149 research outputs found
Efecto de la arginilación de calreticulina sobre su degradación : implicancia de la arginilación en la degradación a través de la ubiquitina-proteosoma
Get PDFTesis (Doctor en Ciencias Químicas) - - Universidad Nacional de Córdoba. Facultad de Ciencias Químicas, 2014Fil: Goitea, Víctor Enrique. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Hallak, Marta Elena. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina.Fil: Hallak, Marta Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina.Fil: Alvarez, Cecilia Inés. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Fil: Alvarez, Cecilia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina.Fil: Pérez, Mariela Fernanda. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.Fil: Pérez, Mariela Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.Fil: Maccioni, Hugo José. Fernando Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina.Fil: Maccioni, Hugo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina.Fil: Rossi, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Medicina Trasnacional; Argentina.Las modificaciones postraducción de proteínas son importantes para la regulación
de la fisiología de la célula ya que contribuyen significativamente a la diversidad
estructural y funcional de las proteínas.
Una de estas modificaciones es la arginilación, la cual consiste en la unión
covalente de un residuo de arginina en el extremo NH2 de proteínas aceptoras,
específicamente sobre ácido aspártico, ácido glutámico, o cisteína. Esta reacción es
catalizada por la enzima arginil-ARNt transferasa (Ate1) tanto en el citosol como en el
núcleo celular. En nuestro laboratorio se ha establecido previamente que calreticulina
(CRT), una proteína mayoritariamente residente del retículo endoplásmico (RE), se
retrotransloca al citoplasma donde es uno de los sustratos de la arginilación. Además,
se demostró que en condiciones de estrés que conducen a una disminución de los
niveles intracelulares de Ca2+, CRT arginilada (R-CRT) se asocia a gránulos de estrés
(GSs) que son complejos de ARNm y cuya función se correlaciona con una reducción
selectiva de la traducción proteica.
En el presente trabajo se describe la función de la arginilación de CRT en relación
a la tasa de recambio ("turnover") de CRT citoplasmática, la cual modularía la estabilidad
de la proteína. Además, se establece la vía de degradación de R-CRT en relación al rol
que desempeña la arginilación.
En este estudio se demuestra que tanto R-CRT como CRT se degradan por la vía
proteosomal, aunque R-CRT tiene menor susceptibilidad que CRT a ser degradada por
el proteosoma. Se determinó que la vida media de R-CRT es el doble que la de CRT
citoplasmática sin arginilar. Cuando se sobre expresaron ambas proteínas en células
knockout para la enzima Ate1 (células ATE1–/–), se confirmó que R-CRT es degradada
de manera menos eficaz que CRT por el proteosoma. También, se encontró que CRT
es degradada por una vía independiente de ubiquitina (Ub), mientras que la degradación
de R-CRT es vía dependiente de Ub. En nuestro laboratorio recientemente se demostró
que la arginilación de CRT promueve un alto grado de dimerización. En este sentido, la
sobre expresión de una mutante de CRT (C146A-CRT-EGFP) que impide la formación
de homodímeros, muestra niveles menores de R-CRT respecto de los encontrados
cuando se sobre expresa CRT de tipo salvaje (wt), indicando que la dimerización de RCRT
es en parte responsable de su estabilización. Por último, se encontró que tanto la
expresión citoplasmática de R-CRT como la inhibición del proteosoma incrementan los
niveles de R-CRT en la superficie celular. En su conjunto, estos resultados indican que
una vez que CRT alcanza el citoplasma, la misma puede ser degradada por el
proteosoma a través de una vía independiente de Ub o puede ser modificada por la enzima Ate1 formando R-CRT, la cual también es susceptible a la degradación
proteosomal pero por vía dependiente de Ub, mostrando una vida media más larga que
la CRT no modificada. Por otra parte, la estabilización de CRT por medio de su
arginilación y dimerización, le permitiría a CRT participar en diferentes funciones en el
