Temporary induction of hypoxic adaptations by preconditioning fails to enhance Schwann cell transplant survival after spinal cord injury.

Hypoxic preconditioning is protective in multiple models of injury and disease, but whether it is beneficial for cells transplanted into sites of spinal cord injury (SCI) is largely unexplored. In this study, we analyzed whether hypoxia-related preconditioning protected Schwann cells (SCs) transplanted into the contused thoracic rat spinal cord. Hypoxic preconditioning was induced in SCs prior to transplantation by exposure to either low oxygen (1% O2 ) or pharmacological agents (deferoxamine or adaptaquin). All preconditioning approaches induced hypoxic adaptations, including increased expression of HIF-1α and its target genes. These adaptations, however, were transient and resolved within 24 h of transplantation. Pharmacological preconditioning attenuated spinal cord oxidative stress and enhanced transplant vascularization, but it did not improve either transplanted cell survival or recovery of sensory or motor function. Together, these experiments show that hypoxia-related preconditioning is ineffective at augmenting either cell survival or the functional outcomes of SC-SCI transplants. They also reveal that the benefits of hypoxia-related adaptations induced by preconditioning for cell transplant therapies are not universal.

Constraint of the Nuclear Dissipation Coefficient in Fission of Hypernuclei.

Experimental studies of nuclear fission induced by fusion, transfer, spallation, fragmentation, and electromagnetic reactions in combination with state-of-the-art calculations are successful to investigate the nuclear dissipation mechanism in normal nuclear matter, containing only nucleons. The dissipation mechanism has been widely studied by the use of many different fission observables and nowadays the dissipation coefficients involved in transport theories are well constrained. However, the existence of hypernuclei and the possible presence of hyperons in neutron stars make it necessary to extend the investigation of the nuclear dissipation coefficient to the strangeness sector. In this Letter, we use fission reactions of hypernuclei to constrain for the first time the dissipation coefficient in hypernuclear matter, observing that this coefficient increases a factor of 6 in the presence of a single Λ hyperon with respect to normal nuclear matter.

Defective Monocyte Enzymatic Function and an Inhibitory Immune Phenotype in Human Immunodeficiency Virus-Exposed Uninfected African Infants in the Era of Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus-exposed uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa and are highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated whether human immunodeficiency virus (HIV)-exposure dysregulates HEU immunity, vaccine-antibody production, and human herpes virus amplify this effect. METHODS: Thirty-four HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort and observed up to 6 weeks of age; and then a subsequent 43 HIV-infected and 61 HIV-uninfected mother-infant pairs were recruited into a longitudinal infant cohort at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HIV-unexposed uninfected (HU) infants. RESULTS: We demonstrate (1) altered monocyte phagosomal function and B-cell subset homeostasis and (2) lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-tetanus toxoid immunoglobulin G titers in HEU compared with HU infants. Human herpes virus infection was similar between HEU and HU infants. CONCLUSIONS: In the era of antiretroviral therapy-mediated viral suppression, HIV exposure may dysregulate monocyte and B-cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.

Treatment with hypoxia-mimetics protects cultured rat Schwann cells against oxidative stress-induced cell death.

Schwann cell (SC) grafts promote axon regeneration in the injured spinal cord, but transplant efficacy is diminished by a high death rate in the first 2-3 days postimplantation. Both hypoxic preconditioning and pharmacological induction of the cellular hypoxic response can drive cellular adaptations and improve transplant survival in a number of disease/injury models. Hypoxia-inducible factor 1 alpha (HIF-1α), a regulator of the cellular response to hypoxia, is implicated in preconditioning-associated protection. HIF-1α cellular levels are regulated by the HIF-prolyl hydroxylases (HIF-PHDs). Pharmacological inhibition of the HIF-PHDs mimics hypoxic preconditioning and provides a method to induce adaptive hypoxic responses without direct exposure to hypoxia. In this study, we show that hypoxia-mimetics, deferoxamine (DFO) and adaptaquin (AQ), enhance HIF-1α stability and HIF-1α target gene expression. Expression profiling of hypoxia-related genes demonstrates that HIF-dependent and HIF-independent expression changes occur. Analyses of transcription factor binding sites identify several candidate transcriptional co-regulators that vary in SCs along with HIF-1α. Using an in vitro model system, we show that hypoxia-mimetics are potent blockers of oxidative stress-induced death in SCs. In contrast, traditional hypoxic preconditioning was not protective. The robust protection induced by pharmacological preconditioning, particularly with DFO, indicates that pharmacological induction of hypoxic adaptations could be useful for promoting transplanted SC survival. These agents may also be more broadly useful for protecting SCs, as oxidative stress is a major pathway that drives cellular damage in the context of neurological injury and disease, including demyelinating diseases and peripheral neuropathies.

