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The effects of enhanced UV-B radiation on three examples of European shrub-dominated vegetation were studied in situ. The experiments were in High Arctic Greenland, northern Sweden and Greece, and at all sites investigated the interaction of enhanced UV-B radiation (simulating a 15% reduction in the ozone layer) with artificially increased precipitation. The Swedish experiment also involved a study of the interaction between enhanced UV-B radiation and elevated CO2 (600 ppm). These field studies were supported by an outdoor controlled environment study in the United Kingdom involving modulated enhancement of UV-B radiation in combination with elevated CO2 (700 ppm). Effects of the treatments on plant growth, morphology, phenology and physiology were measured. The effects observed were species specific, and included both positive and negative responses to the treatments. In general the negative responses to UV-B treatments of up to three growing seasons were small, but included reductions in shoot growth and premature leaf senescence. Positive responses included a marked increase in flowering in some species and a stimulation of some photosynthetic processes. UV-B treatment enhanced the drought tolerance of Pinus pinea and Pinus halepensis by increasing leaf cuticle thickness. In general, there were few interactions between the elevated CO2 and enhanced UV-B treatments. There was evidence to suggest that although the negative responses to the treatments were small, damage may be increasing with time in some long-lived woody perennials. There was also evidence in the third year of treatments for effects of UV-B on insect herbivory in Vaccinium species. The experiments point to the necessity for long-term field investigations to predict the likely ecological consequences of increasing UV-B radiation. [ABSTRACT FROM AUTHOR]

1. The flow in two dimensions of an oscillating incompressible fluid near a circular cylinder with its axis normal to the direction of oscillation, is studied theoretically and experimentally. Starting from Navier-Stoke's differential equations the method of successive approximations has been used in order to get approximative solutions, when the appropriate boundary conditions are applied. The zeroth approximation gives the modified field of oscillation near the cylinder as a function of the viscosity. The first approximation also gives a stationary flow, which is found from the solution of an ordinary linear differential equation of 4th order. 2. Experiments have been carried out in air in a Kundt's tube. The velocities in the plane normal to the axis of the cylinder have been found by photographing smoke particles in air. The experimental and theoretical results agree fairly well. Comparison with corresponding data obtained by Schlichting is also made. Some G functions, derived from Hankel functions which have been used in the theoretical solutions, have been tabulated to 6 digits. [ABSTRACT FROM AUTHOR]

After the sudden and violent death of a loved one, many bereaved experience symptoms of prolonged grief (PG) and posttraumatic stress (PTS). The present study investigated the cross-sectional and longitudinal associations of grief-related rumination with PG and PTS symptoms among bereaved parents and siblings after the Utøya terror attack in Norway on 22 July 2011 (N = 110, M age  = 43.2 years, 59.1% female). Participants' responses on the Rumination Scale, the Inventory of Complicated Grief and the Impact of Event Scale-Revised 28, 40 and 102 months after the loss were analysed. Cross-sectionally and longitudinally, grief-related rumination was positively and strongly linked with PG and PTS symptoms. When controlling for the baseline levels of PG and PTS symptoms and demographics of the sample, grief-related rumination predicted PG symptoms after 12 months but not after 74 months. Further, grief-related rumination predicted significantly the PTS symptoms of avoidance after 12 and 74 months and hyperarousal after 74 months beyond sample demographics and baseline symptoms. The results suggest that grief-related rumination is an important factor in PG and PTS symptoms after traumatic bereavement., (© 2024 The Authors. Clinical Psychology & Psychotherapy published by John Wiley & Sons Ltd.)

Background: Prolonged grief disorder (PGD) has been added to the ICD-11 and DSM-5-TR. The Traumatic Grief Inventory-Self Report Plus (TGI-SR+) assesses self-rated PGD intensity as defined in ICD-11 and DSM-5-TR. The TGI-SR + is available in multiple languages, but has not been validated yet in Norwegian. Objective: The aim of this study was to evaluate the psychometric properties of the Norwegian TGI-SR + . Method: Bereaved adults ( N  = 307) whose child or sibling died ≥6 months ago due to a sudden or violent loss completed the TGI-SR + and measures for posttraumatic stress, depression, and precursor PGD symptoms. We examined the factor structure and internal consistency of the ICD-11 and DSM-5-TR PGD items. Convergent validity and known-groups validity was evaluated. Probable PGD cases, pair-wise agreement between diagnostic scoring rules for both PGD criteria-sets, and cut-off scores were calculated. Results: The 1-factor model for ICD-11 and DSM-5-TR PGD showed the best fit and demonstrated good internal consistency. Convergent validity was supported by strong associations between summed ICD-11 and DSM-5-TR PGD scores and summed posttraumatic stress, depression, and precursor prolonged grief scores. Known-groups validity was supported by PGD intensity being related to educational level and time since loss. The perfect pair-wise agreement was reached using the ICD-11 and DSM-5-TR PGD diagnostic scoring rules. The optimal cut-off score for detecting probable PGD cases, when summing all TGI-SR + items, was ≥73. Conclusions: The Norwegian TGI-SR + seems a valid and reliable instrument to assess ICD-11 and DSM-5-TR PGD intensity after losing a child or sibling under traumatic circumstances.

