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Reach-scale river restoration or environmental water allocation (EWA) exercises typically address the magnitude and temporal dynamics (frequency, duration, timing, rate of change) of flows required to sustain desirable ecological conditions along a river. The role of geomorphology in this process is to broaden the gaze beyond flows to consider larger and longer-terminteractions between valley lithological structure, and the feed and fate of flow-sediment mixtures. This paper proposes the integration of numerical morphodynamic modelling in evaluations of environmental water requirements for non-perennial riverscapes (channel--riparian--floodplain environments). The paper presents a methodological framework, and proof of concept case study from the Touws River, South Africa, for the application of morphodynamic modelling in EWA. The paper illustrates operational approaches to modelling the complexity of dryland mixed bedrock-alluvial (and mixed-load) riverscapes with highly variable non-perennial flow regimes, including an approach to generating initial bed conditions for numerical experiments by 'morphodynamic spin-up', and approaches to synthesising and presenting numerical experiment output in the formof a dynamic range of potential variability inmetrics of physical habitat suitability and diversity, and disturbance/renewal regimes. Such efforts can assist in enhancing field observations and testing field-based hypotheses of flow-sediment regime--physical habitat associations, extending the timescales of analysis beyond field observation, and constraining uncertainty about the dynamic range of variability in responses to predicted future flow-sediment regime modifications. Further research is needed to develop growth models appropriate for key non-perennial river vegetation types, to support bio- morphodynamic modelling of geomorphology--vegetation interactions, and to determine or predict appropriate inlet sediment concentrations for historical and future modification scenarios. [ABSTRACT FROM AUTHOR]

The co-efficient of variation for inter-annual streamflow of the Mfolozi River is extremely high at 79%. An analysis of flow frequency indicated that streamflow is skewed towards low-flow values, with a number of extremely large flood events occurring as outliers on the histogram. Streamflow variability in the Mfolozi River may be linked to multiple factors including a large catchment size, a seasonal climate of a dry winter and wet summer, evergreen vegetation in the catchment, variable precipitation and the occurrence of regionally pervasive climatic oscillations. This research aimed to address how streamflow variability impacted upon sediment transport and thus, geornorphology. It was found that sediment transport variability occurred at the intra- and inter-annual scale. Analysis of mean monthly sediment concentration and discharge showed a hysteresis effect, such that sediment concentration peaked prior to discharge in the early wet season. During the late wet season, peak discharges often had unexpectedly low sediment concentrations. Furthermore, data suggested the existence of long-term hysteresis that may be related to decadal-scale climatic oscillations that alter sediment availability and stream capacity, resulting in discharge peaking in 2000 and sediment concentration in 2005. However, more data are required to confirm this relationship. Variability in streamflow appears to share a causal relationship with sediment transport variability, as both are linked to variation in precipitation and the resultant impacts on vegetation growth and evapotranspiration rates. The variability of streamflow and sediment transport has implications for stream and floodplain geomorphology, and the hydrology of variable rivers should be considered when interpreting their geomorphology. [ABSTRACT FROM AUTHOR]

Purpose: Up to 90% of people with Parkinson's disease (PD) develop communication difficulties over the course of the disease. While the negative effect of dysarthria on communicative participation has been well-documented, the impact of the occurrence of acquired stuttered disfluencies on communication in different speech situations is unknown. This study aimed to determine if the frequency of occurrence of stuttered disfluencies affects communicative participation in individuals with PD, and whether such a relationship is mediated by examiner- and self-rated measures of disease severity., Method: Conversational speech samples were collected from 100 people with PD aged 53-91 years to calculate the frequency of occurrence of stuttered disfluencies. Participants completed the Communicative Participation Item Bank to assess participation in communicative situations. Information on overall speech, cognitive, and motor performance was collected using both self-rated and examiner-rated methods., Results: Participants with PD presented with 0.2%-9.9% stuttered disfluencies during conversation. Overall, participants with PD reported their communicative participation to be impacted "a little" (19.5 ± 7.0), but there was considerable interindividual variation. A higher frequency of stuttered disfluencies was associated with significantly lower communicative participation (ρ = -0.32, p < .01). In addition, examiner-rated frequency of stuttered disfluencies ( p < .01), speech ( p < .01), and motor severity ( p = .04) were all significant predictors of communicative participation. Using self-ratings, speech ( p < .01) and cognitive ( p < .01) measures significantly predicted communicative participation., Conclusions: In people with PD, communicative participation was significantly worse for those with a higher frequency of stuttered disfluencies. Examiner- and self-rated measures of disease severity contributed different information related to communicative constraints. Together, these results highlight the importance of individualized and holistic speech therapy that considers a wide variety of symptoms, including stuttered disfluencies, to ensure positive functional outcomes., Supplemental Material: https://doi.org/10.23641/asha.26850169.

