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1.
Heliyon ; 10(7): e27680, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586405

RESUMO

Indonesia, a key player in the global energy transition, faces surging electricity demand and ambitious renewable energy goals. In response, the government introduced a new regulation about renewable energy tariffs, including tariffs for photovoltaic (PV). However, there remains a gap in the academic literature regarding PV power plant feasibility studies under these tariffs. To address this gap, this study investigates the feasibility of a utility-scale solar photovoltaic (PV) power plant in Indonesia, focusing on the newly implemented renewable energy tariffs based on Independent Power Producers (IPPs) and Indonesia's state-owned electricity company (PLN) perspectives. Five scenarios were developed based on the proposed 26 MW solar power plant on Nias Island utilizing RETScreen software. The results showed that based on the IPP perspective, the newly implemented renewable energy tariff was inadequate to make the project feasible, however, an introduction of a 10 USD/t CO2 emission incentive would make the project financially viable for IPPs. Therefore, it is recommended to introduce emission incentives as a strategic approach to attract investors and stimulate investment in Indonesia's PV power plants market, to accelerate Indonesia's energy transition. Conversely, the results also showed that the project is very profitable for PLN due to the significant cost-savings from the de-dieselization, leading to a reduction in the average generation cost for Nias.

2.
Lancet Child Adolesc Health ; 8(6): 433-442, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38640941

RESUMO

BACKGROUND: The main data available on the safety of radiation during pregnancy originate from animal studies and from studies of survivors of atomic or nuclear disasters. The effect of radiotherapy to treat maternal cancer on fetal development is uncertain. This report presents a unique cohort and aims to determine the long-term neurocognitive, psychosocial and physical outcomes of offspring of mothers treated with radiotherapy during pregnancy. METHODS: In this international, multicentre, mixed retrospective-prospective cohort study, we recruited participants between Aug 5, 2006, and Aug 24, 2023, aged between 1·5 and 46 years, at three referral centres in Belgium, the Netherlands, and the USA. Participants were eligible if they were born from mothers treated with radiotherapy during pregnancy. Fetal radiation doses were obtained from medical records and participants were followed up at predefined ages (1·5, 3, 6, 9, 12, 15, and 18 years) and 5-yearly in adulthood, based on age at enrolment, using a neurocognitive test battery (measuring intelligence, attention, and memory), parent-reported executive function and psychosocial questionnaires, and a medical assessment. Results were compared with test-specific normative data. Linear regression models investigated associations between radiotherapy factors (fetal radiation dose, gestational age at the start and end of radiotherapy, and radiotherapy duration) and outcomes. FINDINGS: 68 maternal cases of radiotherapy during pregnancy were registered by the three participating centres, of which 61 resulted in a livebirth and were therefore eligible to participate in the child follow-up study. After excluding those who did not give consent, 43 participants born from 42 mothers treated with radiotherapy during pregnancy were included in the study (median age at first assessment 3 years [IQR 2-11]; median age at last assessment 12 years [9-18]; median number of assessments two [1-4]). 18 (42%) of the included participants were female and 25 (58%) male, and 37 (86%) were of White ethnicity. Mean neurocognitive outcomes of the entire cohort were within normal ranges. No associations were found with fetal radiation dose or timing of radiotherapy during pregnancy. Six (16%) of 38 participants with neurocognitive outcomes scored lower than one SD on at least one neurocognitive outcome, three (7%) reported chronic medical conditions (spasmophilia, spastic diplegia, and IgG deficiency), and three (7%) were diagnosed with attention-deficit hyperactivity disorder (of whom two scored lower on attention). Of ten (23%) participants with lower neurocognitive score(s), a chronic medical condition, or attention-deficit hyperactivity disorder, eight were born preterm. The remaining 33 (77%) participants showed no neurocognitive, psychosocial, or chronic physical problems. INTERPRETATION: We show on average normal neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy. Differences in outcomes could not be explained by exposure to radiotherapy during pregnancy. These results suggest that extra-abdomino-pelvic radiotherapy exposure during pregnancy in general does not adversely affect outcomes of liveborn children. Further research with a larger sample is necessary to confirm these findings. FUNDING: Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Research Foundation Flanders.