Aim: An individual with a blood-injection-injury (BII) phobia often avoids exposure to triggers, such as blood tests and clinic appointments, leading to potentially serious health complications. This population-based study examined the prevalence, stability and course of BII phobia in children and adolescents., Methods: The data came from the Trondheim Early Secure Study, conducted from 2007 to 2018. All children born in Trondheim, Norway, in 2003 and 2004 were invited to attend. Clinical interviews were conducted by trained personnel to assess BII phobia in 1042 children (51% female) every 2 years from 4 to 14 years of age. Latent growth curves and logistic regression analyses were used in the data analysis., Results: Just under 20% of the cohort experienced a BII phobia at least once, with no significant sex differences. The prevalence of BII phobias increased from 3% at 4 years of age and peaked at about 8% at 10 years of age, before levelling off. The two-year stability increased as 12-14 years of age approached., Conclusion: The prevalence of BII was affected by age, but not sex. Early BII phobias often recede with time, but children may need treatment if they persist from 8 years of age., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Pests often evolve resistance to pest controls used in agriculture and aquaculture. The rate of pest adaptation is influenced by the type of control, the selective pressure it imposes, and the gene flow between farms. By understanding how these factors influence evolution at the metapopulation level, pest management strategies that prevent resistance from evolving can be developed. We developed a model for the metapopulation and evolutionary dynamics of the salmon louse ( Lepeophtheirus salmonis ), which is a major parasite affecting salmon aquaculture. Different management scenarios were simulated across a network of salmon farms covering half of Norway, and their effects on louse epidemiology and evolution were investigated. We compared louse controls that differed in how they were deployed through time (discrete vs. continuous), how they impacted the louse life cycle, and in their overall efficacy. We adjusted the strength of selection imposed by treatments, the dominance effect of the resistant allele, and the geographic location at which resistance originated. Continuously acting strategies (e.g., louse-resistant salmon) were generally more effective than discrete strategies at controlling lice, especially when they increased louse mortality during early developmental stages. However, effective strategies also risked imposing frequent and/or strong selection on lice, thus driving rapid adaptation. Resistant alleles were more likely to be lost through genetic drift when they were recessive, had a low-fitness advantage, or originated in low-farm-density areas. The north-flowing current along the Norwegian coastline dispersed resistant genes from south to north, and limited gene flow in the opposite direction. We demonstrate how evolutionary models can produce quantitative predictions over large spatial and temporal scales and for a range of pest control scenarios. Quantitative outputs can be translated into practical management decisions applied at a regional level to minimise the risk of resistance developing., Competing Interests: The authors declare that they have no conflicts of interest., (© 2023 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Introduction: Root canal treatment (RCT) is often considered a difficult procedure for both the patient and treatment provider. The American Association of Endodontists case difficulty assessment form categorizes cases as minimal, moderate, and high difficulty level. We recently showed that endodontic mishaps occur frequently during treatment of teeth in high difficulty category. The aims were to investigate the clinical and radiographic outcome at least 4 years after RCT and to evaluate patients' perceived oral health-related quality of life (OHRQoL)., Methods: Two hundred thirty-four patients (257 endodontically treated teeth) who were previously included in a quality assurance study were offered a recall appointment at the Department of Clinical Dentistry, University of Bergen, Norway. Patients were given a thorough clinical, radiographic examination and asked to fill out the Oral Health Impact Profile-14 questionnaire., Results: A total of 149 patients (160 teeth) attended the 4-year (range, 4-6 years) recall appointment. An unchanged or lower Periapical Index (PAI) score at recall visit was registered on 153 teeth (95.6%) (P < .001). Radiographic success rate (PAI score ≤ 2) was 87.5%, and clinical success (absence of clinical signs and symptoms) was 88.8%. Both radiographic and clinical success was observed in 78.8% of teeth. Teeth in high difficulty category, instrumented with engine-driven files, and molars presented with significantly more clinical signs and symptoms but not high PAI score (PAI score ≥ 3) (P < .05). Endodontic mishaps such as overinstrumentation and overfill with gutta-percha resulted in significantly high PAI score (P < .05). Patients with no clinical signs and symptoms after RCT and elderly had a significantly better OHRQoL (P < .05)., Conclusions: Presence of clinical signs and symptoms rather than PAI score affected patients' OHRQoL., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Close friends are often an overlooked group of bereaved people. This study is based on a sub-project on young adults who experienced the loss of a close friend in the terrorist attack on Utøya, Norway, on 22 July 2011. Objective: The aim of this longitudinal study was to explore the relationship between complicated grief reactions, the need for help, and help received after losing a close friend to a traumatic death. Method: In total, data from 89 people (with a mean age of 21 years, 76.4% female) were collected at one or more of the four time-points: 18, 28, 40, and 102 months after the incident. Latent growth modelling was used to analyse levels of grief reactions and change over time, experienced need for help, and help received. Results: According to the results, the bereaved friends in our study were profoundly impacted by the loss and experienced level of reactions indicating complicated grief (mean scores on the Inventory of Complicated Grief varied from 36.2 to 23.7). A need for help was related to a decrease in grief symptoms, whereas a prolonged need for help was related to no reduction or an increase in grief. Received help was not related to decrease in grief symptoms. Conclusions: These findings underscore the need for continuous professional help, and demonstrate that the present help measures used after traumatic events may not adequately meet the needs of close bereaved friends. This emphasizes the importance of acknowledging friends as bereaved and that follow-up measures should also include this group. Finally, the study highlights the need to learn more about how professional can help bereaved friends.

