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1.
Article in English | MEDLINE | ID: mdl-38715897

ABSTRACT

Objectives: Cold snare polypectomy (CSP) is widely performed for small colorectal polyps. However, small colorectal polyps sometimes include high-grade adenomas or carcinomas that require endoscopic resection with electrocautery. This study aimed to evaluate the efficacy and safety of a novel resection technique, hot snare polypectomy with low-power pure-cut current (LPPC-HSP) for small colorectal polyps, compared with CSP and conventional endoscopic mucosal resection (EMR). Methods: Records of patients who underwent CSP, EMR, or LPPC-HSP for nonpedunculated colorectal polyps less than 10 mm between April 2021 and March 2022 were retrospectively evaluated. We analyzed and compared the treatment outcomes of CSP and EMR with those of LPPC-HSP using propensity score matching. Results: After propensity score matching of 396 pairs, an analysis of CSP and LPPC-HSP indicated that LPPC-HSP had a significantly higher R0 resection rate (84% vs. 68%; p < 0.01). Delayed bleeding was observed in only two cases treated with CSP before matching. Perforation was not observed with either treatment. After propensity score matching of 176 pairs, an analysis of EMR and LPPC-HSP indicated that their en bloc and R0 resection rates were not significantly different (99.4% vs. 100%, p = 1.00; 79% vs. 81%, p = 0.79). Delayed bleeding and perforation were not observed with either treatment. Conclusions: The safety of LPPC-HSP was comparable to that of CSP. The treatment outcomes of LPPC-HSP were comparable to those of conventional EMR for small polyps. These results suggest that this technique is a safe and effective treatment for nonpedunculated polyps less than 10 mm.

2.
J Biol Chem ; : 107808, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39307308

ABSTRACT

Sphingolipids are essential in membrane trafficking and cellular homeostasis. Here, we show that sphingolipids containing very long-chain fatty acids (VLCFAs) promote homotypic vacuolar fusion in Saccharomyces cerevisiae. The elongase Elo3 adds the last two carbons to VLCFAs that are incorporated into sphingolipids. Cells lacking Elo3 have fragmented vacuoles, which is also seen when WT cells are treated with the sphingolipid synthesis inhibitor Aureobasidin-A. Isolated elo3Δ vacuoles show acidification defects and increased membrane fluidity, and this correlates with deficient fusion. Fusion arrest occurs at the tethering stage as elo3Δ vacuoles fail to cluster efficiently in vitro. Unlike HOPS and fusogenic lipids, GFP-Ypt7 does not enrich at elo3Δ vertex microdomains, a hallmark of vacuole docking prior to fusion. Pulldown assays using bacterially expressed GST-Ypt7 showed that HOPS from elo3Δ vacuole extracts failed to bind GST-Ypt7 while HOPS from WT extracts interacted strongly with GST-Ypt7. Treatment of WT vacuoles with the fluidizing anesthetic dibucaine recapitulates the elo3Δ phenotype and shows increased membrane fluidity, mislocalized GFP-Ypt7, inhibited fusion, and attenuated acidification. Together these data suggest that sphingolipids contribute to Rab-mediated tethering and docking required for vacuole fusion.

4.
Front Cell Dev Biol ; 12: 1451988, 2024.
Article in English | MEDLINE | ID: mdl-39286483

ABSTRACT

Exosomes are extracellular vesicles involved in intercellular signaling, carrying various cargo from microRNAs to metabolites and proteins. They are released by practically all cells and are highly heterogenous due to their origin and content. Several groups of exosomes are known to be involved in various pathological conditions including autoimmune, neurodegenerative, and infectious diseases as well as cancer, and therefore a substantial understanding of their biogenesis and release is crucial. Polarized cells display an array of specific functions originated from differentiated membrane trafficking systems and could lead to hints in untangling the complex process of exosomes. Indeed, recent advances have successfully revealed specific regulation pathways for releasing different subsets of exosomes from different sides of polarized epithelial cells, underscoring the importance of polarized cells in the field. Here we review current evidence on exosome biogenesis and release, especially in polarized cells, highlight the challenges that need to be combatted, and discuss potential applications related to exosomes of polarized-cell origin.

