Seafloor primary production in a changing Arctic Ocean.

Phytoplankton and sea ice algae are traditionally considered to be the main primary producers in the Arctic Ocean. In this Perspective, we explore the importance of benthic primary producers (BPPs) encompassing microalgae, macroalgae, and seagrasses, which represent a poorly quantified source of Arctic marine primary production. Despite scarce observations, models predict that BPPs are widespread, colonizing ~3 million km2 of the extensive Arctic coastal and shelf seas. Using a synthesis of published data and a novel model, we estimate that BPPs currently contribute ~77 Tg C y-1 of primary production to the Arctic, equivalent to ~20 to 35% of annual phytoplankton production. Macroalgae contribute ~43 Tg C y-1, seagrasses contribute ~23 Tg C y-1, and microalgae-dominated shelf habitats contribute ~11 to 16 Tg C y-1. Since 2003, the Arctic seafloor area exposed to sunlight has increased by ~47,000 km2 y-1, expanding the realm of BPPs in a warming Arctic. Increased macrophyte abundance and productivity is expected along Arctic coastlines with continued ocean warming and sea ice loss. However, microalgal benthic primary production has increased in only a few shelf regions despite substantial sea ice loss over the past 20 y, as higher solar irradiance in the ice-free ocean is counterbalanced by reduced water transparency. This suggests complex impacts of climate change on Arctic light availability and marine primary production. Despite significant knowledge gaps on Arctic BPPs, their widespread presence and obvious contribution to coastal and shelf ecosystem production call for further investigation and for their inclusion in Arctic ecosystem models and carbon budgets.

Forest edge effects on moss growth are amplified by drought.

Forest fragmentation increases the amount of edges in the landscape. Differences in wind, radiation, and vegetation structure create edge-to-interior gradients in forest microclimate, and these gradients are likely to be more pronounced during droughts and heatwaves. Although the effects of climate extremes on edge influences have potentially strong and long-lasting impacts on forest understory biodiversity, they are not well understood and are not often considered in management and landscape planning. Here we used a novel method of retrospectively quantifying growth to assess biologically relevant edge influences likely caused by microclimate using Hylocomium splendens, a moss with annual segments. We examined how spatio-temporal variation in drought across 3 years and 46 sites in central Sweden, affected the depth and magnitude of edge influences. We also investigated whether edge effects during drought were influenced by differences in forest structure. Edge effects were almost twice as strong in the drought year compared to the non-drought years, but we did not find clear evidence that they penetrated deeper into the forest in the drought year. Edge influences were also greater in areas that had fewer days with rain during the drought year. Higher levels of forest canopy cover and tree height buffered the magnitude of edge influence in times of drought. Our results demonstrate that edge effects are amplified by drought, suggesting that fragmentation effects are aggravated when droughts become more frequent and severe. Our results suggest that dense edges and buffer zones with high canopy cover can be important ways to mitigate negative drought impacts in forest edges.

The nanofluidic capacitor: Differential capacitance in the absence of reservoirs.

Within the framework of the classical, mean-field Poisson-Boltzmann (PB) theory, we carry out direct numerical simulations to determine the differential capacitance of a closed nanochannel of a circular cross section, embedded in a polymeric host with charged walls and sealed at both ends by metal electrodes under an external potential bias. Our approach employs the modified PB equation, which accounts for the finite size of ions and the dependency of the electrolyte's relative permittivity on the local electric field. In view of the absence of reservoirs, the modified PB equation becomes subject to global algebraic constraints, without prior knowledge of a bulk electrolyte concentration. Equilibrium ion distributions and differential capacitance curves are investigated as functions of electrolyte properties and the surface charge density modulation. This modulation leads to asymmetric differential capacitance curves that can be tuned. More generally, our approach provides a transparent numerical framework for accurately simulating confined nanofluidic systems with new physical properties that may be exploited in novel iontronic circuit elements.

Practical Guide to Measuring Wetland Carbon Pools and Fluxes.