Introduction: Recent work suggests that amyloid beta (Aβ) positron emission tomography (PET) tracer uptake shortly after injection ("early phase") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid-negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early-phase 18 F-florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD., Methods: One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual-phase Aβ PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion., Results: Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism-associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions., Discussion: EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual-phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment., Highlights: Images taken at amyloid beta (Aβ) positron emission tomography tracer injection may reflect brain perfusion and metabolism.Parkinson's disease (PD) is a predominantly amyloid-negative condition.Early-phase florbetaben (eFBB) in PD was associated with cognitive performance.eFBB uptake reflects hypometabolism-related cognitive decline in PD.eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion.eFBB distinguished dementia from normal cognition and mild cognitive impairment.Findings were independent of late-phase Aβ burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion., Competing Interests: The authors declare no conflicts of interest related to this research. The principal author confirms that all authors have read the manuscript, and the paper has not previously been published or is under consideration at another journal. The authors take full responsibility for the data, analyses, and interpretation, and the conduct of the research, and have full access to all the data and the right to publish it. All authors have agreed to the conditions noted on the authorship agreement form., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Parkinson’s disease affects millions worldwide with a large rise in expected burden over the coming decades. More easily accessible tools and techniques to diagnose and monitor Parkinson’s disease can improve the quality of life of patients. With the advent of new wearable technologies such as smart rings and watches, this is within reach. However, it is unclear what method for these new technologies may provide the best opportunity to capture the patient-specific severity. This study investigates which locations on the hand can be used to capture and monitor maximal movement/tremor severity. Using a Leap Motion device and custom-made software the volume, velocity, acceleration, and frequency of Parkinson’s (n = 55, all right-handed, majority right-sided onset) patients’ hand locations (25 joints inclusive of all fingers/thumb and the wrist) were captured simultaneously. Distal locations of the right hand, i.e., the ends of fingers and the wrist showed significant trends (p < 0.05) towards having the largest movement velocities and accelerations. The right hand, compared with the left hand, showed significantly greater volumes, velocities, and accelerations (p < 0.01). Supplementary analysis showed that the volumes, acceleration, and velocities had significant correlations (p < 0.001) with clinical MDS-UPDRS scores, indicating the potential suitability of using these metrics for monitoring disease progression. Maximal movements at the distal hand and wrist area indicate that these locations are best suited to capture hand tremor movements and monitor Parkinson’s disease.

Aims: Stress plays a key role in Parkinson's disease (PD) by acting on the dopaminergic system and worsening patients' motor function. The impact of New Zealand's strict lockdown measures to contain COVID-19 on perceived stress and PD motor symptoms remains unknown. Here we examined the relationship between perceived levels of stress, changes in physical activity levels and PD motor symptoms during lockdown., Methods: During lockdown, 134 participants with PD and 49 controls completed a survey assessing perceived stress, self-reported changes in PD motor symptoms and physical activity duration and intensity prior to and during lockdown., Results: Perceived stress was higher in PD than controls, and in those reporting a worsening of tremor, balance/gait, dyskinesia and bradykinesia compared to those indicating no change during the COVID-19 lockdown. These effects were not modulated by physical activity., Conclusions: Reducing stressors may be an important adjunct treatment strategy to improve motor function in PD., Competing Interests: Nil.

