The application of sediment fingerprinting to floodplain and lake sediment cores: assumptions and uncertainties evaluated through case studies in the Nene Basin, UK

Purpose: Fine sediment has been shown to be a major cause of the degradation of lakes and rivers and, as a result, research has been directed towards the understanding of fine sediment dynamics and the minimisation of sediment inputs. The use of tracers within a sediment fingerprinting framework has become a heavily used technique to investigate the sources of fine sediment pressures. When combined with the use of historically deposited sediment, the technique provides the opportunity to reconstruct past changes to the environment. However, alterations to tracer signatures during sediment transport and storage are a major potential source of uncertainty associated with tracer use. At present, few studies have quantified the uncertainties associated with tracer use. Materials and methods: This paper investigated uncertainty by determining the differences between sediment provenance predictions obtained using lithogenic radionuclide, geochemical and mineral magnetic signatures when fingerprinting lake and floodplain sedimentary deposits. It also investigated the potential causes of the observed differences. Results and discussion: A reservoir core was fingerprinted with the least uncertainty, with tracer group predictions ∼28 % apart and a consistent down-core trend in changing sediment provenance produced. When fingerprinting an on-line lake core and four floodplain cores, differences between tracer group predictions were as large as 100 %; the down-core trends in changing sediment provenance were also different. The differences between tracer group predictions could be attributed to the organic matter content and particle size of the sediment. There was also evidence of the in-growth of bacterially derived magnetite and chemical dissolution affecting the preservation of tracer signatures. Simple data corrections for sediment organic matter content and particle size did not result in significantly greater agreement between the predictions of the different tracer groups. Likewise, the inclusions of weightings for tracer discriminatory efficiency and within-source variability had minimal effects on the fingerprinting results. Conclusions: This paper highlights the importance of tracer selection and the consideration of recognising tracer non-conservatism when using lake and floodplain sediment deposits to reconstruct anthropogenic changes to the environment and changing sediment dynamics. It was recommended that future research focus on the assessment of uncertainty using the artificial mixing of sediment source samples, the limitation of the fingerprinting to narrow particle size fractions and the development of specific particle size and organic matter correction factors for each tracer

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Conflict in object affordance revealed by grip force

Viewing objects can result in automatic, partial activation of motor plans associated with them—“object affordance”. Here, we recorded grip force simultaneously from both hands in an object affordance task to investigate the effects of conflict between coactivated responses. Participants classified pictures of objects by squeezing force transducers with their left or right hand. Responses were faster on trials where the object afforded an action with the same hand that was required to make the response (congruent trials) compared to the opposite hand (incongruent trials). In addition, conflict between coactivated responses was reduced if it was experienced on the preceding trial, just like Gratton adaptation effects reported in “conflict” tasks (e.g., Eriksen flanker). This finding suggests that object affordance demonstrates conflict effects similar to those shown in other stimulus–response mapping tasks and thus could be integrated into the wider conceptual framework on overlearnt stimulus–response associations. Corrected erroneous responses occurred more frequently when there was conflict between the afforded response and the response required by the task, providing direct evidence that viewing an object activates motor plans appropriate for interacting with that object. Recording continuous grip force, as here, provides a sensitive way to measure coactivated responses in affordance tasks

Disorder Predictors Also Predict Backbone Dynamics for a Family of Disordered Proteins

Several algorithms have been developed that use amino acid sequences to predict whether or not a protein or a region of a protein is disordered. These algorithms make accurate predictions for disordered regions that are 30 amino acids or longer, but it is unclear whether the predictions can be directly related to the backbone dynamics of individual amino acid residues. The nuclear Overhauser effect between the amide nitrogen and hydrogen (NHNOE) provides an unambiguous measure of backbone dynamics at single residue resolution and is an excellent tool for characterizing the dynamic behavior of disordered proteins. In this report, we show that the NHNOE values for several members of a family of disordered proteins are highly correlated with the output from three popular algorithms used to predict disordered regions from amino acid sequence. This is the first test between an experimental measure of residue specific backbone dynamics and disorder predictions. The results suggest that some disorder predictors can accurately estimate the backbone dynamics of individual amino acids in a long disordered region

Trait Rumination Influences Neural Correlates of the Anticipation but Not the Consumption Phase of Reward Processing

Cumulative evidence suggests that trait rumination can be defined as an abstract information processing mode, which leads people to constantly anticipate the likely impact of present events on future events and experiences. A previous study with remitted depressed patients suggested that enhanced rumination tendencies distort brain mechanisms of anticipatory processes associated with reward and loss cues. In the present study, we explored the impact of trait rumination on neural activity during reward and loss anticipation among never-depressed people. We analyzed the data of 37 healthy controls, who performed the monetary incentive delay (MID) task which was designed for the simultaneous measurement of the anticipation (motivational) and consumption (hedonic) phase of reward processing, during functional magnetic resonance imaging (fMRI). Our results show that rumination-after controlling for age, gender, and current mood-significantly influenced neural responses to reward (win) cues compared to loss cues. Blood-oxygenation-level-dependent (BOLD) activity in the left inferior frontal gyrus (IFG) triangularis, left anterior insula, and left rolandic operculum was positively related to Ruminative Response Scale (RRS) scores. We did not detect any significant rumination-related activations associated with win-neutral or loss-neutral cues and with reward or loss consumption. Our results highlight the influence of trait rumination on reward anticipation in a non-depressed sample. They also suggest that for never-depressed ruminators rewarding cues are more salient than loss cues. BOLD response during reward consumption did not relate to rumination, suggesting that rumination mainly relates to processing of the motivational (wanting) aspect of reward rather than the hedonic (liking) aspect, at least in the absence of pathological mood

