Insights into the regulation of DMSP synthesis in the diatom Thalassiosira pseudonana through APR activity, proteomics and gene expression analyses on cells acclimating to changes in salinity, light and nitrogen

Despite the importance of dimethylsulphoniopropionate (DMSP) in the global sulphur cycle and climate regulation, the biological pathways underpinning its synthesis in marine phytoplankton remain poorly understood. The intracellular concentration of DMSP increases with increased salinity, increased light intensity and nitrogen starvation in the diatom Thalassiosira pseudonana. We used these conditions to investigate DMSP synthesis at the cellular level via analysis of enzyme activity, gene expression and proteome comparison. The activity of the key sulphur assimilatory enzyme, adenosine 5′- phosphosulphate reductase was not coordinated with increasing intracellular DMSP concentration. Under all three treatments coordination in the expression of sulphur assimilation genes was limited to increases in sulphite reductase transcripts. Similarly, proteomic 2D gel analysis only revealed an increase in phosphoenolpyruvate carboxylase following increases in DMSP concentration. Our findings suggest that increased sulphur assimilation might not be required for increased DMSP synthesis, instead the availability of carbon and nitrogen substrates may be important in the regulation of this pathway. This contrasts with the regulation of sulphur metabolism in higher plants, which generally involves upregulation of several sulphur assimilatory enzymes. In T. pseudonana changes relating to sulphur metabolism were specific to the individual treatments and, given that little coordination was seen in transcript and protein responses across the three growth conditions, different patterns of regulation might be responsible for the increase in DMSP concentration seen under each treatment

Cold gas accretion in galaxies

Evidence for the accretion of cold gas in galaxies has been rapidly accumulating in the past years. HI observations of galaxies and their environment have brought to light new facts and phenomena which are evidence of ongoing or recent accretion: 1) A large number of galaxies are accompanied by gas-rich dwarfs or are surrounded by HI cloud complexes, tails and filaments. It may be regarded as direct evidence of cold gas accretion in the local universe. It is probably the same kind of phenomenon of material infall as the stellar streams observed in the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI have been found in nearby spiral galaxies. While a large fraction of this gas is produced by galactic fountains, it is likely that a part of it is of extragalactic origin. 3) Spirals are known to have extended and warped outer layers of HI. It is not clear how these have formed, and how and for how long the warps can be sustained. Gas infall has been proposed as the origin. 4) The majority of galactic disks are lopsided in their morphology as well as in their kinematics. Also here recent accretion has been advocated as a possible cause. In our view, accretion takes place both through the arrival and merging of gas-rich satellites and through gas infall from the intergalactic medium (IGM). The infall may have observable effects on the disk such as bursts of star formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates needed to sustain the observed star formation (~1 Msol/yr), additional infall of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages. Full-resolution version available at http://www.astron.nl/~oosterlo/accretionRevie

Inhibiting cardiac myeloperoxidase alleviates the relaxation defect in hypertrophic cardiomyocytes.

AIMS: Hypertrophic cardiomyopathy (HCM) is characterised by cardiomyocyte hypertrophy and disarray, and myocardial stiffness due to interstitial fibrosis, which result in impaired left ventricular filling and diastolic dysfunction. The latter manifests as exercise intolerance, angina, and dyspnoea. There is currently no specific treatment for improving diastolic function in HCM. Here, we investigated whether myeloperoxidase (MPO) is expressed in cardiomyocytes and provides a novel therapeutic target for alleviating diastolic dysfunction in HCM. METHODS AND RESULTS: Human cardiomyocytes derived from control induced pluripotent stem cells (iPSC-CMs) were shown to express MPO, with MPO levels being increased in iPSC-CMs generated from two HCM patients harbouring sarcomeric mutations in the MYBPC3 and MYH7 genes. The presence of cardiomyocyte MPO was associated with higher chlorination and peroxidation activity, increased levels of 3-chlorotyrosine-modified cardiac myosin binding protein-C (MYBPC3), attenuated phosphorylation of MYBPC3 at Ser-282, perturbed calcium signalling, and impaired cardiomyocyte relaxation. Interestingly, treatment with the MPO inhibitor, AZD5904, reduced 3-chlorotyrosine-modified MYBPC3 levels, restored MYBPC3 phosphorylation, and alleviated the calcium signalling and relaxation defects. Finally, we found that MPO protein was expressed in healthy adult murine and human cardiomyocytes, and MPO levels were increased in diseased hearts with left ventricular hypertrophy. CONCLUSION: This study demonstrates that MPO inhibition alleviates the relaxation defect in hypertrophic iPSC-CMs through MYBPC3 phosphorylation. These findings highlight cardiomyocyte MPO as a novel therapeutic target for improving myocardial relaxation associated with HCM, a treatment strategy which can be readily investigated in the clinical setting, given that MPO inhibitors are already available for clinical testing. TRANSLATIONAL PERSPECTIVE: There are currently no specific therapies for improving diastolic function in patients with HCM. We show for the first time that myeloperoxidase (MPO) is present in and is up-regulated in cardiomyocytes derived from human iPSCs obtained from HCM patients, where it impairs cardiomyocyte relaxation by reducing phosphorylation of cardiac MYBPC3. Treatment with the MPO inhibitor, AZD5904, restored MYBPC3 phosphorylation and alleviated the relaxation defect, demonstrating cardiomyocyte MPO to be a novel therapeutic target for improving diastolic function in HCM, a treatment strategy which can be evaluated in HCM patients given that MPO inhibitors are already available for clinical testing

