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1.
Biochim Biophys Acta Mol Basis Dis ; 1870(1): 166928, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38660915

RESUMO

Huntington's disease (HD) is a progressive neurodegenerative disorder with clinical presentations of moderate to severe cognitive, motor, and psychiatric disturbances. HD is caused by the trinucleotide repeat expansion of CAG of the huntingtin (HTT) gene. The mutant HTT protein containing pathological polyglutamine (polyQ) extension is prone to misfolding and aggregation in the brain. It has previously been observed that copper and iron concentrations are increased in the striata of post-mortem human HD brains. Although it has been shown that the accumulation of mutant HTT protein can interact with copper, the underlying HD progressive phenotypes due to copper overload remains elusive. Here, in a Drosophila model of HD, we showed that copper induces dose-dependent aggregational toxicity and enhancement of Htt-induced neurodegeneration. Specifically, we found that copper increases mutant Htt aggregation, enhances the accumulation of Thioflavin S positive ß-amyloid structures within Htt aggregates, and consequently alters autophagy in the brain. Administration of copper chelator D-penicillamine (DPA) through feeding significantly decreases ß-amyloid aggregates in the HD pathological model. These findings reveal a direct role of copper in potentiating mutant Htt protein-induced aggregational toxicity, and further indicate the potential impact of environmental copper exposure in the disease onset and progression of HD.


Assuntos
Cobre , Proteína Huntingtina , Doença de Huntington , Animais , Humanos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/genética , Autofagia/efeitos dos fármacos , Autofagia/genética , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , Cobre/metabolismo , Cobre/toxicidade , Modelos Animais de Doenças , Drosophila melanogaster/efeitos dos fármacos , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Doença de Huntington/genética , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Mutação , Agregação Patológica de Proteínas/genética , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/patologia
2.
Heliyon ; 8(4): e09283, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35497041

RESUMO

In this work, the excision of hexavalent chromium (Cr(VI)) was studied from an aqueous solution using the chemically modified arecanut leaf sheath (CALS) as a novel bio-adsorbent. The as-prepared adsorbent was characterized by using instrumental methods including Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The effect of several factors, including solution pH, contact time, and sorbent dosages were examined to identify the optimum condition for the sorption ability. The optimal pH of Cr(VI) biosorption was 2.0, and equilibrium was reached in 150 min. Adsorption was shown to be pseudo-second-order in kinetic investigations, and the Langmuir isotherm with maximal adsorption efficiency was determined as 109.89 mg/g. The spent biosorbent can be easily regenerated and reused. For the biosorption of oxyanions of chromium, both electrostatic attraction and ligand exchange mechanism play critical roles. From the results, the CALS appears to be a potential low-cost effective sorbent to remove Cr (VI) from water.

3.
Cult Med Psychiatry ; 38(4): 642-68, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25234302

RESUMO

In Nepal, spirit possession is a common phenomenon occurring both in individuals and in groups. To identify the cultural contexts and psychosocial correlates of spirit possession, we conducted a mixed-method study in a village in central Nepal experiencing a cluster of spirit possession events. The study was carried out in three stages: (1) a pilot study consisting of informal interviews with possessed individuals, observations of the possession spells, and video recording of possession events; (2) a case-control study comparing the prevalence of symptoms of common mental disorders in women who had and had not experienced possession; and (3) a follow-up study with focus group discussions and in-depth interviews with possessed and non-possessed men and women, and key informants. Quantitative results indicated that possessed women reported higher rates of traumatic events and higher levels of symptoms of mental disorder compared to non-possessed women (Anxiety 68 vs. 18 %, Depression 41 vs. 19 %, and PTSD 27 vs. 0 %). However, qualitative interviews with possessed individuals, family members, and traditional healers indicated that they did not associate possession states with mental illness. Spirit possession was viewed as an affliction that provided a unique mode of communication between humans and spirits. As such, it functioned as an idiom of distress that allowed individuals to express suffering related to mental illness, socio-political violence, traumatic events, and the oppression of women. The study results clearly indicate that spirit possession is a multi-dimensional phenomenon that cannot be mapped onto any single psychiatric or psychological diagnostic category or construct. Clinical and public health efforts to address spirit possession must take the socio-cultural context and systemic dynamics into account to avoid creating iatrogenic illness, undermining coping strategies, and exacerbating underlying social problems.


Assuntos
Transtornos Mentais , Bruxaria/psicologia , Adaptação Psicológica , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Nepal , Projetos Piloto , Psicopatologia , Pesquisa Qualitativa , População Rural
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