RESUMO
Recent structural and functional characterization of the pseudoknot in the Saccharomyces cerevisiae telomerase RNA (TLC1) has demonstrated that tertiary structure is present, similar to that previously described for the human and Kluyveromyces lactis telomerase RNAs. In order to biophysically characterize the identified pseudoknot secondary and tertiary structures, UV-monitored thermal denaturation experiments, nuclear magnetic resonance spectroscopy, and native gel electrophoresis were used to investigate various potential conformations in the pseudoknot domain in vitro, in the absence of the telomerase protein. Here, we demonstrate that alternative secondary structures are not mutually exclusive in the S. cerevisiae telomerase RNA, tertiary structure contributes 1.5 kcal mol(-1) to the stability of the pseudoknot (≈ half the stability observed for the human telomerase pseudoknot), and identify additional base pairs in the 3' pseudoknot stem near the helical junction. In addition, sequence conservation in an adjacent overlapping hairpin appears to prevent dimerization and alternative conformations in the context of the entire pseudoknot-containing region. Thus, this work provides a detailed in vitro characterization of the thermodynamic features of the S. cerevisiae TLC1 pseudoknot region for comparison with other telomerase RNA pseudoknots.
Assuntos
RNA/química , RNA/metabolismo , Saccharomyces cerevisiae/metabolismo , Telomerase/química , Telomerase/metabolismo , Termodinâmica , Pareamento de Bases , Sequência de Bases , Dimerização , Sequências Repetidas Invertidas , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Estabilidade de RNA , Cloreto de Sódio/química , Soluções/química , Temperatura de TransiçãoRESUMO
BACKGROUND: Suicide is a major public health concern. The elderly have the highest rate of suicide and they make more lethal suicide attempts and have fewer psychiatric interventions than young people. Furthermore, they have old-age specific psychosocial difficulties. The present study investigated psychosocial risk factors and characteristics of an index suicide attempt of the elderly suicide attempters. METHODS: Subjects included 388 patients who were admitted to the emergency room following self-poisoning. Two age groups were defined: younger patients (aged less than 65 years) and older patients (aged over 65 years). Data including demographic factors, suicidal risk factors and information about the current suicide attempt were obtained from a retrospective chart review. RESULTS: The number of suicide attempters over the age of 65 years old was 57, and their mean age was 73.5 ± 7.5 years. The elderly patients had more underlying medical illnesses than the under-65 group (p < 0.001). Depression was the most common psychiatric diagnosis. Psychotropics were the most commonly ingested drugs in both groups, but the use of pesticides was more notable in the elderly. The elderly suicide attempters had higher risk-rating scores (p < 0.001) and lower rescue-rating scores (p = 0.014) than the under-65 group. Male-to-female ratio of the elderly group was nearly 1:1 unlike the under-65 group (p = 0.004). CONCLUSION: Elderly suicide attempters had different psychosocial stressors such as physical illness and more lethal suicide attempts. Our study suggests the need for development of specific preventive strategies and management guidelines for the elderly suicide attempters.
Assuntos
Intoxicação/psicologia , Adulto , Fatores Etários , Idoso , Depressão/psicologia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Intoxicação/epidemiologia , Intoxicação/etiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Estresse Psicológico/complicações , Estresse Psicológico/psicologia , Tentativa de SuicídioRESUMO
This study employed a hierarchical linear model analysis to examine the effects of ego depletion and state anxiety on performance changes in golf putting. We randomly assigned 51 female college students with no previous golf putting experience to either an ego-depletion (experimental) group (n = 26) or a non-ego-depletion (control) group (n = 25). Putting performance changes over repeated trials displayed a quadratic curve, and both ego depletion and state anxiety exerted negative effects on early, but not late, putting performance. Contrary to previous findings, the interaction effect between ego depletion and state anxiety on performance was nonsignificant.
Assuntos
Ansiedade/psicologia , Ego , Golfe , Desempenho Psicomotor , Autocontrole/psicologia , Feminino , Humanos , Modelos Lineares , Personalidade , Estudantes , Adulto JovemRESUMO
Various biocompatible polymers have been developed using electrospun nanofibers for local drug delivery matrices, but many of them are non-FDA-approved polymers or chemicals. Material safety should be considered in biomedical devices, but the effectiveness of electrospun nanofibers is limited with only the approved chemicals. Therefore, we considered the material in FDA-approved polymers and solvents and developed nanofibers using the general additives in the pharmaceutical industry, such as hypromellose, poly(vinyl alcohol) (PVA), and Gellan. The nanofiber, mainly composed of hypromellose and PVA, was applied to a local peptide drug delivery system. Electrostatically complexed Gellan and peptide were loaded in the nanofiber by co-electrospinning. The morphology of the nanofibers with different PVA blending ratios was visualized by scanning electron microscope. The nanofiber composed of only hydrophilic polymers quickly wetted in water and became a transparent gel-like lump. A drug release test of peptide-loaded nanofiber was performed resulted in 37% of initial burst release suppression with the gellan and peptide loaded nanofiber compared with solely peptide loaded hypromellose nanofiber. In addition, higher PVA blending to hypromellose was slightly effective for sustained release of peptide compared with pure peptide-loaded hypromellose nanofiber. Therefore, we suggest the potential application of hypromellose/PVA nanofiber-loaded Gellan/peptide complex to a mucosal layer drug delivery patch.
Assuntos
Nanofibras , Álcool de Polivinil , Sistemas de Liberação de Medicamentos , Derivados da Hipromelose , PeptídeosRESUMO
OBJECTIVE: The availability of suicide methods affects the risk of suicide attempts. This study examined the patterns of substances ingested by suicide attempters (SAs) and the characteristics of SAs using psychotropic overdoses. METHODS: Data for 384 of the 462 eligible SAs who used self-poisoning were analyzed. Demographic variables, clinical characteristics, and factors related to the suicide attempts were examined. RESULTS: There were 256 (66.7%) females and 128 (33.3%) males. Roughly half the SAs ingested psychotropics (n=179, 46.6%). Agricultural chemicals (n=84, 21.9%) were the second most frequently ingested substances, followed by analgesics (n=62, 16.1%), household products (n=27, 7.0%), and other prescribed medications (n=23, 6.0%). Among psychotropics, the most frequently overdosed drugs were sedative-hypnotics, including hypnotics (n=104) and benzodiazepines (n=78). SAs favored Z-drugs and alprazolam. When compared with SAs with non-psychotropic overdoses, significantly more SAs with psychotropic overdoses were female (76% vs. 58.5%, p<0.001) and had a psychiatric history (59.8% vs. 29.8%, p<0.001). They had significantly more previous suicide attempts (0.52±1.02 vs. 0.32±0.80, p<0.05) and lower risk (7.96±1.49 vs. 8.44±1.99, p<0.01) and medical severity (3.06±0.81 vs. 3.37±0.93, p<0.005) scores. CONCLUSION: Psychotropic overdose, especially with sedative-hypnotics, was a major method in suicide attempts. It is important that psychiatric patients are carefully evaluated and monitored for suicidality when prescribing psychotropics.