Osmoregulatory bicarbonate secretion exploits H(+)-sensitive haemoglobins to autoregulate intestinal O2 delivery in euryhaline teleosts

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Marine teleost fish secrete bicarbonate (HCO3 (-)) into the intestine to aid osmoregulation and limit Ca(2+) uptake by carbonate precipitation. Intestinal HCO3 (-) secretion is associated with an equimolar transport of protons (H(+)) into the blood, both being proportional to environmental salinity. We hypothesized that the H(+)-sensitive haemoglobin (Hb) system of seawater teleosts could be exploited via the Bohr and/or Root effects (reduced Hb-O2 affinity and/or capacity with decreasing pH) to improve O2 delivery to intestinal cells during high metabolic demand associated with osmoregulation. To test this, we characterized H(+) equilibria and gas exchange properties of European flounder (Platichthys flesus) haemoglobin and constructed a model incorporating these values, intestinal blood flow rates and arterial-venous acidification at three different environmental salinities (33, 60 and 90). The model suggested red blood cell pH (pHi) during passage through intestinal capillaries could be reduced by 0.14-0.33 units (depending on external salinity) which is sufficient to activate the Bohr effect (Bohr coefficient of -0.63), and perhaps even the Root effect, and enhance tissue O2 delivery by up to 42 % without changing blood flow. In vivo measurements of intestinal venous blood pH were not possible in flounder but were in seawater-acclimated rainbow trout which confirmed a blood acidification of no less than 0.2 units (equivalent to -0.12 for pHi). When using trout-specific values for the model variables, predicted values were consistent with measured in vivo values, further supporting the model. Thus this system is an elegant example of autoregulation: as the need for costly osmoregulatory processes (including HCO3 (-) secretion) increases at higher environmental salinity, so does the enhancement of O2 delivery to the intestine via a localized acidosis and the Bohr (and possibly Root) effect.Underlying research materials, i.e. raw data, is accessible by contacting the corresponding author, Dr. Rod Wilson at [email protected]. This research was supported by BBSRC and NERC grants (BB/D005108/1 and NE/H010041/1) to RWW and an NSERC Discovery grant to CJB. We would like to thank Jan Shears for excellent technical support and fish husbandry

Seizure during hyperbaric oxygen therapy for carbon monoxide toxicity: a case series and five-year experience.

BACKGROUND: Hyperbaric oxygen (HBO) therapy is recommended to reduce the delayed neurologic sequelae resulting from carbon monoxide (CO) toxicity. Although HBO is generally well tolerated, there exists a risk of seizure in all patients that may be increased in patients with predisposing factors including: fever, hypothermia, prior seizure, or brain injury. CASE REPORT: We present two cases of patients without known risk factors who experienced seizures associated with HBO therapy during treatment for CO toxicity. CONCLUSION: This facility\u27s 5-year experience and a review of the germane literature are also presented to elucidate the risk factors and incidence of seizures in patients treated with HBO for CO toxicity

Exploring lncRNAs associated with human pancreatic islet cell death induced by transfer of adoptive lymphocytes in a humanized mouse model

BackgroundLong noncoding RNA (lncRNA)-mediated posttranscriptional and epigenetic landscapes of gene regulation are associated with numerous human diseases. However, the regulatory mechanisms governing human β-cell function and survival remain unknown. Owing to technical and ethical constraints, studying the direct role of lncRNAs in β-cell function and survival in humans in vivo is difficult. Therefore, we utilized humanized mice with human islets to investigate lncRNA expression using whole transcriptome shotgun sequencing. Our study aimed to characterize lncRNAs that may be crucial for human islet cell function and survival.MethodsHuman β-cell death was induced in humanized mice engrafted with functional human islets. Using these humanized mice harboring human islets with induced β-cell death, we investigated lncRNA expression through whole transcriptome shotgun sequencing. Additionally, we systematically identified, characterized, and explored the regulatory functions of lncRNAs that are potentially important for human pancreatic islet cell function and survival.ResultsHuman islet cell death was induced in humanized mice engrafted with functional human islets. RNA sequencing analysis of isolated human islets, islet grafts from humanized mice with and without induced cell death, revealed aberrant expression of a distinct set of lncRNAs that are associated with the deregulated mRNAs important for cellular processes and molecular pathways related to β-cell function and survival. A total of 10 lncRNA isoforms (SCYL1-1:22, POLG2-1:1, CTRB1-1:1, SRPK1-1:1, GTF3C5-1:1, PPY-1:1, CTRB1-1:5, CPA5-1:1, BCAR1-2:1, and CTRB1-1:4) were identified as highly enriched and specific to human islets. These lncRNAs were deregulated in human islets from donors with different BMIs and with type 2 diabetes (T2D), as well as in cultured human islets with glucose stimulation and induced cell death induced by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the medium used to culture islets with cytokines.ConclusionIslet-enriched and specific human lncRNAs are deregulated in human islet grafts and cultured human islets with induced cell death. These lncRNAs may be crucial for human β-cell function and survival and could have an impact on identifying biomarkers for β-cell loss and discovering novel therapeutic targets to enhance β-cell function and survival

