A Network of microRNAs Acts to Promote Cell Cycle Exit and Differentiation of Human Pancreatic Endocrine Cells.

Pancreatic endocrine cell differentiation is orchestrated by the action of transcription factors that operate in a gene regulatory network to activate endocrine lineage genes and repress lineage-inappropriate genes. MicroRNAs (miRNAs) are important modulators of gene expression, yet their role in endocrine cell differentiation has not been systematically explored. Here we characterize miRNA-regulatory networks active in human endocrine cell differentiation by combining small RNA sequencing, miRNA over-expression, and network modeling approaches. Our analysis identified Let-7g, Let-7a, miR-200a, miR-127, and miR-375 as endocrine-enriched miRNAs that drive endocrine cell differentiation-associated gene expression changes. These miRNAs are predicted to target different transcription factors, which converge on genes involved in cell cycle regulation. When expressed in human embryonic stem cell-derived pancreatic progenitors, these miRNAs induce cell cycle exit and promote endocrine cell differentiation. Our study delineates the role of miRNAs in human endocrine cell differentiation and identifies miRNAs that could facilitate endocrine cell reprogramming

Association of EP2 receptor and SLC19A3 in regulating breast cancer metastasis

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N‑Linked Glycosylation Prevents Deamidation of Glycopeptide and Glycoprotein

Deamidation has been recognized as a common spontaneous pathway of protein degradation and a prevalent concern in the pharmaceutical industry; deamidation caused the reduction of protein/peptide drug efficacy and shelf life in several cases. More importantly, deamidation of physiological proteins is related to several human diseases and considered a timer for the diseases. N-linked glycosylation has a variety of significant biological functions, and it interestingly occurs right on the deamidation site-asparagine. It has been perceived that N-glycosylation could prevent deamidation, but experimental support is still lacking for clearly understanding the role of N-glycosylation on deamidation. Our results presented that deamidation is prevented by naturally occurring N-linked glycosylation. Glycopeptides and corresponding nonglycosylated peptides were used to compare their deamidation rates. All the nonglycosylated peptides have different half-lives ranging from one to 20 days, for the corresponding glycosylated peptides; all the results showed that the deamidation reaction was significantly reduced by the introduction of N-linked glycosylation. A glycoprotein, RNase B, also showed a significantly elongated deamidation half-life compared to nonglycosylated protein RNase A. At last, N-linked glycosylation on INGAP-P, a therapeutic peptide, increased the deamidation half-life of INGAP-P as well as its therapeutic potency

Ge quantum dot arrays grown by ultrahigh vacuum molecular beam epitaxy on the Si(001) surface: nucleation, morphology and CMOS compatibility

Issues of morphology, nucleation and growth of Ge cluster arrays deposited by ultrahigh vacuum molecular beam epitaxy on the Si(001) surface are considered. Difference in nucleation of quantum dots during Ge deposition at low (<600 deg C) and high (>600 deg. C) temperatures is studied by high resolution scanning tunneling microscopy. The atomic models of growth of both species of Ge huts---pyramids and wedges---are proposed. The growth cycle of Ge QD arrays at low temperatures is explored. A problem of lowering of the array formation temperature is discussed with the focus on CMOS compatibility of the entire process; a special attention is paid upon approaches to reduction of treatment temperature during the Si(001) surface pre-growth cleaning, which is at once a key and the highest-temperature phase of the Ge/Si(001) quantum dot dense array formation process. The temperature of the Si clean surface preparation, the final high-temperature step of which is, as a rule, carried out directly in the MBE chamber just before the structure deposition, determines the compatibility of formation process of Ge-QD-array based devices with the CMOS manufacturing cycle. Silicon surface hydrogenation at the final stage of its wet chemical etching during the preliminary cleaning is proposed as a possible way of efficient reduction of the Si wafer pre-growth annealing temperature.Comment: 30 pages, 11 figure

The HETDEX Pilot Survey III: The Low Metallicities of High-Redshift Lyman Alpha Galaxies

We present Keck/NIRSPEC spectroscopic observations of three Lyman alpha emitting galaxies (LAEs) at z ~ 2.3 discovered with the HETDEX pilot survey. We detect Halpha, [OIII], and Hbeta emission from two galaxies at z = 2.29 and 2.49, designated HPS194 and HPS256, respectively, representing the first detection of multiple rest-frame optical emission lines in galaxies at high-redshift selected on the basis of their Lyman alpha emission. The redshifts of the Lyman alpha emission from these galaxies are offset redward of the systemic redshifts by Delta_v = 162 +/- 37 (photometric) +/- 42 (systematic) km/s for HPS194, and Delta_v = 36 +/- 35 +/- 18 km/s for HPS256. An interpretation for HPS194 is that a large-scale outflow may be occurring in its interstellar medium. The emission line ratios imply that neither LAE hosts an active galactic nucleus. Using the upper limits on the [NII] emission we place meaningful constraints on the gas-phase metallicities in these two LAEs of Z < 0.17 and < 0.28 Zsol (1 sigma). Measuring the stellar masses of these objects via spectral energy distribution (SED) fitting (~ 10^10 and 6 x 10^8 Msol, respectively), we study the nature of LAEs in a mass-metallicity plane. At least one of these two LAEs appears to be more metal poor than continuum-selected star-forming galaxies at the same redshift and stellar mass, implying that objects exhibiting Lyman alpha emission may be systematically less chemically enriched than the general galaxy population. We use the SEDs of these two galaxies to show that neglecting the emission lines when fitting stellar population models to the observed photometry can result in overestimates of the population age by orders of magnitude, and the stellar mass by a factor of ~ 2. This effect is particularly important at z > 7, where similarly strong emission lines may masquerade in the photometry as a 4000 A break (abridged).Comment: Replaced with the accepted (to ApJ) versio