Physiological response to groundwater depth varies among species and with river flow regulation

We investigated the physiological response of two native riparian tree species (Populus fremontii and Salix gooddingii) and one exotic species (Tamarix chinensis) to groundwater availability along gradients of depth to groundwater at two rivers in Arizona. Depth to groundwater (DGW) at the dam-regulated Bill Williams River (BWR) was relatively constant and shallow (,4 m). Populus fremontii at BWR did not experience reduced water availability at deeper groundwater depths, as evidenced by high predawn water potential. However, leaf gas exchange of P. fremontii was sensitive to high vapor pressure deficit where surface flow was ephemeral at BWR. Lower predawn water potentials of S. gooddingii at BWR suggested reduced water availability at deeper groundwater depths, but these reductions did not adversely affect net photosynthetic rate. Along the range of depth to groundwater at BWR, all three species suffered little canopy dieback, and dieback was not related to depth to groundwater. Depth to groundwater at the free-flowing Hassayampa River (HRP) was much greater and declined more rapidly in the ephemeral reaches than at BWR. Both P. fremontii and S. gooddingii experienced reduced water availability at deeper groundwater depths at HRP, as evidenced by lower predawn water potential. Both species also experienced reduced leaf gas exchange at deeper groundwater depths. Canopy dieback of all species was higher at HRP than at BWR and increased with increasing DGW, especially when DGW fell below 3 m. There was evidence to support branch sacrifice in these three riparian tree species as a means of improving water status in the surviving shoot. However, branch sacrifice was insufficient to prevent mortality in some of the native trees where DGW fell below 3 m at HRP. In contrast to the native species, T. chinensis showed no change in water availability, leaf gas exchange, or canopy dieback with increasing DGW at either river. Leaf gas exchange was lower and dieback was greater for T. chinensis at HRP where depth to groundwater was greater than at BWR, but there was no mortality at either river. Our results show that deep groundwater is more detrimental to the physiological condition of P. fremontii and S. gooddingii than it is to T. chinensis. Also, the pronounced differences in DGW and tree physiological performance between BWR and HRP suggest that dam regulation can increase water availability to mature trees in some desert riparian ecosystems. Finally, our study also provides estimates of the range of DGW that can maintain healthy, mature P. fremontii and S. gooddingii trees

Eye Choice for Acquisition of Targets in Alternating Strabismus

In strabismus, potentially either eye can inform the brain about the location of a target so that an accurate saccade can be made. Sixteen human subjects with alternating exotropia were tested dichoptically while viewing stimuli on a tangent screen. Each trial began with a fixation cross visible to only one eye. After the subject fixated the cross, a peripheral target visible to only one eye flashed briefly. The subject's task was to look at it. As a rule, the eye to which the target was presented was the eye that acquired the target. However, when stimuli were presented in the far nasal visual field, subjects occasionally performed a “crossover” saccade by placing the other eye on the target. This strategy avoided the need to make a large adducting saccade. In such cases, information about target location was obtained by one eye and used to program a saccade for the other eye, with a corresponding latency increase. In 10/16 subjects, targets were presented on some trials to both eyes. Binocular sensory maps were also compiled to delineate the portions of the visual scene perceived with each eye. These maps were compared with subjects' pattern of eye choice for target acquisition. There was a correspondence between suppression scotoma maps and the eye used to acquire peripheral targets. In other words, targets were fixated by the eye used to perceive them. These studies reveal how patients with alternating strabismus, despite eye misalignment, manage to localize and capture visual targets in their environment

Physiological response to groundwater depth varies among species and with river flow regulation

