Intensifying existing urban wastewater Winkler, M-K H; van Loosdrecht, M C M
Science (American Association for the Advancement of Science),
01/2022, Letnik:
375, Številka:
6579
Journal Article
INTRODUCTION: Despite all our dreams and enthusiasm, the essential question of whether our species can ever live permanently in space remains unanswered. The 1975 NASA Ames Design Study on Space ...Settlements demonstrated how human physiology constrains and determines human habitat
design in space. Our scientific understanding about the risks of and standards for microgravity (and rotation rate if centrifugally generated), ionizing radiation, and atmosphere pressure and composition, remains inadequate a half century later. In addition, there are newly recognized physiological
challenges to living safely in space, including spaceflight-associated neuro-ocular syndrome (SANS), extravascular hemolytic anemia, and other factors that affect every human cell and organ system. A comprehensive review was conducted to establish what we have learned and what is still required
to know about the pathophysiology of long-term space travel and living in space since my first report in 1978. The results determine not only how, but if we can realistically plan to inhabit the cosmos that surrounds us.Winkler LH. Human physiological limitations to long-term spaceflight
and living in space. Aerosp Med Hum Perform. 2023; 94(6):444-456.
The minimal physical activity intensity that would confer health benefits among adolescents is unknown. The purpose of this study was to examine the associations of accelerometer-derived ...light-intensity (split into low and high) physical activity, and moderate- to vigorous-intensity physical activity with cardiometabolic biomarkers in a large population-based sample.
The study is based on 1,731 adolescents, aged 12-19 years from the 2003/04 and 2005/06 National Health and Nutrition Examination Survey. Low light-intensity activity (100-799 counts/min), high light-intensity activity (800 counts/min to <4 METs) and moderate- to vigorous-intensity activity (≥ 4 METs, Freedson age-specific equation) were accelerometer-derived. Cardiometabolic biomarkers, including waist circumference, systolic blood pressure, diastolic blood pressure, HDL-cholesterol, and C-reactive protein were measured. Triglycerides, LDL- cholesterol, insulin, glucose, and homeostatic model assessments of β-cell function (HOMA-%B) and insulin sensitivity (HOMA-%S) were also measured in a fasting sub-sample (n=807).
Adjusted for confounders, each additional hour/day of low light-intensity activity was associated with 0.59 (95% CI: 1.18-0.01) mmHG lower diastolic blood pressure. Each additional hour/day of high light-intensity activity was associated with 1.67 (2.94-0.39) mmHG lower diastolic blood pressure and 0.04 (0.001-0.07) mmol/L higher HDL-cholesterol. Each additional hour/day of moderate- to vigorous-intensity activity was associated with 3.54 (5.73-1.35) mmHG lower systolic blood pressure, 5.49 (1.11-9.77)% lower waist circumference, 25.87 (6.08-49.34)% lower insulin, and 16.18 (4.92-28.53)% higher HOMA-%S.
Time spent in low light-intensity physical activity and high light-intensity physical activity had some favorable associations with biomarkers. Consistent with current physical activity recommendations for adolescents, moderate- to vigorous-intensity activity had favorable associations with many cardiometabolic biomarkers. While increasing MVPA should still be a public health priority, further studies are needed to identify dose-response relationships for light-intensity activity thresholds to inform future recommendations and interventions for adolescents.
High amounts of time spent sitting can increase cardiovascular disease risk and are deleteriously associated cardio-metabolic risk biomarkers. Though evidence suggests that accruing sitting time in ...prolonged periods may convey additional risk, verification using high-quality measures is needed. We examined this issue in adults from the Australian Diabetes, Obesity and Lifestyle Study, using accurate measures of sitting accumulation.
In 2011/12, 739 adults aged 36 to 89 years (mean±SD 58±10 years) wore activPAL3™ monitors (which provide accurate objective measures of sitting); 678 provided ≥4 valid days of monitor data and complete cardio-metabolic biomarker and confounder data. Multivariable linear regression models examined associations of sitting time, sitting time accrued in ≥30 minute bouts (prolonged sitting time), and three measures of sitting accumulation patterns with cardio-metabolic risk markers: body mass index (BMI), waist circumference, blood pressure, high- and low- density lipoprotein (HDL and LDL) cholesterol, triglycerides, glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and 2-hour post-load glucose (PLG). Interactions tests examined whether associations of sitting time with biomarkers varied by usual sitting bout duration.
