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2.
Development ; 146(21)2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31582415

RESUMO

Cytokinesis in animal cells requires the assembly and constriction of a contractile actomyosin ring. Non-muscle myosin II is essential for cytokinesis, but the role of its motor activity remains unclear. Here, we examine cytokinesis in C. elegans embryos expressing non-muscle myosin motor mutants generated by genome editing. Two non-muscle motor-dead myosins capable of binding F-actin do not support cytokinesis in the one-cell embryo, and two partially motor-impaired myosins delay cytokinesis and render rings more sensitive to reduced myosin levels. Further analysis of myosin mutants suggests that it is myosin motor activity, and not the ability of myosin to crosslink F-actin, that drives the alignment and compaction of F-actin bundles during contractile ring assembly, and that myosin motor activity sets the pace of contractile ring constriction. We conclude that myosin motor activity is required at all stages of cytokinesis. Finally, characterization of the corresponding motor mutations in C. elegans major muscle myosin shows that motor activity is required for muscle contraction but is dispensable for F-actin organization in adult muscles.This article has an associated 'The people behind the papers' interview.


Assuntos
Citocinese , Miosina Tipo II/metabolismo , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Actomiosina/metabolismo , Animais , Plaquetas/metabolismo , Caenorhabditis elegans , Fase de Clivagem do Zigoto/metabolismo , Edição de Genes , Proteínas de Fluorescência Verde/metabolismo , Homozigoto , Humanos , Camundongos , Músculos/metabolismo , Mutação , Miosinas/metabolismo , Fosforilação , Interferência de RNA
3.
East Asia (Piscataway) ; 38(3): 249-269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33850414

RESUMO

This study is to analyze how the fragmentation of the pro-democracy camp affected their council voting and policy stances before 2019. The quantitative measurements including the rice and unity indices are adopted to evaluate the cohesions of the pro-Beijing and pro-democracy camps in bill voting, in which the strategies employed by the pro-democracy camp are further analyzed. Before the 2010s, the moderate democrats deliberately separated from the administration and some of them also kept distance from the radical groups. However, since the radical ideologies gained supports from time to time, the moderate democrats had been forced to follow more pro-active lines against the administration. Although the political sphere of Hong Kong has drastically changed after the 2019 Anti-extradition Protests, the cohesion of the pro-democracy parties in the previous terms of the Legislative Council still facilitates to understand the legislative process in the city. In this article, 18 then members of the Legislative Council from different parties were interviewed in 2018, providing various insights on the analysis of pro-democracy cohesion and fragmented politics in Hong Kong.

4.
Cell Mol Life Sci ; 75(11): 2027-2044, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29196797

RESUMO

The sorting nexins family of proteins (SNXs) plays pleiotropic functions in protein trafficking and intracellular signaling and has been associated with several disorders, namely Alzheimer's disease and Down's syndrome. Despite the growing association of SNXs with neurodegeneration, not much is known about their function in the nervous system. The aim of this work was to use the nematode Caenorhabditis elegans that encodes in its genome eight SNXs orthologs, to dissect the role of distinct SNXs, particularly in the nervous system. By screening the C. elegans SNXs deletion mutants for morphological, developmental and behavioral alterations, we show here that snx-3 gene mutation leads to an array of developmental defects, such as delayed hatching, decreased brood size and life span and reduced body length. Additionally, ∆snx-3 worms present increased susceptibility to osmotic, thermo and oxidative stress and distinct behavioral deficits, namely, a chemotaxis defect which is independent of the described snx-3 role in Wnt secretion. ∆snx-3 animals also display abnormal GABAergic neuronal architecture and wiring and altered AIY interneuron structure. Pan-neuronal expression of C. elegans snx-3 cDNA in the ∆snx-3 mutant is able to rescue its locomotion defects, as well as its chemotaxis toward isoamyl alcohol. Altogether, the present work provides the first in vivo evidence of the SNX-3 role in the nervous system.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/genética , Deleção de Genes , Nexinas de Classificação/genética , Animais , Tamanho Corporal , Caenorhabditis elegans/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Locomoção , Longevidade , Sistema Nervoso/crescimento & desenvolvimento , Sistema Nervoso/metabolismo , Fenômenos Fisiológicos do Sistema Nervoso , Neurônios/metabolismo , Neurônios/patologia , Pressão Osmótica , Estresse Oxidativo , Filogenia
5.
J Chem Inf Model ; 53(8): 2131-40, 2013 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-23848971

