TNF-α and IL-10 downregulation and marked oxidative stress in Neuromyelitis Optica

<p>Abstract</p> <p>Background</p> <p>Neuromyelitis optica is a central nervous system demyelinating and inflammatory syndrome. The objective of this study is to identify cytokines related to the cellular immune response as well as blood brain barrier integrity and oxidative stress.</p> <p>Methods</p> <p>We performed a molecular characterization of cellular immune response and oxidative stress in serum from relapsing-NMO (R-NMO) patients and established the correlations between the clinical measurements and molecular parameters using the Bayesian approach.</p> <p>Serum samples from 11 patients with R-NMO diagnosed according to Wingerchuk criteria and matched in terms of age, gender and ethnicity with the healthy controls were analyzed. The levels of TNF-<it>α</it>, IFN-<it>γ</it>, IL-10, MMP-9, TIMP-1 and oxidative stress markers: malondialdehyde, advanced oxidation protein products, peroxidation potential, superoxide dismutase, catalase, and total hydroperoxides were measured.</p> <p>Results</p> <p>We found almost undetectable levels of TNF-<it>α</it>, a decreased production of IL-10 and a significant up-regulation of every oxidative stress biomarker studied. The insufficient production of TNF-<it>α </it>and IL-10 in R-NMO patients, which are two important players of T cell mediated immunoregulation, suggest an effector – regulator imbalance. The overproduction of oxygen reactive species as a consequence of the chronic inflammatory milieu is reflected on the excess of oxidative damage mediators detected. Furthermore, Multidimensional Scaling and a Bayesian linear regression model revealed a significant linear dependence between Expanded Disability Status Scale Kurtzke and TIMP-1; pointing to a possible predictive or prognostic value of this clinical-molecular relationship.</p> <p>Conclusion</p> <p>These results suggest that there is a breakdown in immunoregulatory mechanisms and noteworthy pro-oxidant environment contributing to NMO pathogenesis.</p

Zircon Dates Long-Lived Plume Dynamics in Oceanic Islands

In this contribution we report the first systematic study of zircon U-Pb geochronology and δO-εHf isotope geochemistry from 10 islands of the hot-spot related Galapagos Archipelago. The data extracted from the zircons allow them to be grouped into three types: (a) young zircons (0–∼4 Ma) with εHf (∼5–13) and δO (∼4–7) isotopic mantle signature with crystallization ages dating the islands, (b) zircons with εHf (∼5–13) and δO (∼5–7) isotopic mantle signature (∼4–164 Ma) which are interpreted to date the time of plume activity below the islands (∼164 Ma is the minimum time of impingement of the plume below the lithosphere), and (c) very old zircons (∼213–3,000 Ma) with mostly continental (but also juvenile) εHf (∼−28–8) and δO (∼5–11) isotopic values documenting potential contamination from a number of sources. The first two types with similar isotopic mantle signature define what we call the Galápagos Plume Array (GPA). Given lithospheric plate motion, this result implies that GPA zircon predating the Galápagos lithosphere (i.e., >14–164 Ma) formed and were stored at sublithospheric depths for extended periods of time. In order to explain these observations, we performed 2D and 3D thermo-mechanical numerical experiments of plume-lithosphere interaction which show that dynamic plume activity gives rise to complex asthenospheric flow patterns and results in distinct long-lasting mantle domains beneath a moving lithosphere. This demonstrates that it is physically plausible that old plume-derived zircons survive at asthenospheric depths below ocean islands.This study was supported by the Deutsche Forschungsgemeinschaft Grant RO4174/3‐1 and RO4174/3‐3 to YR‐A and SB, MICINN PID2019‐105625RB‐C21, PY20_00550 to AG‐C. BK acknowledges funding from ERC Consolidator Grant MAGMA 771143