Background: Neuropsychiatric symptoms in Parkinson's disease (PD) may increase dementia (PDD) risk. The predictive value of these symptoms, however, has not been compared to clinical and demographic predictors of future PDD., Objectives: Determine if neuropsychiatric symptoms are useful markers of PDD risk., Methods: 328 PD participants completed baseline neuropsychiatric and MDS-Task Force-Level II assessments. Of these, 202 non-demented individuals were followed-up over a four-years period to detect conversion to PDD; 51 developed PDD. ROC analysis tested associations between baseline neuropsychiatric symptoms and future PDD. The probability of developing PDD was also modeled as a function of neuropsychiatric inventory (NPI)-total score, PD Questionnaire (PDQ)-hallucinations, PDQ-anxiety, and contrasted to cognitive ability, age, and motor function. Leave-one-out information criterion was used to evaluate which models provided useful information when predicting future PDD., Results: The PDD group experienced greater levels of neuropsychiatric symptoms compared to the non-PDD groups at baseline. Few differences were found between the PD-MCI and PD-N groups. Six neuropsychiatric measures were significantly, but weakly, associated with future PDD. The strongest was NPI-total score: AUC = 0.66 [0.57-0.75]. There was, however, no evidence it contained useful out-of-sample predictive information of future PDD (delta ELPD = 1.8 (SD 2.5)); Similar results held for PDQ-hallucinations and PDQ-anxiety. In contrast, cognitive ability (delta ELPD = 36 (SD 8)) and age (delta ELPD = 11 (SD 5)) provided useful predictive information of future PDD., Conclusions: Cognitive ability and age strongly out-performed neuropsychiatric measures as markers of developing PDD within 4 years. Therefore, neuropsychiatric symptoms do not appear to be useful markers of PDD risk., Competing Interests: The research conducted in this article was funded by research support from the New Zealand Health Research Council, Brain Research New Zealand—Rangahau Roro Aotearoa, University of Otago, University of Canterbury, Neurological Foundation of New Zealand, Canterbury Medical Research Foundation, and the New Zealand Brain Research Institute. The authors of this article have no financial relationships relevant to this article to disclose or conflicts of interest., (© 2021 International Parkinson and Movement Disorder Society.)

The extent to which Alzheimer neuropathology, particularly the accumulation of misfolded beta-amyloid, contributes to cognitive decline and dementia in Parkinson's disease (PD) is unresolved. Here, we used Florbetaben PET imaging to test for any association between cerebral amyloid deposition and cognitive impairment in PD, in a sample enriched for cases with mild cognitive impairment. This cross-sectional study used Movement Disorders Society level II criteria to classify 115 participants with PD as having normal cognition (PDN, n = 23), mild cognitive impairment (PD-MCI, n = 76), or dementia (PDD, n = 16). We acquired 18F-Florbetaben (FBB) amyloid PET and structural MRI. Amyloid deposition was assessed between the three cognitive groups, and also across the whole sample using continuous measures of both global cognitive status and average performance in memory domain tests. Outcomes were cortical FBB uptake, expressed in centiloids and as standardized uptake value ratios (SUVR) using the Centiloid Project whole cerebellum region as a reference, and regional SUVR measurements. FBB binding was higher in PDD, but this difference did not survive adjustment for the older age of the PDD group. We established a suitable centiloid cut-off for amyloid positivity in Parkinson's disease (31.3), but there was no association of FBB binding with global cognitive or memory scores. The failure to find an association between PET amyloid deposition and cognitive impairment in a moderately large sample, particularly given that it was enriched with PD-MCI patients at risk of dementia, suggests that amyloid pathology is not the primary driver of cognitive impairment and dementia in most patients with PD.

