RESUMO
Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. Reviews indicated a positive relationship between exposure to pesticides and the development of cancers. In the present study, we have estimated the level of oxidative stress markers in serum samples of pesticide exposure and unexposed cancer patients as compared to normal control. We have found a significant decrease in peroxygenase (PON) and arylesterase (ARE) activity and substantial increases in homocysteine levels in both cancer groups. The level of heme biosynthesis rate-limiting enzymes delta-aminolevulinic acid dehydratase (δ-ALA-D) also significantly decreased compared to control. The statistical comparison between the cancer groups does not show significant changes. We concluded the involvement of oxidative stress in carcinogenesis in both cancer group patients. However, more study is needed to put homocysteine as a novel marker for a variety of diseases on a single platform.
RESUMO
INTRODUCTION: Iron oxide nanoparticles demonstrate tremendous potential in preserving the ecological balance of the environment since they act as antimicrobial agents and efficient photocatalysts. However, environmental sustainability has challenged the synthesis protocols of nanomaterials. METHOD: This study compares the green synthesis method with the scalable chemical synthesis method. In this work, Iron oxide nanoparticles were fabricated via the green chemistry technique utilizing the leaf extract of Mentha spicata (M-IONP) and also via the chemical co-precipitation method (C-IONP). The synthesized IONPs were analyzed by different characterization methods such as XRD, FTIR, SEM analysis, ZETA potential measurements, and DLS spectroscopy analysis. RESULTS: The biosynthesized and chemically synthesized IONPs were analyzed for their mechanistic action against different applications like antimicrobial, antioxidant, and degradation of harmful dyes. Interestingly, the biosynthesized IONPs (M-IONP) exhibited more effective antimicrobial efficacy towards Gram-positive and Gram-negative organisms than chemically synthesized IONPs. CONCLUSION: The green synthesized M-IONP also showed significant antioxidant propensity similar to that of the standards taken. Additionally, green-synthesized M-IONP exhibited enhanced degradation efficacies against Methylene blue, chromium, and sulphamethoxazole in comparison to chemically synthesized IONP.
RESUMO
OBJECTIVES: Our study aimed to evaluate the effect of superior hypogastric nerve plexus (SHNP) block in postoperative pain management in the first 24 h after minimally invasive gynecological (MIG) surgeries. METHODS: We conducted a double-blinded, randomized controlled trial in the Department of Obstetrics and Gynecology at a tertiary care centre from May 1, 2023 to September 30, 2023 in women undergoing major MIG surgeries. At the completion of the surgery, women were randomized to the intervention group who received SHNP block with ropivacaine 10 mL (0.75%) before port removal, whereas no intervention was taken in the control group. The extubation time was noted, and the pain score was assessed after 1, 2, 6, 12, and 24 h of extubation in the postoperative period using the visual analog scale (VAS). Statistical analysis was done, with a significance level of 0.05, to test the differences between the two groups. RESULTS: A total of 64 patients were randomly allocated to intervention and control groups. The median pain score was lower at 1 and 2 h post-extubation and comparable between the two groups at 6, 12, and 24 h. The surrogate markers that is need for additional analgesia and duration of stay did not differ significantly in the two groups, with P-values of 0.08 and 0.943, respectively. CONCLUSION: Although the SHNP group experienced considerably lower immediate postoperative pain levels in the initial hours following extubation, the impact of this benefit remains uncertain in the longer postoperative period. The effectiveness of this modality for pain control needs further study, particularly at later postoperative hours.