5.
bioRxiv ; 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39257774

ABSTRACT

SNARE proteins drive membrane fusion as their core domains zipper into a parallel four-helix bundle1,2. After fusion, these bundles are disassembled by the AAA+ protein Sec18/NSF and its adaptor Sec17/ α-SNAP3,4 to make them available for subsequent rounds of membrane fusion. SNARE domains are often flanked by C-terminal transmembrane or N-terminal domains5. Previous structures of the NSF-α-SNAP-SNARE complex revealed SNARE domain threaded through the D1 ATPase ring6, posing a topological constraint as SNARE transmembrane domains would prevent complete substrate threading as suggested for other AAA+ systems7. Here, in vivo mass-spectrometry reveals N-terminal SNARE domain interactions with Sec18, exacerbating this topological issue. Cryo-EM structures of a yeast SNARE complex, Sec18, and Sec17 in a non-hydrolyzing condition shows SNARE Sso1 threaded through the D1 and D2 ATPase rings of Sec18, with its folded, N-terminal Habc domain interacting with the D2 ring. This domain does not unfold during Sec18/NSF activity. Cryo-EM structures under hydrolyzing conditions revealed substrate-released and substrate-free states of Sec18 with a coordinated opening in the side of the ATPase rings. Thus, Sec18/NSF operates by substrate side-loading and unloading topologically constrained SNARE substrates.

6.
Adv Sci (Weinh) ; : e2403417, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39234822

ABSTRACT

The VCPIP1-P97/VCP (Valosin-Containing Protein) complex is required for post-mitotic Golgi cisternae reassembly and maintenance in interphase. However, the organization and mechanism of this complex in regulating Golgi membrane fusion is still elusive. Here, the cryo-electron microscopy (cryo-EM) structures of the human VCPIP1-P97/VCP complex are presented. These studies reveal that three independent VCPIP1 molecules sit over the C-terminal substrate exit tunnel formed by P97/VCP homo-hexamer, resulting in an unusual C3 to C6 symmetric barrel architecture. The UFD1 (unknown function domain 1) from VCPIP1, but not the N-terminal OTU domain and the C-terminal UBL domain, docks to the two adjacent D2 domains of P97/VCP, allosterically causing the cofactors binding domain-NTDs (N-terminal domains) of P97/VCP in a "UP" and D1 domain in an ATPase competent conformation. Conversely, VCPIP1 bound P97/VCP hexamer favors the binding of P47, and thus the intact SNARE complex, promoting Golgi membrane fusion. These studies not only reveal the unexpected organization of humanVCPIP1-P97/VCP complex, but also provide new insights into the mechanism of VCPIP1-P97/VCP mediated Golgi apparatus reassembly, which is a fundamental cellular event for protein and lipid processing.

7.
Sci Rep ; 14(1): 20335, 2024 09 02.
Article in English | MEDLINE | ID: mdl-39223224

ABSTRACT

Incomplete resection rates vary among endoscopists performing cold snare polypectomy. Cold snare endoscopic mucosal resection (CS-EMR) is the technique of cold resection after submucosal injection to reduce incomplete resection. This study aimed to evaluate the efficacy and safety of CS-EMR for small colorectal polyps compared to hot snare endoscopic mucosal resection (HS-EMR). Preplanned sample size required 70 polyps to CS-EMR group or HS-EMR group, respectively. Patients with polyps sized 6-9 mm were randomly allocated to either the CS-EMR or the HS-EMR group. The primary outcome was residual or recurrent adenoma (RAA) rate. A total of 70 and 68 polyps were resected using CS-EMR and HS-EMR, respectively. In the intention-to-treat population, the RAA rate was 0% in the CS-EMR group and 1.5% in the HS-EMR group (risk difference [RD], - 1.47; 95% confidence interval [CI] - 4.34 to 1.39). En bloc resection rate was 98.6% and 98.5% (RD, - 0.04; 95% CI - 4.12 to 4.02); the R0 resection rate was 55.7% and 82.4% (RD, - 27.80; 95% CI - 42.50 to - 13.10). The total procedure time was 172 s (IQR, 158-189) in the CS-EMR group and 186 s (IQR, 147-216) in the HS-EMR group (median difference, - 14; 95% CI - 32 to 2). Delayed bleeding was 2.9% vs 1.5% (RD, 1.37; 95% CI - 3.47 to 6.21) in both groups, respectively. CS-EMR was non-inferior to HS-EMR for the treatment of small colorectal polyps. CS-EMR can be considered one of the standard methods for the removal of colorectal polyps sized 6-9 mm.


