The effect of local thermal fluctuations on the folding kinetics: a study from the perspective of the nonextensive statistical mechanics

Protein folding is a universal process, very fast and accurate, which works consistently (as it should be) in a wide range of physiological conditions. The present work is based on three premises, namely: ($i$) folding reaction is a process with two consecutive and independent stages, namely the search mechanism and the overall productive stabilization; ($ii$) the folding kinetics results from a mechanism as fast as can be; and ($iii$) at nanoscale dimensions, local thermal fluctuations may have important role on the folding kinetics. Here the first stage of folding process (search mechanism) is focused exclusively. The effects and consequences of local thermal fluctuations on the configurational kinetics, treated here in the context of non extensive statistical mechanics, is analyzed in detail through the dependence of the characteristic time of folding ($\tau$) on the temperature $T$ and on the nonextensive parameter $q$.The model used consists of effective residues forming a chain of 27 beads, which occupy different sites of a $3-$D infinite lattice, representing a single protein chain in solution. The configurational evolution, treated by Monte Carlo simulation, is driven mainly by the change in free energy of transfer between consecutive configurations. ...Comment: 19 pages, 3 figures, 1 tabl

Nonextensive statistical mechanics applied to protein folding problem: kinetics aspects

A reduced (stereo-chemical) model is employed to study kinetic aspects of globular protein folding process, by Monte Carlo simulation. Nonextensive statistical approach is used: transition probability p i j between configurations i &#8594; j is given by p i j =[1 +(1 - q)&#916;Gi j/kB T ]1/(1-q), where q is the nonextensive (Tsallis) parameter. The system model consists of a chain of 27 beads immerse in its solvent; the beads represent the sequence of amino acids along the chain by means of a 10-letter stereo-chemical alphabet; a syntax (rule) to design the amino acid sequence for any given 3D structure is embedded in the model. The study focuses mainly kinetic aspects of the folding problem related with the protein folding time, represented in this work by the concept of first passage time (FPT). Many distinct proteins, whose native structures are represented here by compact self avoiding (CSA) configurations, were employed in our analysis, although our results are presented exclusively for one representative protein, for which a rich statistics was achieved. Our results reveal that there is a specific combinations of value for the nonextensive parameter q and temperature T, which gives the smallest estimated folding characteristic time (t). Additionally, for q = 1.1, (t) stays almost invariable in the range 0.9 < T < 1.3, slightly oscillating about its average value <img border=0 width=32 height=32 src="../../../../../../../img/revistas/bjp/v39n2a/a16txt01.gif" align=absmiddle > or = 27 ±&#963;, where &#963; = 2 is the standard deviation. This behavior is explained by comparing the distribution of the folding times for the Boltzmann statistics (q &#8594; 1), with respect to the nonextensive statistics for q = 1.1, which shows that the effect of the nonextensive parameter q is to cut off the larger folding times present in the original (q &#8594; 1) distribution. The distribution of natural logarithm of the folding times for Boltzmann statistics is a triple peaked Gaussian, while, for q = 1.1 (Tsallis), it is a double peaked Gaussian, suggesting that a log-normal process with two characteristic times replaced the original process with three characteristic times. Finally we comment on the physical meaning of the present results, as well its significance in the near future works

Life after hip fracture - Impact of home rehabilitation versus conventional care and patients' experiences of the recovery process in a short- and long-term perspective

