH in vivo in miR-143-/- and antimiR143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. Conclusions: MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while inhibition of miR-143-3p blocked experimental PH. Taken together these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology

Impaired natural killer cell phenotype and function in idiopathic and heritable pulmonary arterial hypertension

BACKGROUND: Beyond their role as innate immune effectors, natural killer (NK) cells are emerging as important regulators of angiogenesis and vascular remodeling. Pulmonary arterial hypertension (PAH) is characterized by severe pulmonary vascular remodeling and has long been associated with immune dysfunction. Despite this association, a role for NK cells in disease pathology has not yet been described. METHODS AND RESULTS: Analysis of whole blood lymphocytes and isolated NK cells from PAH patients revealed an expansion of the functionally defective CD56(-)/CD16(+) NK subset that was not observed in patients with chronic thromboembolic pulmonary hypertension. NK cells from PAH patients also displayed decreased levels of the activating receptor NKp46 and the killer immunoglobulin-like receptors 2DL1/S1 and 3DL1, reduced secretion of the cytokine macrophage inflammatory protein-1β, and a significant impairment in cytolytic function associated with decreased killer immunoglobulin-like receptor 3DL1 expression. Genotyping patients (n=222) and controls (n=191) for killer immunoglobulin-like receptor gene polymorphisms did not explain these observations. Rather, we show that NK cells from PAH patients exhibit increased responsiveness to transforming growth factor-β, which specifically downregulates disease-associated killer immunoglobulin-like receptors. NK cell number and cytotoxicity were similarly decreased in the monocrotaline rat and chronic hypoxia mouse models of PAH, accompanied by reduced production of interferon-γ in NK cells from hypoxic mice. NK cells from PAH patients also produced elevated quantities of matrix metalloproteinase 9, consistent with a capacity to influence vascular remodeling. CONCLUSIONS: Our work is the first to identify an impairment of NK cells in PAH and suggests a novel and substantive role for innate immunity in the pathobiology of this disease