Prolyl hydroxylation- and glycosylation-dependent functions of Skp1 in O2-regulated development of Dictyostelium

AbstractO2 regulates multicellular development of the social amoeba Dictyostelium, suggesting it may serve as an important cue in its native soil environment. Dictyostelium expresses an HIFα-type prolyl 4-hydroxylase (P4H1) whose levels affect the O2-threshold for culmination implicating it as a direct O2-sensor, as in animals. But Dictyostelium lacks HIFα, a mediator of animal prolyl 4-hydroxylase signaling, and P4H1 can hydroxylate Pro143 of Skp1, a subunit of E3SCFubiquitin-ligases. Skp1 hydroxyproline then becomes the target of five sequential glycosyltransferase reactions that modulate the O2-signal. Here we show that genetically induced changes in Skp1 levels also affect the O2-threshold, in opposite direction to that of the modification enzymes suggesting that the latter reduce Skp1 activity. Consistent with this, overexpressed Skp1 is poorly hydroxylated and Skp1 is the only P4H1 substrate detectable in extracts. Effects of Pro143 mutations, and of combinations of Skp1 and enzyme level perturbations, are consistent with pathway modulation of Skp1 activity. However, some effects were not mirrored by changes in modification of the bulk Skp1 pool, implicating a Skp1 subpopulation and possibly additional unknown factors. Altered Skp1 levels also affected other developmental transitions in a modification-dependent fashion. Whereas hydroxylation of animal HIFα results in its polyubiquitination and proteasomal degradation, Dictyostelium Skp1 levels were little affected by its modification status. These data indicate that Skp1 and possibly E3SCFubiquitin-ligase activity modulate O2-dependent culmination and other developmental processes, and at least partially mediate the action of the hydroxylation/glycosylation pathway in O2-sensing

The Brown Dwarf Kinematics Project (BDKP). III. Parallaxes for 70 Ultracool Dwarfs

We report parallax measurements for 70 ultracool dwarfs (UCDs). Using both literature values and our sample, we report new polynomial relations between spectral type and M$_{JHK}$. Including resolved L/T transition binaries in the relations, we find no reason to differentiate between a "bright" (unresolved binary) and "faint" (single source) sample across the L/T boundary. Isolating early T dwarfs, we find that the brightening of T0-T4 sources is prominent in M$_{J}$ where there is a [1.2 - 1.4] magnitude difference. A similar yet dampened brightening of [0.3 - 0.5] magnitude happens at M$_{H}$ and a plateau or dimming of [-0.2 - -0.3] magnitude is seen in M$_{K}$. Comparing with evolutionary models that vary gravity, metallicity, and cloud thickness we find that a near constant temperature of 1200 $\pm$100 K along a narrow spectral subtype of T0-T4 is required to account for the brightening and color magnitude diagram of the L-dwarf/T-dwarf transition. Furthermore, there is a significant population of both L and T dwarfs which are red or potentially "ultra-cloudy" compared to the models, many of which are known to be young indicating a correlation between enhanced photospheric dust and youth. For the low surface-gravity or young companion L dwarfs we find that 8 out of 10 are at least [0.2-1.0] magnitude underluminous in M$_{JH}$ and/or M$_{K}$ compared to equivalent spectral type objects. We speculate that this is a consequence of increased dust opacity and conclude that low-surface gravity L dwarfs require a completely new spectral-type/absolute magnitude polynomial for analysis.Comment: 65 pages, Accepted for publication to Ap

Bacterial vaginosis, vaginal flora patterns and vaginal hygiene practices in patients presenting with vaginal discharge syndrome in The Gambia, West Africa

BACKGROUND: Bacterial vaginosis (BV) – a syndrome characterised by a shift in vaginal flora – appears to be particularly common in sub-Saharan Africa, but little is known of the pattern of vaginal flora associated with BV in Africa. We conducted a study aimed at determining the prevalence of BV and patterns of BV-associated vaginal micro-flora among women with vaginal discharge syndrome (VDS) in The Gambia, West Africa. METHODS: We enrolled 227 women with VDS from a large genito-urinary medicine clinic in Fajara, The Gambia. BV was diagnosed by the Nugent's score and Amsel's clinical criteria. Vaginal swabs were collected for T vaginalis and vaginal flora microscopy, and for Lactobacillus spp, aerobic organisms, Candida spp and BV-associated bacteria (Gardnerella vaginalis, anaerobic bacteria, and Mycoplasma spp) cultures; and cervical swabs were collected for N gonorrhoeae culture and C trachomatis PCR. Sera were tested for HIV-1 and HIV-2 antibodies. Sexual health history including details on sexual hygiene were obtained by standardised questionnaire. RESULTS: BV prevalence was 47.6% by Nugent's score and 30.8% by Amsel's clinical criteria. Lactobacillus spp were isolated in 37.8% of women, and 70% of the isolates were hydrogen-peroxide (H(2)0(2))-producing strains. Prevalence of BV-associated bacteria were: G vaginalis 44.4%; Bacteroides 16.7%; Prevotella 15.2%; Peptostretococcus 1.5%; Mobiluncus 0%; other anaerobes 3.1%; and Mycoplasma hominis 21.4%. BV was positively associated with isolation of G vaginalis (odds-ratio [OR] 19.42, 95%CI 7.91 – 47.6) and anaerobes (P = 0.001 [OR] could not be calculated), but not with M hominis. BV was negatively associated with presence of Lactobacillus (OR 0.07, 95%CI 0.03 – 0.15), and H(2)O(2)-producing lactobacilli (OR 0.12, 95% CI 0.05 – 0.28). Presence of H(2)O(2)-producing lactobacilli was associated with significantly lower prevalence of G vaginalis, anaerobes and C trachomatis. HIV prevalence was 12.8%. Overall, there was no association between BV and HIV, and among micro-organisms associated with BV, only Bacteroides spp. and Prevotella spp. were associated with HIV. BV or vaginal flora patterns were not associated with any of the factors relating to sexual hygiene practices (vaginal douching, menstrual hygiene, female genital cutting). CONCLUSION: In this population, BV prevalence was higher than in corresponding populations in industrialised countries, but the pattern of vaginal micro-flora associated with BV was similar. BV or vaginal flora patterns were not associated with HIV nor with any of the vaginal hygiene characteristics