Assuntos
Neoplasias , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Gravidez , Adulto , Adolescente , Criança , Masculino , Pré-Escolar , Adulto Jovem , Neoplasias/radioterapia , Neoplasias/psicologia , Lactente , Estudos Retrospectivos , Estudos Prospectivos , Pessoa de Meia-Idade , Radioterapia/efeitos adversos , Países Baixos , Estados Unidos/epidemiologia , Bélgica/epidemiologia
3.
Acta Obstet Gynecol Scand ; 103(4): 757-760, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38419133

RESUMO

The incidence of antenatal cancer is increasing, prompting a medical-ethical evaluation. The International Network on Cancer, Infertility, and Pregnancy (INCIP) was established to study cancer treatment safety during pregnancy and its impact on maternal and child health. Pivotal research has led to a paradigm shift in clinical management, demonstrating the feasibility and safety of most antenatal oncological treatments. Short-term outcomes reveal normal growth and cardiac function in the exposed offspring, but caution is advised against first-trimester chemotherapy. Psychological impact studies highlight the elevated levels of distress in pregnant cancer patients, underscoring the need for personalized information and ongoing psychological support. Long-term follow-up studies address gaps in postnatal impacts, while research into specific chemotherapeutic agents continues. Despite generally reassuring outcomes, continued monitoring is crucial, especially in families, such as those where the child was born premature after cancer (treatment) during pregnancy or where mothers are frequently absent due to continued illness or have died from. The ongoing INCIP child follow-up initiative aims to further elucidate knowledge gaps, emphasizing the importance of large-scale studies and personalized patient care.


Assuntos
Neoplasias , Efeitos Tardios da Exposição Pré-Natal , Criança , Humanos , Gravidez , Feminino , Cuidado Pré-Natal , Mães , Primeiro Trimestre da Gravidez , Neoplasias/terapia
4.
J Hosp Infect ; 141: 49-54, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37385452

RESUMO

INTRODUCTION: Recent reports implicated heater-cooler units (HCUs), which are used for warming infusions, blood or in extracorporeal membrane oxygenation devices, as a possible origin of healthcare-associated infections (HAIs) with potentially pathogenic bacteria, such as non-tuberculous mycobacteria [1]. This represents a source of contamination in a usually sterile setting. AIM: To analyse water from infusion heating devices (IHDs) for bacterial contamination, and to determine if IHDs are a potential source in the transmission of HAIs. METHODS: Thermal transfer fluid (TTF; 300-500 mL) was collected from the reservoirs of 22 independent IHDs and processed on different selective and non-selective media for colony count and identification of bacteria. Strains of Mycobacterium spp. were analysed by whole-genome sequencing. RESULTS: Bacterial growth was observed in all 22 TTF samples after cultivation at 22 °C and 36 °C. Pseudomonas aeruginosa was the most frequent pathogen identified, present in 13.64% (3/22) of samples at >100 colony-forming units/100 mL. Colonization with Mycobacterium chimaera, Ralstonia pickettii and Ralstonia mannitolilytica was detectable in 9.09% (2/22) of samples. Primary sequencing of the detected M. chimaera suggests a close relationship with a M. chimaera strain detected in an outbreak in Switzerland which led to the death of two patients. DISCUSSION: Contamination of TTF represents a germ reservoir in a sensitive setting. Handling errors of IHDs may lead to the distribution of opportunistic or facultative bacterial pathogens, increasing the risk of transmission of nosocomial infections.


Assuntos
Infecção Hospitalar , Infecções por Mycobacterium , Humanos , Infecções por Mycobacterium/epidemiologia , Água , Contaminação de Equipamentos , Microbiologia da Água , Micobactérias não Tuberculosas , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/microbiologia
6.
J Clin Oncol ; 41(8): 1527-1532, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36634293

