Wellbuilt for wellbeing: Controlling relative humidity in the workplace matters for our health.

This study offers a new perspective on the role of relative humidity in strategies to improve the health and wellbeing of office workers. A lack of studies of sufficient participant size and diversity relating relative humidity (RH) to measured health outcomes has been a driving factor in relaxing thermal comfort standards for RH and removing a lower limit for dry air. We examined the association between RH and objectively measured stress responses, physical activity (PA), and sleep quality. A diverse group of office workers (n = 134) from four well-functioning federal buildings wore chest-mounted heart rate variability monitors for three consecutive days, while at the same time, RH and temperature (T) were measured in their workplaces. Those who spent the majority of their time at the office in conditions of 30%-60% RH experienced 25% less stress at the office than those who spent the majority of their time in drier conditions. Further, a correlational study of our stress response suggests optimal values for RH may exist within an even narrower range around 45%. Finally, we found an indirect effect of objectively measured poorer sleep quality, mediated by stress responses, for those outside this range.

B-cell inhibition by cross-linking CD79b is superior to B-cell depletion with anti-CD20 antibodies in treating murine collagen-induced arthritis.

Depletion of B cells with the anti-CD20 antibody rituximab is an established therapy for rheumatoid arthritis. However, rituximab has only moderate efficacy, most likely due to insufficient depletion of B cells in lymphoid organs and expansion of pathogenic B cells. We found that an antibody against mouse CD79b profoundly blocks B-cell proliferation induced via the B-cell receptor, CD40, CD180, and chondroitin sulfate, but not via TLR4 or TLR9. Treatment with anti-CD79b also induces death in resting and activated B cells. B-cell inhibition is mediated by cross-linkage of CD79b, but independent of Fc-receptor engagement. In the model of collagen-induced arthritis, an antibody against mouse CD20 depletes B cells very efficiently but fails to suppress the humoral immune response against collagen and the development of arthritis. In contrast, the antibody against CD79b, and a deglycosylated variant of this antibody, almost completely inhibits the increase in anti-collagen antibodies and the development of arthritis. In mice with established arthritis only the fully glycosylated antibody against CD79b is effective. Our data show that targeting B cells via CD79b is much more effective than B-cell depletion with anti-CD20 antibodies for therapy of arthritis. These findings may have important implications for treatment of B-cell-mediated autoimmune diseases.

Modeled diversity effects on microbial ecosystem functions of primary production, nutrient uptake, and remineralization.

Ecosystem-wide primary productivity generally increases with primary producer diversity, emphasizing the importance of diversity for ecosystem function. However, most studies that demonstrate this positive relationship have focused on terrestrial and aquatic benthic systems, with little attention to the diverse marine pelagic primary producers that play an important role in regulating global climate. Here we show how phytoplankton biodiversity enhances overall marine ecosystem primary productivity and other ecosystem functions using a self-organizing ecosystem model. Diversity manipulation numerical experiments reveal positive, asymptotically saturating relationships between ecosystem-wide phytoplankton diversity and functions of productivity, nutrient uptake, remineralization, and diversity metrics used to identify mechanisms shaping these relationships. Increase in productivity with increasing diversity improves modeled ecosystem stability and model robustness and leads to productivity rates that exceed expected yields primarily through niche complementarity and facilitative interactions between coexisting phytoplankton types; the composition of traits in assemblages determines the magnitude of complementarity and selection effects. While findings based on these aggregate measures of diversity effects parallel those from the majority of experimental outcomes of terrestrial and benthic biodiversity-ecosystem function studies, we combine analyses of community diversity effects and investigations of the underlying interactions among phytoplankton types to demonstrate how an increase in recycled production of non-diatoms through an increase in new production of diatoms drives this diversity-cosystem function response. We demonstrate the important role that facilitation plays in the modeled marine plankton and how this facilitative interaction could amplify future climate-driven changes in ocean ecosystem productivity.

Discovery of associative patterns between workplace sound level and physiological wellbeing using wearable devices and empirical Bayes modeling.

