The Methylococcus capsulatus (Bath) Secreted Protein, MopE*, Binds Both Reduced and Oxidized Copper

Under copper limiting growth conditions the methanotrophic bacterium Methylococcus capsulatus (Bath) secrets essentially only one protein, MopE*, to the medium. MopE* is a copper-binding protein whose structure has been determined by X-ray crystallography. The structure of MopE* revealed a unique high affinity copper binding site consisting of two histidine imidazoles and one kynurenine, the latter an oxidation product of Trp130. In this study, we demonstrate that the copper ion coordinated by this strong binding site is in the Cu(I) state when MopE* is isolated from the growth medium of M. capsulatus. The conclusion is based on X-ray Near Edge Absorption spectroscopy (XANES), and Electron Paramagnetic Resonance (EPR) studies. EPR analyses demonstrated that MopE*, in addition to the strong copper-binding site, also binds Cu(II) at two weaker binding sites. Both Cu(II) binding sites have properties typical of non-blue type II Cu (II) centres, and the strongest of the two Cu(II) sites is characterised by a relative high hyperfine coupling of copper (

Untreated PKU patients without intellectual disability: What do they teach us?

Phenylketonuria (PKU) management is aimed at preventing neurocognitive and psychosocial dysfunction by keeping plasma phenylalanine concentrations within the recommended target range. It can be questioned, however, whether universal plasma phenylalanine target levels would result in optimal neurocognitive outcomes for all patients, as similar plasma phenylalanine concentrations do not seem to have the same consequences to the brain for each PKU individual. To better understand the inter-individual differences in brain vulnerability to high plasma phenylalanine concentrations, we aimed to identify untreated and/or late-diagnosed PKU patients with near-normal outcome, despite high plasma phenylalanine concentrations, who are still alive. In total, we identified 16 such cases. While intellectual functioning in these patients was relatively unaffected, they often did present other neurological, psychological, and behavioral problems. Thereby, these “unusual” PKU patients show that the classical symptomatology of untreated or late-treated PKU may have to be rewritten. Moreover, these cases show that a lack of intellectual dysfunction despite high plasma phenylalanine concentrations does not necessarily imply that these high phenylalanine concentrations have not been toxic to the brain. Also, these cases may suggest that different mechanisms are involved in PKU pathophysiology, of which the relative importance seems to differ between patients and possibly also with increasing age. Further research should aim to better distinguish PKU patients with respect to their cerebral effects to high plasma phenylalanine concentrations

Dynamical models for sand ripples beneath surface waves

We introduce order parameter models for describing the dynamics of sand ripple patterns under oscillatory flow. A crucial ingredient of these models is the mass transport between adjacent ripples, which we obtain from detailed numerical simulations for a range of ripple sizes. Using this mass transport function, our models predict the existence of a stable band of wavenumbers limited by secondary instabilities. Small ripples coarsen in our models and this process leads to a sharply selected final wavenumber, in agreement with experimental observations.Comment: 9 pages. Shortened version of previous submissio

Aphasia and Spirituality: the feasibility of assessment and intervention using WELLHEAD and SHALOM

Background: Spiritual aspects of aphasia rehabilitation are poorly understood, though identified within adjustment. Existing spiritual health assessments have not been used with people with aphasia, and no structured program to facilitate intervention has been documented, despite acknowledgments that spirituality is important in health and wellbeing and distinct from quality of life and mental health. Aims: Mixed methods were used to investigate the accessibility and acceptability of a spiritual health assessment (SHALOM) and WELLHEAD, a toolkit originated by Mumby for spiritual health assessment and intervention, using the religiously neutral dimensions of ‘WIDE, LONG, HIGH and DEEP’. Method: A Steering group (five people with aphasia) shaped the feasibility study cyclically, agreeing that ‘Meaning and purpose’ defined spirituality, and selecting SHALOM. WELLHEAD was modified collaboratively with the Steering group and Hospital Chaplain. A convenience sample of 10 people with aphasia (discharged from therapy) represented diverse aphasia histories, ages and religious backgrounds. Participants completed a two-hour session using SHALOM, the WELLHEAD toolkit and a feedback questionnaire within video-recorded interviews. Quantitative results from all three components were integrated with a qualitative thematic analysis in NVivo 11 including numerical and descriptive summaries verified by the participants, feedback interview transcripts and field notes with reflections. The thematic analysis was systematically and independently verified by a co-researcher. Feedback from participants was further verified by incorporating their comments from reviewing the overall findings. Results: Quantitative and qualitative feedback evaluated the materials positively. Thematic analysis provided evidence of the accessibility, acceptability and positive impact of WELLHEAD irrespective of aphasia severity or aetiology, and religious background. ‘Belief’, ‘Faith’ and ‘Religion’ were disambiguated. SHALOM was also linguistically and cognitively accessible with communication support even for those with severe aphasia. Scores from WELLHEAD and SHALOM were compared and set into the context of wider standardisation of SHALOM, providing the first evidence of spiritual health measures in participants with aphasia. Conclusions: This preliminary work lays foundations for spiritual assessment and intervention in aphasia. Establishing the psychometric properties of SHALOM and WELLHEAD in people with aphasia requires a larger sample. Additional study of intervention is proposed, with clear potential for wider application of WELLHEAD in diverse settings and populations

Untreated PKU patients without intellectual disability: what do they teach us?