Aim In a short- and long-term perspective compare a geriatric home rehabilitation programme (HR) for patients with hip fracture with conventional care (CC), and to capture the patients experience of the consequences of the injury and their conceptions of what influences the recovery process. Method The thesis is based on two quantitative and two qualitative studies. The two quantitative studies were randomized and controlled, longitudinal intervention studies in which 102 community-dwelling elderly patients who had received either HR (n = 48) or CC (n = 54) were followed for one year after discharge. The HR programme, which started immediately after admission to hospital, included active participation from patients in setting goals and planning discharge. The programme was focused on encouraging the participants’ self-efficacy and exercising daily activities. Assessment of balance confidence, degree of independence and frequency of daily activities, health-related quality of life, mood, perceived recovery, and basic physical performance were made one month, six months and one year after hospital discharge. In the qualitative, phenomenographic studies 18 patients were interviewed one month and one year after discharge about how they experienced the consequences of the hip fracture and their conceptions of the recovery process. Results The main recovery for all participants took place during the first six months after discharge. The results show that those who had participated in the HR programme recovered faster than those who hade received CC. Additionally, in a longer perspective they were more confident and independent than the CC group, although the differences between the groups had diminished at one year. Only 14 persons in the HR group and five persons in the CC group considered themselves fully recovered after one year. The results from the interviews showed that the hip fracture caused social and existential cracks in the individuals’ lives. The hip fracture came unexpectedly and resulted in an experience of a changed body and a more restricted life. The interviewees experienced that they had increased difficulties to move and to manage independently. One reaction was that their pre-fracture self-view as being healthy and stable had been punctured by the injury. Although positive experiences, such as being satisfied with the recovery, were also expressed, many of the negative consequences remained or had even deepened one year after discharge. A dominating experience was that they were more cautious, afraid of further falls, and felt more sedentary and isolated than before the fracture. Conclusions The results show that the negative consequences of a hip fracture are substantial and long-lasting. However, the HR programme had a more significant impact than CC on the participants’ functioning and confidence, which was most evident in the early phase of the recovery. An essential task for health care should be to create continued possibilities for rehabilitation after discharge from hospital also in a longer perspective, and not primarily focus on the medical and physical needs. The patients’ experiences and psychological reactions that may follow a hip fracture should also be considered

Canine lymphoma: use of immunohistochemistry for accurate typing

El linfoma es una neoplasia hematopoyética, con un comportamiento biológico definido por la morfología celular y las características tisulares, con una alta incidencia en la especie canina. Debido a que existen diversos subtipos de linfomas, con dificultad para diferenciar mediante métodos complementarios convencionales, resulta necesario recurrir a técnicas como la histopatología e inmunohistoquímica para identificar su origen celular. Se presenta el caso de un canino macho entero Labrador retriever de 8 años de edad. El motivo de la consulta fue adelgazamiento progresivo y tos seca. En función del examen clínico, se continuó con el diagnóstico mediante los siguientes métodos complementarios: ecografía abdominal, punción aspiración con aguja fina de linfonódulo poplíteo, radiografía de tórax y analítica sanguínea. Se estableció como diagnóstico presuntivo linfoma multicéntrico, etapa IV, sub estadio clínico B. El tratamiento sugerido para el linfoma de células B de alto grado, como el que padecía el individuo reportado, es ciclofosfamida, vincristina, prednisolona y doxorrubicina (CHOP), ya que existe una óptima respuesta a esta terapia multimodal. Por razones económicas del propietario, se comenzó con un tratamiento paliativo monoquimioterápicocon prednisolona. Debido al deterioro rápido y progresivo del paciente, sumado al pronóstico desfavorable del mismo, el veterinario decidió, con el consentimiento del propietario, la eutanasia del animal. Post-mortem se realizaron estudios histopatológicos e inmunohistoquímicos del tejido neoplásico, para determinar el origen celular específico. Se utilizaron anticuerpos anti-CD20 y anti-CD3. La lectura fue positiva para el marcador de membrana CD20, que indica el origen celular de linfoctios B para este caso.El diagnóstico histopatológico fue compatible con la presencia de un linfoma difuso de células grandes inmunoblástico de alto grado originado en centros germinativos. El estudio inmunohistoquímico permitió establecer un diagnóstico definitivo según la clasificación de la OMS: linfoma difuso de células grandes inmunoblástico de linfocitos B.La determinación del inmunofenotipo permite establecer el origen celular preciso de la neoplasia y apunta a implementar tratamientos específicos y a la posibilidad de cruzar información con los conocimientos de linfomas humanos en pos de una medicina traslacional.Fil: Caliri, M. N.. Universidad "Juan Agustín Maz"Facultad de Ciencias Veterinarias y Ambientales. Laboratorio de Investigación En Genética, Ambiente y Reproducción; ArgentinaFil: Tapia, A.. Universidad "Juan Agustín Maz"Facultad de Ciencias Veterinarias y Ambientales. Laboratorio de Investigación En Genética, Ambiente y Reproducción; ArgentinaFil: Gorla, Nora Bibiana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad "Juan Agustín Maz"Facultad de Ciencias Veterinarias y Ambientales. Laboratorio de Investigación En Genética, Ambiente y Reproducción; ArgentinaXII Reunión Argentina de Patología Veterinaria; 14° Seminario de la Fundación Davis ThompsonBalcarceArgentinaInstituto Nacional de Tecnología Agropecuaria. Estación Experimental Balcarc

