Stereochemical features of the envelope protein Domain III of dengue virus reveals putative antigenic site in the five-fold symmetry axis

AbstractWe bring to attention a characteristic parasitic pattern present in the dengue virus: it undergoes several intensive thermodynamic variations due to host environmental changes, from a vector's digestive tract, through the human bloodstream and intracellular medium. Comparatively, among the known dengue serotypes, we evaluate the effects that these medium variations may induce to the overall structural characteristics of the Domain III of the envelope (E) protein, checking for stereochemical congruences that could lead to the identification of immunologic relevant regions. We used molecular dynamics and principal component analysis to study the protein in solution, for all four dengue serotypes, under distinct pH and temperature. We stated that, while the core of Domain III is remarkably rigid and effectively unaffected by most of the mentioned intensive variations, the loops account for major and distinguishable flexibilities. Therefore, the rigidity of the Domain III core provides a foothold that projects specifically two of these high flexible loop regions towards the inner face of the envelope pores, which are found at every five-fold symmetry axis of the icosahedron-shaped mature virus. These loops bear a remarkable low identity though with high occurrence of ionizable residues, including histidines. Such stereochemical properties can provide very particular serotype-specific electrostatic surface patterns, suggesting a viral fingerprint region, on which other specific molecules and ions can establish chemical interactions in an induced fit mechanism. We assert that the proposed regions share enough relevant features to qualify for further immunologic and pharmacologic essays, such as target peptide synthesis and phage display using dengue patients' sera

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

La Escuela de Enfermería de Ribeirão Preto/USP, y la Sociedad Honorífica de Enfermería Pró Sigma Theta Tau Internacional

The FIERP Honor Society will become a Sigma Theta Tau International chapter in 2002. The Honor Society had to face significant challenges, but the opportunity to participate in this international network will be of great importance to Brazilian and Latin American Nursing.A Sociedade Honorífica da FIERP - Pró Sigma Theta Tau Internacional será transformada em um capítulo da Sociedade Internacional de Enfermagem Sigma Theta Tau Internacional, a partir de 2002. Após uma série de dificuldades e desafios, o Brasil terá o primeiro capítulo da STTI. A possibilidade de participar dessa rede internacional de enfermagem será de grande importância para a enfermagem brasileira e da América Latina.La Sociedad Honorífica de la FIERP - Pro Sigma Theta Tau Internacional será transformada en un capítulo de la Sociedad Internacional de Enfermería Sigma Theta Tau Internacional (STTI) a partir de 2002. Después de una serie de dificultades y desafíos, el Brasil va a crear el primer capítulo de la STTI. La posibilidad de participar de ésta red internacional de enfermería va a ser de gran importancia para la enfermería brasileña y de América Latina

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

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

Afecciones respiratorias superiores en aves de criaderos de Mendoza

En los últimos meses de 2010 criaderos de gallinas de la provincia de Mendoza padecieron afecciones respiratorias superiores de características agudas. La incidencia fue alta, siendo muy baja la letalidad de los casos. Se presenta la metodología de trabajo utilizada para diagnóstico virológico, bacteriológico y micológico, junto a los resultados hallados