A preliminary study on the induction of dioestrous ovulation in the mare – a possible method for inducing prolonged luteal phase

BACKGROUND: Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules), there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares. METHODS: In this preliminary study, in an attempt to induce ovulation during the luteal phase, human chorionic gonadotropin (hCG) (3000 IU) was injected intramuscularly in four mares (experimental group) in the luteal phase when a dioestrous follicle ≥ 30 mm was detected. A fifth mare included in this group was not treated due to no detectable dioestrous follicles ≥ 30 mm. Four control mares were similarly injected with saline. The mares were followed with ultrasound for 72 hours post injection or until ovulation. Blood samples for progesterone analysis were obtained twice weekly for one month and thereafter once weekly for another two to four months. RESULTS: Three of the hCG-treated mares ovulated within 72 hours after treatment and developed prolonged luteal phases of 58, 68 and 82 days respectively. One treated mare never ovulated after the hCG injection and progesterone levels fell below 3 nmol/l nine days post treatment. Progesterone levels in the control mares were below 3 nmol/l within nine days after saline injection, except for one mare, which developed a spontaneously prolonged luteal phase of 72 days. CONCLUSION: HCG treatment may be a method to induce prolonged luteal phases in the mare provided there is a dioestrous follicle ≥ 30 mm that ovulates post-treatment. However, the method needs to be tested on a larger number of mares to be able to draw conclusions regarding its effectiveness

Supervolcanoes Within an Ancient Volcanic Province in Arabia Terra, Mars

Several irregularly shaped craters located within Arabia Terra, Mars represent a new type of highland volcanic construct and together constitute a previously unrecognized martian igneous province. Similar to terrestrial supervolcanoes, these low-relief paterae display a range of geomorphic features related to structural collapse, effusive volcanism, and explosive eruptions. Extruded lavas contributed to the formation of enigmatic highland ridged plains in Arabia Terra. Outgassed sulfur and erupted fine-grained pyroclastics from these calderas likely fed the formation of altered, layered sedimentary rocks and fretted terrain found throughout the equatorial region. Discovery of a new type of volcanic construct in the Arabia volcanic province fundamentally changes the picture of ancient volcanism and climate evolution on Mars. Other eroded topographic basins in the ancient Martian highlands that have been dismissed as degraded impact craters should be reconsidered as possible volcanic constructs formed in an early phase of widespread, disseminated magmatism on Mars

Buffering of Segmental and Chromosomal Aneuploidies in Drosophila melanogaster

Chromosomal instability, which involves the deletion and duplication of chromosomes or chromosome parts, is a common feature of cancers, and deficiency screens are commonly used to detect genes involved in various biological pathways. However, despite their importance, the effects of deficiencies, duplications, and chromosome losses on the regulation of whole chromosomes and large chromosome domains are largely unknown. Therefore, to explore these effects, we examined expression patterns of genes in several Drosophila deficiency hemizygotes and a duplication hemizygote using microarrays. The results indicate that genes expressed in deficiency hemizygotes are significantly buffered, and that the buffering effect is general rather than being mainly mediated by feedback regulation of individual genes. In addition, differentially expressed genes in haploid condition appear to be generally more strongly buffered than ubiquitously expressed genes in haploid condition, but, among genes present in triploid condition, ubiquitously expressed genes are generally more strongly buffered than differentially expressed genes. Furthermore, we show that the 4th chromosome is compensated in response to dose differences. Our results suggest general mechanisms have evolved that stimulate or repress gene expression of aneuploid regions as appropriate, and on the 4th chromosome of Drosophila this compensation is mediated by Painting of Fourth (POF)