RESUMO
BACKGROUND: Studies have shown inconclusive results on the effectiveness of cerebral protection devices (CPDs) with transcatheter aortic valve replacement. We aimed to analyze the national statistics on stroke and other outcomes with CPD use. METHODS AND RESULTS: The Nationwide Readmissions Database (2017-2020) was queried to obtain data on patients undergoing transcatheter aortic valve replacement. Outcomes were compared between patients with a CPD and patients without a CPD. Of 271 804 patients undergoing transcatheter aortic valve replacement, CPD was used in 7.3% of patients. In a multivariable logistic regression analysis, CPD use was not associated with lower overall stroke rates (1.6% versus 1.9% without CPD; odds ratio, 0.95 [95% CI, 0.84-1.07]; P=0.364), but it was significantly associated with lower major stroke rates (1.2% versus 1.5% without CPD; odds ratio, 0.85 [95% CI, 0.74-0.98]; P=0.02). Patients with a CPD also had a shorter length of stay, higher routine discharges to home/self-care (74.9% versus 70.6%), and lower mortality rates (0.7% versus 1.3%). The 30-day (9.6% versus 11.7%) and 180-day (24.6% versus 28.2%) readmission rates were significantly lower in the CPD cohort. Among patients who developed stroke, patients with a CPD had more frequent routine discharges. Prior valve surgery was associated with the highest risk of overall and major stroke. CONCLUSIONS: CPD use during transcatheter aortic valve replacement was not independently associated with a lower risk of overall stroke but was associated with a lower risk of major stroke in a multivariable model. Data from future randomized trials that may offset any potential confounders in our study are required to help identify patients who would benefit from the use of these devices.
Assuntos
Acidente Vascular Cerebral , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/instrumentação , Masculino , Feminino , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Idoso de 80 Anos ou mais , Idoso , Fatores de Risco , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/mortalidade , Estados Unidos/epidemiologia , Dispositivos de Proteção Embólica , Medição de Risco/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Resultado do Tratamento , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Bases de Dados Factuais , Incidência , Fatores de TempoRESUMO
Pericytes line the microvasculature throughout the body and play a key role in regulating blood flow by constricting and dilating vessels. However, the biophysical mechanisms through which pericytes transduce microenvironmental chemical and mechanical cues to mediate vessel diameter, thereby impacting oxygen and nutrient delivery, remain largely unknown. This knowledge gap is clinically relevant as numerous diseases are associated with the aberrant contraction of pericytes, which are unusually susceptible to injury. Here, we report the development of a high-throughput hydrogel-based pericyte contraction cytometer that quantifies single-cell contraction forces from murine and human pericytes in different microvascular microenvironments and in the presence of competing vasoconstricting and vasodilating stimuli. We further show that murine pericyte survival in hypoxia is mediated by the mechanical microenvironment and that, paradoxically, pre-treating pericytes to reduce contraction increases hypoxic cell death. Moreover, using the contraction cytometer as a drug-screening tool, we found that cofilin-1 could be applied extracellularly to release murine pericytes from hypoxia-induced contractile rigor mortis and, therefore, may represent a novel approach for mitigating the long-lasting decrease in blood flow that occurs after hypoxic injury.
RESUMO
Cellular actin networks assemble by actin filament elongation at barbed ends and are thought to disassemble primarily by depolymerization at filament pointed ends. Contrary to this conventional understanding of actin dynamics, twinfilin was recently shown to promote barbed-end depolymerization. Twinfilin has additionally been suggested to sequester monomers and cap as well as uncap filament barbed ends. As a result, the exact mechanisms by which twinfilin affects barbed-end dynamics remain controversial. Using multicolor single-molecule microscopy, we show that both mouse and yeast twinfilin are non-processive depolymerases that interact only transiently with barbed ends (~0.2-0.5 s). Each twinfilin binding event, on average, results in the removal of one or two actin subunits. At CP-capped barbed ends, twinfilin synergizes with formin to accelerate uncapping by up to ~320-fold. We find that uncapping by twinfilin, alone and together with formin, depends on the nucleotide state of the filament, with the two proteins causing a much more modest enhancement of uncapping of newly assembled filaments. Our study thus establishes twinfilin as a multifunctional barbed-end binding protein capable of non-processively depolymerizing, transiently capping, and synergizing with formin to rapidly uncap actin filament barbed ends.
