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1.
Nat Immunol ; 25(6): 1033-1045, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38745085

RESUMO

The etiology and effect of age-related immune dysfunction in cancer is not completely understood. Here we show that limited priming of CD8+ T cells in the aged tumor microenvironment (TME) outweighs cell-intrinsic defects in limiting tumor control. Increased tumor growth in aging is associated with reduced CD8+ T cell infiltration and function. Transfer of T cells from young mice does not restore tumor control in aged mice owing to rapid induction of T cell dysfunction. Cell-extrinsic signals in the aged TME drive a tumor-infiltrating age-associated dysfunctional (TTAD) cell state that is functionally, transcriptionally and epigenetically distinct from canonical T cell exhaustion. Altered natural killer cell-dendritic cell-CD8+ T cell cross-talk in aged tumors impairs T cell priming by conventional type 1 dendritic cells and promotes TTAD cell formation. Aged mice are thereby unable to benefit from therapeutic tumor vaccination. Critically, myeloid-targeted therapy to reinvigorate conventional type 1 dendritic cells can improve tumor control and restore CD8+ T cell immunity in aging.


Assuntos
Envelhecimento , Linfócitos T CD8-Positivos , Células Dendríticas , Microambiente Tumoral , Animais , Microambiente Tumoral/imunologia , Linfócitos T CD8-Positivos/imunologia , Camundongos , Células Dendríticas/imunologia , Envelhecimento/imunologia , Camundongos Endogâmicos C57BL , Células Matadoras Naturais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Humanos , Neoplasias/imunologia , Linhagem Celular Tumoral , Feminino , Ativação Linfocitária/imunologia
2.
Nat Immunol ; 25(10): 1871-1883, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39289557

RESUMO

PD-1 is a key negative regulator of CD8+ T cell activation and is highly expressed by exhausted T cells in cancer and chronic viral infection. Although PD-1 blockade can improve viral and tumor control, physiological PD-1 expression prevents immunopathology and improves memory formation. The mechanisms driving high PD-1 expression in exhaustion are not well understood and could be critical to disentangling its beneficial and detrimental effects. Here, we functionally interrogated the epigenetic regulation of PD-1 using a mouse model with deletion of an exhaustion-specific PD-1 enhancer. Enhancer deletion exclusively alters PD-1 expression in CD8+ T cells in chronic infection, creating a 'sweet spot' of intermediate expression where T cell function is optimized compared to wild-type and Pdcd1-knockout cells. This permits improved control of chronic infection without additional immunopathology. Together, these results demonstrate that tuning PD-1 via epigenetic editing can reduce CD8+ T cell dysfunction while avoiding excess immunopathology.


Assuntos
Linfócitos T CD8-Positivos , Epigênese Genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Morte Celular Programada 1 , Animais , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/genética , Linfócitos T CD8-Positivos/imunologia , Camundongos , Ativação Linfocitária/imunologia , Coriomeningite Linfocítica/imunologia , Coriomeningite Linfocítica/virologia , Elementos Facilitadores Genéticos/genética
3.
PLoS Genet ; 18(6): e1010225, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35704668

RESUMO

Domestication of transposable elements (TEs) into functional cis-regulatory elements is a widespread phenomenon. However, the mechanisms behind why some TEs are co-opted as functional enhancers while others are not are underappreciated. SINE-VNTR-Alus (SVAs) are the youngest group of transposons in the human genome, where ~3,700 copies are annotated, nearly half of which are human-specific. Many studies indicate that SVAs are among the most frequently co-opted TEs in human gene regulation, but the mechanisms underlying such processes have not yet been thoroughly investigated. Here, we leveraged CRISPR-interference (CRISPRi), computational and functional genomics to elucidate the genomic features that underlie SVA domestication into human stem-cell gene regulation. We found that ~750 SVAs are co-opted as functional cis-regulatory elements in human induced pluripotent stem cells. These SVAs are significantly closer to genes and harbor more transcription factor binding sites than non-co-opted SVAs. We show that a long DNA motif composed of flanking YY1/2 and OCT4 binding sites is enriched in the co-opted SVAs and that these two transcription factors bind consecutively on the TE sequence. We used CRISPRi to epigenetically repress active SVAs in stem cell-like NCCIT cells. Epigenetic perturbation of active SVAs strongly attenuated YY1/OCT4 binding and influenced neighboring gene expression. Ultimately, SVA repression resulted in ~3,000 differentially expressed genes, 131 of which were the nearest gene to an annotated SVA. In summary, we demonstrated that SVAs modulate human gene expression, and uncovered that location and sequence composition contribute to SVA domestication into gene regulatory networks.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Elementos de DNA Transponíveis/genética , Redes Reguladoras de Genes/genética , Genômica , Humanos
4.
J Am Chem Soc ; 146(11): 7822-7830, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38456811

