Seasonal changes of Antarctic marine bacterioplankton

During a one-year period the development of the Antarctic coastal seawater bacterioplankton was followed. Two field stations (surface and deep water = 20 m, respectively) were sampled daily in 1989 in " Terre Adelie area". The survey included physicochemical (temperature and particulate organic matter) and bacteriological (total and heterotrophic bacteria, bacterial production) measurements. Whereas bacterial parameters at the deep water station remained fairly constant, bacterial parameters in surface waters generally increased during the year obviously related to the formation of sea ice

Impact of heat stress on dairy cattle and selection strategies for thermotolerance: a review

Climate change is a problem that causes many environmental issues that impact the productivity of livestock species. One of the major issues associated with climate change is an increase of the frequency of hot days and heat waves, which increases the risk of heat stress for livestock species. Dairy cattle have been identified as being susceptible to heat stress due to their high metabolic heat load. Studies have shown heat stress impacts several biological processes that can result in large economic consequences. When heat stress occurs, dairy cattle employ several physiological and cellular mechanisms in order to dissipate heat and protect cells from damage. These mechanisms require an increase and diversion in energy toward protection and away from other biological processes. Therefore, in turn heat stress in dairy cattle can lead numerous issues including reductions in milk production and reproduction as well as increased risk for disease and mortality. This indicates a need to select dairy cattle that would be thermotolerant. Various selection strategies to confer thermotolerance have been discussed in the literature, including selecting for reduced milk production, crossbreeding with thermotolerant breeds, selecting based on physiological traits and most recently selecting for enhanced immune response. This review discusses the various issues associated with heat stress in dairy cattle and the pros and cons to the various selection strategies that have been proposed to select for thermotolerance in dairy cattle

A Systematic Review of Magnesium Sulfate for Perinatal Neuroprotection: What Have We Learnt From the Past Decade?

There is an important unmet need to improve long term outcomes of encephalopathy for preterm and term infants. Meta-analyses of large controlled trials suggest that maternal treatment with magnesium sulfate (MgSO4) is associated with a reduced risk of cerebral palsy and gross motor dysfunction after premature birth. However, to date, follow up to school age has found an apparent lack of long-term clinical benefit. Because of this inconsistency, it remains controversial whether MgSO4 offers sustained neuroprotection. We systematically reviewed preclinical and clinical studies reported from January 1 2010, to January 31 2020 to evaluate the most recent advances and knowledge gaps relating to the efficacy of MgSO4 for the treatment of perinatal brain injury. The outcomes of MgSO4 in preterm and term-equivalent animal models of perinatal encephalopathy were highly inconsistent between studies. None of the perinatal rodent studies that suggested benefit directly controlled body or brain temperature. The majority of the studies did not control for sex, study long term histological and functional outcomes or use pragmatic treatment regimens and many did not report controlling for potential study bias. Finally, most of the recent preterm or term human studies that tested the potential of MgSO4 for perinatal neuroprotection were relatively underpowered, but nevertheless, suggest that any improvements in neurodevelopment were at best modest or absent. On balance, these data suggest that further rigorous testing in translational preclinical models of perinatal encephalopathy is essential to ensure safety and best regimens for optimal preterm neuroprotection, and before further clinical trials of MgSO4 for perinatal encephalopathy at term are undertaken

Experimental investigation of planar ion traps

Chiaverini et al. [Quant. Inf. Comput. 5, 419 (2005)] recently suggested a linear Paul trap geometry for ion trap quantum computation that places all of the electrodes in a plane. Such planar ion traps are compatible with modern semiconductor fabrication techniques and can be scaled to make compact, many zone traps. In this paper we present an experimental realization of planar ion traps using electrodes on a printed circuit board to trap linear chains of tens of 0.44 micron diameter charged particles in a vacuum of 15 Pa (0.1 torr). With these traps we address concerns about the low trap depth of planar ion traps and develop control electrode layouts for moving ions between trap zones without facing some of the technical difficulties involved in an atomic ion trap experiment. Specifically, we use a trap with 36 zones (77 electrodes) arranged in a cross to demonstrate loading from a traditional four rod linear Paul trap, linear ion movement, splitting and joining of ion chains, and movement of ions through intersections. We further propose an additional DC biased electrode above the trap which increases the trap depth dramatically, and a novel planar ion trap geometry that generates a two dimensional lattice of point Paul traps.Comment: 11 pages, 20 figure

