Radiological Outcomes of Re-tethering for Adolescent Idiopathic Scoliosis: A 2-to-5-year Follow-Up Case Series After Index Vertebral Body Tethering Failure.

PURPOSE: Vertebral Body Tethering (VBT) has been shown to have a less predictable outcome compared to spinal fusion in patients with adolescent idiopathic scoliosis (AIS). Tether breakage is a common mechanical event that sometimes leads to loss of correction. No data has been published that evaluates the outcome of re-tethering in patients who underwent revision surgery for failed VBT, which was the purpose of this study. METHODS: This is an analysis of a prospectively collected single center database of 290 patients who have had VBT. Patients for this study were included if they have had re-tethering after failed VBT and a minimum follow up of 24 months after index surgery as well as a minimum follow up of 12 months after revision surgery. Revision surgeries included tether exchange, tether reinforcement and/or mono- and bisegmental lateral fusion. Main outcome of interest was curve magnitude at latest follow up. RESULTS: 11 patients were identified who received VBT for 16 curves of which 13 curves have had failed index surgery. Mean follow up from index surgery was 40 months, time between index and revision surgery was 22 months and latest follow up after revision surgery 19 months. Re-tethering resulted in an additional correction of 42% for thoracic and 63% for thoracolumbar curves. These results remained clinically stable with only minor loss of correction at final follow up. No patient underwent or was indicated for spinal fusion. CONCLUSION: Re-tethering is feasible and able to achieve additional correction and a sustainable result.

Different ER-plasma membrane tethers play opposing roles in autophagy of the cortical ER.

The endoplasmic reticulum (ER) undergoes degradation by selective macroautophagy (ER-phagy) in response to starvation or the accumulation of misfolded proteins within its lumen. In yeast, actin assembly at sites of contact between the cortical ER (cER) and endocytic pits acts to displace elements of the ER from their association with the plasma membrane (PM) so they can interact with the autophagosome assembly machinery near the vacuole. A collection of proteins tether the cER to the PM. Of these, Scs2/22 and Ist2 are required for cER-phagy, most likely through their roles in lipid transport, while deletion of the tricalbins, TCB1/2/3, bypasses those requirements. An artificial ER-PM tether blocks cER-phagy in both the wild type (WT) and a strain lacking endogenous tethers, supporting the importance of cER displacement from the PM. Scs2 and Ist2 can be cross-linked to the selective cER-phagy receptor, Atg40. The COPII cargo adaptor subunit, Lst1, associates with Atg40 and is required for cER-phagy. This requirement is also bypassed by deletion of the ER-PM tethers, suggesting a role for Lst1 prior to the displacement of the cER from the PM during cER-phagy. Although pexophagy and mitophagy also require actin assembly, deletion of ER-PM tethers does not bypass those requirements. We propose that within the context of rapamycin-induced cER-phagy, Scs2/22, Ist2, and Lst1 promote the local displacement of an element of the cER from the cortex, while Tcb1/2/3 act in opposition, anchoring the cER to the plasma membrane.

Three-dimensional vertebral shape changes confirm growth modulation after anterior vertebral body tethering for idiopathic scoliosis.

PURPOSE: To evaluate three-dimensional (3D) vertebra and disk shape changes over 2 years following anterior vertebral body tether (AVBT) placement in patients with idiopathic scoliosis (IS). METHODS: Patients with right thoracic IS treated with AVBT were retrospectively evaluated. 3D reconstructions were created from biplanar radiographs. Vertebral body and disk height (anterior, posterior, left and right) and shape (wedging angle) were recorded over the three apical segments in the local vertebral reference planes. Changes in height and wedging were measured through 2 years postoperatively. Change in patient height was correlated with changes in the spine dimensions. RESULTS: Forty-nine patients (Risser 0-3, Sanders 2-4) were included. The mean age was 12.2 ± 1.4 years (range 8-14). The mean coronal curve was 51 ± 10° preoperatively, 31 ± 9° at first postoperative time point and 27 ± 11° at 2-year follow-up (p < 0.001). The mean patient height increased 8 cm by 2 years (p < 0.001). The left side of the spine (vertebra + disc) grew in height by 2.2 mm/level versus 0.7 mm/level on the right side (p < 0.001). This differential growth was composed of 0.5 mm/vertebral level and 1.0 mm/disk level. Evaluation of the change in disk heights showed significantly decreased height anteriorly (- 0.4 mm), posteriorly (- 0.3 mm) and on the right (- 0.5 mm) from FE to 2 years. Coronal wedging reduced 2.3°/level with 1.1°/vertebral level change and 1.2°/disk level. There was no differential growth in the sagittal plane (anterior/posterior height). Patient height change moderately correlated with 3D measures of vertebra + disk shape changes. CONCLUSIONS: Three-dimensional analysis confirms AVBT in skeletally immature patients results in asymmetric growth of the apical spine segments. The left (untethered) side length increased more than 3 × than the right (tethered) side length with differential effects observed within the vertebral bodies and disks, each correlating with overall patient height change.