RESUMO

Understanding the effects of pressure on actinide compounds is an integral part of safe nuclear waste storage in deep geologic repositories and provides a means of systematically altering the structure and properties. However, detailing how the effects of pressure evolve across the actinide series in the later elements is not typically undertaken because of the challenges of conducting research on these unstable isotopes. Here, a family of bimetallic actinide complexes, [(An(pmtz)2(H2O)3)2(µ-pmtz)]2(pmtz)2·nH2O (An3+ = Cm3+, Bk3+, and Cf3+, pmtz- = 5-(pyrimidyl)tetrazolate; Cm1, Bk1, and Cf1), are reported and represent the first structurally characterized bimetallic berkelium and californium compounds. The pressure response as determined from UV-vis-NIR transitions varies for Cm1, Bk1, and Cf1. The 5f → 5f transitions in Cm1 are notably more sensitive to pressure compared to those in Bk1 and Cf1 and show substantial bathochromic shifting of several 5f → 5f transitions. In the case of Bk1, an ingrowth of a metal-to-ligand charge-transfer transition occurs at elevated pressures because of the accessible Bk3+/Bk4+ couple. For Cf1, no substantial transition shifting or emergence of MLCT transitions is observed at elevated pressures because of the prohibitive energetics of the Cf3+/Cf4+ couple and reduced sensitivity of the 5f → 5f transitions to the local coordination environment because of the more contracted 5f shell versus Cm3+ and Bk3+.

5.
Pediatr Res ; 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39482497

RESUMO

BACKGROUND: Compromised myocardial function and persistent elevated pulmonary vascular resistance are common among neonates treated with therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy (HIE). There is a lack of data regarding persistence of cardiac alterations after discharge from the neonatal intensive care unit (NICU). METHODS: We assessed cardiovascular profiles after NICU discharge. Echocardiogram data, including speckle-tracking echocardiography (STE), were extracted from the latest outpatient scan. Data were compared by initial amplitude-integrated encephalography (aEEG) profiles on admission [normal vs. abnormal]. RESULTS: In total, 70 (19%) neonates had a follow-up echocardiogram (22 with initial normal aEEG, 48 with abnormal aEEG). Age at follow-up was similar between the two groups (6.2 vs. 7.7 months, [p = 0.08]). Neonates with an initially abnormal aEEG showed more negative Right Ventricle (RV)-peak global longitudinal strain (-28.2 vs. -26.0%, [p = 0.02]), RV-peak free wall longitudinal strain rate (-1.24 vs. -1.10 [1/second], [p = 0.01]), and RV-peak free wall longitudinal strain rate (-1.50 vs. -1.27 [1/second], [p = 0.001]). These associations remained after multilinear regression analysis, indicating persistent enhanced RV contraction in the abnormal aEEG group. CONCLUSION: Neonates with initial abnormal aEEG profiles exhibited increased RV contraction after NICU discharge. Future studies should explore long-term cardiovascular follow-up of neonates with HIE, beyond the perinatal period. IMPACT: What is the key message of your article? Cardiac performance in hypoxic ischemic encephalopathy is linked to adverse outcomes. Survivors with an abnormal aEEG at admission showed increased right ventricular contractility at follow-up, possibly related to an adverse adaptation to the initial insult. What does it add to the existing literature? This study offers insights into long-term cardiovascular outcomes in neonates with HIE, focusing on the link between initial aEEG abnormalities and later RV function. What is the impact? The findings underscore the importance of early cardiovascular assessments and monitoring in neonates undergoing TH for HIE, potentially guiding future follow-up protocols.

