Ring Constriction Research Articles

Revisiting the unrepaired unilateral cleft lip and nasal deformity using 3D surface image analysis: A data-driven model and its implications

Current descriptions of the unilateral cleft lip and nasal deformity (uCLND) are based upon limited sample sets and subjective observations. While those descriptions are inconsistent and contradictory, theoretical models, including Hogan's "tilted tripod" and Fisher's "nasal arch forms", have never been tested. Given that favorable outcomes of treatment remain elusive, detailed study of the deformity is critical in devising better treatments. The purpose of this study was to develop a data-driven three-dimensional (3D) model of uCLND that spans the spectrum of presentation and involves a pervasive underlying mechanism. We studied 3D images of 100 infants with unrepaired cleft lip at 6 months of age. Objective assessment included the landmark positions, anthropometric dimensions, and shape-based measures. Cleft severity was stratified by the lateral displacement of subnasale, so that a model could be developed using linear regression. With progressive deviation of subnasale, the non-cleft alar base moved lateral, the cleft alar base was left posterior, and the nasal dorsum followed the caudal septum (deviating towards the non-cleft side). The "twist" resulted in opposing cleft alar dome collapse, non-cleft alar ring constriction (the non-cleft nasal sill narrowed, lateral genu rose, and alar-cheek junction became more acute), and displacement of the philtrum from midline. Our study not only supports theoretical models of uCLND but also clarifies vectors of change and reveals significant non-cleft side alterations. On the basis of our findings, the objectives of treatment should involve centralization of the columella and philtrum and rebalancing the nose by untwisting the orthogonal displacement of the alar bases.

Salvage Reconstruction of a Congenital Hypoplastic Thumb Due to Constriction Ring Syndrome Using a Third Toe Transfer, When the Usual Donor Sites of Index Finger, Great and Second Toes Are Not Available.

Isolated third toe-to-thumb transfers have been rarely reported and none in the pediatric population. We describe a third toe-to-thumb transfer for reconstruction of a congenital hypoplastic thumb with excellent functional results and no morbidity in the donor foot.

Early release of amniotic bands using a 1.0-mm fetoscope

A 27-year-old pregnant woman, gravida 1, was referred to our fetal surgery center because of amniotic band (AB) syndrome at 155/7 weeks’ gestation. Fetal ultrasound showed distal edema of the right foot and ABs around the left hand and umbilical cord. With local maternal anesthesia, a percutaneous transabdominal fetoscopy was performed at 16 weeks using a 1.0-mm fetoscope. Constriction rings with tight AB wrapped around the fingers of the left hand (Figure 1), right foot (Figure 2), and umbilical cord (Figure 3) were observed during fetoscopy.

Further insights into unusual acrania-exencephaly-anencephaly sequence caused by amniotic band – first trimester fetoscopic correlation with two- and three-dimensional ultrasound

Abstract Objectives Antenatal detection of acrania-exencephaly-anencephaly (AEA) sequence beyond 10 completed weeks of gestation is usually straight-forward. An earlier detection and classification of the causative conditions prior to disaggregation of exposed dysplastic brain tissue remains challenging. Case presentation We present two- and three-dimensional ultrasound correlated with fetoscopic findings of an unusual type of neural tube defect at 11 gestational weeks caused by an amniotic constriction ring resulting in cystic degeneration of the developing skull. Conclusions By giving further illustrative insights into early defective brain development, this report confirms recent findings of an unusual subtype of acrania-exencephaly-anencephaly sequence suggesting early disruption of the developing brain, following an amniotic entrapment of the skull.

Surgical treatment of phimosis due to preputial stenosis in a Thoroughbred colt

SummaryA 6‐month‐old Thoroughbred colt was referred to Rossdales Equine Hospital with a recent history of discomfort and inability to protrude the penis whilst urinating, resulting in accumulation of urine within the prepuce. Careful examination and manual palpation revealed a constrictive ring of fibrous tissue at the level of the preputial orifice. With no evidence of trauma or a persistent penile frenulum, a tentative diagnosis of phimosis due to congenital preputial stenosis was made. Exploratory surgery confirmed the diagnosis and surgical transection and release of the fibromuscular ring at three sites allowed the colt to protrude the penis and urinate normally immediately post‐operatively. At follow‐up examination 11 months later, the colt continued to be able to extrude the penis and urinate conventionally. A slight excess of skin was present at the end of the prepuce but this was only of minor cosmetic concern.

