Inhibition of histone deacetylase as a treatment for cardiac hypertrophy

The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.Board of Regents, University of Texas Syste

GENERAL COMBINING ABILITY EFFECTS FOR REPRODUCTIVE HEAT TOLERANCE IN SNAP BEAN

GENERAL COMBINING ABILITY EFFECTS FOR REPRODUCTIVE HEAT TOLERANCE IN SNAP BEA

Whole Genome Sequencing for Public Health Surveillance of Shiga Toxin-Producing Escherichia coli Other than Serogroup O157

Shiga toxin-producing Escherichia coli (STEC) are considered to be a significant threat to public health due to the severity of gastrointestinal symptoms associated with human infection. In England STEC O157 is the most commonly detected STEC serogroup, however, the implementation of PCR at local hospital laboartories has resulted in an increase in the detection of STEC other than serogroup O157 (non-O157 STEC). The aim of this study was to evaluate the use of whole genome sequencing (WGS) for routine public health surveillance of non-O157 STEC by comparing this approach to phenotypic serotyping and PCR for subtyping the stx-encoding genes. Of the 102 isolates where phenotypic and genotypic serotyping could be compared, 98 gave fully concordant results. The most common non-O157 STEC serogroups detected were O146 (22) and O26 (18). All but one of the 38 isolates that could not be phenotypically serotyped (designated O unidentifiable or O rough) were serotyped using the WGS data. Of the 73 isolates where a flagella type was available by traditional phenotypic typing, all results matched the H-type derived from the WGS data. Of the 140 sequenced non-O157 isolates, 52 (37.1%) harboured stx1 only, 42 (30.0%) had stx2 only, 46 (32.9%) carried stx1 and stx2. Of these, stx subtyping PCR results were available for 131 isolates and 121 of these had concordant results with the stx subtype derived from the WGS data. Non-specific primer binding during PCR amplification, due to the similarity of the stx2 subtype gene sequences was the most likely cause. The results of this study showed WGS provided a reliable and robust one-step process for characterisation of STEC. Deriving the full serotype from WGS data in real time has enabled us to report a higher level of strain discrimination while stx subtyping provides data on the pathogenic potential of each isolate, enabling us to predict clinical outcome of each case and to monitor the emergence of hyper-virulent strains

RAFT polymerization of temperature- and salt-responsive block copolymers as reversible hydrogels

Reversible-addition fragmentation chain transfer (RAFT) polymerization enabled the synthesis of novel, stimuli-responsive, AB and ABA block copolymers. The B block contained oligo(ethylene glycol) methyl ether methacrylate (OEG) and was permanently hydrophilic in the conditions examined. The A block consisted of diethylene glycol methyl ether methacrylate (DEG) and [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMA). The A block displayed both salt- and temperature-response with lower critical solution temperatures (LCSTs) dependent on the molar content of TMA and the presence of salt. Higher TMA content in the AB diblock copolymers increased the critical micelle temperatures (CMT) in HPLC-grade water due to an increased hydrophilicity of the A block. Upon addition of 0.9 wt% NaCl, the CMTs of poly(OEG-b-DEG95TMA5) decreased from 50 °C to 36 °C due to screening of electrostatic repulsion between the TMA units. ABA triblock copolymers displayed excellent hydrogel properties with salt- and temperature-dependent gel points. TMA incorporation in the A block increased the gel points for all triblock copolymers, and salt-response increased with higher TMA composition in the A block. For example, poly(DEG98TMA2-b-OEG-b-DEG98TMA2) formed a hydrogel at 40 °C in HPLC-grade water and 26 °C in 0.9 wt% NaCl aqueous solution. These salt- and temperature-responsive AB diblock and ABA triblock copolymers find applications as drug delivery vehicles, adhesives, and hydrogels

A Lyman-alpha-only AGN from the Sloan Digital Sky Survey

The Sloan Digital Sky Survey has discovered a z=2.4917 radio-loud active galactic nucleus (AGN) with a luminous, variable, low-polarization UV continuum, H I two-photon emission, and a moderately broad Lyman-alpha line (FWHM = 1430 km/s) but without obvious metal-line emission. SDSS J113658.36+024220.1 does have associated metal-line absorption in three distinct, narrow systems spanning a velocity range of 2710 km/s. Despite certain spectral similarities, SDSS J1136+0242 is not a Lyman-break galaxy. Instead, the Ly-alpha and two-photon emission can be attributed to an extended, low-metallicity narrow-line region. The unpolarized continuum argues that we see SDSS J1136+0242 very close to the axis of any ionization cone present. We can conceive of two plausible explanations for why we see a strong UV continuum but no broad-line emission in this `face-on radio galaxy' model for SDSS J1136+0242: the continuum could be relativistically beamed synchrotron emission which swamps the broad-line emission; or, more likely, SDSS J1136+0242 could be similar to PG 1407+265, a quasar in which for some unknown reason the high-ionization emission lines are very broad, very weak, and highly blueshifted.Comment: AJ, in press, 10 pages emulateapj forma

