Oxygen depletion of Mycobacterium tuberculosis engages the DosR regulon that coordinates an overall down-regulation of metabolism while up-regulating specific genes involved in respiration and ...central metabolism. We have developed a chemostat model of M. tuberculosis where growth rate was a function of dissolved oxygen concentration to analyze metabolic adaptation to hypoxia. A drop in dissolved oxygen concentration from 50 mmHg to 0.42 mmHg led to a 2.3 fold decrease in intracellular ATP levels with an almost 70-fold increase in the ratio of NADH/NAD(+). This suggests that re-oxidation of this co-factor becomes limiting in the absence of a terminal electron acceptor. Upon oxygen limitation genes involved in the reverse TCA cycle were upregulated and this upregulation was associated with a significant accumulation of succinate in the extracellular milieu. We confirmed that this succinate was produced by a reversal of the TCA cycle towards the non-oxidative direction with net CO(2) incorporation by analysis of the isotopomers of secreted succinate after feeding stable isotope ((13)C) labeled precursors. This showed that the resulting succinate retained both carbons lost during oxidative operation of the TCA cycle. Metabolomic analyses of all glycolytic and TCA cycle intermediates from (13)C-glucose fed cells under aerobic and anaerobic conditions showed a clear reversal of isotope labeling patterns accompanying the switch from normoxic to anoxic conditions. M. tuberculosis encodes three potential succinate-producing enzymes including a canonical fumarate reductase which was highly upregulated under hypoxia. Knockout of frd, however, failed to reduce succinate accumulation and gene expression studies revealed a compensatory upregulation of two homologous enzymes. These major realignments of central metabolism are consistent with a model of oxygen-induced stasis in which an energized membrane is maintained by coupling the reductive branch of the TCA cycle to succinate secretion. This fermentative process may offer unique targets for the treatment of latent tuberculosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Targeting Mycobacterium tuberculosis bacilli in low-oxygen microenvironments, such as caseous granulomas, has been hypothesized to have the potential to shorten therapy for active tuberculosis (TB) ...and prevent reactivation of latent infection. We previously reported that upon low-dose M. tuberculosis infection, equal proportions of cynomolgus macaques develop active disease or latent infection and that latently infected animals reactivated upon neutralization of TNF. Using this model we now show that chemoprophylaxis of latently infected cynomolgus macaques with 6 mo of isoniazid (INH) effectively prevented anti-TNF antibody-induced reactivation. Similarly, 2-mo treatment of latent animals with a combination of INH and rifampicin (RIF) was highly effective at preventing reactivation disease in this model. Metronidazole (MTZ), which has activity only against anaerobic, nonreplicating bacteria, was as effective as either of these treatments in preventing reactivation of latent infection. Because hypoxic lesions also occur during active TB, we further showed that addition of MTZ to INH/RIF effectively treated animals with active TB within 2 mo. Healing lesions were associated with distinct changes in cellular pathology, with a shift toward increasingly fibrotic and calcified lesions. Our data in the nonhuman primate model of active and latent TB supports targeting bacteria in hypoxic environments for preventing reactivation of latent infection and possibly shortening the duration of therapy in active TB.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The quality of data in charge detection mass spectrometry depends on accurate determination of ion charge. While the method of selective temporal overview of resonant ions (STORI) has proven to be ...highly enabling for determining the charge of ions that survive for variable amounts of time, it assumes that the ion frequency exactly matches the frequency being used in the calculation. Any mismatches result in low charge estimates. To address this, the misSTORI method was developed to correct these discrepancies. This can significantly reduce the charge measurement errors for samples with unstable masses. As an example, the misSTORI approach can eliminate a 5.7% charge determination error for a VP3-only AAV capsid that shifts 25 ppm in mass.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
We demonstrate the feasibility and potential of using large integral field spectroscopic surveys to investigate the prevalence of galactic-scale outflows in the local Universe. Using integral field ...data from the Sydney-AAO Multi-object Integral field spectrograph (SAMI) and the Wide Field Spectrograph, we study the nature of an isolated disc galaxy, SDSS J090005.05+000446.7 (z = 0.053 86). In the integral field data sets, the galaxy presents skewed line profiles changing with position in the galaxy. The skewed line profiles are caused by different kinematic components overlapping in the line-of-sight direction. We perform spectral decomposition to separate the line profiles in each spatial pixel as combinations of (1) a narrow kinematic component consistent with H ii regions, (2) a broad kinematic component consistent with shock excitation, and (3) an intermediate component consistent with shock excitation and photoionization mixing. The three kinematic components have distinctly different velocity fields, velocity dispersions, line ratios, and electron densities. We model the line ratios, velocity dispersions, and electron densities with our mappings iv shock and photoionization models, and we reach remarkable agreement between the data and the models. The models demonstrate that the different emission line properties are caused by major galactic outflows that introduce shock excitation in addition to photoionization by star-forming activities. Interstellar shocks embedded in the outflows shock-excite and compress the gas, causing the elevated line ratios, velocity dispersions, and electron densities observed in the broad kinematic component. We argue from energy considerations that, with the lack of a powerful active galactic nucleus, the outflows are likely to be driven by starburst activities. Our results set a benchmark of the type of analysis that can be achieved by the SAMI Galaxy Survey on large numbers of galaxies.