Early T Cell Differentiation with Well-Maintained Function across the Adult Life Course in Sub-Saharan Africa.

Immune senescence is a significant contributor to health problems in the developed world and may be accelerated by chronic viral infections. To date, there have been few studies of immune function in healthy older people in sub-Saharan Africa. We assessed T cell and B cell phenotypes and immune responses to CMV, EBV, and influenza virus in Malawians aged 20-69 y. Notably, the proportion of naive (CCR7+CD45RA+) CD4 and CD8 T cells was only 14% of the lymphoid repertoire even in donors aged under 30 y but did not decrease further with age. A small increase in the late differentiated (CD27-CD28-) CD8 T cell subpopulation was observed in older donors but the CD4/CD8 T cell ratio remained stable in all age groups. Interestingly, the regulatory (CD25hiFOXP3hi) T cell subpopulation was small in all age groups, and we observed no age-associated accumulation of cells expressing the senescence- and exhaustion-associated markers CD57 and PD-1. We assessed functional T cell responses to mitogenic and viral antigenic stimulation by the expression of CD154, IFN-γ, TNF-α, IL-2, and IL-17 and proliferation. All responses were robust across the life course, although we observed an age-associated shift from IFN-γ to TNF-α in the response to EBV. In summary, we found the naive T cell subpopulation of young adult Malawians was smaller than in their contemporaries in high-income settings but remains stable thereafter and that lymphocyte function is retained across the life course. These observations indicate that studies of the genetic and environmental factors influencing immune function in different environments may provide insights into minimizing immune ageing.

Low- and High-Drag Intermittencies in Turbulent Channel Flows.

Recent direct numerical simulations (DNS) and experiments in turbulent channel flow have found intermittent low- and high-drag events in Newtonian fluid flows, at Reτ=uτh/ν between 70 and 100, where uτ, h and ν are the friction velocity, channel half-height and kinematic viscosity, respectively. These intervals of low-drag and high-drag have been termed "hibernating" and "hyperactive", respectively, and in this paper, a further investigation of these intermittent events is conducted using experimental and numerical techniques. For experiments, simultaneous measurements of wall shear stress and velocity are carried out in a channel flow facility using hot-film anemometry (HFA) and laser Doppler velocimetry (LDV), respectively, for Reτ between 70 and 250. For numerical simulations, DNS of a channel flow is performed in an extended domain at Reτ = 70 and 85. These intermittent events are selected by carrying out conditional sampling of the wall shear stress data based on a combined threshold magnitude and time-duration criteria. The use of three different scalings (so-called outer, inner and mixed) for the time-duration criterion for the conditional events is explored. It is found that if the time-duration criterion is kept constant in inner units, the frequency of occurrence of these conditional events remain insensitive to Reynolds number. There exists an exponential distribution of frequency of occurrence of the conditional events with respect to their duration, implying a potentially memoryless process. An explanation for the presence of a spike (or dip) in the ensemble-averaged wall shear stress data before and after the low-drag (or high-drag) events is investigated. During the low-drag events, the conditionally-averaged streamwise velocities get closer to Virk's maximum drag reduction (MDR) asymptote, near the wall, for all Reynolds numbers studied. Reynolds shear stress (RSS) characteristics during these conditional events are investigated for Reτ = 70 and 85. Except very close to the wall, the conditionally-averaged RSS is higher than the time-averaged value during the low-drag events.

Analysis of the 148Gd and 154Dy Content in Proton-Irradiated Lead Targets.

This work presents the determination of the 148Gd and 154Dy content in Pb targets irradiated by 220-2600 MeV protons. It includes the chemical separation of lanthanides, followed by the preparation of proper samples, by molecular plating technique, for α-spectrometry measurements. The experimental cross section results were compared with theoretical predictions, calculated with the INCL++-ABLA07 code. The comparisons showed a satisfactory agreement for 148Gd (less than within a factor two), while measured 154Dy cross sections are higher than the theoretical values.

A restatement of the natural science evidence base concerning the health effects of low-level ionizing radiation.