Wetlands cover a small portion of the world, but have disproportionate influence on global carbon (C) sequestration, carbon dioxide and methane emissions, and aquatic C fluxes. However, the underlying biogeochemical processes that affect wetland C pools and fluxes are complex and dynamic, making measurements of wetland C challenging. Over decades of research, many observational, experimental, and analytical approaches have been developed to understand and quantify pools and fluxes of wetland C. Sampling approaches range in their representation of wetland C from short to long timeframes and local to landscape spatial scales. This review summarizes common and cutting-edge methodological approaches for quantifying wetland C pools and fluxes. We first define each of the major C pools and fluxes and provide rationale for their importance to wetland C dynamics. For each approach, we clarify what component of wetland C is measured and its spatial and temporal representativeness and constraints. We describe practical considerations for each approach, such as where and when an approach is typically used, who can conduct the measurements (expertise, training requirements), and how approaches are conducted, including considerations on equipment complexity and costs. Finally, we review key covariates and ancillary measurements that enhance the interpretation of findings and facilitate model development. The protocols that we describe to measure soil, water, vegetation, and gases are also relevant for related disciplines such as ecology. Improved quality and consistency of data collection and reporting across studies will help reduce global uncertainties and develop management strategies to use wetlands as nature-based climate solutions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13157-023-01722-2.

Random pore-network model for polymer electrolyte membranes.

A random pore-network model for polymer electrolyte membranes (PEM) is presented that couples the flow of protons and water through cylindrical channels to the swelling of the membrane. While the flows are determined by closed-form solutions of the Poisson-Nernst-Planck-Stokes equations, the fluid-structure interaction is described by a pressure balance at the channel walls. Macroscopic membrane properties, such as the conductivity, permeability and electro-osmotic coefficient, are computed and compared to experimental data in the literature. In light of the model simplifications, the results compare favourably to data but they also point to the importance of describing proton diffusion in PEM nanopores accurately.

Towards advancing scientific knowledge of climate change impacts on short-duration rainfall extremes.

A large number of recent studies have aimed at understanding short-duration rainfall extremes, due to their impacts on flash floods, landslides and debris flows and potential for these to worsen with global warming. This has been led in a concerted international effort by the INTENSE Crosscutting Project of the GEWEX (Global Energy and Water Exchanges) Hydroclimatology Panel. Here, we summarize the main findings so far and suggest future directions for research, including: the benefits of convection-permitting climate modelling; towards understanding mechanisms of change; the usefulness of temperature-scaling relations; towards detecting and attributing extreme rainfall change; and the need for international coordination and collaboration. Evidence suggests that the intensity of long-duration (1 day+) heavy precipitation increases with climate warming close to the Clausius-Clapeyron (CC) rate (6-7% K-1), although large-scale circulation changes affect this response regionally. However, rare events can scale at higher rates, and localized heavy short-duration (hourly and sub-hourly) intensities can respond more strongly (e.g. 2 × CC instead of CC). Day-to-day scaling of short-duration intensities supports a higher scaling, with mechanisms proposed for this related to local-scale dynamics of convective storms, but its relevance to climate change is not clear. Uncertainty in changes to precipitation extremes remains and is influenced by many factors, including large-scale circulation, convective storm dynamics andstratification. Despite this, recent research has increased confidence in both the detectability and understanding of changes in various aspects of intense short-duration rainfall. To make further progress, the international coordination of datasets, model experiments and evaluations will be required, with consistent and standardized comparison methods and metrics, and recommendations are made for these frameworks. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.

Asymmetric double-layer charging in a cylindrical nanopore under closed confinement.

This article presents a physical-mathematical treatment and numerical simulations of electric double layer charging in a closed, finite, and cylindrical nanopore of circular cross section, embedded in a polymeric host with charged walls and sealed at both ends by metal electrodes under an external voltage bias. Modified Poisson-Nernst-Planck equations were used to account for finite ion sizes, subject to an electroneutrality condition. The time evolution of the formation and relaxation of the double layers was explored. Moreover, equilibrium ion distributions and differential capacitance curves were investigated as functions of the pore surface charge density, electrolyte concentration, ion sizes, and pore size. Asymmetric properties of the differential capacitance curves reveal that the structure of the double layer near each electrode is controlled by the charge concentration along the pore surface and by charge asymmetry in the electrolyte. These results carry implications for accurately simulating cylindrical capacitors and electroactuators.

Treatment of menstrual migraine; multidisciplinary or mono-disciplinary approach.