citoplasma e incluso en otros compartimientos subcelulares a los que podría acceder
desde el citoplasma.Fil: Goitea, Víctor Enrique. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Hallak, Marta Elena. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina.Fil: Hallak, Marta Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina.Fil: Alvarez, Cecilia Inés. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Fil: Alvarez, Cecilia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina.Fil: Pérez, Mariela Fernanda. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.Fil: Pérez, Mariela Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.Fil: Maccioni, Hugo José. Fernando Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina.Fil: Maccioni, Hugo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina.Fil: Rossi, Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Medicina Trasnacional; Argentina
An introduction to leadership in tourism and hospitality
No full textDrawing on diverse empirical studies and theoretical analyses, this chapter highlights leadership's evolution from traditional stewardship approaches in destination management (Albrecht & Haid, Chapter 2) to more inclusive practices that address diversity and equity in organizational culture (Coetzee, Chapter 3). Adaptive leadership models that foster innovation are examined through studies by Dias (Chapter 4) and Hallak (Chapter 14), while the importance of need-supportive leadership for employee well-being is underscored by Houge Mackenzie (Chapter 5). Additionally, research on hospitable leadership practices (Williamson & Harris, Chapter 6) and dynamic strategies for managing organizational change (Vera et al., Chapter 7) demonstrates how leadership can enhance work climates (Wickel et al., Chapter 8) and facilitate effective conflict resolution through quality leader-member exchanges (Wang, Chapter 9). The chapter further explores strategic human resource development in ecotourism (Ramos, Chapter 10), comprehensive safety models (Basurto-Cedeno et al., Chapter 11), and responsible leadership in community tourism (Gan & Sim, Chapter 12). Finally, the integration of digital strategies (O’Connor, Chapter 13) highlights the necessity for adaptive, contextually grounded leadership to navigate an increasingly complex and technology-driven environment
Effervescent inhalable nanoparticles for treating lung cancer
No full textThis is an abstract of a presentation made at the conference titled \"The Aerosol Society Drug Delivery to the Lungs 20,\" at the Edinburgh International Conference Centre, Scotland, UK, December 9-11, 2009
Estudios bioquímicos y funcionales de la isoespecie arginilada de carlreticulina en el citoplasma y la superficie celular
Get PDFTesis (Doctor en Ciencia Químicas) – Universidad Nacional de Córdoba, 2012.Fil: López Sambrooks, Cecilia. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.En el presente trabajo de tesis se expondrán resultados concernientes a la isoforma arginilada de calreticulina (CRT). La arginilación postraducción confiere a CRT una nueva localización, funcionalidad y destino celular desde el citoplasma y la membrana plasmática. Además, a esta modificación se la involucra en eventos de adhesión celular y señalización de apoptosis. En relación a ello, a continuación, serán introducidos varios conceptos necesarios para comprender estos fenómenos. Arginhlación postraducción de proteínas Las modificaciones postrad uccionales de las proteínas pueden impartir una gran complejidad a los proteomas eucariotas los cuales son de varios órdenes de magnitud mayor que la capacidad de codificación del genoma. La modificación de la secuencia de aminoácidos o de sus cadenas laterales juega un papel crítico en la regulación de la biología de la célula, ya que contribuyen significativamente a la diversidad estructural y funcional de las proteínas. Las modificaciones postrad uccionales potencialmente pueden cambiar las propiedades físicas o químicas de una proteína, influir en la actividad de una enzima, en su localización, en las interacciones con otras moléculas, en la modulación de cascadas de señalización e incluso en su estabilidad. Las modificaciones más comunes incluyen la fosforilación (Morandeil y col. 