•We grew seven C3 annuals at a factorial of CO2 (160-450-750 ppm) and soil water availability (100-40-20%).•Compared to well-watered conditions the relative effect of drought was the same at all CO2 ...conditions.•Across all traits measured, we found mostly additive effects of CO2 and water.•In drought prone regions, results suggest CO2 fertilization will not counter the effects of reduced water availability.
Carbon dioxide and water are crucial resources for plant growth. With anthropogenic fossil fuel emissions, CO2 availability is and has been increasing since the last glacial maximum. Simultaneously water availability is expected to decrease and the frequency and severity of drought episodes to increase in large parts of the world. How plants respond to these two changes will help in understanding plants’ responses to climate of the future. Here we sought to understand how drought affects plant traits responses to CO2 and whether there are trade-offs in responsiveness to low and elevated CO2 and drought. We grew seedlings of seven C3 annuals at past low (160 μl l−1), ambient (450 μl l−1) and elevated (750 μl l−1) CO2. At each concentration plants were subjected to well-watered conditions (100% soil water availability, SWA), 40% SWA or 20% SWA. We measured biomass allocation, relative growth rate, tissue N concentration, and gas exchange. Compared to well-watered conditions plant size was an important element in the absolute response to SWA decrease, i.e. the smaller, slow growing species were unaffected by drought at low CO2. Plants allocated less mass to root tissue at low CO2 contrasting with increased root mass fraction at lower SWA at ambient CO2. Across all traits measured, we found mostly additive effects of CO2 and water. As due to climate change regions become more drought prone these results suggest CO2 fertilization will not counteract the effects of reduced water availability.
Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense ...mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype–phenotype/–ataluren benefit correlations and ataluren safety.
Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018).
Kaplan–Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p ≤ 0.05). There were no DMD genotype–phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice.
NCT02369731.
NCT02369731.
To examine the effects of vitamin C supplementation on the concentration of oxidation markers, in particular, circulating oxidized LDL (OxLDL) and on endothelial activation markers.
Randomized ...double-blind, placebo-controlled crossover trial.
Belgian population of the city of Leuven.
A total of 34 healthy male smokers aged 26-73 y.
Smokers were randomly assigned to receive either vitamin C (250 mg twice daily) or placebo capsules, each to be taken for 4 weeks. After a 1-week washout period, participants then crossed over to the alternative capsules for further 4 weeks.
Markers of oxidation (bilirubin, uric acid, alpha-tocopherol, retinol, malondialdehyde, circulating Oxidized LDL (OxLDL)) and markers of endothelial activation (sICAM-1, sVCAM-1, vWF-antigen) were analysed.
Plasma ascorbate concentrations significantly increased from 46.6+/-17.6 to 70.1+/-21.2 mumol/l after a 4-week treatment with 500 mg vitamin C per day. The other plasma antioxidants concentrations, including bilirubin, uric acid, alpha-tocopherol and retinol, were similar in both treatment periods. Vitamin C did not change plasma malondialdehyde and circulating OxLDL compared with placebo (vitamin C 0.73+/-0.25 mg/dl OxLDL; placebo 0.72+/-0.21 mg/dl OxLDL). After vitamin C supplementation, neither sICAM-1 and sVCAM-1 levels nor the concentration of vWF-antigen significantly differed from placebo condition.
Oral supplementation of vitamin C is not associated with changes in markers of oxidation or endothelial activation in healthy male smokers.
Introduction
A risk associated with cystic fibrosis newborn screening (CFNBS) is parental misunderstanding of genetic information generated by the over 6600 positive screens reported annually in the ...United States. CFNBS algorithms incorporating DNA analysis can generate genetic information that requires clinical interpretation and has significance for the newborn, parents, and other relatives. Engagement between CF care centers and trained genetic counseling providers, such as licensed and/or certified genetic counselors (GCs), is variable and limited in providing information to CFNBS positive (CFNBS+) families.