Wild Atlantic salmon populations have declined in many regions and are affected by diverse natural and anthropogenic factors. To facilitate management guidelines, precise knowledge of mechanisms driving population changes in demographics and life history traits is needed.Our analyses were conducted on (a) age and growth data from scales of salmon caught by angling in the river Etneelva, Norway, covering smolt year classes from 1980 to 2018, (b) extensive sampling of the whole spawning run in the fish trap from 2013 onwards, and (c) time series of sea surface temperature, zooplankton biomass, and salmon lice infestation intensity.Marine growth during the first year at sea displayed a distinct stepwise decline across the four decades. Simultaneously, the population shifted from predominantly 1SW to 2SW salmon, and the proportion of repeat spawners increased from 3 to 7%. The latter observation is most evident in females and likely due to decreased marine exploitation. Female repeat spawners tended to be less catchable than males by anglers.Depending on the time period analyzed, marine growth rate during the first year at sea was both positively and negatively associated with sea surface temperature. Zooplankton biomass was positively associated with growth, while salmon lice infestation intensity was negatively associated with growth.Collectively, these results are likely to be linked with both changes in oceanic conditions and harvest regimes. Our conflicting results regarding the influence of sea surface temperature on marine growth are likely to be caused by long-term increases in temperature, which may have triggered (or coincided with) ecosystem shifts creating generally poorer growth conditions over time, but within shorter datasets warmer years gave generally higher growth. We encourage management authorities to expand the use of permanently monitored reference rivers with complete trapping facilities, like the river Etneelva, generating valuable long-term data for future analyses., Competing Interests: None declared., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Although many lose a close friend each year, they are seldom the focus of grief research. However, these losses often cause severe and long-lasting reactions. Deaths among adolescents and young adults are also often caused by traumatic events, e.g. from accidents, suicides, and homicides, placing them at significant risk for complicated grief reactions. The focus of this paper is bereaved friends after the shootings at Utøya, Norway in 2011, which is among a few studies that focus on bereaved friends, exploring how attachment affects the grief process after the loss of a close friend., Methods: This paper explores qualitative data from in-depth interviews with thirteen bereaved friends, conducted about 28 months after the loss. The interview sample consisted of eight females and five males, aged 18-31 years. The interviews were semi-structured, with a theme guide of 14 questions, and the method used for analyses was systematic text condensation., Results: Two main themes were identified from the analyses of the interviews: Friendship and Grief, with the subordinate themes: The importance of the friendship, Longing and remembrance, How the loss has affected other relationships, How the loss has affected the friend's daily lives, Processing of the grief and Not being family. For most of the bereaved friends the loss and the grief had a profound effect on them and their overall lives, from daily functioning in school or at work, to changes in attitudes, and the way they were met as bereaved., Conclusions: The support, intimacy, and feelings of togetherness we share with our friends are of great importance and value for all people, but maybe especially for young people. When adolescents and young adults experience losses, their reactions are often intense and long-lasting, and especially complicated grief reactions can affect school performance and concentration, health, result in emotional problems; and disrupt development (e.g. identity formation and social skills). We don't know much about the grief of bereaved friends and how their reactions can be explained. Thus, we hope that these findings could shed light on their grief reactions, and provide new knowledge on the short- and long-term psychological impact of losses of friends., (© 2022. The Author(s).)