2006), acetilación (Polevoda y Sherman 2002), glicosilación (Harvey 2005), acilación (Mclhinney 1990), aminoacilación (Kaji y col. 1963), nitrosilación (Kim y col. 2002), tirosinación y detirosinación (Barra y col. 1973; Hallak y col. 1977) algunas de las cuales pueden establecerse y/o ser removidas de forma dinámica como un mecanismo para el control de la función de las proteínas. El estudio de las modificaciones postrad uccionales comprende un campo de significancia biológica creciente ya que la evidencia sugiere que desempeña un rol fundamental en una gran variedad de procesos fisiológicos. Entre las modificaciones postraducción se encuentra la arginilación de proteínas, la cual consiste en la adición de una arginina (R), mediante unión peptídica en el extremo NH2 de varias proteínas aceptoras en el citosol, sobre ácido aspártico, ácido glutámico, o cisteína o bien en la cadena lateral del ácido glutámico, (Soffer 1971; Kaji 1976; Hallak y col. 1991; Eriste y col. 2005). La arginina es activada bajo la forma de arginil-ARNt por acción de la arginil-ARNt sintetasa, usando ATP, Mg2 y K como cofactores. Luego, en una segunda etapa, la arginina es transferida a la proteína aceptora desde el arginil-ARNt por acción de la enzima arginil-ARNt transferasa (Atel) (Esquema 1). Esta enzima se encuentra presente en todas las especies eucariotas, 16 desde levaduras hasta humanos, los cuales, parecen contener un sólo gen que la codifica. Por otro lado, una modificación similar existe en procariotas, donde una enzima homóloga, la transferasa UF modifica proteínas por adición de leucina y fenilalanina. Por lo tanto, la adición postraducción de aminoácidos a proteínas se halla altamente conservado en la evolución. La enzima Atel es esencial para la embriogénesis en mamíferos ya que ratones deficientes presentan letalidad embrionaria y defectos graves en el desarrollo cardiovascular y angiogénesis (Kwon y col. 2002). Así, resulta claro que Atel es importante desde el punto de vista fisiológico, y que su función en procesos de desarrollo es requerida para la supervivencia. Atel parecería tener una localización citosólica y nuclear, ya en experimentos de fusión de esta enzima con la proteína fluorescente verde, se la ha localizada tanto en citosol como en núcleo y no posee secuencias de translocación al retículo endoplásmico (RE) (Kwon y col. 1999). NH2:Asp, Glu,Cys ATE-1 (Arg)Fil: López Sambrooks, Cecilia. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina
تقييم نوعية حياة مرضى التليف الكيسي في الضفة الغربية والخيارات العلاجية الجديدة
Get PDFBackground
The number of cystic fibrosis patients is increasing around the world, Latest forecasts
published in the European Respiratory Journal indicate an increase of approximately
50% by 2025 (20% in the child population; 75% in the adult population).
There is no accurate epidemiological data on CF disease in Palestine. The general
impression has been that the disease is rare, but this is most likely the result of underdiagnosis
or misdiagnosis due to limited awareness of the condition in the region.
This disease has high treatment burden and some of the novel technology used for
drug delivery is highly beneficial because it may ease patient burden by decreasing
administration time and offer more efficacy and safety. These options are not
available for CF patients in Palestine, only basic traditional therapies are available and
this is the fundamental problem.
Assessment of the patient's perspective of symptom improvement, satisfaction and
their reported increase in health related quality of life (HRQoL) should be part of the
treatment decision making. Most of the cystic fibrosis patients QoL studies have been
conducted in developed countries and only a few in developing countries but no
studies were done in Palestine.
Objective
The purpose of this project was to study the Palestinian health situation by using
specific comparison tools including; Quality of life issues of Palestinian CF patients
attending the Caritas baby hospital, their health status, their related cost effective
treatment (Economical burden) and summarize the available evidence on the use of
new options for the treatment by using a willingness to pay survey.
