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1.
Pathogens ; 12(1)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36678474

RESUMO

Invasive fungal infections caused by Candida species remain a significant public health problem worldwide. The increasing prevalence of drug-resistant infections and a limited arsenal of antifungal drugs underscore the need for novel interventions. Here, we screened several classes of pharmacologically active compounds against mammalian diseases for antifungal activity. We found that the synthetic triazine-based compound melanogenin (Mel) 56 is fungicidal in Candida albicans laboratory and clinical strains with minimal inhibitory concentrations of 8−16 µg/mL. Furthermore, Mel56 has general antifungal activity in several non-albicans Candida species and the non-pathogenic yeast Saccharomyces cerevisiae. Surprisingly, Mel56 inhibited the yeast-to-hyphae transition at sublethal concentrations, revealing a new role for triazine-based compounds in fungi. In human cancer cell lines, Mel56 targets the inner mitochondrial integral membrane prohibitin proteins, PHB1 and PHB2. However, Mel56 treatment did not impact C. albicans mitochondrial activity, and antifungal activity was similar in prohibitin single, double, and triple homozygous mutant strains compared to the wild-type parental strain. These results suggests that Mel56 has a novel mechanism-of-action in C. albicans. Therefore, Mel56 is a promising antifungal candidate warranting further analyses.

2.
Gerontologist ; 62(9): 1359-1368, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-35323945

RESUMO

BACKGROUND AND OBJECTIVES: Adult Protective Services (APS) are the frontline agencies investigating elder mistreatment and providing/coordinating postinvestigation services. Yet, their effectiveness in reducing different types of mistreatment in relation to services is unknown. This study aimed to address the knowledge gap by identifying services provided by mistreatment type, and examining the associations of services with mistreatment reduction. RESEARCH DESIGN AND METHODS: A pretest-post-test design was implemented using the Identification, Services, and Outcomes (ISO) Matrix to assess mistreatment levels during case investigation and at case closure after services were provided. San Francisco and Napa APS participated in a 6-month data collection. RESULTS: The 4 most prevalent types of mistreatment were examined: emotional, physical, financial abuse, and neglect by others. On average, level of mistreatment decreased across mistreatment types after APS intervention. Care/case management, mental health, and other services were most common, while specific services differed depending on type of mistreatment. Care/case management services were associated with physical and emotional abuse reduction, legal services further correlated with emotional abuse reduction; financial planning services were associated with financial abuse reduction; care/case management and other services were associated with neglect reduction. DISCUSSION AND IMPLICATIONS: This is the first study to address APS services by mistreatment type and the outcomes of services. Adoption of the ISO Matrix by APS programs opens the possibility of research and practice collaboration in APS outcomes research using a standardized approach.


Assuntos
Abuso de Idosos , Humanos , Idoso , Abuso de Idosos/psicologia , Seguridade Social , São Francisco
3.
J Elder Abuse Negl ; 33(1): 47-64, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33535908

RESUMO

Background and Objectives. In testing a comprehensive decision support system for Adult Protective Services (APS), this study addressed two problems common in APS research and practice: the psychometric quality of the measures and measurement burden. Research Design and Methods. Data were generated on 1,472 APS cases over six months in two California counties using the Identification, Services and Outcomes (ISO) Matrix, a comprehensive decision support system for APS. The ISO Matrix uses Short-Forms developed from the Elder Abuse Decision Support System (EADSS). Mini-Forms were developed from the Short-Forms and tested in order to reduce measurement burden. Mini-Forms were developed on each measure using sensitivity and specificity of the items in predicting the criterion of substantiation (yes/no). Psychometric quality was addressed by estimating predictive validity and Cronbach's alpha of Short-Forms. Predictive validity and reliability were also estimated on the Mini-Forms as was their correlation with the Short-Forms. Results. On Short-Forms, good predictive validity was found for all measures except those that were very rare. Results for even shorter Mini-Forms were mixed, and some will require further research on their reliability and validity. Discussion and Implications. Short-Forms had good psychometric properties and some Mini-Forms did as well. Ongoing adoption by several California counties and Montana demonstrates the viability and sustainability of using the ISO Matrix for research and practice.


