Spectroscopic and theoretical investigation of the [Fe2(bdt)(CO)6] hydrogenase mimic and some catalyst intermediates.

In [Fe-Fe] hydrogenase mimic systems the ene-1,2-dithiolene ligands play an important role in the stabilisation of the redox-active metal center. This is demonstrated by the benzenedithiolene (bdt) analogue, featuring six terminal carbonyl ligands connected to a di-iron metal center, i.e. [Fe2(bdt)(CO)6]. Here we present a combined experimental and theoretical study that elucidates key intermediates [Fe2(bdt)(CO)6]1- and [Fe2(bdt)(µ-CO)(CO)5]2- in the electrocatalytic production of dihydrogen. A DFT study shows that [Fe2(bdt)(CO)6]1- is the kinetic product after the first one electron reduction, while the previously proposed bridging intermediate species [Fe2(bdt)(µ-CO)(CO)5]1- is kinetically inaccessible. The doubly reduced species [Fe2(bdt)(µ-CO)(CO)5]2- was for the first time structurally characterized using EXAFS. XANES analysis confirms the existence of reduced iron zero species and confirms the distorted geometry that was suggested by the DFT calculations. Combining IR, UV-vis and XAS spectroscopic results with TD-DFT and FEFF calculations enabled us to assign the key-intermediate [Fe2(bdt)(CO)6]2-. This study emphasizes the strengths of combining computational chemistry with advanced spectroscopy techniques.

Carbon assimilation and transfer through kelp forests in the NE Atlantic is diminished under a warmer ocean climate.

Global climate change is affecting carbon cycling by driving changes in primary productivity and rates of carbon fixation, release and storage within Earth's vegetated systems. There is, however, limited understanding of how carbon flow between donor and recipient habitats will respond to climatic changes. Macroalgal-dominated habitats, such as kelp forests, are gaining recognition as important carbon donors within coastal carbon cycles, yet rates of carbon assimilation and transfer through these habitats are poorly resolved. Here, we investigated the likely impacts of ocean warming on coastal carbon cycling by quantifying rates of carbon assimilation and transfer in Laminaria hyperborea kelp forests-one of the most extensive coastal vegetated habitat types in the NE Atlantic-along a latitudinal temperature gradient. Kelp forests within warm climatic regimes assimilated, on average, more than three times less carbon and donated less than half the amount of particulate carbon compared to those from cold regimes. These patterns were not related to variability in other environmental parameters. Across their wider geographical distribution, plants exhibited reduced sizes toward their warm-water equatorward range edge, further suggesting that carbon flow is reduced under warmer climates. Overall, we estimated that Laminaria hyperborea forests stored ~11.49 Tg C in living biomass and released particulate carbon at a rate of ~5.71 Tg C year-1 . This estimated flow of carbon was markedly higher than reported values for most other marine and terrestrial vegetated habitat types in Europe. Together, our observations suggest that continued warming will diminish the amount of carbon that is assimilated and transported through temperate kelp forests in NE Atlantic, with potential consequences for the coastal carbon cycle. Our findings underline the need to consider climate-driven changes in the capacity of ecosystems to fix and donate carbon when assessing the impacts of climate change on carbon cycling.

Arctic marine phytobenthos of northern Baffin Island.

Global climate change is expected to alter the polar bioregions faster than any other marine environment. This study assesses the biodiversity of seaweeds and associated eukaryotic pathogens of an established study site in northern Baffin Island (72° N), providing a baseline inventory for future work assessing impacts of the currently ongoing changes in the Arctic marine environment. A total of 33 Phaeophyceae, 24 Rhodophyceae, 2 Chlorophyceae, 12 Ulvophyceae, 1 Trebouxiophyceae, and 1 Dinophyceae are reported, based on collections of an expedition to the area in 2009, complemented by unpublished records of Robert T. Wilce and the first-ever photographic documentation of the phytobenthos of the American Arctic. Molecular barcoding of isolates raised from incubated substratum samples revealed the presence of 20 species of brown seaweeds, including gametophytes of kelp and of a previously unsequenced Desmarestia closely related to D. viridis, two species of Pylaiella, the kelp endophyte Laminariocolax aecidioides and 11 previously unsequenced species of the Ectocarpales, highlighting the necessity to include molecular techniques for fully unraveling cryptic algal diversity. This study also includes the first records of Eurychasma dicksonii, a eukaryotic pathogen affecting seaweeds, from the American Arctic. Overall, this study provides both the most accurate inventory of seaweed diversity of the northern Baffin Island region to date and can be used as an important basis to understand diversity changes with climate change.