Galectin-3 Modulates Microglia Inflammation in vitro but Not Neonatal Brain Injury in vivo under Inflammatory Conditions

Microglia may contribute to injury but may also have neuroprotective properties. Galectin-3 has immunomodulatory properties that may affect the microglia phenotype and subsequent development of injury. Galectin-3 contributes to experimental hypoxic-ischemic (HI) injury in the neonatal brain, but it is unclear if galectin-3 has similar effects on infectious and sterile inflammation. Thus, we investigated the effect of galectin-3 on microglia in vitro under normal as well as infectious and sterile inflammatory conditions, and the effect of galectin-3 on neonatal brain injury following an infectious challenge in vivo. Conditions mimicking infectious or sterile inflammation were evaluated in primary microglia cell cultures from newborn mice, using LPS (10 ng/mL) and TNF-alpha (100 ng/mL). The response to galectin-3 was tested alone or together with LPS or TNF-alpha. Supernatants were collected 24 h after treatment and analyzed for 23 inflammatory mediators including pro- and anti-inflammatory cytokines and chemokines using multiplex protein analysis, as well as ELISA for MCP-1 and insulin-like growth factor (IGF)-1. Phosphorylation of proteins (AKT, ERK1/2, I kappa B-alpha, JNK, and p38) was determined in microglia cells. Neonatal brain injury was induced by a combination of LPS and HI (LPS + HI) in postnatal day 9 transgenic mice lacking functional galectin-3 and wild-type controls. LPS and TNF-alpha induced pro-inflammatory (9/11 vs. 9/10) and anti-inflammatory (6/6 vs. 2/6) cytokines, as well as chemokines (6/6 vs. 4/6) in a similar manner, except generally lower amplitude of the TNF-alpha-induced response. Galectin-3 alone had no effect on any of the proteins analyzed. Galectin-3 reduced the LPS- and TNF-alpha-induced microglia response for cytokines, chemokines, and phosphorylation of I kappa B-alpha. LPS decreased baseline IGF-1 levels, and the levels were restored by galectin-3. Brain injury or microglia response after LPS + HI was not affected by galectin-3 deficiency. Galectin-3 has no independent effect on microglia but modulates inflammatory activation in vitro. The effect was similar under infectious and sterile inflammatory conditions, suggesting that galectin-3 regulates inflammation not just by binding to LPS or toll-like receptor-4. Galectin-3 restores IGF-1 levels reduced by LPS-induced inflammation, suggesting a potential protective effect on infectious injury. However, galectin-3 deficiency did not affect microglia activation and was not beneficial in an injury model encompassing an infectious challenge

Evidence for Sexual Dimorphism in the Response to TLR3 Activation in the Developing Neonatal Mouse Brain: A Pilot Study

Toll-like receptor (TLR)3 activation during the neonatal period produces responses linked to the origins of neuropsychiatric disorders. Although there is sexual dimorphism in neuropsychiatric disorders, it is unknown if brain responses to TLR3 activation are sex-specific. We hypothesized that poly I:C in a post-natal day (P)8 model induces a sexually dimorphic inflammatory responses. C57BL6 mice received intraperitoneal injection of poly I:C (10 mg/kg) or vehicle [normal saline (NS)] at P8. Pups were killed at 6 or 14 h for caspase 3 and 8 activity assays, NFkB ELISA, IRF3, AP1, and GFAP western blotting and cytokines/chemokines gene expression real time qRT-PCR (4–6/group). A second group of pups were killed at 24 h (P9) or 7 days (P15) after poly I:C to assess astrocytic (GFAP) and microglia (Iba1) activation in the hippocampus, thalamus and cortex using immunohistochemistry, and gene and protein expression of cytokines/chemokines using real time RT-PCR and MSD, respectively (4–6/group). Non-parametric analysis was applied. Six hours after poly I:C, caspase-3 and -8 activities in cytosolic fractions were 1.6 and 2.8-fold higher in poly I:C-treated than in NS-treated female mice, respectively, while gene expressions of pro-inflammatory cytokines were upregulated in both sexes. After poly I:C, IRF3 nuclear translocation occurred earlier (6 h) in female mice and later (14 h) in male mice. At 14 h after poly I:C, only male mice also had increased nuclear NFκB levels (88%, p < 0.001) and GFAP expression coinciding with persistent IL-6 and FAS gene upregulation (110 and 77%, respectively; p < 0.001) and IL-10 gene downregulation (-42%, p < 0.05). At 24 h after poly I:C, IL-1β, CXCL-10, TNF-α, and MCP-1 were similarly increased in both sexes but at 7 days after exposure, CXCL-10 and INFγ were increased and IL-10 was decreased only in female mice. Accordingly, microglial activation persisted at 7 days after poly I:C in the hippocampus, thalamus and cortex of female mice. This preliminary study suggests that TLR3 activation may produce in the developing neonatal mouse brain a sexually dimorphic response with early activation of caspase-dependent pathways in female mice, activation of inflammatory cascades in both sexes, which then persists in female mice. Further well-powered studies are essential to confirm these sex-specific findings