6.
Inorg Chem ; 63(20): 9237-9244, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38722713

RESUMO

Mixed-donor ligands, such as those containing a combination of O/N or O/S, have been studied extensively for the selective extraction of trivalent actinides, especially Am3+ and Cm3+, from lanthanides during the recycling of used nuclear fuel. Oxygen/sulfur donor ligand combinations also result from the hydrolytic and/or radiolytic degradation of dithiophosphates, such as the Cyanex class of extractants, which are initially converted to monothiophosphates. To understand potential differences between the binding of such degraded ligands to Nd3+ and Am3+, the monothiophosphate complexes [M(OPS(OEt)2)5(H2O)2]2- (M3+ = Nd3+, Am3+) were prepared and characterized by single-crystal X-ray diffraction and optical spectroscopy and studied as a function of pressure up to ca. 14 GPa using diamond-anvil techniques. Although Nd3+ and Am3+ have nearly identical eight-coordinated ionic radii, these structures reveal that while the M-O bond distances in these complexes are almost equal, the M-S distances are statistically different. Moreover, for [Nd(OPS(OEt)2)5(H2O)2]2-, the hypersensitive 4I9/2 → 4G5/2 transition shifts as a function of pressure by -11 cm-1/GPa. Whereas for [Am(OPS(OEt)2)5(H2O)2]2-, the 7F0 → 7F6 transition shows a slightly stronger pressure dependence with a shift of -13 cm-1/GPa and also exhibits broadening of the 5f → 5f transitions at high pressures. These data likely indicate an increased involvement of the 5f orbitals in bonding with Am3+ relative to that of Nd3+ in these complexes.

7.
Inorg Chem ; 63(2): 1266-1273, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38165641

RESUMO

The salt metathesis reaction of Na(pmtz)·H2O [pmtz- = 5-(pyrimidyl)tetrazolate] and PuBr3·nH2O in an aqueous media leads to the formation of the mononuclear compound [Pu(pmtz)3(H2O)3]·(3 + n) H2O (Pu1, n = ∼8) that is isotypic with the lanthanide compounds [Ln(pmtz)3(H2O)3]·(3 + n) H2O (Ln = Ce-Nd). Dissolution and recrystallization of Pu1 in water yields the dinuclear compound {[Pu(pmtz)2(H2O)3]2(µ-pmtz)}2(pmtz)2·14H2O (Pu2), which is isotypic with the lanthanide compounds {[Ln(pmtz)2(H2O)3]2(µ-pmtz)}2(pmtz)2·14H2O (Ln = Nd and Sm). Like their nine-coordinate ionic radii, the M-O and M-N bond lengths in Pu1/Pu2 and Nd1/Nd2, respectively, are within error of one another. The Laporte-forbidden 4f → 4f and 5f → 5f transitions are also assigned in the UV-vis-NIR spectra for these f-element tetrazolate coordination compounds.

8.
Mycoses ; 67(8): e13780, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39132817

RESUMO

BACKGROUND: Invasive fungal diseases (IFD) are high morbidity and mortality infections in children with cancer suffering episodes of high-risk febrile neutropenia (HRFN). IFD epidemiology has changed in the last two decades, with an increasing incidence in recent years due to the growing number of immunocompromised children at risk for IFD. The aim of this study was to evaluate the incidence of IFD in children with cancer in the period 2016-2020 compared to 2004-2006 in six hospitals in Chile. METHODS: Prospective, multicentre study, carried out between 2016 and 2020 in six hospitals in Chile. The defined cohort corresponds to a dynamic group of HRFN episodes in patients <18 years old with cancer, who at the fourth day of evolution still presented fever and neutropenia (persistent HRFN). Each episode was followed until resolution of FN. The incidence of IFD was calculated between 2016 and 2020 and compared with data obtained in the period 2004-2006. The incidence rate was estimated. RESULTS: A total of 777 episodes of HRFN were analysed; 257 (33.1%) were considered as persistent-HRFN occurring in 174 patients. The median age was 7 years (IQR: 3-12 years) and 52.3% (N = 91) were male. Fifty-three episodes of IFD were detected: 21 proven, 14 probable and 18 possible. Possible IFD were excluded, leaving 239 episodes of persistent-HRFN with an IFD incidence of 14.6% (95% CI 10.5-19.9) and an incidence rate of 13.6 IFD cases per 1000 days of neutropenia (95% CI 9.5-20.0). Compared to 2004-2006 cohort (incidence: 8.5% (95% CI 5.2-13.5)), a significant increase in incidence of 6.1% (95% CI 0.2-12.1, p = .047) was detected in cohorts between 2016 and 2020. CONCLUSION: We observed a significant increase in IFD in 2016-2020, compared to 2004-2006 period.