MethodA descriptive narrative study conducted for patients from West Bank suffering from
cystic fibrosis disease. These patients used basic classic therapies and attending
pediatric pulmonology clinic in Caritas Baby Hospital. Around 77 participants
completed four quantitative assessment measures and provided demographic
information. The status of CF patients were studied by using different aspect. Their
quality of life score using CFQ-R questionnaire were measured. Their health status
were screened by measuring different parameter; pulmonary function test, body mass
index, their age at diagnosis and mortality rate related to CF disease. Their health
related cost and the amount of money they are able to pay for improving their
treatment options using a willingness to pay survey were calculated. Caritas Baby
Hospital (CBH) Medical Research Committee/Ethical Review Board approved this
study and a written informed consents form for the patients and their families were
obtained. Results were analyzed using scoring software and SPSS softwareResults and conclusion
The overall score for CF patients QoL parameters is less than 60% (ranges from 14.5-
55.6) which indicate poor quality of life relative to other countries worldwide. The
lowest score is for body (14.5), treatment (17.5), and respiratory (27.5). The highest
score appears to be for eat (55.6) and emotion (50). Illness severity as measured by
FEV1 percent predicted with mean value of 69.6%. BMI recorded with mean value
15.998 (Kg/m2
). With the overall mean age at diagnosis in our sample was 4.16 years
of age. The study showed that 58.3% (7/12) of patients from Hebron district had high
mortality rate related to CF disease.
The result revealed that quality of life for CF patients is influenced by age, gender,
taking vacation without disease, work or school status, BMI measures, age at
diagnosis for the patient's parameters. In addition, QoL as scored by their parents
parameter which included: the age, educational level and work status of both parents
and is also affected by total number of CF patients in each family.
QoL for CF patients is not influenced by marital status, geographic distribution, place
of residency (city, village and camp), FEV1 measures, willingness to pay answers,
their parent's relationship (father or mother), monthly income, and the effect of taking
influenza vaccine yearly.
For willingness to pay, results indicate that 93.5% said yes and 6.5% said no. 51.4%
of patients are able to pay 100 NIS out of pocket to 2.7% able to pay 2000 NIS or
more out of pocket to get new drugs. With economical evaluation for CF patient, the
total costs for patient with the mean age of our sample 10.7 years of age were
estimated to be around 35650.2 NIS per patient per year. Cost reduction were
estimated after applying Dornase-alfa as a mucolytic drug and Tobramycin nebulizer
solution. This added value can help in part of the cost for making these drugs
available for CF patients in our region.
Overall, quality of life for patients with CF is poor relative to international standards,
the medications used including Hypertonic saline and Gentamycin IV form used asnebulizer solution are not first line therapies around the world, patients and their
families demand better treatment and are willing to pay to get better treatment. Now
we have an objective proof to submit for the need of new therapies for CF patients in
Palestine in order to improve their QoL, health status and longevity
Societal perspectives on community pharmacy services in West Bank - Palestine
Get PDFUnderstanding the public's view of professional competency is extremely important; however little has been reported on the public’s perception of community pharmacists in PalestineObjectives: To determine the perception of Palestinian consumers of the community pharmacist and the services they offerMethod: This project used the survey methodology administered by structured interviews to consumers who attended the 39 randomly selected pharmacies, in six main cities in Palestine. The questionnaire had range of structured questions covering: Consumers’ patronage patterns, consumers’ interaction with community pharmacists, consumers’ views on how the pharmacist dealt with personal health issues, procedure with regard to handling private consultations.Results: Of 1,017 consumers approached, 790 consumers completed the questionnaire (77.7 %). Proximity to home and presence of knowledgeable pharmacist were the main reasons for patients to visit the same pharmacy. Physicians were identified as the preferred source of advice by 57.2% and pharmacists by 23.8%. Only 17% of respondents considered pharmacists as health professionals who know a lot about drugs and are concerned about and committed to caring for the public. In addition, 49% indicated that pharmacists spoke more quietly cross the counter during counseling and almost one third reported that the pharmacist used a private area within the pharmacy. The majority of respondents would be happy to receive different extended services in the community pharmacy like blood pressure monitoring.Conclusions: Palestinian consumers have a positive overall perception of community pharmacists and the services they offer. Awareness should be created amongst the public about the role of pharmacist and the added value they can provide as health care professional. There is a need to consider privacy when giving patient counseling to increase user satisfaction
Necessity and concerns about lipid-lowering medical treatments and risk factors for non-adherence: A cross-sectional study in Palestine
Get PDFAims: Strong evidence indicates that drugs reduce blood lipids and improve cardiovascular
end-points, leading to their wide usage. However, the success of these drugs
can be affected by poor patient's adherence to prescribed medication. This study
aimed to evaluate medication adherence in patients with dyslipidaemia in association
with patient beliefs about medicines.
