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1.
Psychol Trauma ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976387

RESUMO

OBJECTIVE: Bisexual women experience higher rates of sexual assault (SA) and posttrauma distress compared to monosexual women. We examined the patterns of reactions to SA disclosure (positive and two types of negative) and bisexual minority stress (antibisexual stigma from heterosexual and lesbian/gay people, internalized binegativity) experienced by young bisexual women who experienced adult SA. We also examined differences in assault-related experiences, posttraumatic stress disorder and depression symptoms, and hazardous drinking based on the identified patterns. METHOD: The current sample was drawn from two parent samples of women and included survivors who had disclosed an adult SA: (a) n = 149 bisexual women (98% cisgender, ages 18-35, 87.9% White) recruited via Amazon's Mechanical Turk and (b) n = 81 cisgender bisexual women (ages 18-25, 84% White) recruited via online ads. Latent profile analyses and analyses of variance were conducted. RESULTS: Analyses identified four latent profiles characterized by: (a) low stigmatizing responses, (b) high negative SA disclosure reactions, (c) high antibisexual stigma, and (d) highest stigmatizing responses. The fourth profile had higher posttraumatic stress disorder and depression symptoms and hazardous drinking compared to the other profiles. CONCLUSIONS: Results suggest women in the profile characterized by highest negative reactions to SA disclosure and highest bisexual minority stress (antibisexual stigma and internalized binegativity) may experience greatest distress postassault. Results highlight the importance for researchers, policymakers, and clinicians to consider and address both SA-related and identity-related stigma among bisexual survivors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

2.
AIDS ; 38(9): 1412-1423, 2024 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-38742881

RESUMO

BACKGROUND: HIV preexposure prophylaxis (PrEP) has proven to be efficacious and effective in preventing HIV infections, but few studies have reported its impact in the real world. METHODS: We conducted an ecological analysis and compared the trends in HIV PrEP prescriptions with the trends in age-adjusted HIV diagnosis rates in New York City (NYC). Joinpoint regression analyses were used to identify any temporal trends in HIV diagnosis rates in NYC. RESULTS: The number of people filling at least one PrEP prescription in NYC increased from 2551 in 2014 to 35 742 in 2022. The overall age-adjusted HIV diagnosis rate steadily decreased from 48.1 per 100 000 in 2003 to 17.1 per 100 000 in 2022. After the rollout of PrEP, accelerated decreases were detected in some subpopulations including white men [2014-2019 annual percentage change (APC): -16.6%; 95% confidence interval (CI) -22.7 to -10.0], Asian/Pacific Islander men (2016-2022 APC: -9.8%), men aged 20-29 years (2017-2020 APC: -9.4%) and 40 -49 years (2014-2020 APC: -12.2%), Latino/Hispanic people aged 40-49 years (2015-2020 APC: -13.0%), white people aged 20-29 years (2012-2022 APC: -11.4%) and 40-49 years (2014-2018 APC: -27.8%), and Asian/Pacific Islander people aged 20-29 years (2017-2022 APC: -13.0%). CONCLUSION: With a high coverage, PrEP can have a long-term impact in reducing HIV infections in a population, but if preexisting social determinants that contribute to racial, ethnic, and gender inequities are not well addressed, the implementation of PrEP can exacerbate these inequalities.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Profilaxia Pré-Exposição/estatística & dados numéricos , Cidade de Nova Iorque/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Infecções por HIV/diagnóstico , Masculino , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Feminino , Adolescente , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Idoso , Prescrições de Medicamentos/estatística & dados numéricos
3.
Protein Sci ; 33(4): e4924, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38501590