Bacillus subtilis vegetative isolate surviving chlorine dioxide exposure: an elusive mechanism of resistance.

AIMS: Oxidizing agents such as chlorine dioxide are widely used microbicides, including for disinfection of medical equipment. We isolated a Bacillus subtilis isolate from a washer-disinfector whose vegetative form demonstrated unique resistance to chlorine dioxide (0·03%) and hydrogen peroxide (7·5%). The aim of this study was to understand the mechanisms of resistance expressed by this isolate. METHODS AND RESULTS: A range of resistance mechanisms were investigated in the B. subtilis isolate and a reference B. subtilis strain (ATCC 6051) to include bacterial cell aggregation, the presence of profuse exopolysaccharide (EPS), and the expression of detoxification enzymes. The basis of resistance of the isolate to high concentrations of oxidizing agents was not linked to the presence of endospores. Although, the presence of EPS, aggregation and expression of detoxification enzymes may play a role in bacterial survival to low concentrations of chlorine dioxide, it is unlikely that the mechanisms helped tested to survive the bactericidal effect of higher oxidizer concentrations. CONCLUSIONS: Overall, the mechanisms conferring resistance to chlorine dioxide and hydrogen peroxide remains elusive. Based on recent advances in the mode of action of oxidizing agents and notably hydrogen peroxide, we postulate that additional efficient intracellular mechanisms may be involved to explain significant resistance to in-use concentrations of commonly used high-level disinfectants. SIGNIFICANCE AND IMPACT OF STUDY: The isolation of a highly resistant vegetative Gram-positive bacterium to a highly reactive oxidizing agent is worrying. Understanding the mechanisms conferring such resistance is essential to effectively control such bacterial isolates. Here, we postulate that there are still mechanisms of bacterial resistance that have not been fully characterized.

Ecosystem engineers enhance the multifunctionality of an urban novel ecosystem: Population persistence and ecosystem resilience since the 1980s.

In degraded urban habitats, nature-based solutions aim to enhance ecosystem functioning and service provision. Bivalves are increasingly reintroduced to urban environments to enhance water quality through biofiltration, yet their long-term sustainability remains uncertain. Following the restoration of the disused South Docks in Liverpool in the 1980s, natural colonization of mussels rapidly improved dock-basin water quality and supported diverse taxa, including other filter feeders. While the initial colonization phase has been well documented, there has been limited published research since the mid-1990s, despite ongoing routine water quality monitoring. Here, we assessed the long-term persistence of mussel populations, their associated biodiversity, and physico-chemical parameters of the water in Queens and Albert Docks by comparing historical (1980s to 1990s) and contemporary data from follow-up surveys (2012,2022). Following an initial period of poor water quality (high contamination and turbidity, low oxygen), the natural colonization of mussels from Albert Dock in 1988 extended throughout the South Docks. By the mid-1990s, the environment of the South Docks and its mussel populations had stabilized. The dock walls were dominated by mussels which provided important complex secondary substrate for invertebrates and macroalgae. Surveys conducted in 2012 and 2022 confirmed the continued dominance of mussels and estimates of mussel biofiltration rates confirm that mussels are continuing to contribute to maintaining water quality. A decline in salinity was observed in both docks in 2022, with evidence of recovery. While these ecosystems appear relatively stable, careful management of the hydrological regime is crucial to ensuring the persistence of mussels and resilient ecosystem service provision through biofiltration.

Inactivation of WT1 in nephrogenic rests, genetic precursors to Wilms' tumour.

Nephrogenic rests consist of foci of primitive renal cells, typically microscopic, that are found within the normal kidney tissue of children with Wilms' tumour. To study the relationship between nephrogenic rests and the associated tumours, we screened these lesions for mutations in the 11p13 Wilms' tumour suppressor gene, WT1. In two cases in which the Wilms' tumour contained a somatic WT1 mutation, the nephrogenic rest had the identical mutation. Nephrogenic rests and Wilms' tumours are therefore topographically distinct lesions that are clonally derived from an early renal stem cell. Inactivation of WT1 appears to be an early genetic event which can lead to the formation of nephrogenic rests, enhancing the probability that additional genetic hits will lead to Wilms' tumour.

WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant.

A human Wilms tumor cell line (RM1) was developed to test the tumor suppressor activity of WT1, a zinc finger transcription factor that is expressed in the developing human kidney and is mutationally inactivated in a subset of Wilms tumors. Transfection of each of four wild-type WT1 isoforms suppressed the growth of RM1 cells. The endogenous WT1 transcript in these cells was devoid of exon 2 sequences, a splicing alteration that was also detected in varying amounts in all Wilms tumors tested but not in normal kidney. Production of this abnormal transcript, which encodes a functionally altered protein, may represent a distinct mechanism for inactivating WT1 in Wilms tumors.

Long-term follow-up of a randomized clinical trial comparing Beger with pylorus-preserving Whipple procedure for chronic pancreatitis.

BACKGROUND: Duodenum-preserving pancreatic head resection according to Beger and the pylorus-preserving Whipple (ppWhipple) procedure were compared in patients with chronic pancreatitis (CP) in a randomized clinical trial. Perioperative data and short-term outcome have been reported previously. The present study evaluated long-term follow-up. METHODS: Forty patients were enrolled originally, 20 in each group. Long-term follow-up included mortality, morbidity, pain status, occupational rehabilitation, quality of life (QoL), and endocrine and exocrine function at median follow-up of 7 and 14 years. RESULTS: One patient who had a ppWhipple procedure was lost to follow-up. There were five late deaths in each group. No differences were noted in pain status and exocrine pancreatic function. Loss of appetite was significantly worse in the ppWhipple group at 14 years' follow-up, but there were no other differences in QoL parameters examined. After 14 years, diabetes mellitus was present in seven of 15 patients who had the Beger procedure and 11 of 14 patients after ppWhipple resection (P = 0.128). CONCLUSION: After long-term follow-up of up to 14 years early advantages of the Beger procedure were no longer present.

Resistance and cross-resistance to oxidising agents of bacterial isolates from endoscope washer disinfectors.

Bacteria isolated from washer disinfectors using chlorine dioxide as a high-level disinfectant were exposed to peracetic acid, chlorine dioxide and hydrogen peroxide to investigate their susceptibility and possible bacterial cross-resistance to these highly reactive oxidising biocides. A standard suspension test was used to establish a rate of kill of these biocides against two stable isolates (Bacillus subtilis and Micrococcus luteus). Suspension tests demonstrated that 'in use' concentrations were not always effective to provide the required disinfection efficacy within recommended exposure times and in some instances a 60min exposure was necessary to achieve a reduction in number by a factor of 10(5). It appears that vegetative Gram-positive isolates can become resistant to oxidising agents in vitro, and that cross-resistance to related compounds can occur. Since these bacteria are deemed to be susceptible to highly reactive biocides, there should be further study of the resistance mechanisms in these isolates to explain their survival.

Does systematic 2-field lymphadenectomy for esophageal malignancy offer a survival advantage? Results from 178 consecutive patients.

More extensive resection for esophageal cancer has been reported to improve survival in several series. We compared results from an unselected consecutive cohort of patients undergoing radical esophagectomy, including removal of all periesophageal tissue with a 2-field abdominal and mediastinal lymphadenectomy for esophageal and gastroesophageal malignancy. A prospective electronic database was reviewed for patients with esophageal malignancy undergoing an open esophagectomy between 1991 and 2004. Data were analyzed on an SPSS file (version 12.0, Chicago, IL, USA) using chi(2) or Fisher's exact test; odds ratio and 95% confidence interval; and the Kaplan-Meier method, log-rank test and Cox's proportional hazards regression for survival analysis. There were 178 patients with a median age of 65 years and a 70/30 male to female ratio. Median follow-up was 20.4 months. Pathology comprised adenocarcinoma in 64% of patients, squamous cell carcinoma 30%, and other malignancies 6%. Seventeen patients had neoadjuvant therapy. Hospital mortality was 3.3%. Complete resection was achieved in 87%. Local recurrence occurred at a median of 13 months in 6.7% of patients. Overall 5-year survival was 42%. For patients with invasive squamous cell carcinoma and adenocarcinoma the 5-year survival was 47% and 40.3%, respectively, and for patients without nodal involvement it was 71.5%, with one to four nodes involved, 23.5% and with >4 nodes, 5% (P < 0.001). Survival decreased with increasing direct tumor spread (P < 0.001) and pathological stage (P < 0.001). Esophageal resection with systematic 2-field lymphadenectomy can be performed with acceptable operative mortality and favorable survival.

