Stage-Specific Sampling by Pattern Recognition Receptors during Candida albicans Phagocytosis

Candida albicans is a medically important pathogen, and recognition by innate immune cells is critical for its clearance. Although a number of pattern recognition receptors have been shown to be involved in recognition and phagocytosis of this fungus, the relative role of these receptors has not been formally examined. In this paper, we have investigated the contribution of the mannose receptor, Dectin-1, and complement receptor 3; and we have demonstrated that Dectin-1 is the main non-opsonic receptor involved in fungal uptake. However, both Dectin-1 and complement receptor 3 were found to accumulate at the site of uptake, while mannose receptor accumulated on C. albicans phagosomes at later stages. These results suggest a potential role for MR in phagosome sampling; and, accordingly, MR deficiency led to a reduction in TNF-α and MCP-1 production in response to C. albicans uptake. Our data suggest that pattern recognition receptors sample the fungal phagosome in a sequential fashion

Britain’s highest bog: can we unlock its secrets?

The Glenfeshie Mòine Mhór (Great Moss) is Britain’s highest bog, the largest bog in the Cairngorm Mountains (Scotland) and a water source area for the River Spey. The area was managed primarily for sport hunting for about two centuries, but deer numbers have been heavily reduced in the last decade to allow regeneration of natural woodland and the return to more natural condition of all ecosystems including peatland. However, it may not be realistic to expect spontaneous improvement in peatland condition and ecosystem services provision in the harsh environment of the Mòine Mhór, which retains snow cover for more than half the year and differs floristically from lower-altitude bogs. To understand whether and where management intervention may be required, we need first to understand how the system works at scales ranging from microform to macrotope, and from sub-catchment to whole-system level. Multi-disciplinary condition and process studies (involving various collaborators) are in progress, with a current emphasis on streamflow generation and fluvial carbon loads. This presentation develops two sub-themes. First, ground survey and GIS analysis are used to address the questions: what are the special features of this bog; what is the nature and extent of degradation; and what are the implications for water delivered to the outflow streams? Secondly, a striking feature is the bare peat patches which were favourite resting places for deer on warm, dry summer days. The occurrence of seasonally extreme surface conditions seems a likely factor in preventing their recolonisation by bog plants now. Information about these conditions that cannot readily be accessed through direct observation, originating from temperature sensors and delivered at 60-minute intervals via a low power internet link, is explored in this context. Finally, we discuss aspects of the suitability of our investigation methods for remote and intermittently accessible field sites such as the Mòine Mhór

Factors Impacting COVID-19 Vaccine Hesitancy and Resistance Among College Students in Northwest Ohio

Background: Vaccination is a critical strategy for controlling the transmission of COVID-19 and for returning to normalcy on college campuses; however, vaccine hesitancy and resistance persist as a significant barrier. This study utilized the integrated behavior model (IBM) and the precaution adoption process model (PAPM) to identify factors predictive of COVID-19 vaccine willingness (receptive, hesitant, and resistant) among college students. Methods: A sample of 1248 students at 2 universities in northwest Ohio were surveyed online in 2021. Stata/SE, version 17 (StataCorp) software was used to conduct stepwise logistic regression to investigate the association of theoretical constructs with vaccine willingness, after controlling for COVID-19 related factors and sociodemographic factors. Results: Most students (82.5%) were vaccine receptive, 6.9% were vaccine hesitant, and 10.6% were vaccine resistant. Vaccine hesitancy was higher among students aged 18 to 22 years (9.3%), undergraduates (16.5%), and students who identified as Black (13%) or Middle Eastern (14.3%). Lower vaccine hesitance was significantly predicted by IBM constructs of positive attitudes, high self-efficacy, and high salience. Not getting an influenza vaccine in the past 3 years and viewing vaccination as a personal choice were significantly associated with higher vaccine hesitancy. Lower odds of vaccine resistance were predicted by higher subjective norms. Descriptive norms, not getting an influenza vaccine in the past 3 years, agreeing with conspiracies, and viewing vaccination as a personal choice were strongly predictive of higher vaccine resistance. Conclusion: Identifying the factors that predict vaccine hesitancy and resistance among college students is critical for college administrators, and for those who are designing health communication campaigns, to increase vaccination among this priority population

Spitzer Mid-Infrared Spectroscopy of Infrared Luminous Galaxies at z~2 III: Far-IR to Radio Properties and Optical Spectral Diagnostics

