Frequency of Th17 CD20+ cells in the peripheral blood of rheumatoid arthritis patients is higher compared to healthy subjects

Introduction  

Rheumatoid arthritis (RA) is considered a T cell driven autoimmune disease, therefore, the ability of B cell depleting biologics, e.g., anti-CD20 antibodies, to alleviate RA is unclear. This study examined the proportions of IL-17-secreting lymphocytes in the blood of healthy subjects and RA patients and determined if Th17 cells belong to a CD20+ subset of T cells.     

Cellular crosstalk between TNF-α, NADPH oxidase, PKCβ2, and C2GNT in human leukocytes

Increasing evidence suggests that chronic, sub-clinical inflammation plays an important role in the pathogenesis of diabetic retinopathy. We have established the potential role of the inflammatory enzyme, core 2 β-1, 6-N-acetylglucosaminyltransferase (C2GNT) in diabetic retinopathy. The present study was designed to explore the NADPH oxidase signaling pathway in the tumor necrosis factor-alpha (TNF-α)-induced activity of C2GNT in leukocytes. Human leukocytes (U937 cells) and an Epstein-Barr-transformed lymphoblastoid cell line deficient in p47phox (F10007 cells) were used for the study. Cells were exposed to TNF-α for 24 h in the presence and absence of 1) NADPH oxidase inhibitors (apocynin and scrambled and unscrambled gp91ds-tat), 2) LY379196 (specific protein kinase C β1/2 (PKCβ1/2) inhibitor), and 3) the antioxidant tiron. Subsequent C2GNT and NADPH activity was measured and the adhesion of U937 and F10007 cells to endothelial cells was assessed. TNF-α-induced C2GNT activity (1813 ± 326 pmol/h/mg protein) (mean ± SEM) in human leukocytes was significantly reversed with apocynin (153 ± 82 pmol/h/mg protein), unscrambled gp91ds-tat (244 ± 122 pmol/h/mg protein) and tiron (756 ± 87 pmol/h/mg protein). We further supported this C2GNT-NADPH oxidase link using p47phox-deficient leukocytes. The deficiency in p47phox prevented TNF-α-induced NADPH oxidase and C2GNT activity and adherence to endothelial cells. The response to TNF-α was restored by transfection with an expression plasmid containing a p47phox cDNA inserted in the sense direction. Our results demonstrate for the first time a novel signaling crosstalk between TNF-α, NADPH oxidase, PKCβ1/2 and C2GNT in leukocytes.     

Seed germination temperatures of eight Mexican Agave species with economic importance

The genetic diversity of Agave plants is threatened by clonal commercial reproduction and climatic change. Sexual reproduction is uncommon and research on seed germination is scarce. The present study evaluated the seed germination of Agave lechuguilla, Agave striata, Agave americana var. marginata, Agave asperrima, Agave cupreata, Agave duranguesis, Agave angustifolia ssp. tequilana and Agave salmiana at constant temperatures (10, 15, 20, 25, 30, 35 and 40°C). Initial imbibition (after the first 12 h) was significantly variable among species, positively correlated with seed weight (r = 0.6560, P < 0.001) and increased with temperature (from 35% at 10°C to 66% at 40°C). Temperature affected maximum imbibition (83–150%) for A. asperrima, A. lechuguilla, A. salmiana and A. striata; other species averaged 110%. Most germination kinetics best fitted a logistic model, whereas only a few treatments fit a Weibull model. The time to germination onset diminished (P < 0.05) from 125–173 h at 15°C to 68–84 h at 25°C, and then ascended to 84–196 h at 35°C. The mean germination rate and seed germination percentage after 312 h peaked at 25°C (0.50–0.95% seeds/h and 85–99%, respectively) and fell (P < 0.05) to near zero at 10 and 40°C. Temperatures of 10, 35 and 40°C were partially lethal to A. asperrima, A. duranguensis and A. salmiana seeds. The time to germination onset, seed germination percentage after 312 h and mean germination rate are best described by a Gaussian distribution, with its optimum at approximately 25°C. Thus, optimum temperatures are related to the ecological characteristics of each species area.     

Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging

The study of complex computational systems is facilitated by network maps, such as circuit diagrams. Such mapping is particularly informative when studying the brain, as the functional role that a brain area fulfills may be largely defined by its connections to other brain areas. In this report, we describe a novel, non-invasive approach for relating brain structure and function using magnetic resonance imaging (MRI). This approach, a combination of structural imaging of long-range fiber connections and functional imaging data, is illustrated in two distinct cognitive domains, visual attention and face perception. Structural imaging is performed with diffusion-weighted imaging (DWI) and fiber tractography, which track the diffusion of water molecules along white-matter fiber tracts in the brain (Figure 1). By visualizing these fiber tracts, we are able to investigate the long-range connective architecture of the brain. The results compare favorably with one of the most widely-used techniques in DWI, diffusion tensor imaging (DTI). DTI is unable to resolve complex configurations of fiber tracts, limiting its utility for constructing detailed, anatomically-informed models of brain function. In contrast, our analyses reproduce known neuroanatomy with precision and accuracy. This advantage is partly due to data acquisition procedures: while many DTI protocols measure diffusion in a small number of directions (e.g., 6 or 12), we employ a diffusion spectrum imaging (DSI)^{1, 2} protocol which assesses diffusion in 257 directions and at a range of magnetic gradient strengths. Moreover, DSI data allow us to use more sophisticated methods for reconstructing acquired data. In two experiments (visual attention and face perception), tractography reveals that co-active areas of the human brain are anatomically connected, supporting extant hypotheses that they form functional networks. DWI allows us to create a "circuit diagram" and reproduce it on an individual-subject basis, for the purpose of monitoring task-relevant brain activity in networks of interest.     

Culture-independent tracking of Vibrio cholerae lineages reveals complex spatiotemporal dynamics in a natural population

Populations of the bacterium Vibrio cholerae consist of dozens of distinct lineages, with primarily (but not exclusively) members of the pandemic generating lineage capable of causing the diarrhoeal disease cholera. Assessing the composition and temporal dynamics of such populations requires extensive isolation efforts and thus only rarely covers large geographic areas or timeframes exhaustively. We developed a culture-independent amplicon sequencing strategy based on the protein-coding gene viuB (vibriobactin utilization) to study the structure of a V. cholerae population over the course of a summer. We show that the 26 co-occurring V. cholerae lineages continuously compete for limited space on nutrient-rich particles where only a few of them can grow to large numbers. Differential abundance of lineages between locations and size-fractions associated with a particle-attached or free-swimming lifestyle could reflect adaptation to various environmental niches. In particular, a major V. cholerae lineage occasionally grows to large numbers on particles but remain undetectable using isolation-based methods, indicating selective culturability for some members of the species. We thus demonstrate that isolation-based studies may not accurately reflect the structure and complex dynamics of V. cholerae populations and provide a scalable high-throughput method for both epidemiological and ecological approaches to studying this species.     

Molecular characterization reveals similar virulence gene content in unrelated clonal groups of Escherichia coli of serogroup O174 (OX3)

Most severe illnesses that are attributed to Shiga toxin-producing Escherichia coli are caused by isolates that also carry a pathogenicity island called the locus of enterocyte effacement (LEE). However, many cases of severe disease are associated with LEE-negative strains. We characterized the virulence gene content and the evolutionary relationships of Escherichia coli isolates of serogroup O174 (formerly OX3), strains of which have been implicated in cases of hemorrhagic colitis and hemolytic uremic syndrome. A total of 56 isolates from humans, farm animals, and food were subjected to multilocus virulence gene profiling (MVGP), and a subset of 16 isolates was subjected to multilocus sequence analysis (MLSA). The MLSA revealed that the O174 isolates fall into four separate evolutionary clusters within the E. coli phylogeny and are related to a diverse array of clonal groups, including enteropathogenic E. coli 2 (EPEC 2), enterohemorrhagic E. coli 2 (EHEC 2), and EHEC-O121. Of the 15 genes that we surveyed with MVGP, only 6 are common in the O174 strains. The different clonal groups within the O174 serogroup appear to have independently acquired and maintained similar sets of genes that include the Shiga toxins (stx₁ and stx₂) and two adhesins (saa and iha). The absence of certain O island (OI) genes, such as those found on OI-122, is consistent with the notion that certain pathogenicity islands act cooperatively with the LEE island.     