This article presents results from one of the first longitudinal studies exploring the effects of losing a close friend to traumatic death, focusing on complicated grief over time and how this is affected by avoidant behavior and rumination about the loss. The sample consists of 88 persons (76% women and 24% men, mean age = 21) who lost a close friend in the Utøya killings in Norway on July 22, 2011.Quantitative data were collected at three time-points; 18, 28, and 40 months postloss. Main findings are that bereaved friends are heavily impacted by the loss and their grief reactions are affected negatively by avoidant behavior and rumination. This indicates that close bereaved friends are a group to be aware of and that there is a need for better strategies for identifying individuals in need for follow-up.

An accurate representation of the particle organic matter (POM) footprint is necessary in order to effectively predict impacts upon benthic communities and the risk of excessive organic enrichment beneath aquaculture sea-cages. Consequently, bottom-related processes such as particle resuspension must be adequately parametrized and evaluated in the available numerical models. We implemented two approaches to model POM resuspension in a Lagrangian particle tracking model and compared their influence on footprint extension and gradients of depositional flux against a no-resuspension scenario. We performed simulations in both exposed and protected aquaculture locations, and at different stages of the Atlantic Salmon (Salmo salar) production cycle in Norway. Our results indicate that the use of sediment-dependent thresholds for resuspension has the potential to regulate the high levels of erosion produced when selecting a low critical value in constant-threshold approaches, particularly in dynamic environments with mixed sediment types., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Maladaptive plasticity involving increased expression of AMPA-type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell-permeable, high-affinity (~2 nM) peptide inhibitor, Tat-P 4 -(C5) 2 , of the PDZ domain protein PICK1 to interfere with increased AMPAR expression. The affinity is obtained partly from the Tat peptide and partly from the bivalency of the PDZ motif, engaging PDZ domains from two separate PICK1 dimers to form a tetrameric complex. Bivalent Tat-P 4 -(C5) 2 disrupts PICK1 interaction with membrane proteins on supported cell membrane sheets and reduce the interaction of AMPARs with PICK1 and AMPA-receptor surface expression in vivo. Moreover, Tat-P 4 -(C5) 2 administration reduces spinal cord transmission and alleviates mechanical hyperalgesia in the spared nerve injury model of neuropathic pain. Taken together, our data reveal Tat-P 4 -(C5) 2 as a novel promising lead for neuropathic pain treatment and expand the therapeutic potential of bivalent inhibitors to non-tandem protein-protein interaction domains., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

People rarely specify what "early intervention" following bereavement means, so we explored the views of experienced professionals working primarily with bereaved children. In an anonymous online survey, 84 mental health professionals answered questions about the content and timeframe of early intervention. The types of interventions varied, but conversation and support were most frequent. Most considered early intervention to mean before or during the first month following the loss. Although meta-analyses show little benefit of early intervention, professionals disagree and see the need to tailor interventions to the type of death, the situation of the family, and the intensity of reactions.

Marine ecosystems are beset by disease outbreaks, and efficient strategies to control dispersal of pathogens are scarce. We tested whether introducing no-farming areas or 'firebreaks' could disconnect dispersal networks of a parasitic disease affecting the world's largest marine fish farming industry (∼1000 farms). Larval salmon lice (Lepeophtheirus salmonis) are released from and transported among salmon farms by ocean currents, creating inter-farm networks of louse dispersal. We used a state-of-the-art biophysical model to predict louse movement along the Norwegian coastline and network analysis to identify firebreaks to dispersal. At least one firebreak that fragmented the network into two large unconnected groups of farms was identified for all seasons. During spring, when wild salmon migrate out into the ocean, and louse levels per fish at farms must be minimised, two effective firebreaks were created by removing 13 and 21 farms (1.3% and 2.2% of all farms in the system) at ∼61°N and 67°N, respectively. We have demonstrated that dispersal models coupled with network analysis can identify no-farming zones that fragment dispersal networks. Reduced dispersal pathways should lower infection pressure at farms, slow the evolution of resistance to parasite control measures, and alleviate infection pressure on wild salmon populations., (Copyright © 2019 Australian Society for Parasitology. All rights reserved.)