RESUMO
INTRODUCTION: Anatomy teaching has traditionally been based on dissection. However, reduced hours in total and laboratory hours in gross anatomy along with a dearth of cadavers have ensued the search for a less time-consuming tool. MATERIALS AND METHODS: The study was conducted in the Department of Anatomy in Sheikh Bhikhari Medical College, Hazaribag. A total of 282 medical students were taught gross anatomy, using three different learning modalities: dissection (n = 95), plastic models (n = 94), and three-dimensional (3D) anatomy software (n = 93). The knowledge of the students was examined by 100 multiple-choice question (MCQ) and tag questions followed by an evaluation questionnaire. RESULTS: When performance is considered, the dissection and 3D group performed better than the plastic models group in total, MCQs, and tag questions. In the evaluation questionnaire, dissection performed better than the other two modalities. Moreover, dissection and 3D software emerged as superior to the plastic models group. STATISTICAL ANALYSIS: All data were analyzed using the one-way ANOVA and t-test. Group-based analysis by ANOVA and gender-based analysis were done by Student's t-test. A comparison of students' perceptions was done by Kruskal-Wallis H-test. CONCLUSION: Dissection remains a favorite with students and accomplishes a significantly higher attainment of knowledge. Plastic models are less effective but are a valuable tool in preparation for cadaveric laboratories.
Résumé Introduction:L'enseignement de l'anatomie est traditionnellement basé sur la dissection. Cependant, la réduction des heures totales et des heures de laboratoire en anatomie globale ainsi que la pénurie de cadavres ont entraîné la recherche d'un outil moins chronophage.Méthodologie:L'étude a été menée dans le département d'anatomie du Sheikh Bhikhari Medical College, Hazaribag. Au total, 282 étudiants en médecine ont appris l'anatomie globale, en utilisant trois modalités d'apprentissage différentes : dissection (n = 95), modèles plastiques (n = 94) et logiciel d'anatomie 3D (n = 93). Les connaissances des étudiants ont été examinées par 100 questions QCM et tags suivies d'un questionnaire d'évaluation.Résultats:Lorsque les performances sont prises en compte, le groupe dissection et 3D a obtenu de meilleurs résultats que le groupe modèles plastiques au total, questions à choix multiples et questions d'étiquettes. Dans le questionnaire d'évaluation, la dissection a donné de meilleurs résultats que les deux autres modalités. De plus, les logiciels de dissection et de 3D se sont révélés supérieurs au groupe des modèles plastiques.Analyse Statistique:Toutes les données ont été analysées à l'aide du test ANOVA et T unidirectionnel. L'analyse basée sur le groupe par Anova et l'analyse comparative entre les sexes ont été réalisées à l'aide du test t des étudiants. Une comparaison des perceptions des étudiants a été réalisée par le test Krushal Wallis H.Conclusion:La dissection reste l'une des préférées des étudiants et permet d'atteindre un niveau de connaissances nettement plus élevé. Les modèles en plastique sont moins efficaces mais constituent un outil précieux pour la préparation des laboratoires cadavériques.
Assuntos
Anatomia , Cadáver , Dissecação , Educação de Graduação em Medicina , Avaliação Educacional , Estudantes de Medicina , Humanos , Anatomia/educação , Educação de Graduação em Medicina/métodos , Feminino , Masculino , Avaliação Educacional/métodos , Inquéritos e Questionários , Aprendizagem , Currículo , Adulto Jovem , Adulto , Modelos AnatômicosRESUMO
Profilin binds microtubules in vitro. However, a new study by Vitriol and colleagues (https://doi.org/10.1083/jcb.202309097) now suggests that effects of profilin on microtubule dynamics in cells are indirect and result from its impact on actin dynamics rather than its direct binding to microtubules.
