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Although perceived control is a well-established predictor of cognitive aging, less is known about how and under what developmental circumstances these beliefs about personal influence may protect against cognitive declines. Our study examined light physical activity (LPA) as an unexplored mechanism that may link changes in two facets of perceived control (personal mastery, perceived constraints) to longitudinal trajectories of cognitive functioning. We also examined whether mediated pathways were moderated by age (i.e., differed across the adult lifespan). We analyzed two-wave, 9-year data from the national Midlife in the United States Study (n = 2,456; Mage = 56 years, range = 30-84; 56% female) using autoregressive mediation and moderated mediation models. Mediation models showed that changes in personal mastery and perceived constraints predicted episodic memory and executive functioning via self-reported change in LPA. Only the mediated effects of constraints remained significant in a model that included both mastery and constraints as predictors. Moderated mediation models showed that, for episodic memory, the mediated pathways were strongest in old age and emerged only for constraints: For older but not younger adults, declines in constraints were associated with less decline in episodic memory, as mediated by increases in LPA. Results were consistent in sensitivity analyses that controlled for levels and change in moderate-to-vigorous physical activity. Findings inform lifespan theories of control and provide initial evidence that change in a largely overlooked health behavior (LPA) may underlie the link between perceived constraints and cognitive functioning, with this pathway becoming more pronounced in late life. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Although it is well established that moderate-to-vigorous physical activity (MVPA) buffers against declines in cognitive health, less is known about the benefits of light physical activity (LPA). Research on the role of LPA is crucial to advancing behavioral interventions to improve late life health outcomes, including cognitive functioning, because this form of physical activity remains more feasible and amenable to change in old age. Our study examined the extent to which increases in LPA frequency protected against longitudinal declines in cognitive functioning and whether such a relationship becomes pronounced in old age when opportunities for MVPA are typically reduced. We analyzed 9-year data from the national Midlife in the United States Study (n = 2,229; Mage = 56 years, range = 33-83; 56% female) using autoregressive models that assessed whether change in LPA frequency predicted corresponding changes in episodic memory and executive functioning in middle and later adulthood. Increases in LPA frequency predicted less decline in episodic memory (ß = 0.06, p = .004) and executive functioning (ß = 0.14, p < .001) over the 9-year follow-up period, even when controlling for moderate and vigorous physical activity. Effect sizes for moderate and vigorous physical activity were less than half that observed for LPA. Moderation models showed that, for episodic memory, the benefits of increases in LPA frequency were more pronounced at older ages. Findings suggest that increases in LPA over extended periods of time may help slow age-related cognitive declines, particularly in later life when opportunities for MVPA are often diminished.
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Função Executiva , Exercício Físico , Humanos , Feminino , Exercício Físico/psicologia , Masculino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Função Executiva/fisiologia , Adulto , Memória Episódica , Estudos Longitudinais , Envelhecimento/psicologia , Envelhecimento/fisiologia , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/psicologia , Estados Unidos , CogniçãoRESUMO
OBJECTIVES: New absolute and normalized handgrip strength (HGS) cut-points may not yield similar predictive value for cognitive performance. We sought to determine the associations of (1) each absolute and normalized weakness cut-point, and (2) compounding weakness on future cognitive impairment in older Americans. DESIGN: Longitudinal panel. SETTING AND PARTICIPANTS: The analytic sample included 11,116 participants aged ≥65 years from the 2006 to 2018 waves of the Health and Retirement Study. Participants from the Health and Retirement Study completed detailed interviews that included physical measures and core interviews. METHODS: The modified Telephone Interview of Cognitive Status assessed cognitive function and persons scoring <11 were classified as having a cognitive impairment. A handgrip dynamometer measured HGS. Men were considered weak if their HGS was <35.5 kg (absolute), <0.45 kg/kg (body mass normalized), or <1.05 kg (body mass index normalized), whereas women were classified as weak if their HGS was <20.0 kg, <0.337 kg/kg, or <0.79 kg. Compounding weakness included those below 1, 2, or all 3 cut-points. Generalized estimating equations quantified the associations. RESULTS: Persons considered weak under the absolute cut-point had 1.62 (95% CI 1.34-1.96) greater odds for future cognitive impairment, but no significant associations were observed for those classified as weak under the body mass [odds ratio (OR) 1.12, CI 0.91-1.36] and body mass index normalized (OR 1.17, CI 0.95-1.43) cut-points. Older Americans below all 3 weakness cut-points had 1.47 (CI 1.15-1.88) greater odds for future cognitive impairment, but no significant associations were found for persons classified as weak under 1 (OR 1.08, CI 0.83-1.42) or 2 (OR 1.19, CI 0.91-1.55) cut-points. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that each weakness cut-point has differential prognostic value for future cognitive impairment, and aggregating weakness cut-points may improve their predictive utility. Consideration should be given to how weakness categories are uniquely linked to cognitive function.