Exposure to ionizing radiation is ubiquitous, and it is well established that moderate and high doses cause ill-health and can be lethal. The health effects of low doses or low dose-rates of ionizing radiation are not so clear. This paper describes a project which sets out to summarize, as a restatement, the natural science evidence base concerning the human health effects of exposure to low-level ionizing radiation. A novel feature, compared to other reviews, is that a series of statements are listed and categorized according to the nature and strength of the evidence that underpins them. The purpose of this restatement is to provide a concise entrée into this vibrant field, pointing the interested reader deeper into the literature when more detail is needed. It is not our purpose to reach conclusions on whether the legal limits on radiation exposures are too high, too low or just right. Our aim is to provide an introduction so that non-specialist individuals in this area (be they policy-makers, disputers of policy, health professionals or students) have a straightforward place to start. The summary restatement of the evidence and an extensively annotated bibliography are provided as appendices in the electronic supplementary material.

Progressively heterogeneous mismatch of regional oxygen delivery to consumption during graded coronary stenosis in pig left ventricle.

In normal hearts, myocardial perfusion is fairly well matched to regional metabolic demand, although both are distributed heterogeneously. Nonuniform regional metabolic vulnerability during coronary stenosis would help to explain nonuniform necrosis during myocardial infarction. In the present study, we investigated whether metabolism-perfusion correlation diminishes during coronary stenosis, indicating increasing mismatch of regional oxygen supply to demand. Thirty anesthetized male pigs were studied: controls without coronary stenosis (n = 11); group I, left anterior descending (LAD) coronary stenosis leading to coronary perfusion pressure reduction to 70 mmHg (n = 6); group II, stenosis with perfusion pressure of about 35 mmHg (n = 6); and group III, stenosis with perfusion pressure of 45 mmHg combined with adenosine infusion (n = 7). [2-(13)C]- and [1,2-(13)C]acetate infusion was used to calculate regional O2 consumption from glutamate NMR spectra measured for multiple tissue samples of about 100 mg dry mass in the LAD region. Blood flow was measured with microspheres in the same regions. In control hearts without stenosis, regional oxygen extraction did not correlate with basal blood flow. Average myocardial O2 delivery and consumption decreased during coronary stenosis, but vasodilation with adenosine counteracted this. Regional oxygen extraction was on average decreased during stenosis, suggesting adaptation of metabolism to lower oxygen supply after half an hour of ischemia. Whereas regional O2 delivery correlated with O2 consumption in controls, this relation was progressively lost with graded coronary hypotension but partially reestablished by adenosine infusion. Therefore, coronary stenosis leads to heterogeneous metabolic stress indicated by decreasing regional O2 supply to demand matching in myocardium during partial coronary obstruction.

Geographical variation in species' population responses to changes in temperature and precipitation.

Despite increasing concerns about the vulnerability of species' populations to climate change, there has been little overall synthesis of how individual population responses to variation in climate differ between taxa, with trophic level or geographically. To address this, we extracted data from 132 long-term (greater than or equal to 20 years) studies of population responses to temperature and precipitation covering 236 animal and plant species across terrestrial and freshwater habitats. Our results identify likely geographical differences in the effects of climate change on populations and communities in line with macroecological theory. Temperature tended to have a greater overall impact on populations than precipitation, although the effects of increased precipitation varied strongly with latitude, being most positive at low latitudes. Population responses to increased temperature were generally positive, but did not vary significantly with latitude. Studies reporting significant climatic trends through time tended to show more negative effects of temperature and more positive effects of precipitation upon populations than other studies, indicating climate change has already impacted many populations. Most studies of climate change impacts on biodiversity have focused on temperature and are from middle to high northern latitudes. Our results suggest their findings may be less applicable to low latitudes.

Acetaldehyde, not ethanol, impairs myelin formation and viability in primary mouse oligodendrocytes.

