Cyanobacterial nitrogen fixation in arid soils of Central Australia

Abstract The distribution of nitrogen-fixing cyanobacteria was studied in two regions of Central Australia, one near Yulara and the other in the Ti-Tree Basin. Soil and other samples were tested in situ for nitrogen fixation by the acethylene reduction assay. They were then enriched in low light in suitable growth medium containing no fixed carbon or nitrogen over a period of months. The cyanobacterial components were identified and their nitrogen-fixing capacity measured again both in the light and in darkness. It is concluded that a variety of genera of cyanobacteria survive in the arid region of Central Australia and can be assumed to contribute fixed nitrogen to the soils of the region.     

“Infant Mortality in Armenia 1992–2003”: A comment

The purpose of this comment is to counsel caution in some of the conclusions drawn in an otherwise fine article recently published in Economics and Human Biology on infant mortality in Armenia by Hakobyan, Mkrtchyan and Yepiskoposyan. These relate first, to the reliability of estimates and trends in infant mortality estimated from DHS data; second, to the interpretation of what the authors consider to be a ‘low’ infant mortality rate in former communist countries given their level of economic development; and third, to the role of the health care infrastructure in countries of the former Soviet Union in producing these ‘low’ infant mortality levels. This comment argues that trends in infant mortality in Armenia and other CIS countries, although probably declining, are perhaps less certain than the authors allow, that existing evidence does not suggest that they are uniformly low by global standards, or that the health care systems in CIS countries are uniformly effective in reducing infant deaths.     

Development of a novel mammalian display system for selection of antibodies against membrane proteins

Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 10⁹ variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (K_D) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies.     

The critical role of T cells in glucocorticoid-induced osteoporosis

Glucocorticoids (GC) are widely used clinically, despite the presence of significant side effects, including glucocorticoid-induced osteoporosis (GIOP). While GC are believed to act directly on osteoblasts and osteoclasts to promote osteoporosis, the detailed underlying molecular mechanism of GC-induced osteoporosis is still not fully elucidated. Here, we show that lymphocytes play a pivotal role in regulating GC-induced osteoporosis. We show that GIOP could not be induced in SCID mice that lack T cells, but it could be re-established by adoptive transfer of splenic T cells from wild-type mice. As expected, T cells in the periphery are greatly reduced by GC; instead, they accumulate in the bone marrow where they are protected from GC-induced apoptosis. These bone marrow T cells in GC-treated mice express high steady-state levels of NF-κB receptor activator ligand (RANKL), which promotes the formation and maturation of osteoclasts and induces osteoporosis. Taken together, these findings reveal a critical role for T cells in GIOP.Subject terms: Mechanisms of disease, Osteoimmunology     

International gestational age-specific centiles for blood pressure in pregnancy from the INTERGROWTH-21st Project in 8 countries: A longitudinal cohort study

BackgroundGestational hypertensive and acute hypotensive disorders are associated with maternal morbidity and mortality worldwide. However, physiological blood pressure changes in pregnancy are insufficiently defined. We describe blood pressure changes across healthy pregnancies from the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Fetal Growth Longitudinal Study (FGLS) to produce international, gestational age-specific, smoothed centiles (third, 10th, 50th, 90th, and 97th) for blood pressure.Methods and findingsSecondary analysis of a prospective, longitudinal, observational cohort study (2009 to 2016) was conducted across 8 diverse urban areas in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States of America. We enrolled healthy women at low risk of pregnancy complications. We measured blood pressure using standardised methodology and validated equipment at enrolment at <14 weeks, then every 5 ± 1 weeks until delivery.We enrolled 4,607 (35%) women of 13,108 screened. The mean maternal age was 28·4 (standard deviation [SD] 3.9) years; 97% (4,204/4,321) of women were married or living with a partner, and 68% (2,955/4,321) were nulliparous. Their mean body mass index (BMI) was 23.3 (SD 3.0) kg/m². Systolic blood pressure was lowest at 12 weeks: Median was 111.5 (95% CI 111.3 to 111.8) mmHg, rising to a median maximum of 119.6 (95% CI 118.9 to 120.3) mmHg at 40 weeks’ gestation, a difference of 8.1 (95% CI 7.4 to 8.8) mmHg. Median diastolic blood pressure decreased from 12 weeks: 69.1 (95% CI 68.9 to 69.3) mmHg to a minimum of 68.5 (95% CI 68.3 to 68.7) mmHg at 19⁺⁵ weeks’ gestation, a change of −0·6 (95% CI −0.8 to −0.4) mmHg. Diastolic blood pressure subsequently increased to a maximum of 76.3 (95% CI 75.9 to 76.8) mmHg at 40 weeks’ gestation. Systolic blood pressure fell by >14 mmHg or diastolic blood pressure by >11 mmHg in fewer than 10% of women at any gestational age. Fewer than 10% of women increased their systolic blood pressure by >24 mmHg or diastolic blood pressure by >18 mmHg at any gestational age. The study’s main limitations were the unavailability of prepregnancy blood pressure values and inability to explore circadian effects because time of day was not recorded for the blood pressure measurements.ConclusionsOur findings provide international, gestational age-specific centiles and limits of acceptable change to facilitate earlier recognition of deteriorating health in pregnant women. These centiles challenge the idea of a clinically significant midpregnancy drop in blood pressure.

Lauren Green and colleagues study blood pressure in pregnant women across a range of countries.     

Sodium bicarbonate can be used as an ergogenic aid in high-intensity, competitive cycle ergometry of 1?h duration

The aim of this study was to determine whether a dose of 300-mg x kg(-1) body mass of sodium bicarbonate would effect a high-intensity, 1-h maximal cycle ergometer effort. Ten male, well-trained [maximum oxygen consumption 67.3 (3.3) ml x kg(-1) x min(-1), mean (SD)] volunteer cyclists acted as subjects. Each undertook either a control (C), placebo (P), or experimental (E) ride in a random, double-blind fashion on a modified, air-braked cycle ergometer, attached to a personal computer to which the work and power data was downloaded at 10 Hz. Fingertip blood was sampled at 10-min intervals throughout the exercise. Blood was also sampled at 1, 3, 5, and 10 min post-exercise. Blood was analysed for lactate, partial pressure of Carbon dioxide and oxygen, pH and plasma bicarbonate (HCO-) concentration. Randomly chosen pairs of subjects were asked to complete as much work as possible during the 60-min exercise periods in an openly competitive situation. The sodium bicarbonate had the desired effect of increasing blood HCO3- prior to the start of the test. The subjects in E completed 950.9 (81.1) kJ of work, which was significantly more (F(2,27) = 5.28, P < 0.01) than during either the C [835.5 (100.2) kJ] or P [839.0 (88.6) kJ] trials. No differences were seen in peak power or in the power:mass ratio between these three groups. The results of this study suggest that sodium bicarbonate may be used to offset the fatigue process during high-intensity, aerobic cycling lasting 60 min.