Tracing the Conversion of Gas into Stars in Young Massive Cluster Progenitors

Whilst young massive clusters (YMCs; $M$ $\gtrsim$ 10$^{4}$ M$_{\odot}$, age $\lesssim$ 100 Myr) have been identified in significant numbers, their progenitor gas clouds have eluded detection. Recently, four extreme molecular clouds residing within 200 pc of the Galactic centre have been identified as having the properties thought necessary to form YMCs. Here we utilise far-IR continuum data from the Herschel Infrared Galactic Plane Survey (HiGAL) and millimetre spectral line data from the Millimetre Astronomy Legacy Team 90 GHz Survey (MALT90) to determine their global physical and kinematic structure. We derive their masses, dust temperatures and radii and use virial analysis to conclude that they are all likely gravitationally bound -- confirming that they are likely YMC progenitors. We then compare the density profiles of these clouds to those of the gas and stellar components of the Sagittarius B2 Main and North proto-clusters and the stellar distribution of the Arches YMC. We find that even in these clouds -- the most massive and dense quiescent clouds in the Galaxy -- the gas is not compact enough to form an Arches-like ($M$ = 2x10$^{4}$ M$_{\odot}$, R$_{eff}$ = 0.4 pc) stellar distribution. Further dynamical processes would be required to condense the resultant population, indicating that the mass becomes more centrally concentrated as the (proto)-cluster evolves. These results suggest that YMC formation may proceed hierarchically rather than through monolithic collapse

High-mass star-forming cloud G0.38+0.04 in the Galactic Center Dust Ridge contains H2CO and SiO masers

We have discovered a new H$_2$CO (formaldehyde) $1_{1,0}-1_{1,1}$ 4.82966 GHz maser in Galactic Center Cloud C, G0.38+0.04. At the time of submission, this is the eighth region containing an H$_2$CO maser detected in the Galaxy. Cloud C is one of only two sites of confirmed high-mass star formation along the Galactic Center Ridge, affirming that H$_2$CO masers are exclusively associated with high-mass star formation. This discovery led us to search for other masers, among which we found new SiO vibrationally excited masers, making this the fourth star-forming region in the Galaxy to exhibit SiO maser emission. Cloud C is also a known source of CH$_3$OH Class-II and OH maser emission. There are now two known SiO and H$_2$CO maser containing regions in the CMZ, compared to two and six respectively in the Galactic disk, while there is a relative dearth of H$_2$O and CH$_3$OH Class-II masers in the CMZ. SiO and H$_2$CO masers may be preferentially excited in the CMZ, perhaps due to higher gas-phase abundances from grain destruction and heating, or alternatively H$_2$O and CH$_3$OH maser formation may be suppressed in the CMZ. In any case, Cloud C is a new testing ground for understanding maser excitation conditions

Generic hyperbolicity of Aubry sets on surfaces

International audienceGiven a Tonelli Hamiltonian of class C2 on the cotangent bundle of a compact surface, we show that there is an open dense set of potentials in the C2 topology for which the Aubry set is hyperbolic in its energy level

Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1β and Tumor Necrosis Factor α

Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBPβ and NF-κB. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. © 2013 Adamik et al

'The Brick' is not a brick: A comprehensive study of the structure and dynamics of the Central Molecular Zone cloud G0.253+0.016

In this paper we provide a comprehensive description of the internal dynamics of G0.253+0.016 (a.k.a. 'the Brick'); one of the most massive and dense molecular clouds in the Galaxy to lack signatures of widespread star formation. As a potential host to a future generation of high-mass stars, understanding largely quiescent molecular clouds like G0.253+0.016 is of critical importance. In this paper, we reanalyse Atacama Large Millimeter Array cycle 0 HNCO $J=4(0,4)-3(0,3)$ data at 3 mm, using two new pieces of software which we make available to the community. First, scousepy, a Python implementation of the spectral line fitting algorithm scouse. Secondly, acorns (Agglomerative Clustering for ORganising Nested Structures), a hierarchical n-dimensional clustering algorithm designed for use with discrete spectroscopic data. Together, these tools provide an unbiased measurement of the line of sight velocity dispersion in this cloud, $\sigma_{v_{los}, {\rm 1D}}=4.4\pm2.1$ kms$^{-1}$, which is somewhat larger than predicted by velocity dispersion-size relations for the Central Molecular Zone (CMZ). The dispersion of centroid velocities in the plane of the sky are comparable, yielding $\sigma_{v_{los}, {\rm 1D}}/\sigma_{v_{pos}, {\rm 1D}}\sim1.2\pm0.3$. This isotropy may indicate that the line-of-sight extent of the cloud is approximately equivalent to that in the plane of the sky. Combining our kinematic decomposition with radiative transfer modelling we conclude that G0.253+0.016 is not a single, coherent, and centrally-condensed molecular cloud; 'the Brick' is not a \emph{brick}. Instead, G0.253+0.016 is a dynamically complex and hierarchically-structured molecular cloud whose morphology is consistent with the influence of the orbital dynamics and shear in the CMZ