BACKGROUND: Excessive ethanol (EtOH) drinking is associated with white matter loss in the brain at all stages of life. Myelin-forming oligodendrocytes (OLs) are a major component of white matter, but their involvement in EtOH-mediated white matter loss is unclear. Myelination continues throughout the life with highest rates during fetal development and adolescence. However, little is known about the effects of EtOH and its principal metabolite acetaldehyde (ACD) on OLs at the cellular level. METHODS: We compared the responses to different concentrations of EtOH or ACD by primary OLs in culture. RESULTS: EtOH did not cause significant cell death at concentrations lower than 120 mM, even after 24 hours. In comparison, ACD was highly lethal at doses above 50 µM. High concentrations of EtOH (120 mM) and ACD (500 µM) for 24 hours did not reduce myelin in mature OLs. Myelin production and OL differentiation were significantly impaired by 7 days exposure to 500 or 50 µM ACD but not 120 mM EtOH. CONCLUSIONS: This study shows that OLs are relatively resistant to EtOH, even at a concentration more than 4 times the typical blood EtOH concentrations associated with social drinking (10 to 30 mM). In contrast, OLs are much more sensitive to ACD than EtOH, particularly with long-term exposure. This suggests that part of white matter loss in response to EtOH, especially during high rates of myelin formation, may be due in part to the effects of its principal metabolite ACD.

Coherent structures in wall-bounded turbulence.

The inherent difficulty of understanding turbulence has led to researchers attacking the topic in many different ways over the years of turbulence research. Some approaches have been more successful than others, but most only deal with part of the problem. One approach that has seen reasonable success (or at least popularity) is that of attempting to deconstruct the complex and disorganised turbulent flow field into to a set of motions that are in some way organised. These motions are generally called "coherent structures". There are several strands to this approach, from identifying the coherent structures within the flow, defining their characteristics, explaining how they are created, sustained and destroyed, to utilising their features to model the turbulent flow. This review considers research on coherent structures in wall-bounded turbulent flows: a class of flow which is extremely interesting to many scientists (mainly, but not exclusively, physicists and engineers) due to their prevalence in nature, industry and everyday life. This area has seen a lot of activity, particularly in recent years, much of which has been driven by advances in experimental and computational techniques. However, several ideas, developed many years ago based on flow visualisation and intuition, are still both informative and relevant. Indeed, much of the more recent research is firmly indebted to some of the early pioneers of the coherent structures approach. Therefore, in this review, selected historical research is discussed along with the more contemporary advances in an attempt to provide the reader with a good overview of how the field has developed and to highlight the perspicacity of some of the early researchers, as well as providing an overview of our current understanding of the role of coherent structures in wall-bounded turbulent flows.

Mechanisms underpinning climatic impacts on natural populations: altered species interactions are more important than direct effects.

Shifts in species' distribution and abundance in response to climate change have been well documented, but the underpinning processes are still poorly understood. We present the results of a systematic literature review and meta-analysis investigating the frequency and importance of different mechanisms by which climate has impacted natural populations. Most studies were from temperate latitudes of North America and Europe; almost half investigated bird populations. We found significantly greater support for indirect, biotic mechanisms than direct, abiotic mechanisms as mediators of the impact of climate on populations. In addition, biotic effects tended to have greater support than abiotic factors in studies of species from higher trophic levels. For primary consumers, the impact of climate was equally mediated by biotic and abiotic mechanisms, whereas for higher level consumers the mechanisms were most frequently biotic, such as predation or food availability. Biotic mechanisms were more frequently supported in studies that reported a directional trend in climate than in studies with no such climatic change, although sample sizes for this comparison were small. We call for more mechanistic studies of climate change impacts on populations, particularly in tropical systems.

Distinct organizational States of fully developed turbulent pipe flow.

Organizational states of turbulence are identified through novel analysis of large scale pipe flow experiments at a Reynolds number of 35 000. The distinct states are revealed by an azimuthal decomposition of the two-point spatial correlation of the streamwise velocity fluctuation. States with dominant azimuthal wave numbers corresponding to k_{θ}=2,3,4,5,6 are discovered and their structure revealed as a series of alternately rotating quasistreamwise vortices. Such organizational states are highly reminiscent of the nonlinear traveling wave solutions previously identified at Reynolds numbers an order of magnitude lower.

A video-based intervention to overcome pregnancy smoking stigma among healthcare students: a randomised controlled trial.