PDZ domain scaffold proteins are molecular modules orchestrating cellular signalling in space and time. Here, we investigate assembly of PDZ scaffolds using supported cell membrane sheets, a unique experimental setup enabling direct access to the intracellular face of the cell membrane. Our data demonstrate how multivalent protein-protein and protein-lipid interactions provide critical avidity for the strong binding between the PDZ domain scaffold proteins, PICK1 and PSD-95, and their cognate transmembrane binding partners. The kinetics of the binding were remarkably slow and binding strength two-three orders of magnitude higher than the intrinsic affinity for the isolated PDZ interaction. Interestingly, discrete changes in the intrinsic PICK1 PDZ affinity did not affect overall binding strength but instead revealed dual scaffold modes for PICK1. Our data supported by simulations suggest that intrinsic PDZ domain affinities are finely tuned and encode specific cellular responses, enabling multiplexed cellular functions of PDZ scaffolds., Competing Interests: SE, TT, GV, IA, VW, KM, KT, UG, KM No competing interests declared, (© 2019, Erlendsson et al.)

BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation. This was accompanied by reduced hormone storage in the INS-1E cells. In Drosophila, disruption of the helix compromised growth regulation. By demonstrating size-dependent binding on insulin granules, our finding highlights the function of MCS for BAR domain proteins in a biological context distinct from their function, e.g., at the plasma membrane during endocytosis., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Synaptopathies contributing to neurodevelopmental disorders are linked to mutations in synaptic organizing molecules, including postsynaptic neuroligins, presynaptic neurexins, and MDGAs, which regulate their interaction. The role of MDGA1 in suppressing inhibitory versus excitatory synapses is controversial based on in vitro studies. We show that genetic deletion of MDGA1 in vivo elevates hippocampal CA1 inhibitory, but not excitatory, synapse density and transmission. Furthermore, MDGA1 is selectively expressed by pyramidal neurons and regulates perisomatic, but not distal dendritic, inhibitory synapses. Mdga1 -/- hippocampal networks demonstrate muted responses to neural excitation, and Mdga1 -/- mice are resistant to induced seizures. Mdga1 -/- mice further demonstrate compromised hippocampal long-term potentiation, consistent with observed deficits in spatial and context-dependent learning and memory. These results suggest that mutations in MDGA1 may contribute to cognitive deficits through altered synaptic transmission and plasticity by loss of suppression of inhibitory synapse development in a subcellular domain- and cell-type-selective manner., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Previous meta-analyses examined the effectiveness of interventions for bereaved children showing small to moderate effect sizes. However, no mixed methods systematic review was conducted on bereavement interventions following the loss of a parent focusing on the time since death in regard to the prevention of grief complications., Objective: The overall purpose of the review is to provide a rigorous synthesis of early intervention after parental death in childhood. Specifically, the aims are twofold: (1) to determine the rationales, contents, timeframes, and outcomes of early bereavement care interventions for children and/or their parents and (2) to assess the quality of current early intervention studies., Methods: Quantitative, qualitative, and mixed methods intervention studies that start intervention with parentally bereaved children (and/or their parents) up to 6 months postloss will be included in the review. The search strategy was based on the Population, Interventions, Comparator, Outcomes, and Study Designs (PICOS) approach, and it was devised together with a university librarian. The literature searches will be carried out in the Medical Literature Analysis and Retrieval System Online (MEDLINE), PsycINFO, Excerpta Medica Database (EMBASE), and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The Mixed Methods Appraisal Tool will be used to appraise the quality of eligible studies. All data will be narratively synthetized following the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews., Results: The systematic review is ongoing and the data search has started. The review is expected to be completed by the end of 2017. Findings will be submitted to leading journals for publication., Conclusions: In accordance with the current diagnostic criteria for prolonged grief as well as the users' perspectives literature, this systematic review outlines a possible sensitive period for early intervention following the death of a parent. The hereby presented protocol ensures the groundwork and transparency for the process of conducting the systematic review., Trial Registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42017064077; http://www.crd.york.ac.uk/PROSPERO/display&#95;record.asp?ID=CRD42017064077 (Archived by WebCite at http://www.webcitation.org/6rMq6F0fv)., (©Mariana Pereira, Iren Johnsen, May Aa Hauken, Pål Kristensen, Atle Dyregrov. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 29.06.2017.)