We conducted a field study using multiple wearable devices on 231 federal office workers to assess the impact of the indoor environment on individual wellbeing. Past research has established that the workplace environment is closely tied to an individual's wellbeing. Since sound is the most-reported environmental factor causing stress and discomfort, we focus on quantifying its association with physiological wellbeing. Physiological wellbeing is represented as a latent variable in an empirical Bayes model with heart rate variability measures-SDNN and normalized-HF as the observed outcomes and with exogenous factors including sound level as inputs. We find that an individual's physiological wellbeing is optimal when sound level in the workplace is at 50 dBA. At lower (<50dBA) and higher (>50dBA) amplitude ranges, a 10 dBA increase in sound level is related to a 5.4% increase and 1.9% decrease in physiological wellbeing respectively. Age, body-mass-index, high blood pressure, anxiety, and computer use intensive work are person-level factors contributing to heterogeneity in the sound-wellbeing association.

Basophils support the survival of plasma cells in mice.

We have previously shown that basophils support humoral memory immune responses by increasing B cell proliferation and Ig production as well as inducing a Th2 and B helper phenotype in T cells. Based on the high frequency of basophils in spleen and bone marrow, in this study we investigated whether basophils also support plasma cell survival and Ig production. In the absence of basophils, plasma cells of naive or immunized mice rapidly undergo apoptosis in vitro and produce only low amounts of Igs. In contrast, in the presence of basophils and even more in the presence of activated basophils, the survival of plasma cells is markedly increased and continuous production of Igs enabled. This effect is partially dependent on IL-4 and IL-6 released from basophils. Similar results were obtained when total bone marrow cells or bone marrow cells depleted of basophils were cultured in the presence or absence of substances activating basophils. When basophils were depleted in vivo 6 mo after immunization with an Ag, specific Ig production in subsequent bone marrow cultures was significantly reduced. In addition, depletion of basophils for 18 d in naive mice significantly reduced the number of plasma cells in the spleen. These data indicate that basophils are important for survival of plasma cells in vitro and in vivo.

Abundance and distribution of major groups of diazotrophic cyanobacteria and their potential contribution to N2 fixation in the tropical Atlantic Ocean.

The abundances of six N2-fixing cyanobacterial phylotypes were profiled at 22 stations across the tropical Atlantic Ocean during June 2006, and used to model the contribution of the diazotrophs to N2 fixation. Diazotroph abundances were measured by targeting the nifH gene of Trichodesmium, unicellular groups A, B, C (UCYN-A, UCYN-B and UCYN-C), and diatom-cyanobiont symbioses Hemiaulus-Richelia, Rhizosolenia-Richelia and Chaetoceros-Calothrix. West to east gradients in temperature, salinity and nutrients [NO3⁻ + NO2⁻, PO4³â», Si(OH)4] showed the influence of the Amazon River plume and its effect on the distributions of the diazotrophs. Trichodesmium accounted for more than 93% of all nifH genes detected, dominated the warmer waters of the western Atlantic, and was the only diazotroph detected at the equatorial upwelling station. UCYN-A was the next most abundant (> 5% of all nifH genes) and dominated the cooler waters of the eastern Atlantic near the Cape Verde Islands. UCYN-C was found at a single depth (200 m) of high salinity and low temperature and nutrients, whereas UCYN-B cells were widespread but in very low abundance (6.1 × 10¹ ± 4.6 × 10² gene copies l⁻¹). The diatom-cyanobionts were observed primarily in the western Atlantic within or near the high Si(OH)4 input of the Amazon River plume. Overall, highest diazotroph abundances were observed at the surface and declined with depth, except for some subsurface peaks in Trichodesmium, UCYN-B and UCYN-A. Modelled contributions of Trichodesmium, UCYN-B and UCYN-A to total N2 fixation suggested that Trichodesmium had the largest input, except for the potential of UCYN-A at the Cape Verde Islands.

Secondary use of routine data in hospitals: description of a scalable analytical platform based on a business intelligence system.