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Disfunção Cognitiva , Força da Mão , Masculino , Humanos , Feminino , Idoso , Índice de Massa Corporal , Disfunção Cognitiva/diagnóstico , Cognição , Avaliação GeriátricaRESUMO
Background: Instrumental activities of daily living (IADL) are neuropsychological-driven tasks that are linked to cognitive dysfunction. Examining population-based IADL deficits may reveal insights for the presence of these impairments in the United States. Objective: This investigation sought to evaluate the prevalence and trends of IADL impairments in Americans. Methods: A secondary analysis of data from the 2006-2018 waves of the Health and Retirement Study was conducted. The overall unweighted analytic sample included 29,764 Americans aged≥50 years. Respondents indicated their ability to perform six IADLs: manage money, manage medications, use a telephone, prepare hot meals, shop for groceries, and use a map. Persons reporting difficulty or an inability to complete an individual IADL were considered as having a task-specific impairment. Similarly, those indicating difficulty or an inability to perform any IADL were classified as having an IADL impairment. Sample weights were utilized to generate nationally-representative estimates. Results: Having an impairment in using a map (2018 wave: 15.7% (95% confidence interval (CI): 15.0-16.4) had the highest prevalence in individual IADLs regardless of wave examined. The overall prevalence of IADL impairments declined during the study period (pâ<â0.001) to 25.4% (CI: 24.5-26.2) in the 2018 wave. Older Americans and women had a consistently higher prevalence of IADL impairments compared to middle-aged Americans and men, respectively. The prevalence of IADL impairments was also highest among Hispanics and non-Hispanic Blacks. Conclusion: IADL impairments have declined over time. Continued surveillance of IADLs may help inform cognitive screening, identify subpopulations at risk of impairment, and guide relevant policy.
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BACKGROUND: Older adults with a cognitive impairment, including those not yet diagnosed, may have deficits in their physical function. OBJECTIVE: We sought to determine the associations of cognitive impairment consistent with dementia (CICD) diagnosis status on handgrip strength, gait speed, and functional disability in older adults. METHODS: The analytical sample included 8,383 adults aged ≥65-years without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010-2016 waves of the Health and Retirement Study. A handgrip dynamometer measured handgrip strength. Men with handgrip strength <26âkg and women <16âkg were weak. Gait speed was timed across a 2.5-m course and those with slowness had gait speed <0.8âm/s. Participants with difficulty or an inability in completing any basic activities of daily living had a functional disability. The adapted Telephone Interview of Cognitive Status evaluated cognitive function. Persons with scores <7 had a CICD. Healthcare provider dementia-related diagnosis was self-reported. Undiagnosed CICD was defined as no reported dementia-related diagnosis but had CICD, while diagnosed CICD was classified as reporting a dementia-related diagnosis. Covariate-adjusted logistic models were used for the analyses. RESULTS: Persons with undiagnosed CICD had 1.37 (95% confidence interval (CI): 1.04-1.80) greater odds for weakness and 2.02 (CI: 1.39-2.94) greater odds for slow gait speed. Older adults with diagnosed CICD had 2.29 (CI: 1.32-3.97) greater odds for slowness and 1.85 (CI: 1.19-2.90) greater odds for functional disability. CONCLUSION: Screening for CICD could be recommended when defects in physical function are observed in older adults.