Identification of a germ line transcript from the unrearranged kappa gene in human B cells.

A novel kappa immunoglobulin-hybridizing mRNA in cell lines derived from human B cells arrested at several stages of development has been identified. Hybridization studies demonstrate that this 1.5-kilobase mRNA species is the spliced product of a precursor germ line transcript initiating upstream of the unrearranged JKappa locus.

Initiation and processing of two kappa immunoglobulin germ line transcripts in mouse B cells.

The splicing patterns and sequences of two processed kappa immunoglobulin germ line mRNAs are presented. A 1.1-kilobase (kb) mRNA appeared to be derived from splicing of the previously characterized 8.4-kb germ line transcript, while a 0.8-kb mRNA was the splice product of a second 4.7-kb germ line transcript that initiated 50 base pairs upstream of J kappa 1. The interaction of the two kappa germ line promoters with nuclear binding factors is also examined. The potential role of these germ line transcripts in establishing the rearrangement potential of the locus is discussed.

Effect of pain neurophysiology education on physiotherapy students' understanding of chronic pain, clinical recommendations and attitudes towards people with chronic pain: a randomised controlled trial.

OBJECTIVE: To investigate the effect of pain neurophysiology education (PNE) on student physiotherapists': (1) knowledge of chronic pain; (2) attitudes towards patients with chronic pain; and (3) clinical recommendations for patients with chronic pain. DESIGN: Multicentre single-blind randomised controlled trial. SETTING: One UK and one Irish university. PARTICIPANTS: Seventy-two student physiotherapists. INTERVENTION: Participants received either PNE (intervention) or a control education. Both were delivered in a 70-minute group lecture. MAIN OUTCOME MEASURES: (1) The Revised Pain Neurophysiology Quiz to assess knowledge; (2) the Health Care Pain Attitudes and Impairment Relationship Scale (HC-PAIRS) to assess attitudes; and (3) a case vignette to assess the appropriateness of clinical recommendations. RESULTS: Post education, the PNE group had a greater increase in pain neurophysiology knowledge [mean difference 4.0 (95% confidence interval 3.2 to 4.7), P<0.01] and more improved attitudes [-17.5 (95% confidence interval -22.1 to -12.9), P<0.01] compared with the control group. Post education, students in the PNE group were more likely to make appropriate recommendations regarding work (94% vs 56%), exercise (92% vs 56%), activity (94% vs 67%) and bed rest (69% vs 33%) compared with those in the control group (P<0.05). CONCLUSION: The improvements in knowledge, attitudes and recommendations for pain management show that PNE is a potentially valuable part of the education of physiotherapy students, and could be used on a more widespread basis. There is a need to investigate whether these findings can be replicated in other healthcare professions, and how well these reported changes lead to changes in actual clinical behaviour and the clinical outcomes of patients.

Assessing the shock state of the lunar highlands: Implications for the petrogenesis and chronology of crustal anorthosites.

Our understanding of the formation and evolution of the primary lunar crust is based on geochemical systematics from the lunar ferroan anorthosite (FAN) suite. Recently, much effort has been made to understand this suite's petrologic history to constrain the timing of crystallisation and to interpret FAN chemical diversity. We investigate the shock histories of lunar anorthosites by combining Optical Microscope (OM) 'cold' cathodoluminescence (CL)-imaging and Fourier Transform Infrared (FTIR) spectroscopy analyses. In the first combined study of its kind, this study demonstrates that over ~4.5 Ga of impact processing, plagioclase is on average weakly shocked (<15 GPa) and examples of high shock states (>30 GPa; maskelynite) are uncommon. To investigate how plagioclase trace-element systematics are affected by moderate to weak shock (~5 to 30 GPa) we couple REE+Y abundances with FTIR analyses for FAN clasts from lunar meteorite Northwest Africa (NWA) 2995. We observe weak correlations between plagioclase shock state and some REE+Y systematics (e.g., La/Y and Sm/Nd ratios). This observation could prove significant to our understanding of how crystallisation ages are evaluated (e.g., plagioclase-whole rock Sm-Nd isochrons) and for what trace-elements can be used to differentiate between lunar lithologies and assess magma source compositional differences.

