Добірка наукової літератури з теми "14-helix"

Although considerable scientific research data is available for sepsis and cytokine storm syndrome, there is a need to develop new treatments or drugs for sepsis management. Antimicrobial peptides (AMPs) possess anti-bacterial and anti-inflammatory activity, neutralizing toxins such as lipopolysaccharides (LPS, endotoxin). Most AMPs have been designed as a substitute for conventional antibiotics, which kill drug-resistant pathogens. The present study aimed to determine the anti-inflammatory potential of 10 designed XIW (X: lysine, arginine, or glutamic acid) α-helical peptides in macrophages and a mouse model in the presence of LPS. Among them, WIKE-14, a peptide with a helix-to-helix structure, having the 12th amino acid substituted with glutamic acid, suppressed pro-inflammatory cytokines in RAW 264.7 macrophages. This reaction was mediated by the inhibition of the binding between LPS and macrophages. In addition, the WIKE-14 peptide exhibited a potent anti-inflammatory activity in mice ears and lungs inflamed using LPS. Thus, our results may provide useful insights for the development of anti-sepsis agents via the sequence and structure information of the WIKE-14 peptide.

Details are provided on 124 land snail species and varieties from New Zealand, and a further 14 species putatively from New Zealand, all of which were described by European and North American taxonomists between 1830 and 1934, based on specimens collected between 1824 and 1924. Primary type material of 95 of these taxa was located in Northern Hemisphere museums during the present study. Lectotypes are designated for: Helix chimmoi Pfeiffer, 1857, Helix glabriuscula Reeve, 1852, Helix (Paryphanta) gilliesi Smith, 1880, Nanina ? celinde Gray, 1850, Zonites chiron Gray, 1850 and Zonites coma Gray, 1843. Neotypes are designated for Helix conella Pfeiffer, 1861 and Helix tau Pfeiffer, 1861. Primary type material of the following taxa is figured herein for the first time: Bulimus? (Laoma) leimonias Gray, 1850, Cyclophorus cytora Gray, 1850, Cyclostoma (Cyclophorus?) lignarium Pfeiffer, 1857, Helix chimmoi Pfeiffer, 1857, Helix egesta Gray, 1850, Helix fatua Pfeiffer, 1857, Helix greenwoodi Gray, 1850, Helix guttula Pfeiffer, 1853, Helix kermandeci Pfeiffer, 1857, Helix portia Gray, 1850, Helix sciadium Pfeiffer, 1857, Helix venulata Pfeiffer, 1857, Helix (Paryphanta) gilliesi Smith, 1880, Hydrocena (Omphalotropis) vestita Pfeiffer, 1855, Nanina ? celinde Gray, 1850, Nanina erigone Gray, 1850, Nanina mariae Gray, 1843, Patula modicella var. vicinalis Mousson, 1873, Realia egea Gray, 1850, Vitrina kermadecensis Smith, 1873 and Zonites chiron Gray, 1850. New taxonomic combinations introduced herein include: Allodiscus nematophora (Reeve, 1854), Cavellia biconcava (Reeve, 1852), Charopa chimmoi (Pfeiffer, 1857), Coneuplecta regularis (Reeve, 1854), Delos jeffreysiana (Reeve, 1852), Fectola tau (Pfeiffer, 1861), Fectola varicosa (Reeve, 1852), Flammulina crebriflammea (Reeve, 1852), Lyrotropis vestita (Pfeiffer, 1855), ?Neophenacohelix ziczac (Gould, 1846), Parabalea peregrina (Gould, 1847), Phacussa hypopolea (Reeve, 1852), Phenacharopa novoseelandica (Küster, 1852), Phrixgnathus glabriusculus (Reeve, 1852), Phrixgnathus poecilostictus (Reeve, 1852), Thalassohelix obnubila (Reeve, 1852), Tornatellinops novoseelandica (Küster, 1852) and Wainuia urnula (Reeve, 1854). Helix collyrula Reeve, 1852 and Nanina tullia Gray, 1850 are treated as junior synonyms of Phenacohelix (Neophenacohelix) giveni Cumber 1961 nomen protectum and Helix (Huttonella) pseudoleioda Suter, 1890 nomen protectum, respectively. A brief account is given of the history of research on the New Zealand land snail fauna from 1824 to 1917.