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Disfunção Cognitiva , Demência , Atividades Cotidianas , Idoso , Disfunção Cognitiva/psicologia , Demência/diagnóstico , Demência/epidemiologia , Feminino , Força da Mão , Humanos , Masculino , Velocidade de CaminhadaRESUMO
Electron microscopy of soft and biological materials, or "soft electron microscopy", is essential to the characterization of macromolecules. Soft microscopy is governed by enhancing contrast while maintaining low electron doses, and sample preparation and imaging methodologies are driven by the length scale of features of interest. While cryo-electron microscopy offers the highest resolution, larger structures can be characterized efficiently and with high contrast using low-voltage electron microscopy by performing scanning transmission electron microscopy in a scanning electron microscope (STEM-in-SEM). Here, STEM-in-SEM is demonstrated for a four-lobed protein assembly where the arrangement of the proteins in the construct must be examined. STEM image simulations show the theoretical contrast enhancement at SEM-level voltages for unstained structures, and experimental images with multiple STEM modes exhibit the resolution possible for negative-stained proteins. This technique can be extended to complex protein assemblies, larger structures such as cell sections, and hybrid materials, making STEM-in-SEM a valuable high-throughput imaging method.
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Elétrons , Microscopia Crioeletrônica/métodos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão e Varredura/métodosRESUMO
Introduction: College students experience high levels of depression, anxiety, and stress during the academic year as they juggle the competing demands of young adulthood and their studies. The COVID-19 pandemic heightened this experience. Healthful diets and sleep patterns are associated with improved physical and mental well-being. Purpose: The goal of this study was to identify if there was a relationship between changes in sleep and diet during the COVID-19 pandemic. Methods: A group of college students was surveyed online using Qualtrics software during the first two months of lockdown restrictions at a large, midwestern university in the United States. Results: More participants reported no changes in diet and increased hours of sleep than reported declines or improvements in diet, or reductions or retained sleep patterns. Participants who maintained their diet were likely to maintain their current sleep pattern. Conclusion: College students demonstrated resilience in healthful behaviors during the first two months of COVID-19 lockdown.
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BACKGROUND: Screening for dementia in relevant healthcare settings may help in identifying low cognitive functioning for comprehensive cognitive assessments and subsequent dementia treatment after diagnosis. AIMS: This study sought to estimate the prevalence of no reported dementia-related diagnosis in a nationally-representative sample of older Americans with a cognitive impairment consistent with dementia (CICD) by healthcare utilization. METHODS: The unweighted analytical sample included 1514 Americans aged ≥ 65 years that were identified as having a CICD without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010-2016 waves of the Health and Retirement Study. An adapted Telephone Interview of Cognitive Status assessed cognitive functioning. Those with scores ≤ 6 had a CICD. Dementia-related diagnosis was self-reported. Respondents indicated if they visited a physician, received home healthcare, or experienced an overnight nursing home stay in the previous two years. RESULTS: The prevalence of no reported dementia-related diagnosis in persons with a CICD who visited a physician was 89.9% (95% confidence interval (CI): 85.4%-93.1%). Likewise, the prevalence of no reported diagnosis in those with a CICD who received home healthcare was 84.3% (CI: 75.1-90.5%). For persons with a CICD that had an overnight nursing home stay, the prevalence of no reported dementia-related diagnosis was 83.0% (CI: 69.1-91.4%). DISCUSSION: Although the prevalence of no reported dementia-related diagnosis in individuals with a CICD differed across healthcare settings, the prevalence was generally high nonetheless. CONCLUSIONS: We recommend increased awareness and efforts be given to dementia screenings in various clinical settings.