Subject(s)
Colonic Polyps , Endoscopic Mucosal Resection , Humans , Endoscopic Mucosal Resection/methods , Male , Female , Middle Aged , Colonic Polyps/surgery , Colonic Polyps/pathology , Aged , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology , Colonoscopy/methods , Treatment Outcome , Adenoma/surgery , Adenoma/pathology , Neoplasm Recurrence, Local/surgery , Intestinal Mucosa/surgery , Intestinal Mucosa/pathology
8.
Gut Liver ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39228253

ABSTRACT

An increasing number of superficial non-ampullary duodenal epithelial tumors (SNADETs) have been detected recently owing to the development of endoscopic imaging technology and increased awareness of this disease. Endoscopic resection is the first-line treatment for SNADETs, with methods including cold snare polypectomy (CSP), conventional endoscopic mucosal resection (cEMR), underwater EMR (uEMR), and endoscopic submucosal dissection (ESD). Here, we review the current status and recent advances in endoscopic resection for SNADETs. Endoscopic resection in the duodenum is more difficult and has a higher risk of adverse events than that in other organs owing to specific anatomical disadvantages. SNADETs ≤10 mm in size are candidates for CSP, cEMR, and uEMR. Among these lesions, suspected carcinoma lesions should not be treated using CSP because of their low curability. cEMR or uEMR is considered for lesions sized 10 to 20 mm, whereas piecemeal EMR or ESD is considered for tumors >20 mm in size. In particular, ESD or surgical resection should be considered for suspected carcinoma lesions >30 mm in size. The treatment plan should be selected on a case-to-case basis, considering the balance between the risk of adverse events and the necessity of en bloc resection.

9.
Dev Cell ; 59(17): 2287-2301.e6, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39111309

ABSTRACT

Autophagy is a universal degradation system in eukaryotic cells. In plants, although autophagosome biogenesis has been extensively studied, the mechanism of how autophagosomes are transported to the vacuole for degradation remains largely unexplored. In this study, we demonstrated that upon autophagy induction, Arabidopsis homotypic fusion and protein sorting (HOPS) subunit VPS41 converts first from condensates to puncta, then to ring-like structures, termed VPS41-associated phagic vacuoles (VAPVs), which enclose autophagy-related gene (ATG)8s for vacuolar degradation. This process is initiated by ADP ribosylation factor (ARF)-like GTPases ARLA1s and occurs concurrently with autophagy progression through coupling with the synaptic-soluble N-ethylmaleimide-sensitive factor attachment protein rmleceptor (SNARE) proteins. Unlike in other eukaryotes, autophagy degradation in Arabidopsis is largely independent of the RAB7 pathway. By contrast, dysfunction in the condensates-to-VAPVs conversion process impairs autophagosome structure and disrupts their vacuolar transport, leading to a significant reduction in autophagic flux and plant survival rate. Our findings suggest that the conversion pathway might be an integral part of the autophagy program unique to plants.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Autophagosomes , Autophagy , Vacuoles , Arabidopsis/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Vacuoles/metabolism , Autophagosomes/metabolism , Vesicular Transport Proteins/metabolism , Vesicular Transport Proteins/genetics , Autophagy-Related Protein 8 Family/metabolism , Autophagy-Related Protein 8 Family/genetics , SNARE Proteins/metabolism , SNARE Proteins/genetics , rab7 GTP-Binding Proteins , rab GTP-Binding Proteins/metabolism , rab GTP-Binding Proteins/genetics
10.
J Investig Med High Impact Case Rep ; 12: 23247096241274299, 2024.
Article in English | MEDLINE | ID: mdl-39171727