Assuntos
Abuso de Idosos , Idoso , Abuso de Idosos/diagnóstico , Humanos , Psicometria , Reprodutibilidade dos Testes
4.
Assist Technol ; 33(5): 278-287, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31306079

RESUMO

The use of stair descent devices is an important part of a comprehensive emergency evacuation plan. To date, there is little research on consumer opinion of these devices. A pilot study was performed at a local center for independent living, enabling 14 consumers with mobility impairments to state their initial impressions of 14 devices, representing three general designs: carry-type, track-type, and sled-type. Consumers were able to view the devices, ask questions, and view short videos of the devices in use. Afterwards, consumers were given the opportunity to try out one or more of the devices, and provide their opinion after each trial run. Consumers provided feedback on specific design features, how they anticipated they would feel about using each, and whether they considered each device acceptable for use. Trial use enabled more in-depth opinions, and in some cases, a change in opinion on acceptability.


Assuntos
Planejamento em Desastres , Arquitetura de Instituições de Saúde , Planejamento em Desastres/métodos , Elevadores e Escadas Rolantes , Humanos , Projetos Piloto , Estudos de Tempo e Movimento
5.
PLoS Genet ; 16(7): e1008908, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32639995

RESUMO

The human fungal pathogen Candida albicans is constantly exposed to environmental challenges impacting the cell wall. Signaling pathways coordinate stress adaptation and are essential for commensalism and virulence. The transcription factors Sko1, Cas5, and Rlm1 control the response to cell wall stress caused by the antifungal drug caspofungin. Here, we expand the Sko1 and Rlm1 transcriptional circuit and demonstrate that Rlm1 activates Sko1 cell wall stress signaling. Caspofungin-induced transcription of SKO1 and several Sko1-dependent cell wall integrity genes are attenuated in an rlm1Δ/Δ mutant strain when compared to the treated wild-type strain but not in a cas5Δ/Δ mutant strain. Genome-wide chromatin immunoprecipitation (ChIP-seq) results revealed numerous Sko1 and Rlm1 directly bound target genes in the presence of caspofungin that were undetected in previous gene expression studies. Notable targets include genes involved in cell wall integrity, osmolarity, and cellular aggregation, as well as several uncharacterized genes. Interestingly, we found that Rlm1 does not bind to the upstream intergenic region of SKO1 in the presence of caspofungin, indicating that Rlm1 indirectly controls caspofungin-induced SKO1 transcription. In addition, we discovered that caspofungin-induced SKO1 transcription occurs through self-activation. Based on our ChIP-seq data, we also discovered an Rlm1 consensus motif unique to C. albicans. For Sko1, we found a consensus motif similar to the known Sko1 motif for Saccharomyces cerevisiae. Growth assays showed that SKO1 overexpression suppressed caspofungin hypersensitivity in an rlm1Δ/Δ mutant strain. In addition, overexpression of the glycerol phosphatase, RHR2, suppressed caspofungin hypersensitivity specifically in a sko1Δ/Δ mutant strain. Our findings link the Sko1 and Rlm1 signaling pathways, identify new biological roles for Sko1 and Rlm1, and highlight the complex dynamics underlying cell wall signaling.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Candida albicans/efeitos dos fármacos , Caspofungina/farmacologia , Proteínas de Domínio MADS/genética , Proteínas Repressoras/genética , Proteínas de Saccharomyces cerevisiae/genética , Antifúngicos/farmacologia , Candida albicans/genética , Candida albicans/patogenicidade , Parede Celular/efeitos dos fármacos , Parede Celular/genética , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Humanos , Fosforilação/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética
6.
mBio ; 10(5)2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594814

