Silk-fibronectin protein alloy fibres support cell adhesion and viability as a high strength, matrix fibre analogue

Silk is a natural polymer with broad utility in biomedical applications because it exhibits general biocompatibility and high tensile material properties. While mechanical integrity is important for most biomaterial applications, proper function and integration also requires biomaterial incorporation into complex surrounding tissues for many physiologically relevant processes such as wound healing. In this study, we spin silk fibroin into a protein alloy fibre with whole fibronectin using wet spinning approaches in order to synergize their respective strength and cell interaction capabilities. Results demonstrate that silk fibroin alone is a poor adhesive surface for fibroblasts, endothelial cells, and vascular smooth muscle cells in the absence of serum. However, significantly improved cell attachment is observed to silk-fibronectin alloy fibres without serum present while not compromising the fibres' mechanical integrity. Additionally, cell viability is improved up to six fold on alloy fibres when serum is present while migration and spreading generally increase as well. These findings demonstrate the utility of composite protein alloys as inexpensive and effective means to create durable, biologically active biomaterials.T32 EB006359 - NIBIB NIH HH

Model-driven analysis of experimentally determined growth phenotypes for 465 yeast gene deletion mutants under 16 different conditions

An iterative approach that integrates high-throughput measurements of yeast deletion mutants and flux balance model predictions improves understanding of both experimental and computational results

Having a family doctor is associated with some better patient-reported outcomes of primary care consultations

<b>Background</b> Hong Kong (HK) has pluralistic primary care that is provided by a variety of doctors. The aim of our study was to assess patient-reported outcomes of primary care consultations in HK and whether having a family doctor (FD) made any difference.<p></p> <b>Methods</b> We interviewed by telephone 3148 subjects from 5174 contacted households (response rate 60.8%) randomly selected from the general population of HK about the experience of their last primary care consultations in September 2007 and April 2008. We compared the patient-reported outcomes (PRO) and patient-centered process of care in those with a FD, those with other types of regular primary care doctors (ORD) and those without any regular primary care doctor (NRD). PRO included patient enablement, global improvement in health, overall satisfaction, and likelihood of recommending their doctors to family and friends. Patient-centered process of care indicators was explanations about the illness, and address of patient’s concerns.<p></p> <b>Results</b> One thousand one hundred fifty, 746, and 1157 reported to have FD, ORD, and NRD, respectively. Over 80% of those with FD consulted their usual primary care doctors in the last consultation compared with 27% of those with NRD. Compared with subjects having ORD or NRD, subjects with FD reported being more enabled after the consultation and were more likely to recommend their doctors to family and friends. Subjects with FD and ORD were more likely than those having NRD to report a global improvement in health and satisfaction. FD group was more likely than the other two groups to report receiving an explanation on the diagnosis, nature, and expected course of the illness, and having their concerns addressed. Patient enablement was associated with explanation of diagnosis, nature, and expected course of illness, and address of patient’s concerns.<p></p> <b>Conclusion</b> People with a regular FD were more likely to feel being enabled and to experience patient-centered care in consultations

Lineage dynamics of murine pancreatic development at single-cell resolution.

Organogenesis requires the complex interactions of multiple cell lineages that coordinate their expansion, differentiation, and maturation over time. Here, we profile the cell types within the epithelial and mesenchymal compartments of the murine pancreas across developmental time using a combination of single-cell RNA sequencing, immunofluorescence, in situ hybridization, and genetic lineage tracing. We identify previously underappreciated cellular heterogeneity of the developing mesenchyme and reconstruct potential lineage relationships among the pancreatic mesothelium and mesenchymal cell types. Within the epithelium, we find a previously undescribed endocrine progenitor population, as well as an analogous population in both human fetal tissue and human embryonic stem cells differentiating toward a pancreatic beta cell fate. Further, we identify candidate transcriptional regulators along the differentiation trajectory of this population toward the alpha or beta cell lineages. This work establishes a roadmap of pancreatic development and demonstrates the broad utility of this approach for understanding lineage dynamics in developing organs

Inhibition of Ape1 nuclease activity by lead, iron, and cadmium.