RESUMO

The Filamenting temperature-sensitive mutant Z (FtsZ), an essential GTPase in bacterial cell division, is highly conserved among Gram-positive and Gram-negative bacteria and thus considered an attractive target to treat antibiotic-resistant bacterial infections. In this study, a new class of FtsZ inhibitors bearing the pyrimidine-quinuclidine scaffold was identified from structure-based virtual screening of natural product libraries. Iterative rounds of in silico studies and biological evaluation established the preliminary structure-activity relationships of the new compounds. Potent FtsZ inhibitors with low micromolar IC50 and antibacterial activity against S. aureus and E. coli were found. These findings support the use of virtual screening and structure-based design for the rational development of new antibacterial agents with innovative mechanisms of action.


Assuntos
Antibacterianos/farmacologia , Desenho de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , GTP Fosfo-Hidrolases/antagonistas & inibidores , Animais , Antibacterianos/química , Sítios de Ligação , Bovinos , Avaliação Pré-Clínica de Medicamentos , Escherichia coli/efeitos dos fármacos , GTP Fosfo-Hidrolases/química , GTP Fosfo-Hidrolases/metabolismo , Guanosina Trifosfato/metabolismo , Humanos , Simulação de Acoplamento Molecular , Conformação Proteica , Multimerização Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína , Pirimidinas/química , Quinuclidinas/química , Homologia de Sequência de Aminoácidos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Relação Estrutura-Atividade , Tubulina (Proteína)/química
6.
Nucleic Acids Res ; 39(14): 5955-66, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21478169

RESUMO

Dominant mutations in the rhodopsin gene, which is expressed in rod photoreceptor cells, are a major cause of the hereditary-blinding disease, autosomal dominant retinitis pigmentosa. Therapeutic strategies designed to edit such mutations will likely depend on the introduction of double-strand breaks and their subsequent repair by homologous recombination or non-homologous end joining. At present, the break repair capabilities of mature neurons, in general, and rod cells, in particular, are undefined. To detect break repair, we generated mice that carry a modified human rhodopsin-GFP fusion gene at the normal mouse rhodopsin locus. The rhodopsin-GFP gene carries tandem copies of exon 2, with an ISceI recognition site situated between them. An ISceI-induced break can be repaired either by non-homologous end joining or by recombination between the duplicated segments, generating a functional rhodopsin-GFP gene. We introduced breaks using recombinant adeno-associated virus to transduce the gene encoding ISceI nuclease. We found that virtually 100% of transduced rod cells were mutated at the ISceI site, with ∼85% of the genomes altered by end joining and ∼15% by the single-strand annealing pathway of homologous recombination. These studies establish that the genomes of terminally differentiated rod cells can be efficiently edited in living organisms.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , Mutação , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Rodopsina/genética , Animais , Dependovirus/genética , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Técnicas de Introdução de Genes , Vetores Genéticos/administração & dosagem , Proteínas de Fluorescência Verde/genética , Humanos , Injeções , Camundongos , Modelos Animais , Mutagênese
7.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37396793

RESUMO

The C. elegans vulva is a polarized epithelial tube that has been studied extensively as a model for cell-cell signaling, cell fate specification, and tubulogenesis. Here we used endogenous fusions to show that the spectrin cytoskeleton is polarized in this organ, with conventional beta-spectrin ( UNC-70 ) found only at basolateral membranes and beta heavy spectrin ( SMA-1 ) found only at apical membranes. The sole alpha-spectrin ( SPC-1 ) is present at both locations but requires SMA-1 for its apical localization. Thus, beta spectrins are excellent markers for vulva cell membranes and polarity.