Surgical versus endoscopic treatment of bile duct stones.

BACKGROUND: 10% to 18% of patients undergoing cholecystectomy for gallstones have common bile duct (CBD) stones. Treatment options for these stones include pre- or post-operative endoscopic retrograde cholangiopancreatography (ERCP) or open or laparoscopic surgery. OBJECTIVES: To systematically review the management of CBD stones by four approaches: (1) ERCP versus open surgical bile duct clearance. (2) Pre-operative ERCP versus laparoscopic bile duct clearance. (3) Post-operative ERCP versus laparoscopic bile duct clearance. (4) ERCP versus laparoscopic bile duct clearance in patients with previous cholecystectomy. SEARCH STRATEGY: We systematically searched key relevant electronic databases, bibliographies of relevant papers, and abstracts of relevant subspecialty meetings until November 2005. SELECTION CRITERIA: The quality of included trials was assessed by adequacy of allocation sequence generation, allocation concealment, blinding, and follow-up. DATA COLLECTION AND ANALYSIS: Published and unpublished data relevant to 12 predefined outcome measures were used to conduct fixed- and random-effects models meta-analyses, with exploration of heterogeneity and use of sensitivity and subgroup analysis where required. MAIN RESULTS: Thirteen trials randomised 1351 patients. Eight trials (n = 760) compared ERCP with open surgical clearance, three (n = 425) compared pre-operative ERCP with laparoscopic clearance, and two (n = 166) compared post-operative ERCP with laparoscopic clearance. There were no trials of ERCP versus laparoscopic clearance in patients without an intact gallbladder. Methodology was considered adequate in at least two of three assessable fields in ten trials. A significantly increased number of total procedures (including for complications) per patient was seen in the ERCP arms in all three comparisons with weighted mean differences of 0.62 (95% CI 0.15 to 1.09), 0.96 (95% CI 0.96 to 0.96), and 1.09 (95% CI 0.93 to 1.24), respectively. ERCP was less successful than open surgery in CBD stone clearance (Peto OR 2.89, 95% CI 1.81 to 4.61) with a tendency towards higher mortality (risk difference 1%, 95% CI -1% to 4%). Laparoscopic CBD stone clearance was as efficient as pre- (Peto OR 1.00, CI 0.53 to 1.80) and post-operative ERCP (OR 2.27, 95% CI 0.37 to 13.9) and with no significant difference in morbidity and mortality. Laparoscopic trials universally reported shorter hospital stays in surgical arms. Insufficient data were reported for cost analysis. AUTHORS' CONCLUSIONS: In the era of open cholecystectomy, open bile duct surgery was superior to ERCP in achieving CBD stone clearance. In the laparoscopic era, data are close to excluding a significant difference between laparoscopic and ERCP clearance of CBD stones. The use of ERCP necessitates increased number of procedures per patient.

The intra- and inter-observer reliability of a novel protocol for two-point discrimination in individuals with chronic low back pain.

Two-point discrimination is measured as an indicator of cortical reorganisation in musculoskeletal medicine. Nevertheless, data are lacking for the reliability of this measure in patients with non-specific chronic low back pain (NSCLBP). We aimed to quantify the intra- and inter-observer reliability of a novel protocol for measuring two-point discrimination in these patients. 35 participants (12 males, 23 females, mean age 52, SD 15 years) with NSCLBP were recruited. Three clinicians made 14 consecutive measurements of two-point discrimination with callipers. One of these clinicians repeated the assessment protocol within 7 d. During each measurement, the calliper width was widened in 5 mm increments until participants could consistently identify two points. Intra- and inter-observer agreement was quantified using mean difference, within-subject SD and limits of agreement (LOA). After using the first measurement for familiarisation, the mean of measurements 2-5 within an assessment resulted in the optimum compromise between clinic time constraints and acceptable intra-observer reliability; the within-subjects SD being 7.5 mm (LOA: 20.8 mm). Inter-observer reliability was generally poorer; requiring the mean of measurements 2-9 within an assessment for a similar within-subjects SD of 8.6 mm (LOA: 23.7 mm). It was estimated that these within-subjects SDs were small enough for a clinically-important change to be detected with a feasible sample size in future studies. The intra-observer reliability of our assessment protocol is acceptable for detecting a clinically relevant difference in two-point discrimination for future research purposes. Nevertheless, individual patient measurement variability is relatively high, especially between different clinicians.