Adjusted for potential confounders, greater amounts of sitting time and prolonged sitting time were significantly (p<0.05) deleteriously associated with BMI, waist circumference, HDL cholesterol, and triglycerides. Total sitting time was also significantly associated with higher PLG. Sitting accumulation patterns of frequently interrupted sitting (compared to patterns with relatively more prolonged sitting) were significantly beneficially associated with BMI, waist circumference, HDL cholesterol, triglycerides, PLG, and with FPG. Effect sizes were typically larger for accumulation patterns than for sitting time. Significant interactions (p<0.05) showed that associations of sitting time with HDL, triglycerides and PLG became more deleterious the longer at a time sitting was usually accumulated.
Adding to previous evidence reliant on low-quality measures, our study showed that accumulating sitting in patterns where sitting was most frequently interrupted had significant beneficial associations with several cardio-metabolic biomarkers and that sitting for prolonged periods at a time may exacerbate some of the effects of sitting time. The findings support sedentary behavior guidelines that promote reducing and regularly interrupting sitting.
Human cytomegalovirus (HCMV) is an important, ubiquitous pathogen that causes severe clinical disease in immunocompromised individuals, such as organ transplant recipients and infants infected in ...utero. Antiviral chemotherapy remains problematic due to toxicity of the available compounds and the emergence of viruses resistant to available antiviral therapies. Antiviral antibodies could represent a valuable alternative strategy to limit the clinical consequences of viral disease in patients. The envelope glycoprotein B (gB) of HCMV is a major antigen for the induction of virus neutralizing antibodies. However, the role of anti-gB antibodies in the course of the infection in-vivo remains unknown. We have used a murine CMV (MCMV) model to generate and study a number of anti-gB monoclonal antibodies (mAbs) with differing virus-neutralizing capacities. The mAbs were found to bind to similar antigenic structures on MCMV gB that are represented in HCMV gB. When mAbs were used in immunodeficient RAG-/- hosts to limit an ongoing infection we observed a reduction in viral load both with mAbs having potent neutralizing capacity in-vitro as well as mAbs classified as non-neutralizing. In a therapeutic setting, neutralizing mAbs showed a greater capacity to reduce the viral burden compared to non-neutralizing antibodies. Efficacy was correlated with sustained concentration of virus neutralizing mAbs in-vivo rather than their in-vitro neutralizing capacity. Combinations of neutralizing mAbs further augmented the antiviral effect and were found to be as potent in protection as polyvalent serum from immune animals. Prophylactic administration of mAbs before infection was also protective and both neutralizing and non-neutralizing mAbs were equally effective in preventing lethal infection of immunodeficient mice. In summary, our data argue that therapeutic application of potently neutralizing mAbs against gB represent a strategy to modify the outcome of CMV infection in immunodeficient hosts. When present before infection, both neutralizing and non-neutralizing anti-gB exhibited protective capacity.
Metastasis is the major cause of cancer-associated death. Partial activation of the epithelial-to-mesenchymal transition program (partial EMT) was considered a major driver of tumour progression from ...initiation to metastasis. However, the role of EMT in promoting metastasis has recently been challenged, in particular concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in pancreatic cancer. In contrast, we show here that in the same pancreatic cancer model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model), the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion and notably metastasis. Depletion of Zeb1 suppresses stemness, colonization capacity and in particular phenotypic/metabolic plasticity of tumour cells, probably causing the observed in vivo effects. Accordingly, we conclude that different EMT-TFs have complementary subfunctions in driving pancreatic tumour metastasis. Therapeutic strategies should consider these potential specificities of EMT-TFs to target these factors simultaneously.
Ammonia-oxidizing archaea (AOA) are among the most abundant and ubiquitous microorganisms in the ocean, exerting primary control on nitrification and nitrogen oxides emission. Although united by a ...common physiology of chemoautotrophic growth on ammonia, a corresponding high genomic and habitat variability suggests tremendous adaptive capacity. Here, we compared 44 diverse AOA genomes, 37 from species cultivated from samples collected across diverse geographic locations and seven assembled from metagenomic sequences from the mesopelagic to hadopelagic zones of the deep ocean. Comparative analysis identified seven major marine AOA genotypic groups having gene content correlated with their distinctive biogeographies. Phosphorus and ammonia availabilities as well as hydrostatic pressure were identified as selective forces driving marine AOA genotypic and gene content variability in different oceanic regions. Notably, AOA methylphosphonate biosynthetic genes span diverse oceanic provinces, reinforcing their importance for methane production in the ocean. Together, our combined comparative physiological, genomic, and metagenomic analyses provide a comprehensive view of the biogeography of globally abundant AOA and their adaptive radiation into a vast range of marine and terrestrial habitats.