Methods: The study was conducted from January 2019 to July 2019 at the middle
governmental primary healthcare clinics in Ramallah and Bethlehem cities, and
used a cross-sectional design. Adherence was determined using the 4-item Morisky
medication adherence scale, while beliefs were determined using the Beliefs about
Medicines Questionnaire.
Results: Of 220 patients, 185 agreed to participate in the study, resulting in a response
rate of 84.1%. Of the participants, 106 (57.3%) were men, and almost half (88,
46.5%) were ≥56 years. Medication non-adherence was high (47.6%), but a majority
(65.5%) reported believing their treatment to be necessary for their continued good
health. Accordingly, the mean necessity score (17.3, SD 3.7) significantly outweighed
(P < .001) the mean concerns score (14.0, SD 3.5). Multivariate regression demonstrated
four variables to be significantly correlated with non-adherence: illiterate
(OR = 2.52; CI: 0.9-4.3; P = .03), polypharmacy (OR = 3.18; CI: 1.9-5.7; P = .007),
having comorbidity (OR = 3.10; CI: 2.2-4.6; P = .005) and having concerns about side
effects (OR = 2.89; CI: 1.1-4.6, P = .04).
Conclusion: Non-adherence among patients taking lipid-lowering agents was high despite
most holding positive beliefs regarding medication necessity. This may be due to
concern also being high. Physicians should identify and target high-risk patients and individualise
their treatment plans in order to achieve adequate control of dyslipidaemia.We thank all workers at health clinics at Ramallah and Bethlehem
who helped in finishing this study and also we thank the participants
who willingly accepted to share for the purpose of this study
Mobile Positioning Technique using Signal Strength Measurement method with the aid of Passive Mobile Listener Grid
No full textClinical characteristics and outcomes of cystic fibrosis in Palestine: Cross sectional study
Get PDFObjective: To assess the clinical characteristics and outcomes of cystic fibrosis in Palestine by studying the quality of life (QoL) of participants.
Method: This cross‐sectional study involved the application of Cystic Fibrosis Questionnaire‐Revised (CFQ‐R) to participants attending the pediatric pulmonology clinic at Caritas Baby Hospital between January and May 2017. Health status was assessed by measuring pulmonary function test (FEV1), body mass index (BMI), age of CF diagnosis, and presence of other affected siblings or deaths in the family.
Results: There were 77 participants from 58 families: 46.8% (36/77) were males, and 53.3% (41/77) were females. The mean age was 10.7 years (range: 0.5–36 years). The participants were divided into three groups by age in years: group I (< 6), II (6–13), and III (≥ 14). The highest and lowest CFQ scores were for the eating domain in group III (55.6 ± 22.5) and the body domain in group II (14.5 ± 17.7), respectively. Mean illness severity was 69.6% (range: 33%–111%). The mean BMI was 15.9 (range: 9.6–23.1). The mean age at the time of diagnosis was 4.2 years (± 6.3). The study showed that 1.7% of the families (1/58) had four affected siblings, and 21% (12/58) had death cases related to CF, of which 58.3% (7/12) were from the Hebron district. Finally, all parameters for CF participants in West Bank, Palestine were noticeably lower than those reported in other countries.
Conclusions: This study illustrates the need for new therapies for CF participants in Palestine to improve QoL, health status, and longevity.A C KN O W L E D G M E N T S: We would like to thank Caritas Baby Hospital in Bethlehem, West Bank for their cooperation in collecting the data for this study
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