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Disfunção Cognitiva , Demência , Serviços de Assistência Domiciliar , Idoso , Demência/diagnóstico , Demência/epidemiologia , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Prevalência , Estados Unidos/epidemiologiaRESUMO
The genus Pedioplanis reaches its northernmost limit in western Angola, where it is represented by three species, Pedioplanis benguelensis, P. haackei and P. huntleyi. The taxonomic status of P. benguelensis remains problematic, mainly due to the vague original description and the loss of the original type material. Here we provide a revision of the Angolan representatives of the genus, with the description of a new species, Pedioplanis serodioi sp. nov., from the lowlands of southwestern Angola. Phylogenetic analyses using a combination of mitochondrial (16S and ND2) and nuclear (RAG-1) markers, as well as morphological data, support the recognition of the new species. For purposes of nomenclatural stability, we designate a neotype for P. benguelensis and provide motivation to correct the spelling of the specific epithet to benguelensis. The clarification of the status of P. benguelensis and the description of a new species contribute to a better understanding of the taxonomy and biogeography of the genus Pedioplanis, as well as the general biogeographic context of southwestern Angola, adding to the growing evidence in favor of the recognition of this region as a hotspot of lizard diversity and endemism. An updated key to the genus is also provided.
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Lagartos , Animais , Núcleo Celular , Lagartos/genética , Mitocôndrias , FilogeniaRESUMO
This paper describes the synthesis, characterization, and modeling of a series of molecules having four protein domains attached to a central core. The molecules were assembled with the "megamolecule" strategy, wherein enzymes react with their covalent inhibitors that are substituted on a linker. Three linkers were synthesized, where each had four oligo(ethylene glycol)-based arms terminated in a para-nitrophenyl phosphonate group that is a covalent inhibitor for cutinase. This enzyme is a serine hydrolase and reacts efficiently with the phosphonate to give a new ester linkage at the Ser-120 residue in the active site of the enzyme. Negative-stain transmission electron microscopy (TEM) images confirmed the architecture of the four-armed megamolecules. These cutinase tetramers were also characterized by X-ray crystallography, which confirmed the active-site serine-phosphonate linkage by electron-density maps. Molecular dynamics simulations of the tetracutinase megamolecules using three different force field setups were performed and compared with the TEM observations. Using the Amberff99SB-disp + pH7 force field, the two-dimensional projection distances of the megamolecules were found to agree with the measured dimensions from TEM. The study described here, which combines high-resolution characterization with molecular dynamics simulations, will lead to a comprehensive understanding of the molecular structures and dynamics for this new class of molecules.
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Organofosfonatos , Domínio Catalítico , Cristalografia por Raios X , Estrutura Molecular , Domínios ProteicosRESUMO
OBJECTIVES: To identify factors associated with opioid use after pediatric urologic surgery, use this data to educate our patients and colleagues on decreasing post-operative opioid use, and assess the effectiveness of this approach. METHODS: From 1/2018 - 12/2019, a written questionnaire asking which pain medications were used after surgery was given to patients' families before routine post-operative appointments. A retrospective review of the surveys and patient charts was performed. Demographic factors were compared between patients who did and did not use opioids with Fisher's exact and t tests. Midway through the study, the results were presented to the urology department in an attempt to reduce opioid use over the next year. The number of opioid prescriptions and patients who used opioids after surgery in 2018 versus 2019 was compared. RESULTS: 1001 patients were included with a mean age of 5 years, 96% male. Patients used a mean of 4.5 doses of opioids and 83% had leftover opioids. Factors significantly associated with not using opioids included age less than 3, penile, and endoscopic surgery. Between 2018 and 2019-despite no significant difference in patient age, gender, or procedure type-the number of patients who were prescribed (61% vs 34%, P < .0001) and who used opioids (55 vs 28%, P < .0001) was significantly decreased. CONCLUSION: After pediatric urologic surgery, many patients do not need opioid prescriptions. Reviewing our own opioid use practices and providing education within our department allowed us to significantly decrease the number of opioids prescribed and used after surgery.