RESUMO

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.This multicenter cohort study reports on the long-term effects of prenatal exposure to maternal cancer and its treatment on cognitive and behavioral outcomes in 9-year-old children. In total, 151 children (mean age, 9.3 years; range, 7.8-10.6 years) were assessed using a neurocognitive test battery and parent-report behavioral questionnaires. During pregnancy, 109 children (72.2%) were exposed to chemotherapy (only or in combination with other treatment modalities), 18 (11.9%) to surgery only, 16 (10.6%) to radiotherapy, one to trastuzumab, and 16 (10.6%) were not exposed to oncologic treatment. Mean cognitive and behavioral outcomes were within normal ranges. Gestational age at birth showed a positive association with Full Scale Intelligence Quotient (FSIQ), with the average FSIQ score increasing by 1.6 points for each week increase in gestational age (95% CI, 0.7 to 2.5; P < .001). No difference in FSIQ was found between treatment types (F[4,140] = 0.45, P = .776). In children prenatally exposed to chemotherapy, no associations were found between FSIQ and chemotherapeutic agent, exposure level, or timing during pregnancy. These results indicate a reassuring follow-up during the critical maturational period of late childhood, when complex functions develop and rely on the integrity of early brain development. However, associations were observed with preterm birth, maternal death, and maternal education.


Assuntos
Neoplasias , Nascimento Prematuro , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Criança , Humanos , Recém-Nascido , Estudos de Coortes , Estudos Prospectivos , Neoplasias/tratamento farmacológico , Cognição
7.
J Behav Med ; 46(1-2): 179-184, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-34981306

RESUMO

Vaccine hesitancy can impact maternal and child vaccination rates. We examined factors associated with mothers' hesitancy to receive a COVID-19 vaccine using data from an online survey conducted from mid-February to mid-March 2021. Among unvaccinated participants (N = 203), 28% reported that they would probably not or definitely not get a COVID-19 vaccine. Mothers with high school/GED/trade/technical education (38% hesitant, aOR = 4.0, 95% CI: 1.2-13.2), Associate's degree (43%, aOR = 6.8, 95% CI: 2.4-19.5), and Bachelor's degree (30%, aOR = 3.1, 95% CI: 1.1-8.4) were more likely to report vaccine hesitancy compared to mothers with a graduate degree (19%). Non-Hispanic Black mothers (40% hesitant, aOR = 2.8, 95% CI: 1.0-7.6) were more likely to be vaccine hesitant compared to non-Hispanic white mothers (19%). Mothers with low pandemic-related anxiety were more likely to report vaccine hesitancy than mothers with high pandemic-related anxiety (56% vs 23% hesitant; aOR = 4.8, 95% CI: 1.7-14.1). Research is needed to understand informational, emotional, and attitudinal factors contributing to COVID-19 vaccine hesitancy among mothers to develop and test effective public health messaging to increase vaccination rates.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Criança , Feminino , Humanos , COVID-19/prevenção & controle , Ansiedade , Transtornos de Ansiedade , Mães , Vacinação
8.
Infection ; 51(2): 489-495, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36178603

RESUMO

PURPOSE: Raising awareness of respiratory diphtheria and for the importance of early antitoxin administration. METHODS: Report of a case of fulminant, imported respiratory diphtheria in an otherwise healthy 24-year-old Afghan refugee in Austria in May 2022. RESULT: This was the first case of respiratory diphtheria in Austria since 1993. Diphtheria antitoxin was administered at an already progressed disease stage. This delay contributed to a fulminant disease course with multiorgan failure and death. CONCLUSION: In high-income countries with low case numbers, awareness of respiratory diphtheria and for the importance of early antitoxin administration must be raised.


Assuntos
Corynebacterium diphtheriae , Difteria , Refugiados , Humanos , Adulto Jovem , Adulto , Difteria/diagnóstico , Difteria/tratamento farmacológico , Áustria , Antitoxina Diftérica
9.
Lab Anim (NY) ; 51(11): 293-300, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36266512