Improved Dynamical Masses for Six Brown Dwarf Companions Using Hipparcos and Gaia EDR3

We present comprehensive orbital analyses and dynamical masses for the substellar companions Gl~229~B, Gl~758~B, HD~13724~B, HD~19467~B, HD~33632~Ab, and HD~72946~B. Our dynamical fits incorporate radial velocities, relative astrometry, and most importantly calibrated Hipparcos-Gaia EDR3 accelerations. For HD~33632~A and HD~72946 we perform three-body fits that account for their outer stellar companions. We present new relative astrometry of Gl~229~B with Keck/NIRC2, extending its observed baseline to 25 years. We obtain a $<$1\% mass measurement of $71.4 \pm 0.6\,M_{\rm Jup}$ for the first T dwarf Gl~229~B and a 1.2\% mass measurement of its host star ($0.579 \pm 0.007\,M_{\odot}$) that agrees with the high-mass-end of the M dwarf mass-luminosity relation. We perform a homogeneous analysis of the host stars' ages and use them, along with the companions' measured masses and luminosities, to test substellar evolutionary models. Gl~229~B is the most discrepant, as models predict that an object this massive cannot cool to such a low luminosity within a Hubble time, implying that it may be an unresolved binary. The other companions are generally consistent with models, except for HD~13724~B that has a host-star activity age 3.8$\sigma$ older than its substellar cooling age. Examining our results in context with other mass-age-luminosity benchmarks, we find no trend with spectral type but instead note that younger or lower-mass brown dwarfs are over-luminous compared to models, while older or higher-mass brown dwarfs are under-luminous. The presented mass measurements for some companions are so precise that the stellar host ages, not the masses, limit the analysis.Comment: Accepted for publication in AJ. References updated in version 2. See the journal version for the full quality figures. Figure sets and the MCMC chains (reduced to just 1000 samples however) are included with the journal version of the article, and pre-publication at https://drive.google.com/drive/folders/1_A8QYn9NyPgmGqJaY5sMHyT_wAS3uRRK?usp=sharin

Crystal structure of the mitochondrial protein mitoNEET bound to a benze-sulfonide ligand

MitoNEET (gene cisd1) is a mitochondrial outer membrane [2Fe-2S] protein and is a potential drug target in several metabolic diseases. Previous studies have demonstrated that mitoNEET functions as a redox-active and pH-sensing protein that regulates mitochondrial metabolism, although the structural basis of the potential drug binding site(s) remains elusive. Here we report the crystal structure of the soluble domain of human mitoNEET with a sulfonamide ligand, furosemide. Exploration of the high-resolution crystal structure is used to design mitoNEET binding molecules in a pilot study of molecular probes for use in future development of mitochondrial targeted therapies for a wide variety of metabolic diseases, including obesity, diabetes and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease

Crystal Structure of the Mitochondrial Protein mitoNEET Bound to a Benze-sulfonide Ligand

MitoNEET (gene cisd1) is a mitochondrial outer membrane [2Fe-2S] protein and is a potential drug target in several metabolic diseases. Previous studies have demonstrated that mitoNEET functions as a redox-active and pH-sensing protein that regulates mitochondrial metabolism, although the structural basis of the potential drug binding site(s) remains elusive. Here we report the crystal structure of the soluble domain of human mitoNEET with a sulfonamide ligand, furosemide. Exploration of the high-resolution crystal structure is used to design mitoNEET binding molecules in a pilot study of molecular probes for use in future development of mitochondrial targeted therapies for a wide variety of metabolic diseases, including obesity, diabetes and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease

SDSSJ103913.70+533029.7: A Super Star Cluster in the Outskirts of a Galaxy Merger

We describe the serendipitous discovery in the spectroscopic data of the Sloan Digital Sky Survey of a star-like object, SDSSJ103913.70+533029.7, at a heliocentric radial velocity of +1012 km/s. Its proximity in position and velocity to the spiral galaxy NGC 3310 suggests an association with the galaxy. At this distance, SDSSJ103913.70+533029.7 has the luminosity of a super star cluster and a projected distance of 17 kpc from NGC 3310. Its spectroscopic and photometric properties imply a mass of > 10^6 solar masses and an age close to that of the tidal shells seen around NGC 3310, suggesting that it formed in the event which formed the shells.Comment: Accepted by AJ: 4 figures (1 color