Assuntos
Infecções Fúngicas Invasivas , Neoplasias , Humanos , Chile/epidemiologia , Masculino , Estudos Prospectivos , Criança , Feminino , Pré-Escolar , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/tratamento farmacológico , Neoplasias/epidemiologia , Neoplasias/complicações , Incidência , Hospedeiro Imunocomprometido , Adolescente , Lactente , Antineoplásicos/uso terapêutico
9.
Proc Natl Acad Sci U S A ; 118(7)2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33574059

RESUMO

Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to 5 kg) body size. We assemble and annotate a de novo reference genome for Cebus imitator Through high-depth sequencing of DNA derived from blood, various tissues, and feces via fluorescence-activated cell sorting (fecalFACS) to isolate monkey epithelial cells, we compared genomes of capuchin populations from tropical dry forests and lowland rainforests and identified population divergence in genes involved in water balance, kidney function, and metabolism. Through a comparative genomics approach spanning a wide diversity of mammals, we identified genes under positive selection associated with longevity and brain development. Additionally, we provide a technological advancement in the use of noninvasive genomics for studies of free-ranging mammals. Our intra- and interspecific comparative study of capuchin genomics provides insights into processes underlying local adaptation to diverse and physiologically challenging environments, as well as the molecular basis of brain evolution and longevity.


Assuntos
Adaptação Fisiológica , Encéfalo/crescimento & desenvolvimento , Cebus/genética , Genoma , Longevidade/genética , Animais , Evolução Molecular , Citometria de Fluxo/métodos , Florestas , Genômica/métodos
10.
Am J Perinatol ; 41(15): 2098-2108, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38569505

RESUMO

OBJECTIVE: Fetal diagnosis of coarctation of the aorta (CoA) is currently associated with a high false-positive rate. Many predictive markers may be gestational age (GA)-specific. We sought to establish GA-specific traditional and speckle-tracking fetal echocardiography (STE) markers predictive of true CoA in neonates with prenatal suspicion. STUDY DESIGN: This is a retrospective case-control study. We compared the fetal ventricular and arch dimensions, as well as the deformation parameters by STE, of infants who required a postnatal intervention for their CoA with those who did not. Cohort was stratified based on GA before or after 30 weeks. Data extractors were masked to the outcome. The first fetal echocardiogram available was used. RESULTS: Seventy-five newborns with a fetal echocardiography performed between October 2013 and May 2022 for an antenatal suspicion of CoA were included, of which 59 (79%) had an aortic arch with nonsignificant obstruction upon ductal closure, and 16 (21%) underwent a neonatal intervention for a confirmed CoA. Before 30 weeks' GA, the right ventricular to left ventricular (RV/LV) end-diastolic width and end-diastolic area (EDA) ratios were most associated with postnatal CoA confirmation (area under the curve [AUCs] = 0.96 and 0.92). After 30 weeks' GA, the RV/LV end-diastolic width ratio (AUC = 0.95), the Z-score for the ascending aorta (AUC = 0.93), and the LV end-diastolic width Z-score (AUC = 0.91) performed the best. A decreased RV peak longitudinal strain was observed in those who developed true CoA and performed well by receiver operating characteristic analysis after 30 weeks (AUC = 0.85). In the overall cohort, the RV/LV EDA ratio was the most sensitive predictor of CoA and identified all cases with CoA. Indeed, a cutoff > 1.24 had a specificity of 69.5% and a sensitivity of 100% (receiver operating characteristic curve with an AUC of 0.88). CONCLUSION: We outlined sensitive and specific fetal markers associated with postnatal CoA based on GA at suspicion. KEY POINTS: · Fetal ventricular disproportion predicts postnatal coarctation.. · A decreased right ventircular contraction was observed in those with coarctation.. · Fetal markers differ based on gestational age at fetal evaluation..