8.
J Cell Biol ; 222(1)2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36219157

RESUMO

Cytokinesis requires the constriction of an actomyosin-based contractile ring and involves multiple F-actin crosslinkers. We show that partial depletion of the C. elegans cytokinetic formin generates contractile rings with low F-actin levels that constrict but are structurally fragile, and we use this background to investigate the roles of the crosslinkers plastin/PLST-1 and ß-heavy-spectrin/SMA-1 during ring constriction. We show that the removal of PLST-1 or SMA-1 has opposite effects on the structural integrity of fragile rings. PLST-1 loss reduces cortical tension that resists ring constriction and makes fragile rings less prone to ruptures and regressions, whereas SMA-1 loss exacerbates structural defects, leading to frequent ruptures and cytokinesis failure. Fragile rings without SMA-1 or containing a shorter SMA-1, repeatedly rupture at the same site, and SMA-1::GFP accumulates at repair sites in fragile rings and in rings cut by laser microsurgery. These results establish that ß-heavy-spectrin stabilizes the constricting ring and reveals the importance of ß-heavy-spectrin size for network connectivity at low F-actin density.


Assuntos
Citoesqueleto de Actina , Citocinese , Espectrina , Actinas , Actomiosina , Animais , Caenorhabditis elegans/citologia , Proteínas de Caenorhabditis elegans/metabolismo , Forminas , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Espectrina/metabolismo
9.
Cell Rep ; 42(9): 113076, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37665665

RESUMO

During cytokinesis, a contractile ring consisting of unbranched filamentous actin (F-actin) and myosin II constricts at the cell equator. Unbranched F-actin is generated by formin, and without formin no cleavage furrow forms. In Caenorhabditis elegans, depletion of septin restores furrow ingression in formin mutants. How the cleavage furrow ingresses without a detectable unbranched F-actin ring is unknown. We report that, in this setting, anillin (ANI-1) forms a meshwork of circumferentially aligned linear structures decorated by non-muscle myosin II (NMY-2). Analysis of ANI-1 deletion mutants reveals that its disordered N-terminal half is required for linear structure formation and sufficient for furrow ingression. NMY-2 promotes the circumferential alignment of the linear ANI-1 structures and interacts with various lipids, suggesting that NMY-2 links the ANI-1 network with the plasma membrane. Collectively, our data reveal a compensatory mechanism, mediated by ANI-1 linear structures and membrane-bound NMY-2, that promotes furrowing when unbranched F-actin polymerization is compromised.


Assuntos
Actinas , Proteínas de Caenorhabditis elegans , Proteínas Contráteis , Animais , Actinas/metabolismo , Septinas/genética , Septinas/metabolismo , Forminas/metabolismo , Citocinese/fisiologia , Membrana Celular/metabolismo , Caenorhabditis elegans/metabolismo , Miosina Tipo II/metabolismo , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo
10.
J Chem Inf Model ; 52(5): 1367-75, 2012 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-22559726

RESUMO

AmpC ß-lactamase confers resistance to ß-lactam antibiotics in multiple Gram-negative bacteria. Therefore, identification of non-ß-lactam compounds that inhibit the enzyme is considered crucial to the development of novel antibacterial therapies. Given the highly solvent-exposed active site, it is important to study the induced-fit movements and water-mediated interactions to improve docking accuracy and virtual screening enrichments in structure-based design of new AmpC inhibitors. Here, we tested multiple models of the AmpC binding site to investigate the importance of conserved water molecules and binding site plasticity on molecular docking. The results indicate that at least one conserved water molecule greatly improves the binding pose predictions and virtual screening enrichments of known noncovalent AmpC inhibitors. The best model was tested prospectively in the virtual screening of about 6 million commercially available compounds. Sixty-one chemically diverse top-scoring compounds were experimentally tested, which led to the identification of seven previously unknown inhibitors. These findings validate the essential features of the AmpC binding site for molecular recognition and are useful for further optimization of identified inhibitors.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Inibidores Enzimáticos/farmacologia , Bibliotecas de Moléculas Pequenas/química , Inibidores de beta-Lactamases , beta-Lactamases/metabolismo , Proteínas de Bactérias/química , Sítios de Ligação , Cristalografia por Raios X , Enterobacter cloacae/enzimologia , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/química , Humanos , Concentração Inibidora 50 , Ligantes , Estrutura Molecular , Ligação Proteica/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , beta-Lactamases/química
11.
Dis Model Mech ; 15(5)2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35275162

