Organized Chaos: Scatter in the relation between stellar mass and halo mass in small galaxies

We use Local Group galaxy counts together with the ELVIS N-body simulations to explore the relationship between the scatter and slope in the stellar mass vs. halo mass relation at low masses, $M_\star \simeq 10^5 - 10^8 M_\odot$. Assuming models with log-normal scatter about a median relation of the form $M_\star \propto M_\mathrm{halo}^\alpha$, the preferred log-slope steepens from $\alpha \simeq 1.8$ in the limit of zero scatter to $\alpha \simeq 2.6$ in the case of $2$ dex of scatter in $M_\star$ at fixed halo mass. We provide fitting functions for the best-fit relations as a function of scatter, including cases where the relation becomes increasingly stochastic with decreasing mass. We show that if the scatter at fixed halo mass is large enough ($\gtrsim 1$ dex) and if the median relation is steep enough ($\alpha \gtrsim 2$), then the "too-big-to-fail" problem seen in the Local Group can be self-consistently eliminated in about $\sim 5-10\%$ of realizations. This scenario requires that the most massive subhalos host unobservable ultra-faint dwarfs fairly often; we discuss potentially observable signatures of these systems. Finally, we compare our derived constraints to recent high-resolution simulations of dwarf galaxy formation in the literature. Though simulation-to-simulation scatter in $M_\star$ at fixed $M_\mathrm{halo}$ is large among separate authors ($\sim 2$ dex), individual codes produce relations with much less scatter and usually give relations that would over-produce local galaxy counts.Comment: 15 pages, 6 figures, 1 table. Accepted for publication into MNRA

Organized Chaos: Scatter in the relation between stellar mass and halo mass in small galaxies

We use Local Group galaxy counts together with the ELVIS N-body simulations to explore the relationship between the scatter and slope in the stellar mass versus halo mass relation at low masses, M⋆ ≃ 10^5–10^8 M⊙. Assuming models with lognormal scatter about a median relation of the form M⋆ ∝ M^α_(halo), the preferred log-slope steepens from α ≃ 1.8 in the limit of zero scatter to α ≃ 2.6 in the case of 2 dex of scatter in M⋆ at fixed halo mass. We provide fitting functions for the best-fitting relations as a function of scatter, including cases where the relation becomes increasingly stochastic with decreasing mass. We show that if the scatter at fixed halo mass is large enough (≳ 1 dex) and if the median relation is steep enough (α ≳ 2), then the ‘too-big-to-fail’ problem seen in the Local Group can be self-consistently eliminated in about ∼5–10 per cent of realizations. This scenario requires that the most massive subhaloes host unobservable ultra-faint dwarfs fairly often; we discuss potentially observable signatures of these systems. Finally, we compare our derived constraints to recent high-resolution simulations of dwarf galaxy formation in the literature. Though simulation-to-simulation scatter in M⋆ at fixed M_(halo) is large among different authors (∼2 dex), individual codes produce relations with much less scatter and usually give relations that would overproduce local galaxy counts

Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1

Many eukaryotic genes are acutely regulated by extra-cellular signals. The c-fos serum response element (SRE) mediates transcriptional activation in response to mitogens through serum response factor (SRF)-dependent recruitment of Elk-1, a mitogen-activated protein kinase (MAPK)-responsive transcription factor. How subsequent events at SRE promoters stimulate initiation of transcription has yet to be fully resolved. Here we show that extra-cellular signal-regulated kinase (ERK) and mitogen and stress-activated kinase (MSK) are recruited to SRE promoter complexes in vitro and in vivo. Their recruitment in vitro correlates with Elk-1 binding and for ERK the D domain/KIM of Elk-1 is specifically involved. In vivo, recruitment of ERK and MSK is stimulated by mitogens, correlates with histone H3 phosphorylation and is impaired by Elk-1 knockdown. Immunocytochemistry and confocal microscopy reveal that ERK appears to associate to some extent with initiating rather than elongating RNA polymerase II. Taken together, our data add to the body of evidence implying that ERK and related MAPKs may fulfil a generic role at the promoters of acutely regulated genes

Structural and biochemical characterisation of the oxidoreductase NmDsbA3 from Neisseria meningitidis

DsbA is an enzyme found in the periplasm of Gram-negative bacteria that catalyses the formation of disulfide bonds in a diverse array of protein substrates, many of which are involved in bacterial pathogenesis. Whilst most bacteria possess only a single essential DsbA, Neisseria meningitidis is unusual in that it possesses three DsbAs, although the reason for this additional redundancy is unclear. Two of these N. meningitidis enzymes (NmDsbA1 and NmDsbA2) play an important role in meningococcal attachment to human epithelial cells, whilst NmDsbA3 is considered to have a narrow substrate repertoire. To begin to address the role of DsbAs in the pathogenesis of N. meningitidis, we have determined the structure of NmDsbA3 to 2.3 &Aring; resolution. Although the sequence identity between NmDsbA3 and other DsbAs is low, the NmDsbA3 structure adopted a DsbA-like fold. Consistent with this finding, we demonstrated that NmDsbA3 acts as a thiol-disulfide oxidoreductase in vitro and is reoxidised by Escherichia coli DsbB (EcDsbB). However, pronounced differences in the structures between DsbA3 and EcDsbA, which are clustered around the active site of the enzyme, suggested a structural basis for the unusual substrate specificity that is observed for NmDsbA3.<br /

Lymphocyte telomere length is long in BRCA1 and BRCA2 mutation carriers regardless of cancer-affected status

BACKGROUND: Telomere length has been linked to risk of common diseases, including cancer, and has previously been proposed as a biomarker for cancer risk. Germline BRCA1 and BRCA2 mutations predispose to breast, ovarian, and other cancer types. METHODS: We investigated telomere length in BRCA mutation carriers and their non-carrier relatives and further examined whether telomere length is a modifier of cancer risk in mutation carriers. We measured mean telomere length in DNA extracted from whole blood using high-throughput quantitative PCR. Participants were from the EMBRACE study in United Kingdom and Eire (n = 4,822) and comprised BRCA1 (n = 1,628) and BRCA2 (n = 1,506) mutation carriers and their non-carrier relatives (n = 1,688). RESULTS: We find no significant evidence that mean telomere length is associated with breast or ovarian cancer risk in BRCA mutation carriers. However, we find mutation carriers to have longer mean telomere length than their non-carrier relatives (all carriers vs. non-carriers, Ptrend = 0.0018), particularly in families with BRCA2 mutations (BRCA2 mutation carriers vs. all non-carriers, Ptrend = 0.0016). CONCLUSIONS: Our findings lend little support to the hypothesis that short mean telomere length predisposes to cancer. Conversely, our main and unexpected finding is that BRCA mutation carriers (regardless of cancer status) have longer telomeres than their non-mutation carrier, non-cancer-affected relatives. The longer telomere length in BRCA2 mutation carriers is consistent with its role in DNA damage response. Overall, it seems that increased telomere length may be a consequence of these mutations, but is not itself directly related to the increased cancer risk in carriers. IMPACT: The finding that mutation carriers have longer mean telomere lengths than their non-carrier relatives is unexpected but biologically plausible and could open up new lines of research into the functions of the BRCA proteins. To our knowledge, this is the largest study of telomere length in BRCA mutation carriers and their relatives. The null cancer-risk association supports recent large prospective studies of breast and ovarian cancer and indicates that mean telomere length would not be a useful biomarker in these cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1018-24. (c)2014 AACR.This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text