The conformation of four peptides (N-terminal acetylated and unacetylated 14-mers DEASGIGPEEHFPENH2 and 24-mers AcQKGLFDFMLEDEASGIGPEEHFPENH2 with a normal and an oxidized methionine residue) containing the sequence Asp-Glu-Ala-Ser-Gly-Ile-Gly (DEASGIG), which is known to play an important role in the xylosylation reactions involving the glycosaminoglycan-bearing serine of decorin/DS-PGII, were studied by two-dimensional proton NMR techniques, circular dichroism spectroscopy, and molecular dynamics in a methanol–water mixture. The 14-residue peptide comprises the first (i.e., N-terminal) 14 amino acids of the mature decorin protein and the 24-residue peptide incorporates an additional (N-terminal) sequence of 10 amino acids derived from the procore of decorin. The resonance heterogeneity induced by the isomerization of the two prolines (Pro8, Pro13 in the 14-mer, and Pro18, Pro23 in the 24-mer) in the peptides studied was evaluated from TOCSY and NOESY NMR spectra. The trans-trans, trans-cis, and cis-trans isomers exist in approximate 68:25:7 proportions in the methanol–water mixture. The NOE distance constraints were used as input parameters for molecular dynamics and restrained energy minimization calculations. It was demonstrated that the conformation of the DEASGIG fragment was affected by the presence of the 10 amino acids at the N-terminal end of the 24-mer, and that the serine is part of an α-helix. The results indicate that an α-helix is present in the 24-mer beginning at the N-terminal end with Lys2 and ending at Gly15, and suggest that this could be the signal for the xylosylation of serine Ser14. A type VIb β turn was observed, involving the C-terminal cis-proline in the sequence His-Phe-Pro-Glu. Key words: xylosylation, nascent helix, α-helix, csi-proline, type VIb β-turn, molecular dynamics.

The overall objective of this study was to understand the mechanisms that control antigen processing and binding of peptides to major histocompatibility complex (MHC) molecules. Towards this goal I investigated (a) the structural features of T cell-presented peptides with a focus on the role of recurrent hydrophobic residues in catalysis of helix formation by these peptides and (b) the biochemical events that determine the fates of the invariant chain molecule (Ii) in its various post-translational processing pathways. In the structural studies, I tested the hypothesis that the recurrence of hydrophobic amino acids in a polypeptide at positions falling in an axial, hydrophobic strip if the sequence were coiled as an α-helix can lead to helical nucleation on a hydrophobic surface.For a series of HPLC-purified peptides, including some T cell-presented peptides varying considerably in primary sequence, percentage helicity in the presence of lipid vesicles correlated with strip-of-helix hydrophobicity index (SOHHI), as shown by circular dichroism (CD) analysis. A prototypic helix peptide PH-1.0 (LYQELQKLTQTLK) was designed with a strong axial hydrophobic strip of 4 leucine residues. PH-1.0 formed about 38% helical structure in 10 mM phosphate buffer at pH 7.0 with di-O-hexadecyl phosphatidylcholine (DHPC) lipid vesicles, but no helical structure was detected when the peptide was in phosphate buffer alone. The helix-forming tendencies of 9 analogs of PH-1.0 with one or two amino acid variations from the parent peptide were examined in the presence of lipid vesicles and the results showed that (a) decreasing the strip-of-helix hydrophobicity by substituting even one of the four leucine residues in the axial hydrophobic strip with a less hydrophobic threonine residue reduced the helix-forming tendency of a peptide in the presence of lipid vesicles; (b) the placement of recurrent hydrophobic residues within the axial hydrophobic strip appeared to be critical for a peptide to be induced to form an α-helix by a hydrophobic surface; (c) there was an orientation preference for these peptides to interact with lipid vesicles and to form helical structure; (d) extra hydrophobic residues in other positions appeared to compete with the hydrophobic residues within the axial hydrophobic strip for interaction with the lipid vesicles and therefore to decrease the helix-forming tendency of peptides. For the biochemical studies of the function of Ii, a 17-residue peptide, Ii-3 (Ii 148-164), was synthesized. The CD analysis of Ii-3 showed mainly an α-helical conformation when the peptide was examined in the presence of lipid vesicles. [125I]-labeled Ii-3, after coupling at the N-terminus with a photoactivatable, heterobifunctional crosslinker N-hydroxysuccinimidyl-4-azidobenzoate (HSAB), was able to bind to both α and β chains of class II MHC molecules, indicating that this region of Ii might cover the desetope of