RESUMO

The human fungal commensal Candida albicans can become a serious opportunistic pathogen in immunocompromised hosts. The C. albicans cell adhesion protein Als1p is a highly expressed member of a large family of paralogous adhesins. Als1p can mediate binding to epithelial and endothelial cells, is upregulated in infections, and is important for biofilm formation. Als1p includes an amyloid-forming sequence at amino acids 325 to 331, identical to the sequence in the paralogs Als5p and Als3p. Therefore, we mutated Val326 to test whether this sequence is important for activity. Wild-type Als1p (Als1pWT) and Als1p with the V326N mutation (Als1pV326N) were expressed at similar levels in a Saccharomyces cerevisiae surface display model. Als1pV326N cells adhered to bovine serum albumin (BSA)-coated beads similarly to Als1pWT cells. However, cells displaying Als1pV326N showed visibly smaller aggregates and did not fluoresce in the presence of the amyloid-binding dye Thioflavin-T. A new analysis tool for single-molecule force spectroscopy-derived surface mapping showed that statistically significant force-dependent Als1p clustering occurred in Als1pWT cells but was absent in Als1pV326N cells. In single-cell force spectroscopy experiments, strong cell-cell adhesion was dependent on an intact amyloid core sequence on both interacting cells. Thus, the major adhesin Als1p interacts through amyloid-like ß-aggregation to cluster adhesin molecules in cis on the cell surface as well as in trans to form cell-cell bonds.IMPORTANCE Microbial cell surface adhesins control essential processes such as adhesion, colonization, and biofilm formation. In the opportunistic fungal pathogen Candida albicans, the agglutinin-like sequence (ALS) gene family encodes eight cell surface glycoproteins that mediate adherence to biotic and abiotic surfaces and cell-cell aggregation. Als proteins are critical for commensalism and virulence. Their activities include attachment and invasion of endothelial and epithelial cells, morphogenesis, and formation of biofilms on host tissue and indwelling medical catheters. At the molecular level, Als5p-mediated cell-cell aggregation is dependent on the formation of amyloid-like nanodomains between Als5p-expressing cells. A single-site mutation to valine 326 abolishes cellular aggregation and amyloid formation. Our results show that the binding characteristics of Als1p follow a mechanistic model similar to Als5p, despite its differential expression and biological roles.


Assuntos
Amiloide/metabolismo , Candida albicans/fisiologia , Moléculas de Adesão Celular/metabolismo , Adesão Celular , Proteínas Fúngicas/metabolismo , Substituição de Aminoácidos , Amiloide/genética , Candida albicans/genética , Moléculas de Adesão Celular/genética , Técnicas de Visualização da Superfície Celular , Análise Mutacional de DNA , Proteínas Fúngicas/genética , Expressão Gênica , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/fisiologia
7.
Gerontologist ; 59(5): e403-e414, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30085117

RESUMO

BACKGROUND AND OBJECTIVES: Within the elder abuse field, research on the characteristics of the abusers is scant, and no validated measure of abuser risk exists. The purpose of this study was to develop and test the Abuser Risk Measure (ARM). RESEARCH DESIGN AND METHODS: The Rasch measurement model and traditional psychometrics were used on a sample of 425 elder abuse cases that completed an elder abuse investigation and had a substantiation decision (yes/no). All had usable ARM responses that were obtained primarily from the alleged victim. ARM construct/criterion validity was tested against four types of elder abuse using substantiation decision as the criterion. Item analyses guided the development of a full 21-item ARM measure and, subsequently, a short, 9-item screener. RESULTS: The 21-item ARM met the Rasch criteria. Although the screener was borderline on Rasch criteria, the combination of a good Cronbach's alpha with strong criterion validation provided a rationale for endorsing its validity. Both versions of the ARM were significantly and most strongly predictive of physical and emotional abuse, and significant for financial exploitation. While not significantly predictive of neglect alone, they were strongly and significantly predictive of total types of abuse. DISCUSSION AND IMPLICATIONS: This study was innovative in developing abuser risk items, analyzing client data, and generally supporting ARM validity for elder abuse. Theoretically, and now empirically, it is becoming clear that measures of abuser risk have an important role to play in both case assessment and in research.