ABSTRACT

Ectopic pancreas, also known as heterotopic pancreas, is a rare condition in which the pancreatic tissue is found outside its usual location in the gastrointestinal (GI) tract. It is commonly asymptomatic and benign, and is often discovered incidentally during routine imaging, endoscopy, surgery, or autopsy. However, complications can arise, such as inflammation, bleeding, obstruction, or even malignant transformation, necessitating surgical intervention in some cases. Ectopic pancreas at the ampulla of Vater (EPAV) is an extremely rare condition and a diagnostic and therapeutic nightmare. Most cases have been diagnosed through invasive surgery due to concerns for malignancy, which carries significant morbidity and mortality. In our case, endoscopic snare papillectomy (ESP) was employed to establish a diagnosis. Thus far, only one other case has been reported in which ESP was used to diagnose and resect a pancreatic heterotopia at the ampulla.


Subject(s)
Ampulla of Vater , Choristoma , Pancreas , Humans , Ampulla of Vater/surgery , Choristoma/surgery , Choristoma/diagnosis , Choristoma/pathology , Female , Male , Middle Aged , Cholangiopancreatography, Endoscopic Retrograde
11.
Cell Rep ; 43(8): 114624, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39154341

ABSTRACT

Chlamydia trachomatis, a leading cause of bacterial sexually transmitted infections, creates a specialized intracellular replicative niche by translocation and insertion of a diverse array of effectors (Incs [inclusion membrane proteins]) into the inclusion membrane. Here, we characterize IncE, a multifunctional Inc that encodes two non-overlapping short linear motifs (SLiMs) within its short cytosolic C terminus. The proximal SLiM, by mimicking just a small portion of an R-N-ethylmaleimide-sensitive factor adaptor protein receptor (SNARE) motif, binds and recruits syntaxin (STX)7- and STX12-containing vesicles to the inclusion. The distal SLiM mimics the sorting nexin (SNX)5 and SNX6 cargo binding site to recruit SNX6-containing vesicles to the inclusion. By simultaneously binding two distinct vesicle classes, IncE brings these vesicles in close apposition with each other at the inclusion to facilitate C. trachomatis intracellular development. Our work suggests that Incs may have evolved SLiMs to enable rapid evolution in a limited protein space to disrupt host cell processes.


Subject(s)
Bacterial Proteins , Chlamydia trachomatis , Chlamydia trachomatis/metabolism , Humans , Bacterial Proteins/metabolism , HeLa Cells , Amino Acid Motifs , Protein Transport , Sorting Nexins/metabolism , Sorting Nexins/genetics , Qa-SNARE Proteins/metabolism , Protein Binding
12.
Dig Dis ; : 1-9, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39128468

ABSTRACT

INTRODUCTION: Cold snare polypectomy (CSP) and underwater endoscopic mucosal resection (UEMR) have been developed recently, in addition to conventional methods, but adverse events of each method have not been fully clarified. We compared the outcomes of each method for the appropriate choice. METHODS: Patients who underwent CSP, endoscopic mucosal resection (EMR)/hot snare polypectomy (HSP), or UEMR for small and intermediate-sized colorectal polyps between April 2017 and June 2020 were retrospectively examined. The rate of adverse events and recurrences due to each method were determined as the main outcomes. Clinical factors related to adverse events were examined. RESULTS: A total of 1,025 patients with 3,163 polyps underwent polypectomy using any of the methods. CSP, EMR/HSP, and UEMR were performed for 704 (22.2%), 2,145 (67.8%), and 314 polyps (9.9%), and the median size for each method was 4, 6, and 7 mm, respectively. Delayed bleeding for CSP, EMR/HSP, and UEMR was 0%, 0.2%, and 0.6% (p = 0.15), and perforation was 0%, 0.1%, and 0%, respectively (p = 0.62). Recurrence after CSP, EMR/HSP, and UEMR was 0.3%, 0.09%, and 1.3%, respectively (p < 0.01). Recurrence for UEMR was significantly higher in the early stage of procedure introduction (p = 0.015). Oral anticoagulants were the risk factor for delayed bleeding (p < 0.01, respectively). CONCLUSION: There was no significant difference regarding adverse events among each method for small and intermediate-sized polyps, although the recurrence rate after UEMR was higher than other methods.