Los bovinos domésticos como potenciales bioindicadores ambientales: análisis del epitelio oral y aplicación en el ensayo de micronúcleos

Domestic cattle (Bos Taurus) could be used as bioindicators of the quality of agroecosystems, with the possibility of alerting through cellular biomarkers about possible adverse effects of drugs administered in them or toxic contaminants in the surrounding environment. The micronucleus buccal cytome (MN-cyt buccal) assay is used in human populations for this purpose. The aim of this study was to perform the structural characterization of the epithelium in the anatomical site proposed for performing the oral MN-cyt buccal assay in this species and to describe the types and frequencies of cells with nuclear abnormalities (NA) of the bovine oral lining epithelium. Exfoliative cytology of the buccal labial epithelium of twelve castrated males was performed and 1,000 cells per animal were analyzed. The frequencies of basal and differentiated cells with NAs were established. The most frequently observed cell types and NAs were: karyolytic, condensed chromatin, karyorrhexis, pyknotic, kidney-shaped, notched nuclei, binucleated, micronucleated and buds. Four grades of progression were described in nuclei with karyorrhexis. A keratinized flat stratified epithelium of 866.67±75.44 μm thick (Mean ± SD) was evidenced and the characteristics of the cells of the strata germinativum, granulosum, spinosum and corneum are delineated. In addition to being keratinized, the bovine epithelium is three to five times thicker than that recorded in humans due to more differentiated cells. In the prospective use of buccal MN-cyt in bovines, indicators of cell death should not be considered as a result of genotoxic effects that induce apoptosis, as occurs in humans; the rest of the NAs could be used as biomarkers.Los bovinos domésticos (Bos Taurus) podrían utilizarse como bioindicadores de la calidad de los agroecosistemas, con la posibilidad de alertar mediante biomarcadores celulares sobre posibles efectos adversos de fármacos administrados en ellos o de contaminantes tóxicos en el ambiente circundante. El ensayo de micronúcleos citoma bucal (MN-cit bucal) se utiliza en poblaciones humanas con este fin. El objetivo de este estudio fue realizar la caracterización estructural del epitelio en el sitio anatómico propuesto para la realización del test MN-cit bucal en esta especie y describir los tipos y frecuencias de células con anormalidades nucleares (AN) del epitelio bucal bovino. Además, se realizó citología exfoliativa del epitelio bucal labial de doce machos castrados y se analizaron 1.000 células por animal, estableciéndose frecuencia de células basales y diferenciadas con AN. Los tipos celulares y AN observados con mayor frecuencia fueron: cariolíticas, cromatina condensada, cariorrexis, picnóticos, en forma de riñón, núcleos con muescas, binucleados, micronucleados y brotes. Se describieron cuatro grados de progresión en núcleos con cariorrexis. Se evidenció un epitelio estratificado plano queratinizado de 866,67 ± 75,44 μm de espesor (media ± DE) y se delinean las características de las células de los estratos germinativum, granulosum, spinosum y corneum. Además de estar queratinizado, el epitelio bovino es entre tres y cinco veces más grueso que el registrado en humanos debido a un número mayor de células diferenciadas. En el uso prospectivo de MN-cit bucal en bovinos, los indicadores de muerte celular no deben considerarse como resultado de efectos genotóxicos que inducen apoptosis, como ocurre en humanos; el resto de las AN si pueden ser utilizados como biomarcadores