We present the far-IR, millimeter, and radio photometry as well as optical and near-IR spectroscopy of a sample of 48 z~1-3 Spitzer-selected ULIRGs with IRS mid-IR spectra. Our goals are to compute their bolometric emission, and to determine both the presence and relative strength of their AGN and starburst components. We find that strong-PAH sources tend to have higher 160um and 1.2mm fluxes than weak-PAH sources. The depth of the 9.7um silicate feature does not affect MAMBO detectability. We fit the far-IR SEDs of our sample and find an average ~7x10^{12}Lsun for our z>1.5 sources. Spectral decomposition suggests that strong-PAH sources typically have ~20-30% AGN fractions. Weak-PAH sources by contrast tend to have >~70% AGN fractions, with a few sources having comparable contributions of AGN and starbursts. The optical line diagnostics support the presence of AGN in the bulk of the weak-PAH sources. With one exception, our sources are narrow-line sources, show no obvious correspondence between the optical extinction and the silicate feature depth, and, in two cases, show evidence for outflows. Radio AGN are present in both strong-PAH and weak-PAH sources. This is supported by our sample's far-IR-to-radio ratios (q) being consistently below the average value of 2.34 for local star-forming galaxies. We use survival analysis to include the lower-limits given by the radio-undetected sources, arriving at =2.07+/-0.01 for our z>1.5 sample. In total, radio and, where available, optical line diagnostics support the presence of AGN in 57% of the z>1.5 sources, independent of IR-based diagnostics. For higher-z sources, the AGN luminosities alone are estimated to be >10^{12}Lsun, which, supported by the [OIII] luminosities, implies that the bulk of our sources host obscured quasars.Comment: 22 pages, 14 figures, accepted for publication in Ap

A permeability-increasing drug synergizes with bacterial efux pump inhibitors and restores susceptibility to antibiotics in multi-drug resistant Pseudomonas aeruginosa strains

Resistance to antibiotics poses a major global threat according to the World Health Organization. Restoring the activity of existing drugs is an attractive alternative to address this challenge. One of the most efficient mechanisms of bacterial resistance involves the expression of efflux pump systems capable of expelling antibiotics from the cell. Although there are efflux pump inhibitors (EPIs) available, these molecules are toxic for humans. We hypothesized that permeability-increasing antimicrobial peptides (AMPs) could lower the amount of EPI necessary to sensitize bacteria to antibiotics that are efflux substrates. To test this hypothesis, we measured the ability of polymyxin B nonapeptide (PMBN), to synergize with antibiotics in the presence of EPIs. Assays were performed using planktonic and biofilm-forming cells of Pseudomonas aeruginosa strains overexpressing the MexAB-OprM efflux system. Synergy between PMBN and EPIs boosted azithromycin activity by a factor of 2,133 and sensitized P. aeruginosa to all tested antibiotics. This reduced several orders of magnitude the amount of inhibitor needed for antibiotic sensitization. The selected antibiotic-EPI-PMBN combination caused a 10 million-fold reduction in the viability of biofilm forming cells. We proved that AMPs can synergize with EPIs and that this phenomenon can be exploited to sensitize bacteria to antibiotics

Dectin-1 Is A Major β-Glucan Receptor On Macrophages

Zymosan is a β-glucan– and mannan-rich particle that is widely used as a cellular activator for examining the numerous responses effected by phagocytes. The macrophage mannose receptor (MR) and complement receptor 3 (CR3) have historically been considered the major macrophage lectins involved in the nonopsonic recognition of these yeast-derived particles. Using specific carbohydrate inhibitors, we show that a β-glucan receptor, but not the MR, is a predominant receptor involved in this process. Furthermore, nonopsonic zymosan binding was unaffected by genetic CD11b deficiency or a blocking monoclonal antibody (mAb) against CR3, demonstrating that CR3 was not the β-glucan receptor mediating this activity. To address the role of the recently described β-glucan receptor, Dectin-1, we generated a novel anti–Dectin-1 mAb, 2A11. Using this mAb, we show here that Dectin-1 was almost exclusively responsible for the β-glucan–dependent, nonopsonic recognition of zymosan by primary macro-phages. These findings define Dectin-1 as the leukocyte β-glucan receptor, first described over 50 years ago, and resolves the long-standing controversy regarding the identity of this important molecule. Furthermore, these results identify Dectin-1 as a new target for examining the immunomodulatory properties of β-glucans for therapeutic drug design

Fungal Recognition Enhances Mannose Receptor Shedding Through Dectin-1 Engagement

The mannose receptor (MR) is an endocytic type I membrane molecule with a broad ligand specificity that is involved in both hemostasis and pathogen recognition. Membrane-anchored MRis cleaved by a metalloproteinase into functional soluble MR (sMR) composed of the extracellular domains of intact MR. Although sMR production was initially considered a constitutive process, enhanced MR shedding has been observed in response to the fungal pathogen Pneumocystis carinii. In this work, we have investigated the mechanism mediating enhanced MR shedding in response to fungi. We show that other fungal species, including Candida albicans and Aspergillus fumigatus, together with zymosan, a preparation of the cell wall of Saccharomyces cerevisiae, mimic the effect of P. carinii on sMR production and that this effect takes place mainly through β-glucan recognition. Additionally, we demonstrate that MR cleavage in response to C. albicans and bioactive particulate β-glucan requires expression of dectin-1. Our data, obtained using specific inhibitors, are consistent with the canonical Syk-mediated pathway triggered by dectin-1 being mainly responsible for inducing MR shedding, with Raf-1 being partially involved. As in the case of steady-state conditions, MR shedding in response to C. albicans and β-glucan particles requires metalloprotease activity. The induction of MR shedding by dectin-1 has clear implications for the role of MR in fungal recognition, as sMR was previously shown to retain the ability to bind fungal pathogens and can interact with numerous host molecules, including lysosomal hydrolases. Thus, MR cleavage could also impact on the magnitude of inflammation during fungal infection

Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research