Escape from mitotic catastrophe by actin-dependent nuclear displacement in fission yeast

SummaryEukaryotic cells position the nucleus within the proper intracellular space, thereby safeguarding a variety of cellular processes. In fission yeast, the interphase nucleus is placed in the cell middle in a microtubule-dependent manner. By contrast, how the mitotic nucleus is positioned remains elusive. Here we show that several cell-cycle mutants that arrest in mitosis all displace the nucleus toward one end of the cell. Intriguingly, the actin cytoskeleton is responsible for nuclear movement. Time-lapse live imaging indicates that mitosis-specific F-actin cables possibly push the nucleus through direct interaction with the nuclear envelope, and subsequently actomyosin ring constriction further shifts the nucleus away from the center. This nuclear movement is beneficial, because if the nuclei were retained in the center, unseparated chromosomes would be intersected by the contractile actin ring and the septum, imposing the lethal cut phenotype. Thus, fission yeast escapes from mitotic catastrophe by means of actin-dependent nuclear movement.

Calcium spikes accompany cleavage furrow ingression and cell separation during fission yeast cytokinesis.

The role of calcium signaling in cytokinesis has long remained ambiguous. Past studies of embryonic cell division discovered that calcium concentration increases transiently at the division plane just before cleavage furrow ingression, suggesting that these calcium transients could trigger contractile ring constriction. However, such calcium transients have only been found in animal embryos and their function remains controversial. We explored cytokinetic calcium transients in the fission yeast Schizosaccharomyces pombe by adopting GCaMP, a genetically encoded calcium indicator, to determine the intracellular calcium level of this model organism. We validated GCaMP as a highly sensitive calcium reporter in fission yeast, allowing us to capture calcium transients triggered by osmotic shocks. We identified a correlation between the intracellular calcium level and cell division, consistent with the existence of calcium transients during cytokinesis. Using time-lapse microscopy and quantitative image analysis, we discovered calcium spikes both at the start of cleavage furrow ingression and the end of cell separation. Inhibition of these calcium spikes slowed the furrow ingression and led to frequent lysis of daughter cells. We conclude that like the larger animal embryos, fission yeast triggers calcium transients that may play an important role in cytokinesis (197).

A novel checkpoint pathway controls actomyosin ring constriction trigger in fission yeast.

In fission yeast, the septation initiation network (SIN) ensures temporal coordination between actomyosin ring (CAR) constriction with membrane ingression and septum synthesis. However, questions remain about CAR regulation under stress conditions. We show that Rgf1p (Rho1p GEF), participates in a delay of cytokinesis under cell wall stress (blankophor, BP). BP did not interfere with CAR assembly or the rate of CAR constriction, but did delay the onset of constriction in the wild type cells but not in the rgf1Δ cells. This delay was also abolished in the absence of Pmk1p, the MAPK of the cell integrity pathway (CIP), leading to premature abscission and a multi-septated phenotype. Moreover, cytokinesis delay correlates with maintained SIN signaling and depends on the SIN to be achieved. Thus, we propose that the CIP participates in a checkpoint, capable of triggering a CAR constriction delay through the SIN pathway to ensure that cytokinesis terminates successfully.

C. elegans CLASP/CLS-2 negatively regulates membrane ingression throughout the oocyte cortex and is required for polar body extrusion.

