2,4-Dioxo-1-(prop-2-yn­yl)-1,2,3,4-tetra­hydro­pyrimidine-5-carbaldehyde

In the crystal structure of the title compound, C8H6N2O3, the mol­ecules are linked by a pairs of inter­molecular N—H⋯O hydrogen bonds, forming inversion dimers. The aldehyde group is in the same plane as the pyrimidine ring [with a maximum deviation of 0.083 (2) Å for the O atom), and the linear propargyl group [C—C—C = 178.99 (19)°] makes a dihedral angle of 74.36 (13)° with the ring

[(2R,3S,5R)-3-Acet­oxy-5-(5-formyl-2,4-dioxo-1,2,3,4-tetra­hydro­pyrimidin-1-yl)-2,3,4,5-tetra­hydro­furan-2-yl]methyl acetate

In the two independent but very similar mol­ecules (A and B) of the title compound, C14H16N2O8, both six-membered pyrimidine rings are nearly planar [maximum deviations = 0.010 (3) Å in A and 0.028 (3) Å in B]. The five-membered furan­ose ring in mol­ecule A adopts an envelope conformation, while the same ring in mol­ecule B has a twisted conformation. In the crystal, the A mol­ecules are linked via a pair of inter­molecular N—H⋯O hydrogen bonds, forming dimers. Each A mol­ecule is further linked to a B mol­ecule via a second N—H⋯O hydrogen bond. There are also a number of C—H⋯·O inter­actions present, leading to the formation of a three-dimensional network

Genetic polymorphisms of TLR3 are associated with Nasopharyngeal carcinoma risk in Cantonese population

<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carcinoma is endemic in Southern China, displays a strong relationship with genetic susceptibility and associates with Epstein-Barr virus infection. Toll-like receptor 3 (TLR3) plays an important role in the antivirus response. Therefore, we examined the association between <it>TLR3 </it>gene polymorphisms and NPC susceptibility.</p> <p>Methods</p> <p>We performed a case-control study of 434 NPC cases and 512 healthy controls matched on age, sex and residence. Both cases and controls are of Cantonese origin from Southern China. Genetic variants in <it>TLR3 </it>were determined by polymerase chain reaction (PCR)-based DNA direct sequencing and four SNPs were genotyped in all samples.</p> <p>Results</p> <p>Our results showed that allele C for SNP 829A/C increased NPC risk significantly ((p = 0.0068, OR = 1.49, 95%CI:1.10–2.00). When adjusted for age, gender and VCA-IgA antibody titers, the NPC risk was reduced significantly among individuals who carried the haplotype "ATCT" compared to those who carried the most common haplotype "ACCT" (p = 0.0054, OR = 0.028; 95% CI (0.002–0.341).</p> <p>Conclusion</p> <p>The <it>TLR3 </it>polymorphisms may be relevant to NPC susceptibility in the Cantonese population, although the reduction in NPC risk is modest and the biological mechanism of the observed association merits further investigation.</p

A spectroscopic study of the blue stragglers in M67

Based on spectrophotometric observations from the Guillermo Haro Observatory (Cananea, Mexico), a study of the spectral properties of the complete sample of 24 blue straggler stars (BSs) in the old Galactic open cluster M67 (NGC 2682) is presented. All spectra, calibrated using spectral standards, were recalibrated by means of photometric magnitudes in the Beijing-Arizona-Taipei-Connecticut system, which includes fluxes in 11 bands covering ~3500-10000 A. The set of parameters was obtained using two complementary approaches that rely on a comparison of the spectra with (i) an empirical sample of stars with well-established spectral types and (ii) a theoretical grid of optical spectra computed at both low and high resolution. The overall results indicate that the BSs in M67 span a wide range in Teff(~ 5600 -12600 K) and surface gravities that are fully compatible with those expected for main-sequence objects (log g = 3.5 -5.0 dex).Comment: 10 pages, 10 figures, published in MNRAS (2008, Volume 390, Issue 2, pp. 665-674

Purkinje-cell-specific MeCP2 deficiency leads to motor deficits and autistic-like behavior due to aberrations in PTP1B-TrkB-SK signaling

Patients with Rett syndrome suffer from a loss-of-function mutation of the Mecp2 gene, which results in various symptoms including autistic traits and motor deficits. Deletion of Mecp2 in the brain mimics part of these symptoms, but the specific function of methyl-CpG-binding protein 2 (MeCP2) in the cerebellum remains to be elucidated. Here, we demonstrate that Mecp2 deletion in Purkinje cells (PCs) reduces their intrinsic excitability through a signaling pathway comprising the small-conductance calcium-activated potassium channel PTP1B and TrkB, the receptor of brain-derived neurotrophic factor. Aberration of this cascade, in turn, leads to autistic-like behaviors as well as reduced vestibulocerebellar motor learning. Interestingly, increasing activity of TrkB in PCs is sufficient to rescue PC dysfunction and abnormal motor and non-motor behaviors caused by Mecp2 deficiency. Our findings highlight how PC dysfunction may contribute to Rett syndrome, providing insight into the underlying mechanism and paving the way for rational therapeutic designs.</p