Assuntos
Abuso de Idosos/prevenção & controle , Programas de Rastreamento/normas , Inquéritos e Questionários/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Fatores de Risco , Adulto Jovem
8.
PLoS One ; 13(2): e0192250, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29389961

RESUMO

The ubiquitous presence of SPFH (Stomatin, Prohibitin, Flotillin, HflK/HflC) proteins in all domains of life suggests that their function would be conserved. However, SPFH functions are diverse with organism-specific attributes. SPFH proteins play critical roles in physiological processes such as mechanosensation and respiration. Here, we characterize the stomatin ORF19.7296/SLP3 in the opportunistic human pathogen Candida albicans. Consistent with the localization of stomatin proteins, a Slp3p-Yfp fusion protein formed visible puncta along the plasma membrane. We also visualized Slp3p within the vacuolar lumen. Slp3p primary sequence analyses identified four putative S-palmitoylation sites, which may facilitate membrane localization and are conserved features of stomatins. Plasma membrane insertion sequences are present in mammalian and nematode SPFH proteins, but are absent in Slp3p. Strikingly, Slp3p was present in yeast cells, but was absent in hyphal cells, thus categorizing it as a yeast-phase specific protein. Slp3p membrane fluorescence significantly increased in response to cellular stress caused by plasma membrane, cell wall, oxidative, or osmotic perturbants, implicating SLP3 as a general stress-response gene. A slp3Δ/Δ homozygous null mutant had no detected phenotype when slp3Δ/Δ mutants were grown in the presence of a variety of stress agents. Also, we did not observe a defect in ion accumulation, filamentation, endocytosis, vacuolar structure and function, cell wall structure, or cytoskeletal structure. However, SLP3 over-expression triggered apoptotic-like death following prolonged exposure to oxidative stress or when cells were induced to form hyphae. Our findings reveal the cellular localization of Slp3p, and for the first time associate Slp3p function with the oxidative stress response.


Assuntos
Apoptose , Candida albicans/genética , Proteínas Fúngicas/genética , Genes Fúngicos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Sequência de Aminoácidos , Citometria de Fluxo , Proteínas Fúngicas/química , Mutação , Homologia de Sequência de Aminoácidos
9.
Nat Commun ; 8(1): 1908, 2017 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-29199275

RESUMO

Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) contributes to endosomal and lysosomal function. LIMP-2 deficiency is associated with neurological abnormalities and kidney failure and, as an acid glucocerebrosidase receptor, impacts Gaucher and Parkinson's diseases. Here we report a crystal structure of a LIMP-2 luminal domain dimer with bound cholesterol and phosphatidylcholine. Binding of these lipids alters LIMP-2 from functioning as a glucocerebrosidase-binding monomer toward a dimeric state that preferentially binds anionic phosphatidylserine over neutral phosphatidylcholine. In cellular uptake experiments, LIMP-2 facilitates transport of phospholipids into murine fibroblasts, with a strong substrate preference for phosphatidylserine. Taken together, these biophysical and cellular studies define the structural basis and functional importance of a form of LIMP-2 for lipid trafficking. We propose a model whereby switching between monomeric and dimeric forms allows LIMP-2 to engage distinct binding partners, a mechanism that may be shared by SR-BI and CD36, scavenger receptor proteins highly homologous to LIMP-2.


Assuntos
Antígenos CD36/metabolismo , Colesterol/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidilserinas/metabolismo , Receptores Depuradores/metabolismo , Animais , Cristalografia por Raios X , Fibroblastos/metabolismo , Células HEK293 , Humanos , Camundongos , Fosfolipídeos/metabolismo
10.
EMBO J ; 35(15): 1707-19, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27340124

RESUMO

In the Neurospora crassa circadian clock, a protein complex of frequency (FRQ), casein kinase 1a (CK1a), and the FRQ-interacting RNA Helicase (FRH) rhythmically represses gene expression by the white-collar complex (WCC). FRH crystal structures in several conformations and bound to ADP/RNA reveal differences between FRH and the yeast homolog Mtr4 that clarify the distinct role of FRH in the clock. The FRQ-interacting region at the FRH N-terminus has variable structure in the absence of FRQ A known mutation that disrupts circadian rhythms (R806H) resides in a positively charged surface of the KOW domain, far removed from the helicase core. We show that changes to other similarly located residues modulate interactions with the WCC and FRQ A V142G substitution near the N-terminus also alters FRQ and WCC binding to FRH, but produces an unusual short clock period. These data support the assertion that FRH helicase activity does not play an essential role in the clock, but rather FRH acts to mediate contacts among FRQ, CK1a and the WCC through interactions involving its N-terminus and KOW module.