User settings on dive computers: reliability in aiding conservative diving.

INTRODUCTION: Divers can make adjustments to diving computers when they may need or want to dive more conservatively (e.g., diving with a persistent (patent) foramen ovale). Information describing the effects of these alterations or how they compare to other methods, such as using enriched air nitrox (EANx) with air dive planning tools, is lacking. METHODS: Seven models of dive computer from four manufacturers (Mares, Suunto, Oceanic and UWATEC) were subjected to single square-wave compression profiles (maximum depth: 20 or 40 metres' sea water, msw), single multi-level profiles (maximum depth: 30 msw; stops at 15 and 6 msw), and multi-dive series (two dives to 30 msw followed by one to 20 msw). Adjustable settings were employed for each dive profile; some modified profiles were compared against stand-alone use of EANx. RESULTS: Dives were shorter or indicated longer decompression obligations when conservative settings were applied. However, some computers in default settings produced more conservative dives than others that had been modified. Some computer-generated penalties were greater than when using EANx alone, particularly at partial pressures of oxygen (PO2) below 1.40 bar. Some computers 'locked out' during the multi-dive series; others would continue to support decompression with, in some cases, automatically-reduced levels of conservatism. Changing reduced gradient bubble model values on Suunto computers produced few differences. DISCUSSION: The range of possible adjustments and the non-standard computer response to them complicates the ability to provide accurate guidance to divers wanting to dive more conservatively. The use of EANx alone may not always generate satisfactory levels of conservatism.

SCUBA divers as oceanographic samplers: The potential of dive computers to augment aquatic temperature monitoring.

Monitoring temperature of aquatic waters is of great importance, with modelled, satellite and in-situ data providing invaluable insights into long-term environmental change. However, there is often a lack of depth-resolved temperature measurements. Recreational dive computers routinely record temperature and depth, so could provide an alternate and highly novel source of oceanographic information to fill this data gap. In this study, a citizen science approach was used to obtain over 7,000 scuba diver temperature profiles. The accuracy, offset and lag of temperature records was assessed by comparing dive computers with scientific conductivity-temperature-depth instruments and existing surface temperature data. Our results show that, with processing, dive computers can provide a useful and novel tool with which to augment existing monitoring systems all over the globe, but especially in under-sampled or highly changeable coastal environments.

Role of Ca2+ stores in metabotropic L-glutamate receptor-mediated supralinear Ca2+ signaling in rat hippocampal neurons.

The role of metabotropic l-glutamate (mGlu) receptors in supralinear Ca(2+) signaling was investigated in cultured hippocampal cells using Ca(2+) imaging techniques and whole-cell voltage-clamp recording. In neurons, but not glia, global supralinear Ca(2+) release from intracellular stores was observed when the mGlu receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) was combined with elevated extracellular K(+) levels (10.8 mm), moderate depolarization (15-30 mV), or NMDA (3 micrometer). There was a delay (2-8 min) before the stores were fully charged, and the enhancement persisted for a short period (up to 10 min) after removal of the store-loading stimulus. Studies with the mGlu receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine demonstrated that these effects were mediated by activation of the mGlu(5) receptor subtype. The L-type voltage-gated Ca(2+) channel antagonist nifedipine (10 micrometer) substantially reduced responses to DHPG obtained in the presence of elevated extracellular K(+) but not NMDA. This suggests that the Ca(2+) that is required to load the stores can enter either through L-type voltage-gated Ca(2+) channels or directly through NMDA receptors. The findings that both depolarization and NMDA receptor activation can facilitate mGlu receptor Ca(2+) signaling adds considerable flexibility to the processes that underlie activity-dependent changes in synaptic strength. In particular, a temporal separation between the store-loading stimulus and the activation of mGlu receptors could be used as a recency detector in neurons.