A portable electrochemical DNA sensor for sensitive and tunable detection of piconewton-scale cellular forces.

Cell-generated forces are a key player in cell biology, especially during cellular shape formation, migration, cancer development, and immune response. A new type of label-free smartphone-based electrochemical DNA sensor is developed here for cellular force measurement. When cells apply tension forces to the DNA sensors, the rapid rupture of DNA duplexes allows multiple redox reporters to reach the electrode and generate highly sensitive electrochemical signals. The sensitivity of these portable sensors can be further enhanced by incorporating a CRISPR-Cas12a system. Meanwhile, the threshold force values of these DNA-based sensors can be rationally tuned based on the force application geometries and also DNA intercalating agents. Overall, these highly sensitive, portable, cost-efficient, and easy-to-use electrochemical sensors can be powerful tools for detecting different cell-generated molecular forces.

Anterior vertebral body tethering shows clinically comparable shoulder balance outcomes to posterior spinal fusion.

PURPOSE: Posterior spinal fusion (PSF) is the current gold standard in surgical treatment for adolescent idiopathic scoliosis. Vertebral body tethering (VBT) is a fusionless alternative. Shoulder balance is an important metric for outcomes and patient satisfaction. Here we compare shoulder balance outcomes between PSF and VBT. METHODS: In this retrospective review, the pre-operative and post-operative absolute radiographic shoulder height (|RSH|) of 45 PSF patients were compared to 46 VBT patients. Mean values were compared and then collapsed into discrete groups (|RSH| GROUP) and compared. Patients were propensity score matched. Regression models based on pretest-posttest designs were used to compare procedure type on post-operative outcomes. RESULTS: Pre-operatively there were no differences in |RSH| between PSF and VBT, however, at latest post-operative follow-up PSF maintained a larger |RSH| imbalance compared to VBT (0.91 cm vs 0.63 cm, p = 0.021). In an ANCOVA regression, PSF was associated with a larger |RSH| imbalance compared to VBT, F(1, 88) = 5.76, p = 0.019. An ordinal logistic regression found that the odds ratio of being in a worse |RSH| GROUP for PSF vs VBT is 2.788 (95% CI = 1.099 to 7.075), a statistically significant effect χ2(1) = 4.658, p = 0.031. Results were similar in subgroup analyses of Lenke 1 and Lenke 2 patients, though to less statistical significance. CONCLUSION: While PSF was found to be associated with worse |RSH| outcomes, the actual numbers (2-3 mm) are unlikely to be clinically meaningful. Thus, in this analysis, VBT can be said to show comparable shoulder balance outcomes to PSF.

Electrochemical DNA-based sensors for measuring cell-generated forces.

Mechanical forces play an important role in cellular communication and signaling. We developed in this study novel electrochemical DNA-based force sensors for measuring cell-generated adhesion forces. Two types of DNA probes, i.e., tension gauge tether and DNA hairpin, were constructed on the surface of a smartphone-based electrochemical device to detect piconewton-scale cellular forces at tunable levels. Upon experiencing cellular tension, the unfolding of DNA probes induces the separation of redox reporters from the surface of the electrode, which results in detectable electrochemical signals. Using integrin-mediated cell adhesion as an example, our results indicated that these electrochemical sensors can be used for highly sensitive, robust, simple, and portable measurements of cell-generated forces.

Reinforcement learning-based attitude control for a barbell electric sail.