Assuntos
Actinas , Microtúbulos , Profilinas , Actinas/metabolismo , Microtúbulos/metabolismo , Profilinas/metabolismo , Profilinas/genética , Ligação ProteicaRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE). However, the incidence, predictors, and outcomes of clinical thrombosis for inpatients with COVID-19 are not well known. This study aimed to enhance our understanding of clinical thrombosis in COVID-19, its associated factors, and mortality outcomes. METHOD: Hospitalised adult (≥18 years of age) patients with COVID-19 in 2020 were retrospectively identified from the US National Inpatient Sample database. Clinical characteristics, incident VTE, ATE, and in-hospital mortality outcomes were recorded. Multivariable logistic regression was performed to identify clinical factors associated with thrombosis and in-hospital mortality in COVID-19 inpatients. RESULTS: A total of 1,583,135 adult patients with COVID-19 in the year 2020 were identified from the National Inpatient Sample database; patients with thrombosis were 41% females with a mean age of 65.4 (65.1-65.6) years. The incidence of thrombosis was 6.1% (97,185), including VTE at 4.8% (76,125), ATE at 3.0% (47,790), and the in-hospital mortality rate was 13.4% (212,785). Patients with thrombosis were more likely to have respiratory symptoms of COVID-19 (76.7% vs 75%, p<0.001) compared with patients without thrombosis. The main factors associated with overall thrombosis, VTE, and ATE were paralysis, ventilation, solid tumours without metastasis, metastatic cancer, and acute liver failure. Although all thrombosis categories were associated with higher in-hospital mortality for COVID-19 inpatients in univariable analyses (p<0.001), they were not in multivariable analyses-thrombosis (odds ratio [OR] 1.24; 95% confidence interval [CI] 0.90-1.70; p=0.19), VTE (OR 0.70; 95% CI 0.52-1.00; p=0.05), and ATE (OR 1.07; 95% CI 0.92-1.25; p=0.36). CONCLUSIONS: The association of COVID-19 with thrombosis and VTE increases with increasing severity of the COVID-19 disease. Risk stratification of thrombosis is crucial in COVID-19 patients to determine the necessity of thromboprophylaxis.
RESUMO
Background: Cervical cancer is a public health problem, and nursing personnel are crucial for successful implementation of low-cost cervical cancer screening approaches in low-resource settings. The following study assessed and compared the knowledge, attitude, and practices regarding cervical cancer and its screening among female nursing staff at different levels of health care facilities in western Rajasthan, India. Methodology: An anonymous pre-validated, structured questionnaire was used as the study tool among 233 female nursing personnel of primary, secondary, and tertiary care health facilities. Multiple logistic regression was performed to determine the association between level of knowledge with level of health care and other demographic variables. Results: The nursing staff of the tertiary care health facility demonstrated significantly higher knowledge compared to those working at primary and secondary levels [adjusted odds ratio (95% confidence interval) 11.01 (3.80-32.40)]. At tertiary care, the practices of the nursing professionals were not found significantly associated with any socio-demographic variable including age, marital status, or level of health care facility. Conclusion: The overall knowledge of cervical cancer was poor, especially among staff nurses at primary and secondary levels of health care. In order to implement a successful population-based screening program in India, it is important to update the nursing curriculum and start in-service trainings at primary and secondary levels of health care facilities.
RESUMO
Intracellular actin networks assemble through the addition of ATP-actin subunits at the growing barbed ends of actin filaments. This is followed by "aging" of the filament via ATP hydrolysis and subsequent phosphate release. Aged ADP-actin subunits thus "treadmill" through the filament before being released back into the cytoplasmic monomer pool as a result of depolymerization at filament pointed ends. The necessity for aging before filament disassembly is reinforced by preferential binding of cofilin to aged ADP-actin subunits over newly-assembled ADP-Pi actin subunits in the filament. Consequently, investigations into how cofilin influences pointed-end depolymerization have, thus far, focused exclusively on aged ADP-actin filaments. Using microfluidics-assisted Total Internal Reflection Fluorescence (mf-TIRF) microscopy, we reveal that, similar to their effects on ADP filaments, cofilin and cyclase-associated protein (CAP) also promote pointed-end depolymerization of ADP-Pi filaments. Interestingly, the maximal rates of ADP-Pi filament depolymerization by CAP and cofilin together remain approximately 20-40 times lower than for ADP filaments. Further, we find that the promotion of ADP-Pi pointed-end depolymerization is conserved for all three mammalian cofilin isoforms. Taken together, the mechanisms presented here open the possibility of newly-assembled actin filaments being directly disassembled from their pointed-ends, thus bypassing the slow step of Pi release in the aging process.
