Environmental Quenching of Low-Mass Field Galaxies

In the local Universe, there is a strong division in the star-forming properties of low-mass galaxies, with star formation largely ubiquitous amongst the field population while satellite systems are predominantly quenched. This dichotomy implies that environmental processes play the dominant role in suppressing star formation within this low-mass regime (${M}_{\star} \sim 10^{5.5-8}~{\rm M}_{\odot}$). As shown by observations of the Local Volume, however, there is a non-negligible population of passive systems in the field, which challenges our understanding of quenching at low masses. By applying the satellite quenching models of Fillingham et al. (2015) to subhalo populations in the Exploring the Local Volume In Simulations (ELVIS) suite, we investigate the role of environmental processes in quenching star formation within the nearby field. Using model parameters that reproduce the satellite quenched fraction in the Local Group, we predict a quenched fraction -- due solely to environmental effects -- of $\sim 0.52 \pm 0.26$ within $1< R/R_{\rm vir} < 2$ of the Milky Way and M31. This is in good agreement with current observations of the Local Volume and suggests that the majority of the passive field systems observed at these distances are quenched via environmental mechanisms. Beyond $2~R_{\rm vir}$, however, dwarf galaxy quenching becomes difficult to explain through an interaction with either the Milky Way or M31, such that more isolated, field dwarfs may be self-quenched as a result of star-formation feedback.Comment: 9 pages, 4 figures, MNRAS accepted version, comments welcome - RIP Ducky...gone but never forgotte

Taking Care of Business in a Flash: Constraining the Timescale for Low-Mass Satellite Quenching with ELVIS

The vast majority of dwarf satellites orbiting the Milky Way and M31 are quenched, while comparable galaxies in the field are gas-rich and star-forming. Assuming that this dichotomy is driven by environmental quenching, we use the ELVIS suite of N-body simulations to constrain the characteristic timescale upon which satellites must quench following infall into the virial volumes of their hosts. The high satellite quenched fraction observed in the Local Group demands an extremely short quenching timescale (~ 2 Gyr) for dwarf satellites in the mass range Mstar ~ 10^6-10^8 Msun. This quenching timescale is significantly shorter than that required to explain the quenched fraction of more massive satellites (~ 8 Gyr), both in the Local Group and in more massive host halos, suggesting a dramatic change in the dominant satellite quenching mechanism at Mstar < 10^8 Msun. Combining our work with the results of complementary analyses in the literature, we conclude that the suppression of star formation in massive satellites (Mstar ~ 10^8 - 10^11 Msun) is broadly consistent with being driven by starvation, such that the satellite quenching timescale corresponds to the cold gas depletion time. Below a critical stellar mass scale of ~ 10^8 Msun, however, the required quenching times are much shorter than the expected cold gas depletion times. Instead, quenching must act on a timescale comparable to the dynamical time of the host halo. We posit that ram-pressure stripping can naturally explain this behavior, with the critical mass (of Mstar ~ 10^8 Msun) corresponding to halos with gravitational restoring forces that are too weak to overcome the drag force encountered when moving through an extended, hot circumgalactic medium.Comment: 12 pages, 6 figures; resubmitted to MNRAS after referee report (August 25, 2015

6-OHDA generated ROS induces DNA damage and p53- and PUMA-dependent cell death

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN), resulting in tremor, rigidity, and bradykinesia. Although the etiology is unknown, insight into the disease process comes from the dopamine (DA) derivative, 6-hydroxydopamine (6-OHDA), which produces PD-like symptoms. Studies show that 6-OHDA activates stress pathways, such as the unfolded protein response (UPR), triggers mitochondrial release of cytochrome-c, and activates caspases, such as caspase-3. Because the BH3-only protein, Puma (p53-upregulated mediator of apoptosis), is activated in response to UPR, it is thought to be a link between cell stress and apoptosis.</p> <p>Results</p> <p>To test the hypothesis that Puma serves such a role in 6-OHDA-mediated cell death, we compared the response of dopaminergic neurons from wild-type and <it>Puma</it>-null mice to 6-OHDA. Results indicate that Puma is required for 6-OHDA-induced cell death, in primary dissociated midbrain cultures as well as <it>in vivo</it>. In these cultures, 6-OHDA-induced DNA damage and p53 were required for 6-OHDA-induced cell death. In contrast, while 6-OHDA led to upregulation of UPR markers, loss of ATF3 did not protect against 6-OHDA.</p> <p>Conclusions</p> <p>Together, our results indicate that 6-OHDA-induced upregulation of <it>Puma </it>and cell death are independent of UPR. Instead, p53 and DNA damage repair pathways mediate 6-OHDA-induced toxicity.</p