RESUMO

Post-traumatic stress disorder (PTSD) is a debilitating mental health condition for which current treatments have long-term efficacy in 50% of patients. There is a clear need for better understanding of the mechanisms underlying PTSD and the development of new treatment approaches. Analog trauma procedures in animals, such as the stress-enhanced fear learning (SEFL) procedure, can be used to produce behavioral and neurobiological changes that have validity in modeling PTSD. However, by necessity, the modeling of PTSD in animals requires them to potentially experience pain and suffering. Consistent with the '3Rs' (reduction, refinement and replacement) of animal research, this study aimed to determine whether the SEFL procedure can be refined to reduce potential animal pain and suffering while retaining the same behavioral and neurobiological changes. Here we showed that PTSD-relevant changes could be produced in both behavior and the brain of rats that were group- rather than single-housed and that received lower-magnitude electric shocks in the 'trauma analog' session. We also varied the number of shock exposures in the trauma analog session, finding SEFL-susceptible and SEFL-resilient populations at all levels of shock exposure, but with greater levels of shock increasing the proportion of rats showing the SEFL-susceptible phenotype. These data demonstrate that the SEFL procedure can be used as an animal analog of PTSD with reduced potential pain and suffering to the animals and that variations in the procedure could be used to generate specific proportions of SEFL-susceptible and SEFL-resilient animals in future studies.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Ratos , Animais , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/psicologia , Modelos Animais de Doenças , Medo/psicologia , Aprendizagem , Estresse Psicológico/psicologia , Dor
10.
Crit Rev Oncol Hematol ; 179: 103824, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36174901

RESUMO

Cancer during pregnancy threatens the lives of mother and foetus and its incidence is rising, making it an emerging medical challenge. Evidence on the direct impact of cancer therapies on neonatal outcomes resulted in general guidelines for maternal treatment that safeguards foetal development. Less focus has been placed on indirect factors, in pre- and postnatal periods, that may exert long-term impacts specifically on child neurocognition. Foetal development, in the context of maternal cancer during pregnancy, may be influenced directly by exposure to cancer diagnostics and (co-)treatment, or indirectly through maternal inflammation, malnutrition, hormonal fluctuations, prematurity, and psycho-biological stress. Maternal stress and insecure mother-infant bonding related to postpartum cancer treatment may further impact child cognitive-behavioural development. Understanding the independent and synergistic effects of the factors impacting neurocognitive development creates the opportunity to intervene during the oncological treatment to improve the child's long-term outcome, both by medical and psychosocial care and support.


Assuntos
Neoplasias , Efeitos Tardios da Exposição Pré-Natal , Criança , Feminino , Desenvolvimento Fetal , Feto , Humanos , Lactente , Recém-Nascido , Mães/psicologia , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/terapia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/psicologia
11.
Science ; 376(6597): 1087-1094, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35653469

RESUMO

Structural maintenance of chromosomes (SMC) protein complexes structure genomes by extruding DNA loops, but the molecular mechanism that underlies their activity has remained unknown. We show that the active condensin complex entraps the bases of a DNA loop transiently in two separate chambers. Single-molecule imaging and cryo-electron microscopy suggest a putative power-stroke movement at the first chamber that feeds DNA into the SMC-kleisin ring upon adenosine triphosphate binding, whereas the second chamber holds on upstream of the same DNA double helix. Unlocking the strict separation of "motor" and "anchor" chambers turns condensin from a one-sided into a bidirectional DNA loop extruder. We conclude that the orientation of two topologically bound DNA segments during the SMC reaction cycle determines the directionality of DNA loop extrusion.


Assuntos
Adenosina Trifosfatases , Proteínas de Ligação a DNA , DNA , Complexos Multiproteicos , Adenosina Trifosfatases/química , Microscopia Crioeletrônica , DNA/química , Proteínas de Ligação a DNA/química , Complexos Multiproteicos/química , Conformação de Ácido Nucleico , Imagem Individual de Molécula
12.
J Phys Condens Matter ; 34(15)2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35073536

RESUMO

We report a ferroelectric order around ∼99 K (TFE), which is considerably above the long range ferrimagnetic order at 25 K (TN). The value of saturation electric polarization is considerable as ∼570µC m-2for a poling field of 5 kV cm-1. The ferroelectric order is associated with a significant magnetoelectric coupling below ∼90 K. A weak signature ofTFEis observed in the dielectric constant, which is associated with a linear magnetodielectric response at 18 K(

13.
Psychiatry Res ; 307: 114275, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34847512

RESUMO

In this cross-sectional study we examined whether the prevalence of treatment resistant depression (TRD) can be partly attributed to level of bipolarity. We included data of 201 patients with either episodic depression or TRD, who received treatment for their depression at either an outpatient or 2nd opinion/daytime setting, within a specialised mental healthcare department in the Netherlands. Whether level of TRD, assessed by the 'Dutch Measure for quantification of Treatment Resistance in Depression', can be partly explained by level of bipolarity, assessed by 'the Bipolarity Index', was examined using linear regression. We found no direct association between level of TRD and level of bipolarity, nor did comorbid anxiety disorders obscure an existing association. In this study we found no evidence for overlooked bipolarity contributing to the high prevalence of TRD. If replicated, we could state that additional screening on bipolarity with an instrument such as the 'Bipolarity Index' in the specialised mental health care is unnecessary.