13.
Int J Mol Sci ; 25(15)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39125587

ABSTRACT

Age-related conditions, such as sarcopenia, cause physical disabilities for an increasing section of society. At the neuromuscular junction, the postsynaptic-derived neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4) have neuroprotective functions and contribute to the correct regulation of the exocytotic machinery. Similarly, presynaptic muscarinic signalling plays a fundamental modulatory function in this synapse. However, whether or not these signalling pathways are compromised in ageing neuromuscular system has not yet been analysed. The present study analyses, through Western blotting, the differences in expression and activation of the main key proteins of the BDNF/NT-4 and muscarinic pathways related to neurotransmission in young versus ageing Extensor digitorum longus (EDL) rat muscles. The main results show an imbalance in several sections of these pathways: (i) a change in the stoichiometry of BDNF/NT-4, (ii) an imbalance of Tropomyosin-related kinase B receptor (TrkB)-FL/TrkB-T1 and neurotrophic receptor p 75 (p75NTR), (iii) no changes in the cytosol/membrane distribution of phosphorylated downstream protein kinase C (PKC)ßI and PKCε, (iv) a reduction in the M2-subtype muscarinic receptor and P/Q-subtype voltage-gated calcium channel, (v) an imbalance of phosphorylated mammalian uncoordinated-18-1 (Munc18-1) (S313) and synaptosomal-associated protein 25 (SNAP-25) (S187), and (vi) normal levels of molecules related to the management of acetylcholine (Ach). Based on this descriptive analysis, we hypothesise that these pathways can be adjusted to ensure neurotransmission rather than undergoing negative alterations caused by ageing. However, further studies are needed to assess this hypothetical suggestion. Our results contribute to the understanding of some previously described neuromuscular functional age-related impairments. Strategies to promote these signalling pathways could improve the neuromuscular physiology and quality of life of older people.


Subject(s)
Aging , Brain-Derived Neurotrophic Factor , Neuromuscular Junction , Receptor, trkB , Signal Transduction , Brain-Derived Neurotrophic Factor/metabolism , Animals , Neuromuscular Junction/metabolism , Aging/metabolism , Rats , Receptor, trkB/metabolism , Nerve Growth Factors/metabolism , Male , Receptors, Muscarinic/metabolism , Synaptic Transmission , Receptors, Nerve Growth Factor/metabolism , Rats, Wistar
14.
PeerJ Comput Sci ; 10: e2149, 2024.
Article in English | MEDLINE | ID: mdl-39145217

ABSTRACT

Agriculture is the main source of livelihood for most of the population across the globe. Plants are often considered life savers for humanity, having evolved complex adaptations to cope with adverse environmental conditions. Protecting agricultural produce from devastating conditions such as stress is essential for the sustainable development of the nation. Plants respond to various environmental stressors such as drought, salinity, heat, cold, etc. Abiotic stress can significantly impact crop yield and development posing a major threat to agriculture. SNARE proteins play a major role in pathological processes as they are vital proteins in the life sciences. These proteins act as key players in stress responses. Feature extraction is essential for visualizing the underlying structure of the SNARE proteins in analyzing the root cause of abiotic stress in plants. To address this issue, we developed a hybrid model to capture the hidden structures of the SNAREs. A feature fusion technique has been devised by combining the potential strengths of convolutional neural networks (CNN) with a high dimensional radial basis function (RBF) network. Additionally, we employ a bi-directional long short-term memory (Bi-LSTM) network to classify the presence of SNARE proteins. Our feature fusion model successfully identified abiotic stress in plants with an accuracy of 74.6%. When compared with various existing frameworks, our model demonstrates superior classification results.