RESUMO

The P23H mutation in rhodopsin (Rho), the rod visual pigment, is the most common allele associated with autosomal-dominant retinitis pigmentosa (adRP). The fate of misfolded mutant Rho in rod photoreceptors has yet to be elucidated. We generated a new mouse model, in which the P23H-Rho mutant allele is fused to the fluorescent protein Tag-RFP-T (P23HhRhoRFP). In heterozygotes, outer segments formed, and wild-type (WT) rhodopsin was properly localized, but mutant P23H-Rho protein was mislocalized in the inner segments. Heterozygotes exhibited slowly progressing retinal degeneration. Mislocalized P23HhRhoRFP was contained in greatly expanded endoplasmic reticulum (ER) membranes. Quantification of mRNA for markers of ER stress and the unfolded protein response revealed little or no increases. mRNA levels for both the mutant human rhodopsin allele and the WT mouse rhodopsin were reduced, but protein levels revealed selective degradation of the mutant protein. These results suggest that the mutant rods undergo an adaptative process that prolongs survival despite unfolded protein accumulation in the ER. The P23H-Rho-RFP mouse may represent a useful tool for the future study of the pathology and treatment of P23H-Rho and adRP. This article has an associated First Person interview with the first author of the paper.


Assuntos
Degeneração Retiniana , Retinose Pigmentar , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Mutação/genética , RNA Mensageiro/genética , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Retinose Pigmentar/metabolismo , Rodopsina/genética , Rodopsina/metabolismo
12.
Curr Biol ; 31(24): 5415-5428.e10, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34666005

RESUMO

Cytokinesis, the process that partitions the mother cell into two daughter cells, requires the assembly and constriction of an equatorial actomyosin network. Different types of non-motor F-actin crosslinkers localize to the network, but their functional contribution remains poorly understood. Here, we describe a synergy between the small rigid crosslinker plastin and the large flexible crosslinker spectrin in the C. elegans one-cell embryo. In contrast to single inhibitions, co-inhibition of plastin and the ßH-spectrin (SMA-1) results in cytokinesis failure due to progressive disorganization and eventual collapse of the equatorial actomyosin network. Cortical localization dynamics of non-muscle myosin II in co-inhibited embryos mimic those observed after drug-induced F-actin depolymerization, suggesting that the combined action of plastin and spectrin stabilizes F-actin in the contractile ring. An in silico model predicts that spectrin is more efficient than plastin at stabilizing the ring and that ring formation is relatively insensitive to ßH-spectrin length, which is confirmed in vivo with a sma-1 mutant that lacks 11 of its 29 spectrin repeats. Our findings provide the first evidence that spectrin contributes to cytokinesis and highlight the importance of crosslinker interplay for actomyosin network integrity.


Assuntos
Actomiosina , Citocinese , Actinas/metabolismo , Actomiosina/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Glicoproteínas de Membrana , Proteínas dos Microfilamentos , Espectrina/genética
13.
Methods Mol Biol ; 2101: 297-325, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31879911

RESUMO

Cytokinesis is the process that completes cell division by partitioning the contents of the mother cell between the two daughter cells. It involves the highly regulated assembly and constriction of an actomyosin contractile ring, whose function is to pinch the mother cell in two. Research on the contractile ring has particularly focused on the signaling mechanisms that dictate when and where the ring is formed. In vivo studies of ring constriction are however scarce and its mechanistic understanding is therefore limited. Here we present several experimental approaches for monitoring ring constriction in vivo, using the four-cell C. elegans embryo as model. These approaches allow for the ring to be perturbed only after it forms and include the combination of live imaging with acute drug treatments, temperature-sensitive mutants and rapid temperature shifts, as well as laser microsurgery. In addition, we explain how to combine these with RNAi-mediated depletion of specific components of the cytokinetic machinery.