The requirements for oocyte meiotic cytokinesis during polar body extrusion are not well understood. In particular, the relationship between the oocyte meiotic spindle and polar body contractile ring dynamics remains largely unknown. We have used live cell imaging and spindle assembly defective mutants lacking the function of CLASP/CLS-2, kinesin-12/KLP-18, or katanin/MEI-1 to investigate the relationship between meiotic spindle structure and polar body extrusion in C. elegans oocytes. We show that spindle bipolarity and chromosome segregation are not required for polar body contractile ring formation and chromosome extrusion in klp-18 mutants. In contrast, oocytes with similarly severe spindle assembly defects due to loss of CLS-2 or MEI-1 have penetrant and distinct polar body extrusion defects: CLS-2 is required early for contractile ring assembly or stability, while MEI-1 is required later for contractile ring constriction. We also show that CLS-2 both negatively regulates membrane ingression throughout the oocyte cortex during meiosis I, and influences the dynamics of the central spindle-associated proteins Aurora B/AIR-2 and MgcRacGAP/CYK-4. We suggest that proper regulation by CLS-2 of both oocyte cortical stiffness and central spindle protein dynamics may influence contractile ring assembly during polar body extrusion in C. elegans oocytes.

One-stage circumferential limb ring constriction release and direct circular skin closure in amniotic band syndrome: a 14-case series

The aim of the present study was to report results of direct circular suture after 1-stage circumferential resection of limb ring constriction in amniotic band syndrome. A multicentre retrospective study included 14 patients with amniotic band syndrome (mean age, 13.3 months) operated on between 2004 and 2019 by circumferential release of ≥1 ring constriction. Assessment was based on limb function and clinical scar aspect on the POSAS and Vancouver scales. Mean follow-up was 3.9 years. There were no scar-related, vascular or neurologic complications, postoperatively or at last follow-up. POSAS and Vancouver scores were satisfactory. One-stage circumferential release with direct closure is a simple technique that provides satisfactory functional and esthetic results.

Unusual and delayed presentation of chronic uterine inversion in a young woman as a result of negligence by an\xa0untrained birth attendant: a case report

BackgroundUterine inversion is a rare but known complication following parturition and may prove fatal due to neurogenic shock or postpartum hemorrhage if not corrected immediately. The incidence is variable, occurring in 1 in 2000 to 1 in 50,000 deliveries, as reported in the past. Nowadays, the incidence is declining due to better antenatal care and increasing institutional deliveries. However, in a developing country such as India, due to cultural and financial reasons, most of the deliveries are still being conducted by untrained birth attendants (“dais”) who have sparse knowledge of oxytocic drugs. Hence, proper education and training should be imparted to the traditional birth attendants and local village health practitioners about the management of labor, placental delivery, timely diagnosis, and proper management of uterine inversion to avoid this grave complication. We report this case because only a limited number of such cases have been reported so far with delayed presentation of chronic uterine inversion 8 months after delivery as a result of the negligence of an untrained birth attendant.Case presentationWe report a case of a patient with chronic uterine inversion presenting 8 months after childbirth as a result of ignorance at the time of delivery. A 22-year-old P1L1 (Para 1 Live 1) Asian woman of Punjabi ethnicity presented to our institute with a progressively increasing painless vaginal mass along with blood-stained vaginal discharge for the last 6 months and progressive dyspareunia (pain during intercourse) for the last 5 months that had worsened with time. She had experienced a full-term normal vaginal delivery at home 8 months earlier with the assistance of an untrained birth attendant (dai). Her history revealed that she had an unduly prolonged second stage of labor and was given aggressive fundal pressure due to inadequate bearing-down efforts and had collapsed after delivery but was managed conservatively by an untrained birth attendant. A provisional diagnosis of chronic uterine inversion was made on the basis of vaginal findings of a globular mass protruding from the cervix and approaching the vagina with thinning of the cervix around the mass, forming a tight constriction ring, in addition to ultrasound findings. The patient’s condition was corrected surgically using Haultain’s approach. She had a satisfactory outcome and was discharged symptom-free.ConclusionAwareness of this complication with timely diagnosis and prompt management can significantly minimize maternal morbidity and mortality, especially in a low- and middle-income country such as India, where 70–80% of deliveries still occur in a rural setting with untrained birth attendants.

Mitochondrial morphology and activity regulate furrow ingression and contractile ring dynamics in Drosophila cellularization.

