A complex dynamo inferred from the hemispheric dichotomy of Jupiter's magnetic field.

The Juno spacecraft, which is in a polar orbit around Jupiter, is providing direct measurements of the planet's magnetic field close to its surface1. A recent analysis of observations of Jupiter's magnetic field from eight (of the first nine) Juno orbits has provided a spherical-harmonic reference model (JRM09)2 of Jupiter's magnetic field outside the planet. This model is of particular interest for understanding processes in Jupiter's magnetosphere, but to study the field within the planet and thus the dynamo mechanism that is responsible for generating Jupiter's main magnetic field, alternative models are preferred. Here we report maps of the magnetic field at a range of depths within Jupiter. We find that Jupiter's magnetic field is different from all other known planetary magnetic fields. Within Jupiter, most of the flux emerges from the dynamo region in a narrow band in the northern hemisphere, some of which returns through an intense, isolated flux patch near the equator. Elsewhere, the field is much weaker. The non-dipolar part of the field is confined almost entirely to the northern hemisphere, so there the field is strongly non-dipolar and in the southern hemisphere it is predominantly dipolar. We suggest that Jupiter's dynamo, unlike Earth's, does not operate in a thick, homogeneous shell, and we propose that this unexpected field morphology arises from radial variations, possibly including layering, in density or electrical conductivity, or both.

Randomized Controlled Study of Self-Managed Music-Guided Exercise Intervention Following Intensive Care.

BACKGROUND: Patients who are discharged from the intensive care unit (ICU; termed ICU survivors) often experience persistent physical impairment. OBJECTIVE: The aim of this study was to explore the effects of a self-managed, music-guided exercise intervention on physical outcomes and adherence rates among ICU survivors. METHODS: A randomized controlled design was used. Following ICU discharge, participants admitted to the ICU for at least 5 days were randomly assigned to a music group ( n = 13) or an active control group ( n = 13). Activity counts were measured using an Actiwatch, and the physical health score was measured using the Patient-Reported Outcomes Measurement Information System global health subscale. Adherence to exercise was documented daily. Independent t -tests were used for data analysis. RESULTS: Data were analyzed for 26 participants. The mean age was 62.8 ± 13.8 years, 53.8% were male, 65.4% were White, and mean Acute Physiology and Chronic Health Evaluation severity of illness score was 59 ± 23.4. Global health physical scores were significantly higher in the music group than in the active control group. Although not significantly different, music group participants tended to be more active and had higher physical activity and adherence rates compared to those in the active control group. CONCLUSION: A self-managed, music-guided exercise intervention demonstrated positive benefits on physical outcomes. Future clinical trials with a larger sample size should be conducted to examine the effects of this tailored, cost-effective, innovative, self-managed exercise intervention among ICU survivors.

The need for future coronary access following surgical or transcatheter aortic valve replacement.

The aim of the study was to estimate the percentage of Medicare patients needing coronary access for percutaneous coronary intervention (PCI) or coronary angiography following aortic valve replacement (AVR). Indications for TAVR have expanded to include younger and low-risk patients, raising the question of coronary access for future procedures. Medicare patients <80 years old with an AVR between 2011 and 2018 were included. Time-to-event analyses were conducted using Cox hazard models to estimate risk of coronary access up to 7 years after AVR. Model adjustments included age, sex, race, region, comorbidity, concomitant CABG, and smoking. A total of 13,469 Medicare patients (mean age 70.6) met inclusion criteria. Models estimated that 2.5% of patients at 1-year post-index and 17% at over 7 years would need coronary access. For patients who had SAVR (with or without CABG), estimates for coronary access were similar and over 15% after 6.5 years. For TAVR patients, with a previous PCI, 28% at 4.5 years required coronary access, which was higher than TAVR patients without a previous PCI. SAVR patients with and without CAD at baseline were similar; however, TAVR patients with CAD had a 22% rate of coronary access versus 7% for those without at 3 years. Approximately half of patients who needed coronary access returned to the same hospital as their initial AVR. Coronary access is required in a substantial portion of AVR patients especially those with PCI or a history of CAD undergoing TAVR. The need for coronary access may increase as transcatheter AVR becomes accessible to younger patients with a longer life expectancy.

Statistical measures of motor, sensory and cognitive performance across repeated robot-based testing.

