Polymerization of hemoglobins in Arctic fish: Lycodes reticulatus and Gadus morhua

In vitro, and possibly in vivo, hemoglobin polymerization and red blood cell sickling appear to be widespread in codfish. In this article, we show that the hemoglobins of the two Arctic fish Lycodes reticulatus and Gadus morhua also have the tendency to polymerize, as monitored by dynamic light scattering experiments. The elucidation of the primary structure of the single hemoglobin of the zoarcid L. reticulatus shows the presence of a large number of cysteyl residues in α and β chains. Their role in eliciting the ability to produce polymers was also addressed by MALDI-TOF and TOF-TOF mass spectrometry. The G.morhua globins are also rich in Cys, but unlike in L. reticulatus, polymerization does not seem to be disulfide driven. The widespread occurrence of the polymerization phenomenon displayed by hemoglobins of Arctic fish supports the hypothesis that this feature may bea response to stressful environmental conditions.     

Combinatorial Screening of Polymer:Fullerene Blends for Organic Solar Cells by Inkjet Printing

Polymer:fullerene blends were screened in a combinatorial approach using inkjet printing thin film libraries for photovoltaic devices. The application of inkjet printing enabled a fast and simple experimental workflow from film preparation to the study of structure‐property‐relationships with a very high material efficiency. Inkjet printing requires less material for the preparation of thin film libraries in comparison to other dispensing techniques, like spin‐coating. Two polymers (PCPDTBT, PSBTBT) and two fullerene derivatives (mono‐PCBM, bis‐PCBM) were investigated in various blend ratios, concentrations, solvent ratios, and film thicknesses. Morphological and optical properties of the inkjet printed films were investigated and compared with spin‐coated films. This study shows the principle of an experimental setup from solution preparation to film characterization for the combinatorial investigation of large polymer:fullerene libraries.     

The role of Hedgehog signaling in fibrogenic liver repair

Repair of adult liver, like many tissues, involves the coordinated response of a number of different cell types. In adult livers, fibroblastic cells, ductular cells, inflammatory cells, and progenitor cells contribute to this process. Our studies demonstrate that the fates of such cells are dictated, at least in part, by Hedgehog, a fetal morphogenic pathway that was once thought to be active mainly during embryogenesis. Studies of injured adult human and rodent livers demonstrate that injury-related activation of the Hedgehog pathway modulates several important aspects of repair, including the growth of hepatic progenitor populations, hepatic accumulation of myofibroblasts, repair-related inflammatory responses, vascular remodeling, liver fibrosis and hepatocarcinogenesis. These findings identify the Hedgehog pathway as a potentially important target for biomarker development and therapeutic manipulation, and emphasize the need for further research to advance knowledge about how this pathway is regulated by and interacts with other signals that regulate adult liver repair.     

In vitro grown sheep preantral follicles yield oocytes with normal nuclear-epigenetic maturation

Background

Assisted reproductive technologies allow to utilize a limited number of fully grown oocytes despite the presence in the ovary of a large pool of meiotically incompetent gametes potentially able to produce live births. In vitro folliculogenesis could be useful to recruit these oocytes by promoting their growth and differentiation.

Methodology/Principal Findings

In vitro folliculogenesis was performed starting from sheep preantral (PA) follicles to evaluate oocyte nuclear/epigenetic maturation. Chromatin configuration, quantification of global DNA methylation, and epigenetic remodelling enzymes were evaluated with immunocytochemistry, telomere elongation was assessed with the Q-FISH technique, while the DNA methylation status at the DMRs of maternally IGF2R and BEGAIN, and paternally H19 methylated imprinted genes was determined by bisulfite sequencing and COBRA. Specifically, 70% of PA underwent early antrum (EA) differentiation and supported in culture oocyte global DNA methylation, telomere elongation, TERT and Dnmt3a redistribution thus mimicking the physiological events that involve the oocyte during the transition from secondary to tertiary follicle. Dnmt1 anticipated cytoplasmic translocation in in vitro grown oocytes did not impair global and single gene DNA methylation. Indeed, the in vitro grown oocytes acquired a methylation profile of IGF2R and BEGAIN compatible with the follicle/oocyte stage reached, and maintained an unmethylated status of H19. In addition, the percentage of oocytes displaying a condensed chromatin configuration resulted lower in in vitro grown oocytes, however, their ability to undergo meiosis and early embryo development after IVF and parthenogenetic activation was similar to that recorded in EA follicle in vivo grown oocytes.

Conclusions/Significance

In conclusion, the in vitro folliculogenesis was able to support the intracellular/nuclear mechanisms leading the oocytes to acquire a meiotic and developmental competence. Thus, the in vitro culture may increase the availability of fertilizable oocytes in sheep, and become an in vitro translational model to investigate the mechanisms governing nuclear/epigenetic oocyte maturation.     

7-Valent Pneumococcal Conjugate Vaccination in England and Wales: Is It Still Beneficial Despite High Levels of Serotype Replacement?

Background

The UK introduced the 7-valent pneumococcal conjugate vaccine (PCV7) into the national vaccination program in September 2006. Previous modelling assumed that the likely impact of PCV7 on invasive pneumococcal disease (IPD) would be similar to the US experience with PCV7. However, recent surveillance data show a more rapid replacement of PCV7 IPD cases by non-PCV7 IPD cases than was seen in the US.

Methods and Findings

A previous model of pneumococcal vaccination was re-parameterised using data on vaccine coverage and IPD from England and Wales between 2006 and 2009. Disease incidence was adjusted for the increasing trend in reported IPD cases prior to vaccination. Using this data we estimated that individuals carrying PCV7 serotypes have much higher protection (96%;95% CI 72%-100%) against acquisition of NVT carriage than the 15% previously estimated from US data, which leads to greater replacement. However, even with this level of replacement, the annual number of IPD cases may be 560 (95% CI, -100 to 1230) lower ten years after vaccine introduction compared to what it may have been without vaccination. A particularly marked fall of 39% in children under 15 years by 2015/6 is predicted.

Conclusion

Our model suggests that PCV7 vaccination could result in a decrease in overall invasive pneumococcal disease, particularly in children, even in an environment of rapid replacement with non-PCV7 serotypes within 5 years of vaccine introduction at high coverage.     

A dynamical model of genetic networks for cell differentiation

A mathematical model is proposed which is able to describe the most important features of cell differentiation, without requiring specific detailed assumptions concerning the interactions which drive the phenomenon. On the contrary, cell differentiation is described here as an emergent property of a generic model of the underlying gene regulatory network, and it can therefore be applied to a variety of different organisms. The model points to a peculiar role of cellular noise in differentiation and leads to non trivial predictions which could be subject to experimental testing. Moreover, a single model proves able to describe several different phenomena observed in various differentiation processes.