RESUMO

Targeted delivery of small-molecule drugs via covalent attachments to monoclonal antibodies has proved successful in clinic. For this purpose, full-length antibodies are mainly used as drug-carrying vehicles. Despite their flexible conjugation sites and versatile biological activities, intact immunoglobulins with conjugated drugs, which feature relatively large molecular weights, tend to have restricted tissue distribution and penetration and low fractions of payloads. Linking small-molecule therapeutics to other formats of antibody may lead to conjugates with optimal properties. Here, we designed and synthesized ADP-ribosyl cyclase-enabled fragment antigen-binding (Fab) drug conjugates (ARC-FDCs) by utilizing CD38 catalytic activity. Through rapidly forming a stable covalent bond with a nicotinamide adenine dinucleotide (NAD+ )-based drug linker at its active site, CD38 genetically fused with Fab mediates robust site-specific drug conjugations via enzymatic reactions. Generated ARC-FDCs with defined drug-to-Fab ratios display potent and antigen-dependent cytotoxicity against breast cancer cells. This work demonstrates a new strategy for developing site-specific FDCs. It may be applicable to different antibody scaffolds for therapeutic conjugations, leading to novel targeted agents.


Assuntos
Antígenos CD , NAD+ Nucleosidase , ADP-Ribosil Ciclase , ADP-Ribosil Ciclase 1 , Antígenos CD/química , NAD+ Nucleosidase/química , Preparações Farmacêuticas , NAD/química
4.
Data Brief ; 53: 110140, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38357452

RESUMO

The current dataset aims to support and enhance the research reliability of neuromelanin regions in the brainstem, such as locus coeruleus (LC), by offering raw neuromelanin-sensitive images. The dataset includes raw neuromelanin-sensitive images from 157 healthy individuals (8-64 years old). In addition, leveraging individual neuromelanin-sensitive images, a non-linear neuromelanin-sensitive atlas, generated through an iterative warping process, is included to tackle the common challenge of a limited field of view in neuromelanin-sensitive images. Finally, the dataset encompasses a probabilistic LC atlas generated through a majority voting approach with pre-existing multiple atlas-based segmentations. This process entails warping pre-existing atlases onto individual spaces and identifying voxels with a majority consensus of over 50 % across the atlases. This LC probabilistic atlas can minimize uncertainty variance associated with choosing a specific single atlas.

5.
J Appl Gerontol ; : 7334648241230015, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321751

RESUMO

Objective: The current longitudinal study examined how (1) cognitive measures, including episodic memory, executive function, and global cognition, predict later healthcare access and how (2) healthcare access predicts later cognition. Methods: Drawing a sample (n = 9920) from the Health and Retirement Study dataset, we created a cross-lagged panel model to examine the longitudinal association between cognitive measures and healthcare access from 2012 to 2018. Results: Results revealed that cognitive measures significantly predict later healthcare access, with effects increasing across waves. However, within sub-domains, memory was more predictive of later healthcare access over time compared to executive function. Discussions: Our study suggested an increased link between cognition and healthcare access during aging. Even outside of the context of AD, there are likely both policy-based and practical implications to ensure those experiencing cognitive decline continue to maintain access to care.

6.
Clin Psychol Sci ; 12(1): 115-132, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38288008

RESUMO

Sexual-minority adolescents frequently endure peer rejection, yet scant research has investigated sexual-orientation differences in behavioral and neural reactions to peer rejection and acceptance. In a community sample of adolescents approximately 15 years old (47.2% female; same-sex attracted: n = 36, exclusively other-sex attracted: n = 310), we examined associations among sexual orientation and behavioral and neural reactivity to peer feedback and the moderating role of family support. Participants completed a social-interaction task while electroencephalogram data were recorded in which they voted to accept/reject peers and, in turn, received peer acceptance/rejection feedback. Compared with heterosexual adolescents, sexual-minority adolescents engaged in more behavioral efforts to ingratiate after peer rejection and demonstrated more blunted neural reactivity to peer acceptance at low, but not medium or high, levels of family support. By using a simulated real-world social-interaction task, these results demonstrate that sexual-minority adolescents display distinct behavioral and neural reactions to peer acceptance and rejection.