Assuntos
Relógios Circadianos , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Neurospora crassa/enzimologia , RNA Helicases/química , RNA Helicases/metabolismo , Cristalografia por Raios X , Proteínas Fúngicas/genética , Modelos Moleculares , Proteínas Mutantes/química , Proteínas Mutantes/genética , Ligação Proteica , Conformação Proteica , Domínios Proteicos , RNA Helicases/genética
11.
Eval Rev ; 39(4): 395-427, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26275980

RESUMO

BACKGROUND: Substance use disorders (SUDs) are one of the nation's most costly problems in terms of dollars, disability, and death. Self-help programs are among the varied recovery support options available to address SUD, and evaluation of these programs depends on good measurement. There exists an unmet need for a psychometrically sound, brief, efficient measure of self-help involvement for individuals with SUD that is valid across different substances and age-groups. METHODS: Using data from 2,101 persons presenting for SUD treatment, the full 21-item Global Appraisal of Individual Needs Self-Help Involvement Scale (SHIS) and a newly developed 11-item short-form version were validated against the Rasch measurement model and each other. Differential item functioning (DIF) was assessed by primary substance and age. RESULTS: Both versions met Rasch psychometric criteria. The full scale had minor misfit with no DIF for alcohol, marijuana, or opioids but a few instances of DIF for amphetamine and cocaine users as well as for age, in that youth tended to endorse several easier items more frequently than did adults. The 11-item short form had neither misfit nor DIF by substance and only minor DIF by age was highly correlated with the full version and was relatively more efficient. Criterion-related validity was supported for both. CONCLUSIONS: Both the long and short versions of SHIS are psychometrically sound measures of a more comprehensive conceptualization of self-help involvement for SUDs that can be used as part of an in-depth assessment or as a short measure that lessens respondent burden.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/métodos , Psicometria , Grupos de Autoajuda/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Avaliação de Resultados em Cuidados de Saúde/normas , Reprodutibilidade dos Testes , Grupos de Autoajuda/normas , Transtornos Relacionados ao Uso de Substâncias/economia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Estados Unidos , Adulto Jovem
12.
Appl Ergon ; 50: 87-97, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25959322

RESUMO

The physical demands on evacuators were investigated when using different types of sled-type stair descent devices designed for the emergency evacuation of high rise buildings. Twelve firefighters used six sled-type stair descent devices during simulated evacuations. The devices were evaluated under two staircase width conditions (1.12, and 1.32 m). Dependent measures included electromyographic (EMG) data, heart rates, Borg Scale ratings, and descent velocities. All stair descent speeds were below those reported during pedestrian egress trials. With the exception of the inflatable device, the devices operated by two evacuators had higher descent speeds than those operated by a single evacuator. High friction materials under the sleds facilitated control and reduced the muscle demands on stairs but increased physical demands on the landings. Usability assessments found devices with shorter overall lengths had fewer wall contacts on the landing, and handles integrated in the straps were preferred by the evacuators.


Assuntos
Emergências , Limitação da Mobilidade , Esforço Físico , Adulto , Fenômenos Biomecânicos/fisiologia , Eletromiografia , Desenho de Equipamento , Bombeiros , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Esforço Físico/fisiologia
13.
Inorg Chem ; 54(8): 3736-47, 2015 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-25839944