Assuntos
Citoesqueleto de Actina , Actinas , Citoesqueleto de Actina/metabolismo , Animais , Actinas/metabolismo , Fatores de Despolimerização de Actina/metabolismo , Difosfato de Adenosina/metabolismo , Coelhos , Camundongos , Polimerização , Cofilina 1/metabolismoRESUMO
BACKGROUND: Absent or hypoplastic nasal bone (AHNB) on first or second-trimester ultrasonography (USG) is an important soft marker of Down syndrome. However, due to its varied incidence in euploid and aneuploid fetuses, there is always a dilemma of whether to go for invasive fetal testing for isolated AHNB. This study aims to assess outcomes specifically within the context of Indian ethnicity women. MATERIALS AND METHODS: This was a prospective observational study. All patients who reported with AHNB in the first- or second-trimester USG were included. Genetic counseling was done, and noninvasive and invasive testing was offered. Chromosomal anomalies were meticulously recorded, and pregnancy was monitored. RESULTS: The incidence of AHNB in our study was 1.16% (47/4051). Out of 47 women with AHNB, the isolated condition was seen in 32 (0.78%) cases, while AHNB with structural anomalies was seen in nine cases (0.22%). Thirty-nine women opted for invasive testing. Six out of 47 had aneuploidy (12.7%), while two euploid cases (4.25%) developed nonimmune hydrops. The prevalence of Down syndrome in fetuses with AHNB was 8.5% (4/47) and 0.42% (17/4004) in fetuses with nasal bone present. This difference was statistically significant (p = .001). CONCLUSION: The results indicate that isolated AHNB cases should be followed by a comprehensive anomaly scan rather than immediately recommending invasive testing. However, invasive testing is required when AHNB is associated with other soft markers or abnormalities. As chromosomal microarray is more sensitive than standard karyotype in detecting chromosomal aberrations, it should be chosen over karyotype.
Assuntos
Síndrome de Down , Osso Nasal , Ultrassonografia Pré-Natal , Humanos , Feminino , Osso Nasal/anormalidades , Osso Nasal/diagnóstico por imagem , Gravidez , Estudos Prospectivos , Síndrome de Down/genética , Adulto , Ultrassonografia Pré-Natal/métodos , Aneuploidia , Índia , Aconselhamento Genético , Diagnóstico Pré-Natal/métodos , Pais , Segundo Trimestre da Gravidez , Aberrações CromossômicasRESUMO
The hydrogen bonding interaction between an amide N-H and the amide N of the preceding residue is prevalent in proline-containing proteins and peptides. However, the N-Hâ â â N hydrogen bonding interaction is rare in non-prolyl natural peptides due to restricted dihedral angles. Herein, we stabilize this type of interaction in 8-aminoquinoline appended non-prolyl peptides through bifurcated Nâ â â Hâ â â N hydrogen bond. The 8-aminoquinoline-incorporated model peptides 2 a-i were designed, synthesized, and the crystal structures of 2 a-c and 2 i were solved. Analysis of crystal data reveals that the amide N-H of aminoquinoline is involved in bifurcated hydrogen bonding interaction with the nitrogen of the preceding amino acid residue and the nitrogen in quinoline. Analysis of crystal packing, Hirshfeld surface and fingerprint plots confirms that the intermolecular Oâ â â H contacts significantly contribute to stabilizing bifurcated Nâ â â Hâ â â N hydrogen bonding interaction. Furthermore, NMR experiments and CD spectroscopy were conducted to examine the preferred conformation in solution, and the data corroborate with the crystal structure conformation.