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Analgésicos Opioides/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Dor Pós-Operatória/tratamento farmacológico , Procedimentos Cirúrgicos Urológicos , Pré-Escolar , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
(1) Background: Integrated models of primary care deliver the comprehensive and preventative approach needed to identify and manage frailty in older people. Seniors' Community Hub (SCH) was developed to deliver person-centered, evidence-informed, coordinated, and integrated care services to older community dwelling adults living with frailty. This paper aims to describe the SCH model, and to present patient-oriented results of the pilot. (2) Methods: SCH was piloted in an academic clinic with six family physicians. Eligible patients were community dwelling, 65 years of age and older, and considered to be at risk of frailty (eFI > 0.12). Health professionals within the clinic received training in geriatrics and interprofessional teamwork to form the SCH team working with family physicians, patients and caregivers. The SCH intervention consisted of a team-based multi-domain assessment with person-centered care planning and follow-up. Patient-oriented outcomes (EQ-5D-5L and EQ-VAS) and 4-metre gait speed were measured at initial visit and 12 months later. (3) Results: 88 patients were enrolled in the pilot from April 2016-December 2018. No statistically significant differences in EQ-5D-5L/VAS or the 4-metre gait speed were detected in 38 patients completing the 12-month assessment. (4) Conclusions: Future larger scale studies of longer duration are needed to demonstrate impacts of integrated models of primary care on patient-oriented outcomes for older adults living with frailty.
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OBJECTIVE: The aim of this research was to determine the relationships among diabetes, Alzheimer's disease warning signs, and lifestyle factors such as fruit and vegetable intake and physical activity. METHOD: Adults over the age of 50 (N = 147) responded to a survey about their health, family history, and experience of Alzheimer's warning signs in the previous year. RESULTS: Pearson's correlation revealed significant relationships between fruit and vegetable intake and education, gender, and physical activity. Alzheimer's warning signs were associated with relatives having an Alzheimer's disease diagnosis. Other results were nonsignificant. CONCLUSIONS: Diabetes impacts one-third of older adults in the United States and increases the risk of Alzheimer's disease. This survey revealed that women, who are more at risk for Alzheimer's disease, are less likely to engage in physical activity, a behavior that could decrease their risk. Similarly, those with higher education were more likely to consume colorful fruits and vegetables, potentially decreasing their risk of Alzheimer's disease.
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Doença de Alzheimer , Idoso , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/prevenção & controle , Escolaridade , Frutas , Humanos , Fatores de Risco , Estados Unidos , VerdurasRESUMO
OBJECTIVES: Examining strength asymmetries in assessments of muscle function may improve screenings for limitations in independent living tasks such as instrumental activities of daily living (IADL). We sought to determine the associations between handgrip strength (HGS) asymmetry and future IADL limitations in aging Americans. DESIGN: Longitudinal panel. SETTING AND PARTICIPANTS: Secondary analyses of data from participants aged at least 50 years from the 2006-2016 waves of the Health and Retirement Study. The analytic sample included 18,235 Americans who identified hand dominance and had measures of HGS for both hands in a single wave. METHODS: Hand dominance was self-reported, and a handgrip dynamometer measured HGS on each hand. The highest HGS values on each hand were used to calculate the HGS asymmetry ratio: (nondominant HGS/dominant HGS). Individuals with HGS asymmetry ratio <0.80 or >1.20 had HGS asymmetry. Persons with HGS asymmetry ratio <0.80 had dominant HGS asymmetry, whereas participants with HGS asymmetry ratio >1.20 had nondominant HGS asymmetry. Persons with HGS asymmetry ratio <1.0 also had their ratio inversed to make all HGS asymmetry ratios ≥1.0. IADL were self-reported. Covariate-adjusted generalized estimating equations were used for the analyses. RESULTS: Participants with HGS asymmetry had 1.12 [95% confidence interval (CI): 1.03-1.20] greater odds for future IADL limitations. Each HGS asymmetry dominance group also had greater odds for future IADL limitations: 1.09 (CI: 1.01-1.18) for individuals with dominant HGS asymmetry and 1.29 (CI: 1.09-1.52) for persons with nondominant HGS asymmetry. Every 0.10 increase in inverted HGS asymmetry ratio was associated with 1.30 (CI: 1.07-1.57) greater odds for future IADL limitations. CONCLUSIONS AND IMPLICATIONS: Assessing HGS asymmetry, as another potential biomarker of impaired muscle function, may provide novel insights for predicting IADL limitations. Future research should continue examining how strength asymmetries, and other aspects of muscle function beyond maximal strength, factor into the disabling cascade.