RESUMO

5'-deoxyadenosylcobalamin (coenzyme B12, AdoCbl) serves as the cofactor for several enzymes that play important roles in fermentation and catabolism. All of these enzymes initiate catalysis by promoting homolytic cleavage of the cofactor's Co-C bond in response to substrate binding to their active sites. Despite considerable research efforts, the role of the lower axial ligand in facilitating Co-C bond homolysis remains incompletely understood. In the present study, we characterized several derivatives of AdoCbl and its one-electron reduced form, Co(II)Cbl, by using electronic absorption and magnetic circular dichroism spectroscopies. To complement our experimental data, we performed computations on these species, as well as additional Co(II)Cbl analogues. The geometries of all species investigated were optimized using a quantum mechanics/molecular mechanics method, and the optimized geometries were used to compute absorption spectra with time-dependent density functional theory. Collectively, our results indicate that a reduction in the basicity of the lower axial ligand causes changes to the cofactor's electronic structure in the Co(II) state that replicate the effects seen upon binding of Co(II)Cbl to Class I isomerases, which replace the lower axial dimethylbenzimidazole ligand of AdoCbl with a protein-derived histidine (His) residue. Such a reduction of the basicity of the His ligand in the enzyme active site may be achieved through proton uptake by the catalytic triad of conserved residues, DXHXGXK, during Co-C bond homolysis.


Assuntos
Carbono/química , Cobalto/química , Cobamidas/química , Compostos Organometálicos/química , Teoria Quântica , Carbono/metabolismo , Dicroísmo Circular , Cobalto/metabolismo , Cobamidas/metabolismo , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/metabolismo
14.
Appl Ergon ; 46 Pt A: 96-106, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25113864

RESUMO

The physical demands on firefighting personnel were investigated when using different types of track-type stair descent devices designed for the emergency evacuation of high rise buildings as a function of staircase width and evacuation urgency. Twelve firefighters used five track-type stair descent devices during simulated urgent and non-urgent evacuations. The devices were evaluated under two staircase width conditions (1.12, and 1.32 m), and three devices were also evaluated under a narrower staircase condition (0.91 m). Dependent measures included electromyographic (EMG) data, spine motion, heart rates, Borg Scale ratings, task durations and descent velocities. Stair descent speeds favored the devices that had shorter fore/aft dimensions when moving through the landing. EMG results indicated that there were tradeoffs due to design features, particularly on the landings where the physical demands tended to be greater. On the landings, devices that could be rolled on four wheels reduced the deltoid and bicep activation levels.


Assuntos
Bombeiros , Limitação da Mobilidade , Músculo Esquelético/fisiologia , Esforço Físico/fisiologia , Transporte de Pacientes/métodos , Adulto , Acessibilidade Arquitetônica , Eletromiografia , Desenho de Equipamento , Arquitetura de Instituições de Saúde , Frequência Cardíaca/fisiologia , Humanos , Masculino , Manequins , Pessoa de Meia-Idade , Coluna Vertebral/fisiologia , Análise e Desempenho de Tarefas , Gravação em Vídeo , Suporte de Carga/fisiologia
15.
Nat Chem Biol ; 10(10): 801-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25229449

RESUMO

Three major classes of flavin photosensors, light oxygen voltage (LOV) domains, blue light sensor using FAD (BLUF) proteins and cryptochromes (CRYs), regulate diverse biological activities in response to blue light. Recent studies of structure, spectroscopy and chemical mechanism have provided unprecedented insight into how each family operates at the molecular level. In general, the photoexcitation of the flavin cofactor leads to changes in redox and protonation states that ultimately remodel protein conformation and molecular interactions. For LOV domains, issues remain regarding early photochemical events, but common themes in conformational propagation have emerged across a diverse family of proteins. For BLUF proteins, photoinduced electron transfer reactions critical to light conversion are defined, but the subsequent rearrangement of hydrogen bonding networks key for signaling remains highly controversial. For CRYs, the relevant photocycles are actively debated, but mechanistic and functional studies are converging. Despite these challenges, our current understanding has enabled the engineering of flavoprotein photosensors for control of signaling processes within cells.