The class C G protein-coupled receptor GPRC6A is a putative nutrient-sensing receptor and represents a possible new drug target in metabolic disorders. However, the specific physiological role of this receptor has yet to be identified, and the mechanisms regulating its activity and cell surface availability also remain enigmatic. In the present study, we investigated the trafficking properties of GPRC6A by use of both a classical antibody feeding internalization assay in which cells were visualized using confocal microscopy and a novel internalization assay that is based on real-time measurements of fluorescence resonance energy transfer. Both assays revealed that GPRC6A predominantly undergoes constitutive internalization, whereas the agonist-induced effects were imperceptible. Moreover, postendocytic sorting was investigated by assessing the co-localization of internalized GPRC6A with selected Rab protein markers. Internalized GPRC6A was mainly co-localized with the early endosome marker Rab5 and the long loop recycling endosome marker Rab11 and to a much lesser extent with the late endosome marker Rab7. This suggests that upon agonist-independent internalization, GPRC6A is recycled via the Rab11-positive slow recycling pathway, which may be responsible for ensuring a persistent pool of GPRC6A receptors at the cell surface despite chronic agonist exposure. Distinct trafficking pathways have been reported for several of the class C receptors, and our results thus substantiate that non-canonical trafficking mechanisms are a common feature for the nutrient-sensing class C family that ensure functional receptors in the cell membrane despite prolonged agonist exposure., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Mutations in a synaptic organizing pathway contribute to autism. Autism-associated mutations in MDGA2 (MAM domain containing glycosylphosphatidylinositol anchor 2) are thought to reduce excitatory/inhibitory transmission. However, we show that mutation of Mdga2 elevates excitatory transmission, and that MDGA2 blocks neuroligin-1 interaction with neurexins and suppresses excitatory synapse development. Mdga2(+/-) mice, modeling autism mutations, demonstrated increased asymmetric synapse density, mEPSC frequency and amplitude, and altered LTP, with no change in measures of inhibitory synapses. Behavioral assays revealed an autism-like phenotype including stereotypy, aberrant social interactions, and impaired memory. In vivo voltage-sensitive dye imaging, facilitating comparison with fMRI studies in autism, revealed widespread increases in cortical spontaneous activity and intracortical functional connectivity. These results suggest that mutations in MDGA2 contribute to altered cortical processing through the dual disadvantages of elevated excitation and hyperconnectivity, and indicate that perturbations of the NRXN-NLGN pathway in either direction from the norm increase risk for autism., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The high affinity transporters for the monoamine neurotransmitters, dopamine, norepinephrine, and serotonin, play a key role in controlling monoaminergic neurotransmission. It is believed that the transporters (DAT, NET and SERT, respectively) are subject to tight regulation by the cellular signaling machinery to maintain monoaminergic homeostasis. Kinases constitute a pivotal role in cellular signaling, however, the regulation of monoamine transporters by the entire ensemble of kinases is unknown. Here, we perform a whole human kinome RNA interference screen to identify novel kinases involved in regulation of monoamine transporter function and surface expression. A primary screen in HEK 293 cells stably expressing DAT or SERT with siRNAs against 573 human kinases revealed 93 kinases putatively regulating transporter function. All 93 hits, which also included kinases previously implicated in monoamine transporter regulation, such as Protein kinase B (Akt) and mitogen-activated protein kinases (MAPK), were validated with a new set of siRNAs in a secondary screen. In this screen we assessed both changes in uptake and surface expression leading to selection of 11 kinases for further evaluation in HEK 293 cells transiently expressing DAT, SERT or NET. Subsequently, three kinases; salt inducible kinase 3 (SIK3), cAMP-dependent protein kinase catalytic subunit alpha (PKA C-α) and protein kinase X-linked (PrKX); were selected for additional exploration in catecholaminergic CATH.a differentiated cells (CAD) and rat chromocytoma (PC12) cells. Whereas SIK3 likely transcriptionally regulated expression of the three transfected transporters, depletion of PKA C-α was shown to decrease SERT function. Depletion of PrKX caused decreased surface expression and function of DAT without changing protein levels, suggesting that PrKX stabilizes the transporter at the cell surface. Summarized, our data provide novel insight into kinome regulation of the monoamine transporters and identifies PrKX as a yet unappreciated possible regulator of monoamine transporter function., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Postnatal inhibition or deletion of angiotensin II (ANG II) AT1 receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary for the development of the renal medullary microcirculation. Endothelial cell-specific immunolabeling of kidney sections from rats showed immature vascular bundles at postnatal day (P) 10 with subsequent expansion of bundles until P21. Medullary VEGF protein abundance coincided with vasa recta bundle formation. In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg·kg(-1)·day(-1)) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria. Stereological quantification showed a significant reduction in total length (386 ± 13 vs. 219 ± 16 m), surface area, and volume of medullary microvessels. Vascular bundle architecture was unaffected. ANG II-AT1A/1B (-/-) mice kidneys displayed poorly defined vasa recta bundles whereas mice with collecting duct principal cell-specific AT1A deletion displayed no medullary microvascular phenotype. In conclusion, VEGFR2 signaling during postnatal development is necessary for expansion of the renal medullary microcirculation but not structural patterning of the vasa recta bundles, which occurs through an AT1-mediated mechanism.