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Atividades Cotidianas , Força da Mão , Envelhecimento , Humanos , Aposentadoria , AutorrelatoRESUMO
This paper presents a method to synthetically tune atomically precise megamolecule nanobody-enzyme conjugates for prodrug cancer therapy. Previous efforts to create heterobifunctional protein conjugates suffered from heterogeneity in domain stoichiometry, which in part led to the failure of antibody-enzyme conjugates in clinical trials. We used the megamolecule approach to synthesize anti-HER2 nanobody-cytosine deaminase conjugates with tunable numbers of nanobody and enzyme domains in a single, covalent molecule. Linking two nanobody domains to one enzyme domain improved avidity to a human cancer cell line by 4-fold but did not increase cytotoxicity significantly due to lowered enzyme activity. In contrast, a megamolecule composed of one nanobody and two enzyme domains resulted in an 8-fold improvement in the catalytic efficiency and increased the cytotoxic effect by over 5-fold in spheroid culture, indicating that the multimeric structure allowed for an increase in local drug activation. Our work demonstrates that the megamolecule strategy can be used to study structure-function relationships of protein conjugate therapeutics with synthetic control of protein domain stoichiometry.
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Antineoplásicos/uso terapêutico , Enzimas/química , Pró-Fármacos/uso terapêutico , Anticorpos de Domínio Único/química , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Humanos , Pró-Fármacos/administração & dosagem , Estudo de Prova de Conceito , Relação Estrutura-AtividadeRESUMO
The genus Panaspis in Angola is represented by four species, most of them part of taxonomically and nomenclaturally challenging species-complexes. We present a taxonomic revision of the group in the region and describe one new species, Panaspis mocamedensis sp. nov., endemic to the lowland areas of the Namibe province, southwestern Angola. Phylogenetic analysis using a combination of mitochondrial (16S, cytb) and nucleares (RAG1, PDC) markers, as well as morphological and meristic data support the recognition of the new species. In addition, these data support the presence of nominotypical Panaspis cabindae, P. wahlbergi and P. maculicollis in Angola. Reexamination of the Angolan population of P. breviceps was based on morphological analysis, as no molecular data from Angola is available for this species. According to our results, this population likely represents the nominotypical form, but due to its complex taxonomic and nomenclatural history and the lack of molecular data, this population needs to be reconsidered when molecular data become available. The description of a new species and revision of the Angolan Panaspis contributes to a better understanding of the true species richness of the Angolan herpetofauna, as well as to understanding the major biogeographic patterns of the region. A key to Angolan Panaspis species is also presented.