Many environmental metals are co-carcinogens, eliciting their effects via inhibition of DNA repair. Apurinic/apyrimidinic (AP) endonuclease 1 (Ape1) is the major mammalian abasic endonuclease and initiates repair of this cytotoxic/mutagenic lesion by incising the DNA backbone via a Mg(2+)-dependent reaction. In this study we examined the effects of arsenite [As(III)], cadmium [Cd(II)], cobalt [Co(II)], iron [Fe(II)], nickel [Ni(II)], and lead [Pb(II)] at concentrations ranging from 0.3 to 100 microM on the incision activity of Ape1 in the presence of 1 mM MgCl(subscript)2(/subscript). Pb(II) and Fe(II) inhibited Ape1 activity at each of the concentrations tested, with an IC(subscript)50(/subscript) (half-maximal inhibitory concentration) of 0.61 and 1.0 microM, respectively. Cd(II) also inhibited Ape1 activity but only at concentrations > 10 microM. No inhibition was seen with As(III), Co(II), or Ni(II). A similar inhibition pattern was observed with the homologous Escherichia coli protein, exonuclease III, but no inhibition was seen with the structurally distinct AP endonuclease E. coli endonuclease IV, indicating a targeted effect of Pb(II), Fe(II), and Cd(II) on the Ape1-like repair enzymes. Excess nonspecific DNA did not abrogate the metal inactivation, suggesting a protein-specific effect. Notably, Cd(II), Fe(II), and Pb(II) [but not As(III), Co(II), or Ni(II)] inhibited AP endonuclease activity in whole-cell extracts but had no significant effect on single nucleotide gap filling, 5'-flap endonuclease, and nick ligation activities, supporting the idea of selective inactivation of Ape1 in cells. Our results are the first to identify a potential DNA repair enzyme target for lead and suggest a means by which these prevalent environmental metals may elicit their deleterious effects

Questioning the Innovation of Complex Products and Systems with a Case Study of the Boeing 737 Airplane

Complex Products and Systems (CoPS) is an established category of products that are recognized to be underserved in the area of innovation. CoPS tend to be highly costly projects that are characterized by difficult development uncertainties and low rates of production. As a result traditional innovation theories are not seen to be easily applicable particularly as manufacturers of CoPS can tend to struggle with accomplishing dominant designs and enjoying the downstream fruits of product maturity such as commoditization. To further investigate this concern, a case study is performed on the Boeing B737 airplane which is the most successful selling commercial jet airplane series in history. The amazing part of the story is that it has been able to do this and maintain competitive parity in the face of competition from the Airbus A320 airplane which has a design origin close to 20 years ahead of the B737. To perform this study, a review of innovation theory, particularly Disruptive Innovation, is done together with the concept of product platforms and product families. The results show that the challenge of CoPS can in fact be potentially overcome by employing an appropriate strategy of product platforms and continuous upgrading of product architecture

PRIMUS: An observationally motivated model to connect the evolution of the AGN and galaxy populations out to z~1

We present an observationally motivated model to connect the AGN and galaxy populations at 0.2<z<1.0 and predict the AGN X-ray luminosity function (XLF). We start with measurements of the stellar mass function of galaxies (from the Prism Multi-object Survey) and populate galaxies with AGNs using models for the probability of a galaxy hosting an AGN as a function of specific accretion rate. Our model is based on measurements indicating that the specific accretion rate distribution is a universal function across a wide range of host stellar mass with slope gamma_1 = -0.65 and an overall normalization that evolves with redshift. We test several simple assumptions to extend this model to high specific accretion rates (beyond the measurements) and compare the predictions for the XLF with the observed data. We find good agreement with a model that allows for a break in the specific accretion rate distribution at a point corresponding to the Eddington limit, a steep power-law tail to super-Eddington ratios with slope gamma_2 = -2.1 +0.3 -0.5, and a scatter of 0.38 dex in the scaling between black hole and host stellar mass. Our results show that samples of low luminosity AGNs are dominated by moderately massive galaxies (M* ~ 10^{10-11} M_sun) growing with a wide range of accretion rates due to the shape of the galaxy stellar mass function rather than a preference for AGN activity at a particular stellar mass. Luminous AGNs may be a severely skewed population with elevated black hole masses relative to their host galaxies and in rare phases of rapid accretion.Comment: 11 pages, 5 figures, emulateapj format, updated to match version accepted for publication in Ap