Candida albicans adhesion to central venous catheters: Impact of blood plasma-driven germ tube formation and pathogen-derived adhesins

Candida albicans-related bloodstream infections are often associated with infected central venous catheters (CVC) triggered by microbial adhesion and biofilm formation. We utilized single-cell force spectroscopy (SCFS) and flow chamber models to investigate the adhesion behavior of C. albicans yeast cells and germinated cells to naïve and human blood plasma (HBP)-coated CVC tubing. Germinated cells demonstrated up to 56.8-fold increased adhesion forces to CVC surfaces when compared to yeast cells. Coating of CVCs with HBP significantly increased the adhesion of 60-min germinated cells but not of yeast cells and 30-min germinated cells. Under flow conditions comparable to those in major human veins, germinated cells displayed a flow directional-orientated adhesion pattern to HBP-coated CVC material, suggesting the germ tip to serve as the major adhesive region. None of the above-reported phenotypes were observed with germinated cells of an als3Δ deletion mutant, which displayed similar adhesion forces to CVC surfaces as the isogenic yeast cells. Germinated cells of the als3Δ mutant also lacked a clear flow directional-orientated adhesion pattern on HBP-coated CVC material, indicating a central role for Als3 in the adhesion of germinated C. albicans cells to blood exposed CVC surfaces. In the common model of C. albicans, biofilm formation is thought to be mediated primarily by yeast cells, followed by surface-triggered the formation of hyphae. We suggest an extension of this model in which C. albicans germ tubes promote the initial adhesion to blood-exposed implanted medical devices via the germ tube-associated adhesion protein Als3

Dynamic habitat models reflect interannual movement of cetaceans within the California current ecosystem

This modeling project was funded by the Navy, Commander, U.S. Pacific Fleet (U.S. Navy), the Bureau of Ocean Energy Management (BOEM), and by the National Oceanic and Atmospheric Administration (NOAA), National Marine Fisheries Service (NMFS), Southwest Fisheries Science Center (SWFSC). The 2018 survey was conducted as part of the Pacific Marine Assessment Program for Protected Species (PacMAPPS), a collaborative effort between NOAA Fisheries, the U.S. Navy, and BOEM to collect data necessary to produce updated abundance estimates for cetaceans in the CCE study area. BOEM funding was provided via Interagency Agreement (IAA) M17PG00025, and Navy funding via IAA N0007018MP4C560, under the Mexican permit SEMARNAT/SGPA/DGVS/013212/18. The methods used to derive uncertainty estimates were developed as part of “DenMod: Working Group for the Advancement of Marine Species Density Surface Modeling” funded by OPNAV N45 and the SURTASS LFA Settlement Agreement, and managed by the U.S. Navy’s Living Marine Resources (LMR) program under Contract No. N39430-17-C-1982. Other permits included INEGI: Oficio núm. 400./331/2018, INEGI.GMA 1.03 SAGARPA de Oficio B00.02.04.1530/2018 NMFS Permit No. 19091.The distribution of wide-ranging cetacean species often cross national or jurisdictional boundaries, which creates challenges for monitoring populations and managing anthropogenic impacts, especially if data are only available for a portion of the species’ range. Many species found off the U.S. West Coast are known to have continuous distributions into Mexican waters, with highly variable abundance within the U.S. portion of their range. This has contributed to annual variability in design-based abundance estimates from systematic shipboard surveys off the U.S. West Coast, particularly for the abundance of warm temperate species such as striped dolphin, Stenella coeruleoalba, which increases off California during warm-water conditions and decreases during cool-water conditions. Species distribution models (SDMs) can accurately describe shifts in cetacean distribution caused by changing environmental conditions, and are increasingly used for marine species management. However, until recently, data from waters off the Baja California peninsula, México, have not been available for modeling species ranges that span from Baja California to the U.S. West Coast. In this study, we combined data from 1992–2018 shipboard surveys to develop SDMs off the Pacific Coast of Baja California for ten taxonomically diverse cetaceans. We used a Generalized Additive Modeling framework to develop SDMs based on line-transect surveys and dynamic habitat variables from the Hybrid Coordinate Ocean Model (HYCOM). Models were developed for ten species: long- and short-beaked common dolphins (Delphinus delphis delphis and D. d. bairdii), Risso’s dolphin (Grampus griseus), Pacific white-sided dolphin (Lagenorhynchus obliquidens), striped dolphin, common bottlenose dolphin (Tursiops truncatus), sperm whale (Physeter macrocephalus), blue whale (Balaenoptera musculus), fin whale (B. physalus), and humpback whale (Megaptera novaeangliae). The SDMs provide the first fine-scale (approximately 9 x 9 km grid) estimates of average species density and abundance, including spatially-explicit measures of uncertainty, for waters off the Baja California peninsula. Results provide novel insights into cetacean ecology in this region as well as quantitative spatial data for the assessment and mitigation of anthropogenic impacts.Publisher PDFPeer reviewe

Unique Proteomic Signatures Distinguish Macrophages and Dendritic Cells

Monocytes differentiate into heterogeneous populations of tissue macrophages and dendritic cells (DCs) that regulate inflammation and immunity. Identifying specific populations of myeloid cells in vivo is problematic, however, because only a limited number of proteins have been used to assign cellular phenotype. Using mass spectrometry and bone marrow-derived cells, we provided a global view of the proteomes of M-CSF-derived macrophages, classically and alternatively activated macrophages, and GM-CSF-derived DCs. Remarkably, the expression levels of half the plasma membrane proteins differed significantly in the various populations of cells derived in vitro. Moreover, the membrane proteomes of macrophages and DCs were more distinct than those of classically and alternatively activated macrophages. Hierarchical cluster and dual statistical analyses demonstrated that each cell type exhibited a robust proteomic signature that was unique. To interrogate the phenotype of myeloid cells in vivo, we subjected elicited peritoneal macrophages harvested from wild-type and GM-CSF-deficient mice to mass spectrometric and functional analysis. Unexpectedly, we found that peritoneal macrophages exhibited many features of the DCs generated in vitro. These findings demonstrate that global analysis of the membrane proteome can help define immune cell phenotypes in vivo

Cooperativity‐Driven Reactivity of a Dinuclear Copper Dimethylglyoxime Complex

In this report, we present the dinuclear copper(II) dimethylglyoxime (H$_2$dmg) complex [Cu$_2$(H$_2$dmg)(Hdmg)(dmg)]$^+$ (1), which, in contrast to its mononuclear analogue [Cu(Hdmg)$_2$] (2), is subject to a cooperativity-driven hydrolysis. The combined Lewis acidity of both copper centers increases the electrophilicity of the carbon atom in the bridging μ$_2$-O−N=C-group of H$_2$dmg and thus, facilitates the nucleophilic attack of H2O. This hydrolysis yields butane-2,3-dione monoxime (3) and NH$_2$OH that, depending on the solvent, is then either oxidized or reduced. In ethanol, NH$_2$OH is reduced to NH$_4$$^+$, yielding acetaldehyde as the oxidation product. In contrast, in CH$_3$CN, NH$_2$OH is oxidized by Cu$^{II}$ to form N$_2$O and [Cu(CH$_3$CN)4]$^+$. Herein are presented the combined synthetic, theoretical, spectroscopic and spectrometric methods that indicate and establish the reaction pathway of this solvent-dependent reaction

Estimating Foodborne Gastroenteritis, Australia

An estimated 4.0–6.9 million episodes of foodborne gastroenteritis occur in Australia each year

Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration

Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox4(-/-)) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox4(-/-) mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy