A low-mass protostar’s disk-envelope interface: disk-shadowing evidence from ALMA DCO⁺ observations of VLA1623

Context. Historically, due to instrumental limitations and a lack of disk detections, the structure of the transition from the envelope to the rotationally supported disk has been poorly studied. This is now possible with ALMA through observations of CO isotopologues and tracers of freezeout. Class 0 sources are ideal for such studies given their almost intact envelope and young disk. Aims. The structure of the disk-envelope interface of the prototypical Class 0 source, VLA1623A, which has a confirmed Keplerian disk, is constrained through modeling and analysis of ALMA observations of DCO+ (3−2) and C18O (2−1) rotational lines. Methods. The physical structure of VLA1623 is obtained from the large-scale spectral energy distribution (SED) and continuum radiative transfer. An analytic model using a simple network coupled with radial density and temperature profiles is used as input for a 2D line radiative transfer calculation for comparison with the ALMA Cycle 0 12-m array and Cycle 2 ACA observations of VLA1623. Results. The DCO+ emission shows a clumpy structure bordering VLA1623A’s Keplerian disk. This suggests a cold ring-like structure at the disk-envelope interface. The radial position of the observed DCO+ peak is reproduced in our model only if the region’s temperature is between 11 K and 16 K, lower than expected from models constrained by continuum data and source SED. Altering the density profile has little effect on the DCO+ peak position, but increased density is needed to reproduce the observed C18O tracing the disk. Conclusions. The observed DCO+ (3−2) emission around VLA1623A is the product of shadowing of the envelope by the disk observed in C18O. Disk-shadowing causes a drop in the gas temperature outside of the disk on >200 AU scales, encouraging the production of deuterated molecules. This indicates that the physical structure of the disk-envelope interface differs from the rest of the envelope, highlighting the drastic impact that the disk has on the envelope and temperature structure. The results presented here show that DCO+ is an excellent cold temperature tracer

Role of β-Catenin in Post-Meiotic Male Germ Cell Differentiation

Though roles of β-catenin signaling during testis development have been well established, relatively little is known about its role in postnatal testicular physiology. Even less is known about its role in post-meiotic germ cell development and differentiation. Here, we report that β-catenin is highly expressed in post-meiotic germ cells and plays an important role during spermiogenesis in mice. Spermatid-specific deletion of β-catenin resulted in significantly reduced sperm count, increased germ cell apoptosis and impaired fertility. In addition, ultrastructural studies show that the loss of β-catenin in post-meiotic germ cells led to acrosomal defects, anomalous release of immature spermatids and disruption of adherens junctions between Sertoli cells and elongating spermatids (apical ectoplasmic specialization; ES). These defects are likely due to altered expression of several genes reportedly involved in Sertoli cell-germ cell adhesion and germ cell differentiation, as revealed by gene expression analysis. Taken together, our results suggest that β-catenin is an important molecular link that integrates Sertoli cell-germ cell adhesion with the signaling events essential for post-meiotic germ cell development and maturation. Since β-catenin is also highly expressed in the Sertoli cells, we propose that binding of germ cell β-catenin complex to β-catenin complex on Sertoli cell at the apical ES surface triggers a signaling cascade that regulates post-meiotic germ cell differentiation

Synthesis of purine and 7-deazapurine nucleoside analogues of 6-N-(4-Nitrobenzyl)adenosine; inhibition of nucleoside transport and proliferation of cancer cells.

The 7-deazapurine nucleoside antibiotic tubercidin was converted into its 4-N-benzyl and 4-N-(4-nitrobenzyl) derivatives by alkylation at N3 followed by Dimroth rearrangement to the 4-N- isomer or by fluoro-diazotization followed by S(N)Ar displacement of the 4-fluoro group by a benzylamine. The 4-N-(4-nitrobenzyl) derivatives of sangivamycin and toyocamycin antibiotics were prepared by the alkylation approach. Cross-membrane transport of labeled uridine by hENT1 was inhibited to a weaker extent by the 4-nitrobenzylated tubercidin and sangivamycin analogues than was observed with 6-N-(4-nitrobenzyl)adenosine. Type-specific inhibition of cancer cell proliferation was observed at μM concentrations with the 4-N-(4-nitrobenzyl) derivatives of sangivamycin and toyocamycin, and also with 4-N-benzyltubercidin. Treatment of 2′,3′,5′-O-acetyladenosine with aryl isocyanates gave the 6-ureido derivatives but none of them exhibited inhibitory activity against cancer cell proliferation or hENT1

Synthesis of Purine and 7-Deazapurine Nucleoside Analogues of 6-N-(4-Nitrobenzyl)adenosine; Inhibition of Nucleoside Transport and Proliferation of Cancer Cells

Human equilibrative nucleoside transporter 1 (hENT1) is a prototypical nucleoside transporter protein ubiquitously expressed on the cell surface of almost all human tissue. Given the role of hENT1 in the transport of nucleoside drugs, an important class of therapeutics in the treatment of various cancers and viral infections, efforts have been made to better understand the mechanisms by which hENT1 modulates nucleoside transport. To that end, we report here the design and synthesis of novel tool compounds for the further study of hENT1. The 7-deazapurine nucleoside antibiotic tubercidin was converted into its 4-N-benzyl and 4-N-(4-nitrobenzyl) derivatives by alkylation at N3 followed by a Dimroth rearrangement to the 4-N-isomer or by fluoro-diazotization followed by SN Ar displacement of the 4-fluoro group by a benzylamine. The 4-N-(4-nitrobenzyl) derivatives of sangivamycin and toyocamycin antibiotics were prepared by the alkylation approach. Cross-membrane transport of labeled uridine by hENT1 was inhibited to a weaker extent by the 4-nitrobenzylated tubercidin and sangivamycin analogues than was observed with 6-N-(4-nitrobenzyl)adenosine. Type-specific inhibition of cancer cell proliferation was observed at micromolar concentrations with the 4-N-(4-nitrobenzyl) derivatives of sangivamycin and toyocamycin, and also with 4-N-benzyltubercidin. Treatment of 2',3',5'-O-acetyladenosine with aryl isocyanates gave the 6-ureido derivatives but none of them exhibited inhibitory activity against cancer cell proliferation or hENT1.status: publishe