Which Sry Locus Is the Hypertensive Y Chromosome Locus?

The Y chromosome of the spontaneously hypertensive rat (SHR) contains a genetic component that raises blood pressure compared with the Wistar-Kyoto (WKY) Y chromosome. This research tests the Sry gene complex as the hypertensive component of the SHR Y chromosome. The Sry loci were sequenced in 1 strain with a hypertensive Y chromosome (SHR/Akr) and 2 strains with a normotensive Y chromosome (SHR/Crl and WKY/Akr). Both SHR strains have 7 Sry loci, whereas the WKY strain has 6. The 6 loci in common between SHR and WKY strains were identical in the sequence compared (coding region, 392-bp 5\u27 prime flanking, 1200-bp 3\u27 flanking). Both SHR strains have a locus (Sry3) not found in WKY rats, but this locus is different between SHR/Akr and SHR/Crl rats. Six mutations have accumulated in Sry3 between the SHR strains, whereas the other 6 Sry loci are identical. This pattern of an SHR-specific locus and mutation in this locus in SHR/Crl coinciding with the loss of Y chromosome hypertension is an expected pattern if Sry3 is the Y chromosome-hypertensive component. The SHR/y strain showed a significant increase in total Sry expression in the kidney between 4 and 15 weeks of age. There are significant differences in Sry expression between adrenal glands and the kidney (15 to 30 times higher in kidneys) but no significant differences between strains. These results, along with previous studies demonstrating an interaction of Sry with the tyrosine hydroxylase promoter and increased blood pressure with exogenous Sry expression, suggest the Sry loci as the hypertensive component of the SHR Y chromosome

Delivery of sry1, but not sry2, to the kidney increases blood pressure and sns indices in normotensive wky rats

<p>Abstract</p> <p>Background</p> <p>Our laboratory has shown that a locus on the SHR Y chromosome increases blood pressure (BP) in the SHR rat and in WKY rats with the SHR Y chromosome (SHR/y rat). A candidate for this Y chromosome hypertension locus is Sry, a gene that encodes a transcription factor responsible for testes determination. The SHR Y chromosome has six divergent Sry loci. The following study examined if exogenous <it>Sry1 </it>or Sry2 delivered to the kidney would elevate renal tyrosine hydroxylase, renal catecholamines, plasma catecholamines and telemetered BP over a 28 day period. We delivered 50 μg of either the expression construct Sry1/pcDNA 3.1, Sry2/pcDNA 3.1, or control vector into the medulla of the left kidney of normotensive WKY rats by electroporation. Weekly air stress was performed to determine BP responsiveness. Separate groups of animals were tested for renal function and plasma hormone patterns and pharmacological intervention using alpha adrenergic receptor blockade. Pre-surgery baseline and weekly blood samples were taken from <it>Sry1 </it>electroporated and control vector males for plasma renin, aldosterone, and corticosterone. BP was measured by telemetry and tyrosine hydroxylase and catecholamines by HPLC with electrochemical detection.</p> <p>Results</p> <p>In the animals receiving the <it>Sry1 </it>plasmid there were significant increases after 21 days in resting plasma norepinephrine (NE, 27%) and renal tyrosine hydroxylase content (41%, p < .05) compared to controls. BP was higher in animals electroporated with <it>Sry1 </it>(143 mmHg, p < .05) compared to controls (125 mmHg) between 2–4 weeks. Also the pressor response to air stress was significantly elevated in males electroporated with <it>Sry1 </it>(41 mmHg) compared to controls (28 mmHg, p < .001). <it>Sry2 </it>did not elevate BP or SNS indices and further tests were not done. The hormone profiles for plasma renin, aldosterone, and corticosterone between electroporated <it>Sry1 </it>and control vector males showed no significant differences over the 28 day period. Alpha adrenergic receptor blockade prevented the air stress pressor response in both strains. Urinary dopamine significantly increased after 7 days post Sry electroporation.</p> <p>Conclusion</p> <p>These results are consistent with a role for <it>Sry1 </it>in increasing BP by directly or indirectly activating renal sympathetic nervous system activity.</p

The evolution of the cosmic molecular gas density

One of the last missing pieces in the puzzle of galaxy formation and evolution through cosmic history is a detailed picture of the role of the cold gas supply in the star-formation process. Cold gas is the fuel for star formation, and thus regulates the buildup of stellar mass, both through the amount of material present through a galaxy's gas mass fraction, and through the efficiency at which it is converted to stars. Over the last decade, important progress has been made in understanding the relative importance of these two factors along with the role of feedback, and the first measurements of the volume density of cold gas out to redshift 4, (the "cold gas history of the Universe") has been obtained. To match the precision of measurements of the star formation and black-hole accretion histories over the coming decades, a two orders of magnitude improvement in molecular line survey speeds is required compared to what is possible with current facilities. Possible pathways towards such large gains include significant upgrades to current facilities like ALMA by 2030 (and beyond), and eventually the construction of a new generation of radio-to-millimeter wavelength facilities, such as the next generation Very Large Array (ngVLA) concept.Comment: 7 pages, 2 figures, Science White paper submitted to Astro2020 Decadal Surve

Assessing the Societal Impact of Research: The Relational Engagement Approach

Marketing and policy researchers aiming to increase the societal impact of their scholarship should engage directly with relevant stakeholders. For maximum societal effect, this engagement needs to occur both within the research process and throughout the complex process of knowledge transfer. The authors propose that a relational engagement approach to research impact complements and builds on traditional approaches. Traditional approaches to impact employ bibliometric measures and focus on the creation and use of journal articles by scholarly audiences, an important but incomplete part of the academic process. The authors recommend expanding the strategies and measures of impact to include process assessments for specific stakeholders across the entire course of impact, from the creation, awareness, and use of knowledge to societal impact. This relational engagement approach involves the cocreation of research with audiences beyond academia. The authors hope to begin a dialogue on the strategies researchers can use to increase the potential societal benefits of their research

The evolution of the cosmic molecular gas density

One of the last missing pieces in the puzzle of galaxy formation and evolution through cosmic history is a detailed picture of the role of the cold gas supply in the star-formation process. Cold gas is the fuel for star formation, and thus regulates the buildup of stellar mass, both through the amount of material present through a galaxy's gas mass fraction, and through the efficiency at which it is converted to stars. Over the last decade, important progress has been made in understanding the relative importance of these two factors along with the role of feedback, and the first measurements of the volume density of cold gas out to redshift 4, (the "cold gas history of the Universe") has been obtained. To match the precision of measurements of the star formation and black-hole accretion histories over the coming decades, a two orders of magnitude improvement in molecular line survey speeds is required compared to what is possible with current facilities. Possible pathways towards such large gains include significant upgrades to current facilities like ALMA by 2030 (and beyond), and eventually the construction of a new generation of radio-to-millimeter wavelength facilities, such as the next generation Very Large Array (ngVLA) concept

Cosmological Synergies Enabled by Joint Analysis of Multi-probe data from WFIRST, Euclid, and LSST

WFIRST, Euclid, and LSST are all missions designed to perform dedicated cosmology surveys that offer unprecedented statistical constraining power and control of systematic uncertainties. There is a growing realization that these missions will be significantly more powerful when the data are processed and analyzed in unison