Assuntos
Coartação Aórtica , Ecocardiografia , Idade Gestacional , Ultrassonografia Pré-Natal , Humanos , Coartação Aórtica/diagnóstico por imagem , Estudos Retrospectivos , Feminino , Recém-Nascido , Estudos de Casos e Controles , Gravidez , Masculino , Ventrículos do Coração/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Curva ROC
11.
J Fish Biol ; 104(6): 1698-1708, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38420688

RESUMO

Knowledge of thermal tolerance limits provides important clues to the capacity of a species to withstand acute and chronic thermal changes. Climate models predict the increase and intensification of events such as heat waves, therefore understanding the upper thermal limits that a species can tolerate has become of utmost importance. We measured the upper thermal tolerance of the endemic Magdalena river stingray Potamotrygon magdalenae acclimated to experimental conditions, and then used critical thermal methodology to find the temperature at which an organism reaches a critical endpoint where locomotory activity becomes disorganized and the animal loses its ability to escape from conditions that will promptly lead to its death. We also describe the behavioral response of individuals to acute thermal stress and infer the possible consequences of temperature increases in the habitats of P. magdalenae populations. There were no significant differences between sexes in temperature tolerance or behavior. The critical thermal maximum (39°C) was 5.9°C above the maximum recorded temperature for the study area. Although P. magdalenae was tolerant to high temperature and currently is not living at its upper thermal limit, its survival in Guarinocito Pond will be threatened if temperatures continue to increase, considering the warming scenarios predicted for tropical regions due to climate change, even including short-term climate phenomena such as El Niño.


Assuntos
Rajidae , Animais , Masculino , Rajidae/fisiologia , Feminino , Rios , Termotolerância , Temperatura , Temperatura Alta , Comportamento Animal , Aclimatação
12.
Nurs Ethics ; : 9697330241295376, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39437538

RESUMO

BACKGROUND: Challenging false beliefs are common situations among people living with dementia. They frequently imply time-shifts, that is, situations in which the person re-lives past experiences. Since they have emotional implications and important ethical implications, they are difficult to manage by caregivers, who are faced with the decision of telling or not telling the truth. AIMS: The study aimed to explore professional staff's perceptions of common and best practices to manage a situation in which a person living with dementia is having a false belief, specifically a time-shift. The study compares technical staff's and assistant carers' responses. PARTICIPANTS AND RESEARCH CONTEXT: Forty-two staff members working in four Spanish long-term care facilities were interviewed. 21 were assistant carers and 21 were technical staff. RESEARCH DESIGN: This study involved a qualitative design, content-analyzing participant's responses to semi-structured interviews. Participants read a vignette about a person living with dementia having a time-shift and were asked (1) how a situation like that is commonly managed and (2) how it should be managed. ETHICAL CONSIDERATIONS: The principles of informed consent, confidentiality, and assessment of consequences for participants were observed throughout the entire study, which was approved by the University of Barcelona Ethics Committee (IRB 00003099). Written participant's consent was obtained prior to interviews. FINDINGS: All the participants mentioned having experienced a situation similar to that described in the vignette. In the case of common practices, lying was the most frequently mentioned strategy. As for best practices, lying and telling the truth were mentioned as well as responses that lie in-between, such as distracting or relaxing. However, most assistant carers reported that they do not know how a challenging false belief should be managed. CONCLUSION: Our findings stress the importance of organizational guidelines and staff development in the management of challenging false beliefs (and specifically time-shifts) in PLWD.

13.
Chromosoma ; 131(3): 147-161, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35511360

RESUMO

In the Brassica genus, we find both diploid species (one genome) and allotetraploid species (two different genomes) but no naturally occurring hexaploid species (three different genomes, AABBCC). Although hexaploids can be produced via human intervention, these neo-polyploids have quite unstable genomes and usually suffer from severe genome reshuffling. Whether these genome rearrangements continue in later generations and whether genomic arrangements follow similar, reproducible patterns between different lineages is still unknown. We crossed Brassica hexaploids resulting from different species combinations to produce five F1 hybrids and analyzed the karyotypes of the parents and the F1 hybrids, as well as allele segregation in a resulting test-cross population via molecular karyotyping using SNP array genotyping. Although some genomic regions were found to be more likely to be duplicated, deleted, or rearranged, a consensus pattern was not shared between genotypes. Brassica hexaploids had a high tolerance for fixed structural rearrangements, but which rearrangements occur and become fixed over many generations does not seem to show either strong reproducibility or to indicate selection for stability. On average, we observed 10 de novo chromosome rearrangements contributed almost equally from both parents to the F1 hybrids. At the same time, the F1 hybrid meiosis produced on average 8.6 new rearrangements. Hence, the increased heterozygosity in the F1 hybrid did not significantly improve genome stability in our hexaploid hybrids and might have had the opposite effect. However, hybridization between lineages was readily achieved and may be exploited for future genetics and breeding purposes.