The electric solar wind sail (E-sail) is a new propellant-free propulsion concept. The under-actuated and highly nonlinear features of E-sail systems pose a great challenge to their attitude controller design. Conventional control schemes may not be capable of dealing with this tough problem. To this end, a reinforcement learning (RL)-based control scheme, which can explore and obtain optimal policies in the absence of training datasets, is proposed for the attitude control of a barbell E-sail system. The barbell E-sail comprises two end satellites linked to an insulated confluence point through long and conductive tethers. The voltages of the two tethers can be individually modulated for attitude control. The system attitude dynamics is described using a nonsingular formulation. The control scheme has a two-stage design. In the first stage, an RL controller based on the Proximal Policy Optimization (PPO) algorithm is used to obtain an RL control strategy, which is emulated and updated by neural networks. In the second stage, the attitude feedback control is accomplished with low computation and energy consumption and fast convergence speed by performing a real-time mapping from the system state to the control output using the updated control strategy. Finally, the simulation results demonstrate that the proposed RL-based control scheme can effectively adjust the E-sail to the design attitude by regulating the tether voltage difference. The comparisons with the NMPC scheme also indicate that the developed control scheme can significantly reduce the computation time with control accuracy maintained.

Mechanical force determines chimeric antigen receptor microclustering and signaling.

Chimeric antigen receptor (CAR) T cells are activated to trigger the lytic machinery after antigen engagement, and this has been successfully applied clinically as therapy. The mechanism by which antigen binding leads to the initiation of CAR signaling remains poorly understood. Here, we used a set of short double-stranded DNA (dsDNA) tethers with mechanical forces ranging from ∼12 to ∼51 pN to manipulate the mechanical force of antigen tether and decouple the microclustering and signaling events. Our results revealed that antigen-binding-induced CAR microclustering and signaling are mechanical force dependent. Additionally, the mechanical force delivered to the antigen tether by the CAR for microclustering is generated by autonomous cell contractility. Mechanistically, the mechanical-force-induced strong adhesion and CAR diffusion confinement led to CAR microclustering. Moreover, cytotoxicity may have a lower mechanical force threshold than cytokine generation. Collectively, these results support a model of mechanical-force-induced CAR microclustering for signaling.

The potential of proximal junctional kyphosis prevention using a novel tether pedicle screw construct: an in silico study comparing the influence of standard and dynamic techniques on adjacent-level range of motion and load pattern.

OBJECTIVE: A tether pedicle screw (TPS) enables individual stepless pretensioning and is placed at one or two levels above the upper instrumented vertebra (UIV+1 and UIV+2, respectively). This study aimed to evaluate a novel customized TPS for the prevention of proximal junctional kyphosis (PJK) and to investigate the potential to generate a smoother force transition from cranial to long fusion during trunk flexion, instead of an abrupt change at the UIV, following adult spinal deformity surgery. METHODS: A finite element model was designed based on an adult patient with spinal deformity instrumented from T10 to S1. Five different sagittal balance types and implant configurations were tested. The proximal range of motion (ROM) and intervertebral stress were examined, with a special focus on their respective discontinuities. RESULTS: Tension shielding at UIV/UIV+1 by the TPS was consistent irrespective of sagittal profiles. The use of TPSs at UIV+1 and UIV+2 increased the efficacy in reducing spinal ROM discontinuity at UIV/UIV+1, as compared with the use of TPSs at UIV+1 only. Through the use of two pairs of TPSs cranial to the UIV, the optimal tension configuration could be defined to avoid a reduction effect at UIV+1. Neither the addition of transition rods to the TPSs nor the use of transition rods in combination with standard pedicle screws improved the junctional mechanics when compared with TPSs at UIV+1/UIV+2. CONCLUSIONS: A smoother motion discontinuity at the UIV can be achieved via implementation of a TPS strategy. This new technology shows favorable in silico mechanics for reducing the risk of PJK.

Automated measurements of interscrew angles in vertebral body tethering patients with deep learning.