We examine the kinematic morphology of early-type galaxies (ETGs) in eight galaxy clusters in the Sydney-AAO Multi-object Integral-field spectrograph Galaxy Survey. The clusters cover a mass range of ...and we measure spatially resolved stellar kinematics for 315 member galaxies with stellar masses within 1 R200 of the cluster centers. We calculate the spin parameter, λR, and use this to classify the kinematic morphology of the galaxies as fast or slow rotators (SRs). The total fraction of SRs in the ETG population is FSR = 0.14 0.02 and does not depend on host cluster mass. Across the eight clusters, the fraction of SRs increases with increasing local overdensity. We also find that the slow-rotator fraction increases at small clustercentric radii (Rcl < 0.3 R200), and note that there is also an increase in the slow-rotator fraction at Rcl ∼ 0.6 R200. The SRs at these larger radii reside in the cluster substructure. We find that the strongest increase in the slow-rotator fraction occurs with increasing stellar mass. After accounting for the strong correlation with stellar mass, we find no significant relationship between spin parameter and local overdensity in the cluster environment. We conclude that the primary driver for the kinematic morphology-density relationship in galaxy clusters is the changing distribution of galaxy stellar mass with the local environment. The presence of SRs in the substructure suggests that the cluster kinematic morphology-density relationship is a result of mass segregation of slow-rotating galaxies forming in groups that later merge with clusters and sink to the cluster center via dynamical friction.
Abstract
The fraction of galaxies supported by internal rotation compared to galaxies stabilized by internal pressure provides a strong constraint on galaxy formation models. In integral field ...spectroscopy surveys, this fraction is biased because survey instruments typically only trace the inner parts of the most massive galaxies. We present aperture corrections for the two most widely used stellar kinematic quantities V/σ and λR (spin parameter proxy). Our demonstration involves integral field data from the SAMI (Sydney-AAO Multi-object Integral-field spectrograph) Galaxy Survey and the ATLAS3D survey. We find a tight relation for both V/σ and λR when measured in different apertures that can be used as a linear transformation as a function of radius, i.e. a first-order aperture correction. In degraded seeing, however, the aperture corrections are more significant as the steeper inner profile is more strongly affected by the point spread function than the outskirts. We find that V/σ and λR radial growth curves are well approximated by second-order polynomials. By only fitting the inner profile (0.5Re), we successfully recover the profile out to one Re if a constraint between the linear and quadratic parameter in the fit is applied. However, the aperture corrections for V/σ and λR derived by extrapolating the profiles perform as well as applying a first-order correction. With our aperture-corrected λR measurements, we find that the fraction of slow rotating galaxies increases with stellar mass. For galaxies with log M*/M⊙ > 11, the fraction of slow rotators is 35.9 ± 4.3 per cent, but is underestimated if galaxies without coverage beyond one Re are not included in the sample (24.2 ± 5.3 per cent). With measurements out to the largest aperture radius, the slow rotator fraction is similar as compared to using aperture-corrected values (38.3 ± 4.4 per cent). Thus, aperture effects can significantly bias stellar kinematic integral field spectrograph studies, but this bias can now be removed with the method outlined here.
The main objective of this study was to compare trends in final course grades earned by undergraduate students with disabilities (DSS) with those earned by students without disabilities (non‐DSS) ...across various large enrollment, introductory science, technology, engineering, and mathematics (STEM) courses, and non‐STEM courses. It was hypothesized that a larger proportion of DSS students in both STEM and non‐STEM courses would earn lower grades compared to non‐DSS students. Furthermore, it was hypothesized that grades earned by DSS students between STEM and non‐STEM courses would be similar. Finally, it was hypothesized that a higher proportion of DSS students in anatomy would earn lower grades compared to non‐DSS students, and that the proportion of grades earned by DSS students in anatomy would be similar to DSS students in other STEM courses broadly.
Quantitative analysis involved using learning analytics to examine trends in final course grades earned. Retrospective de‐identified data was obtained for undergraduate students enrolled at Indiana University – Bloomington between Fall 2014‐Spring 2020 who either had or had not identified to the university as having a disability. Final course grades were compared across twelve large, introductory STEM courses, and six large, introductory non‐STEM courses.
The following results were observed:
1) DSS students in both STEM and non‐STEM courses were less likely to earn an A compared to non‐DSS students. The proportion of DSS students earning other grades in STEM and non‐STEM courses were similar to non‐DSS students. However, DSS students in both types of courses were twice as likely to withdraw from a course.