A Blueberry-Enriched Diet Attenuates Nephropathy in a Rat Model of Hypertension via Reduction in Oxidative Stress

To assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Oxidative stress (OS) appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-induced renal injury; however, attention has shifted recently to the therapeutic potential of natural products as antioxidants. Blueberries (BB) have among the highest antioxidant capacities of fruits and vegetables.Male spontaneously hypertensive rats received a BB-enriched diet (2% w/w) or an isocaloric control diet for 6 or 12 weeks or 2 days. Compared to controls, rats fed BB-enriched diet for 6 or 12 weeks exhibited lower blood pressure, improved glomerular filtration rate, and decreased renovascular resistance. As measured by electron paramagnetic resonance spectroscopy, significant decreases in total reactive oxygen species (ROS), peroxynitrite, and superoxide production rates were observed in kidney tissues in rats on long-term dietary treatment, consistent with reduced pathology and improved function. Additionally, measures of antioxidant status improved; specifically, renal glutathione and catalase activities increased markedly. Contrasted to these observations indicating reduced OS in the BB group after long-term feeding, similar measurements made in rats fed the same diet for only 2 days yielded evidence of increased OS; specifically, significant increases in total ROS, peroxynitrite, and superoxide production rates in all tissues (kidney, brain, and liver) assayed in BB-fed rats. These results were evidence of "hormesis" during brief exposure, which dissipated with time as indicated by enhanced levels of catalase in heart and liver of BB group.Long-term feeding of BB-enriched diet lowered blood pressure, preserved renal hemodynamics, and improved redox status in kidneys of hypertensive rats and concomitantly demonstrated the potential to delay or attenuate development of hypertension-induced renal injury, and these effects appear to be mediated by a short-term hormetic response

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

Swedish high school students' knowledge and attitudes regarding fertility and family building

<p>Abstract</p> <p>Background</p> <p>Infertility is a serious problem for those who suffer. Some of the risks for infertility are preventable and the individual should therefore have knowledge of them. The purposes of this study were to investigate high-school students' knowledge about fertility, plans for family building and to compare views and knowledge between female and male students.</p> <p>Methods</p> <p>A questionnaire containing 34 items was answered by 274 students. Answers from male and female students were compared using student's <it>t</it>-test for normally distributed variables and Mann-Whitney <it>U</it>-test for non-normal distributions. The chi-square test was used to compare proportions of male and female students who answered questions on nominal and ordinal scales. Differences were considered as statistically significant at a <it>p</it>-value of 0.05.</p> <p>Results</p> <p>Analyses showed that 234 (85%) intended to have children. Female students felt parenthood to be significantly more important than male students: <it>p </it>= <it><</it>0.01. The mean age at which the respondents thought they would like to start to build their family was 26 (± 2.9) years. Men believed that women's fertility declined significantly later than women did: <it>p </it>= <it><</it>0.01. Women answered that 30.7% couples were involuntarily infertile and men answered 22.5%: <it>p </it>= <it><</it>0.01. Females thought it significantly more likely that they would consider IVF or adoption than men, <it>p = </it>0.01. Men felt they were more likely to abstain from having children than women: <it>p = <</it>0.01. Women believed that body weight influenced fertility significantly more often than men: <it>p = <</it>0.01 and men believed significantly more often that smoking influenced fertility: <it>p </it>= 0.03. Both female and male students answered that they would like to have more knowledge about the area of fertility.</p> <p>Conclusions</p> <p>Young people plan to start their families when the woman's fertility is already in decline. Improving young people's knowledge about these issues would give them more opportunity to take responsibility for their sexual health and to take an active role in shaping political change to improve conditions for earlier parenthood.</p