class II MHC molecules from the time of their synthesis until their charging with foreign peptides at an endosomal compartment. The biosynthesis of a chondroitin sulfate proteoglycan-form of Ii (CS-Ii) was examined in a class II MHC-negative cell line P3HR-1. [35S]sulfate-labeled microsomal membrane proteins of P3HR-1 were immunoprecipitated with anti-Ii monoclonal antibody and the results of SDS-PAGE analysis demonstrated that P3HR-1 could process Ii to CS-li in the absence of class II MHC molecules and the chondroitin sulfate identity of this molecule was confirmed by chondroitinase-ABC treatment. We conclude that there might be a class II MHC-independent pathway to process Ii to a chondroitin sulfate proteoglycan form as compared to the pathway in which Ii was associated with class II MHC and later cleaved by proteases residing in the endosomal compartment. In an effort to demonstrate in vitro that the class II MHC-associated Ii was eventually dissociated from class II MHC molecules by a proteolytic cleavage process, it was found that cathepsin B could completely remove Ii without damage to class II α and β chains. In order to identify those cleaved Ii fragments, three polyclonal anti-Ii peptide sera were produced by immunizing rabbits with keyhole limpet hemocyanin (KLH)-conjugated Ii peptides. Anti-Ii (146-169) was shown to be able to precipitate a p18 molecule only in cells expressing Ii. Anti-Ii (148-164 )and anti-Ii(78-92) were specific for their respective antigenic peptides as tested by enzyme-linked immunosorbent assay (ELISA).

grado de magíster en farmacología
Las condiciones de vida actuales, que incluyen nuevas características dietarías, nutricionales y comportamentales, han modificado el perfil epidemiológico en las últimas décadas, lo que incrementa la incidencia y prevalencia de las enfermedades crónicas no transmisibles, entre las que se encuentra la Diabetes Mellitus. El comportamiento de este grupo de patologías, cómo su nombre lo indica, tiende a la cronicidad, generando una serie de alteraciones en la fisiología y anatomía del paciente, que afecta considerablemente su calidad y expectativa de vida. Entre las múltiples complicaciones tardías que se manifiestan, tenemos el pie diabético, la cual es la consecuencia de los daños microangiopáticos, macroangiopáticos y neuropáticos de la Diabetes Mellitus. El problema clínico a resolver, es determinar la mejoría y aminorar en lo posible las altas tasas de hospitalización por infecciones en los grados avanzados de pie diabético, lo cual puede avanzar a situaciones complejas como la amputación. Se estima que la incidencia anual de esta complicación (pie diabético) está en alrededor del 2%, y su presencia, al menos una vez en la vida oscila entre el 15 y el 25% [1]. La Federación Internacional de Diabetes, hizo un llamado de atención al referirse que cada 30 segundos, una extremidad se pierde en algún lugar del mundo como consecuencia de la diabetes [1]. Un estimativo, según estudios de Kerr et al llevados a cabo en el Reino Unido, es que la tasa de progresión hacia la amputación es del 28% y ahonda en el tema, considerando que una persona con diabetes mellitus tiene 23 veces más posibilidades de sufrir una amputación por úlcera en comparación con una persona sin dicho diagnóstico [2]. Al respecto, se ha planteado el presente ensayo clínico, considerado de Fase I-II, (de evaluación de seguridad y eficacia), para una formulación de baba de caracol y extractos naturales, que persigue ser analizada en la evaluación de la mejoría clínica, de úlceras de los pacientes afectados con pié diabético, además de demostrar un perfil de seguridad. El estudio clínico en mención, será controlado, abierto y aleatorizado. La formulación en estudio, llamada MUCIDERM® (contenida en parches), será complementada al tratamiento convencional de pie diabético, indicado tanto en la Norma Clínica del manejo integral del pie diabético como en la Guía Clínica de curación avanzada de pie diabético del Ministerio de Salud (MINSAL) [3,4]. Los individuos en estudio fueron pacientes con Diabetes Mellitus tipo 2, que presentaron heridas ulcerosas de pie Grado 1 y 2 de la clasificación de Wagner y entre otros criterios de inclusión se consideraron: lesión unilateral, sin foco infeccioso a distancia (exceptuando onicomicosis), con condiciones higiénico-sanitarias adecuadas, con regularidad en sus controles, adecuado apoyo familiar, evidencia de cumplimiento de sus indicaciones terapéuticas y la consolidación del proceso de consentimiento informado. Se excluyeron quienes refirieron historia de alergia a alguno de los componentes de la formulación, pacientes con diagnóstico de cáncer o alguna otra situación medico quirúrgica que a juicio del investigador pudiese colocar