BACKGROUND: The aim of this study was to compare a multidisciplinary approach of menstrual (related) migraine, combining the neurological and gynaecological consultation, to a mono-disciplinary approach involving neurological treatment. There is a clear relationship between the menstruation cycle and the occurrence of migraine (menstrual migraine). Nowadays the treatment of menstrual (related) migraine is performed by a neurologist. A treatment with attention to hormonal treatment seems more convenient. METHODS: This retrospective study was performed in a cohort using data of 88 women with menstrual (related) migraine who visited the menstrual migraine clinic between 2012 and 2014 (intervention group). The results were compared to a historical control group, which consisted of women with menstrual (related) migraine who were treated before 2012 and received a mono-disciplinary approach. RESULTS: In the intervention group the Headache Impact (HIT) score significantly improved (65 to 59 points). The mean headache days per month declined significantly (from 6 to 3.83 days) and these women needed less use of pain medication. In the control group the decline in HIT score was less striking (65 to 63.5 points) and the mean headache days per month increased (6 to 6,5 days). It appeared that 20 out of 27 patients in the control group required a gynaecological consultation in course of time. CONCLUSION: A multidisicplinary treatment of women with menstrual (related) migraine gives better results compared to a mono-disciplinary approach. These results should be interpreted with caution as we performed a retrospective study with a relative small control group.

Single-Cell Analysis of the Dps Response to Oxidative Stress.

UNLABELLED: Microorganisms have developed an elaborate spectrum of mechanisms to respond and adapt to environmental stress conditions. Among these is the expression of dps, coding for the DNA-binding protein from starved cells. Dps becomes the dominant nucleoid-organizing protein in stationary-phase Escherichia coli cells and is required for robust survival under stress conditions, including carbon or nitrogen starvation, oxidative stress, metal exposure, and irradiation. To study the complex regulation of Dps in E. coli, we utilized time-lapse fluorescence microscopy imaging to examine the kinetics, input encoding, and variability of the Dps response in single cells. In the presence of an oxidative stressor, we observed a single pulse of activation of Dps production. Increased concentrations of H2O2 led to increased intensity and duration of the pulse. While lower concentrations of H2O2 robustly activated the Dps response with little effect on the growth rate, higher concentrations of H2O2 resulted in dramatically lower and highly varied growth rates. A comparison of cells exposed to the same concentration of H2O2 revealed that increased levels of Dps expression did not confer a growth advantage, indicating that recovery from stress may rely primarily upon variation in the amount of damage caused to individual cells. IMPORTANCE: We show for the first time the response of the DNA-binding protein from starved cells (Dps) to oxidative stress in single cells of E. coli Through time-lapse fluorescence microscopy, a single pulse of Dps production is observed in cells exposed to H2O2, with a duration and intensity of induction proportional to the concentration of the applied stress. More intense Dps expression did not provide a growth benefit to the bacteria, suggesting that healing from oxidative stress may largely depend upon the amount of damage in each individual cell.

Benthic Carbon Mineralization and Nutrient Turnover in a Scottish Sea Loch: An Integrative In Situ Study.

Based on in situ microprofiles, chamber incubations and eddy covariance measurements, we investigated the benthic carbon mineralization and nutrient regeneration in a ~65-m-deep sedimentation basin of Loch Etive, UK. The sediment hosted a considerable amount of infauna that was dominated by the brittle star A. filiformis. The numerous burrows were intensively irrigated enhancing the benthic in situ O2 uptake by ~50 %, and inducing highly variable redox conditions and O2 distribution in the surface sediment as also documented by complementary laboratory-based planar optode measurements. The average benthic O2 exchange as derived by chamber incubations and the eddy covariance approach were similar (14.9 ± 2.5 and 13.1 ± 9.0 mmol m-2 day-1) providing confidence in the two measuring approaches. Moreover, the non-invasive eddy approach revealed a flow-dependent benthic O2 flux that was partly ascribed to enhanced ventilation of infauna burrows during periods of elevated flow rates. The ratio in exchange rates of ΣCO2 and O2 was close to unity, confirming that the O2 uptake was a good proxy for the benthic carbon mineralization in this setting. The infauna activity resulted in highly dynamic redox conditions that presumably facilitated an efficient degradation of both terrestrial and marine-derived organic material. The complex O2 dynamics of the burrow environment also concurrently stimulated nitrification and coupled denitrification rates making the sediment an efficient sink for bioavailable nitrogen. Furthermore, bioturbation mediated a high efflux of dissolved phosphorus and silicate. The study documents a high spatial and temporal variation in benthic solute exchange with important implications for benthic turnover of organic carbon and nutrients. However, more long-term in situ investigations with like approaches are required to fully understand how environmental events and spatio-temporal variations interrelate to the overall biogeochemical functioning of coastal sediments.