7.
ACS Nano ; 18(4): 3002-3010, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38227309

RESUMO

Silver cations can mediate base pairing of guanine (G) DNA oligomers, yielding linear parallel G-Ag+-G duplexes with enhanced stabilities compared to those of canonical DNA duplexes. To enable their use in programmable DNA nanotechnologies, it is critical to understand solution-state formation and the nanomechanical stiffness of G-Ag+-G duplexes. Using temperature-controlled circular dichroism (CD) spectroscopy, we find that heating mixtures of G oligomers and silver salt above 50 °C fully destabilizes G-quadruplex structures and converts oligomers to G-Ag+-G duplexes. Electrospray ionization mass spectrometry supports that G-Ag+-G duplexes form at stoichiometries of 1 Ag+ per base pair, and CD spectroscopy suggests that as the Ag+/base stoichiometry increases further, G-Ag+-G duplexes undergo additional morphological changes. Using liquid-phase atomic force microscopy, we find that this excess Ag+ enables assembly of long fiberlike structures with ∼2.5 nm heights equivalent to a single DNA duplex but with lengths that far exceed a single duplex. Finally, using the conditions established to form single G-Ag+-G duplexes, we use a surface forces apparatus (SFA) to compare the solution-phase stiffness of single G-Ag+-G duplexes with dG-dC Watson-Crick-Franklin duplexes. SFA shows that G-Ag+-G duplexes are 1.3 times stiffer than dG-dC duplexes, confirming gas-phase ion mobility spectrometry measurements and computational predictions. These findings may guide the development of structural DNA nanotechnologies that rely on silver-mediated base pairing.


Assuntos
Guanina , Prata , Guanina/química , Prata/química , DNA/química , Pareamento de Bases , Temperatura , Conformação de Ácido Nucleico
8.
ACS Nano ; 17(22): 22388-22398, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37947443

RESUMO

MoTe2 can be converted from the semiconducting (2H) phase to the semimetallic (1T') phase by several stimuli including heat, electrochemical doping, and strain. This type of phase transition, if reversible and gate-controlled, could be useful for low-power memory and logic. In this work, a gate-controlled and fully reversible 2H to 1T' phase transition is demonstrated via strain in few-layer suspended MoTe2 field effect transistors. Strain is applied by the electric double layer gating of a suspended channel using a single ion conducting solid polymer electrolyte. The phase transition is confirmed by simultaneous electrical transport and Raman spectroscopy. The out-of-plane vibration peak (A1g)─a signature of the 1T' phase─is observed when VSG ≥ 2.5 V. Further, a redshift in the in-plane vibration mode (E2g) is detected, which is a characteristic of a strain-induced phonon shift. Based on the magnitude of the shift, strain is estimated to be 0.2-0.3% by density functional theory. Electrically, the temperature coefficient of resistance transitions from negative to positive at VSG ≥ 2 V, confirming the transition from semiconducting to metallic. The approach to gate-controlled, reversible straining presented here can be extended to strain other two-dimensional materials, explore fundamental material properties, and introduce electronic device functionalities.

9.
Appl Plant Sci ; 11(5): e11539, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37915436

RESUMO

Premise: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a chemical imaging method that can visualize spatial distributions of particular molecules. Plant tissue imaging has so far mostly used cryosectioning, which can be impractical for the preparation of large-area imaging samples, such as full flower petals. Imaging unsectioned plant tissue presents its own difficulties in extracting metabolites to the surface due to the waxy cuticle. Methods: We address this by using established delipidation techniques combined with a solvent vapor extraction prior to applying the matrix with many low-concentration sprays. Results: Using this procedure, we imaged tissue from three different plant species (two flowers and one carnivorous plant leaf). Material factorization analysis of the resulting data reveals a wide range of plant-specific small molecules with varying degrees of localization to specific portions of the tissue samples, while facilitating detection and removal of signal from background sources. Conclusions: This work demonstrates applicability of MALDI-MSI to press-dried plant samples without freezing or cryosectioning, setting the stage for spatially resolved molecule identification. Increased mass resolution and inclusion of tandem mass spectrometry are necessary next steps to allow more specific and reliable compound identification.