Assuntos
Brassica , Alelos , Brassica/genética , Cromossomos de Plantas/genética , Genoma de Planta , Hibridização Genética , Melhoramento Vegetal , Poliploidia , Reprodutibilidade dos Testes
14.
Mol Biol Evol ; 39(2)2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34971383

RESUMO

Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested. We analyzed dN/dS rates, positive selection, gene expression (RNA-seq), and gene regulation (ChIP-seq). By analyzing the correlation between dN/dS, maximum lifespan, and body mass, we identified 276 genes whose rate of evolution positively correlates with maximum lifespan in primates. Further, we identified five genes, important for tumor suppression, adaptive immunity, metastasis, and inflammation, under positive selection exclusively in the great ape lineage. RNA-seq data, generated from the liver of six species representing all the primate lineages, revealed that 8% of approximately 1,500 genes previously associated with longevity are differentially expressed in apes relative to other primates. Importantly, by integrating RNA-seq with ChIP-seq for H3K27ac (which marks active enhancers), we show that the differentially expressed longevity genes are significantly more likely than expected to be located near a novel "ape-specific" enhancer. Moreover, these particular ape-specific enhancers are enriched for young transposable elements, and specifically SINE-Vntr-Alus. In summary, we demonstrate that multiple evolutionary forces have contributed to the evolution of lifespan and body size in primates.


Assuntos
Hominidae , Longevidade , Animais , Evolução Molecular , Hominidae/genética , Longevidade/genética , Primatas/genética , Sequências Reguladoras de Ácido Nucleico
15.
J Pediatr ; 261: 113585, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37354991

RESUMO

We evaluated the association between left cardiac 3-dimensional echocardiographic parameters and brain injury in a single-center prospective study of neonates with neonatal encephalopathy. On day 2 of life, neonates with brain injury had greater left ventricle end-diastolic and stroke volume but also greater peak global circumferential strain detected by 3-dimensional echocardiogram.


Assuntos
Lesões Encefálicas , Ecocardiografia Tridimensional , Disfunção Ventricular Esquerda , Recém-Nascido , Humanos , Lactente , Função Ventricular Esquerda , Estudos Prospectivos , Ecocardiografia/métodos , Ecocardiografia Tridimensional/métodos , Volume Sistólico , Ventrículos do Coração/diagnóstico por imagem , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem
16.
J Pediatr ; 257: 113369, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36868306

RESUMO

OBJECTIVES: To compare trends in the anterior cerebral artery (ACA) Doppler markers of vascular flow for neonates with a congenital heart defect (CHD) with and without diastolic systemic steal during the first 7 days of life. METHODS: Prospective study recruiting newborns (≥35 weeks of gestation) with a CHD. Doppler ultrasound and echocardiography were performed daily from day 1 to 7. The cohort was divided into the presence/absence of holo-diastolic retrograde flow in the postductal aorta ("retrograde") on the last-available echocardiogram. Data extractors were masked to retrograde status. Mixed effect models (random slope/intercept) were constructed using RStudio. RESULTS: We enrolled 38 neonates with CHD. Retrograde aortic flow was present on the last echocardiogram in 23 (61%). Peak systolic velocity and mean velocity increased significantly over time, independent of retrograde status. However, having a "retrograde" flow status conferred a significant decrease over time of their ACA-end-diastolic velocity (ß = -5.75 cm/s, 95% CI -8.38 to -3.12, P < .001, when compared with the nonretrograde group), and a significant increase in the ACA resistive (ß = 0.16, 95% CI 0.10-0.22, P < .001) and pulsatility (ß = 0.49, 95% CI 0.28-0.69, P < .001) indexes. No subject presented retrograde diastolic flow in the ACA. CONCLUSIONS: In neonates with CHD in the first week of life, infants with echocardiographic signs of systemic diastolic steal within the pulmonary circulation have Doppler signs of cerebrovascular steal in the ACA.