A distant trophoblast-specific enhancer controls HLA-G expression at the maternal–fetal interface

HLA-G, a nonclassical HLA molecule uniquely expressed in the placenta, is a central component of fetus-induced immune tolerance during pregnancy. The tissue-specific expression of HLA-G, however, remains poorly understood. Here, systematic interrogation of the HLA-G locus using massively parallel reporter assay (MPRA) uncovered a previously unidentified cis-regulatory element 12 kb upstream of HLA-G with enhancer activity, Enhancer L. Strikingly, clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of this enhancer resulted in ablation of HLA-G expression in JEG3 cells and in primary human trophoblasts isolated from placenta. RNA-seq analysis demonstrated that Enhancer L specifically controls HLA-G expression. Moreover, DNase-seq and chromatin conformation capture (3C) defined Enhancer L as a cell type-specific enhancer that loops into the HLA-G promoter. Interestingly, MPRA-based saturation mutagenesis of Enhancer L identified motifs for transcription factors of the CEBP and GATA families essential for placentation. These factors associate with Enhancer L and regulate HLA-G expression. Our findings identify long-range chromatin looping mediated by core trophoblast transcription factors as the mechanism controlling tissue-specific HLA-G expression at the maternal–fetal interface. More broadly, these results establish the combination of MPRA and CRISPR/Cas9 deletion as a powerful strategy to investigate human immune gene regulation

The potential effects of climate change on air quality across the conterminous US at 2030 under three Representative Concentration Pathways

The potential impacts of climate change on regional ozone (O3) and fine particulate (PM2.5) air quality in the United States (US) are investigated by linking global climate simulations with regional-scale meteorological and chemical transport models. Regional climate at 2000 and at 2030 under three Representative Concentration Pathways (RCPs) is simulated by using the Weather Research and Forecasting (WRF) model to downscale 11-year time slices from the Community Earth System Model (CESM). The downscaled meteorology is then used with the Community Multiscale Air Quality (CMAQ) model to simulate air quality during each of these 11-year periods. The analysis isolates the future air quality differences arising from climate-driven changes in meteorological parameters and specific natural emissions sources that are strongly influenced by meteorology. Other factors that will affect future air quality, such as anthropogenic air pollutant emissions and chemical boundary conditions, are unchanged across the simulations. The regional climate fields represent historical daily maximum and daily minimum temperatures well, with mean biases of less than 2&thinsp;K for most regions of the US and most seasons of the year and good representation of variability. Precipitation in the central and eastern US is well simulated for the historical period, with seasonal and annual biases generally less than 25&thinsp;%, with positive biases exceeding 25&thinsp;% in the western US throughout the year and in part of the eastern US during summer. Maximum daily 8&thinsp;h ozone (MDA8 O3) is projected to increase during summer and autumn in the central and eastern US. The increase in summer mean MDA8 O3 is largest under RCP8.5, exceeding 4&thinsp;ppb in some locations, with smaller seasonal mean increases of up to 2&thinsp;ppb simulated during autumn and changes during spring generally less than 1&thinsp;ppb. Increases are magnified at the upper end of the O3 distribution, particularly where projected increases in temperature are greater. Annual average PM2.5 concentration changes range from −1.0 to 1.0&thinsp;µg&thinsp;m−3. Organic PM2.5 concentrations increase during summer and autumn due to increased biogenic emissions. Aerosol nitrate decreases during winter, accompanied by lesser decreases in ammonium and sulfate, due to warmer temperatures causing increased partitioning to the gas phase. Among meteorological factors examined to account for modeled changes in pollution, temperature and isoprene emissions are found to have the largest changes and the greatest impact on O3 concentrations.</p