Methods
Using a modified Delphi process, a workgroup of CFNBS experts developed recommendation statements for engagement of genetic counseling services in CF care centers where CFNBS + diagnostic evaluations are performed. Statements were assessed over three rounds of surveys, one face‐to‐face meeting, and through public feedback.
Results
Seventeen statements achieved >80% consensus (range: 82%–100%). The workgroup affirmed prior CFF policy statements recommending genetic counseling for parents of infants with CFNBS+. The remaining statements addressed infrastructure and logistics of genetic counseling services, including defining appropriate training for genetic counseling providers and counseling content, establishing a path to equal access to genetic counseling providers across CF care centers, and setting a standard for client‐centered CFNBS genetic counseling that is respectful of diverse patient needs and autonomy.
Conclusions
Implementation of client‐centered genetic counseling for CFNBS+ families in CF care centers by providers with expertise in both CF and genetic counseling will require efforts to further define core concepts, enhance the education of providers, and develop opportunities for access via telemedicine.
The gap junctional protein connexin32 is expressed in hepatocytes, exocrine pancreatic cells, Schwann cells, and other cell types. We have inactivated the connexin32 gene by homologous recombination ...in the mouse genome and have generated homozygous connexin32-deficient mice that were viable and fertile but weighed on the average ≈ 17% less than wild-type controls. Electrical stimulation of sympathetic nerves in connexin32-deficient liver triggered a 78% lower amount of glucose mobilization from glycogen stores, when compared with wild-type liver. Thus, connexin32-containing gap junctions are essential in mouse liver for maximal intercellular propagation of the noradrenaline signal from the periportal (upstream) area, where it is received from sympathetic nerve endings, to perivenous (downstream) hepatocytes. In connexin32-defective liver, the amount of connexin26 protein expressed was found to be lower than in wild-type liver, and the total area of gap junction plaques was ≈ 1000-fold smaller than in wild-type liver. In contrast to patients with connexin32 defects suffering from X chromosome-linked Charcot--Marie--Tooth disease (CMTX) due to demyelination in Schwann cells of peripheral nerves, connexin32-deficient mice did not show neurological abnormalities when analyzed at 3 months of age. It is possible, however, that they may develop neurodegenerative symptoms at older age.
Genetic counseling summary letters are intended to reinforce information received during genetic counseling, but little information is available on patient/family responses to these letters. We ...conducted a case–control study to assess the effectiveness of two different letter formats. Parents of children receiving a new diagnosis were enrolled. The control group (
n
= 85) received a genetic counseling summary letter in a narrative format, 4–5 pages in length. After the control enrollment period, genetic counselors were trained by a professional medical writer to develop a concise letter format. The case group (
n
= 64) received a concise letter, approximately 1.5 pages in length, utilizing simple sentences, lay terms, and lists/bullet points. Parents completed a survey 4 weeks after the visit to rate the letter’s format, usefulness, and their emotional reaction. Results show that parents in the case group rated the letter more highly (
p
= 0.023), particularly in the emotional response dimension (rating changes in anxiety, depression, fear, ability to cope, and confidence in response to the letter). Parents in the case group also rated the genetic counseling session more highly (
p
= 0.039). In the control group, parents without a college degree were more likely to rate the letter as too long and the level of medical detail as too high. In the case group, no significant differences were seen between parents with or without a college degree. These data suggest that a short genetic counseling summary letter is rated higher by parents, and is particularly associated with a more positive emotional reaction. A short letter format highlighting the basic facts related to the genetic condition may be more useful to parents of diverse educational backgrounds, and may support a positive emotional adaptation at the time of a new diagnosis. Genetic counselors may benefit from specific instruction in medical and educational writing.
