Characterization of interactions of eggPC lipid structures with different biomolecules

In this paper we study the interactions of two biomolecules (ascorbic acid and Annonacin) with a bilayer lipid membrane. Egg yolk phosphatidylcholine (eggPC) liposomes (in crystalline liquid state) were prepared in solutions of ascorbic acid (AA) at different concentration levels. On the other hand, liposomes were doped with Annonacin (Ann), a mono-tetrahydrofuran acetogenin (ACG), which is an effective citotoxic substance. While AA pharmacologic effect and action mechanisms are widely known, those of Ann’s are only very recently being studied. Both Fourier Transformed Infrared (FTIR) and Raman spectroscopic techniques were used to study the participation of the main functional groups of the lipid bilayer involved in the membrane-solution interaction. The obtained spectra were comparatively analyzed, studying the spectral bands corresponding to both the hydrophobic and the hydrophilic regions in the lipid bilayer. Electrochemical experiments namely; impedance spectroscopy (EIS) and cyclic voltamperometry (CV) were used as the main characterization techniques to analyse stability and structural changes of a model system of supported EggPC bilayer in connection with its interactions with AA and Ann. At high molar ratios of AA, there is dehydration in both populations of the carbonyl group of the polar head of the lipid. On the other hand, Ann promotes the formation of hydrogen bonds with the carbonyl groups. No interaction between AA and phosphate groups is observed at low and intermediate molar ratios. Ann is expected to be able to induce the dehydration of the phosphate groups without the subsequent formation of H bonds with them. According to the electrochemical analysis, the interaction of AA with the supported lipid membrane does not alter its dielectric properties. This fact can be related to the conservation of structured water of the phosphate groups in the polar heads of the lipid. On the other hand, the incorporation of Ann into the lipid membrane generates an increase in the number of defects while changes the dielectric constant. This, in turn, can be associated with the induced dehydration of the phosphate groups.Facultad de Ciencias ExactasFacultad de Ingeniería (FI)Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA

Fibrohistiocitoma maligno óseo tras degeneración de enfermedad de Paget Caso clínico y revisión de la literatura

El fibrohistiocitoma maligno óseo es un tumor de estirpe mesenquimal poco frecuente, pero de alta agresividad. Se suele presentar de forma primaria, aunque a veces lo hace sobre lesiones previas en el hueso. Puede ser difícil de diferenciar histológicamente de otros tumores, pero es una entidad propia desde el punto de vista anatomopatológico. Presentamos un paciente con enfermedad de Paget que desarrolló un fibrohistiocitoma maligno óseo en el fémur sobre el hueso pagético. Fue tratado mediante desarticulación de cadera. No se usó quimioterapia como tratamiento coadyuvante debido a su avanzada edad y situación basal. A los 18 meses se encuentra asintomático y sin signos de recurrencia. Se hace una revisión de la literatura acerca de este tumor.Malignant fibrous histiocytoma of bone is a rare but highly agressive mesenchimal tumor. It usually arises as a primary tumor but sometimes it can be associated with pre-existing bone abnormalities. Histologically it can be missdiagnosed with other tumors. We report a case of malignant fibrous histiocytoma of bone in the femur in a patient with Paget's disease treated by hip desarticulation. We didn't use chemotherapy because his elderly status. At 18 months follow up, the patient is symptom-free and neither local recurrence nor metastasis have been found. A review of the literature has been carried out

Paleoseismological evidence of holocene activity of the Los Tollos fault (Murcia, se Spain): a lately formed quaternary tectonic feature of the eastern betic shear zone

The Los Tollos Fault is a recent and important feature of the Eastern Betic Shear Zone, one of the major tectonic structures in South Iberia accommodating the convergence between Nubian and Eurasian plates in the western Mediterranean. The Los Tollos Fault became active by the end of Middle Pleistocene introducing some paleogeographical modifications. Previously mapped as a secondary normal fault related to the Carrascoy Fault, recent research evidences that the Los Tollos Fault is an independent Holocene active left-lateral reverse fault extending for at least 15 km. Data analysis from 4 trenches dug across the fault has revealed the occurrence of at least two paleo-earthquake events during the Holocene. The most recent event is dated between 2,740 and 2,140 yr BP (8th to 2nd centuries BC). The size of the paleoevents is calculated to be Mw 6.3 – 6.6 following empirical regressions on surface rupture length. The recurrence interval is estimated to be between 2,200-6,860 years, fitting a slip rate for the fault between 0.12 and 0.17 mm/yr. Such parameters highlight the Los Tollos Fault as a tectonic structure with a considerable activity located relatively close to densely populated areas. These seismogenic parameters should be considered in future reassessments of the seismic hazard of the regionThis work forms part of the research activities carried out in the FASEGEO Project (CGL2009-09726) funded by the Spanish Ministry of Science and Innovatio