Salmon lice is one of the major parasitic problems affecting wild and farmed salmonid species. The planktonic larval stages of these marine parasites can survive for extended periods without a host and are transported long distances by water masses. Salmon lice larvae have limited swimming capacity, but can influence their horizontal transport by vertical positioning. Here, we adapted a coupled biological-physical model to calculate the distribution of farm-produced salmon lice (Lepeophtheirus salmonis) during winter in the southwest coast of Norway. We tested 4 model simulations to see which best represented empirical data from two sources: (1) observed lice infection levels reported by farms; and (2) experimental data from a vertical exposure experiment where fish were forced to swim at different depths with a lice-barrier technology. Model simulations tested were different development time to the infective stage (35 or 50°-days), with or without the presence of temperature-controlled vertical behaviour of lice early planktonic stages (naupliar stages). The best model fit occurred with a 35°-day development time to the infective stage, and temperature-controlled vertical behaviour. We applied this model to predict the effectiveness of depth-based preventive lice-barrier technologies. Both simulated and experimental data revealed that hindering fish from swimming close to the surface efficiently reduced lice infection. Moreover, while our model simulation predicted that this preventive technology is widely applicable, its effectiveness will depend on environmental conditions. Low salinity surface waters reduce the effectiveness of this technology because salmon lice avoid these conditions, and can encounter the fish as they sink deeper in the water column. Correctly parameterized and validated salmon lice dispersal models can predict the impact of preventive approaches to control this parasite and become an essential tool in lice management strategies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Neurotrophin-3 (NT-3) and its high-affinity receptor TrkC play crucial trophic roles in neuronal differentiation, axon outgrowth, and synapse development and plasticity in the nervous system. We demonstrated previously that postsynaptic TrkC functions as a glutamatergic synapse-inducing (synaptogenic) cell adhesion molecule trans-interacting with presynaptic protein tyrosine phosphatase σ (PTPσ). Given that NT-3 and PTPσ bind distinct domains of the TrkC extracellular region, here we tested the hypothesis that NT-3 modulates TrkC/PTPσ binding and synaptogenic activity. NT-3 enhanced PTPσ binding to cell surface-expressed TrkC and facilitated the presynapse-inducing activity of TrkC in rat hippocampal neurons. Imaging of recycling presynaptic vesicles combined with TrkC knockdown and rescue approaches demonstrated that NT-3 rapidly potentiates presynaptic function via binding endogenous postsynaptic TrkC in a tyrosine kinase-independent manner. Thus, NT-3 positively modulates the TrkC-PTPσ complex for glutamatergic presynaptic assembly and function independently from TrkC kinase activation. Our findings provide new insight into synaptic roles of neurotrophin signaling and mechanisms controlling synaptic organizing complexes. Significance statement: Although many synaptogenic adhesion complexes have been identified in recent years, little is known about modulatory mechanisms. Here, we demonstrate a novel role of neurotrophin-3 in synaptic assembly and function as a positive modulator of the TrkC-protein tyrosine phosphatase σ complex. This study provides new insight into the involvement of neurotrophin signaling in synapse development and plasticity, presenting a molecular mechanism that may underlie previous observations of short- and long-term enhancement of presynaptic function by neurotrophin. Given the links of synaptogenic adhesion molecules to autism and schizophrenia, this study might also contribute to a better understanding of the pathogenesis of these disorders and provide a new direction for ameliorating imbalances in synaptic signaling networks., (Copyright © 2015 the authors 0270-6474/15/3512425-07$15.00/0.)

PICK1 is a neuronal scaffolding protein containing a PDZ domain and an auto-inhibited BAR domain. BAR domains are membrane-sculpting protein modules generating membrane curvature and promoting membrane fission. Previous data suggest that BAR domains are organized in lattice-like arrangements when stabilizing membranes but little is known about structural organization of BAR domains in solution. Through a small-angle X-ray scattering (SAXS) analysis, we determine the structure of dimeric and tetrameric complexes of PICK1 in solution. SAXS and biochemical data reveal a strong propensity of PICK1 to form higher-order structures, and SAXS analysis suggests an offset, parallel mode of BAR-BAR oligomerization. Furthermore, unlike accessory domains in other BAR domain proteins, the positioning of the PDZ domains is flexible, enabling PICK1 to perform long-range, dynamic scaffolding of membrane-associated proteins. Together with functional data, these structural findings are compatible with a model in which oligomerization governs auto-inhibition of BAR domain function., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This article presents qualitative interview data from the research project "Grief Support Groups in Norway" (2009-2011). The aim of this part of the study was to investigate grief group participant's experiences, benefits, and satisfaction with the grief group. Positive aspects were to meet with peers, share thoughts and feelings, normalization, exchange advice and information, and share hope. On the negative side were unfulfilled needs or expectations, additional personal stress, and unsatisfactory structure, organization, and leadership. Importantly, lack of screening caused bereaved with complicated grief to participate in groups that were non-therapeutic, leaving them with insufficient help. Also, group leaders were not always considered knowledgeable of group processes and impacts of different organizational and structural factors on groups. Conclusively, participants' needs and expectations should be considered when planning and organizing groups, in order to conduct helpful groups and increase the experience of a positive outcome.