Premisa: Matrix­assisted laser desorption/ionization mass spectrometry imaging (MALDI­MSI) es un método de imagen química que puede visualizar distribuciones espaciales de moléculas particulares. Hasta ahora, las imágenes de tejido vegetal han utilizado principalmente la criosección, lo cual puede ser poco práctico para la preparación de muestras de imágenes con áreas grandes, tales como los pétalos completos de una flor. La obtención de imágenes de tejido vegetal no seccionado presenta sus propias dificultades durante la extracción de metabolitos a la superficie, debido a la cutícula cerosa de la planta. Métodos: Abordamos esto usando técnicas establecidas de deslipidación combinados con una extracción de vapor por solvente antes de aplicar por aspersión la matriz en bajas concentraciones. Resultados: Usando este procedimiento, obtuvimos imágenes de tejido de tres especies de plantas diferentes (dos flores y una hoja de planta carnívora). Análisis de factorización material de los datos obtenidos revelaron una amplia gama de pequeñas moléculas específicas en plantas con diversos grados de localización en porciones específicas de las muestras de tejido, al igual que facilitó la detección y remoción de las señales de fondo. Conclusión: Nuestro trabajo demuestra la aplicabilidad de MALDI­MSI hacía muestras de plantas secadas a presión sin congelación o criosección, creando el marco para la identificación de moléculas resueltas espacialmente. Aumento de la resolución de masas e inclusión de la espectrometría de masas en tándem son pasos necesarios para obtener identificación de compuestos más específica y confiable.

10.
Contemp Clin Trials ; 135: 107381, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37935307

RESUMO

BACKGROUND: The greatest age-related weight gain occurs in the early/mid-20s. Overall dietary quality among adolescents and emerging adults (age 18-25) is poor, with ultra-processed foods (UPF) representing more than two-thirds of adolescents' total energy intake (i.e., 68%). UPF consumption may impact cognitive and neurobiological factors that influence dietary decision-making and energy intake (EI). To date, no research has addressed this in this population. METHODS: Participants aged 18-25 will undergo two 14-day controlled feeding periods (81% UPF, 0% UPF) using a randomly assigned crossover design, with a 4-week washout between conditions. Brain response to a UPF-rich milkshake, as well as behavioral measures of executive function, will be evaluated before and after each diet. Following each diet, measurements include ad libitum buffet meal EI, food selection, eating rate, and eating in the absence of hunger (EAH). Prior to initiating recruitment, controlled diet menus, buffet, and EAH snacks were developed and evaluated for palatability. Sensory and texture attributes of buffet and EAH snack foods were also evaluated. RESULTS: Overall diet palatability was rated "like very much" (8)/"like moderately"(7) (UPF: 7.6 ± 1.0; Non-UPF: 6.8 ± 1.5). Subjective hardness rating (range = 1-9 [1 = soft, 9 = hard] was similar between UPF and Non-UPF buffet and snack items (UPF:4.22 ± 2.19, Non-UPF: 4.70 ± 2.03), as was the objective measure of hardness (UPF: 2874.33 ± 2497.06 g, Non-UPF: 2243.32 ± 1700.51 g). CONCLUSIONS: Findings could contribute to an emerging neurobiological understanding of the effects of UPF consumption including energy overconsumption and weight gain among individuals at a critical developmental stage.


Assuntos
Fast Foods , Alimento Processado , Adolescente , Adulto , Humanos , Adulto Jovem , Dieta , Ingestão de Energia , Aumento de Peso , Estudos Cross-Over
11.
Chem Sci ; 14(41): 11340-11350, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37886084

RESUMO

Near-infrared (NIR) emissive DNA-stabilized silver nanoclusters (AgN-DNAs) are promising fluorophores in the biological tissue transparency windows. Hundreds of NIR-emissive AgN-DNAs have recently been discovered, but their structure-property relationships remain poorly understood. Here, we investigate 19 different far-red and NIR emissive AgN-DNA species stabilized by 10-base DNA templates, including well-studied emitters whose compositions and chiroptical properties have never been reported before. The molecular formula of each purified species is determined by high-resolution mass spectrometry and correlated to its optical absorbance, emission, and circular dichroism (CD) spectra. We find that there are four distinct compositions for AgN-DNAs emissive at the far red/NIR spectral border. These emitters are either 8-electron clusters stabilized by two DNA oligomer copies or 6-electron clusters with one of three different ligand compositions: two oligomer copies, three oligomer copies, or two oligomer copies with additional chlorido ligands. Distinct optical and chiroptical signatures of 6-electron AgN-DNAs correlate with each ligand composition. AgN-DNAs with three oligomer ligands exhibit shorter Stokes shifts than AgN-DNAs with two oligomers, and AgN-DNAs with chlorido ligands have increased Stokes shifts and significantly suppressed visible CD transitions. Nanocluster electron count also significantly influences electronic structure and optical properties, with 6-electron and 8-electron AgN-DNAs exhibiting distinct absorbance and CD spectral features. This study shows that the optical and chiroptical properties of NIR-emissive AgN-DNAs are highly sensitive to nanocluster composition and illustrates the diversity of structure-property relationships for NIR-emissive AgN-DNAs, which could be harnessed to precisely tune these emitters for bioimaging applications.