BACKGROUND: Traditional clinical assessments are used extensively in neurology; however, they can be coarse, which can also make them insensitive to change. Kinarm is a robotic assessment system that has been used for precise assessment of individuals with neurological impairments. However, this precision also leads to the challenge of identifying whether a given change in performance reflects a significant change in an individual's ability or is simply natural variation. Our objective here is to derive confidence intervals and thresholds of significant change for Kinarm Standard Tests™ (KST). METHODS: We assessed participants twice within 15 days on all tasks presently available in KST. We determined the 5-95% confidence intervals for each task parameter, and derived thresholds for significant change. We tested for learning effects and corrected for the false discovery rate (FDR) to identify task parameters with significant learning effects. Finally, we calculated intraclass correlation of type ICC [1, 2] (ICC-C) to quantify consistency across assessments. RESULTS: We recruited an average of 56 participants per task. Confidence intervals for Z-Task Scores ranged between 0.61 and 1.55, and the threshold for significant change ranged between 0.87 and 2.19. We determined that 4/11 tasks displayed learning effects that were significant after FDR correction; these 4 tasks primarily tested cognition or cognitive-motor integration. ICC-C values for Z-Task Scores ranged from 0.26 to 0.76. CONCLUSIONS: The present results provide statistical bounds on individual performance for KST as well as significant changes across repeated testing. Most measures of performance had good inter-rater reliability. Tasks with a higher cognitive burden seemed to be more susceptible to learning effects, which should be taken into account when interpreting longitudinal assessments of these tasks.

Feasibility and acceptability of a self-managed exercise to rhythmic music intervention for ICU survivors.

BACKGROUND: Post-ICU rehabilitation is a challenging clinical issue for patients discharged from an Intensive Care Unit ("ICU survivors"). Our exercise to rhythmic music intervention was designed to allow ICU survivors to self-manage their exercise by following a personalized, recorded exercise playlist. AIM: Our study reports the feasibility and acceptability of an innovative music intervention among ICU survivors enrolled in a randomized controlled pilot study. METHODS: ICU survivors, admitted in ICU for at least 5 days and cognitively intact, were randomly assigned to an exercise to rhythmic music group (n = 10) or an active control group (n = 10). Participants in the music group were taught to self-manage exercise by listening to a recorded playlist of instructions and music-facilitated movements tailored to their musical preference and exercise ability. Participants in the control group were provided a brochure with exercise instructions. After 5 days or at hospital discharge, participants completed an 8-item acceptability questionnaire and were interviewed. Content analysis was conducted. RESULTS: 18 Participants were included for final analysis. Participants were 61.8 ± 14.7 years old, predominantly male (66.7%), and Caucasian (55.6%). Results demonstrated feasibility, as the study team was able to meet the enrollment goal of 5-6 participants per month. Three themes related to general, physical, and psychosocial benefits were identified. Based on positive feedback, the exercise to rhythmic music intervention was deemed acceptable. CONCLUSION: The exercise to rhythmic music intervention was feasible and acceptable, suggesting that clinical trials with larger sample sizes should investigate the effects of the intervention on outcomes among ICU survivors.

Branching, flowering and fruiting of Jatropha curcas treated with ethephon or benzyladenine and gibberellins.

Jatropha curcas L. has been identified for biofuel production but it presents limited commercial yields due to limited branching and a lack of yield uniformity. The objective of this study was to evaluate the effects of single application of ethephon or a combination of 6-benzyladenine (BA) with gibberellic acid isomers A4 and A7 (GA4+7) on branch induction, flowering and fruit production in jatropha plants with and without leaves. Plants with and without leaves showed differences for growth and reproductive variables. For all variables except inflorescence set, there were no significant statistical interactions between the presence of leaves and plant growth regulators concentration. The total number of flowers per inflorescence was reduced as ethephon concentration was increased. As BA + GA4 +7 concentration increased, seed dry weight increased. Thus, ethephon and BA + GA4 +7 applications appeared to affect flowering and seed production to a greater extent than branching. The inability to discern significant treatment effects for most variables might have been due to the large variability within plant populations studied and thus resulting in an insufficient sample size. Therefore, data collected from this study were used for statistical estimations of sample sizes to provide a reference for future studies.