Linkage disequilibrium, persistence of phase, and effective population size in Spanish local beef cattle breeds assessed through a high-density single nucleotide polymorphism chip

We have used the BovineHD Genotyping BeadChip to obtain high density genotypes (>700, 000 SNP after quality control) from 116 trios in five Spanish local beef cattle breeds. Linkage disequilibrium (LD) was meas- ured through the r2 statistic. Average r2 for adjacent markers in the five breeds were very close, around 0.52, and de- creased with increasing distance between markers, although in long distances some LD remained (0.07 and 0.05 for markers 200 kb and 1000 kb apart, respectively). At all distances the standard deviations were large and the shape of the distribution varied depending upon the marker dis- tance. Average r2 varied also between chromosomes. Pair- wise correlations between the r’s estimated in two breeds at short distances (5 kb) was in the rank of 0.6 – 0.7. Similarly to r2 estimates, this correlation decreased with increasing marker distance

Expression, purification and initial characterization of human serum albumin domain I and its cysteine 34

Human serum albumin presents in its primary structure only one free cysteine (Cys34) which constitutes the most abundant thiol of plasma. An antioxidant role can be attributed to this thiol, which is located in domain I of the protein. Herein we expressed domain I as a secretion protein using the yeast Pichia pastoris. In the initial step of ammonium sulfate precipitation, a brown pigment co-precipitated with domain I. Three chromatographic methods were evaluated, aiming to purify domain I from the pigment and other contaminants. Purification was achieved by cation exchange chromatography. The protein behaved as a noncovalent dimer. The primary sequence of domain I and the possibility of reducing Cys34 to the thiol state while avoiding the reduction of internal disulfides were confirmed by mass spectrometry. The reactivity of the thiol towards the disulfide 5,5´-dithiobis(2-nitrobenzoate) was studied and compared to that of full-length albumin. A ~24-fold increase in the rate constant was observed for domain I with respect to the entire protein. These results open the door to further characterization of the Cys34 thiol and its oxidized derivatives

Paleoseismological evidence of Holocene activity of the Los Tollos Fault (Murcia, SE Spain): A lately formed Quaternary tectonic feature of the Eastern Betic Shear Zone

The Los Tollos Fault is a recent and important feature of the Eastern Betic Shear Zone, one of the major tectonic structures in South Iberia accommodating the convergence between Nubian and Eurasian plates in the western Mediterranean. The Los Tollos Fault became active by the end of Middle Pleistocene introducing some paleogeographical modifications. Previously mapped as a secondary normal fault related to the Carrascoy Fault, recent research evidences that the Los Tollos Fault is an independent Holocene active left-lateral reverse fault extending for at least 15 km. Data analysis from 4 trenches dug across the fault has revealed the occurrence of at least two paleo-earthquake events during the Holocene. The most recent event is dated between 2,740 and 2,140 yr BP (8th to 2nd centuries BC). The size of the paleoevents is calculated to be Mw 6.3 – 6.6 following empirical regressions on surface rupture length. The recurrence interval is estimated to be between 2,200-6,860 years, fitting a slip rate for the fault between 0.12 and 0.17 mm/yr. Such parameters highlight the Los Tollos Fault as a tectonic structure with a considerable activity located relatively close to densely populated areas. These seismogenic parameters should be considered in future reassessments of the seismic hazard of the region.La falla de Los Tollos es una estructura reciente e importante de la Zona de Cizalla de la Bética Oriental, la principal estructura del sureste de la Península Ibérica que acomoda gran parte de la convergencia entre las placas de Eurasia y Nubia en el Mediterráneo Occidental. La falla de Los Tollos, descrita inicialmente como una falla normal secundaria relacionada con la falla de Carrascoy, comenzó su actividad a finales del Pleistoceno Medio generando algunas modificaciones paleogeográficas significativas. El trabajo que aquí presentamos demuestra su activad durante el Holoceno con una cinemática lateral sinestral con componente inversa a lo largo de una longitud de 15 km, e independiente de la Falla de Carrascoy. Del análisis de los datos obtenidos en 4 trincheras paleosismológicas realizadas a lo largo de la traza de la falla, se han podido interpretar la ocurrencia de al menos 2 paleoterremotos durante el Holoceno, acotándose el evento más reciente entre hace 2.740 y 2.140 años (siglos VIII a II a.C.). La magnitud máxima de estos paleoterremotos, estimada mediante correlaciones empíricas que consideran la longitud de rotura en superficie de la falla, se encuentra entre Mw 6,3 y 6,6, con un periodo de recurrencia comprendido entre 2.200 y 6.860 años. La tasa de deslizamiento neta calculada para la falla se estima entre 0,12 y 0,17 mm/a. Estos parámetros identifican la falla de Los Tollos como una estructura activa situada en las cercanías de áreas densamente pobladas y ponen de manifiesto el interés que tendría considerarla en futuras reevaluaciones de la peligrosidad sísmica en la región