We describe a scalable platform for research-oriented analyses of routine data in hospitals, which evolved from a state-of-the-art business intelligence architecture for enterprise resource planning. This platform involves an in-memory database management system for data modeling and analytics and a high-performance cluster for more computing-intensive analytical tasks. Setting up platforms for research-oriented analyses is a highly dynamic, time-consuming, and costly process. In some health care institutions, effective research platforms may be derived from existing business intelligence systems.

IL-3 promotes the development of experimental autoimmune encephalitis.

Little is known about the role of IL-3 in multiple sclerosis (MS) in humans and in experimental autoimmune encephalomyelitis (EAE). Using myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE, we show that CD4+ T cells are the main source of IL-3 and that cerebral IL-3 expression correlates with the influx of T cells into the brain. Blockade of IL-3 with monoclonal antibodies, analysis of IL-3 deficient mice, and adoptive transfer of leukocytes demonstrate that IL-3 plays an important role for development of clinical symptoms of EAE, for migration of leukocytes into the brain, and for cerebral expression of adhesion molecules and chemokines. In contrast, injection of recombinant IL-3 exacerbates EAE symptoms and cerebral inflammation. In patients with relapsing-remitting MS (RRMS), IL-3 expression by T cells is markedly upregulated during episodes of relapse. Our data indicate that IL-3 plays an important role in EAE and may represent a new target for treatment of MS.

Chondroitin sulfate activates B cells in vitro, expands CD138+ cells in vivo, and interferes with established humoral immune responses.

Glycosaminoglycans have anti-inflammatory properties and interact with a variety of soluble and membrane-bound molecules. Little is known about their effects on B cells and humoral immune responses. We show that CS but not dextran or other glycosaminoglycans induces a pronounced proliferation of B cells in vitro compared with TLR4 or TLR9 ligands. With the use of inhibitors and KO mice, we demonstrate that this proliferation is mediated by the tyrosine kinases BTK and Syk but independent of CD44. Antibodies against Ig-α or Ig-ß completely block CS-induced B cell proliferation. Injection of CS in mice for 4-5 days expands B cells in the spleen and results in a marked increase of CD138(+) cells in the spleen that is dependent on BTK but independent of CD4(+) T cells. Long-term treatment with CS for 14 days also increases CD138(+) cells in the bone marrow. When mice were immunized with APC or collagen and treated with CS for up to 14 days during primary or after secondary immune responses, antigen-specific humoral immune responses and antigen-specific CD138(+) plasma cells in the bone marrow were reduced significantly. These data show that CD138(+) cells, induced by treatment with CS, migrate into the bone marrow and may displace other antigen-specific plasma cells. Overall, CS is able to interfere markedly with primary and fully established humoral immune responses in mice.

Important role of interleukin-3 in the early phase of collagen-induced arthritis.

OBJECTIVE: Activation of basophils contributes to memory immune responses and results in exacerbation of collagen-induced arthritis (CIA). We undertook the present study to analyze the production and biologic effects of interleukin-3 (IL-3), a strong activator of basophils, in CIA. METHODS: Arthritis was induced by immunization with type II collagen. Mice were treated with blocking monoclonal antibodies against IL-3 or with recombinant IL-3. Clinical scoring, histologic analysis, fluorescence-activated cell sorter analysis, enzyme-linked immunosorbent assay, and cell culturing were performed to assess disease activity and IL-3 production. RESULTS: IL-3 was produced in large quantities by collagen-specific CD4+ T cells in the spleen and was present in the synovial tissue during onset of arthritis, but was down-regulated in paws with severe inflammation. Blockade of IL-3 during the time of arthritis onset resulted in profound improvement of the disease, with reductions in synovial leukocyte and cytokine levels, peripheral blood basophil levels, and anticollagen antibody titers. Blockade of IL-3 during the late phase of arthritis had no beneficial effect. Administration of recombinant IL-3 during onset of arthritis induced a marked exacerbation of the disease, with increased peripheral blood basophil and plasma IL-6 levels and increased titers of anticollagen antibody. In studies of the regulation of IL-3 expression in CD4+ T cells, IL-6 and IL-4 suppressed the release of IL-3 by activated CD4+ T cells, whereas lipopolysaccharide and CpG DNA up-regulated IL-3 secretion in activated CD4+ T cells by acting on costimulatory cells. CONCLUSION: Taken together, the present results demonstrate for the first time that IL-3 has an important role in the early phase of CIA.