Cost-benefit and effectiveness analysis of rapid testing for MRSA carriage in a hospital setting.

A cost-effectiveness analysis was conducted comparing the polymerase chain reaction assay and traditional microbiological culture as screening tools for the identification of methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to the pediatric and surgical intensive care units (PICU and SICU) at a 722 bed academic medical center. In addition, the cost benefits of identification of colonized MRSA patients were determined. The cost-effectiveness analysis employed actual hospital and laboratory costs, not patient costs. The actual cost of the PCR assay was higher than the microbiological culture identification of MRSA ($602.95 versus $364.30 per positive carrier identified). However, this did not include the decreased turn-around time of PCR assays compared to traditional culture techniques. Patient costs were determined indirectly in the cost-benefit analysis of clinical outcome. There was a reduction in MRSA hospital-acquired infection (3.5 MRSA HAI/month without screening versus 0.6/month with screening by PCR). A cost-benefit analysis based on differences in length of stay suggests an associated savings in hospitalization costs: MRSA HAI with 29.5 day median LOS at $63,810 versus MRSA identified on admission with 6 day median LOS at $14,561, a difference of $49,249 per hospitalization. Although this pilot study was small and it is not possible to directly relate the cost-effectiveness and cost-benefit analysis due to confounding factors such as patient underlying morbidity and mortality, a reduction of 2.9 MRSA HAI/month associated with PCR screening suggests potential savings in hospitalization costs of $142,822 per month.

The systematic review as a research process in music therapy.

BACKGROUND: Music therapists are challenged to present evidence on the efficacy of music therapy treatment and incorporate the best available research evidence to make informed healthcare and treatment decisions. Higher standards of evidence can come from a variety of sources including systematic reviews. OBJECTIVE: To define and describe a range of research review methods using examples from music therapy and related literature, with emphasis on the systematic review. In addition, the authors provide a detailed overview of methodological processes for conducting and reporting systematic reviews in music therapy. METHODS: The systematic review process is described in five steps. Step 1 identifies the research plan and operationalized research question(s). Step 2 illustrates the identification and organization of the existing literature related to the question(s). Step 3 details coding of data extracted from the literature. Step 4 explains the synthesis of coded findings and analysis to answer the research question(s). Step 5 describes the strength of evidence evaluation and results presentation for practice recommendations. RESULTS: Music therapists are encouraged to develop and conduct systematic reviews. This methodology contributes to review outcome credibility and can determine how information is interpreted and used by clinicians, clients or patients, and policy makers. CONCLUSIONS: A systematic review is a methodologically rigorous research method used to organize and evaluate extant literature related to a clinical problem. Systematic reviews can assist music therapists in managing the ever-increasing literature, making well-informed evidence based practice and research decisions, and translating existing music-based and nonmusic based literature to clinical practice and research development.

Synaptic transmission regulated by a presynaptic MALS/Liprin-alpha protein complex.

Neurotransmission requires proper organization of synaptic vesicle pools and rapid release of vesicle contents upon presynaptic depolarization. Genetic studies have begun to reveal a critical role for scaffolding proteins in such processes. Mutations in genes encoding components of the highly conserved MALS/CASK/Mint-1 complex cause presynaptic defects. In all three mutants, neurotransmitter release is reduced in a manner consistent with aberrant vesicle cycling to the readily releasable pool. Recently, liprin-alpha proteins, which define active zone size and morphology, were found to associate with MALS/CASK, suggesting that this complex links the presynaptic release machinery to the active zone, thereby regulating neurotransmitter release.

A systematic review on the neural effects of music on emotion regulation: implications for music therapy practice.

BACKGROUND: Emotion regulation (ER) is an internal process through which a person maintains a comfortable state of arousal by modulating one or more aspects of emotion. The neural correlates underlying ER suggest an interplay between cognitive control areas and areas involved in emotional reactivity. Although some studies have suggested that music may be a useful tool in ER, few studies have examined the links between music perception/production and the neural mechanisms that underlie ER and resulting implications for clinical music therapy treatment. Objectives of this systematic review were to explore and synthesize what is known about how music and music experiences impact neural structures implicated in ER, and to consider clinical implications of these findings for structuring music stimuli to facilitate ER. METHODS: A comprehensive electronic database search resulted in 50 studies that met predetermined inclusion and exclusion criteria. Pertinent data related to the objective were extracted and study outcomes were analyzed and compared for trends and common findings. RESULTS: Results indicated there are certain music characteristics and experiences that produce desired and undesired neural activation patterns implicated in ER. Desired activation patterns occurred when listening to preferred and familiar music, when singing, and (in musicians) when improvising; undesired activation patterns arose when introducing complexity, dissonance, and unexpected musical events. Furthermore, the connection between music-influenced changes in attention and its link to ER was explored. CONCLUSIONS: Implications for music therapy practice are discussed and preliminary guidelines for how to use music to facilitate ER are shared.