Resistivity of dilute 2D electrons in an undoped GaAs heterostructure

We report resistivity measurements from 0.03 K to 10 K in a dilute high mobility 2D electron system. Using an undoped GaAs/AlGaAs heterojunction in a gated field-effect transistor geometry, a wide range of densities, $0.16 \times 10^{10} {cm}^{-2}$ to $7.5 \times 10^{10} {cm}^{-2}$, are explored. For high densities, the results are quantitatively shown to be due to scattering by acoustic phonons and impurities. In an intermediate range of densities, a peak in the resistivity is observed for temperatures below 1 K. This non-monotonic resistivity can be understood by considering the known scattering mechanisms of phonons, bulk and interface ionized impurities. Still lower densities appear insulating to the lowest temperature measured.Comment: 4 pages, 4 figure

Dynamics of the Globular Cluster System Associated with M87 (NGC 4486). II. Analysis

We present a dynamical analysis of the globular cluster system associated with M87 (= NGC 4486), the cD galaxy near the dynamical center of the Virgo cluster. The analysis utilizes a new spectroscopic and photometric database which is described in a companion paper (Hanes et al. 2001). Using a sample of 278 globular clusters with measured radial velocities and metallicities, and new surface density profiles based on wide-field Washington photometry, we study the dynamics of the M87 globular cluster system both globally --- for the entire cluster sample --- and separately --- for the metal-rich and metal-poor globular cluster samples. This constitutes the largest sample of radial velocities for pure Population II tracers yet assembled for any galaxy. We discuss the implications of our findings for models for the formation of giant elliptical galaxies, globular cluster systems, and the Virgo cluster. (ABRIDGED)Comment: 28 pages, 19 postscript figures, 1 jpeg image. See http://www.physics.rutgers.edu/ast/ast-rap.html to download the manuscript with higher quality figures. Accepted for publication in the Astrophysical Journa

Patients with immune mediated inflammatory diseases are insufficiently protected against vaccine-preventable infections

Background Patients with Immune Mediated Inflammatory Diseases (IMIDs) using immunosuppressive therapy are at increased risk of infections, including vaccine-preventable infections. In this study, we aimed to evaluate whether patients with IMIDs on systemic immunosuppressive therapy are vaccinated according to current guidelines. Methods A survey was sent out, between August 2022 and March 2023, to all patients with IMIDs that visited the departments of dermatology, rheumatology and gastroenterology at an academic and regional hospital in Rotterdam, the Netherlands. Patient-reported vaccination status was compared to the Dutch guidelines on vaccinations in patients with chronic inflammatory diseases. Results A total of 1,905/5,987 patients responded to the survey (response rate 32%). After exclusion of patients without systemic immunosuppressive medication, the study population comprised 1,390 patients, median age 56 years (IQR 42-66) and 41% male. Most patients (92%) had been vaccinated according to the Dutch National Immunization Program. Before starting immunosuppressive therapy, 2% of the patients who were still considered at risk according to the Dutch guideline were vaccinated for measles, and 4% for diphtheria/tetanus/polio (DT-IPV). Additionally, 62% of patients received an annual influenza vaccine, 16% received a five-yearly pneumococcal vaccine, and 91% were fully vaccinated against COVID-19. Conclusion Patients with IMIDs on immunosuppressive therapy are not vaccinated in accordance with the guidelines. Implementation strategies to improve the vaccination rates for patients with IMIDs should specifically focus on vaccinating against measles and diphtheria/tetanus/polio, and periodic vaccination against pneumococcal and influenza infections

Validity of the self-administered comorbidity questionnaire in patients with inflammatory bowel disease

