Interferons Reshape the 3D Conformation and Accessibility of Macrophage Chromatin

Engagement of macrophages in innate immune responses is directed and enhanced by type I and type II interferons. An essential component of IFN activity is the use of JAK-STAT signal transduction for the transcriptional control of interferon-stimulated genes (ISG). Here, we study the immediate early nuclear response to type I IFN and IFN-γ in murine macrophages. Despite their distinct immunological activities, both IFN types triggered highly overlapping epigenomic and transcriptional changes. These changes included a rapid rearrangement of the 3D chromatin organization and an increase of DNA accessibility at ISG loci. ISGF3, the major transcriptional regulator of ISG, controlled homeostatic as well as induced-state DNA accessibility at a subset of ISG. Increases in DNA accessibility correlated with the appearance of activating histone marks at surrounding nucleosomes. Collectively our data emphasize changes in the three-dimensional nuclear space and epigenome as an important facet of transcriptional control by the IFN-induced JAK-STAT pathway.

Lamin A/C Mechanotransduction in Laminopathies

Mechanotransduction translates forces into biological responses and regulates cell functionalities. It is implicated in several diseases, including laminopathies which are pathologies associated with mutations in lamins and lamin-associated proteins. These pathologies affect muscle, adipose, bone, nerve, and skin cells and range from muscular dystrophies to accelerated aging. Although the exact mechanisms governing laminopathies and gene expression are still not clear, a strong correlation has been found between cell functionality and nuclear behavior. New theories base on the direct effect of external force on the genome, which is indeed sensitive to the force transduced by the nuclear lamina. Nuclear lamina performs two essential functions in mechanotransduction pathway modulating the nuclear stiffness and governing the chromatin remodeling. Indeed, A-type lamin mutation and deregulation has been found to affect the nuclear response, altering several downstream cellular processes such as mitosis, chromatin organization, DNA replication-transcription, and nuclear structural integrity. In this review, we summarize the recent findings on the molecular composition and architecture of the nuclear lamina, its role in healthy cells and disease regulation. We focus on A-type lamins since this protein family is the most involved in mechanotransduction and laminopathies.

Response functions and cross sections for inclusive neutrino scattering off $^2$H, $^3$H and $^3$He

For several decades there has been an interest in studying neutrino scattering on light nuclei, with the hope of increasing knowledge about the theory of weak interactions and electroweak unification. A study of several neutrino induced reactions on light nuclei (^22H, ^33H and ^33He) is presented here. The cross section for these reactions is evaluated using the nuclear response functions, which holds the information about the nuclear interactions and structure. This approach has been tested for break-up reactions on the deuteron before and is now extended to three-nucleon break-up reactions.

Cross sections for the neutral current νe - 116Cd scattering reaction

The cross sections for neutrino scattering off the 116Cd nucleus have been computed by utilizing the Quasi-particle Random Phase Approximation (QRPA). An- gular and initial energy dependence of the neutrino-nucleus cross sections have been calculated at low and intermediate electron neutrino energies up to 100 MeV. By solving the QRPA equations and fixing the appropriate parameters the lowest lying excitation energies spectrum was reproduced. The contributions from multipole ex- citations was examined. The obtained results could be used for studying the nuclear response of this isotope to supernova neutrino spectra.