4MOST Consortium Survey 3: Milky Way Disc and Bulge Low-Resolution Survey (4MIDABLE-LR)

The mechanisms of the formation and evolution of the Milky Way are encoded in the orbits, chemistry and ages of its stars. With the 4MOST MIlky way Disk And BuLgE Low-Resolution Survey (4MIDABLE-LR) we aim to study kinematic and chemical substructures in the Milky Way disc and bulge region with samples of unprecedented size out to larger distances and greater precision than conceivable with Gaia alone or any other ongoing or planned survey. Gaia gives us the unique opportunity for target selection based almost entirely on parallax and magnitude range, hence increasing the efficiency in sampling larger Milky Way volumes with well-defined and effective selection functions. Our main goal is to provide a detailed chrono-chemo-kinematical extended map of our Galaxy and the largest Gaia follow-up down to $G = 19$ magnitudes (Vega). The complex nature of the disc components (for example, large target densities and highly structured extinction distribution in the Milky Way bulge and disc area), prompted us to develop a survey strategy with five main sub-surveys that are tailored to answer the still open questions about the assembly and evolution of our Galaxy, while taking full advantage of the Gaia data.Comment: Part of the 4MOST issue of The Messenger, published in preparation of 4MOST Community Workshop, see http://www.eso.org/sci/meetings/2019/4MOST.htm

Pseudogap phase formation in the crossover from Bose-Einstein condensation to BCS superconductivity

A phase diagram for a 2D metal with variable carrier density has been derived. It consists of a normal phase, where the order parameter is absent; a so-called ``abnormal normal'' phase where this parameter is also absent but the mean number of composite bosons (bound pairs) exceeds the mean number of free fermions; a pseudogap phase where the absolute value of the order parameter gradually increases but its phase is a random value, and finally a superconducting (here Berezinskii-Kosterlitz-Thouless) phase. The characteristic transition temperatures between these phases are found. The chemical potential and paramagnetic susceptibility behavior as functions of the fermion density and the temperature are also studied. An attempt is made to qualitatively compare the resulting phase diagram with the features of underdoped high-$T_{c}$ superconducting compounds above their critical temperature.Comment: 26 pages, revtex, 5 EMTeX figures; more discussion and references added; to be published in JET

RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2

Genomic instability is a key hallmark of cancer leading to tumour heterogeneity and therapeutic resistance. ​BRCA2 has a fundamental role in error-free DNA repair but also sustains genome integrity by promoting ​RAD51 nucleofilament formation at stalled replication forks. ​CDK2 phosphorylates ​BRCA2 (pS3291-​BRCA2) to limit stabilizing contacts with polymerized ​RAD51; however, how replication stress modulates ​CDK2 activity and whether loss of pS3291-​BRCA2 regulation results in genomic instability of tumours are not known. Here we demonstrate that the Hippo pathway kinase ​LATS1 interacts with ​CDK2 in response to genotoxic stress to constrain pS3291-​BRCA2 and support ​RAD51 nucleofilaments, thereby maintaining genomic fidelity during replication stalling. We also show that ​LATS1 forms part of an ​ATR-mediated response to replication stress that requires the tumour suppressor ​RASSF1A. Importantly, perturbation of the ​ATR–​RASSF1A–​LATS1 signalling axis leads to genomic defects associated with loss of ​BRCA2 function and contributes to genomic instability and ‘BRCA-ness’ in lung cancers

Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery

An essential feature of meiosis is Spo11 catalysis of programmed DNA double strand breaks (DSBs). Evidence suggests that the number of DSBs generated per meiosis is genetically determined and that this ability to maintain a pre-determined DSB level, or "DSB homeostasis", might be a property of the meiotic program. Here, we present direct evidence that Rec114, an evolutionarily conserved essential component of the meiotic DSB-machinery, interacts with DSB hotspot DNA, and that Tel1 and Mec1, the budding yeast ATM and ATR, respectively, down-regulate Rec114 upon meiotic DSB formation through phosphorylation. Mimicking constitutive phosphorylation reduces the interaction between Rec114 and DSB hotspot DNA, resulting in a reduction and/or delay in DSB formation. Conversely, a non-phosphorylatable rec114 allele confers a genome-wide increase in both DSB levels and in the interaction between Rec114 and the DSB hotspot DNA. These observations strongly suggest that Tel1 and/or Mec1 phosphorylation of Rec114 following Spo11 catalysis down-regulates DSB formation by limiting the interaction between Rec114 and DSB hotspots. We also present evidence that Ndt80, a meiosis specific transcription factor, contributes to Rec114 degradation, consistent with its requirement for complete cessation of DSB formation. Loss of Rec114 foci from chromatin is associated with homolog synapsis but independent of Ndt80 or Tel1/Mec1 phosphorylation. Taken together, we present evidence for three independent ways of regulating Rec114 activity, which likely contribute to meiotic DSBs-homeostasis in maintaining genetically determined levels of breaks

Nonperturbative XY-model approach to strong coupling superconductivity in two and three dimensions

For an electron gas with delta-function attraction we investigate the crossover from weak- to strong-coupling supercoductivity in two and three dimensions. We derive analytic expressions for the stiffness of phase fluctuations and set up effective XY-models which serve to determine nonperturbatively the temperature of phase decoherence where superconductivity breaks down. We find the transition temperature T_c as a monotonous function of the coupling strength and carrier density both in two and three dimensions, and give analytic formulas for the merging of the temperature of phase decoherence with the temperature of pair formation in the weak-coupling limit.Comment: Few typos corrected. Emails that were sent to the address [email protected] in June and July 1999 were lost in a computer crash, so if your comments were not answered please send them once mor

4MOST Consortium Survey 4: Milky Way Disc and Bulge High-Resolution Survey (4MIDABLE-HR)

The signatures of the formation and evolution of a galaxy are imprinted in its stars. Their velocities, ages, and chemical compositions present major constraints on models of galaxy formation, and on various processes such as the gas inflows and outflows, the accretion of cold gas, radial migration, and the variability of star formation activity. Understanding the evolution of the Milky Way requires large observational datasets of stars via which these quantities can be determined accurately. This is the science driver of the 4MOST MIlky way Disc And BuLgE High-Resolution (4MIDABLE-HR) survey: to obtain high-resolution spectra at $R \sim 20\,000$ and to provide detailed elemental abundances for large samples of stars in the Galactic disc and bulge. High data quality will allow us to provide accurate spectroscopic diagnostics of two million stellar spectra: precise radial velocities; rotation; abundances of many elements, including those that are currently only accessible in the optical, such as Li, s-, and r-process; and multi-epoch spectra for a sub-sample of stars. Synergies with complementary missions like Gaia and TESS will provide masses, stellar ages and multiplicity, forming a multi-dimensional dataset that will allow us to explore and constrain the origin and structure of the Milky Way.Comment: Part of the 4MOST issue of The Messenger, published in preparation of 4MOST Community Workshop, see http://www.eso.org/sci/meetings/2019/4MOST.htm

cGAL, a temperature-robust GAL4–UAS system for Caenorhabditis elegans

The GAL4–UAS system is a powerful tool for manipulating gene expression, but its application in Caenorhabditis elegans has not been described. Here we systematically optimize the system's three main components to develop a temperature-optimized GAL4–UAS system (cGAL) that robustly controls gene expression in C. elegans from 15 to 25 °C. We demonstrate this system's utility in transcriptional reporter analysis, site-of-action experiments and exogenous transgene expression; and we provide a basic driver and effector toolkit

Seroepidemiology of Bovine Viral Diarrhoea Virus (BVDV) in the Adamawa Region of Cameroon and Use of the SPOT Test to Identify Herds with PI Calves

