Leukocytes Are Recruited through the Bronchial Circulation to the Lung in a Spontaneously Hypertensive Rat Model of COPD

Chronic obstructive pulmonary disease (COPD) kills approximately 2.8 million people each year, and more than 80% of COPD cases can be attributed to smoking. Leukocytes recruited to the lung contribute to COPD pathology by releasing reactive oxygen metabolites and proteolytic enzymes. In this work, we investigated where leukocytes enter the lung in the early stages of COPD in order to better understand their effect as a contributor to the development of COPD. We simultaneously evaluated the parenchyma and airways for neutrophil accumulation, as well as increases in the adhesion molecules and chemokines that cause leukocyte recruitment in the early stages of tobacco smoke induced lung disease. We found neutrophil accumulation and increased expression of adhesion molecules and chemokines in the bronchial blood vessels that correlated with the accumulation of leukocytes recovered from the lung. The expression of adhesion molecules and chemokines in other vascular beds did not correlate with leukocytes recovered in bronchoalveolar lavage fluid (BALF). These data strongly suggest leukocytes are recruited in large measure through the bronchial circulation in response to tobacco smoke. Our findings have important implications for understanding the etiology of COPD and suggest that pharmaceuticals designed to reduce leukocyte recruitment through the bronchial circulation may be a potential therapy to treat COPD

Global gene expression patterns in the post-pneumonectomy lung of adult mice

<p>Abstract</p> <p>Background</p> <p>Adult mice have a remarkable capacity to regenerate functional alveoli following either lung resection or injury that exceeds the regenerative capacity observed in larger adult mammals. The molecular basis for this unique capability in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling mechanisms used in this species during lung regeneration.</p> <p>Methods</p> <p>Unilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points). Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days) and analyzed using microarray technology.</p> <p>Results</p> <p>The observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1), as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts and up-regulation of genes involved in T cell development/function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This again appears to differ from embryonic alveologenesis.</p> <p>Conclusion</p> <p>These data suggest that modulation of mesenchymal cell transcriptome patterns and proliferation of S100A4 positive mesenchymal cells, as well as modulation of pro-inflammatory transcriptome patterns, are important during post-pneumonectomy lung regeneration in adult mice.</p

Evidence of Segregated Spawning in a Single Marine Fish Stock: Sympatric Divergence of Ecotypes in Icelandic Cod?

There is increasing recognition of intraspecific diversity and population structure within marine fish species, yet there is little direct evidence of the isolating mechanisms that maintain it or documentation of its ecological extent. We analyzed depth and temperature histories collected by electronic data storage tags retrieved from 104 Atlantic cod at liberty ≥1 year to evaluate a possible isolating mechanisms maintaining population structure within the Icelandic cod stock. This stock consists of two distinct behavioral types, resident coastal cod and migratory frontal cod, each occurring within two geographically distinct populations. Despite being captured together on the same spawning grounds, we show the behavioral types seem reproductively isolated by fine-scale differences in spawning habitat selection, primarily depth. Additionally, the different groups occupied distinct seasonal thermal and bathymetric niches that generally demonstrated low levels of overlap throughout the year. Our results indicate that isolating mechanisms, such as differential habitat selection during spawning, might contribute to maintaining diversity and fine-scale population structure in broadcast-spawning marine fishes

Ramipril mitigates radiation-induced impairment of neurogenesis in the rat dentate gyrus

<p>Abstract</p> <p>Background</p> <p>Sublethal doses of whole brain irradiation (WBI) are commonly administered therapeutically and frequently result in late delayed radiation injuries, manifesting as severe and irreversible cognitive impairment. Neural progenitors within the subgranular zone (SGZ) of the dentate gyrus are among the most radiosensitive cell types in the adult brain and are known to participate in hippocampal plasticity and normal cognitive function. These progenitors and the specialized SZG microenvironment required for neuronal differentiation are the source of neurogenic potential in the adult dentate gyrus, and provide a continuous supply of immature neurons which may then migrate into the adjacent granule cell layer to become mature granule cell neurons. The extreme radiosensitivity of these progenitors and the SGZ microenvironment suggests the hippocampus as a prime target for radiation-induced cognitive impairment. The brain renin-angiotensin system (RAS) has previously been implicated as a potent modulator of neurogenesis within the SGZ and selective RAS inhibitors have been implicated as mitigators of radiation brain injury. Here we investigate the angiotensin converting enzyme (ACE) inhibitor, ramipril, as a mitigator of radiation injury in this context.</p> <p>Methods</p> <p>Adult male Fisher 344 rats received WBI at doses of 10 Gy and 15 Gy. Ramipril was administered beginning 24 hours post-WBI and maintained continuously for 12 weeks.</p> <p>Results</p> <p>Ramipril produced small but significant reductions in the deleterious effects of radiation on progenitor proliferation and neuronal differentiation in the rat dentate gyrus following 10 Gy-WBI, but was not effective following 15 Gy-WBI. Ramipril also reduced the basal rate of neurogenesis within the SGZ in unirradiated control rats.</p> <p>Conclusions</p> <p>Our results indicate that chronic ACE inhibition with ramipril, initiated 24 hours post-irradiation, may reduce apoptosis among SGZ progenitors and/or inflammatory disruption of neurogenic signaling within SGZ microenvironment, and suggest that angiotensin II may participate in maintaining the basal rate of granule cell neurogenesis.</p