Assuntos
Actomiosina/metabolismo , Caenorhabditis elegans/embriologia , Citocinese , Embrião não Mamífero , Animais , Divisão Celular , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Processamento de Imagem Assistida por Computador , Microscopia Confocal/métodos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Mutação , Interferência de RNA
14.
Front Cell Dev Biol ; 8: 573393, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102479

RESUMO

Cytokinesis is the last step of cell division that physically partitions the mother cell into two daughter cells. Cytokinesis requires the assembly and constriction of a contractile ring, a circumferential array of filamentous actin (F-actin), non-muscle myosin II motors (myosin), and actin-binding proteins that forms at the cell equator. Cytokinesis is accompanied by long-range cortical flows from regions of relaxation toward regions of compression. In the C. elegans one-cell embryo, it has been suggested that anterior-directed cortical flows are the main driver of contractile ring assembly. Here, we use embryos co-expressing motor-dead and wild-type myosin to show that cortical flows can be severely reduced without major effects on contractile ring assembly and timely completion of cytokinesis. Fluorescence recovery after photobleaching in the ingressing furrow reveals that myosin recruitment kinetics are also unaffected by the absence of cortical flows. We find that myosin cooperates with the F-actin crosslinker plastin to align and compact F-actin bundles at the cell equator, and that this cross-talk is essential for cytokinesis. Our results thus argue against the idea that cortical flows are a major determinant of contractile ring assembly. Instead, we propose that contractile ring assembly requires localized concerted action of motor-competent myosin and plastin at the cell equator.

15.
J Psychiatr Ment Health Nurs ; 27(5): 509-520, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31958205

RESUMO

WHAT IS KNOWN ON THE SUBJECT?: Many Western countries have abandoned the wearing of nurse uniforms on inpatient mental health wards. The adoption of a non-uniform policy in Hong Kong was recently introduced in select rehabilitation units to align with the philosophy of the recovery model. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The findings suggest that nurses perceived wearing non-uniform might help to reduce the self-stigma of service users and develop better self-esteem. The perceived potential benefits of the introduction of a non-uniform policy seemed to outweigh the perceived drawbacks. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The results further acknowledge the potential positive effects of nurses wearing non-uniform on facilitating psychiatric service users' recovery process. However, further research on service users' perspectives is required. The wearing of non-uniform may be considered to be extended to other psychiatric wards in Hong Kong and other similar Asian settings in order to potentially help promote patient's recovery and to reduce emotional distance between staff and service users. ABSTRACT: Introduction A non-uniform policy was recently adopted in selected Hong Kong rehabilitation wards to align with the philosophy of the recovery model. The change in policy is relatively novel in Asia, where no previous studies have reported how this may influence nursing care and service users' recovery. Aim To explore Hong Kong Mental Health Nurses' views about wearing non-uniform within an inpatient rehabilitation unit in regard to facilitating service users' recovery process. Method A qualitative descriptive study was conducted, utilizing individual in-depth semi-structured research interviews. Results A total of 12 interviews were conducted with nurse participants. The analysis process identified 3 main themes and 9 subthemes. Main themes were "building up rapport with service users," "non-uniform helps deinstitutionalization" and "different approaches to maximize the benefit and to minimize the risk." Discussion Despite some concerns, the majority of nurse participants positively viewed the policy of wearing non-uniform and felt it was potentially beneficial to service users' recovery process. Implications for practice Nurses perceived that wearing non-uniform may facilitate meaningful therapeutic engagement, and may help to reduce the self-stigma and develop the self-esteem of service users. Other inpatient units in Hong Kong and similar Asian settings might consider adopting the policy.


Assuntos
Atitude do Pessoal de Saúde , Vestuário , Transtornos Mentais/terapia , Relações Enfermeiro-Paciente , Recursos Humanos de Enfermagem Hospitalar , Unidade Hospitalar de Psiquiatria , Enfermagem Psiquiátrica , Adulto , Feminino , Hong Kong , Humanos , Masculino , Transtornos Mentais/enfermagem , Transtornos Mentais/reabilitação , Pessoa de Meia-Idade , Pesquisa Qualitativa , Autoimagem , Estigma Social , Adulto Jovem
16.
J Paediatr Child Health ; 45(1-2): 48-52, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19208066