To examine the associations of sedentary time and physical activity with biomarkers of cardiometabolic health, including the potential collective impact of shifting mean time use from less- to ...more-active behaviours (cross-sectionally, using isotemporal substitution), in adults with type 2 diabetes.
Participants with overweight/obese body mass index (BMI; ≥25 kg/m2) (n = 279; 158 men, mean SD age = 58.2 8.6 years) wore Actigraph GT1M accelerometers (waking hours; seven days) to assess moderate- to vigorous-intensity physical activity (MVPA), light-intensity activity, and sedentary time (segregated into non-prolonged accumulated in bouts <30min and prolonged accumulated in bouts ≥30 min). Cross-sectional associations with waist circumference, BMI, fasting blood (HbA1c, glucose, triacylglycerols, high-density lipoprotein cholesterol), and blood pressure of these activity variables (30 min/day increments) were examined adjusted for confounders and wear then, if significant, examined using isotemporal substitution modelling.
Waist circumference and BMI were significantly (p<0.05) associated with more prolonged sedentary time and less light-intensity activity. Light intensity activity was also significantly associated with lower fasting plasma glucose (relative rate: 0.98, 95% CI: 0.97, 1.00; p<0.05). No biomarker was significantly associated with non-prolonged sedentary time or MVPA. Lower mean prolonged sedentary time (-30 min/day) with higher mean light intensity time (+30 min/day) was significantly associated with lower waist circumference (β = -0.77, 95% CI: -1.33, -0.22 cm). Lower mean prolonged sedentary time (-30 min/day) with either 30 min/day higher mean non-prolonged sedentary time (β = -0.35, 95%CI: -0.70, -0.01 kg/m2) or light-intensity time (β = -0.36, -0.61, -0.11 kg/m2) was associated with significantly lower average BMI.
Significantly improved mean levels of waist circumference and BMI were observed when shifting time from prolonged sedentary to non-prolonged sedentary or light-intensity activity (cross-sectionally). Lifestyle interventions in overweight/obese adults with type 2 diabetes might consider targeting shifts in these non-MVPA activities to more rigorously evaluate their potential cardiometabolic benefit in this population.
Around four decades ago, it had been observed that there were cell lines as well as cells in the fetal liver that expressed antibody μ heavy (μH) chains in the apparent absence of
light chains. It ...was thus possible that these cells expressed another molecule(s), that assembled with μH chains. The ensuing studies led to the discovery of the pre-B cell receptor (pre-BCR), which is assembled from Ig μH and surrogate light (SL) chains, together with the signaling molecules Igα and β. It is expressed on a fraction of pro-B (pre-BI) cells and most large pre-B(II) cells, and has been implicated in IgH chain allelic exclusion and down-regulation of the recombination machinery, assessment of the expressed μH chains and shaping the IgH repertoire, transition from the pro-B to pre-B stage, pre-B cell expansion, and cessation.
In aerobic granular sludge (AGS), the growth of nitrite oxidizing bacteria (NOB) can be uncoupled from the nitrite supply of ammonia oxidizing bacteria (AOB). Besides, unlike for conventional ...activated sludge, Nitrobacter was found to be the dominant NOB and not Nitrospira. To explain these experimental observations, two possible pathways have been put forward in literature. The first one involves the availability of additional nitrite from partial denitrification (nitrite-loop) and the second one consists of mixotrophic growth of Nitrobacter in the presence of acetate (ping-pong). In this contribution, mathematical models were set up to assess the possibility of these pathways to explain the reported observations. Simulation results revealed that both pathways influenced the nitrifier distribution in the granules. The nitrite-loop pathway led to an elevated NOB/AOB ratio, while mixotrophic growth of Nitrobacter guaranteed their predominance among the NOB population. Besides, mixotrophic growth of Nitrobacter could lead to NO emission from AGS. An increasing temperature and/or a decreasing oxygen concentration led to an elevated NOB/AOB ratio and increased NO emissions.