Covalently bound fluorescent probes as reporters for hydroxyl radical penetration into liposomal membranes

The ability of hydroxyl radicals to penetrate into liposomal model membranes (dimyristoylphosphatidylcholine) has been demonstrated. Liposomes were prepared and then characterized by digital fluorescence microscopy and dynamic light scattering after extrusion to determine liposomal lamellarity, size, and shape. Hydroxyl radicals were generated in the surrounding aqueous medium using a modified Fenton reagent (hydrogen peroxide and Fe²⁺) with the water-soluble iron chelator EDTA. High and low doses of radical were used, and the low dose was achieved with physiologically relevant iron and peroxide concentrations. Fluorescent probes covalently bound to the membrane phospholipid were used, including two lipophilic pyrenyl probes within the membrane bilayer and one polar probe at the water–membrane interface. Radical reactions with the probes were monitored by following the decrease in fluorescence and by observing oxidation products via matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Differences in the probe position within the membrane were correlated with the reactivity of the probe to assess radical access to the site of the probe. For all probes, reaction rates increased with increasing temperature. Within the membrane bilayer, reaction rates were greater for the probe closest to the membrane–water interface. Cholesterol protected these probes from oxidation. Kinetic models, scavenger studies, and product identification studies indicated that hydroxyl radical reacted directly with the in-membrane probes without the mediation of a secondary radical.     

Captivity reduces hippocampal volume but not survival of new cells in a food‐storing bird

In many naturalistic studies of the hippocampus wild animals are held in captivity. To test if captivity itself affects hippocampal integrity, adult black‐capped chickadees (Poecile atricapilla) were caught in the fall, injected with bromodeoxyuridine to mark neurogenesis, and alternately released to the wild or held in captivity. The wild birds were recaptured after 4–6 weeks and perfused simultaneously with their captive counterparts. The hippocampus of captive birds was 23% smaller than wild birds, with no hemispheric differences in volume within groups. Between groups there was no statistically significant difference in the size of the telencephalon, or in the number and density of surviving new cells. Proximate causes of the reduced hippocampal volume could include stress, lack of exercise, diminished social interaction, or limited caching opportunity—a hippocampal‐dependent activity. The results suggest the avian hippocampus—a structure essential for rapid, complex relational and spatial learning—is both plastic and sensitive, much as in mammals, including humans. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009     

Rapid partner switching may facilitate increased broadcast group size in dance compared with conversation groups

Dancing is a universal human activity that involves exertive rhythmic movement to music. It is often conducted in a social environment and often involves synchronization. It has been found to cause dancers to bond socially. Like conversation, it has been suggested that dancing may be an inexpensive form of social bonding, in that both activities facilitate efficient group bonding by allowing multiple individuals to bond simultaneously. However, no previous study has systematically observed the size of naturally occurring dance groups. During unobtrusive observation of natural dance and conversation behavior, we found that the cumulative number of dance partners (cumulative group) was greater than the number of partners at any one moment (instantaneous group), whereas no such difference was found for conversation. Additionally, the length of uninterrupted engagement (bout) was negatively predicted by group size in conversation but not dance groups, and it was significantly longer in conversation groups than dance groups. Finally, instantaneous group size was significantly larger in dance than conversation groups, and also positively related to time spent synchronizing in dance groups. Together, these results suggest that dance may allow a larger number of individuals to simultaneously engage with each other than conversation does because (i) more rapid partner switching increases cumulative broadcast group; and (ii) synchrony facilitates simultaneous interaction with multiple individuals, allowing for larger instantaneous groups. We conclude that the capacity for information transfer provided by language comes at a cost in terms of social bonding, and that dance may have played an important role in bonding large hominin social groups.