The geology of Cuba: A brief overview and synthesis

Cuba is the largest island in the Greater Antilles, and its geology records three important episodes: (1) the Jurassic breakup of North and South America (Pangea) and associated passive margin and oceanic sedimentary and magmatic evolution; (2) the sedimentary, magmatic, and metamorphic evolution of an intra-oceanic Cretaceous-Paleogene ophiolite-arc complex; and (3) the Paleogene 'soft collision' and transfer of the NW Caribbean plate (and Cuba) to the North American plate. Thick sequences of Jurassic-Cretaceous strata (conglomerates, sandstones, limestones, dolo­stones, shales) and interlayered basaltic rocks characterize passive margin sequences preserved in the Guaniguanico terrane (western Cuba, related to the Mayan passive margin and the Gulf of Mexico) and the Bahamas Platform borderlands (north of Cuba). Passive margin deposition ceased in latest Cretaceous time, when increasing relief of accreted (overriding) oceanic arc and ophiolite complexes shed coarse sediments (olistostrome and flysch), followed by carbonate deposition. Fragments of the intervening oceanic lithosphere (Proto-Caribbean, connected to the Central Atlantic) and fore- and back-arc oceanic lithosphere (Caribbean, of Pacific origin) occur as tectonic fragments detached from the ophiolitic units, including serpentinized harzburgites and dunites, banded and isotropic gabbros, basalts (tholeiitic and fore-arc basalts, locally with boninites) and Late Jurassic (Tithonian) through Late Cretaceous (Coniacian and younger) oceanic sediments. Arc activity in the Cuban segment of the Greater Antilles produced sedimentary, volcanic, and plutonic rocks during Cretaceous times (ca. 135-70 Ma). A new arc developed in eastern Cuba during Paleocene-middle Eocene times. Cuban arc sequences include island-arc tholeiitic, calcalkaline, and alkaline bimodal suites of volcanic and plutonic rocks. Remnants of Proto-Caribbean oceanic lithosphere occur as exhumed mélange-bearing eclogite-, blueschist-, and garnet-amphibolite-facies tectonic blocks (oldest age ca. 120 Ma) within a serpentinite matrix intercalated with, or at the base of, the overthrusted ophiolitic bodies. Cuban Cretaceous arc magmatic activity ended due to the subduction of Proto-Caribbean passive margin sequences of the Caribeana terrane, an offshore protuberance of Yucatan. This event formed strongly deformed high-pressure meta­sedimentary and metaigneous rocks at ca. 70 Ma, when the Caribbean plate began to collide with North America. The collision, which included overriding of the ophiolitic and arc units over both subducted and unsubducted passive margin sequences, also produced synorogenic basins and filled them, a process that continued until ca. 40 Ma. This foldbelt was succeeded by local uplift and subsidence to form late Eocene-Recent unconformable post-orogenic continental basins

Modelo de estructuración de contenidos para el perfeccionamiento curricular de la licenciatura en enfermería

Ante la necesidad de gestionar un cambio en los currículos de pregrado de Enfermería, en medio de un contexto social rápidamente cambiante, se consideró la importancia de dar pasos a favor de que el perfeccionamiento curricular sentara las bases para la preservación de los elementos de calidad esencial es para un diseño orientado a la formación pertinente de enfermeros universitarios en el contexto contemporáneo. Como objetivo se establece un modelo teórico de estructuración de contenidos sobre determinadas bases teórico-metodológicas previamente establecidas. Se realizó triangulación metodológica mediante la aplicación de métodos teóricos de análisis y síntesis de toda la base documental revisada y la realización de grupos focales con expertos de dos grupos, en un proceso que transcurrió entre los años 2004 y 2009, conjuntamente con el del perfeccionamiento del currículo de la Licenciatura en Enfermería para su transformación en plan de estudio "D".Se estableció un modelo teórico de estructuración de los contenidos, coherente con el encargo social, en correspondencia con las bases teórico-metodológicas propuestas, como parte de un sistema cubano de formación de enfermeros profesionales, con orientación hacia el desarrollo temprano y creciente de habilidades profesionales, que satisfagan las exigencias actuales del desempeño profesional a cualquier nivel del Sistema Nacional de Salud. La metodología aplicada permitió el logro del objetivo y, adicionalmente, permitió ensayar una metodología de trabajo para la conformación del plan de estudio.Palabras clave: Perfeccionamiento curricular, plan de estudio, interdisciplinariedad, estrategias curriculares</p

