On the fermionic T-duality of the AdS_4 \times CP^3 sigma-model

In this note we consider a fermionic T-duality of the coset realization of the type IIA sigma-model on AdS_4 \times CP^3 with respect to the three flat directions in AdS_4, six of the fermionic coordinates and three of the CP^3 directions. We show that the Buscher procedure fails as it leads to a singular transformation and discuss the result and its implications.Comment: LaTeX2e, 9 pages, no figures, JHEP style; v2: minor clarifications; v3: typos fixed, matches the published versio

Integrability of Type II Superstrings on Ramond-Ramond Backgrounds in Various Dimensions

We consider type II superstrings on AdS backgrounds with Ramond-Ramond flux in various dimensions. We realize the backgrounds as supercosets and analyze explicitly two classes of models: non-critical superstrings on AdS_{2d} and critical superstrings on AdS_p\times S^p\times CY. We work both in the Green--Schwarz and in the pure spinor formalisms. We construct a one-parameter family of flat currents (a Lax connection) leading to an infinite number of conserved non-local charges, which imply the classical integrability of both sigma-models. In the pure spinor formulation, we use the BRST symmetry to prove the quantum integrability of the sigma-model. We discuss how classical \kappa-symmetry implies one-loop conformal invariance. We consider the addition of space-filling D-branes to the pure spinor formalism.Comment: LaTeX2e, 56 pages, 1 figure, JHEP style; v2: references added, typos fixed in some equations; v3: typos fixed to match the published versio

Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells

available in PMC 2011 November 01.Cellular RNA levels are determined by the interplay of RNA production, processing and degradation. However, because most studies of RNA regulation do not distinguish the separate contributions of these processes, little is known about how they are temporally integrated. Here we combine metabolic labeling of RNA at high temporal resolution with advanced RNA quantification and computational modeling to estimate RNA transcription and degradation rates during the response of mouse dendritic cells to lipopolysaccharide. We find that changes in transcription rates determine the majority of temporal changes in RNA levels, but that changes in degradation rates are important for shaping sharp 'peaked' responses. We used sequencing of the newly transcribed RNA population to estimate temporally constant RNA processing and degradation rates genome wide. Degradation rates vary significantly between genes and contribute to the observed differences in the dynamic response. Certain transcripts, including those encoding cytokines and transcription factors, mature faster. Our study provides a quantitative approach to study the integrative process of RNA regulation.Human Frontier Science Program (Strasbourg, France)Howard Hughes Medical InstituteBurroughs Wellcome Fund (Career Award at the Scientific Interface

MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis

Aberrant expression of MYC transcription factor family members predicts poor clinical outcome in many human cancers. Oncogenic MYC profoundly alters metabolism and mediates an antioxidant response to maintain redox balance. Here we show that MYCN induces massive lipid peroxidation on depletion of cysteine, the rate-limiting amino acid for glutathione (GSH) biosynthesis, and sensitizes cells to ferroptosis, an oxidative, non-apoptotic and iron-dependent type of cell death. The high cysteine demand of MYCN-amplified childhood neuroblastoma is met by uptake and transsulfuration. When uptake is limited, cysteine usage for protein synthesis is maintained at the expense of GSH triggering ferroptosis and potentially contributing to spontaneous tumor regression in low-risk neuroblastomas. Pharmacological inhibition of both cystine uptake and transsulfuration combined with GPX4 inactivation resulted in tumor remission in an orthotopic MYCN-amplified neuroblastoma model. These findings provide a proof of concept of combining multiple ferroptosis targets as a promising therapeutic strategy for aggressive MYCN-amplified tumors

Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma

Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients

lincRNAs act in the circuitry controlling pluripotency and differentiation

Although thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells and characterized the effects on gene expression. Here we show that knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state.Broad InstituteHarvard UniversityNational Human Genome Research Institute (U.S.)Merkin Family Foundation for Stem Cell Researc

DestVI identifies continuums of cell types in spatial transcriptomics data

Most spatial transcriptomics technologies are limited by their resolution, with spot sizes larger than that of a single cell. Although joint analysis with single-cell RNA sequencing can alleviate this problem, current methods are limited to assessing discrete cell types, revealing the proportion of cell types inside each spot. To identify continuous variation of the transcriptome within cells of the same type, we developed Deconvolution of Spatial Transcriptomics profiles using Variational Inference (DestVI). Using simulations, we demonstrate that DestVI outperforms existing methods for estimating gene expression for every cell type inside every spot. Applied to a study of infected lymph nodes and of a mouse tumor model, DestVI provides high-resolution, accurate spatial characterization of the cellular organization of these tissues and identifies cell-type-specific changes in gene expression between different tissue regions or between conditions. DestVI is available as part of the open-source software package scvi-tools ( https://scvi-tools.org )

Couples of colloidal semiconductor nanorods formed by self-limited assembly

Colloidal nanocrystal synthesis provides a powerful approach for creating unique nanostructures of relevance for applications. Here, we report that wurtzite ZnSe nanorod couples connected by twinning structures can be synthesized by means of a self-limited assembly process. Unlike for individual nanorods, the band-edge states calculated for the nanorod couples are predominantly confined to the short edges of the structure and this leads to low photoluminescence polarization anisotropy, as confirmed by single-particle fluorescence. Through a cation-exchange approach, the composition of nanorod couples can be readily expanded to additional materials, such as CdSe and PbSe. We anticipate that this family of nanorod-couple structures with distinct compositions and controlled properties will constitute an ideal system for the investigation of electronic coupling effects between individual nanorod components on the nanoscale, with relevance to applications in optics, photocatalysis and optoelectronic devices