Mitochondria are maternally inherited in many organisms. Mitochondrial morphology and activity regulation is essential for cell survival, differentiation, and migration. An analysis of mitochondrial dynamics and function in morphogenetic events in early metazoan embryogenesis has not been carried out. In our study we find a crucial role of mitochondrial morphology regulation in cell formation in Drosophila embryogenesis. We find that mitochondria are small and fragmented and translocate apically on microtubules and distribute progressively along the cell length during cellularization. Embryos mutant for the mitochondrial fission protein, Drp1 (dynamin-related protein 1), die in embryogenesis and show an accumulation of clustered mitochondria on the basal side in cellularization. Additionally, Drp1 mutant embryos contain lower levels of reactive oxygen species (ROS). ROS depletion was previously shown to decrease myosin II activity. Drp1 loss also leads to myosin II depletion at the membrane furrow, thereby resulting in decreased cell height and larger contractile ring area in cellularization similar to that in myosin II mutants. The mitochondrial morphology and cellularization defects in Drp1 mutants are suppressed by reducing mitochondrial fusion and increasing cytoplasmic ROS in superoxide dismutase mutants. Our data show a key role for mitochondrial morphology and activity in supporting the morphogenetic events that drive cellularization in Drosophila embryos.

An Unprecedented Ring-Contraction Mechanism in Cobalamin-Dependent Radical S-Adenosylmethionine Enzymes.

A unique member of the family of cobalamin (Cbl)-dependent radical S-adenosylmethionine (SAM) enzymes, OxsB, catalyzes the ring constriction of deoxyadenosine triphosphate (dATP) to the base oxetane aldehyde phosphate, a crucial precursor for oxetanocin A (OXT-A), which is an antitumor, antiviral, and antibacterial compound. This enzyme reveals a new catalytic function for this big family that is different from the common methylation. On the basis of density functional theory calculations, a mechanism has been proposed to mainly include that the generation of 5'-deoxyadenosine radical, a hydrogen transfer forming 2'-dATP radical, and a Cbl-catalyzed ring contraction of the deoxyribose in 2'-dATP radical. The ring contraction is a concerted rearrangement step accompanied by an electron transfer from the deoxyribose hydroxyl oxygen to CoIII without any ring-opening intermediate. CoIICbl has been ruled out as an active state. Other mechanistic characteristics are also revealed. This unprecedented non-methylation mechanism provides a new catalytic repertoire for the family of radical SAM enzymes, representing a new class of ring-contraction enzymes.

Amelioration of muscular spasm-induced pain of Guangtongxiao recipe in a non-everted gut sac in vitro model