Based on the results from the qualitative part of the study "Grief Groups in Norway" conducted in 2009-2011, this article focuses on grief group participants' recommendations for good or ideal grief groups. Participants have insightful observations about grief groups and how they can be improved, and taking their point of view seriously is one important way of ensuring that users of such group get an optimal experience from joining such groups. Using their experiences to adjust the structure and function of the groups, one can allow for practical solutions for organizations that have difficulties starting up grief support groups, for example, in areas where the population density is low. A major finding in this study was that grief group participants stressed the importance of thorough information before and at the start of grief groups. This concerned information about the aim, structure, organization, and possible effects and limitations of group participation.

The dopamine transporter mediates reuptake of dopamine from the synaptic cleft. The cellular mechanisms controlling dopamine transporter levels in striatal nerve terminals remain poorly understood. The dopamine transporters contain a C-terminal PDZ (PSD-95/Discs-large/ZO-1) domain-binding sequence believed to bind synaptic scaffolding proteins, but its functional significance is uncertain. Here we demonstrate that two different dopamine transporter knock-in mice with disrupted PDZ-binding motifs (dopamine transporter-AAA and dopamine transporter+Ala) are characterized by dramatic loss of dopamine transporter expression in the striatum, causing hyperlocomotion and attenuated response to amphetamine. In cultured dopaminergic neurons and striatal slices from dopamine transporter-AAA mice, we find markedly reduced dopamine transporter surface levels and evidence for enhanced constitutive internalization. In dopamine transporter-AAA neurons, but not in wild-type neurons, surface levels are rescued in part by expression of a dominant-negative dynamin mutation (K44A). Our findings suggest that PDZ-domain interactions are critical for synaptic distribution of dopamine transporter in vivo and thereby for proper maintenance of dopamine homoeostasis.

The natural field margin ecotone from the field border and into a cropped field hosts a diversity of plant species. In conventional cropped fields, biodiversity suffers from fertilizer and pesticide application. In our study at Danish conventional spring-barley fields, we laid out bufferzones with no pesticide application spraying after sowing, with the widths: 24, 12, 6 and 4 m (and control) to the field edge hedgerow. Through one season: plant species number, biodiversity and evenness for each bufferzone at the distances: 18, 9, 5, 2 and 0 m from the hedgerow were significantly affected by distance to the hedge and by width of bufferzone. The bufferzones affected: species number (total of 92 weed species), species diversity (1.27 to 0.44) and species evenness index (0.63 to 0.87), and revealed that the bufferzone of 24 m gave the largest improvementof the field margin for plants. Decreasing the bufferzone widths provided smaller biodiversity and larger evenness of plants at distances larger than the buffer width: the distance at which diversity (Shannons) was reduced by half the difference between hedge- and field diversity was 1.2, 3.1, 6.7, 10.8 and 10.9 m in bufferwidth treatments of 0, 4, 6, 12 and 24 m; likewise, the half-way distance for Smiths and Wilsons evenness index was 1.2, 1.7, 5.4, 14.0 and 30.2 m in the bufferwidth treatments of 0, 4, 6,12 and 24 m. Based on modelled diversity and evenness indexes a positive effect of buffer was evident from 6 m bufferzone. The average diversity over the distances from 0 to 18 m was 0.66, 0.75, 0.98, 1.14 and 1.11 in bufferwidth treatments of 0, 4, 6, 12 and 24 m and the average evenness over the distances from 0 to 18 m was 0.82, 0.80, 0.74, 0.66 and 0.63, in bufferwidth treatments of 0, 4, 6, 12 and 24 m. Furthermore, the accumulated number of species revealed that a bufferzone width of at least 6 m was needed to significantly increase the species richness at all distances between 2 and 18 m. At 18 m distance, the accumulated number of species was 37.1, 39.7, 41.2, 42.4 and 42.7 in bufferwidth treatments of 0, 4, 6, 12 and 24 m.