Comparison and Evaluation of Multiple Users' Usage of the Exposure and Risk Tool: Stoffenmanager 5.1.

Stoffenmanager is an exposure and risk assessment tool that has a control banding part, with risk bands as outcome and a quantitative exposure assessment part, with the 90th percentile of the predicted exposure as a default outcome. The main aim of the study was to investigate whether multiple users of Stoffenmanager came to the same result when modelling the same scenarios. Other aims were to investigate the differences between outcomes of the control banding part with the measured risk quota and to evaluate the conservatism of the tool by testing whether the 90th percentiles are above the measured median exposures. We investigated airborne exposures at companies in four different types of industry: wood, printing, metal foundry, and spray painting. Three scenarios were modelled and measured, when possible, at each company. When modelled, 13 users visited each company on the same occasion creating individual assessments. Consensus assessments were also modelled for each scenario by six occupational hygienists. The multiple users' outcomes were often spread over two risk bands in the control banding part, and the differences in the quantitative exposure outcomes for the highest and lowest assessments per scenario varied between a factor 2 and 100. Four parameters were difficult for the users to assess and had a large impact on the outcome: type of task, breathing zone, personal protection, and control measures. Only two scenarios had a higher measured risk quota than predicted by the control banding part, also two scenarios had slightly higher measured median exposure value than modelled consensus in the quantitative exposure assessment part. Hence, the variability between users was large but the model performed well.

A job-exposure matrix for occupational noise: development and validation.

OBJECTIVE: To develop a job-exposure matrix (JEM) for occupational noise in Sweden and to estimate its validity. METHODS: The JEM, developed by a group of experienced occupational hygienists, contains 321 job families with information regarding occupational noise from 1970 to 2004. The occupational noise information derives from measurements collected from different sources. The time period label has a 5-year scale starting in 1970. The estimated average 8h (TWA) noise level in decibel [dB(A)] for every 5-year period was coded either as <75 dB(A), 75-84 dB(A), or ≥85 dB(A) and the risk of peak level exposure assessed. The validity of the JEM is tested, using Svensson's non-parametric methods based on classification consensus, reached by a second group of occupational hygienists. RESULTS/DISCUSSION: Validation results show ~ 80% agreement and no systematic differences, in classification, between the two different groups of occupational hygienists, classifying the occupational noise exposure. However, classification of peak level exposure did show a systematic difference in relative position. The results will give more power to the JEM that it gives a good general estimate for the occupational noise levels in Sweden for different job families during 1970-2004. We, thus, intend to use it in further studies and also make it available to collaborators.

Comment on "Breakdown of electroneutrality in nanopores".

Levy et al. [1] reported the breakdown of electroneutrality in confined nanopores embedded in a dielectric medium. A Robin boundary condition was derived which eliminates the need to include the dielectric medium explicitly when solving for the electric field within the nanopore. In this comment, we point out issues related to the approximations made during the derivation of the boundary condition. The errors caused by the use of this boundary condition can be significant even for nanochannels of large aspect (length to radius) ratio, a condition on which the approximations in Levy et al. [1] are based.

MAKING WAVES: Effluent to estuary: Does sunshine or shade reduce downstream footprints of cities?

Riparian tree canopies are key components of river systems, and influence the provision of many essential ecosystem services. Their management provides the potential for substantial control of the downstream persistence of pollutants. The recent advent of new advances in mass spectrometry to detect a large suite of emerging contaminants, high-frequency observations of water quality and gas exchange (e.g., aquatic eddy covariance), and improved spatial resolution in remote sensing (e.g., hyperspectral measurements and high-resolution imagery), presents new opportunities to understand and more comprehensively quantify the role of riparian canopies as Nature-based Solutions. The paper outlines how we may now couple these advances in observational technologies with developments in water quality modelling to integrate simulation of eutrophication impacts with organic matter dynamics and fate of synthetic toxic compounds. In particular regarding solar radiation drivers, this enables us to scale-up new knowledge of canopy-mediated photodegradation processes at a basin level, and integrate it with ongoing improvements in understanding of thermal control, eutrophication, and ecosystem metabolism.