12.
J Affect Disord ; 340: 649-657, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37591353

RESUMO

BACKGROUND: Offspring of depressed mothers have elevated risk of developing depression because they are exposed to greater stress. While generally assumed that youth's increased exposure to stress is due to the environmental effects of living with a depressed parent, youth's genes may influence stress exposure through gene-environment correlations (rGEs). To understand the relationship between risk for depression and stress, we examined the effects of polygenic risk for depression on youth stress exposure. METHODS: We examined the relations of a polygenic risk score (PRS) for depression (DEP-PRS), as well as PRSs for 5 other disorders, with youth stress exposure. Data were from a longitudinal study of a community sample of youth and their parents (n = 377) focusing on data collected at youth's aged 12 and 15 assessments. RESULTS: Elevated youth DEP-PRS was robustly associated with increased dependent stress, particularly interpersonal events. Exploratory analyses indicated that findings were driven by major stress and were not moderated by maternal nor paternal history of depression, and of the 5 additional PRSs tested, only elevated genetic liability for bipolar I was associated with increased dependent stress-particularly non-interpersonal events. LIMITATIONS: Like other PRS studies, we focused on those of European ancestry thus, generalizability of findings is limited. CONCLUSION: Polygenic risk contributes to youth experiencing stressful life events which are dependent on their behavior. This rGE appears to be specific to genetic risk for mood disorders.


Assuntos
Depressão , Transtornos do Humor , Humanos , Adolescente , Feminino , Depressão/genética , Estudos Longitudinais , Fatores de Risco , Mães
13.
J Cogn Neurosci ; 35(10): 1557-1569, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37584586

RESUMO

The locus coeruleus (LC) is a brainstem region associated with broad neural arousal because of norepinephrine production, but it has increasingly been associated with specific cognitive processes. These include sustained attention, with deficits associated with various neuropsychological disorders. Neural models of attention deficits have focused on interrupted dynamics between the salience network (SAL) with the frontoparietal network, which has been associated with task-switching and processing of external stimuli, respectively. Conflicting findings for these regions suggest the possibility of upstream signaling leading to attention dysfunction, and recent research suggests LC involvement. In this study, resting-state functional connectivity and behavioral performance on an attention task was examined within 584 individuals. Analysis revealed significant clusters connected to LC activity in the SAL. Given previous findings that attention deficits may be caused by SAL network switching dysfunctions, findings here further suggest that dysfunction in LC-SAL connectivity may impair attention.


Assuntos
Locus Cerúleo , Imageamento por Ressonância Magnética , Humanos , Locus Cerúleo/diagnóstico por imagem , Tronco Encefálico , Vias Neurais/diagnóstico por imagem , Nível de Alerta
14.
J Atten Disord ; 27(11): 1272-1283, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37190750

RESUMO

OBJECTIVE: Understanding the association between polygenic risk for ADHD and cognition throughout aging has not been widely studied. This study aimed to determine whether ADHD risk influences cognitive performance among individuals at both young-old and middle-old age. METHOD: Participants from the Health and Retirement Study, a biennial survey of 20,000 Americans, were compared on executive function and delayed recall measures using regression analyses. RESULTS: There was no significant effect of ADHD risk on memory at both age waves for African-ancestry (AA; n = 403) and European-ancestry (EA; n = 2,286). There was, however, a significant association between ADHD risk and performance on executive function for EA at middle-old age (p = .028), but not young-old age; no such association was observed for AA adults. CONCLUSION: This finding suggests that ADHD risk may differentially influence cognition among older adults throughout the aging process, with important implications for future research.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Idoso , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Função Executiva , Cognição , Análise de Regressão
15.
J Am Chem Soc ; 145(19): 10721-10729, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37155337