Assessing quality and beneficial uses of Sargassum compost.

Sargassum spp. (specifically Sargassum fluitans and S. natans), one of the dominant forms of marine macroalgae (seaweed) found on the beaches of Florida, is washing up on the shores throughout the Caribbean in record quantities. Currently, a common management option is to haul and dispose of beached Sargassum in local landfills, potentially wasting a valuable renewable resource. The objective of this study was to determine whether composting represents a feasible alternative to managing Sargassum inundations through measurements and comparisons to eleven guidelines. Specifically, we assessed the characteristics of the compost [physical-chemical parameters (temperature, moisture content, pH, and conductivity), nutrient ratios (C:N), elemental composition, bacteria levels, and ability to sustain plant growth] in both small- and large scale experiments. Results show that although nutrient concentration ratios were not within the standards outlined by the U.S. Composting Council (USCC), the Sargassum compost was able to sustain the growth of radishes (Raphanus sativus L., var. Champion). Trace metal concentrations in the compost product were within five regulatory guidelines evaluated, except for arsenic (As) (6.64-26.5 mg/kg), which exceeded one of the five (the Florida Soil Cleanup Target Level for residential use). Bacteria levels were consistent with regulatory guidelines for compost produced in large-scale outdoor experiments but not for the small-scale set conducted in enclosed tumblers. Overall results support that Sargassum compost can be beneficially used for fill and some farming applications.

The international reference system for beta-particle emitting radionuclides: Validation through the pilot study CCRI(II)-P1.Co-60.

The Bureau International des Poids et Mesures (BIPM) is developing a new transfer instrument to extend its centralized services for assessing the international equivalence of radioactive standards to new radionuclides. A liquid scintillation counter using the triple/double coincidence ratio method is being studied and tested in the CCRI(II)-P1.Co-60 pilot study. The pilot study, involving 13 participating laboratories with primary calibration capabilities, validated the approach against the original international reference system based on ionization chambers, which has been in operation since 1976. The results are in agreement and an accuracy suitable for purpose, below 5×10-4, is achieved. The pilot study also reveals an issue when impurities emitting low-energy electrons are present in the standard solution, which have a different impact on liquid scintillation counting compared to other primary measurement methods.

Renal defects associated with improper polarization of the CRB and DLG polarity complexes in MALS-3 knockout mice.

Kidney development and physiology require polarization of epithelia that line renal tubules. Genetic studies show that polarization of invertebrate epithelia requires the crumbs, partition-defective-3, and discs large complexes. These evolutionarily conserved protein complexes occur in mammalian kidney; however, their role in renal development remains poorly defined. Here, we find that mice lacking the small PDZ protein mammalian LIN-7c (MALS-3) have hypomorphic, cystic, and fibrotic kidneys. Proteomic analysis defines MALS-3 as the only known core component of both the crumbs and discs large cell polarity complexes. MALS-3 mediates stable assembly of the crumbs tight junction complex and the discs large basolateral complex, and these complexes are disrupted in renal epithelia from MALS-3 knockout mice. Interestingly, MALS-3 controls apico-basal polarity preferentially in epithelia derived from metanephric mesenchyme, and defects in kidney architecture owe solely to MALS expression in these epithelia. These studies demonstrate that defects in epithelial cell polarization can cause cystic and fibrotic renal disease.

The unintended consequences of Medicare's wage index adjustment on device-intensive hospital procedures.