Abstract. We investigated the physiological response of two native riparian tree species (Populus fremontii and Salix gooddingii) and one exotic species (Tamarix chinensis) to groundwater availability along gradients of depth to groundwater at two rivers in Arizona. Depth to groundwater (DGW) at the dam-regulated Bill Williams River (BWR) was relatively constant and shallow (Ͻ4 m). Populus fremontii at BWR did not experience reduced water availability at deeper groundwater depths, as evidenced by high predawn water potential. However, leaf gas exchange of P. fremontii was sensitive to high vapor pressure deficit where surface flow was ephemeral at BWR. Lower predawn water potentials of S. gooddingii at BWR suggested reduced water availability at deeper groundwater depths, but these reductions did not adversely affect net photosynthetic rate. Along the range of depth to groundwater at BWR, all three species suffered little canopy dieback, and dieback was not related to depth to groundwater. Depth to groundwater at the freeflowing Hassayampa River (HRP) was much greater and declined more rapidly in the ephemeral reaches than at BWR. Both P. fremontii and S. gooddingii experienced reduced water availability at deeper groundwater depths at HRP, as evidenced by lower predawn water potential. Both species also experienced reduced leaf gas exchange at deeper groundwater depths. Canopy dieback of all species was higher at HRP than at BWR and increased with increasing DGW, especially when DGW fell below 3 m. There was evidence to support branch sacrifice in these three riparian tree species as a means of improving water status in the surviving shoot. However, branch sacrifice was insufficient to prevent mortality in some of the native trees where DGW fell below 3 m at HRP. In contrast to the native species, T. chinensis showed no change in water availability, leaf gas exchange, or canopy dieback with increasing DGW at either river. Leaf gas exchange was lower and dieback was greater for T. chinensis at HRP where depth to groundwater was greater than at BWR, but there was no mortality at either river. Our results show that deep groundwater is more detrimental to the physiological condition of P. fremontii and S. gooddingii than it is to T. chinensis. Also, the pronounced differences in DGW and tree physiological performance between BWR and HRP suggest that dam regulation can increase water availability to mature trees in some desert riparian ecosystems. Finally, our study also provides estimates of the range of DGW that can maintain healthy, mature P. fremontii and S. gooddingii trees

Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression

<p>Abstract</p> <p>Background</p> <p>The balance between reactive oxygen species (ROS) and endogenous anti-oxidants is important in maintaining healthy tissues. Excessive ROS states occur in diseases such as ARDS and Idiopathic Pulmonary Fibrosis. Redox imbalance breaks down the extracellular matrix component hyaluronan (HA) into fragments that activate innate immune responses and perpetuate tissue injury. HA fragments, via a TLR and NF-κB pathway, induce inflammatory gene expression in macrophages and epithelial cells. NAC and DMSO are potent anti-oxidants which may help balance excess ROS states.</p> <p>Methods</p> <p>We evaluated the effect of H₂O₂, NAC and DMSO on HA fragment induced inflammatory gene expression in alveolar macrophages and epithelial cells.</p> <p>Results</p> <p>NAC and DMSO inhibit HA fragment-induced expression of TNF-α and KC protein in alveolar and peritoneal macrophages. NAC and DMSO also show a dose dependent inhibition of IP-10 protein expression, but not IL-8 protein, in alveolar epithelial cells. In addition, H₂O₂synergizes with HA fragments to induce inflammatory genes, which are inhibited by NAC. Mechanistically, NAC and DMSO inhibit HA induced gene expression by inhibiting NF-κB activation, but NAC had no influence on HA-fragment-AP-1 mediated gene expression.</p> <p>Conclusion</p> <p>ROS play a central role in a pathophysiologic "vicious cycle" of inflammation: tissue injury generates ROS, which fragment the extracellular matrix HA, which in turn synergize with ROS to activate the innate immune system and further promote ROS, HA fragment generation, inflammation, tissue injury and ultimately fibrosis. The anti-oxidants NAC and DMSO, by inhibiting the HA induced inflammatory gene expression, may help re-balance excessive ROS induced inflammation.</p

Longitudinal landscapes of serum antibody repertoires after influenza infection and vaccination