The SDSS-IV extended Baryon Oscillation Spectroscopic Survey: selecting emission line galaxies using the Fisher discriminant

We present a new selection technique of producing spectroscopic target catalogues for massive spectroscopic surveys for cosmology. This work was conducted in the context of the extended Baryon Oscillation Spectroscopic Survey (eBOSS), which will use ~200 000 emission line galaxies (ELGs) at 0.6<zspec<1.0 to obtain a precise baryon acoustic oscillation measurement. Our proposed selection technique is based on optical and near-infrared broad-band filter photometry. We used a training sample to define a quantity, the Fisher discriminant (linear combination of colours), which correlates best with the desired properties of the target: redshift and [OII] flux. The proposed selections are simply done by applying a cut on magnitudes and this Fisher discriminant. We used public data and dedicated SDSS spectroscopy to quantify the redshift distribution and [OII] flux of our ELG target selections. We demonstrate that two of our selections fulfil the initial eBOSS/ELG redshift requirements: for a target density of 180 deg^2, ~70% of the selected objects have 0.6<zspec<1.0 and only ~1% of those galaxies in the range 0.6<zspec<1.0 are expected to have a catastrophic zspec estimate. Additionally, the stacked spectra and stacked deep images for those two selections show characteristic features of star-forming galaxies. The proposed approach using the Fisher discriminant could, however, be used to efficiently select other galaxy populations, based on multi-band photometry, providing that spectroscopic information is available. This technique could thus be useful for other future massive spectroscopic surveys such as PFS, DESI, and 4MOST.Comment: Version published in A&

Real-time loop-mediated isothermal amplification for rapid detection of Enterocytozoon hepatopenaei

Background Enterocytozoon hepatopenaei (EHP) is a newly emerged microsporidian parasite that causes retarded shrimp growth in many countries. But there are no effective approaches to control this disease to date. The EHP could be an immune risk factor for increased dissemination of other diseases. Further, EHP infection involves the absence of obvious clinical signs and it is difficult to identify the pathogen through visual examination, increasing the risk of disease dissemination. It is urgent and necessary to develop a specific, rapid and sensitive EHP-infected shrimp diagnostic method to detect this parasite. In the present study, we developed and evaluated a rapid real-time loop-mediated isothermal amplification (real-time LAMP) for detection of EHP. Methods A rapid and efficient real-time LAMP method for the detection of EHP has been developed. Newly emerged EHP pathogens in China were collected and used as the sample, and three sets of specificity and sensitivity primers were designed. Three other aquatic pathogens were used as templates to test the specificity of the real-time LAMP assay. Also, we compared the real-time LAMP with the conventional LAMP by the serial dilutions of EHP DNA and their amplification curves. Application of real-time LAMP was carried out with clinical samples. Results Positive products were amplified only from EHP, but not from other tested species, EHP was detected from the clinical samples, suggesting a high specificity of this method. The final results of this assay were available within less than 45 min, and the initial amplification curve was observed at about 6 min. We found that the amplification with an exponential of sixfold dilutions of EHP DNA demonstrated a specific positive signal by the real-time LAMP, but not for the LAMP amplicons from the visual inspection. The real-time LAMP amplification curves demonstrated a higher slope than the conventional LAMP. Discussion In this study, pathogen virulence impacts have been increased in aquaculture and continuous observation was predominantly focused on EHP. The present study confirmed that the real-time LAMP assay is a promising and convenient method for the rapid identification of EHP in less time and cost. Its application greatly aids in the detection, surveillance, and prevention of EHP

Systematic differences in simple stellar population model results: Application to the M31 globular-like cluster system

Simple stellar population (SSP) synthesis models are useful tools for studying the nature of unresolved star clusters in external galaxies. However, the plethora of currently available SSP models gives rise to significant and poorly documented systematic differences. Here we consider the outputs of the commonly used Bruzual & Charlot and GALEV models, as well as a recently updated SSP model suite which attempts to include the contributions of binary merger products in the form of blue straggler stars (BS-SSP). We rederive the ages, metallicities, extinction values and masses of 445 previously observed globular-like clusters in M31 based on chi-square minimisation of their spectral energy distributions with respect to these three different SSP models and adopting a Chabrier-like stellar initial mass function. A comparison between our new results and previous estimates of the same parameters shows that the Bruzual & Charlot models yield the youngest ages and lowest masses, while adoption of the BS-SSP models results in the oldest ages and highest mass estimates. Similarly, the GALEV SSP models produce the lowest metallicities, with the highest values resulting from the BS-SSP model suite. These trends are caused by intrinsic differences associated with the models, and are not significantly affected by the well-known age-metallicity degeneracy. Finally, we note that the mass function of the massive M31 star clusters is similar to that of the Milky Way's globular clusters, which implies that the two star cluster systems likely formed under similar environmental conditions.Comment: 15 pages, 12 figures, 2 tables, accepted for publication in MNRA

Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of the USP1-KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC