Tensor distributions on signature-changing space-times

Irregularities in the metric tensor of a signature-changing space-time suggest that field equations on such space-times might be regarded as distributional. We review the formalism of tensor distributions on differentiable manifolds, and examine to what extent rigorous meaning can be given to field equations in the presence of signature-change, in particular those involving covariant derivatives. We find that, for both continuous and discontinuous signature-change, covariant differentiation can be defined on a class of tensor distributions wide enough to be physically interesting.Comment: 9 pages, LaTeX 2.0

Open access and beyond

Uncensored exchange of scientific results hastens progress. Open Access does not stop at the removal of price and permission barriers; still, censorship and reading disabilities, to name a few, hamper access to information. Here, we invite the scientific community and the public to discuss new methods to distribute, store and manage literature in order to achieve unfettered access to literature

Identification and characterization of Smyd2: a split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex

BACKGROUND: Disrupting the balance of histone lysine methylation alters the expression of genes involved in tumorigenesis including proto-oncogenes and cell cycle regulators. Methylation of lysine residues is commonly catalyzed by a family of proteins that contain the SET domain. Here, we report the identification and characterization of the SET domain-containing protein, Smyd2. RESULTS: Smyd2 mRNA is most highly expressed in heart and brain tissue, as demonstrated by northern analysis and in situ hybridization. Over-expressed Smyd2 localizes to the cytoplasm and the nucleus in 293T cells. Although accumulating evidence suggests that methylation of histone 3, lysine 36 (H3K36) is associated with actively transcribed genes, we show that the SET domain of Smyd2 mediates H3K36 dimethylation and that Smyd2 represses transcription from an SV40-luciferase reporter. Smyd2 associates specifically with the Sin3A histone deacetylase complex, which was recently linked to H3K36 methylation within the coding regions of active genes in yeast. Finally, we report that exogenous expression of Smyd2 suppresses cell proliferation. CONCLUSION: We propose that Sin3A-mediated deacetylation within the coding regions of active genes is directly linked to the histone methyltransferase activity of Smyd2. Moreover, Smyd2 appears to restrain cell proliferation, likely through direct modulation of chromatin structure

RETRACTED ARTICLE: The BCL11A transcription factor directly activates RAG gene expression and V(D)J recombination

Recombination-activating gene 1 protein (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The transcription factor BCL11A is required for B cell development, but its molecular function(s) in B cell fate specification and commitment is unknown. We show here that the major B cell isoform, BCL11A-XL, binds the RAG1 promoter and Erag enhancer to activate RAG1 and RAG2 transcription in pre-B cells. We employed BCL11A overexpression with recombination substrates in a cultured pre-B cell line as well as Cre recombinase-mediated Bcl11a(lox/lox) deletion in explanted murine pre-B cells to demonstrate direct consequences of BCL11A/RAG modulation on V(D)J recombination. We conclude that BCL11A is a critical component of a transcriptional network that regulates B cell fate by controlling V(D)J recombination

Cardiac Deletion of Smyd2 Is Dispensable for Mouse Heart Development

Chromatin modifying enzymes play a critical role in cardiac differentiation. Previously, it has been shown that the targeted deletion of the histone methyltransferase, Smyd1, the founding member of the SET and MYND domain containing (Smyd) family, interferes with cardiomyocyte maturation and proper formation of the right heart ventricle. The highly related paralogue, Smyd2 is a histone 3 lysine 4- and lysine 36-specific methyltransferase expressed in heart and brain. Here, we report that Smyd2 is differentially expressed during cardiac development with highest expression in the neonatal heart. To elucidate the functional role of Smyd2 in the heart, we generated conditional knockout (cKO) mice harboring a cardiomyocyte-specific deletion of Smyd2 and performed histological, functional and molecular analyses. Unexpectedly, cardiac deletion of Smyd2 was dispensable for proper morphological and functional development of the murine heart and had no effect on global histone 3 lysine 4 or 36 methylation. However, we provide evidence for a potential role of Smyd2 in the transcriptional regulation of genes associated with translation and reveal that Smyd2, similar to Smyd3, interacts with RNA Polymerase II as well as to the RNA helicase, HELZ

State-Dependent Network Connectivity Determines Gating in a K+ Channel

YesX-ray crystallography has provided tremendous insight into the different structural states of membrane proteins and, in particular, of ion channels. However, the molecular forces that determine the thermodynamic stability of a particular state are poorly understood. Here we analyze the different X-ray structures of an inwardly rectifying potassium channel (Kir1.1) in relation to functional data we obtained for over 190 mutants in Kir1.1. This mutagenic perturbation analysis uncovered an extensive, state-dependent network of physically interacting residues that stabilizes the pre-open and open states of the channel, but fragments upon channel closure. We demonstrate that this gating network is an important structural determinant of the thermodynamic stability of these different gating states and determines the impact of individual mutations on channel function. These results have important implications for our understanding of not only K+ channel gating but also the more general nature of conformational transitions that occur in other allosteric proteins.Wellcome Trus

A Census of Sub-kiloparsec Resolution Metallicity Gradients in Star-forming Galaxies at Cosmic Noon from HST Slitless Spectroscopy

We present the hitherto largest sample of gas-phase metallicity radial gradients measured at sub-kpc resolution in star-forming galaxies in the redshift range of z ∈ [1.2, 2.3]. These measurements are enabled by the synergy of slitless spectroscopy from the Hubble Space Telescope near-infrared channels and the lensing magnification from foreground galaxy clusters. Our sample consists of 76 galaxies with stellar mass ranging from 10⁷ to 10¹⁰ M_⊙, an instantaneous star formation rate in the range of [1, 100] M_⊙ yr⁻¹, and global metallicity [1/12, 2] of solar. At a 2σ confidence level, 15/76 galaxies in our sample show negative radial gradients, whereas 7/76 show inverted gradients. Combining ours and all other metallicity gradients obtained at a similar resolution currently available in the literature, we measure a negative mass dependence of Δlog(O/H)/ Δr [dex kpc⁻¹] = (−0.020 ± 0.007) + (−0.016 ± 0.008) log(M_∗/10^(9.4) M_⊙), with the intrinsic scatter being σ = 0.060 ± 0.006 over 4 orders of magnitude in stellar mass. Our result is consistent with strong feedback, not secular processes, being the primary governor of the chemostructural evolution of star-forming galaxies during the disk mass assembly at cosmic noon. We also find that the intrinsic scatter of metallicity gradients increases with decreasing stellar mass and increasing specific star formation rate. This increase in the intrinsic scatter is likely caused by the combined effect of cold-mode gas accretion and merger-induced starbursts, with the latter more predominant in the dwarf mass regime of M∗ ≲ 10⁹ M_⊙

Structural and Thermodynamic Characterization of the Gating Pathway in a K+ Channel

YesConference abstrac