Assuntos
Criptocromos/química , Proteínas de Escherichia coli/química , Flavina-Adenina Dinucleotídeo/química , Modelos Moleculares , Diester Fosfórico Hidrolases/química , Criptocromos/genética , Criptocromos/metabolismo , Transporte de Elétrons , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Flavina-Adenina Dinucleotídeo/metabolismo , Expressão Gênica , Ligação de Hidrogênio , Luz , Oxirredução , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Processos Fotoquímicos , Engenharia de Proteínas , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
16.
Appl Ergon ; 45(3): 389-97, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23759793

RESUMO

The physical demands on firefighting personnel were investigated when using different types of hand-carried stair descent devices designed for the emergency evacuation of high rise buildings as a function of staircase width and evacuation urgency. Twelve firefighters used three hand-carried stair descent devices during simulated urgent and non-urgent evacuations. The devices were evaluated under three staircase width conditions (0.91, 1.12, and 1.32 m). For comparison, an urgent manual carry was also performed on the 1.12 m wide stairs. Dependent measures included electromyographic (EMG) data, heart rates, Borg Scale ratings, task durations and descent velocities. Results indicated that the stair chair with extended front handles, which allows the front person to descend the stairs facing forward, reduced the time integrated back muscle EMG by half and showed a descent velocity that was 1.8 times faster than the other stair descent devices in the study. There were no differences across staircase widths.


Assuntos
Bombeiros , Limitação da Mobilidade , Esforço Físico/fisiologia , Adulto , Acessibilidade Arquitetônica , Eletromiografia , Arquitetura de Instituições de Saúde , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Suporte de Carga/fisiologia , Adulto Jovem
17.
Ergonomics ; 56(11): 1698-707, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24063664

RESUMO

Patient-handling tasks are integral to Emergency Medical Service (EMS) work as are the musculoskeletal injuries associated with these tasks. The aim of this study was to develop and test a structural equation model that describes the interactions between previously identified factors that contribute to the adoption of a specific ergonomics intervention designed for EMS work. EMS responders (n = 187), from six different organisations, participated in a 2-month longitudinal study following the introduction of a foldable patient transfer-board (slide-board) designed to assist with lateral patient transfers. Surveys administered at baseline, after 1 month and after 2 months sampled factors potentially influencing EMS responders' adoption decisions. Perceived ergonomics advantage, which was influenced by access and storage concerns and prior tool experience, contributed most strongly to intention to use at the end of the first month and to the emergence of champions, which contributed to the intention to use at the end of the second month.


Assuntos
Auxiliares de Emergência/psicologia , Intenção , Movimentação e Reposicionamento de Pacientes/instrumentação , Sistema Musculoesquelético/lesões , Traumatismos Ocupacionais/prevenção & controle , Adolescente , Adulto , Idoso , Atitude do Pessoal de Saúde , Ergonomia , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Modelos Teóricos , Adulto Jovem
18.
Nurs Res ; 62(3): 149-59, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23636342

RESUMO

BACKGROUND: Valid assessment of family functioning can play a vital role in optimizing client outcomes. Because family functioning is influenced by family structure, socioeconomic context, and culture, existing measures of family functioning-primarily developed with nuclear, middle-class European American families-may not be valid assessments of families in diverse populations. The Family Effectiveness Measure was developed to address this limitation. OBJECTIVES: The aim of this study was to test the Family Effectiveness Measure with data from a primarily low-income African American convenience sample using the Rasch measurement model. METHODS: A sample of 607 adult women completed the measure. Rasch analysis was used to assess unidimensionality, response category functioning, item fit, person reliability, differential item functioning by race and parental status, and item hierarchy. Criterion-related validity was tested using correlations with five other variables related to family functioning. RESULTS: The Family Effectiveness Measure measures two separate constructs: The Effective Family Functioning construct was a psychometrically sound measure of the target construct that was more efficient because of the deletion of 22 items. The Ineffective Family Functioning construct consisted of 16 of those deleted items but was not as strong psychometrically. Items in both constructs evidenced no differential item functioning by race. Criterion-related validity was supported for both. DISCUSSION: In contrast to the prevailing conceptualization that family functioning is a single construct, assessed by positively and negatively worded items, use of the Rasch analysis suggested the existence of two constructs. Whereas the Effective Family Functioning scale is a strong and efficient measure of family functioning, the Ineffective Family Functioning scale will require additional item development and psychometric testing.