15.
Eur Heart J Case Rep ; 8(8): ytae341, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39104512

ABSTRACT

Background: Entrapment and fracture of the coronary guidewire are rare but major complications of percutaneous coronary intervention (PCI). The incidence of these complications is reported to be <1%. Case summary: A 52-year-old male patient with diabetes and dyslipidaemia presented with posterior wall myocardial infarction. An angiogram revealed occlusion in the left circumflex (LCX) artery. Attempts to pass a guidewire through the lesion led to its entrapment and eventual fracture. Several techniques and manoeuvres failed to retrieve the fractured guidewire, which remained lodged in the LCX. An endovascular snare catheter also proved unsuccessful. The fragment was eventually removed using the triple-wire technique, although this caused coronary perforation and dissection. The perforation was identified and stented. A subsequent stent addressed a dissection in the left main/left ascending artery area, likely caused by the coronary snare. These interventions were crucial in stabilizing the patient's condition, leading to recovery with a left ventricular ejection fraction of 50% and a viable LCX artery. The patient exhibited an uneventful progression at the 1-year follow-up. Discussion: Coronary guidewire fracture during PCI is a rare event often associated with coronary calcifications. Percutaneous removal remains the mainstay treatment for fragment removal; however, it carries risks. The triple-wire technique, a newer method that entangles and extracts the fractured guidewire without specialized equipment, was effective in removing the fragmented guidewire. If asymptomatic, leaving the wire in situ is documented as a favourable approach. This case highlights that the triple-wire technique can effectively be used for the extraction of fractured guidewire fragments from the coronary vessels.

16.
J Anus Rectum Colon ; 8(3): 204-211, 2024.
Article in English | MEDLINE | ID: mdl-39086880

ABSTRACT

Objectives: Delayed bleeding is the most frequent adverse event associated with endoscopic mucosal resection (EMR) and hot snare polypectomy (HSP) of colorectal polyps. However, whether the incidence of delayed bleeding differs between outpatient and inpatient treatment is unknown. Therefore, in this study, we aimed to evaluate delayed bleeding rates between outpatient and inpatient endoscopic treatments and clarify the safety of outpatient treatment. Methods: We enrolled 469 patients (1077 polyps) and 420 patients (1080 polyps) in the outpatient and inpatient groups, respectively, who underwent EMR or HSP for colorectal polyps at our institution between April 2020 and May 2023. Using propensity score matching, we evaluated the delayed bleeding rates between the two groups. Delayed bleeding was defined as a hemorrhage requiring endoscopic hemostasis occurring within 14 days of the procedure. Results: Propensity score matching created 376 (954 polyps) matched patient pairs. The median maximum diameter of polyps removed was 10 mm in both groups. Delayed bleeding rates per patients were 1.3% (5/376) in the outpatient group and 2.9% (11/376) in the inpatient group (P=0.21). In term of per polyp, early delayed bleeding (occurring within 24 hours) rates were higher in the inpatient group than outpatient group (0.2% [2/954] vs. 1.1% [10/954], respectively; P=0.04). No severe bleeding requiring a transfusion occurred in either group. Conclusions: Outpatient endoscopic treatment did not increase delayed bleeding compared with inpatient treatment. Outpatient treatment would be safe and common for the removal of colorectal polyps.

17.
Protein Sci ; 33(9): e5158, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39180485

ABSTRACT

Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor (SNARE) proteins catalyze the fusion process of vesicles with target membranes in eukaryotic cells. To do this, they assemble in a zipper-like fashion into stable complexes between the membranes. Structural studies have shown that the complexes consist of four different helices, which we subdivide into Qa-, Qb-, Qc-, and R-helix on the basis of their sequence signatures. Using a combination of biochemistry, modeling and molecular dynamics, we investigated how the four different types are arranged in a complex. We found that there is a matching pattern in the core of the complex that dictates the position of the four fundamental SNARE types in the bundle, resulting in a QabcR complex. In the cell, several different cognate QabcR-SNARE complexes catalyze the different transport steps between the compartments of the endomembrane system. Each of these cognate QabcR complexes is compiled from a repertoire of about 20 SNARE subtypes. Our studies show that exchange within the four types is largely tolerated structurally, although some non-cognate exchanges lead to structural imbalances. This suggests that SNARE complexes have evolved for a catalytic mechanism, a mechanism that leaves little scope for selectivity beyond the QabcR rule.