BACKGROUND CONTEXT: Vertebral body tethering is the most popular nonfusion treatment for adolescent idiopathic scoliosis. The effect of the tether cord on the spine can be segmentally assessed by comparing the angle between two adjacent screws (interscrew angle) over time. Tether breakage has historically been assessed radiographically by a change in adjacent interscrew angle by greater than 5° between two sets of imaging. A threshold for growth modulation has not yet been established in the literature. These angle measurements are time consuming and prone to interobserver variability. PURPOSE: The purpose of this study was to develop an automated deep learning algorithm for measuring the interscrew angle following VBT surgery. STUDY DESIGN/SETTING: Single institution analysis of medical images. PATIENT SAMPLE: We analyzed 229 standing or bending AP or PA radiographs from 100 patients who had undergone VBT at our institution. OUTCOME MEASURES: Physiologic Measures: An image processing algorithm was used to measure interscrew angles. METHODS: A total of 229 standing or bending AP or PA radiographs from 100 VBT patients with vertebral body tethers were identified. Vertebral body screws were segmented by hand for all images and interscrew angles measured manually for 60 of the included images. A U-Net deep learning model was developed to automatically segment the vertebral body screws. Screw label maps were used to develop and tune an image processing algorithm which measures interscrew angles. Finally, the completed model and algorithm pipeline was tested on a 30-image test set. Dice score and absolute error were used to measure performance. RESULTS: Inter- and Intra-rater reliability for manual angle measurements were assessed with ICC and were both 0.99. The segmentation model Dice score against manually segmented ground truth across the 30-image test set was 0.96. The average interscrew angle absolute error between the algorithm and manually measured ground truth was 0.66° and ranged from 0° to 2.67° in non-overlapping screws (N=206). The primary modes of failure for the model were overlapping screws on a right thoracic/left lumbar construct with two screws in one vertebra and overexposed images. An algorithm step which determines whether an overlapping screw was present correctly identified all overlapping screws, with no false positives. CONCLUSION: We developed and validated an algorithm which measures interscrew angles for radiographs of vertebral body tether patients with an accuracy of within 1° for the majority of interscrew angles. The algorithm can process five images per second on a standard computer, leading to substantial time savings. This algorithm may be used for rapid processing of large radiographic databases of tether patients and could enable more rigorous definitions of growth modulation and cord breakage to be established.

Tension Parameters of Junctional Tethers in Proximal Junction Kyphosis: A Cadaveric Biomechanical Study.

OBJECTIVE: Proximal junctional failure following surgical correction for adult spinal deformity significantly impacts quality of life and increases the economic burden of treating underlying spinal deformity. The objective of this cadaver study was to determine optimal tension parameters in junctional tethers for proximal junctional kyphosis prevention. METHODS: Cadaveric specimens were used to establish the optimal tension range in polyethylene tethering devices, such as the VersaTie (NuVasive) used in this study. Three specimens were instrumented to test tether tensions of 0, 75, and 150 Newtons (N) at L1-L2, T9-T10, and T3-T4. An optical tracking system was used to measure when specimens reached proximal junctional kyphosis, experienced instrumentation or tissue failure, or reached a cap of 2500 cycles. Radiographs were obtained before and after testing. RESULTS: At all levels, use of a tether at tension forces of 75 N and 150 N elicited a protective effect. The only level in which a higher tension on the tether resulted in more protection was at T3-T4. When averaged, the use of a tether at tension forces of 75 N and 150 N showed 1000 cycles of protection at L1-L2, 2000 cycles at T9-T10, and 1426 cycles at T3-T4. Radiographic analysis corroborated these findings. CONCLUSIONS: The use of a tether in a cadaveric model prevents the development of proximal junctional kyphosis across all tested levels and an increased tension force of 150 N is protective at the proximal thoracic spine. These data can be used to develop further models for a tether system that reproducibly applies a fixed tension force above the thoracolumbar rod construct.

The Double-Opposing Adipofascial Interposition Flap: A Novel Technique to Prevent Scar Tethering and Symptomatic Neuroma of the Superficial Radial Nerve After Trauma.

The superficial radial nerve (SRN) is vulnerable to injury following trauma with a high incidence of resultant nerve tether and neuroma formation. The SRN has an anatomical predisposition to neuroma formation, with research indicating that its propensity to neuroma development is out of proportion with its likelihood for injury. In addition, SRN neuromas have been described as one of the more painful and difficult neuromas to manage. Despite this, the published literature to date is chiefly focused on neuroma and scar tether treatment options rather than more impactful work on neuroma prevention, which can be safely delivered at the time of primary surgery. Treatment of established neuroma or nerve tether is notoriously difficult, and existing techniques have inconsistent outcomes, with patients often requiring multiple trips to the theatre. The authors present a novel technique for neuroma and scar tether prevention using an adipofascial flap accompanied by patient examples of our experience using this approach as an adjunct during the primary SRN repair, creating a gliding, interposing layer to prevent subsequent nerve traction pain and symptomatic neuroma. We identified five patients presenting with dorsal wrist injuries involving the SRN and one or more tendons. Patients' follow-up duration was a mean of 3.5 months (one to eight months). All follow-up patients showed no symptoms of a neuroma or nerve tether pain. All patients were discharged without re-referral or further surgery. Our patient sample demonstrates promising results using an adipofascial interposition flap as a prophylactic measure in traumatic injuries to reduce nerve tether pain and symptomatic neuroma formation in the SRN.

Nonconventional Tether Structure for Quality Factor Enhancement of Thin-Film-Piezoelectric-on-Si MEMS Resonator.