GROWTH AND CARBON CONTENT OF THREE DIFFERENT-SIZED DIAZOTROPHIC CYANOBACTERIA OBSERVED IN THE SUBTROPICAL NORTH PACIFIC(1).

To develop tools for modeling diazotrophic growth in the open ocean, we determined the maximum growth rate and carbon content for three diazotrophic cyanobacteria commonly observed at Station ALOHA (A Long-term Oligotrophic Habitat Assessment) in the subtropical North Pacific: filamentous nonheterocyst-forming Trichodesmium and unicellular Groups A and B. Growth-irradiance responses of Trichodesmium erythraeum Ehrenb. strain IMS101 and Crocosphaera watsonii J. Waterbury strain WH8501 were measured in the laboratory. No significant differences were detected between their fitted parameters (±CI) for maximum growth rate (0.51 ± 0.09 vs. 0.49 ± 0.17 d(-1) ), half-light saturation (73 ± 29 vs. 66 ± 37 µmol quanta · m(-2) · s(-1) ), and photoinhibition (0 and 0.00043 ± 0.00087 [µmol quanta · m(-2) · s(-1) ](-1) ). Maximum growth rates and carbon contents of Trichodesmium and Crocosphaera cultures conformed to published allometric relationships, demonstrating that these relationships apply to oceanic diazotrophic microorganisms. This agreement promoted the use of allometric models to approximate unknown parameters of maximum growth rate (0.77 d(-1) ) and carbon content (480 fg C · µm(-3) ) for the uncultivated, unicellular Group A cyanobacteria. The size of Group A was characterized from samples from the North Pacific Ocean using fluorescence-activated cell sorting and real-time quantitative PCR techniques. Knowledge of growth and carbon content properties of these organisms facilitates the incorporation of different types of cyanobacteria in modeling efforts aimed at assessing the relative importance of filamentous and unicellular diazotrophs to carbon and nitrogen cycling in the open ocean.

Modeled contributions of three types of diazotrophs to nitrogen fixation at Station ALOHA.

A diagnostic model based on biomass and growth was used to assess the relative contributions of filamentous nonheterocystous Trichodesmium and unicellular cyanobacteria, termed Groups A and B, to nitrogen fixation at the North Pacific Station ALOHA over a 2-year period. Average (and 95% confidence interval, CI) annual rates of modeled monthly values for Trichodesmium, Group B and Group A were 92 (52), 14 (4) and 12 (8) mmol N per m(2) per year, respectively. The fractional contribution to modeled instantaneous nitrogen fixation by each diazotroph fluctuated on interannual, seasonal and shorter time scales. Trichodesmium fixed substantially more nitrogen in year 1 (162) than year 2 (12). Group B fixed almost two times more nitrogen in year 1 (17) than year 2 (9). In contrast, Group A fixed two times more nitrogen in year 2 (16) than year 1 (8). When including uncertainties in our estimates using the bootstrap approach, the range of unicellular nitrogen fixation extended from 10% to 68% of the total annual rate of nitrogen fixation for all three diazotrophs. Furthermore, on a seasonal basis, the model demonstrated that unicellular diazotrophs fixed the majority (51%-97%) of nitrogen during winter and spring, whereas Trichodesmium dominated nitrogen fixation during summer and autumn (60%-96%). Sensitivity of the modeled rates to some parameters suggests that this unique attempt to quantify relative rates of nitrogen fixation by different diazotrophs may need to be reevaluated as additional information on cell size, variability in biomass and C:N, and growth characteristics of the different cyanobacterial diazotrophs become available.