Subject(s)
SNARE Proteins , SNARE Proteins/chemistry , SNARE Proteins/metabolism , Humans , Models, Molecular , Molecular Dynamics Simulation , Animals
18.
New Phytol ; 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39180241

ABSTRACT

The retromer complex is a conserved sorting machinery that maintains cellular protein homeostasis by transporting vesicles containing cargo proteins to defined destinations. It is known to sort proteins at the vacuole membranes for retrograde trafficking, preventing their degradation in the vacuole. However, the detailed mechanism of retromer recruitment to the vacuole membrane has not yet been elucidated. Here, we show that the vacuolar SNARE complex MoPep12-MoVti1-MoVam7-MoYkt6 regulates retromer-mediated vesicle trafficking by recruiting the retromer to the vacuole membrane, which promotes host invasion in Magnaporthe oryzae. Such recruitment is also essential for the retrieval of the autophagy regulator MoAtg8 and enables appressorium-mediated host penetration. Furthermore, the vacuolar SNARE subunits are involved in suppressing the host defense response by regulating the deployment of retromer-MoSnc1-mediated effector secretion. Altogether, our results provide insights into the mechanism of vacuolar SNAREs-dependent retromer recruitment which is necessary for pathogenicity-related membrane trafficking events in the rice blast fungus.

19.
World J Gastrointest Endosc ; 16(8): 445-450, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39155992

ABSTRACT

Current guidelines recommend cold snare polypectomy for polyps less than 10 mm in size. Conversely, endoscopic mucosal resection is still the preferred technique for larger polyps. Concerns regarding cold snare polypectomy for larger polyps revolve around the difficulty in conducting en-bloc resection (resulting in piecemeal removal), and the potential for local residual polyp tissue and a high rate of recurrence. On the other hand, cold snare technique has the advantages of shortening procedure time, reducing delayed bleeding risks and lowering cost of treatment. Numerous ongoing and recent studies are focused on evaluating the risks and benefits of this technique for polyps larger than 10 mm, with the goal of providing clear guidelines in the near future. The aim of this editorial is to provide our readers with an overview regarding this subject and the latest developments surrounding it.

20.
Article in English | MEDLINE | ID: mdl-39210617

ABSTRACT

BACKGROUND: Cardiac resynchronization therapy (CRT) improves ventricular function, but a positive response to CRT is often limited due to left ventricular (LV) lead placement in a suboptimal position. Complex coronary venous anatomy can hinder the placement of an LV lead in the target vessel, leading to poor CRT response. OBJECTIVE: To report experience with snare-assisted LV lead delivery in CRT and compare outcomes with the conventional LV lead delivery. METHODS: This is a single-center retrospective case-control study of CRT implants between 2016 and 2021. Snare-assisted lead delivery was performed in cases where conventional lead placement failed or when a preferred target vessel had anatomy amenable to the technique. Safety and outcomes were compared to conventional LV lead placement cases. RESULTS: Among 180 CRT cases, 33 were snare-assisted, and 147 were conventional LV lead placements. Median follow-up was 924 days in the snare and 618.5 days in the control group. The lead placement was successful in 28/33 snare and 138/147 control cases. A mid-vessel segment was attained in 89.3% of snare and 72.5% of control cases(p = .03). The apical position was more frequently observed in the control group (26.8% vs. 7.1%, p = .03). All-cause mortality trended lower in the snare group (6.1%) compared to (17.1%) in the control group (p = .13). CONCLUSION: Snare-assisted LV lead delivery is a safe and effective technique that can be utilized for overcoming complex venous anatomy.

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