RESUMO

DNA-stabilized silver nanoclusters (AgN-DNAs) are known to have one or two DNA oligomer ligands per nanocluster. Here, we present the first evidence that AgN-DNA species can possess additional chloride ligands that lead to increased stability in biologically relevant concentrations of chloride. Mass spectrometry of five chromatographically isolated near-infrared (NIR)-emissive AgN-DNA species with previously reported X-ray crystal structures determines their molecular formulas to be (DNA)2[Ag16Cl2]8+. Chloride ligands can be exchanged for bromides, which red-shift the optical spectra of these emitters. Density functional theory (DFT) calculations of the 6-electron nanocluster show that the two newly identified chloride ligands were previously assigned as low-occupancy silvers by X-ray crystallography. DFT also confirms the stability of chloride in the crystallographic structure, yields qualitative agreement between computed and measured UV-vis absorption spectra, and provides interpretation of the 35Cl-nuclear magnetic resonance spectrum of (DNA)2[Ag16Cl2]8+. A reanalysis of the X-ray crystal structure confirms that the two previously assigned low-occupancy silvers are, in fact, chlorides, yielding (DNA)2[Ag16Cl2]8+. Using the unusual stability of (DNA)2[Ag16Cl2]8+ in biologically relevant saline solutions as a possible indicator of other chloride-containing AgN-DNAs, we identified an additional AgN-DNA with a chloride ligand by high-throughput screening. Inclusion of chlorides on AgN-DNAs presents a promising new route to expand the diversity of AgN-DNA structure-property relationships and to imbue these emitters with favorable stability for biophotonics applications.


Assuntos
Cloretos , Prata , Cloretos/química , Prata/química , Ligantes , Cristalografia por Raios X , DNA/química
17.
Biomolecules ; 13(3)2023 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-36979450

RESUMO

Humanin is the first identified mitochondrial-derived peptide. Humanin-G (HNG) is a variant of Humanin that has significantly higher cytoprotective properties. Here, we describe the stability features of HNG in different conditions and characterize HNG degradation, oxidation, and dimerization patterns over short-term and long-term periods. HNG solutions were prepared in high-performance liquid chromatography (HPLC) water or MO formulation and stored at either 4 °C or 37 °C. Stored HNG samples were analyzed using HPLC and high-resolution mass spectrometry (HRMS). Using HPLC, full-length HNG peptides in HPLC water decreased significantly with time and higher temperature, while HNG in MO formulation remained stable up to 95% at 4 °C on day 28. HNG peptides in HPLC water, phosphate-buffered saline (PBS) and MO formulation were incubated at 37 °C and analyzed at day 1, day 7 and day 14 using HRMS. Concentrations of full-length HNG peptide in HPLC water and PBS declined over time with a corresponding appearance of new peaks that increased over time. These new peaks were identified to be singly oxidized HNG, doubly oxidized HNG, homodimerized HNG, singly oxidized homodimerized HNG, and doubly oxidized homodimerized HNG. Our results may help researchers improve the experimental design to further understand the critical role of HNG in human diseases.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Peptídeos , Humanos , Dimerização
18.
Nat Genet ; 55(4): 631-639, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36973455

RESUMO

Cryptic promoters within transposable elements (TEs) can be transcriptionally reactivated in tumors to create new TE-chimeric transcripts, which can produce immunogenic antigens. We performed a comprehensive screen for these TE exaptation events in 33 TCGA tumor types, 30 GTEx adult tissues and 675 cancer cell lines, and identified 1,068 TE-exapted candidates with the potential to generate shared tumor-specific TE-chimeric antigens (TS-TEAs). Whole-lysate and HLA-pulldown mass spectrometry data confirmed that TS-TEAs are presented on the surface of cancer cells. In addition, we highlight tumor-specific membrane proteins transcribed from TE promoters that constitute aberrant epitopes on the extracellular surface of cancer cells. Altogether, we showcase the high pan-cancer prevalence of TS-TEAs and atypical membrane proteins that could potentially be therapeutically exploited and targeted.