This article presents a new design of supporting tethers through the concept of force distribution. The transmitted force applied on tethers will be distributed on the new tether design area, resulting in low acoustic energy transferred to anchor boundaries and stored energy enhancement. This technique achieves an anchor quality factor of 175,000 compared to 58,000 obtained from the conventional tether design, representing a three-fold enhancement. Furthermore, the unloaded quality factor of the proposed design improved from 23,750 to 27,442, representing a 1.2-fold improvement.

Use of Tethers for Proximal Junctional Kyphosis Prophylaxis in Adult Spinal Deformity Surgery: A Review of Current Clinical Evidence.

BACKGROUND: Surgery for adult spinal deformity (ASD) often involves long-segment posterior instrumentation that introduces stress at the proximal junction that can result in proximal junctional kyphosis (PJK) or proximal junctional failure (PJF). Recently, the use of tethers at the proximal junction has been proposed as a means of buffering the transitional stresses and reducing the risk of PJK/PJF. Our objectives are to summarize the clinical literature on proximal junctional tethers for PJK/PJF prophylaxis. METHODS: Articles published between 1 January 2000 and 10 November 2022 were identified via a PubMed search using combinations of the search terms "spine surgery," "ASD," "complication," "surgery," "PJK," "PJF," "tether," "sublaminar band," and "prophylaxis." No restrictions were placed on the number of patients, surgical indications, or surgical procedures. Relevant articles were reviewed and summarized. RESULTS: Fifteen articles were identified, including 2 prospective cohorts (Level II), 10 retrospective cohorts (Level III), and 3 retrospective case series (Level IV). All studies were published between 2016 and 2022, and all focused on ASD patient populations. The mean age in each study ranged from 55 to 69 years, and most studies had a mean follow-up of at least 12 months (range, 5.5-45.4 months). Eleven studies used a polyethylene tether, 2 used soft sublaminar cables, and 2 used semitendinous allograft. The tether extended to the UIV+1 or UIV+2, passing either through or around the spinous processes, in 13 studies. In the remaining 2 studies, the tether was passed sublaminar at the UIV+1. Fourteen studies favored the use of tethers with regard to reduction of PJK/PJF rates, and one demonstrated similar rates of PJK between the tether and no-tether groups. CONCLUSIONS: PJK/PJF remain major challenges in ASD surgery. Most early studies suggest that the use of tethers for ligamentous augmentation may help to mitigate the development of PJK/PJF. However, the multifactorial etiology of PJK/PJF makes it unlikely that any single technique will solve this complex problem. Further study is needed to address not only the effectiveness of junctional tethers but also to clarify whether there are optimal tether configurations, tether materials, and tether tension. LEVEL EVIDENCE: 3.

Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells.

Cell spreading and migration play central roles in many physiological and pathophysiological processes. We have previously shown that MFN2 regulates the migration of human neutrophil-like cells via suppressing Rac activation. Here, we show that in mouse embryonic fibroblasts, MFN2 suppresses RhoA activation and supports cell polarization. After initial spreading, the wild-type cells polarize and migrate, whereas the Mfn2-/- cells maintain a circular shape. Increased cytosolic Ca2+ resulting from the loss of Mfn2 is directly responsible for this phenotype, which can be rescued by expressing an artificial tether to bring mitochondria and endoplasmic reticulum to close vicinity. Elevated cytosolic Ca2+ activates Ca2+/calmodulin-dependent protein kinase II, RhoA, and myosin light-chain kinase, causing an overactivation of nonmuscle myosin II, leading to a formation of a prominent F-actin ring at the cell periphery and increased cell contractility. The peripheral actin band alters cell physics and is dependent on substrate rigidity. Our results provide a novel molecular basis to understand how MFN2 regulates distinct signaling pathways in different cells and tissue environments, which is instrumental in understanding and treating MFN2-related diseases.

Power tether for long duration multi-copter flight.

The possibilities and promises of unmanned aerial vehicles (UAVs) for smart agriculture, 5G cellular integration, package delivery, and persistent surveillance are but a few of the active drivers for advancing UAV technology and systems. The UAVs' dependence on battery power represents a key limitation for practical deployment. As every remote pilot understands, even a modest research payload can limit a UAV's endurance to under 20 min. When horizontal maneuverability is not required, a power tether from the ground can provide near infinite flight time. Commercial tethers exist but can be prohibitively expensive or underpowered for research payloads. This paper describes the detailed design, construction, and operation of a relatively inexpensive open-source alternative. The designed and prototyped tether system delivers 1 kW of power at the tether base which, on an efficient UAV, corresponds to a payload of approximately 4.75 kg. We discuss the tradeoffs, design choices, best practices, and customization options, and provide empirical data for characterizing the power-payload relationship. The power and payload are scalable thanks to the modular design and the tools presented in this paper. The very low cost compared to commercial heavy-lift tether systems and the open-source design enable reproducibility and widespread use for supporting research, development, and emerging services/applications.