Assuntos
Aminoquinolinas , Ligação de Hidrogênio , Peptídeos , Peptídeos/química , Peptídeos/síntese química , Aminoquinolinas/química , Aminoquinolinas/síntese química , Cristalografia por Raios X , Modelos MolecularesRESUMO
Transverse testicular ectopia (TTE) is an infrequent ectopic testis where both testes descend via the same inguinal canal, located in the same hemiscrotum, and augments the risk of developing testicular tumours. Type II TTE is accompanied by persistent Müllerian duct syndrome, where the Müllerian structures persist for various reasons. Here, we present a case of an adult in his early 30s, who presented with a right testicular swelling and was diagnosed as type II TTE and testicular mixed germ cell tumour after surgery. We could find only 13 similar cases of TTE and testicular tumours in the literature. Our case highlights the importance of clinical acumen with detailed history, meticulous clinical examination, radiological investigations and a detailed pathological examination while dealing with such sporadic presentations.
Assuntos
Transtorno 46,XY do Desenvolvimento Sexual , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Testículo , Humanos , Masculino , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/complicações , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Adulto , Testículo/anormalidades , Testículo/cirurgia , Testículo/diagnóstico por imagem , Transtorno 46,XY do Desenvolvimento Sexual/diagnóstico , Transtorno 46,XY do Desenvolvimento Sexual/cirurgia , Transtorno 46,XY do Desenvolvimento Sexual/complicações , Coristoma/cirurgia , Coristoma/diagnóstico , Coristoma/complicações , Coristoma/diagnóstico por imagemRESUMO
BACKGROUND: Candidates for transcatheter aortic valve replacement (TAVR) occasionally have a "borderline-size" aortic annulus between 2 transcatheter heart valve sizes, based on the manufacturer's sizing chart. Data on TAVR outcomes in such patients are limited. METHODS: We retrospectively reviewed 1816 patients who underwent transfemoral-TAVR with balloon-expandable valve (BEV) at our institution between 2016 and 2020. We divided patients into borderline and non-borderline groups based on computed tomography-derived annular measurements and compared outcomes. Furthermore, we analyzed procedural characteristics and compared outcomes between the smaller- and larger-valve strategies in patients with borderline-size annulus. RESULTS: During a median follow-up of 23.3 months, there was no significant difference between the borderline (n = 310, 17.0 %) and non-borderline (n = 1506) groups in mortality (17.3 % vs. 19.5 %; hazard ratio [HR] = 0.86 [95% CI = 0.62-1.20], p = 0.39), major adverse cardiac/cerebrovascular events (MACCE: death/myocardial infarction/stroke, 21.2 % vs. 21.5 %; HR = 0.97 [0.71-1.32], p = 0.85), paravalvular leak (PVL: mild 21.8 % vs. 20.6 %, p = 0.81; moderate 0 % vs. 1.2 %; p = 0.37), or mean gradient (12.9 ± 5.8 vs. 12.6 ± 5.2 mmHg, p = 0.69) at 1 year. There was no significant difference between the larger-(n = 113) and smaller-valve(n = 197) subgroups in mortality (23.7 % vs. 15.2 %; HR = 1.57 [0.89-2.77], p = 0.12), MACCE (28.1 % vs. 18.4 %; HR = 1.52 [0.91-2.54], p = 0.11), mild PVL (13.3 % vs. 25.9 %; p = 0.12), or mean gradient (12.3 ± 4.5 vs. 13.6 ± 5.3 mmHg, p = 0.16); however, the rate of permanent pacemaker implantation (PPI) was higher in the larger-valve subgroup (15.9 % vs. 2.6 %, p < 0.001). CONCLUSION: Borderline-size annulus is not associated with higher risk of adverse outcomes after BEV-TAVR. However, the larger-valve strategy for borderline-size annulus is associated with higher PPI risk, suggesting a greater risk of injury to the conduction system.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Valvuloplastia com Balão , Próteses Valvulares Cardíacas , Desenho de Prótese , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/instrumentação , Substituição da Valva Aórtica Transcateter/mortalidade , Feminino , Masculino , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Resultado do Tratamento , Idoso , Valvuloplastia com Balão/efeitos adversos , Fatores de Risco , Fatores de Tempo , Complicações Pós-Operatórias/etiologia , Medição de Risco , Recuperação de Função Fisiológica , HemodinâmicaRESUMO
Tropomyosin is an actin binding protein which protects actin filaments from cofilin-mediated disassembly. Distinct tropomyosin isoforms have long been hypothesized to differentially sort to subcellular actin networks and impart distinct functionalities. Nevertheless, a mechanistic understanding of the interplay between Tpm isoforms and their functional contributions to actin dynamics has been lacking. In this study, we present acetylation-mimic engineered mNeonGreen-Tpm fusion proteins that exhibit complete functionality as a sole copy, surpassing limitations of existing probes and enabling real-time dynamic tracking of Tpm-actin filaments in vivo. Using these functional Tpm fusion proteins, we find that both Tpm1 and Tpm2 indiscriminately bind to actin filaments nucleated by either formin isoform- Bnr1 and Bni1 in vivo, in contrast to the long-held paradigm of Tpm-formin pairing. We also show that Tpm2 can protect and organize functional actin cables in absence of Tpm1. Overall, our work supports a concentration-dependent and formin-independent model of Tpm-actin binding and demonstrates for the first time, the functional redundancy of the paralog Tpm2 in actin cable maintenance in S. cerevisiae.