Background: The International Consortium for Health Outcomes Measurement has selected the self-administered comorbidity questionnaire (SCQ) to adjust case-mix when comparing outcomes of inflammatory bowel disease (IBD) treatment between healthcare providers. However, the SCQ has not been validated for use in IBD patients. Objectives: We assessed the validity of the SCQ for measuring comorbidities in IBD patients. Design: Cohort study. Methods: We assessed the criterion validity of the SCQ for IBD patients by comparing patient-reported and clinician-reported comorbidities (as noted in the electronic health record) of the 13 diseases of the SCQ using Cohen’s kappa. Construct validity was assessed using the Spearman correlation coefficient between the SCQ and the Charlson Comorbidity Index (CCI), clinician-reported SCQ, quality of life, IBD-related healthcare and productivity costs, prevalence of disability, and IBD disease activity. We assessed responsiveness by correlating changes in the SCQ with changes in healthcare costs, productivity costs, quality of life, and disease activity after 15 months. Results: We included 613 patients. At least fair agreement (κ &gt; 0.20) was found for most comorbidities, but the agreement was slight (κ &lt; 0.20) for stomach disease [κ = 0.19, 95% CI (−0.03; 0.41)], blood disease [κ = 0.02, 95% CI (−0.06; 0.11)], and back pain [κ = 0.18, 95% CI (0.11; 0.25)]. Correlations were found between the SCQ and the clinician-reported SCQ [ρ = 0.60, 95% CI (0.55; 0.66)], CCI [ρ = 0.39, 95% CI (0.31; 0.45)], the prevalence of disability [ρ = 0.23, 95% CI (0.15; 0.32)], and quality of life [ρ = −0.30, 95% CI (−0.37; −0.22)], but not between the SCQ and healthcare or productivity costs or disease activity (|ρ| ⩽ 0.2). A change in the SCQ after 15 months was not correlated with a change in any of the outcomes.Conclusion: The SCQ is a valid tool for measuring comorbidity in IBD patients, but face and content validity should be improved before being used to correct case-mix differences.</p

The relationships between internal and external threat and right-wing attitudes: A three-wave longitudinal study

The interplay between threat and right-wing attitudes has received much research attention, but its longitudinal relationship has hardly been investigated. In this study, we investigated the longitudinal relationships between internal and external threat and right-wing attitudes using a cross-lagged design at three different time points in a large nationally representative sample (N = 800). We found evidence for bidirectional relationships. Higher levels of external threat were related to higher levels of Right-Wing Authoritarianism and to both the egalitarianism and dominance dimensions of Social Dominance Orientation at a later point in time. Conversely, higher levels of RWA were also related to increased perception of external threat later in time. Internal threat did not yield significant direct or indirect longitudinal relationships with right-wing attitudes. Theoretical and practical implications of these longitudinal effects are discussed

Identification of a Wide, Low-Mass Multiple System Containing the Brown Dwarf 2MASS J0850359+105716

We report our discovery of NLTT 20346 as an M5+M6 companion system to the tight binary (or triple) L dwarf 2MASS J0850359+105716. This nearby (~31 pc), widely separated (~7700 AU) quadruple system was identified through a cross-match of proper motion catalogs. Follow-up imaging and spectroscopy of NLTT 20346 revealed it to be a magnetically active M5+M6 binary with components separated by ~2" (50-80 AU). Optical spectroscopy of the components show only moderate Halpha emission corresponding to a statistical age of ~5 - 7 Gyr for both M dwarfs. However NLTT 20346 is associated with the XMM-Newton source J085018.9+105644, and based on X-ray activity the age of NLTT 20346 is between 250-450 Myr. Strong Li absorption in the optical spectrum of 2MASS J0850+1057 indicates an upper age limit of 0.8 - 1.5 Gyr favoring the younger age for the primary. Using evolutionary models in combination with an adopted system age of 0.25-1.5 Gyr indicates a total mass for 2MASS J0850+1057 of 0.07+/-0.02 Msun if it is a binary. NLTT 20346/2MASS J0850+1057 joins a growing list of hierarchical systems containing brown dwarf binaries and is among the lowest binding energy associations found in the field. Formation simulations via gravitational fragmentation of massive extended disks have successfully produced a specific analog to this system.Comment: 13 pages, accepted for publication to A

Evaluation of cropland maximum light use efficiency using eddy flux measurements in North America and Europe

Croplands cover 12% of the ice-free land surface and play an important role in the global carbon cycle. Light use efficiency (LUE) models have often been employed to estimate the exchange of CO2 between croplands and the atmosphere. A key parameter in these models is the maximum light use efficiency (ε*), but estimates of ε* vary by at least a factor 2. Here we used 12 agricultural eddy-flux measurement sites in North America and Europe to constrain LUE models in general and ε* in particular. We found that LUE models could explain on average about 70% of the variability in net ecosystem exchange (NEE) when we increased the ε* from 0.5 to 0.65-2.0g C per MJ Photosynthetic Active Radiation (PAR). Our results imply that croplands are more important in the global carbon budget than often thought. In addition, inverse modeling approaches that utilize LUE model outputs as a-priori input may have to be revisited in areas where croplands are an important contributor to regional carbon fluxes. Copyright 2011 by the American Geophysical Union