BackgroundThe modern study of the traditional Chinese medicine (TCM) compound recipes is a complex issue because of the large number of components in the recipes that would produce several metabolites after entering the body. The TCM compound recipes are known to have the advantage of synergistic treatment by multiple targets due to diverse components. Therefore, a research method that can reflect the overall effect of compounds with multi-components is essential. The pharmacological studies of the classic TCM compound recipes mainly use the sero-pharmacological method. It is a semi-in vivo study method, and the drug to be tested in the in vitro experiment is the drug-containing serum from the model animals (the drug to be tested is a mixed drug system containing the prototype drugs in animal bodies that have pharmacodynamic effects and the metabolites). Herein, a safe and effective external TCM recipe was used to develop another semi-in vivo experimental method to reflect the overall effects of TCM. AimTo observe the effects of in-vitro intestinal absorption liquid of aqueous extracts of the TCM compound recipe—Guangtongxiao foam aerosol (Guangtongxiao)—on the tension of isolated rectal rings of mouse and investigate the underlying mechanisms of antispasmodic and amelioration of muscular spasm-induced pain. MethodsIntestinal absorption liquid of the Guangtongxiao aqueous extract at the five time points (30, 45, 75, 105, and 120 min) was prepared using a non-everted gut sac method. The isolated rectal rings of mice were prepared by pre-contraction using potassium chloride (KCl) or acetylcholine chloride (ACh) to make steady contraction. The intestinal absorption liquid were added cumulatively to the sink with the constricted rectal rings. The effects of the five groups of the intestinal absorption liquid with different drug concentration were observed on the tension of the isolated rectal rings. Then the ex vivo perfusion of the mouse rectal ring was performed as same as Guangtongxiao intestinal absorption liquid experiments, and the effects of two major components of Guangtongxiao, paeoniflorin (Pae) and tetrahydropalmatine (THP), on the rectal ring pre-treated with high concentration of KCl and ACh to induce contraction were studied. ResultsThe relaxation rate of the five groups of the intestinal canals increased significantly with 3200 μL cumulative sample volume as compared to the blank group (P < 0.01). It suggested that the relaxation activity of the intestinal absorption liquid enhanced significantly with the prolongation of the interaction between isolated rectal rings and intestinal absorption liquid in a time-dependent manner. Also, significant differences were detected while comparing between the 120-min intestinal absorption liquid group and the blank group with respect to various cumulative sampling volumes (P < 0.01). In addition, the intestinal relaxation rate elevated gradually with the increase in sampling volume, indicating that the concentrations of active substances in the intestinal absorption liquid prepared by the non-everted gut sac model increased and the intestinal relaxation activity was enhanced with the prolongation of the absorption time in a dose-dependent manner. And Pae and THP in a concentration-dependent manner caused relaxation of the rectal ring, which is pretreated with high K+(KCl) and ACh to induce contraction. The EC50 of Pae and THP was 8.67 × 10−5 M (6.68 × 10−5-1.13 × 10−4) and 1.41 × 10−4 M (1.24 × 10−4-1.61 × 10−4) in the contraction model induced by KCl, and was 6.15 × 10−5 M (4.47 × 10−5-8.45 × 10−5), and 1.31 × 10−4 M(1.22 × 10−4-1.42 × 10−4) in the model induced by ACh, respectively. ConclusionThe intestinal absorption liquid of Guangtongxiao exerted a remarkable relaxation activity for the rectal rings, and relaxation of the smooth muscle tension might be one of the antispasmodic mechanisms of Guangtongxiao compound recipe. Also, adopting a semi-in-vivo experimental method to study the efficacy of topical external TCM recipe medicine is optimal.

Amniotic band syndrome: a case series

Amniotic band syndrome (ABS) is a rare congenital disorder which involves fetal entrapment in strands of amniotic tissue, which can manifest as constriction rings, limb and digital amputations or complex congenital anomalies and sometimes results in stillbirth. Etiopathogenesis is varied and ABS can be associated with syndromes. Antenatal diagnosis is made by ultrasonography in most cases. Postnatal examination reveals constrictions, amputations and craniofacial or abdominal wall defects. Treatment is case based and surgical intervention is required to release constriction rings. Authors report here six cases (one stillbirth and five live births) of amniotic band syndrome that were encountered over the last one and half years.

Necrotizing Group A Strep Following Use of Penile Constriction Ring

The development and management of necrotizing cellulitis following penile constriction ring use is described. Devastating injuries such as this can be highly distressing for patients and focused counseling is often needed to address concerns regarding cosmetic outcomes. The timeframe and appearance of recovery has not been previously captured. We present a photographic timeline covering the development, management, and postoperative recovery from penile constriction ring injury over the course of 1 month.

Investigating the Protein Kinase C Polarized Growth‐Related Protein Complex in Aspergillus nidulans

The long‐term goal of our research is to advance understanding of the mechanisms involved in hyphal growth, as well as maintenance of cell walls in filamentous fungi. Recently our work has focused on proteins that localize to sites of cell wall synthesis, namely growing cell apices (hyphal tips) and forming septa. This project focusses on Protein kinase C (PkcA). In previous work, we identified a mutation in the gene that encodes an orthologue of protein kinase C in our model organism Aspergillus nidulans, which results in reduced cell wall integrity. We showed that wild type PkcA localizes to growing hyphal apices and the contractile actomyosin ring at forming septa, and we identified amino acid sequences within PkcA that are required for PkcA to localize to these sites of cell wall synthesis. This project seeks to uncover the protein‐protein interactions involving PkcA and determine the PkcA‐complexed proteins it phosphorylates and those that it does not. Previously we reported that PkcA forms a complex with the formin SepA, and that this interaction requires the FH2 domain of SepA. Published results from another group suggested that the Rho‐type GTPase Rho4 plays a role in SepA function and that Bud3 acts as a GEF for Rho4. Here we show that the putative Rho binding domain of PkcA (HR1A) is sufficient for its interaction with SepA. Fluorescence microscopy of a dually labeled A. nidulans strain illustrate that although PkcA‐mRFP and Rho4‐GFP often reside at the contractile actomyosin concurrently, PkcA precedes Rho4 in ring constriction and yeast two‐hybrid assays failed to show an interaction between PkcA and Rho4. Further, neither of 4 other Rho homologues tested interacted with PkcA in yeast two‐hybrid experiments. Sequence analysis of the FH2 domain of SepA revealed a Rho‐like motif encompassing amino acids 377–408 having 43.3% sequence identity with RhoA. This result suggests that the sufficiency of the HR1A domain for PkcA’s interaction with SepA is due to its affinity for the Rho‐like motif within FH2. Co‐immunoprecipitation of GFP‐PkcA followed by tandem mass spectrometry and proteomics analysis of complexed proteins identified chitin synthase B and the glucan synthase FksA within the PkcA complex. Ongoing studies will seek to determine if these proteins are substrates for PkcA.Support or Funding InformationNSF RUI 1615192