Under Pressure: Quenching Star Formation in Low-Mass Satellite Galaxies via Stripping

Recent studies of galaxies in the local Universe, including those in the Local Group, find that the efficiency of environmental (or satellite) quenching increases dramatically at satellite stellar masses below ~ $10^8\ {\rm M}_{\odot}$. This suggests a physical scale where quenching transitions from a slow "starvation" mode to a rapid "stripping" mode at low masses. We investigate the plausibility of this scenario using observed HI surface density profiles for a sample of 66 nearby galaxies as inputs to analytic calculations of ram-pressure and viscous stripping. Across a broad range of host properties, we find that stripping becomes increasingly effective at $M_{*} < 10^{8-9}\ {\rm M}_{\odot}$, reproducing the critical mass scale observed. However, for canonical values of the circumgalactic medium density ($n_{\rm halo} < 10^{-3.5}$${\rm cm}^{-3}$), we find that stripping is not fully effective; infalling satellites are, on average, stripped of < 40 - 70% of their cold gas reservoir, which is insufficient to match observations. By including a host halo gas distribution that is clumpy and therefore contains regions of higher density, we are able to reproduce the observed HI gas fractions (and thus the high quenched fraction and short quenching timescale) of Local Group satellites, suggesting that a host halo with clumpy gas may be crucial for quenching low-mass systems in Local Group-like (and more massive) host halos.Comment: updated version after review, now accepted to MNRAS; Accepted 2016 August 22. Received 2016 August 18; in original form 2016 June 2

JNK1-dependent PUMA expression contributes to hepatocyte lipoapoptosis.

Free fatty acids (FFA) induce hepatocyte lipoapoptosis by a c-Jun N-terminal kinase (JNK)-dependent mechanism. However, the cellular processes by which JNK engages the core apoptotic machinery during lipotoxicity, especially activation of BH3-only proteins, remain incompletely understood. Thus, our aim was to determine whether JNK mediates induction of BH3-only proteins during hepatocyte lipoapoptosis. The saturated FFA palmitate, but not the monounsaturated FFA oleate, induces an increase in PUMA mRNA and protein levels. Palmitate induction of PUMA was JNK1-dependent in primary murine hepatocytes. Palmitate-mediated PUMA expression was inhibited by a dominant negative c-Jun, and direct binding of a phosphorylated c-Jun containing the activator protein 1 complex to the PUMA promoter was identified by electrophoretic mobility shift assay and a chromatin immunoprecipitation assay. Short hairpin RNA-targeted knockdown of PUMA attenuated Bax activation, caspase 3/7 activity, and cell death. Similarly, the genetic deficiency of Puma rendered murine hepatocytes resistant to lipoapoptosis. PUMA expression was also increased in liver biopsy specimens from patients with non-alcoholic steatohepatitis as compared with patients with simple steatosis or controls. Collectively, the data implicate JNK1-dependent PUMA expression as a mechanism contributing to hepatocyte lipoapoptosis