RESUMO

AIM: To determine cardiac outcomes of foetal hydrops as a result of twin-twin transfusion syndrome treated with laser surgery. METHODS: Hydrops identified in 16 recipient foetuses with twin-twin transfusion syndrome was treated with laser ablation surgery to anastomotic vessels. Prior to laser surgery, the foetuses were assessed by echocardiography for cardiac abnormalities and ventricular and valvular dysfunction. After delivery, echocardiography was performed on 15 of the 16 newborn infants. RESULTS: Foetal echocardiography indicated impaired biventricular function in the 16 hydropic foetuses. Five foetuses had little or no forward flow through the pulmonary valve, while four had pulmonary regurgitation. Following laser surgery performed at a mean of 22.9 weeks gestation, hydrops resolved in all cases. Delivery occurred at a mean of 33.6 weeks gestation. Post-natal echocardiography revealed cardiac abnormalities in five neonates, of whom three had right ventricular outflow tract obstruction. One preterm infant with severe pulmonary stenosis died with intractable cardiac failure. CONCLUSION: The majority of hydropic infants with twin-win transfusion syndrome have normal cardiac outcomes following intrauterine laser surgery. As up to one-third may have cardiac abnormalities, cardiological monitoring is recommended during the first year of life.


Assuntos
Transfusão Feto-Fetal/cirurgia , Cardiopatias Congênitas/etiologia , Hidropisia Fetal/cirurgia , Anastomose Arteriovenosa/cirurgia , Débito Cardíaco , Feminino , Coração Fetal/diagnóstico por imagem , Coração Fetal/patologia , Coração Fetal/fisiopatologia , Coração Fetal/cirurgia , Transfusão Feto-Fetal/complicações , Transfusão Feto-Fetal/fisiopatologia , Cardiopatias Congênitas/prevenção & controle , Humanos , Hidropisia Fetal/diagnóstico por imagem , Hidropisia Fetal/etiologia , Terapia a Laser , Gravidez , Resultado do Tratamento , Ultrassonografia Pré-Natal
17.
Aust N Z J Obstet Gynaecol ; 49(1): 22-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19281575

RESUMO

AIMS: To report the perinatal outcomes of a large series of twin pregnancies with severe twin-twin transfusion syndrome (TTTS) managed with laser ablation surgery in an Australian tertiary perinatal centre and to compare the outcome with other large cohorts. METHODS: The outcomes of 100 consecutive pregnancies with severe TTTS managed with selective fetoscopic laser ablation from March 2002 to June 2007 were examined. Survival and neonatal morbidity were analysed. Comparisons were made with the results from other studies of laser surgery with at least 100 pregnancies. RESULTS: There were 100 women with TTTS treated with laser ablation; 34 stage II, 44 stage III and 22 at stage IV. Median gestation at time of laser was 21 weeks (range 18-28) and median gestation at delivery was 31 weeks (range 20-39). Overall perinatal survival rate was 151 of 200 (75.5%). Eighty five per cent had one or more surviving twins. The survival rate for stage IV TTTS was 88.6%, significantly better than for stage II (69.1%) and stage III (73.9%) pregnancies. The perinatal mortality rate for donors (30%) was not significantly different from recipients (19%), but the fetal death rate for donors was significantly greater than that for recipients (P = 0.03). Severe cerebral abnormalities were present in only 2.8% of newborns. The overall survival rate was comparable to other large series. CONCLUSIONS: These results for the management of severe TTTS are comparable to the best reported international series. Long-term follow-up is required and more research needs to be undertaken to further improve these results.


Assuntos
Transfusão Feto-Fetal/cirurgia , Fetoscopia , Terapia a Laser , Estudos de Coortes , Feminino , Mortalidade Fetal , Transfusão Feto-Fetal/mortalidade , Humanos , Recém-Nascido , Mortalidade Perinatal , Gravidez , Segundo Trimestre da Gravidez , Queensland/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
18.
Mol Biol Cell ; 30(1): 96-107, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30403552

RESUMO

Cytokinesis completes cell division by constriction of an actomyosin contractile ring that separates the two daughter cells. Here we use the early Caenorhabditis elegans embryo to explore how the actin filament network in the ring and the surrounding cortex is regulated by the single cytokinesis formin CYK-1 and the ARP2/3 complex, which nucleate nonbranched and branched filaments, respectively. We show that CYK-1 and the ARP2/3 complex are the predominant F-actin nucleators responsible for generating distinct cortical F-actin architectures and that depletion of either nucleator affects the kinetics of cytokinesis. CYK-1 is critical for normal F-actin levels in the contractile ring, and acute inhibition of CYK-1 after furrow ingression slows ring constriction rate, suggesting that CYK-1 activity is required throughout ring constriction. Surprisingly, although the ARP2/3 complex does not localize in the contractile ring, depletion of the ARP2 subunit or treatment with ARP2/3 complex inhibitor delays contractile ring formation and constriction. We present evidence that the delays are due to an excess in formin-nucleated cortical F-actin, suggesting that the ARP2/3 complex negatively regulates CYK-1 activity. We conclude that the kinetics of cytokinesis are modulated by interplay between the two major actin filament nucleators.