Sea-level rise associated with climate change presents a major challenge to plant diversity and ecosystem service provision in coastal wetlands. In this study, we investigate the effect of sea-level rise on benthos, vegetation, and ecosystem diversity in a tidal wetland in west Wales, the UK. Present relationships between plant communities and environmental variables were investigated through 50 plots at which vegetation (species and coverage), hydrological (surface or groundwater depth, conductivity) and soil (matrix chroma, presence or absence of mottles, organic content, particle size) data were collected. Benthic communities were sampled at intervals along a continuum from saline to freshwater. To ascertain future changes to the wetlands' hydrology, a GIS-based empirical model was developed. Using a LiDAR derived land surface, the relative effect of peat accumulation and rising sea levels were modelled over 200 years to determine how frequently portions of the wetland will be inundated by mean sea level, mean high water spring and mean high water neap conditions. The model takes into account changing extents of peat accumulation as hydrological conditions alter. Model results show that changes to the wetland hydrology will initially be slow. However, changes in frequency and extent of inundation reach a tipping point 125 to 175 years from 2010 due to the extremely low slope of the wetland. From then onwards, large portions of the wetland become flooded at every flood tide and saltwater intrusion becomes more common. This will result in a reduction in marsh biodiversity with plant communities switching toward less diverse and occasionally monospecific communities that are more salt tolerant. While the loss of tidal freshwater wetland is in line with global predictions, simulations suggest that in the Teifi marshes the loss will be slow at first, but then rapid. While there will be a decrease in biodiversity, the model indicated that at least for one ecosystem service, carbon storage, there is potential for an increase in the near future., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Preparation for postoperative radioiodine ablation for differentiated thyroid carcinoma is performed by either thyroid hormone withdrawal or recombinant human thyroid-stimulating hormone (rhTSH) administration. There is little information on the impact of the method of preparation with respect to whole-body effective I-131 half-life and its potential clinical implications in the Australian setting., Methods: A retrospective study was performed on patients admitted for adjuvant radioiodine ablation for non-metastatic differentiated thyroid carcinoma at the Royal Adelaide Hospital over a 4½-year period from 2009. Dose rate measurements were analysed for 19 rhTSH and 31 thyroid hormone withdrawal patients., Results: The mean effective I-131 half-lives were 11.51 and 13.29 h for the rhTSH and thyroid hormone withdrawal groups, respectively, with no statistically significant difference between the two groups (P = 0.761). This result differs from previously published data where withdrawal periods were typically longer, resulting in slower renal clearance and longer half-lives for withdrawal patients., Conclusions: Our study did not demonstrate a significant difference in whole-body effective half-life of I-131 between the two methods of preparation for radioiodine ablation. This suggests that putative advantages of rhTSH over withdrawal in terms of whole-body radiation dose, duration of hospital admission and quality of life may be sensitive to duration of withdrawal., (© 2014 The Royal Australian and New Zealand College of Radiologists.)

Introduction: Palmar and plantar fascial fibromatoses are benign hyperproliferative disorders of the deep fascia of the palm and sole. This study seeks to examine the role of radiotherapy in the management of fascial fibromatosis., Method: Six consecutive cases of early-stage fascial fibromatosis treated with radiotherapy at the Adelaide Radiotherapy Centre between July 2008 and May 2011 were analysed. The results of the case series were compared with a systematic review of the literature., Results: All six cases regressed or showed a reduction of symptoms following radiotherapy. Treatment was well tolerated with minor toxicities. Median follow-up for the case series was 38.5 months. The systematic review identified seven studies describing the use of radiotherapy as primary treatment for fascial fibromatosis between 1946 and 2013. The literature indicates that radiotherapy can prevent disease progression and improve symptoms for early-stage disease, with low likelihood of significant toxicities., Conclusion: Early results from our case series are consistent with the literature, showing that radiotherapy can provide an effective management option for patients with early-stage fascial fibromatosis, and justify consideration of radiotherapy as a primary treatment for early-stage disease., (© 2014 The Royal Australian and New Zealand College of Radiologists.)