Preventing the next fragility fracture: a cross-sectional survey of secondary fragility fracture prevention services worldwide.

BACKGROUND: There has been an increasing awareness of the public health impact of fragility fractures due to osteoporosis and the imperative of addressing this health burden with well-designed secondary fragility fracture prevention services (SFFPS). The objectives of this survey, conducted within the international membership of the Fragility Fracture Network (FFN), were to identify gaps in services and identify the needs for further training and mentorship to improve the quality of SFFPS provided to patients who sustain fragility fractures. METHODS: We conducted an electronic cross-sectional survey of FFN Secondary Fracture Prevention Special Interest Group (SIG) members from April 2021 to June 2021 using SurveyMonkey. The survey questions were developed by four SIG members from New Zealand, Australia, Canada and the Netherlands, who have experience in developing, implementing and evaluating SFFPS. The sampling framework was convenience sampling of all 1162 registered FFN Secondary Fracture Prevention SIG members. Descriptive analyses were performed for all variables and presented as frequencies and percentages. RESULTS: 69 individuals participated in the survey, from 34 different countries over six continents, with a response rate of 6% (69/1162). Almost one-third of respondents (22/69) were from 15 countries within the European continent. Key findings included: (1) 25% of SFFPS only included patients with hip fracture; (2) less than 5% of SFFPS had any mandatory core competencies for training; (3) 38.7% of SFFPS were required to collect key performance indicators; and (4) 9% were collecting patient-reported outcome measures. CONCLUSIONS: This survey identified key areas for improving SFFPS, including: expanding the reach of SFFPS to more patients with fragility fracture, developing international core competencies for health provider training, using key performance indicators to improve SFFPS and including the patient voice in SFFPS development. These findings will be used by the FFN to support SFFPS development internationally.

Contralateral hip fractures and other osteoporosis-related fractures in hip fracture patients: incidence and risk factors. An observational cohort study of 1,229 patients.

PURPOSE: To report risk factors, 1-year and overall risk for a contralateral hip and other osteoporosis-related fractures in a hip fracture population. METHODS: An observational study on 1,229 consecutive patients of 50 years and older, who sustained a hip fracture between January 2005 and June 2009. Fractures were scored retrospectively for 2005-2008 and prospectively for 2008-2009. Rates of a contralateral hip and other osteoporosis-related fractures were compared between patients with and without a history of a fracture. Previous fractures, gender, age and ASA classification were analysed as possible risk factors. RESULTS: The absolute risk for a contralateral hip fracture was 13.8 %, for one or more osteoporosis-related fracture(s) 28.6 %. First-, second- and third-year risk for a second hip fracture was 2, 1 and 0 %. Median (IQR) interval between both hip fractures was 18.5 (26.6) months. One-year incidence of other fractures was 6 %. Only age was a risk factor for a contralateral hip fracture, hazard ratio (HR) 1.02 (1.006-1.042, p = 0.008). Patients with a history of a fracture (33.1 %) did not have a higher incidence of fractures during follow-up (16.7 %) than patients without fractures in their history (14 %). HR for a contralateral hip fracture for the fracture versus the non-fracture group was 1.29 (0.75-2.23, p = 0.360). CONCLUSION: The absolute risk of a contralateral hip fracture after a hip fracture is 13.8 %, the 1-year risk was 2 %, with a short interval between the 2 hip fractures. Age was a risk factor for sustaining a contralateral hip fracture; a fracture in history was not.

Aquatic Eddy Covariance: The Method and Its Contributions to Defining Oxygen and Carbon Fluxes in Marine Environments.

Aquatic eddy covariance (AEC) is increasingly being used to study benthic oxygen (O2) flux dynamics, organic carbon cycling, and ecosystem health in marine and freshwater environments. Because it is a noninvasive technique, has a high temporal resolution (∼15 min), and integrates over a large area of the seafloor (typically 10-100 m2), it has provided new insights on the functioning of aquatic ecosystems under naturally varying in situ conditions and has given us more accurate assessments of their metabolism. In this review, we summarize biogeochemical, ecological, and biological insightsgained from AEC studies of marine ecosystems. A general finding for all substrates is that benthic O2 exchange is far more dynamic than earlier recognized, and thus accurate mean values can only be obtained from measurements that integrate over all timescales that affect the local O2 exchange. Finally, we highlight new developments of the technique, including measurements of air-water gas exchange and long-term deployments.