OBJECTIVES: To study the association between Medicare's wage index adjustment and the differential use of labor-intensive surgical procedures and medical device-intensive minimally invasive clinical procedures across the United States. STUDY DESIGN: We combine a conceptual model and an empirical investigation of its predictions, applied to aortic valve replacement, to study the relationship between variation in Medicare wage index payment adjustment across hospital referral regions (HRRs) and the utilization of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in these areas. METHODS: Using detailed individual Medicare claims data for 2013-2018 and a novel geographical crosswalk to nest information on Medicare's wage index and utilization of TAVR and SAVR, we estimate a mixed effects Poisson regression model across HRRs to test our hypotheses. RESULTS: We find regional variation in Medicare wage index adjustment levels to be correlated with differential TAVR and SAVR utilization and growth over time. In particular, in HRRs where the wage index is half the national mean there is a 35% decline in the rate of TAVR use and in HRRs where the wage index is 50% higher than the national mean there is a 52% increase in the rate of TAVR use. CONCLUSIONS: Consistent with our framework and hypothesis, our results highlight the importance of adjusting Medicare hospital inpatient payments for device-intensive procedures. Absent such adjustment, access to appropriate interventions may be reduced in areas with low wage index, and lower reimbursement, when driven by wage index adjustment, may influence the treatment approach selected.

Contemporary Costs Associated With Transcatheter Versus Surgical Aortic Valve Replacement in Medicare Beneficiaries.

BACKGROUND: In patients with severe aortic stenosis, treatment with transcatheter aortic valve replacement (TAVR) has been shown to be cost-effective in the high-risk surgical population and cost-saving in the intermediate-risk population when compared with surgical aortic valve replacement (SAVR) in early pivotal clinical trials. Whether TAVR is associated with comparable or lower costs when compared with SAVR in contemporary clinical practice is unknown. METHODS: Using data from the Medicare Dataset Standard Analytic Files 5% Fee for Service database, patients receiving either TAVR or SAVR between 2016 and 2018 were identified. Patients were categorized as low, intermediate, or high mortality risk based on 2 validated indices-the Hospital Frailty Risk Score and the logEuroScore. Health care costs out to 1 year were compared between TAVR and SAVR among the low, intermediate, and high-risk groups, after adjustment for patient demographics. RESULTS: Nine thousand seven hundred forty-six patients were identified (4834 TAVR; 3760 SAVR) and included in the analysis. Patients receiving TAVR were older and more likely to be female. Index hospitalization costs were significantly lower with TAVR compared with SAVR across all risk strata (logEuroScore: low: $61 845 versus $68 986; intermediate: $64 658 versus $76 965; high: $65 594 versus $91 005; P<0.001 for all). Follow-up costs through 1 year were generally lower with TAVR and this difference was more pronounced in the low risk groups (logEuroScore: $9763 versus $14 073; Hospital Frailty Risk Score: $10 116 versus $12 880). Accordingly, cumulative 1-year costs were substantially lower with TAVR compared with SAVR. CONCLUSIONS: At 1 year, TAVR is associated with lower health care costs across all risk strata when compared with SAVR in contemporary practice. If long-term data continue to demonstrate similar clinical outcomes and valve durability with TAVR and SAVR, these findings suggest that TAVR may be the preferred treatment strategy for patients with aortic stenosis from an economic standpoint.

Self-Managed Music-Guided Exercise Intervention Improved Upper and Lower Extremity Muscle Strength for ICU Survivors-A Pilot Randomized Controlled Study.

ObjectiveThe objective of this study was to evaluate effects of a self-managed music-guided exercise intervention on muscle strength among intensive care unit (ICU) survivors. Methods We used a two-arm randomized-controlled trial. Following ICU discharge, eligible participants were assigned to one of two groups: music group (n = 13) or active control group (n = 13). The music group was taught to self-manage upper and lower extremity exercise movements by listening to an individualized music-guided playlist twice daily for 5 days. The active control group was provided an exercise brochure and advised to perform the same exercises at the same intervals. Dynamometers were used to measure muscle strength. T-tests and Weighted GEE models were used for testing the intervention effect between groups. Results Twenty-six subjects were enrolled. The mean age was 62.8 (SD = 13.8), 53.8% were male, 65.4% were Caucasian, and the mean APACHE severity of illness score was 59 (SD = 23.4). Reasons for ICU admission were mainly cardiac and medical. The music group showed significant improvements in handgrip, plantar flexion, leg extension, elbow flexion, and shoulder adduction strengths on left and right sides. Additionally, left and right leg extensor and left plantar flexor strengths showed significant post-differences, and small to moderately large effect sizes, between the music group and control group. Conclusion These findings suggest that a music-guided exercise intervention has the potential to improve muscle strength in ICU survivors and prevent further post-ICU deterioration in ICU survivors. Future trials should build upon these preliminary findings.