Cytokinesis: An Anillin-RhoGEF Module Sets the Stage for Septin Double Ring Assembly.

In many eukaryotes septin filaments form an hourglass-like structure at the division site that rearranges into a double ring at cytokinesis. A new study elucidates how an anillin-RhoGEF complex guides the assembly of the septin double ring in budding yeast.

Critical Roles of a RhoGEF-Anillin Module in Septin Architectural Remodeling during Cytokinesis.

How septin architecture is remodeled from an hourglass to a double ring during cytokinesis in fungal and animal cells remains unknown. Here, we show that during the hourglass-to-double-ring transition in budding yeast, septins acquire a "zonal architecture" in which paired septin filaments that are organized along the mother-bud axis associate with circumferential single septin filaments, the Rho guanine-nucleotide-exchange factor (RhoGEF) Bud3, and the anillin-like protein Bud4 exclusively at the outer zones and with myosin-II filaments in the middle zone. Deletion of Bud3 or its Bud4-interacting domain, but not its RhoGEF domain, leads to a complete loss of the single filaments, whereas deletion of Bud4 or its Bud3-interacting domain destabilizes the transitional hourglass, especially at the mother side, with partial loss of both filament types. Deletion of Bud3 and Bud4 together further weakens the transitional structure and abolishes the double ring formation while causing no obvious defect in actomyosin ring constriction. This and further analyses suggest that Bud3 stabilizes the single filaments, whereas Bud4 strengthens the interaction between the paired and single filaments at the outer zones of the transitional hourglass, as well as in the double ring. This study reveals a striking zonal architecture for the transitional hourglass that pre-patterns two cytokinetic structures-a septin double ring and an actomyosin ring-and also defines the essential roles of a RhoGEF-anillin module in septin architectural remodeling during cytokinesis at the filament level.

A novel Pezizomycotina‐specific protein with gelsolin domains regulates contractile actin ring assembly and constriction in perforated septum formation

Septum formation in fungi is equivalent to cytokinesis. It differs mechanistically in filamentous ascomycetes (Pezizomycotina) from that of ascomycete yeasts by the retention of a central septal pore in the former group. However, septum formation in both groups is accomplished by contractile actin ring (CAR) assembly and constriction. The specific components regulating septal pore organization during septum formation are poorly understood. In this study, a novel Pezizomycotina-specific actin regulatory protein GlpA containing gelsolin domains was identified using bioinformatics. A glpA deletion mutant exhibited increased distances between septa, abnormal septum morphology and defective regulation of septal pore closure. In glpA deletion mutant hyphae, overaccumulation of actin filament (F-actin) was observed, and the CAR was abnormal with improper assembly and failure in constriction. In wild-type cells, GlpA was found at the septum formation site similarly to the CAR. The N-terminal 329 residues of GlpA are required for its localization to the septum formation site and essential for proper septum formation, while its C-terminal gelsolin domains are required for the regular CAR dynamics during septum formation. Finally, in this study we elucidated a novel Pezizomycotina-specific actin modulating component, which participates in septum formation by regulating the CAR dynamics.