Characterization of interactions of eggPC lipid structures with different biomolecules

In this paper we study the interactions of two biomolecules (ascorbic acid and Annonacin) with a bilayer lipid membrane. Egg yolk phosphatidylcholine (eggPC) liposomes (in crystalline liquid state) were prepared in solutions of ascorbic acid (AA) at different concentration levels. On the other hand, liposomes were doped with Annonacin (Ann), a mono-tetrahydrofuran acetogenin (ACG), which is an effective citotoxic substance. While AA pharmacologic effect and action mechanisms are widely known, those of Ann’s are only very recently being studied. Both Fourier Transformed Infrared (FTIR) and Raman spectroscopic techniques were used to study the participation of the main functional groups of the lipid bilayer involved in the membrane-solution interaction. The obtained spectra were comparatively analyzed, studying the spectral bands corresponding to both the hydrophobic and the hydrophilic regions in the lipid bilayer. Electrochemical experiments namely; impedance spectroscopy (EIS) and cyclic voltamperometry (CV) were used as the main characterization techniques to analyse stability and structural changes of a model system of supported EggPC bilayer in connection with its interactions with AA and Ann. At high molar ratios of AA, there is dehydration in both populations of the carbonyl group of the polar head of the lipid. On the other hand, Ann promotes the formation of hydrogen bonds with the carbonyl groups. No interaction between AA and phosphate groups is observed at low and intermediate molar ratios. Ann is expected to be able to induce the dehydration of the phosphate groups without the subsequent formation of H bonds with them. According to the electrochemical analysis, the interaction of AA with the supported lipid membrane does not alter its dielectric properties. This fact can be related to the conservation of structured water of the phosphate groups in the polar heads of the lipid. On the other hand, the incorporation of Ann into the lipid membrane generates an increase in the number of defects while changes the dielectric constant. This, in turn, can be associated with the induced dehydration of the phosphate groups.Facultad de Ciencias ExactasFacultad de Ingeniería (FI)Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA

Abnormal Distribution and Function of Circulating Monocytes and Enhanced Bacterial Translocation in Major Depressive Disorder

Introduction: Major depressive disorder (MDD) patients experience a systemic inflammatory stage. Monocytes play an important role in innate inflammatory responses and may be modulated by bacterial translocation. Our aim was to investigate the subset distribution and function of circulating monocytes, levels of proinflammatory cytokines, gut barrier damage, and bacterial translocation in MDD patients. Methods: Twenty-two MDD patients without concomitant diseases and 14 sex- and age-matched healthy controls were studied. The levels of circulating CD14++CD16- (classical), CD14++CD16++ (intermediate) and CD14- CD16++ (nonclassical) monocytes and the intracytoplasmic tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 expression in the presence or absence of lipopolysaccharide (LPS) stimulation were analyzed by polychromatic flow cytometry. The serum TNF-α, IL-1β, IL-6, and IL-10 levels were measured by Luminex. LPS-binding protein (LBP), intestinal fatty acidbinding protein (I-FABP), and zonulin were measured by enzyme-linked immunosorbent assay (ELISA). Results: MDD patients had a significant increase in the frequency of intermediate monocytes and a significant decrease in the frequency of classical monocytes compared to those in the healthy controls. MDD patients had a significantly increased percentage of classical monocytes that expressed IL-1β, intermediate monocytes that expressed IL-1β and IL6 and nonclassical monocytes that expressed IL-1β, and decreased levels of nonclassical monocytes that expressed IL6 compared to those in the healthy controls. MDD patients had significantly increased levels of circulating TNF-α, IL-1β, LBP, and I-FABP compared to those in the healthy controls. MDD patients with high LBP levels had a significant reduction in the number of circulating monocytes compared to that in the normal-LBP MDD patients, which can be mainly ascribed to a decrease in the number of intermediate and nonclassical monocytes. Conclusions: We have demonstrated that compared to the healthy controls, MDD patients show a marked alteration in circulating monocytes, with an expansion of the intermediate subset with increased frequency of IL-1β and IL-6 producing cells. These patients also exhibited a systemic proinflammatory state, which was characterized by the enhanced serum TNF-α and IL-1β levels compared to those in the healthy controls. Furthermore, MDD patients showed increased LBP and I-FABP levels compared to those in healthy controls, indicating increased bacterial translocation and gut barrier damage