Self-Organization and Regulation of Intrinsically Disordered Proteins with Folded N-Termini

How do mostly disordered proteins coordinate the specific assembly of very large signal transduction protein complexes? A newly emerging hypothesis may provide some clues towards a molecular mechanism

Identification of Critical Amino Acids in an Immunodominant IgE Epitope of Pen c 13, a Major Allergen from Penicillium citrinum

Background: Pen c 13, identified as a 33-kDa alkaline serine protease, is a major allergen secreted by Penicillium citrinum. Detailed knowledge about the epitopes responsible for IgE binding would help inform the diagnosis/prognosis of fungal allergy and facilitate the rational design of hypoallergenic candidate vaccines. The goal of the present study was to characterize the IgE epitopes of Pen c 13. Methodology/Principal Findings: Serum samples were collected from 10 patients with mold allergy and positive Pen c 13 skin test results. IgE-binding epitopes on rPen c 13 were mapped using an enzymatic digestion and chemical cleavage method, followed by dot-blotting and mass spectrometry. A B-cell epitope-predicting server and molecular modeling were used to predict the residues most likely involved in IgE binding. Theoretically predicted IgE-binding regions were further confirmed by site-directed mutagenesis assays. At least twelve different IgE-binding epitopes located throughout Pen c 13 were identified. Of these, peptides S16 (A 148 –E 166) and S22 (A 243 –K 274) were recognized by sera from 90 % and 100 % of the patients tested, and were further confirmed by inhibition assays. Peptide S22 was selected for further analysis of IgE-binding ability. The results of serum screening showed that the majority of IgE-binding ability resided in the C-terminus. One Pen c 13 mutant, G270A (T 261 –K 274), exhibited clearly enhanced IgE reactivity, whereas another, K274A, exhibited dramatically reduced IgE reactivity

Prediction of Protein Binding Regions in Disordered Proteins

Many disordered proteins function via binding to a structured partner and undergo a disorder-to-order transition. The coupled folding and binding can confer several functional advantages such as the precise control of binding specificity without increased affinity. Additionally, the inherent flexibility allows the binding site to adopt various conformations and to bind to multiple partners. These features explain the prevalence of such binding elements in signaling and regulatory processes. In this work, we report ANCHOR, a method for the prediction of disordered binding regions. ANCHOR relies on the pairwise energy estimation approach that is the basis of IUPred, a previous general disorder prediction method. In order to predict disordered binding regions, we seek to identify segments that are in disordered regions, cannot form enough favorable intrachain interactions to fold on their own, and are likely to gain stabilizing energy by interacting with a globular protein partner. The performance of ANCHOR was found to be largely independent from the amino acid composition and adopted secondary structure. Longer binding sites generally were predicted to be segmented, in agreement with available experimentally characterized examples. Scanning several hundred proteomes showed that the occurrence of disordered binding sites increased with the complexity of the organisms even compared to disordered regions in general. Furthermore, the length distribution of binding sites was different from disordered protein regions in general and was dominated by shorter segments. These results underline the importance of disordered proteins and protein segments in establishing new binding regions. Due to their specific biophysical properties, disordered binding sites generally carry a robust sequence signal, and this signal is efficiently captured by our method. Through its generality, ANCHOR opens new ways to study the essential functional sites of disordered proteins

Gaze-grasp coordination in obstacle avoidance: differences between binocular and monocular viewing

Most adults can skillfully avoid potential obstacles when acting in everyday cluttered scenes. We examined how gaze and hand movements are normally coordinated for obstacle avoidance and whether these are altered when binocular depth information is unavailable. Visual fixations and hand movement kinematics were simultaneously recorded, while 13 right-handed subjects reached-to-precision grasp a cylindrical household object presented alone or with a potential obstacle (wine glass) located to its left (thumb's grasp side), right or just behind it (both closer to the finger's grasp side) using binocular or monocular vision. Gaze and hand movement strategies differed significantly by view and obstacle location. With binocular vision, initial fixations were near the target's centre of mass (COM) around the time of hand movement onset, but usually shifted to end just above the thumb's grasp site at initial object contact, this mainly being made by the thumb, consistent with selecting this digit for guiding the grasp. This strategy was associated with faster binocular hand movements and improved end-point grip precision across all trials than with monocular viewing, during which subjects usually continued to fixate the target closer to its COM despite a similar prevalence of thumb-first contacts. While subjects looked directly at the obstacle at each location on a minority of trials and their overall fixations on the target were somewhat biased towards the grasp side nearest to it, these gaze behaviours were particularly marked on monocular vision-obstacle behind trials which also commonly ended in finger-first contact. Subjects avoided colliding with the wine glass under both views when on the right (finger side) of the workspace by producing slower and straighter reaches, with this and the behind obstacle location also resulting in 'safer' (i.e. narrower) peak grip apertures and longer deceleration times than when the goal object was alone or the obstacle was on its thumb side. But monocular reach paths were more variable and deceleration times were selectively prolonged on finger-side and behind obstacle trials, with this latter condition further resulting in selectively increased grip closure times and corrections. Binocular vision thus provided added advantages for collision avoidance, known to require intact dorsal cortical stream processing mechanisms, particularly when the target of the grasp and potential obstacle to it were fairly closely separated in depth. Different accounts of the altered monocular gaze behaviour converged on the conclusion that additional perceptual and/or attentional resources are likely engaged compared to when continuous binocular depth information is available. Implications for people lacking binocular stereopsis are briefly considered

Interaction between Attention and Bottom-Up Saliency Mediates the Representation of Foreground and Background in an Auditory Scene

Bottom-up (stimulus-driven) and top-down (attentional) processes interact when a complex acoustic scene is parsed. Both modulate the neural representation of the target in a manner strongly correlated with behavioral performance