Assuntos
Depressão , Transtorno Depressivo Resistente a Tratamento , Transtornos de Ansiedade/epidemiologia , Estudos Transversais , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/epidemiologia , Transtorno Depressivo Resistente a Tratamento/terapia , Humanos , Prevalência
14.
J Clin Microbiol ; 60(2): e0173721, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-34911367

RESUMO

Clostridioides difficile is the most common cause of antibiotic-associated gastrointestinal infections. Capillary electrophoresis (CE)-PCR ribotyping is currently the gold standard for C. difficile typing but lacks the discriminatory power to study transmission and outbreaks in detail. New molecular methods have the capacity to differentiate better and provide standardized and interlaboratory exchangeable data. Using a well-characterized collection of diverse strains (N = 630; 100 unique ribotypes [RTs]), we compared the discriminatory power of core genome multilocus sequence typing (cgMLST) (SeqSphere and EnteroBase), whole-genome MLST (wgMLST) (EnteroBase), and single-nucleotide polymorphism (SNP) analysis. A unique cgMLST profile (more than six allele differences) was observed in 82 of 100 RTs, indicating that cgMLST could distinguish most, but not all, RTs. Application of cgMLST in two outbreak settings with RT078 and RT181 (known to have low intra-RT allele differences) showed no distinction between outbreak and nonoutbreak strains in contrast to wgMLST and SNP analysis. We conclude that cgMLST has the potential to be an alternative to CE-PCR ribotyping. The method is reproducible, easy to standardize, and offers higher discrimination. However, adjusted cutoff thresholds and epidemiological data are necessary to recognize outbreaks of some specific RTs. We propose to use an allelic threshold of three alleles to identify outbreaks.


Assuntos
Clostridioides difficile , Clostridioides , Clostridioides difficile/genética , Genoma Bacteriano/genética , Humanos , Tipagem de Sequências Multilocus/métodos , Reação em Cadeia da Polimerase , Ribotipagem
15.
Cells ; 10(3)2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806417

RESUMO

Most Cyclin-dependent kinases (Cdks) are redundant for normal cell division. Here we tested whether these redundancies are maintained during cell cycle recovery after a DNA damage-induced arrest in G1. Using non-transformed RPE-1 cells, we find that while Cdk4 and Cdk6 act redundantly during normal S-phase entry, they both become essential for S-phase entry after DNA damage in G1. We show that this is due to a greater overall dependency for Cdk4/6 activity, rather than to independent functions of either kinase. In addition, we show that inactivation of pocket proteins is sufficient to overcome the inhibitory effects of complete Cdk4/6 inhibition in otherwise unperturbed cells, but that this cannot revert the effects of Cdk4/6 inhibition in DNA damaged cultures. Indeed, we could confirm that, in addition to inactivation of pocket proteins, Cdh1-dependent anaphase-promoting complex/cyclosome (APC/CCdh1) activity needs to be inhibited to promote S-phase entry in damaged cultures. Collectively, our data indicate that DNA damage in G1 creates a unique situation where high levels of Cdk4/6 activity are required to inactivate pocket proteins and APC/CCdh1 to promote the transition from G1 to S phase.


Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Dano ao DNA/genética , Fase G1/fisiologia , Humanos , Transfecção
16.
J Phys Condens Matter ; 33(19)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33542167

RESUMO

The compounds, NiSb2O6(NSO) and MnSb2O6(MSO) attract the community for the quasi one-dimensional and layered structure composed of Ni2+and Mn2+, which orders antiferromagnetically atTN= 6.7 and 12 K, respectively. Here, we report the Griffiths-like phase much aboveTNin the range of 37-85 K and 25-80 K for NSO and MSO, respectively. The dc magnetization results indicate the Griffiths-like phase, following the modified Curie-Weiss law. The magneto-capacitive responses for both the compounds show anomalies at the onset of the Griffiths-like phase. Intriguingly, the low temperature synchrotron diffraction results are conclusive for determining the singularities for both the compounds. Interplay between the low-dimensionality, magnetic frustration, and magneto-elastic coupling correlates the observed short range ordered state, which is suggested as a Griffiths-like phase, aboveTNfor both the compounds.