Experimental evidence for the preservation of U-Pb isotope ratios in mantle-recycled crustal zircon grains

Zircon of crustal origin found in mantle-derived rocks is of great interest because of the information it may provide about crust recycling and mantle dynamics. Consideration of this requires understanding of how mantle temperatures, notably higher than zircon crystallization temperatures, affected the recycled zircon grains, particularly their isotopic clocks. Since Pb2+ diffuses faster than U4+ and Th+4, it is generally believed that recycled zircon grains lose all radiogenic Pb after a few million years, thus limiting the time range over which they can be detected. Nonetheless, this might not be the case for zircon included in mantle minerals with low Pb2+ diffusivity and partitioning such as olivine and orthopyroxene because these may act as zircon sealants. Annealing experiments with natural zircon embedded in cristobalite (an effective zircon sealant) show that zircon grains do not lose Pb to their surroundings, although they may lose some Pb to molten inclusions. Diffusion tends to homogenize the Pb concentration in each grain changing the U-Pb and Th-Pb isotope ratios proportionally to the initial 206Pb, 207Pb and 208Pb concentration gradients (no gradient-no change) but in most cases the original age is still recognizable. It seems, therefore, that recycled crustal zircon grains can be detected, and even accurately dated, no matter how long they have dwelled in the mantle.This paper has been financed by the Spanish Grants CGL2013-40785-P and CGL2017-84469-P

Better than DEET Repellent Compounds Derived from Coconut Oil

Hematophagous arthropods are capable of transmitting human and animal pathogens worldwide. Vector-borne diseases account for 17% of all infectious diseases resulting in 700,000 human deaths annually. Repellents are a primary tool for reducing the impact of biting arthropods on humans and animals. N,N-Diethyl-meta-toluamide (DEET), the most effective and long-lasting repellent currently available commercially, has long been considered the gold standard in insect repellents, but with reported human health issues, particularly for infants and pregnant women. In the present study, we report fatty acids derived from coconut oil which are novel, inexpensive and highly efficacious repellant compounds. These coconut fatty acids are active against a broad array of blood-sucking arthropods including biting flies, ticks, bed bugs and mosquitoes. The medium-chain length fatty acids from C8:0 to C12:0 were found to exhibit the predominant repellent activity. In laboratory bioassays, these fatty acids repelled biting flies and bed bugs for two weeks after application, and ticks for one week. Repellency was stronger and with longer residual activity than that of DEET. In addition, repellency was also found against mosquitoes. An aqueous starch-based formulation containing natural coconut fatty acids was also prepared and shown to protect pastured cattle from biting flies up to 96-hours in the hot summer, which, to our knowledge, is the longest protection provided by a natural repellent product studied to date

IgG Antibodies against Measles, Rubella, and Varicella Zoster Virus Predict Conversion to Multiple Sclerosis in Clinically Isolated Syndrome

BACKGROUND:Multiple sclerosis (MS) is characterized by a polyspecific B-cell response to neurotropic viruses such as measles, rubella and varicella zoster, with the corresponding antibodies measurable in CSF as the so-called "MRZ reaction" (MRZR). We aimed to evaluate the relevance of MRZR to predict conversion of patients with clinically isolated syndrome (CIS) to MS, and to compare it to oligoclonal bands (OCB) and MRI. METHODOLOGY/PRINCIPAL FINDINGS:MRZR was determined in a prospective study over 2 years including 40 patients that remained CIS over follow-up (CIS-CIS) and 49 patients that developed MS (CIS-RRMS) using ELISA. Using logistic regression, a score (MRZS) balancing the predictive value of the antibody indices included in MRZR was defined (9 points measles, 8 points rubella, 1 point varicella zoster, cutpoint: sum of scores greater 10). MRZR and MRZS were significantly more frequent in CIS-RRMS as compared to CIS-CIS (p=0.04 and p=0.02). MRZS showed the best positive predictive value (PPV) of all parameters investigated (79%, 95%-CI: 54-94%), which could be further increased by combination with MRI (91%, 95%-CI: 59-99%). CONCLUSIONS/SIGNIFICANCE:Our data indicate the relevance of MRZR to predict conversion to MS. It furthermore shows the importance of weighting the different antibody indices included in MRZR and suggest that patients with positive MRZR are candidates for an early begin of immunomodulatory therapy