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action

Molecular Gas in Spiral Galaxies

In this review, I highlight a number of recent surveys of molecular gas in nearby spiral galaxies. Through such surveys, more complete observations of the distribution and kinematics of molecular gas have become available for galaxies with a wider range of properties (e.g., brightness, Hubble type, strength of spiral or bar structure). These studies show the promise of both interferometers and single-dish telescopes in advancing our general understanding of molecular gas in spiral galaxies. In particular, I highlight the contributions of the recent BIMA Survey of Nearby Galaxies (SONG).Comment: 8 pages, 1 figure. To appear in the proceedings of the 4th Cologne-Bonn-Zermatt-Symposium, "The Dense Interstellar Medium in Galaxies", which was held in Zermatt, Switzerland in September 200

An Atomic-resolution nanomechanical mass sensor

Mechanical resonators are widely used as inertial balances to detect small quantities of adsorbed mass through shifts in oscillation frequency[1]. Advances in lithography and materials synthesis have enabled the fabrication of nanoscale mechanical resonators[2, 3, 4, 5, 6], which have been operated as precision force[7], position[8, 9] and mass sensors[10, 11, 12, 13, 14, 15]. Here we demonstrate a room-temperature, carbon-nanotube-based nanomechanical resonator with atomic mass resolution. This device is essentially a mass spectrometer with a mass sensitivity of 1.3 times 10^-25 kg Hz^-1/2 or, equivalently, 0.40 gold atoms Hz^-1/2. Using this extreme mass sensitivity, we observe atomic mass shot noise, which is analogous to the electronic shot noise[16, 17] measured in many semiconductor experiments. Unlike traditional mass spectrometers, nanomechanical mass spectrometers do not require the potentially destructive ionization of the test sample, are more sensitive to large molecules, and could eventually be incorporated on a chip

RNA expression of TLR10 in normal equine tissues

Background: Toll like receptors are one of the major innate immune system pathogen recognition systems. There is little data on the expression of the TLR10 member of this family in the horse. Results: This paper describes the genetic structure of the Equine TLR10 gene and its RNA expression in a range of horse tissues. It describes the phylogenetic analysis of the Equine TLR1,6,10,2 annotations in the horse genome, firmly identifying them in their corresponding gene clades compared to other species and firmly placing the horse gene with other TLR10 genes from odd-toed ungulates. Additional 3’ transcript extensions to that annotated for TLR10 in the horse genome have been identified by analysis of RNAseq data. RNA expression of the equine TLR10 gene was highest in peripheral blood mononucleocytes and lymphoid tissue (lymph nodes and spleen), however some expression was detected in all tissues tested (jejunum, caudal mesenteric lymph nodes, bronchial lymph node, spleen, lung, colon, kidney and liver). Additional data on RNAseq expression of all equine TLR genes (1–4 and 6–10) demonstrate higher expression of TLR4 than other equine TLRs in all tissues. Conclusion: The equine TLR10 gene displays significant homology to other mammalian TLR10 genes and could be reasonably assumed to have similar fuctions. Its RNA level expression is higher in resting state PBMCs in horses than in other tissues

European propolis is highly active against trypanosomatids including Crithidia fasciculata.

Extracts of 35 samples of European propolis were tested against wild type and resistant strains of the protozoal pathogens Trypanosoma brucei, Trypanosoma congolense and Leishmania mexicana. The extracts were also tested against Crithidia fasciculata a close relative of Crithidia mellificae, a parasite of bees. Crithidia, Trypanosoma and Leishmania are all members of the order Kinetoplastida. High levels of activity were obtained for all the samples with the levels of activity varying across the sample set. The highest levels of activity were found against L. mexicana. The propolis samples were profiled by using liquid chromatography with high resolution mass spectrometry (LC-MS) and principal components analysis (PCA) of the data obtained indicated there was a wide variation in the composition of the propolis samples. Orthogonal partial least squares (OPLS) associated a butyrate ester of pinobanksin with high activity against T. brucei whereas in the case of T. congolense high activity was associated with methyl ethers of chrysin and pinobanksin. In the case of C. fasciculata highest activity was associated with methyl ethers of galangin and pinobanksin. OPLS modelling of the activities against L. mexicana using the mass spectrometry produced a less successful model suggesting a wider range of active components