Assuntos
Circulação Cerebrovascular , Cardiopatias Congênitas , Lactente , Recém-Nascido , Humanos , Estudos Prospectivos , Velocidade do Fluxo Sanguíneo , Cardiopatias Congênitas/diagnóstico por imagem , Ultrassonografia Doppler
17.
Inorg Chem ; 62(38): 15375-15381, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37700461

RESUMO

High external pressure is found to induce a non-coordinated water molecule to bond to cerium in a previously studied mellitate coordination polymer, as determined by high-pressure single-crystal X-ray diffraction, resulting in a coordination number transition at 3.85 GPa from 9 to 9.5 where half the cerium ions are 10-coordinate. Also, bond length changes due to increased pressure are experimentally measured, whereas the cerium-carboxylate bond lengths overall change by -0.004(9) Å/GPa, the cerium-water bonds by -0.016(3) Å/GPa, and cerium-oxygen bonds overall by -0.010(6) Å/GPa, which corresponds well with theoretical bond length decreases determined for similar compounds. The high-pressure absorbance spectra of the analogous neodymium mellitate are examined and compared with the structural changes observed.

18.
Inorg Chem ; 62(32): 12905-12912, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37523261

RESUMO

N,N,N',N'-tetramethyl diglycolamide (TMDGA), a methylated variant of the diglycolamide extractants being proposed as curium holdback reagents in advanced used nuclear fuel reprocessing technologies, has been crystallized with plutonium, a transuranic actinide that has multiple accessible oxidation states. Two plutonium TMDGA complexes, [PuIII(TMDGA)3][PuIII(NO3)6] and[PuIV(TMDGA)3][PuIV(NO3)6]2·0.75MeOH, were crystallized through solvent diffusion of a reaction mixture containing plutonium(III) nitrate and TMDGA. The sample was then partially oxidized by air to yield [PuIV(TMDGA)3][PuIV(NO3)6]2·0.75MeOH. Single-crystal X-ray diffraction reveals that the multinuclear systems crystallize with hexanitrato anionic species, providing insight into the first solid-state isolation of the elusive trivalent plutonium hexanitrato species. Crystallography data show a change in geometry around the TMDGA metal center from Pu3+ to Pu4+, with the symmetry increasing approximately from C4v to D3h. These complexes provide a rare opportunity to investigate the bond metrics of plutonium in two different oxidation states with similar coordination environments. Further, these new structures provide insight into the potential chemical and structural differences arising from the radiation-induced formation of transient tetravalent curium oxidation states in used nuclear fuel reprocessing streams.

19.
Inorg Chem ; 62(22): 8478-8481, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37210659

RESUMO

The crystallization, single crystal structure, and Raman spectroscopy of Ra(NO3)2 have been investigated by experimentation and theory, which represent the first pure radium compound characterized by single crystal X-ray diffraction. The Ra2+ centers are bound by six chelating nitrate anions to form an anticuboctahedral geometry. The Raman spectrum acquired from a single crystal of Ra(NO3)2 generally occurs at a lower frequency than found in Ba(NO3)2, as expected. Computational studies on Ra(NO3)2 provide an estimation of the bond orders via Wiberg bond indices and indicate that Ra-O interactions are weak with values of 0.025 and 0.026 for Ra-O bonds. Inspection of natural bond orbitals and natural localized molecular orbitals suggest negligible orbital mixing. However, second-order perturbation interactions show that donation from the lone pairs of the nitrate oxygen atoms to the 7s orbitals of Ra2+ stabilizes each Ra-O interaction by ca. 5 kcal mol-1.

20.
Environ Sci Technol ; 57(15): 6296-6308, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37014786

RESUMO

The tendency of organic contaminants (OCs) to partition between different phases is a key set of properties that underlie their human and ecological health impacts and the success of remediation efforts. A significant challenge associated with these efforts is the need for accurate partitioning data for an ever-expanding list of OCs and breakdown products. All-atom molecular dynamics (MD) simulations have the potential to help generate these data, but existing studies have applied these techniques only to a limited variety of OCs. Here, we use established MD simulation approaches to examine the partitioning of 82 OCs, including many compounds of critical concern, at the water-air interface. Our predictions of the Henry's law constant (KH) and interfacial adsorption coefficients (Kiw, Kia) correlate strongly with experimental results, indicating that MD simulations can be used to predict KH, Kiw, and Kia values with mean absolute deviations of 1.1, 0.3, and 0.3 logarithmic units after correcting for systematic bias, respectively. A library of MD simulation input files for the examined OCs is provided to facilitate future investigations of the partitioning of these compounds in the presence of other phases.


Assuntos
Simulação de Dinâmica Molecular , Água , Humanos
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