Assessment of Yellow Fever Epidemic Risk: An Original Multi-criteria Modeling Approach

This article describes the use of an original modeling approach to assess the risk of yellow fever (YF) epidemics. YF is a viral hemorrhagic fever responsible in past centuries for devastating outbreaks. Since the 1930s, a vaccine has been available that protects the individual for at least 10 years, if not for life. However, immunization of populations in African countries was gradually discontinued after the 1960s. With the decrease in immunity against YF in African populations the disease reemerged in the 1980s. In 2005, WHO, UNICEF, and the GAVI Alliance decided to support preventive vaccination of at-risk populations in West African endemic countries in order to tackle the reemergence of YF and reduce the risk of urban YF outbreaks. Financial resources were made available to scale up a global YF vaccine stockpile and to support countries with limited resources in the management of preventive vaccination campaigns. This article describes the process we used to determine the most at-risk populations using a mathematical model to prioritize targeted immunization campaigns. We believe that this approach could be useful for other diseases for which decision making process is difficult because of limited data availability, complex risk variables, and a need for rapid decisions and implementation

Triassic sedimentation and postaccretionary crustal evolution along the Solonker suture zone in Inner Mongolia, China

Detrital zircon U-Pb dating of the Xingfuzhilu Formation in southern Inner Mongolia yields a maximum depositional age of around 220 Ma. The predominantly Permian and Triassic zircons are characterized by oscillatory zoning and euhedral shapes, with mostly positive zircon εHf(t) values (+2.0 to +16.4), indicating that they were derived from a proximal magmatic source. Early-Middle Paleozoic zircons have variable zircon εHf(t) values from −6.2 to +11.2 and are characterized by weak oscillatory zoning and subhedral-subrounded shapes, suggesting that the sources are a proximal magmatic arc, possibly mixed with components of the Ondor Sum magmatic arc and the magmatic arc at the northern margin of the North China Craton. The remnants of Precambrian blocks in the southeastern Central Asian Orogenic Belt (CAOB), and the North China Craton may also have been a minor source region for the Xingfuzhilu succession. These results, combined with regional data, indicate that a closing remnant ocean basin or narrow seaway possibly existed in the Middle Permian (Guadalupian) immediately prior to final collision of the CAOB and closure of the Paleo-Asian Ocean. Subsequent collision resulted in the crustal uplift and thickening along the Solonker suture zone, accompanied by possible slab break-off and lithospheric delamination during the Latest Permian to Middle Triassic. The resultant orogen in the Late Triassic underwent exhumation and denudation of rocks in response to the postorogenic collapse and regional extension. Vertical crustal growth in the Triassic is documented by detrital zircons from the Xingfuzhilu Formation and appears to have been widespread across entire eastern CAOB

Minerales 'exóticos' en cromititas ofiolíticas. Implicaciones para la geodinámica mantélica

Los depósitos ofiolíticos de cromita constituyen un rasgo característico de la secuencia mantélica de las ofiolitas (González-Jiménez et al., 2014 y referencias en éste). Los cuerpos de cromititas se encuentran en dunitas y harzburgitas distribuyéndose a lo largo de una zona de espesor variable, entre 1 y 2 km, debajo de los niveles de gabros bandeados de la corteza inferior oceánica. El origen de cuerpos monominerálicos de cromita en el manto, especialmente el mecanismo de concentración de cromita y el ambiente tectónico de formación, continúa siendo un tema sujeto a debate (e.g., Proenza et al., 1999; González-Jiménez et al., 2014). A tal efecto, se han propuesto hipótesis basadas en: i) cristalización cotéctica de cromita+olivino y su posterior separación mecánica; ii) procesos de mezcla o contaminación de magmas; iii) asimilación de piroxenitas y gabros; iv) aumento del grado de polimerización del fundido debido a la pérdida de agua; v) cambios en la fugacidad de oxígeno. Todas estas hipótesis asumen procesos a baja presión en el manto (<20 km profundidad)