Temporal Changes in Mortality After Transcatheter and Surgical Aortic Valve Replacement: Retrospective Analysis of US Medicare Patients (2012-2019).

Background The treatment of aortic stenosis is evolving rapidly. Pace of change in the care of patients undergoing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) differs. We sought to determine differences in temporal changes in 30-day mortality, 30-day readmission, and length of stay after TAVR and SAVR. Methods and Results We conducted a retrospective cohort study of patients treated in the United States between 2012 and 2019 using data from the Medicare Data Set Analytic File 100% Fee for Service database. We included consecutive patients enrolled in Medicare Parts A and B and aged ≥65 years who had SAVR or transfemoral TAVR. We defined 3 study cohorts, including all SAVR, isolated SAVR (without concomitant procedures), and elective isolated SAVR and TAVR. The primary end point was 30-day mortality; secondary end points were 30-day readmission and length of stay. Statistical models controlled for patient demographics, frailty measured by the Hospital Frailty Risk Score, and comorbidities measured by the Elixhauser Comorbidity Index (ECI). Cox proportional hazard models were developed with TAVR versus SAVR as the main covariates with a 2-way interaction term with index year. We repeated these analyses restricted to full aortic valve replacement hospitals offering both SAVR and TAVR. The main study cohort included 245 269 patients with SAVR and 188 580 patients with TAVR, with mean±SD ages 74.3±6.0 years and 80.7±6.9 years, respectively, and 36.5% and 46.2% female patients, respectively. Patients with TAVR had higher ECI scores (6.4±3.6 versus 4.4±3) and were more frail (55.4% versus 33.5%). Total aortic valve replacement volumes increased 61% during the 7-year span; TAVR volumes surpassed SAVR in 2017. The magnitude of mortality benefit associated with TAVR increased until 2016 in the main cohort (2012: hazard ratio [HR], 0.76 [95% CI, 0.67-0.86]; 2016: HR, 0.39 [95% CI, 0.36-0.43]); although TAVR continued to have lower mortality rates from 2017 to 2019, the magnitude of benefit over SAVR was attenuated. A similar pattern was seen with readmission, with a lower risk of readmission from 2012 to 2016 for patients with TAVR (2012: HR, 0.68 [95% CI, 0.63-0.73]; 2016: HR, 0.43 [95% CI, 0.41-0.45]) followed by a lesser difference from 2017 to 2019. Year over year, TAVR was associated with increasingly shorter lengths of stay compared with SAVR (2012: HR, 1.91 [95% CI, 1.84-1.98]; 2019: HR, 5.34 [95% CI, 5.22-5.45]). These results were consistent in full aortic valve replacement hospitals. Conclusions The rate of improvement in TAVR outpaced SAVR until 2016, with the recent presence of U-shaped phenomena suggesting a narrowing gap between outcomes. Future longitudinal research is needed to determine the long-term implications of lowering risk profiles across treatment options to guide case selection and clinical care.

Neurotransmitter release regulated by a MALS-liprin-alpha presynaptic complex.

Synapses are highly specialized intercellular junctions organized by adhesive and scaffolding molecules that align presynaptic vesicular release with postsynaptic neurotransmitter receptors. The MALS/Veli-CASK-Mint-1 complex of PDZ proteins occurs on both sides of the synapse and has the potential to link transsynaptic adhesion molecules to the cytoskeleton. In this study, we purified the MALS protein complex from brain and found liprin-alpha as a major component. Liprin proteins organize the presynaptic active zone and regulate neurotransmitter release. Fittingly, mutant mice lacking all three MALS isoforms died perinatally with difficulty breathing and impaired excitatory synaptic transmission. Excitatory postsynaptic currents were dramatically reduced in autaptic cultures from MALS triple knockout mice due to a presynaptic deficit in vesicle cycling. These findings are consistent with a model whereby the MALS-CASK-liprin-alpha complex recruits components of the synaptic release machinery to adhesive proteins of the active zone.