Effects of transient donor chimerism on rejection of MHC-mismatched vascularized composite allografts in swine

Background: Despite encouraging outcomes in vascularized composite allograft (VCA) transplantation, the risks of chronic immunosuppression limit widespread applicability. It has been suggested that infusion of donor bone marrow along with the VCA may reduce the level of immunosuppression required to prevent clinical VCA rejection. However, no clear evidence has yet been presented to confirm the role of donor bone marrow in the prevention of rejection. In this study we investigated the immunologic effects of concurrent bone marrow transplantation in a large animal VCA model. Methods: MGH miniature swine (n=4) received a non-myeloablative conditioning regimen consisting of low-dose total body irradiation, T-cell depletion, a short course of Cyclosporine A, with or without varying doses of donor bone marrow cells in combination with a complete MHC-mismatched VCA. Animals were monitored daily for signs of rejection or graft versus host disease. Chimerism levels were assessed using flow cytometry and in vitro assays were performed to assess for donor-specific responses. Results: Transient chimerism was prolonged with increased bone marrow cell doses and total body irradiation. While animals that received BMC infusions did not have significantly prolonged VCA acceptance following cessation of immunosuppression compared to animals that received conditioning without BMCs, they demonstrated better early clinical outcomes and demonstrated donor-specific unresponsiveness during the presence of detectable chimerism. Conclusions: Detectable mixed chimerism following bone marrow transplantation and VCA mitigates donor-specific responses and acute rejection episodes, but does not appear to be sufficient for tolerance induction

Low-cost rapid detection of rifampicin resistant tuberculosis using bacteriophage in Kampala, Uganda

BACKGROUND: Resistance to anti-tuberculosis drugs is a serious public health problem. Multi-drug resistant tuberculosis (MDR-TB), defined as resistance to at least rifampicin and isoniazid, has been reported in all regions of the world. Current phenotypic methods of assessing drug susceptibility of M. tuberculosis are slow. Rapid molecular methods to detect resistance to rifampicin have been developed but they are not affordable in some high prevalence countries such as those in sub Saharan Africa. A simple multi-well plate assay using mycobacteriophage D29 has been developed to test M. tuberculosis isolates for resistance to rifampicin. The purpose of this study was to investigate the performance of this technology in Kampala, Uganda. METHODS: In a blinded study 149 M. tuberculosis isolates were tested for resistance to rifampicin by the phage assay and results compared to those from routine phenotypic testing in BACTEC 460. Three concentrations of drug were used 2, 4 and 10 μg/ml. Isolates found resistant by either assay were subjected to sequence analysis of a 81 bp fragment of the rpoB gene to identify mutations predictive of resistance. Four isolates with discrepant phage and BACTEC results were tested in a second phenotypic assay to determine minimal inhibitory concentrations. RESULTS: Initial analysis suggested a sensitivity and specificity of 100% and 96.5% respectively for the phage assay used at 4 and 10 μg/ml when compared to the BACTEC 460. However, further analysis revealed 4 false negative results from the BACTEC 460 and the phage assay proved the more sensitive and specific of the two tests. Of the 39 isolates found resistant by the phage assay 38 (97.4%) were found to have mutations predictive of resistance in the 81 bp region of the rpoB gene. When used at 2 μg/ml false resistant results were observed from the phage assay. The cost of reagents for testing each isolate was estimated to be 1.3US$ when testing a batch of 20 isolates on a single 96 well plate. Results were obtained in 48 hours. CONCLUSION: The phage assay can be used for screening of isolates for resistance to rifampicin, with high sensitivity and specificity in Uganda. The test may be useful in poorly resourced laboratories as a rapid screen to differentiate between rifampicin susceptible and potential MDR-TB cases