al paciente en riesgo al participar en el estudio o haber recibido algún otro medicamento bajo investigación en el último mes. Se estimó incluir un total de 90 pacientes, divididos en dos grupos de 45 pacientes cada uno, tomándose uno como grupo control (A) y el otro (B) quién recibió el tratamiento innovador (MUCIDERM®), además se administró el producto en estudio en pie sano para evaluar seguridad. El periodo de reclutamiento estimado fue de 18 meses y el seguimiento de los pacientes se realizó durante 60 días aproximadamente. El presente trabajo se constituye en una Actividad Formativa Equivalente (A.F.E.) para obtener el grado de Magíster en Farmacología, en el que se desarrollan una serie de actividades en el marco del proyecto, que permiten obtener las competencias y capacidades requeridas para lograr el grado. En este caso, esta A.F.E. se ha circunscrito en un estudio clínico, cuyos aspectos fundamentales son descritos a continuación.
Current life conditions that include new dietary, nutritional and behavioral characteristics have modified the epidemiological profile in the last decades, which increases the incidence and prevalence of chronic non-communicable diseases, including Diabetes Mellitus. The behavior of this group of pathologies, as its name indicates, tends to the chronicity, generating a series of alterations in the physiology and anatomy of the patient that affects considerably its quality and life expectancy. Among the many late complications that are manifested we can find the diabetic foot, which is the consequence of the microangiopathic, macroangiopathic and neuropathic damages of Diabetes Mellitus. The clinical problem to be resolved is to determine the improvement and to reduce the high rates of hospitalization for infections in the advanced states of diabetic foot, which may lead to complex situations such as amputation. The annual incidence of this complication (diabetic foot) is estimated to be around 2%, and its presence at least once in life ranges from 15% to 25% [1]. The International Diabetes Federation drew attention to the fact that every 30 seconds, somewhere in the world a limb is lost as a result of diabetes [1]. An estimate, according to studies by Kerr et al carried out in the United Kingdom, the rate of progression of amputation is 28% and deepens the subject, considering that a person with diabetes mellitus is 23 times more likely to suffer an ulcer amputation compared to a person without such a diagnosis [2]. The present Phase I-II clinical trial (a safety and efficacy evaluation), for a formulation of snail slime and natural extracts, has been proposed, which aims to be analyzed in the evaluation of the clinical improvement of Ulcers of affected patients with diabetic foot, in addition to demonstrating a safety profile. The clinical study in question will be controlled, open and randomized. The formulation under study (contained in patches) will be complemented with the conventional diabetic foot treatment indicated both in the Clinical Standard of the integral management of the diabetic foot and in the Diabetes Foot Advanced Clinical Guide of the Ministry of Health (MINSAL) [3,4]. The individuals under study are patients with Type 2 Diabetes Mellitus who present Grade 1 and 2 foot ulcers of the Wagner classification and, among other inclusion criteria, will be: unilateral lesion, with no infectious focus at a distance (except for onychomycosis), with conditions Hygienic-sanitary, with regular checks, adequate family support, evidence of compliance with their therapeutic indications and consolidation of the informed consent process. Those who reported a history of allergy to any of the components of the formulation, patients with a diagnosis of cancer or any other surgical medical situation were excluded, which in the opinion of the investigator could put the patient at risk when participating in the study or having received any medication under research in the last month. It is estimated that a total of 90 patients will be divided into 2 groups of 45 patients each, one being taken as the control group (A) and the other (B) receiving the innovative treatment, and the study product will be administered in healthy foot to evaluate security. The estimated recruitment period will be 18 months and the patients will be monitored for approximately 60 days. The present work is constituted in an Equivalent Formative Activity (A.F.E.) to obtain the Master's degree in Pharmacology and that constitute a series of activities within the framework of the project that allow to obtain the competences and capacities required to achieve the degree. In this case, this A.F.E has been circumscribed in a clinical study, whose fundamental aspects are described below.