17.
Nature ; 579(7799): 438-442, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32132705

RESUMO

Condensin, a key component of the structure maintenance of chromosome (SMC) protein complexes, has recently been shown to be a motor that extrudes loops of DNA1. It remains unclear, however, how condensin complexes work together to collectively package DNA into chromosomes. Here we use time-lapse single-molecule visualization to study mutual interactions between two DNA-loop-extruding yeast condensins. We find that these motor proteins, which, individually, extrude DNA in one direction only are able to dynamically change each other's DNA loop sizes, even when far apart. When they are in close proximity, condensin complexes are able to traverse each other and form a loop structure, which we term a Z-loop-three double-stranded DNA helices aligned in parallel with one condensin at each edge. Z-loops can fill gaps left by single loops and can form symmetric dimer motors that pull in DNA from both sides. These findings indicate that condensin may achieve chromosomal compaction using a variety of looping structures.


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Ligação a DNA/metabolismo , DNA/química , DNA/metabolismo , Proteínas Motores Moleculares/metabolismo , Complexos Multiproteicos/metabolismo , Conformação de Ácido Nucleico , Conformação Proteica , Saccharomyces cerevisiae , Adenosina Trifosfatases/química , Montagem e Desmontagem da Cromatina , Proteínas Cromossômicas não Histona/química , Proteínas Cromossômicas não Histona/metabolismo , Cromossomos/química , Cromossomos/metabolismo , Proteínas de Ligação a DNA/química , Proteínas Motores Moleculares/química , Complexos Multiproteicos/química , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Imagem Individual de Molécula , Imagem com Lapso de Tempo
18.
Mol Cell ; 74(6): 1175-1188.e9, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31226277

RESUMO

The condensin protein complex plays a key role in the structural organization of genomes. How the ATPase activity of its SMC subunits drives large-scale changes in chromosome topology has remained unknown. Here we reconstruct, at near-atomic resolution, the sequence of events that take place during the condensin ATPase cycle. We show that ATP binding induces a conformational switch in the Smc4 head domain that releases its hitherto undescribed interaction with the Ycs4 HEAT-repeat subunit and promotes its engagement with the Smc2 head into an asymmetric heterodimer. SMC head dimerization subsequently enables nucleotide binding at the second active site and disengages the Brn1 kleisin subunit from the Smc2 coiled coil to open the condensin ring. These large-scale transitions in the condensin architecture lay out a mechanistic path for its ability to extrude DNA helices into large loop structures.


Assuntos
Adenosina Trifosfatases/química , Trifosfato de Adenosina/química , Proteínas de Transporte/química , Chaetomium/genética , Proteínas Cromossômicas não Histona/química , Proteínas de Ligação a DNA/química , DNA/química , Complexos Multiproteicos/química , Proteínas Nucleares/química , Proteínas de Saccharomyces cerevisiae/química , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular , Chaetomium/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Cromossomos/metabolismo , Cromossomos/ultraestrutura , Cristalografia por Raios X , DNA/genética , DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Expressão Gênica , Células HeLa , Humanos , Modelos Moleculares , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
19.
J Phys Condens Matter ; 31(16): 165801, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30681979

RESUMO

We report the zero-field and longitudinal field muon spin relaxation studies in a spin-chain compound Sm2BaNiO5. Two magnetic transitions, that have not been previously detected by the heat capacity and magnetization measurements, are confirmed at 46 and 9 K. The antiferromagnetic order is suggested at 46 K. Analysis of the muon spin polarization unveils the spin-glass transition at 9 K. Time-field scaling relation of the muon spin polarization verifies the spin-spin autocorrelation function following the cut-off power law, which is approximated by the Ogielski form, as employed numerically for characterizing the spin-glasses.

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