Assuntos
Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/citologia , Caenorhabditis elegans/metabolismo , Citocinese , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Animais , Caenorhabditis elegans/embriologia , Polaridade Celular , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Cinética
19.
J Morphol ; 279(1): 75-85, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29044653

RESUMO

The optic lobe is the largest brain area within the central nervous system of cephalopods and it plays important roles in the processing of visual information, the regulation of body patterning, and locomotive behavior. The oval squid Sepioteuthis lessoniana has relatively large optic lobes that are responsible for visual communication via dynamic body patterning. It has been observed that the visual behaviors of oval squids change as the animals mature, yet little is known about how the structure of the optic lobes changes during development. The aim of the present study was to characterize the ontogenetic changes in neural organization of the optic lobes of S. lessoniana from late embryonic stage to adulthood. Magnetic resonance imaging and micro-CT scans were acquired to reconstruct the 3D-structure of the optic lobes and examine the external morphology at different developmental stages. In addition, optic lobe slices with nuclear staining were used to reveal changes in the internal morphology throughout development. As oval squids mature, the proportion of the brain making up the optic lobes increases continuously, and the optic lobes appear to have a prominent dent on the ventrolateral side. Inside the optic lobe, the cortex and the medulla expand steadily from the late embryonic stage to adulthood, but the cell islands in the tangential zone of the optic lobe decrease continuously in parallel. Interestingly, the size of the nuclei of cells within the medulla of the optic lobe increases throughout development. These findings suggest that the optic lobe undergoes continuous external morphological change and internal neural reorganization throughout the oval squid's development. These morphological changes in the optic lobe are likely to be responsible for changes in the visuomotor behavior of oval squids from hatching to adulthood.


Assuntos
Decapodiformes/anatomia & histologia , Decapodiformes/embriologia , Embrião não Mamífero/anatomia & histologia , Desenvolvimento Embrionário , Lobo Óptico de Animais não Mamíferos/anatomia & histologia , Lobo Óptico de Animais não Mamíferos/embriologia , Animais , Núcleo Celular/metabolismo , Decapodiformes/citologia , Embrião não Mamífero/citologia , Imageamento Tridimensional , Lobo Óptico de Animais não Mamíferos/citologia
20.
Mol Cell Biol ; 23(9): 3152-62, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12697816

RESUMO

Expansion of CTG triplet repeats in the 3' untranslated region of the DMPK gene causes the autosomal dominant disorder myotonic dystrophy. Instability of CTG repeats is thought to arise from their capacity to form hairpin DNA structures. How these structures interact with various aspects of DNA metabolism has been studied intensely for Escherichia coli and Saccharomyces cerevisiae but is relatively uncharacterized in mammalian cells. To examine the stability of (CTG)(17), (CTG)(98), and (CTG)(183) repeats during homologous recombination, we placed them in the second intron of one copy of a tandemly duplicated pair of APRT genes. Cells selected for homologous recombination between the two copies of the APRT gene displayed distinctive patterns of change. Among recombinants from cells with (CTG)(98) and (CTG)(183), 5% had lost large numbers of repeats and 10% had suffered rearrangements, a frequency more than 50-fold above normal levels. Analysis of individual rearrangements confirmed the involvement of the CTG repeats. Similar changes were not observed in proliferating (CTG)(98) and (CTG)(183) cells that were not recombinant at APRT. Instead, they displayed high frequencies of small changes in repeat number. The (CTG)(17) repeats were stable in all assays. These studies indicate that homologous recombination strongly destabilizes long tracts of CTG repeats.


Assuntos
Adenina Fosforribosiltransferase/genética , Rearranjo Gênico , Proteínas Serina-Treonina Quinases/genética , Recombinação Genética , Expansão das Repetições de Trinucleotídeos , Animais , Células CHO , Linhagem Celular , Cricetinae , Dosagem de Genes , Humanos , Íntrons , Miotonina Proteína Quinase , Deleção de Sequência
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