OBJECTIVES: This study tests a video intervention to reduce pregnancy smoking stigma among French healthcare students. DESIGN: The participants were randomly selected to watch online either an experimental video (presenting educational content regarding stigma and contact with pregnant smokers) or a control video (presenting standard educational content about the risks of smoking). The students completed scales assessing stigma, intention to address smoking cessation and self-efficacy to do so, before the intervention (T0, n = 252), one week after the intervention (T1, n = 187), and one month after the intervention (T2, n = 131). RESULTS: Compared to the medical students, especially men, the midwifery students reported lower derogative cognitions (η2p = .18), negative behaviours (η2p = .07) and personal distress (η2p = .06). However, the midwifery students also reported lower levels of intention to address smoking (η2p = .02) than the medical students. The experimental video decreased derogative cognitions to a greater extent than the control video (η2p = .23) in both the short and medium term. This study is the first intervention designed to reduce the stigmatisation of pregnant smokers by healthcare students. We recommend that the issue of stigma should receive more attention in the medical curriculum.

Evaluating the "greenness" of chemical processes and products in the pharmaceutical industry--a green metrics primer.

This tutorial review presents an overview of the main metrics that have been used to test and compare the 'greenness' of processes and products, primarily in the pharmaceutical industry. The green metrics cover areas of resources, materials, processing, cleaning, life cycle assessment, renewability, amongst others. Application examples of these metrics are also presented to illustrate key points and concepts.

Drivers of change in hunter offtake and hunting strategies in Sendje, Equatorial Guinea.

Economic development in Africa is expected to increase levels of bushmeat hunting through rising demand for meat and improved transport infrastructure. However, few studies have tracked long-term changes in hunter behavior as a means of testing this prediction. We evaluated changes in hunter behavior in a rural community in Equatorial Guinea over a period of rapid national economic growth, during which time road access to the regional capital greatly improved. We conducted offtake surveys (Supporting Information) over 3 7-week periods at the same time of year in 1998, 2003, and 2010 and conducted hunter and household interviews (Supporting Information) in 2003 and 2010. We tested whether relations existed among catch, hunting effort, hunting strategy, and income earned through hunting and other livelihoods in 2003 and 2010. Although village offtake increased from 1775 kg in 1998 to 4172 kg in 2003, it decreased in 2010 to 1361 kg. Aggregate catch per unit effort (i.e., number of carcasses caught per hunter and per trap) decreased from 2003 to 2010, and the majority of hunters reported a decrease in abundance of local fauna. Although these results are indicative of unsustainable hunting, cumulative changes in offtake and catch per unit effort were driven by a contraction in the total area hunted following an out-migration of 29 of the village's hunters, most of whom left to gain employment in the construction industry, after 2003. Hunters operating in both 2003 and 2010 hunted closer to the village because an increased abundance of elephants posed a danger and because they desired to earn income through other activities. Our study provides an example of national economic development contributing to a reduction in the intensity and extent of hunting.

Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination.

BACKGROUND: Placental malaria (PM) is associated with prenatal malaise, but many PM+ infants are born without symptoms. As malaria has powerful immunomodulatory effects, we tested the hypothesis that PM predicts reduced T-cell responses to vaccine challenge. METHODS: We recruited healthy PM+ and PM- infants at birth. At six and 12 months, we stimulated PBMCs with tuberculin purified protein derivative (PPD) and compared expression of CD154, IL-2 and IFNγ by CD4 T-cells to a negative control using flow cytometry.We measured the length, weight and head circumference at birth and 12 months. RESULTS: IL-2 and CD154 expression were low in both groups at both timepoints, without discernable differences. Expression of IFNγ was similarly low at 6 months but by 12 months, the median response was higher in PM- than PM + infants (p = 0.026). The PM+ infants also had a lower weight (p = 0.032) and head circumference (p = 0.041) at 12 months, indicating lower growth rates.At birth, the size and weight of the PM+ and PM- infants were equivalent. By 12 months, the PM+ infants had a lower weight and head circumference than the PM- infants. CONCLUSIONS: Placental malaria was associated with reduced immune responses 12 months after immune challenge in infants apparently healthy at birth.

Knowledge and perceptions of antibiotic resistance in the French population.

OBJECTIVE: To draw up an inventory of health behaviors and knowledge of the French population regarding antibiotic resistance. RESULTS: Overall, 44% of participants properly defined antibiotic resistance. Antibiotic abuse was identified as the main cause of antibiotic resistance, and 66% believed that an antibiotic-resistant infection can be fatal. However, 32% did not strictly comply with the dosage and duration of an antibiotic treatment. Analysis of social representations of antibiotic resistance revealed erroneous beliefs about this phenomenon. CONCLUSION: Our results highlight the need to continue to inform the French public of antibiotic resistance. Associated beliefs could be obstacles to the proper use of antibiotics.