Assuntos
Família/etnologia , Relações Interpessoais , Poder Familiar/psicologia , Pobreza/psicologia , Pobreza/estatística & dados numéricos , Prisioneiros/psicologia , Psicometria/instrumentação , Adulto , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Criança , Pré-Escolar , Características Culturais , Feminino , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Illinois , Lactente , Modelos Logísticos , Pessoa de Meia-Idade , Relações Pais-Filho , Testes Psicológicos , Fatores Socioeconômicos , População Branca/psicologia , População Branca/estatística & dados numéricos , Adulto Jovem
19.
Biochemistry ; 52(2): 378-91, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23252338

RESUMO

Light-oxygen-voltage (LOV) domains bind a flavin chromophore to serve as blue light sensors in a wide range of eukaryotic and prokaryotic proteins. LOV domains are associated with a variable effector domain or a separate protein signaling partner to execute a wide variety of functions that include regulation of kinases, generation of anti-sigma factor antagonists, and regulation of circadian clocks. Here we present the crystal structure, photocycle kinetics, association properties, and spectroscopic features of a full-length LOV domain protein from Rhodobacter sphaeroides (RsLOV). RsLOV exhibits N- and C-terminal helical extensions that form an unusual helical bundle at its dimer interface with some resemblance to the helical transducer of sensory rhodopsin II. The blue light-induced conformational changes of RsLOV revealed from a comparison of light- and dark-state crystal structures support a shared signaling mechanism of LOV domain proteins that originates with the light-induced formation of a flavin-cysteinyl photoadduct. Adduct formation disrupts hydrogen bonding in the active site and propagates structural changes through the LOV domain core to the N- and C-terminal extensions. Single-residue variants in the active site and dimer interface of RsLOV alter photoadduct lifetimes and induce structural changes that perturb the oligomeric state. Size exclusion chromatography, multiangle light scattering, small-angle X-ray scattering, and cross-linking studies indicate that RsLOV dimerizes in the dark but, upon light excitation, dissociates into monomers. This light-induced switch in oligomeric state may prove to be useful for engineering molecular associations in controlled cellular settings.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Rhodobacter sphaeroides/química , Rhodobacter sphaeroides/metabolismo , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Cristalografia por Raios X , Flavinas/metabolismo , Luz , Modelos Moleculares , Dados de Sequência Molecular , Oxigênio/metabolismo , Mutação Puntual , Conformação Proteica , Multimerização Proteica , Estrutura Terciária de Proteína , Subunidades Proteicas/química , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Rhodobacter sphaeroides/genética , Homologia de Sequência
20.
Ergonomics ; 55(11): 1362-72, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22928550

RESUMO

This study explored factors contributing to intervention adoption decisions among Emergency Medical Service (EMS) workers. Emergency Medical Service workers (n = 190), from six different organisations, participated in a two-month longitudinal study following the introduction of a patient transfer-board (also known as slide-board) designed to ease lateral transfers of patients to and from ambulance cots. Surveys administered at baseline, after one month and after two months sampled factors potentially influencing the EMS providers' decision process. 'Ergonomics Advantage' and 'Patient Advantage' entered into a stepwise regression model predicting 'intention to use' at the end of month one (R (2 )= 0.78). After the second month, the stepwise regression indicated only two factors were predictive of intention to use: 'Ergonomics Advantage,' and 'Endorsed by Champions' (R (2 )= 0.58). Actual use was predicted by: 'Ergonomics Advantage' and 'Previous Tool Experience.' These results relate to key concepts identified in the diffusion of innovation literature and have the potential to further ergonomics intervention adoption efforts. Practitioner Summary. This study explored factors that potentially facilitate the adoption of voluntarily used ergonomics interventions. EMS workers were provided with foldable transfer-boards (slideboards) designed to reduce the physical demands when laterally transferring patients. Factors predictive of adoption measures included perceived ergonomics advantage, the endorsement by champions, and prior tool experience.


Assuntos
Auxiliares de Emergência/psicologia , Movimentação e Reposicionamento de Pacientes/instrumentação , Sistema Musculoesquelético/lesões , Traumatismos Ocupacionais/prevenção & controle , Atitude do Pessoal de Saúde , Auxiliares de Emergência/estatística & dados numéricos , Falha de Equipamento , Ergonomia , Feminino , Humanos , Estudos Longitudinais , Masculino
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