Environmental quenching of low-mass field galaxies

In the local Universe, there is a strong division in the star-forming properties of low-mass galaxies, with star formation largely ubiquitous amongst the field population while satellite systems are predominantly quenched. This dichotomy implies that environmental processes play the dominant role in suppressing star formation within this low-mass regime (M_* ∼ 10^(5.5–8) M_⊙). As shown by observations of the Local Volume, however, there is a non-negligible population of passive systems in the field, which challenges our understanding of quenching at low masses. By applying the satellite quenching models of Fillingham et al. (2015) to subhalo populations in the Exploring the Local Volume In Simulations suite, we investigate the role of environmental processes in quenching star formation within the nearby field. Using model parameters that reproduce the satellite quenched fraction in the Local Group, we predict a quenched fraction – due solely to environmental effects – of ∼0.52 ± 0.26 within 1 < R/R_(vir) < 2 of the Milky Way and M31. This is in good agreement with current observations of the Local Volume and suggests that the majority of the passive field systems observed at these distances are quenched via environmental mechanisms. Beyond 2R_(vir), however, dwarf galaxy quenching becomes difficult to explain through an interaction with either the Milky Way or M31, such that more isolated, field dwarfs may be self-quenched as a result of star-formation feedback

Examining the BMI-mortality relationship using fractional polynomials

<p>Abstract</p> <p>Background</p> <p>Many previous studies estimating the relationship between body mass index (BMI) and mortality impose assumptions regarding the functional form for BMI and result in conflicting findings. This study investigated a flexible data driven modelling approach to determine the nonlinear and asymmetric functional form for BMI used to examine the relationship between mortality and obesity. This approach was then compared against other commonly used regression models.</p> <p>Methods</p> <p>This study used data from the National Health Interview Survey, between 1997 and 2000. Respondents were linked to the National Death Index with mortality follow-up through 2005. We estimated 5-year all-cause mortality for adults over age 18 using the logistic regression model adjusting for BMI, age and smoking status. All analyses were stratified by sex. The multivariable fractional polynomials (MFP) procedure was employed to determine the best fitting functional form for BMI and evaluated against the model that includes linear and quadratic terms for BMI and the model that groups BMI into standard weight status categories using a deviance difference test. Estimated BMI-mortality curves across models were then compared graphically.</p> <p>Results</p> <p>The best fitting adjustment model contained the powers -1 and -2 for BMI. The relationship between 5-year mortality and BMI when estimated using the MFP approach exhibited a J-shaped pattern for women and a U-shaped pattern for men. A deviance difference test showed a statistically significant improvement in model fit compared to other BMI functions. We found important differences between the MFP model and other commonly used models with regard to the shape and nadir of the BMI-mortality curve and mortality estimates.</p> <p>Conclusions</p> <p>The MFP approach provides a robust alternative to categorization or conventional linear-quadratic models for BMI, which limit the number of curve shapes. The approach is potentially useful in estimating the relationship between the full spectrum of BMI values and other health outcomes, or costs.</p

Influence of HAART on Alternative Reading Frame Immune Responses over the Course of HIV-1 Infection

Background: Translational errors can result in bypassing of the main viral protein reading frames and the production of alternate reading frame (ARF) or cryptic peptides. Within HIV, there are many such ARFs in both sense and the antisense directions of transcription. These ARFs have the potential to generate immunogenic peptides called cryptic epitopes (CE). Both antiretroviral drug therapy and the immune system exert a mutational pressure on HIV-1. Immune pressure exerted by ARF CD8(+) T cells on the virus has already been observed in vitro. HAART has also been described to select HIV-1 variants for drug escape mutations. Since the mutational pressure exerted on one location of the HIV-1 genome can potentially affect the 3 reading frames, we hypothesized that ARF responses would be affected by this drug pressure in vivo. Methodology/Principal findings: In this study we identified new ARFs derived from sense and antisense transcription of HIV-1. Many of these ARFs are detectable in circulating viral proteins. They are predominantly found in the HIV-1 env nucleotide region. We measured T cell responses to 199 HIV-1 CE encoded within 13 sense and 34 antisense HIV-1 ARFs. We were able to observe that these ARF responses are more frequent and of greater magnitude in chronically infected individuals compared to acutely infected patients, and in patients on HAART, the breadth of ARF responses increased. Conclusions/Significance: These results have implications for vaccine design and unveil the existence of potential new epitopes that could be included as vaccine targets.International AIDS Vaccine Initiative (IAVI