Feeding Preferences and the Nutritional Value of Tropical Algae for the Abalone Haliotis asinina

Understanding the feeding preferences of abalone (high-value marine herbivores) is integral to new species development in aquaculture because of the expected link between preference and performance. Performance relates directly to the nutritional value of algae – or any feedstock – which in turn is driven by the amino acid content and profile, and specifically the content of the limiting essential amino acids. However, the relationship between feeding preferences, consumption and amino acid content of algae have rarely been simultaneously investigated for abalone, and never for the emerging target species Haliotis asinina. Here we found that the tropical H. asinina had strong and consistent preferences for the red alga Hypnea pannosa and the green alga Ulva flexuosa, but no overarching relationship between protein content (sum of amino acids) and preference existed. For example, preferred Hypnea and Ulva had distinctly different protein contents (12.64 vs. 2.99 g 100 g−1) and the protein-rich Asparagopsis taxiformis (>15 g 100 g−1 of dry weight) was one of the least preferred algae. The limiting amino acid in all algae was methionine, followed by histidine or lysine. Furthermore we demonstrated that preferences can largely be removed using carrageenan as a binder for dried alga, most likely acting as a feeding attractant or stimulant. The apparent decoupling between feeding preference and algal nutritive values may be due to a trade off between nutritive values and grazing deterrence associated with physical and chemical properties

Effects of adult exposure to bisphenol A on genes involved in the physiopathology of rat prefrontal cortex

Several neurological and behavioral dysfunctions have been reported in animals exposed to bisphenol A (BPA). However, little is known about the impact of adult exposure to BPA on brain physiopathology. Here, we focused on prefrontal cortex (PFC) of rats, because it is an important area for cognitive control, complex behaviors and is altered in many psychopathologies. Gamma-aminobutyric acid (GABA) and serotonin (5-HT) systems are essential for PFC function. Therefore, we examined the effects of adult exposure to BPA on 5α-Reductase (5α-R) and cytochrome P450 aromatase (P450arom), enzymes that synthesize GABAA receptor modulators, and tryptophan hydroxylase (Tph), the rate-limiting enzyme in 5-HT biosynthesis. To gain better understanding of BPA’s action in the adult PFC, 84 genes involved in neurotoxicity were also analysed. Adult male and female rats were subcutaneously injected for 4 days with 50 µg/kg/day, the current reference safe dose for BPA. mRNA and protein levels of 5α-R, P450arom and Tph were quantified by real-time RT-PCR and Western blot. Genes linked to neurotoxicity were analyzed by PCR-Array technology. Adult exposure to BPA increased both P450arom and Tph2 expression in PFC of male and female, but decreased 5α-R1 expression in female. Moreover, we identified 17 genes related to PFC functions such as synaptic plasticity and memory, as potential targets of BPA. Our results provided new insights on the molecular mechanisms underlying BPA action in the physiopathology of PFC, but also raise the question about the safety of short-term exposure to it in the adulthood.This research was supported by grants from Ministerio de Ciencia e Innovación (BFU2008-05340) and by the Junta de Andalucía (CTS202-Endocronología y Metabolismo)

Reduced Proliferation in the Adult Mouse Subventricular Zone Increases Survival of Olfactory Bulb Interneurons

Neurogenesis in the adult brain is largely restricted to the subependymal zone (SVZ) of the lateral ventricle, olfactory bulb (OB) and the dentate subgranular zone, and survival of adult-born cells in the OB is influenced by factors including sensory experience. We examined, in mice, whether survival of adult-born cells is also regulated by the rate of precursor proliferation in the SVZ. Precursor proliferation was decreased by depleting the SVZ of dopamine after lesioning dopamine neurons in the substantia nigra compacta with 6-hydroxydopamine. Subsequently, we examined the effect of reduced SVZ proliferation on the generation, migration and survival of neuroblasts and mature adult-born cells in the SVZ, rostral migratory stream (RMS) and OB. Proliferating cells in the SVZ, measured by 5-bromo-2-deoxyuridine (BrdU) injected 2 hours prior to death or by immunoreactivity against Ki67, were reduced by 47% or 36%, respectively, 7 days after dopamine depletion, and by 29% or 31% 42 days after dopamine depletion, compared to sham-treated animals. Neuroblast generation in the SVZ and their migration along the RMS were not affected, neither 7 nor 42 days after the 6-hydroxydopamine injection, since the number of doublecortin-immunoreactive neuroblasts in the SVZ and RMS, as well as the number of neuronal nuclei-immunoreactive cells in the OB, were stable compared to control. However, survival analysis 15 days after 6-hydroxydopamine and 6 days after BrdU injections showed that the number of BrdU+ cells in the SVZ was 70% higher. Also, 42 days after 6-hydroxydopamine and 30 days after BrdU injections, we found an 82% increase in co-labeled BrdU+/γ-aminobutyric acid-immunoreactive cell bodies in the granular cell layer, while double-labeled BrdU+/tyrosine hydroxylase-immunoreactive cell bodies in the glomerular layer increased by 148%. We conclude that the number of OB interneurons following reduced SVZ proliferation is maintained through an increased survival of adult-born precursor cells, neuroblasts and interneurons