Stranger Twins: A Tale of Resemblance and Contrast Between VAP Proteins.

When considering the vesicle-associated membrane protein-associated protein (VAP) family, major receptors at the surface of the endoplasmic reticulum (ER), it appears that VAP-A and VAP-B paralogs largely overlap in structure and function, and that specific features to distinguish these two proteins hardly exist or are poorly documented. Here, we question the degree of redundancy between VAP-A and VAP-B: is one simply a backup plan, in case of loss of function of one of the two genes, or are there molecular and functional divergences that would explain their maintenance during evolution?

Vertebral body tethering in adolescent idiopathic scoliosis with more than 2 years of follow-up- systematic review and meta-analysis.

BACKGROUND CONTEXT: Whilst spinal fusion remains the gold standard in the treatment of adolescent idiopathic scoliosis (AIS), anterior vertebral body tethering (AVBT) is gaining momentum with relatively few studies on its efficacy thus far. PURPOSE: To conduct a systematic review reporting on the early results of AVBT for patients undergoing surgery for AIS. We aimed to systematically evaluate the relevant literature pertaining to the efficacy of AVBT with respect to degree of correction of the major curve Cobb angle, complications and revision rates. STUDY DESIGN/SETTING: Systematic review. PATIENT SAMPLE: Of a total of 259 articles, 9 studies met the inclusion criteria and were analysed. Overall, 196 patients of (mean age 12.08 years) underwent an AVBT procedure for correction of AIS with a mean follow-up of 34 months. OUTCOME MEASURES: Degree of Cobb angle correction, complications and revision rates were used as outcome measures. METHODS: A systematic review of the literature on AVBT was performed for studies published between Jan 1999-March 2021 applying the PRISMA guidelines. Isolated case reports were excluded. RESULTS: Overall, 196 patients of (mean age 12.08 years) underwent an AVBT procedure for correction of AIS with a mean follow-up of 34 months. There was a significant correction of the main thoracic curve of scoliosis (mean preoperative Cobb angle 48.5°, post-operative Cobb angle at final follow-up of 20.1°, P = 0.01). Overcorrection and mechanical complications were seen in 14.3% and 27.5% of cases, respectively. Pulmonary complications including atelectasis and pleural effusion were seen in 9.7% of patients. Tether revision was performed in 7.85%, and revision to a spinal fusion in 7.88%. CONCLUSION: This systematic review incorporated 9 studies of AVBT and 196 patients with AIS. The complication and revision to spinal fusion rates were 27.5% and 7.88%, respectively. The current literature on AVBT is restricted largely to retrospective studies with non-randomised data. We would recommend a prospective, multi-centre trial of AVBT with strict inclusion criteria and standardised outcome measures.

Extending the Contacts Breaks the Flow.

In this news and views, we discuss our recent publication where we described how ER-PM membrane contact sites (MCS) are modulated during store operated calcium entry (SOCE). We also examine why enforcing ER-PM MCS by tethering proteins does not not enhance, but rather inhibits SOCE.

Gluing yeast peroxisomes - composition and function of membrane contact sites.

Membrane contact sites are defined as regions of close proximity between two membranes; this association is mediated by protein-protein and/or protein-lipid interactions. Contact sites are often involved in lipid transport, but also can perform other functions. Peroxisomal membrane contact sites have obtained little attention compared to those of other cell organelles. However, recent studies resulted in a big leap in our knowledge of the occurrence, composition and function of peroxisomal contact sites. Studies in yeast strongly contributed to this progress. In this Review, we present an overview of our current knowledge on peroxisomal membrane contact sites in various yeast species, including Hansenula polymorpha, Saccharomyces cerevisiae, Pichia pastoris and Yarrowia lipolytica. Yeast peroxisomes form contacts with almost all other cellular organelles and with the plasma membrane. The absence of a component of a yeast peroxisomal contact site complex results in a range of peroxisomal phenotypes, including metabolic and biogenesis defects and alterations in organelle number, size or position.