Unlabelled: In the spring of 2009, the first patients infected with 2009 H1N1 virus were arriving for care in hospitals in the United States. Anticipating a second wave of infection, our hospital leaders initiated multidisciplinary planning activities to prepare to increase capacity by expansion of emergency department (ED) and inpatient functional space and redeployment of medical personnel., Experience: During the fall pandemic surge, this urban, tertiary-care children's hospital experienced a 48% increase in ED visits and a 12% increase in daily peak inpatient census. However, several strategies were effective in mitigating the pandemic's impact including using a portion of the hospital's lobby for ED waiting, using a subspecialty clinic and a 24-hour short stay unit to care for ED patients, and using physicians not board certified in pediatric emergency medicine and inpatient-unit medical nurses to care for ED patients. The average time patients waited to be seen by an ED physician and the proportion of children leaving the ED without being seen by a physician was less than for the period when seasonal influenza peaked in the winter of 2008-2009. Furthermore, the ED did not go on divert status, no elective medical or surgical admissions required cancellation, and there were no increases in serious patient safety events., Summary: Our health center successfully met the challenges posed by the 2009 H1N1 outbreak. The intent in sharing the details of our planning and experience is to allow others to determine which elements of this planning might be adapted for managing a surge of patients in their setting.

Eroding farm tracks represent important spatially distributed features in many agricultural landscapes and there is concern over their role in catchment sediment problems. It is, however, important to place eroding farm tracks in the context of catchment sediment sources more generally, especially since the former afford potential for targeted sediment mitigation. A sediment source tracing procedure was therefore used to assess the importance of eroding farm track surfaces as a contemporary primary suspended sediment source relative to inputs from pasture or cultivated topsoils and channel banks/subsurface sources, in the upper River Piddle catchment (~100km(2)), in southern England. The study provided a timely opportunity to assess the performance of both local and global (genetic algorithm; GA) optimisation techniques in the sediment geochemistry mass balance modelling used to apportion sources. Over the duration of the study, average median source contributions for individual time-integrated suspended sediment samples collected from three sub-catchments ranged between 1±1 and 19±3% for farm track surfaces, 31±3 and 55±2% for pasture topsoils, 1±1 and 19±1% for cultivated topsoils and 23±2 and 49±1% for channel banks/subsurface sources. Comparison of the local and GA optimisation techniques demonstrated that GA with random initial values improved the minimisation of the objective functions compared to local searching by 0.01-0.04% of 5000 repeat Monte Carlo iterations. GA informed by the outputs of the local optimisation as initial values improved corresponding performance by 0.05-0.20%. These findings increased confidence in the outputs from the local optimisation mass balance modelling, but fingerprint property datasets should be treated on an individual basis. Future sediment source tracing studies should always endeavour to combine local and global search tools to avoid the risk of using localised solutions for source apportionment estimates., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The transcription factors Oct-1 and Oct-2 bind differentially to three octamer binding sequences corresponding to the octamer binding site from the H2B promoter [ATGCTAATAA], a simple TAATGARAT motif, found in herpes simplex virus IE4/5 genes [GCGGTAATGAGAT], and a perfect consensus overlapping octamer/TAATGARAT motif [ATGCTAATGAGAT]. By comparing the effects of protein kinase A, protein kinase C and casein kinase 2 in vitro on the binding of Oct-1 and Oct-2 to the three motifs, we show that the actions of these kinases regulate Oct-1 and Oct-2 DNA binding independently of each other in a binding-site-specific manner. Inhibition of cellular phosphatases also regulate Oct-1 and Oct-2 DNA binding in a binding-site-specific manner. Both kinase and phosphatase activity are important for regulating the DNA binding activity of Oct-1 and Oct-2 because, in the presence of phosphatase inhibitors, protein kinase A attenuates the binding of both Oct-1 and Oct-2 to the octamer binding site but enhances binding when phosphatase inhibitors are omitted. Thus the DNA specificity of Oct-1 and Oct-2 can be regulated in vitro by the action of different kinases.

We have studied the receptor mediated endocytosis of interleukin 1 (IL1) by the murine thymoma cell line EL4. These cells express the Type I IL1 receptor which binds its ligand with both high (Kd = 65 pM) and low affinity (Kd = 14.5 nM). We have shown that the two affinity states of the receptor have different rates of turnover both in the absence and presence of ligand. The biological responses of cells to IL1 stimulation are rapid and occur at low levels of receptor occupancy, whereas receptor mediated endocytosis of IL1 is relatively slow. Internalized IL1 appears to accumulate within cells in a non-degraded form and a proportion of this is associated with a detergent insoluble intracellular fraction, which may reflect transport to the nucleus. In this article, we review our previous findings and discuss the possible biological significance of IL1 internalization and nuclear targeting.