Organotypic Brain Cultures for Metastasis Research

We thank members of Brain Metastasis Group for critical discussion. Research in the Brain Metastasis Group is supported by MINECO-Retos SAF2017-89643-R (M.V.), Cancer Research Institute CLIP Award 2018 (M.V.), AECC (GCTRA16015SEOA) (M.V.), Bristol-Myers Squibb Melanoma Research Alliance Young Investigator Award 2017 (M.V.), Beug Foundation’s Prize for Metastasis Research 2017 (M.V.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972) (M.V.), Fundación Ramón Areces (CIVP19S8163), and La Caixa-Severo Ochoa International PhD Program Fellowship (L.Z.). M.V. is a Ramón y Cajal Investigator (RYC-2013-13365) and an EMBO YIP investigator.N

hnRNP A1 and hnRNP F Modulate the Alternative Splicing of Exon 11 of the Insulin Receptor Gene

Exon 11 of the insulin receptor gene (INSR) is alternatively spliced in a developmentally and tissue-specific manner. Linker scanning mutations in a 5′ GA-rich enhancer in intron 10 identified AGGGA sequences that are important for enhancer function. Using RNA-affinity purification and mass spectrometry, we identified hnRNP F and hnRNP A1 binding to these AGGGA sites and also to similar motifs at the 3′ end of the intron. The hnRNPs have opposite functional effects with hnRNP F promoting and hnRNP A1 inhibiting exon 11 inclusion, and deletion of the GA-rich elements eliminates both effects. We also observed specific binding of hnRNP A1 to the 5′ splice site of intron 11. The SR protein SRSF1 (SF2/ASF) co-purified on the GA-rich enhancer and, interestingly, also competes with hnRNP A1 for binding to the splice site. A point mutation -3U→C decreases hnRNP A1 binding, increases SRSF1 binding and renders the exon constitutive. Lastly, our data point to a functional interaction between hnRNP F and SRSF1 as a mutant that eliminates SRSF1 binding to exon 11, or a SRSF1 knockdown, which prevents the stimulatory effect of hnRNP F over expression

Transformation and tumorigenicity testing of simian cell lines and evaluation of poliovirus replication

The key role of cell cultures in different scientific fields is worldwide recognized, both as in vitro research models alternative to laboratory animals and substrates for biological production. However, many safety concerns rise from the use of animal/human cell lines that may be tumorigenic, leading to potential adverse contaminations in cell-derived biologicals. In order to evaluate the suitability of 13 different cell lines for Poliovirus vaccine production, safety and quality, in vitro/in vivo tumorigenicity and Poliovirus propagation properties were evaluated. Our results revealed that non-human primate cell lines CYNOM-K1, FRhK-4, 4MBr-5 and 4647 are free of tumorigenic features and represent highly susceptible substrates for attenuated Sabin Poliovirus strains. In particular, FRhK-4 and 4647 cell lines are characterized by a higher in vitro replication, resulting indicated for the use in large-scale production field

AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors

YesAlternative splicing of pre-mRNAs significantly contributes to the complexity of gene expression in higher organisms, but the regulation of the splice site selection remains incompletely understood. We have previously demonstrated that a chromatin-associated protein, AKAP95 (AKAP8), has a remarkable activity in enhancing chromatin transcription. In this study, we have shown that AKAP95 physically interacts with many factors involved in transcription and RNA processing, and functionally regulates pre-mRNA splicing. AKAP95 directly promotes splicing in vitro and the inclusion of a specific exon of an endogenous gene FAM126A. The N-terminal YG-rich domain of AKAP95 is important for its binding to RNA processing factors including selective groups of hnRNP proteins, and its zinc finger domains are critical for pre-mRNA binding. Genome-wide binding assays revealed that AKAP95 bound preferentially to proximal intronic regions on a large number of pre-mRNAs in human transcriptome, and AKAP95 depletion predominantly resulted in reduced inclusion of many exons. AKAP95 also selectively coordinates with hnRNP H/F and U proteins in regulating alternative splicing events. We have further shown that AKAP95 directly interacts with itself. Taken together, our results establish AKAP95 as a novel and mostly positive regulator of premRNA splicing and a possible integrator of transcription and splicing regulation, and support a model that AKAP95 facilitates the splice site communication by looping out introns through both RNA-binding and protein-protein interaction.This work was supported by a UAB start-up fund to H.J

Coupled variability in primary sensory areas and the hippocampus during spontaneous activity

The cerebral cortex is an anatomically divided and functionally specialized structure. It includes distinct areas, which work on different states over time. The structural features of spiking activity in sensory cortices have been characterized during spontaneous and evoked activity. However, the coordination among cortical and sub-cortical neurons during spontaneous activity across different states remains poorly characterized. We addressed this issue by studying the temporal coupling of spiking variability recorded from primary sensory cortices and hippocampus of anesthetized or freely behaving rats. During spontaneous activity, spiking variability was highly correlated across primary cortical sensory areas at both small and large spatial scales, whereas the cortico-hippocampal correlation was modest. This general pattern of spiking variability was observed under urethane anesthesia, as well as during waking, slow-wave sleep and rapid-eye-movement sleep, and was unchanged by novel stimulation. These results support the notion that primary sensory areas are strongly coupled during spontaneous activity.project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). NAPV was supported by Centro Universitario do Rio Grande do Norte, Champalimaud Foundation, and Brazilian National Council for Scientific and Technological Development (CNPq, Grant 249991/2013-6), CC-S (SFRH/BD/51992/2012). AJR (IF/00883/2013). SR by UFRN, CNPq (Research Productivity Grant 308775/2015-5), and S. Paulo Research Foundation FAPESP - Center for Neuromathematics (Grant 2013/07699-0)info:eu-repo/semantics/publishedVersio