Since hypoxia remains one of the most important physiological hazards the aviation environment poses, military aviators are trained to recognize symptoms of hypoxia in order to implement appropriate ...safety procedures and countermeasures when hypoxia occurs. A widely used commercial instrument for hypoxia training, demonstration, and research is the Reduced Oxygen Breathing Device (ROBD). Here we describe a novel, inexpensive method to use the ROBD's breathing loop pressure (BLP) to measure respiration rate, a critically important response parameter for hypoxia.
The ROBD can be controlled by a computer to export several variables including BLP, via the ROBD's RS232 port. An archived database was reanalyzed to assess the BLP data. New instrumentation added independent measures of respiration and expired oxygen and carbon dioxide; these measures were integrated with the ROBD output.
Analysis of the archived data showed that the BLP reflected realistic breathing patterns. The new instrumentation integrated well with the ROBD, and independently supported the potential of the BLP as a valid measure of respiration.
The ROBD's BLP data may provide a basis for a reliable, sensitive measure of respiration that is available at no additional cost.
A general understanding of the links between atmospheric CO2 concentration and the functioning of the terrestrial biosphere requires not only an understanding of plant trait responses to the ongoing ...transition to higher CO2 but also the legacy effects of past low CO2. An interesting question is whether the transition from current to higher CO2 can be thought of as a continuation of the past trajectory of low to current CO2 levels. Determining this trajectory requires quantifying the effect sizes of plant response to low CO2. We performed a meta‐analysis of low CO2 growth experiments on 34 studies with 54 species. We quantified how plant traits vary at reduced CO2 levels and whether C3 versus C4 and woody versus herbaceous plant species respond differently. At low CO2, plant functioning changed drastically: on average across all species, a 50% reduction in current atmospheric CO2 reduced net photosynthesis by 38%; increased stomatal conductance by 60% and decreased intrinsic water use efficiency by 48%. Total plant dry biomass decreased by 47%, while specific leaf area increased by 17%. Plant types responded similarly: the only significant differences being no increase in SLA for C4 species and a 16% smaller decrease in biomass for woody C3 species at glacial CO2. Quantitative comparison of low CO2 effect sizes to those from high CO2 studies showed that the magnitude of response of stomatal conductance, water use efficiency and SLA to increased CO2 can be thought of as continued shifts along the same line. However, net photosynthesis and dry weight responses to low CO2 were greater in magnitude than to high CO2. Understanding the causes for this discrepancy can lead to a general understanding of the links between atmospheric CO2 and plant responses with relevance for both the past and the future.
We performed a meta‐analysis of low CO2 growth experiments on 34 studies with 54 species. We quantified how plant traits vary at reduced CO2 levels and whether C3 versus C4 and woody versus herbaceous plant species respond differently. At low CO2, plant functioning changed drastically.
Dendritic cells (DCs) are characterized by their unique capacity for primary T cell activation, providing the opportunity for DC-based cancer vaccination protocols. Novel findings reveal that besides ...their role as potent inducers of tumor-specific T cells, human DCs display additional antitumor effects. Most of these data were obtained with monocyte-derived DCs, whereas studies investigating native blood DCs are limited. In the present study, we analyze the tumoricidal capacity of M-DC8(+) DCs, which represent a major subpopulation of human blood DCs. We demonstrate that IFN-gamma-stimulated M-DC8(+) DCs lyse different tumor cell lines but not normal cells. In addition, we show that tumor cells markedly enhance the production of TNF-alpha by M-DC8(+) DCs via cell-to-cell contact and that this molecule essentially contributes to the killing activity of M-DC8(+) DCs. Furthermore, we illustrate the ability of M-DC8(+) DCs to promote proliferation, IFN-gamma production, and tumor-directed cytotoxicity of NK cells. The M-DC8(+) DC-mediated enhancement of the tumoricidal potential of NK cells is mainly dependent on cell-to-cell contact. These results reveal that, in addition to their crucial role in activating tumor-specific T cells, blood DCs exhibit direct tumor cell killing and enhance the tumoricidal activity of NK cells. These findings point to the pivotal role of DCs in triggering innate and adaptive immune responses against tumors.
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