Assuntos
Elementos de DNA Transponíveis , Neoplasias , Adulto , Humanos , Elementos de DNA Transponíveis/genética , Antígenos de Neoplasias/genética , Regiões Promotoras Genéticas/genética , Neoplasias/genética , Linhagem Celular
19.
J Consult Clin Psychol ; 91(5): 313-322, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36729515

RESUMO

OBJECTIVE: Prior research has demonstrated that discrimination is associated with suicidal ideation among bi + individuals, but little is known about resilience factors (both general and bi + specific) that may buffer these associations. This prospective study examined the main and interactive effects of antibisexual discrimination and resilience factors, including general resilience and positive bi + identity factors (community, authenticity, and intimacy), in predicting suicidal ideation at 1- and 2-month follow-up. METHOD: Participants were bi + young adults (N = 396; ages 18-29; 42.7% cisgender men, 42.2% cisgender women, 15.2% transgender/gender diverse individuals; 37.9% racial and ethnic minority individuals) who completed measures of antibisexual discrimination (Brief Antibisexual Experiences Scale), positive bi + identity (Lesbian, Gay, and Bisexual Positive Identity Measure), general resilience (Brief Resilience Scale), and suicidal ideation (Beck Scale for Suicide Ideation) at baseline, and suicidal ideation again at 1- and 2-month follow-up. RESULTS: Greater antibisexual discrimination was significantly associated with increases in suicidal ideation at 1-month follow-up at low levels of community, authenticity, and intimacy, and increases in suicidal ideation at 2-month follow-up at low levels of authenticity. In addition, at high levels of authenticity, greater antibisexual discrimination was significantly associated with decreases in suicidal ideation at 1-month follow-up. In contrast, general resilience did not moderate the associations between antibisexual discrimination and suicidal ideation at 1- or 2-month follow-up. CONCLUSIONS: Results suggest that promoting positive aspects of bi + identity (community, authenticity, and intimacy), but not general resilience, may help attenuate the effects of antibisexual discrimination on suicidal ideation over time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Etnicidade , Ideação Suicida , Masculino , Humanos , Feminino , Adulto Jovem , Estudos Prospectivos , Grupos Minoritários , Bissexualidade
20.
Assessment ; 30(8): 2351-2363, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36632642

RESUMO

The objective of the present study was to examine the reliability and validity of a new semi-structured interview for pediatric psychiatric disorders, which is needed as existing interviews do not cover the full range of anxiety, mood, and obsessive-compulsive disorder (OCD)-related disorders. Three hundred eleven child patients (aged 10-17) were administered the Diagnostic Interview for Anxiety, Mood, and OCD and Related Neuropsychiatric Disorders-Child and Adolescent Version (DIAMOND-KID). Of these, 65 provided interrater reliability data and 59 provided test-retest reliability data. Participants also completed self-report measures that assessed symptoms of anxiety, mood, and OCD and related disorders. Although parents/guardians could participate in the interview at the clinician's discretion, most of the initial interviews and all of the reliability interviews were based on the child's self-report. Test-retest reliability ranged from very good to excellent. Interrater reliability was more variable, with estimates for generalized anxiety disorder and major depressive disorder in the questionable range; the other interrater reliability estimates ranged from good to very good. Convergent validity was established by significant between-group comparisons on applicable self-report measures for all diagnoses. The results of the present study indicate that the DIAMOND-KID is a promising semi-structured diagnostic interview for 5th edition of the Diagnostic and Statistical Manual of Mental Disorders in pediatric populations.


Assuntos
Transtorno Depressivo Maior , Transtorno Obsessivo-Compulsivo , Humanos , Adolescente , Transtorno Depressivo Maior/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Psicometria , Reprodutibilidade dos Testes , Escalas de Graduação Psiquiátrica , Transtornos de Ansiedade/diagnóstico , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Ansiedade
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