Large, strongly connected amounts of data, as collected in knowledge bases or those occurring when describing software, are often read slowly and with difficulty by humans when they are represented as spreadsheets or text. Graphical representations can help people to understand facts more intuitively and offer a quick overview. The electronic representation offers means that are beyond the possibilities of print such as unlimited zoom and hyperlinks. This paper addresses a framework for visualizing connected information in 3D-space taking into account the techniques of media design to build visualization structures and map information to graphical properties
Große, stark vernetzte Datenmengen, wie sie in Wissensbasen oder Softwaremodellen vorkommen, sind von Menschen oft nur langsam und mühsam zu lesen, wenn sie als Tabellen oder Text dargestellt werden. Graphische Darstellungen können Menschen helfen, Tatsachen intuitiver zu verstehen und bieten einen schnellen Überblick. Die elektronische Darstellung bietet Mittel, welche über die Möglichkeiten von Print hinausgehen, wie z.B. unbegrenzten Zoom und Hyperlinks. Diese Arbeit stellt ein Framework für die Visualisierung vernetzter Informationen im 3D-Raum vor, welches Techniken der Gestaltung zur Erstellung von graphischen Strukturen und zur Abbildung von Informationen auf graphische Eigenschaften berücksichtigt

The effect of pressure on the helix-coil transition temperature (Tm) is reported for the double-stranded polymers poly(dA)poly(dT), poly[d(A-T)], poly[d(l-C], and poly[d(G-C] and triple-stranded poly(dA)2poly(dT). The Tm increases as a function of pressure, implying a positive volume change for the transition and leading to the conclusion that the molar volume of the coil form is larger than the molar volume of the helix. From the change in Tm as a function of pressure, molar volume changes of the transition (ΔVt) are calculated using the Clapeyron equation and calorimetrically determined enthalpies. For the doublestranded polymers, ΔVt, increases in the order poly[d(l-C] < polyt[d(A-T)] < poly(dA)-poly(dT) < polylcl(G-C)]. The value of ΔVt, for the triple-stranded to single-stranded transition of poly(dA) 2poly(dT) is larger than that of poly[d(G-C)I. The magnitude of ΔVt increases with salt concentration in all cases studied; however, the change of ΔVt with salt concentration depends on the sequence of the DNA and the number of strands involved in the transition. In the model proposed to explain the results, the overall molar volume change of the transition is a function of a negative volume change arising from changes in the electrostatic interactions of the DNA strands, and a positive volume change due to unstacking the bases. The model predicted the direction of the change in the ΔVt for several experiments. The magnitude of AVJ increases with counter ion radius, thus for polyld(A-T)], ΔVt, increases in the series Na+ , K+, Cs+, The ΔVt also increases if the charge on the phosphodiester groups is removed. The kinetics of the formation of double-stranded (dA)19(dT)19 in 50 mM NaCI are slowed approximately 14-fold at 200 MPa relative to atmospheric pressure. The implied volume of activation of +37 ml mol−l in the direction of this change is also in agreement with the proposed model. The stability of double- and triple-stranded DNA helices in water around neutral pH depends on the base composition and sequence, as well as on the ionic strength of the solution. Each of these dependencies also defines how DNA interacts with water.