RESUMO
Intracellular actin networks assemble through the addition of ATP-actin subunits at the growing barbed ends of actin filaments. This is followed by "aging" of the filament via ATP hydrolysis and subsequent phosphate release. Aged ADP-actin subunits thus "treadmill" through the filament before being released back into the cytoplasmic monomer pool as a result of depolymerization at filament pointed ends. The necessity for aging before filament disassembly is reinforced by preferential binding of cofilin to aged ADP-actin subunits over newly-assembled ADP-Pi actin subunits in the filament. Consequently, investigations into how cofilin influences pointed-end depolymerization have, thus far, focused exclusively on aged ADP-actin filaments. Using microfluidics-assisted Total Internal Reflection Fluorescence (mf-TIRF) microscopy, we reveal that, similar to their effects on ADP filaments, cofilin and cyclase-associated protein (CAP) also promote pointed-end depolymerization of ADP-Pi filaments. Interestingly, the maximal rates of ADP-Pi filament depolymerization by CAP and cofilin together remain approximately 20-40 times lower than for ADP filaments. Further, we find that the promotion of ADP-Pi pointed-end depolymerization is conserved for all three mammalian cofilin isoforms. Taken together, the mechanisms presented here open the possibility of newly-assembled actin filaments being directly disassembled from their pointed-ends, thus bypassing the slow step of Pi release in the aging process.
RESUMO
BACKGROUND: Touch is an essential form of mother-child interaction, instigating better social bonding and emotional stability. METHODS: We used diffuse optical tomography to explore the relationship between total haemoglobin (HbT) responses to affective touch in the child's brain at two years of age and maternal self-reported prenatal depressive symptoms (EPDS). Affective touch was implemented via slow brushing of the child's right forearm at 3 cm/s and non-affective touch via fast brushing at 30 cm/s and HbT responses were recorded on the left hemisphere. RESULTS: We discovered a cluster in the postcentral gyrus exhibiting a negative correlation (Pearson's r = -0.84, p = 0.015 corrected for multiple comparisons) between child HbT response to affective touch and EPDS at gestational week 34. Based on region of interest (ROI) analysis, we found negative correlations between child responses to affective touch and maternal prenatal EPDS at gestational week 14 in the precentral gyrus, Rolandic operculum and secondary somatosensory cortex. The responses to non-affective touch did not correlate with EPDS in these regions. LIMITATIONS: The number of mother-child dyads was 16. However, by utilising high-density optode arrangements, individualised anatomical models, and video and accelerometry to monitor movement, we were able to minimize methodological sources of variability in the data. CONCLUSIONS: The results show that maternal depressive symptoms during pregnancy may be associated with reduced child responses to affective touch in the temporoparietal cortex. Responses to affective touch may be considered as potential biomarkers for psychosocial development in children. Early identification of and intervention in maternal depression may be important already during early pregnancy.