In this study we have investigated the effect that interleukin 1 (IL-1) has on cell surface IL-1 receptor expression in the murine thymoma cell line, EL4 6.1. These cells express IL-1 receptors with both high affinity (Kd = 65 pM, 986 receptors/cell) and low affinity (Kd = 14.5 nM, 10,417 receptors/cell). The high- and low-affinity receptors are indistinguishable by crosslinking studies performed at both high and low ligand concentrations. However, the two affinity states could be functionally distinguished on the basis of their internalization of ligand. Receptor-mediated endocytosis was dependent upon the concentration of ligand bound to the cells. In the presence of low IL-1 concentrations receptor-mediated endocytosis was slow, whereas at high IL-1 concentrations, endocytosis was more rapid. Furthermore, receptor-mediated endocytosis of IL-1 did not result in downregulation of surface IL-1 receptors. Indeed, both kinetic and equilibrium binding studies revealed that pre-incubation of cells with IL-1 alpha resulted in an acute upregulation of 125IL-1 alpha binding to high affinity surface receptors in a time and energy dependent manner. Examination of the association kinetics suggested that increased binding was not attributable to positive co-operativity of the high affinity IL-1 receptor, but was due to increasing IL-1 receptor number. This observation was confirmed by equilibrium binding studies. Moreover, receptor numbers were not enhanced by de novo synthesis, nor release of receptors from an intracellular pool. The observed increases in surface ligand binding were most probably due to conversion of the surface pool of low affinity receptors into high affinity receptors.

In this study we have examined the effect of agents known to perturb certain signal transduction pathways on the biological responses of target cells to stimulation with interleukin-1 (IL-1). In the murine thymoma cell line EL4, IL-1 stimulation results in the secretion of interleukin-2 (IL-2), which was subsequently measured by proliferation of an IL-2-dependent cell line. Agents that elevated intracellular cAMP blocked or partially blocked IL-1 induction of IL-2 secretion, whereas agents that activated protein kinase C (PKC) resulted in a synergistic enhancement. Both pertussis and cholera toxins also inhibited IL-1-induced IL-2 secretion, although probably by acting at different levels. IL-1 simulation of human and murine fibroblasts resulted in release of prostaglandin E2. This response was inhibitable by pertussis toxin but not by cholera toxin, whereas co-stimulation of the fibroblasts with IL-1 and phorbol ester resulted in a synergistic response. Murine fibroblasts could also be stimulated to proliferate by IL-1, and this response was also inhibitable by pertussis toxin. These findings are consistent with coupling of the IL-1 receptor to a signalling pathway via a pertussis toxin substrate.

Kallikrein released during superfusion of rat, monkey and human kidney cortical slices was mainly in the inactive form. Arginine vasopressin and the nonpressor synthetic analogue des-amino-D-arginine vasopressin increased the release of inactive kallikrein to a similar extent in all species. No detectable change in active kallikrein release occurred. These results suggest a role for the kallikrein-kinin system in the regulation of the hydro-osmotic effect of arginine vasopressin.

In this study we demonstrate that 125I-labelled interleukin (IL) 1 alpha binds specifically to its receptor on the surface of EL4 6.1 cells and is subsequently endocytosed and translocated from the cell membrane to the nucleus, where it progressively accumulates. Two-dimensional polyacrylamide-gel electrophoresis revealed that the internalized 125I-IL1 alpha associated with the nucleus was intact, with negligible breakdown products present. Specific and saturable binding of 125I-IL1 alpha was demonstrated on purified nuclei isolated from these cells. Binding of the radiolabelled ligand showed similar kinetics to that of the plasma-membrane receptor, and was inhibited by both unlabelled IL1 alpha and IL1 beta. Equilibrium binding studies on isolated nuclei revealed a single high-affinity binding site, with a Kd of 17 +/- 2 pM, and 79 +/- 12 binding sites per nucleus. These studies demonstrate that receptor-mediated endocytosis of IL1 results in its accumulation in the nucleus, and this mechanism may play an important role in mediating some of the actions of IL1.