Connecting Variability in Global Transcription Rate to Mitochondrial Variability

The authors demonstrate a connection between variability in the rate of transcription and differences in cellular mitochondrial content

Role of deep levels and interface states in the capacitance characteristics of all‐sputtered CuInSe2/CdS solar cell heterojunctions

All‐sputtered CuInSe2/CdS solar cellheterojunctions have been analyzed by means of capacitance‐frequency (C‐F) and capacitance‐bias voltage (C‐V) measurements. Depending on the CuInSe2 layer composition, two kinds of heterojunctions were analyzed: type 1 heterojunctions (based on stoichiometric or slightly In‐rich CuInSe2 layers) and type 2 heterojunctions (based on Cu‐rich CuInSe2 layers). In type 1 heterojunctions, a 80‐meV donor level has been found. Densities of interface states in the range 101 0–101 1 cm2 eV− 1 (type 1) and in the range 101 2–101 3 cm− 2 eV− 1 (type 2) have been deduced. On the other hand, doping concentrations of 1.6×101 6 cm− 3 for stoichiometric CuInSe2 (type 1 heterojunction) and 8×101 7 cm− 3 for the CdS (type 2 heterojunction) have been deduced from C‐Vmeasurements

Can visco-elastic phase separation, macromolecular crowding and colloidal physics explain nuclear organisation?

BACKGROUND: The cell nucleus is highly compartmentalized with well-defined domains, it is not well understood how this nuclear order is maintained. Many scientists are fascinated by the different set of structures observed in the nucleus to attribute functions to them. In order to distinguish functional compartments from non-functional aggregates, I believe is important to investigate the biophysical nature of nuclear organisation. RESULTS: The various nuclear compartments can be divided broadly as chromatin or protein and/or RNA based, and they have very different dynamic properties. The chromatin compartment displays a slow, constrained diffusional motion. On the other hand, the protein/RNA compartment is very dynamic. Physical systems with dynamical asymmetry go to viscoelastic phase separation. This phase separation phenomenon leads to the formation of a long-lived interaction network of slow components (chromatin) scattered within domains rich in fast components (protein/RNA). Moreover, the nucleus is packed with macromolecules in the order of 300 mg/ml. This high concentration of macromolecules produces volume exclusion effects that enhance attractive interactions between macromolecules, known as macromolecular crowding, which favours the formation of compartments. In this paper I hypothesise that nuclear compartmentalization can be explained by viscoelastic phase separation of the dynamically different nuclear components, in combination with macromolecular crowding and the properties of colloidal particles. CONCLUSION: I demonstrate that nuclear structure can satisfy the predictions of this hypothesis. I discuss the functional implications of this phenomenon

Coadministration of the Three Antigenic Leishmania infantum Poly (A) Binding Proteins as a DNA Vaccine Induces Protection against Leishmania major Infection in BALB/c Mice

Highly conserved intracellular proteins from Leishmania have been described as antigens in natural and experimental infected mammals. The present study aimed to evaluate the antigenicity and prophylactic properties of the Leishmania infantum Poly (A) binding proteins (LiPABPs). Three different members of the LiPABP family have been described. Recombinant tools based on these proteins were constructed: recombinant proteins and DNA vaccines. The three recombinant proteins were employed for coating ELISA plates. Sera from human and canine patients of visceral leishmaniasis and human patients of mucosal leishmaniasis recognized the three LiPABPs. In addition, the protective efficacy of a DNA vaccine based on the combination of the three Leishmania PABPs has been tested in a model of progressive murine leishmaniasis: BALB/c mice infected with Leishmania major. The induction of a Th1-like response against the LiPABP family by genetic vaccination was able to down-regulate the IL-10 predominant responses elicited by parasite LiPABPs after infection in this murine model. This modulation resulted in a partial protection against L. major infection. LiPABP vaccinated mice showed a reduction on the pathology that was accompanied by a decrease in parasite burdens, in antibody titers against Leishmania antigens and in the IL-4 and IL-10 parasite-specific mediated responses in comparison to control mice groups immunized with saline or with the non-recombinant plasmid. The results presented here demonstrate for the first time the prophylactic properties of a new family of Leishmania antigenic intracellular proteins, the LiPABPs. The redirection of the immune response elicited against the LiPABP family (from IL-10 towards IFN-γ mediated responses) by genetic vaccination was able to induce a partial protection against the development of the disease in a highly susceptible murine model of leishmaniasisThe study was supported in Spain by grants from Ministerio de Ciencia e Innovación FIS PI11/00095 and FISPI14/00366 from the Instituto de Salud Carlos III within the Network of TropicalDiseases Research (VI P I+D+I 2008-2011, ISCIII -Subdirección General de Redes y Centros de Investigación Cooperativa (RD12/0018/0009)). This work was also supported in Brazil by a grant from CNPq (Ciencia sem Fronteiras-PVE 300174/2014-4). A CBMSO institutional grant from Fundación Ramón Areces is also acknowledged. EAFC is a grant recipient of CNPq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Poised Transcription Factories Prime Silent uPA Gene Prior to Activation

The association of poised genes with transcription factories may contribute to rapid transcriptional activation in response to stimuli and to silencing when genes are located at the interior of their chromosome territories

Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells

Gene expression states influence the three-dimensional conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features, which define promoter activation states or CTCF binding sites. Single cell imaging of the locus folding was performed to test model predictions. While CTCF occupancy alone fails to predict the in vivo folding at genomic length scale of 10 kb, we found that homotypic interactions between active and Polycomb-repressed promoters co-occurring in the same DNA fibre fully explain the HoxB folding patterns imaged in single cells. We identify state-dependent promoter interactions as major drivers of chromatin folding in gene-dense regions

Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior

Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro

Performance Evaluation of the Dual Ring MAMMI breast PET

[Otros] MAMMI is a dedicated breast positron emission tomograph (PET) based on monolythic LYSO crystals, with a transaxial field of view (FOV) of 170 mm. It has been upgraded by adding a second ring of detectors that extends the axial FOV from 40 mm to 94.4 mm, in order to improve its sensitivity and reduce the acquisition time. In this work we present the performance evaluation of the dual ring MAMMI breast PET and a discussion about the contribution of the addition of a second ring of detectors, the compensation of the detector blur and the increase of the scintillator thickness. Experimental measurements suggested on NEMA NU 4-2008 and NEMA NU 2-2007 have been conveniently adapted to the dimensions of the MAMMI. The addition of the second ring of detectors leads to a rise of the sensitivity from 1.8% to 3.6%. The spatial resolution at one-fourth of the axial FOV (1.5 mm axial, 1.6 mm tangential, 1.7 mm radial) is slightly better than that measured at the axial center (1.9 mm axial, 1.8 mm tangential and radial), because of the 14 mm gap in between detection rings. The results obtained after the evaluation reflect a substantial performance improvement, specially in the absolute sensitivity, because of the changes introduced in the MAMMI PET.This work was supported in part bythe Spanish Plan Nacional de Investigacion Científica, Desarrollo e Innovación Tecnologica (I+D+I) under Grant No. FIS2010-21216-CO2-01 and Valencian Local Government under Grants PROMETEOII/2013/010 and ISIC 2011/013Soriano, A.; Sánchez, F.; Carrilero, V.; Pardo, A.; Vidal San Sebastian, LF.; Vazquez, C.; Barbera, J.... (2013). Performance Evaluation of the Dual Ring MAMMI breast PET. IEEE. 1-4. https://doi.org/10.1109/NSSMIC.2013.6829103S1