Bovine viral diarrhoea, caused by the bovine viral diarrhoea virus (BVDV) in the Pestivirus genus of the Flaviviridae, is one of the most important diseases of cattle world wide causing poor reproductive performance in adult cattle and mucosal disease in calves. In addition it causes immunosuppression and increased susceptibility to other infections, the impact of which is uncertain, particularly in sub-Saharan Africa where animals are exposed to a much wider range and higher intensity of infections compared to Europe. There are no previous estimates of the seroprevalence of BVDV in cattle in Cameroon. This paper describes the serological screening for antibodies to BVDV and antigen of BVDV in a cattle population in the Adamawa Region of Cameroon in 2000. The estimates of herd-level and within herd seroprevalences adjusted for test imperfections were 92% and 30% respectively and 16.5% of herds were classed as having a persistently infected calf (PI) in the herd within the last year based on the “spot” test approach. There was evidence of clustering of herds with PI calves across the north and west of the Region which corresponds with the higher cattle density areas and of self-clearance of infection from herds. A multivariable model was developed for the risk of having a PI calf in the herd; proximity to antelope, owning a goat, mixing with 10 other herds at grazing and the catchment area of the veterinary centre the herd was registered at were all significant risk factors. Very little is known about BVDV in sub-Saharan Africa and these high seroprevalences suggest that there is a large problem which may be having both direct impacts on fertility and neonate mortality and morbidity and also indirect effects through immunosuppression and susceptibility to other infections. Understanding and accounting for BVDV should be an important component of epidemiological studies of other diseases in sub-Saharan Africa

A tryptophan-rich peptide acts as a transcription activation domain

<p>Abstract</p> <p>Background</p> <p>Eukaryotic transcription activators normally consist of a sequence-specific DNA-binding domain (DBD) and a transcription activation domain (AD). While many sequence patterns and motifs have been defined for DBDs, ADs do not share easily recognizable motifs or structures.</p> <p>Results</p> <p>We report herein that the N-terminal domain of yeast valyl-tRNA synthetase can function as an AD when fused to a DNA-binding protein, LexA, and turn on reporter genes with distinct LexA-responsive promoters. The transcriptional activity was mainly attributed to a five-residue peptide, WYDWW, near the C-terminus of the N domain. Remarkably, the pentapeptide <it>per se </it>retained much of the transcriptional activity. Mutations which substituted tryptophan residues for both of the non-tryptophan residues in the pentapeptide (resulting in W₅) significantly enhanced its activity (~1.8-fold), while mutations which substituted aromatic residues with alanine residues severely impaired its activity. Accordingly, a much more active peptide, pentatryptophan (W₇), was produced, which elicited ~3-fold higher activity than that of the native pentapeptide and the N domain. Further study indicated that W₇mediates transcription activation through interacting with the general transcription factor, TFIIB.</p> <p>Conclusions</p> <p>Since W₇shares no sequence homology or features with any known transcription activators, it may represent a novel class of AD.</p

The CCR4-NOT Complex Physically and Functionally Interacts with TRAMP and the Nuclear Exosome

BACKGROUND: Ccr4-Not is a highly conserved multi-protein complex consisting in yeast of 9 subunits, including Not5 and the major yeast deadenylase Ccr4. It has been connected functionally in the nucleus to transcription by RNA polymerase II and in the cytoplasm to mRNA degradation. However, there has been no evidence so far that this complex is important for RNA degradation in the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: In this work we point to a new role for the Ccr4-Not complex in nuclear RNA metabolism. We determine the importance of the Ccr4-Not complex for the levels of non-coding nuclear RNAs, such as mis-processed and polyadenylated snoRNAs, whose turnover depends upon the nuclear exosome and TRAMP. Consistently, mutation of both the Ccr4-Not complex and the nuclear exosome results in synthetic slow growth phenotypes. We demonstrate physical interactions between the Ccr4-Not complex and the exosome. First, Not5 co-purifies with the exosome. Second, several exosome subunits co-purify with the Ccr4-Not complex. Third, the Ccr4-Not complex is important for the integrity of large exosome-containing complexes. Finally, we reveal a connection between the Ccr4-Not complex and TRAMP through the association of the Mtr4 helicase with the Ccr4-Not complex and the importance of specific subunits of Ccr4-Not for the association of Mtr4 with the nuclear exosome subunit Rrp6. CONCLUSIONS/SIGNIFICANCE: We propose a model in which the Ccr4-Not complex may provide a platform contributing to dynamic interactions between the nuclear exosome and its co-factor TRAMP. Our findings connect for the first time the different players involved in nuclear and cytoplasmic RNA degradation