Vaccination is the most effective means of infectious disease prevention. Despite its success, however, we still lack a clear understanding of vaccine responses in humans. For example, influenza vaccines still leave a large fraction of population vulnerable. Over the past decade, single B-cell analysis and next-generation sequencing (NGS) technologies have become invaluable tools for studying the antibody repertoire to influenza. Such studies have led to discoveries of broadly-neutralizing antibodies (bNAbs), which can neutralize across multiple strains of influenza virus, promoting the notion of designing a universal vaccine that will elicit such antibodies. One of such isolated bNAbs, called FI6, showed remarkable ability to neutralize all of the influenza A virus strains through targeting the conserved epitope in the stem of hemagglutinin (HA). However, it remains unclear whether such bNAbs actually play a role in conferring protection against influenza since antibody proteins (not B-cells) need to circulate at physiologically relevant concentrations in serum to have implications in protection. Using high-resolution proteomics coupled with NGS, we quantitatively determined the serological antibody repertoire to CA09 HA (H1) at the individual clonotype-level in a donor (whom FI6 was isolated from) following influenza infection (in 2010 with pandemic CA09) and vaccination across five years (2010-2014 with seasonal flu vaccine). We analyzed the temporal changes of head-targeting and stem-binding antibodies, illustrating the gradual increase of stem-targeting antibodies following repeated exposures to CA09 HA. Following vaccination in 2014, \u3e60% of the repertoire consisted of one single clonotype of stem-binding antibody that was present at very low abundance in 2010. Our data demonstrate that the repetitive exposure to influenza skews the serological repertoire toward antibodies that target conserved epitopes, and these antibodies continue to be boosted every time the same epitopes are encountered. Once elicited, stem-binding antibodies displayed a tendency to persist in serum across multiple years while head-specific antibodies decayed quicker. The differential longevity of stem-binding and head-specific antibodies presented here has direct implications for the design of the future universal vaccine

Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials

BACKGROUND: Randomized controlled trials play a central role in evidence-based practice, but recruitment of participants, and retention of them once in the trial, is challenging. Moreover, there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies. As with other healthcare initiatives, the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives, which for recruitment would mean embedding a recruitment trial within an ongoing host trial. Systematic reviews indicate that such studies are rare. Embedded trials are largely delivered in an ad hoc way, with interventions almost always developed in isolation and tested in the context of a single host trial, limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to researchers working in different contexts. METHODS/DESIGN: The Systematic Techniques for Assisting Recruitment to Trials (START) program is funded by the United Kingdom Medical Research Council (MRC) Methodology Research Programme to support the routine adoption of embedded trials to test standardized recruitment interventions across ongoing host trials. To achieve this aim, the program involves three interrelated work packages: (1) methodology - to develop guidelines for the design, analysis and reporting of embedded recruitment studies; (2) interventions - to develop effective and useful recruitment interventions; and (3) implementation - to recruit host trials and test interventions through embedded studies. DISCUSSION: Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or, potentially, other types of intervention linked to trial conduct. It will also increase the evidence base for two types of recruitment intervention. TRIAL REGISTRATION: The START protocol covers the methodology for embedded trials. Each embedded trial is registered separately or as a substudy of the host trial

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium

Evaluating the pathogenicity of a variant is challenging given the plethora of types of genetic evidence that laboratories consider. Deciding how to weigh each type of evidence is difficult, and standards have been needed. In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for the assessment of variants in genes associated with Mendelian diseases. Nine molecular diagnostic laboratories involved in the Clinical Sequencing Exploratory Research (CSER) consortium piloted these guidelines on 99 variants spanning all categories (pathogenic, likely pathogenic, uncertain significance, likely benign, and benign). Nine variants were distributed to all laboratories, and the remaining 90 were evaluated by three laboratories. The laboratories classified each variant by using both the laboratory's own method and the ACMG-AMP criteria. The agreement between the two methods used within laboratories was high (K-alpha = 0.91) with 79% concordance. However, there was only 34% concordance for either classification system across laboratories. After consensus discussions and detailed review of the ACMG-AMP criteria, concordance increased to 71%. Causes of initial discordance in ACMG-AMP classifications were identified, and recommendations on clarification and increased specification of the ACMG-AMP criteria were made. In summary, although an initial pilot of the ACMG-AMP guidelines did not lead to increased concordance in variant interpretation, comparing variant interpretations to identify differences and having a common framework to facilitate resolution of those differences were beneficial for improving agreement, allowing iterative movement toward increased reporting consistency for variants in genes associated with monogenic disease