2) The proportion of DSS students enrolled in STEM courses who earned an A was less than half of that seen for DSS students enrolled in non‐STEM courses. DSS students enrolled in STEM courses were also less likely to earn a B, and approximately twice as likely to earn a C, D, F, or withdraw from a course compared to DSS students in non‐STEM courses.
3) Compared to non‐DSS students, DSS students enrolled in anatomy were less likely to earn an A, less than half as likely to earn a B, and more likely to earn a C or D. The proportion of DSS students who withdrew from anatomy was more than twice that of non‐DSS students.
4) Grades earned by DSS students in anatomy followed a bimodal distribution compared to a normal distribution across other STEM courses broadly. A greater proportion of DSS students enrolled in anatomy achieved an A compared to DSS students in other STEM courses broadly. They were also more likely to earn a C or D, but less than half as likely to earn a B. The proportion of DSS students earning an F or withdrawing from anatomy was similar to other STEM courses broadly.
Altogether, these observations suggest that while DSS students are less likely to earn higher grades in both STEM and non‐STEM courses compared to non‐DSS students, the effect is exacerbated for DSS students enrolled in STEM courses and demands further attention. Potential reasons for the bimodal grade distribution seen for DSS students in anatomy compared to other STEM courses broadly should also be probed further in order to understand why these students are more likely to earn either a higher or lower grade.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
We investigate the energy sources of random turbulent motions of ionized gas from H α emission in eight local star-forming galaxies from the Sydney-AAO Multi-object Integral field ...spectrograph (SAMI) Galaxy Survey. These galaxies satisfy strict pure star-forming selection criteria to avoid contamination from active galactic nuclei (AGNs) or strong shocks/outflows. Using the relatively high spatial and spectral resolution of SAMI, we find that – on sub-kpc scales, our galaxies display a flat distribution of ionized gas velocity dispersion as a function of star formation rate (SFR) surface density. A major fraction of our SAMI galaxies shows higher velocity dispersion than predictions by feedback-driven models, especially at the low SFR surface density end. Our results suggest that additional sources beyond star formation feedback contribute to driving random motions of the interstellar medium in star-forming galaxies. We speculate that gravity, galactic shear and/or magnetorotational instability may be additional driving sources of turbulence in these galaxies.
ABSTRACT
We use data from the Sydney-AAO Multi-object Integral-field spectroscopy (SAMI) Galaxy Survey to study the dynamical scaling relation between galaxy stellar mass M∗ and the general kinematic ...parameter $S_K = \sqrt{K V_{\rm rot}^2 + \sigma ^2}$ that combines rotation velocity Vrot and velocity dispersion σ. We show that the log M∗ – log SK relation: (1) is linear above limits set by properties of the samples and observations; (2) has slightly different slope when derived from stellar or gas kinematic measurements; (3) applies to both early-type and late-type galaxies and has smaller scatter than either the Tully–Fisher relation (log M∗ − log Vrot) for late types or the Faber–Jackson relation (log M∗ − log σ) for early types; and (4) has scatter that is only weakly sensitive to the value of K, with minimum scatter for K in the range 0.4 and 0.7. We compare SK to the aperture second moment (the ‘aperture velocity dispersion’) measured from the integrated spectrum within a 3-arcsecond radius aperture ($\sigma _{3^{\prime \prime }}$). We find that while SK and $\sigma _{3^{\prime \prime }}$ are in general tightly correlated, the log M∗ − log SK relation has less scatter than the $\log M_* - \log \sigma _{3^{\prime \prime }}$ relation.
We examine the kinematic morphology of early-type galaxies (ETGs) in three galaxy clusters Abell 85, 168 and 2399. Using data from the Sydney-AAO Multi-object Integral field spectrograph we measure ...spatially resolved kinematics for 79 ETGs in these clusters. We calculate λ
R
, a proxy for the projected specific stellar angular momentum, for each galaxy and classify the 79 ETGs in our samples as fast or slow rotators. We calculate the fraction of slow rotators in the ETG populations (f
SR) of the clusters to be 0.21 ± 0.08, 0.08 ± 0.08 and 0.12 ± 0.06 for Abell 85, 168 and 2399, respectively, with an overall fraction of 0.15 ± 0.04. These numbers are broadly consistent with the values found in the literature, confirming recent work asserting that the fraction of slow rotators in the ETG population is constant across many orders of magnitude in global environment. We examine the distribution of kinematic classes in each cluster as a function of environment using the projected density of galaxies: the kinematic morphology–density relation. We find that in Abell 85 f
SR increases in higher density regions but in Abell 168 and 2399 this trend is not seen. We examine the differences between the individual clusters to explain this. In addition, we find slow rotators on the outskirts of two of the clusters studied, Abell 85 and 2399. These galaxies reside in intermediate to low density regions and have clearly not formed at the centre of a cluster environment. We hypothesize that they formed at the centres of groups and are falling into the clusters for the first time.
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