Interactive effects of drought and edge exposure on old-growth forest understory species.

Context: Both climatic extremes and land-use change constitute severe threats to biodiversity, but their interactive effects remain poorly understood. In forest ecosystems, the effects of climatic extremes can be exacerbated at forest edges. Objectives: We explored the hypothesis that an extreme summer drought reduced the richness and coverage of old-growth forest species, particularly in forest patches with high edge exposure. Methods: Using a high-resolution spatially explicit precipitation dataset, we could detect variability in drought intensity during the summer drought of 2018. We selected 60 old-growth boreal forest patches in central Sweden that differed in their level of drought intensity and amount of edge exposure. The year after the drought, we surveyed red-listed and old-growth forest indicator species of vascular plants, lichens and bryophytes. We assessed if species richness, composition, and coverage were related to drought intensity, edge exposure, and their interaction. Results: Species richness was negatively related to drought intensity in forest patches with a high edge exposure, but not in patches with less edge exposure. Patterns differed among organism groups and were strongest for cyanolichens, epiphytes associated with high-pH bark, and species occurring on convex substrates such as trees and logs. Conclusions: Our results show that the effects of an extreme climatic event on forest species can vary strongly across a landscape. Edge exposed old-growth forest patches are more at risk under extreme climatic events than those in continuous forests. This suggest that maintaining buffer zones around forest patches with high conservation values should be an important conservation measure. Supplementary information: The online version contains supplementary material available at 10.1007/s10980-022-01441-9.

Room temperature synthesis of perylene diimides facilitated by high amic acid solubility.

A novel protocol for the synthesis of perylene diimides (PDIs), by reacting perylene dianhydride (PDA) with aliphatic amines is reported. Full conversions were obtained at temperatures between 20 and 60 °C, using DBU as the base in DMF or DMSO. A "green" synthesis of PDIs, that runs at higher temperatures, was developed using K2CO3 in DMSO. The reaction sequence for the imidization process, via perylene amic acid intermediates (PAAs), has been confirmed experimentally aided by the synthesis and full characterization of stable model amic acid salts and amic esters. Kinetic studies, using absorption spectroscopy, have established that PDI formation proceeds via fast amic acid formation, followed by a slow conversion to imides. Solubility of the intermediate PAA salts is found to be low and rate-limiting. Based on this finding, quantitative PDI synthesis at room temperature was achieved by diluting the reaction mixture with water, the solvent in which PAA salts have better solubility. Thus, the otherwise harsh synthesis of PDIs has been transformed into an extremely convenient functional group tolerant and highly efficient reaction that runs at room temperature.

The role of the innate immune recognition system in the pathogenesis of primary biliary cirrhosis: a conceptual view.

The aetiology of primary biliary cirrhosis (PBC) remains unknown. Infectious and non-infectious noxious insults in combination with tissue-specific factors may precipitate PBC. Activation of innate immune response because of impending danger signals seems to be a key event in early PBC, as evidenced by granuloma formation, eosinophilic reaction and IgM elevation. Aberrant mitophagy in 'stressed' biliary epithelia cells may initiate the immune response against mitochondrial antigens. Antimitochondrial autoantibodies recognize evolutionarily conserved molecules. The question arises, whether they are pathogenic or rather an expression of beneficial autoimmunity. The generally stable course of PBC suggests that stimulatory and inhibitory autoimmune reactions govern the inflammatory biliary process. Tissue repair and defense are the heart of innate immunity. But continuous exposure of exogenous stimuli may precipitate functional antireceptor autoantibodies that are no more protective but rather harmful. Mitophagy, apoptosis and bile duct proliferation define the inflammatory response within bile ducts. Autoantigens may be clustered in different blebs on the surface of apoptotic cells targeting a variety of membrane and non-membrane-associated antigens. Thus, the autoantibody response in PBC may target, for instance, the pro- and anti-apoptotic proteins of the Bcl-2 family or receptors of the adrenergic or cholinergic system, hereby interfering with the programme of apoptosis and the proliferation of biliary epithelial cells. Consideration of there being functional autoantibodies into the pathogenesis of PBC may help to improve our understanding of the aetiopathogenesis of PBC.