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Lagartos , Angola , Animais , FilogeniaRESUMO
This paper presents a solid-phase strategy to efficiently assemble multiprotein scaffolds-known as megamolecules-without the need for protecting groups and with precisely defined nanoscale architectures. The megamolecules are assembled through sequential reactions of linkers that present irreversible inhibitors for enzymes and fusion proteins containing the enzyme domains. Here, a fusion protein containing an N-terminal cutinase and a C-terminal SnapTag domain react with an ethyl p-nitrophenyl phosphonate (pNPP) or a chloro-pyrimidine (CP) group, respectively, to give covalent products. By starting with resin beads that are functionalized with benzylguanine, a series of reactions lead to linear, branched, and dendritic structures that are released from the solid support by addition of TEV protease and that have sizes up to approximately 25 nm.
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Hidrolases de Éster Carboxílico/química , Substâncias Macromoleculares/síntese química , Proteínas Recombinantes de Fusão/química , Armina/química , Domínios Proteicos , Técnicas de Síntese em Fase SólidaRESUMO
Under an applied magnetic field, superparamagnetic Fe3 O4 nanoparticles with complementary DNA strands assemble into crystalline, pseudo-1D elongated superlattice structures. The assembly process is driven through a combination of DNA hybridization and particle dipolar coupling, a property dependent on particle composition, size, and interparticle distance. The DNA controls interparticle distance and crystal symmetry, while the magnetic field leads to anisotropic crystal growth. Increasing the dipole interaction between particles by increasing particle size or external field strength leads to a preference for a particular crystal morphology (e.g., rhombic dodecahedra, stacked clusters, and smooth rods). Molecular dynamics simulations show that an understanding of both DNA hybridization energetic and magnetic interactions is required to predict the resulting crystal morphology. Taken together, the data show that applied magnetic fields with magnetic nanoparticles can be deliberately used to access nanostructures beyond what is possible with DNA hybridization alone.
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The Charles R. Drew University of Medicine and Science (CDU) recently celebrated its fiftieth anniversary. The university was established to honor Dr. Charles Richard Drew, a pioneer in blood banking. As a tribute to the legacy of CDU and Dr. Drew, the CDU Health Sciences Library examined how CDU is keeping Dr. Drew's legacy alive.
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Bancos de Sangue/história , Bibliotecas Médicas/história , Universidades/história , História do Século XX , História do Século XXI , Humanos , Masculino , Estados UnidosRESUMO
BACKGROUND: Autologous bone grafts remain the gold standard for craniofacial reconstruction despite limitations of donor-site availability and morbidity. A myriad of commercial bone substitutes and allografts are available, yet no product has gained widespread use because of inferior clinical outcomes. The ideal bone substitute is both osteoconductive and osteoinductive. Craniofacial reconstruction often involves irregular three-dimensional defects, which may benefit from malleable or customizable substrates. "Hyperelastic Bone" is a three-dimensionally printed synthetic scaffold, composed of 90% by weight hydroxyapatite and 10% by weight poly(lactic-co-glycolic acid), with inherent bioactivity and porosity to allow for tissue integration. This study examines the capacity of Hyperelastic Bone for bone regeneration in a critical-size calvarial defect. METHODS: Eight-millimeter calvarial defects in adult male Sprague-Dawley rats were treated with three-dimensionally printed Hyperelastic Bone, three-dimensionally printed Fluffy-poly(lactic-co-glycolic acid) without hydroxyapatite, autologous bone (positive control), or left untreated (negative control). Animals were euthanized at 8 or 12 weeks postoperatively and specimens were analyzed for new bone formation by cone beam computed tomography, micro-computed tomography, and histology. RESULTS: The mineralized bone volume-to-total tissue volume fractions for the Hyperelastic Bone cohort at 8 and 12 weeks were 74.2 percent and 64.5 percent of positive control bone volume/total tissue, respectively (p = 0.04). Fluffy-poly(lactic-co-glycolic acid) demonstrated little bone formation, similar to the negative control. Histologic analysis of Hyperelastic Bone scaffolds revealed fibrous tissue at 8 weeks, and new bone formation surrounding the scaffold struts by 12 weeks. CONCLUSION: Findings from our study suggest that Hyperelastic Bone grafts are effective for bone regeneration, with significant potential for clinical translation.