Phenylketonuria (PKU) management is aimed at preventing neurocognitive and psychosocial dysfunction by keeping plasma phenylalanine concentrations within the recommended target range. It can be questioned, however, whether universal plasma phenylalanine target levels would result in optimal neurocognitive outcomes for all patients, as similar plasma phenylalanine concentrations do not seem to have the same consequences to the brain for each PKU individual. To better understand the inter-individual differences in brain vulnerability to high plasma phenylalanine concentrations, we aimed to identify untreated and/or late-diagnosed PKU patients with near-normal outcome, despite high plasma phenylalanine concentrations, who are still alive. In total, we identified 16 such cases. While intellectual functioning in these patients was relatively unaffected, they often did present other neurological, psychological, and behavioral problems. Thereby, these "unusual" PKU patients show that the classical symptomatology of untreated or late-treated PKU may have to be rewritten. Moreover, these cases show that a lack of intellectual dysfunction despite high plasma phenylalanine concentrations does not necessarily imply that these high phenylalanine concentrations have not been toxic to the brain. Also, these cases may suggest that different mechanisms are involved in PKU pathophysiology, of which the relative importance seems to differ between patients and possibly also with increasing age. Further research should aim to better distinguish PKU patients with respect to their cerebral effects to high plasma phenylalanine concentrations

Untreated PKU Patients without Intellectual Disability: What Do They Teach Us?

Phenylketonuria (PKU) management is aimed at preventing neurocognitive and psychosocial dysfunction by keeping plasma phenylalanine concentrations within the recommended target range. It can be questioned, however, whether universal plasma phenylalanine target levels would result in optimal neurocognitive outcomes for all patients, as similar plasma phenylalanine concentrations do not seem to have the same consequences to the brain for each PKU individual. To better understand the inter-individual differences in brain vulnerability to high plasma phenylalanine concentrations, we aimed to identify untreated and/or late-diagnosed PKU patients with near-normal outcome, despite high plasma phenylalanine concentrations, who are still alive. In total, we identified 16 such cases. While intellectual functioning in these patients was relatively unaffected, they often did present other neurological, psychological, and behavioral problems. Thereby, these "unusual" PKU patients show that the classical symptomatology of untreated or late-treated PKU may have to be rewritten. Moreover, these cases show that a lack of intellectual dysfunction despite high plasma phenylalanine concentrations does not necessarily imply that these high phenylalanine concentrations have not been toxic to the brain. Also, these cases may suggest that different mechanisms are involved in PKU pathophysiology, of which the relative importance seems to differ between patients and possibly also with increasing age. Further research should aim to better distinguish PKU patients with respect to their cerebral effects to high plasma phenylalanine concentrations

Location of studies and evidence of effects of herbivory on Arctic vegetation : a systematic map

Background: Herbivores modify the structure and function of tundra ecosystems. Understanding their impacts is necessary to assess the responses of these ecosystems to ongoing environmental changes. However, the effects of herbivores on plants and ecosystem structure and function vary across the Arctic. Strong spatial variation in herbivore effects implies that the results of individual studies on herbivory depend on local conditions, i.e., their ecological context. An important first step in assessing whether generalizable conclusions can be produced is to identify the existing studies and assess how well they cover the underlying environmental conditions across the Arctic. This systematic map aims to identify the ecological contexts in which herbivore impacts on vegetation have been studied in the Arctic. Specifically, the primary question of the systematic map was: "What evidence exists on the effects of herbivores on Arctic vegetation?". Methods: We used a published systematic map protocol to identify studies addressing the effects of herbivores on Arctic vegetation. We conducted searches for relevant literature in online databases, search engines and specialist websites. Literature was screened to identify eligible studies, defined as reporting primary data on herbivore impacts on Arctic plants and plant communities. We extracted information on variables that describe the ecological context of the studies, from the studies themselves and from geospatial data. We synthesized the findings narratively and created a Shiny App where the coded data are searchable and variables can be visually explored. Review findings We identified 309 relevant articles with 662 studies (representing different ecological contexts or datasets within the same article). These studies addressed vertebrate herbivory seven times more often than invertebrate herbivory. Geographically, the largest cluster of studies was in Northern Fennoscandia. Warmer and wetter parts of the Arctic had the largest representation, as did coastal areas and areas where the increase in temperature has been moderate. In contrast, studies spanned the full range of ecological context variables describing Arctic vertebrate herbivore diversity and human population density and impact. Conclusions: The current evidence base might not be sufficient to understand the effects of herbivores on Arctic vegetation throughout the region, as we identified clear biases in the distribution of herbivore studies in the Arctic and a limited evidence base on invertebrate herbivory. In particular, the overrepresentation of studies in areas with moderate increases in temperature prevents robust generalizations about the effects of herbivores under different climatic scenarios.Peer reviewe