Barrier dysfunction or drainage reduction: differentiating causes of CSF protein increase

BACKGROUND Cerebrospinal fluid (CSF) protein analysis is an important element in the diagnostic chain for various central nervous system (CNS) pathologies. Among multiple existing approaches to interpreting measured protein levels, the Reiber diagram is particularly robust with respect to physiologic inter-individual variability, as it uses multiple subject-specific anchoring values. Beyond reliable identification of abnormal protein levels, the Reiber diagram has the potential to elucidate their pathophysiologic origin. In particular, both reduction of CSF drainage from the cranio-spinal space as well as blood-CNS barrier dysfunction have been suggested ρas possible causes of increased concentration of blood-derived proteins. However, there is disagreement on which of the two is the true cause. METHODS We designed two computational models to investigate the mechanisms governing protein distribution in the spinal CSF. With a one-dimensional model, we evaluated the distribution of albumin and immunoglobulin G (IgG), accounting for protein transport rates across blood-CNS barriers, CSF dynamics (including both dispersion induced by CSF pulsations and advection by mean CSF flow) and CSF drainage. Dispersion coefficients were determined a priori by computing the axisymmetric three-dimensional CSF dynamics and solute transport in a representative segment of the spinal canal. RESULTS Our models reproduce the empirically determined hyperbolic relation between albumin and IgG quotients. They indicate that variation in CSF drainage would yield a linear rather than the expected hyperbolic profile. In contrast, modelled barrier dysfunction reproduces the experimentally observed relation. CONCLUSIONS High levels of albumin identified in the Reiber diagram are more likely to originate from a barrier dysfunction than from a reduction in CSF drainage. Our in silico experiments further support the hypothesis of decreasing spinal CSF drainage in rostro-caudal direction and emphasize the physiological importance of pulsation-driven dispersion for the transport of large molecules in the CSF

RA-specific expression profiles and new candidate genes

Objective: To identify rheumatoid arthritis- (RA)-specific profiles of differentially expressed genes. Methods: Synovial tissues from RA and osteoarthritis (OA) patients and from normal joints were selected according to their disease-characteristic histology. Gene expression was analyzed using DNA microarrays (GeneChip; Unigene-array) and representational difference analysis (RDA). Data were validated on larger cohorts of patients by RT-PCR. Results: Nine hundred and eighty genes were significantly regulated in RA synovial tissue as compared with non-RA. Specialized cluster analysis identified a set of 312 genes as sufficient of unequivocally discriminating RA from non-RA patterns (class discovery). Genes of highest regulation were associated with leukocyte activation (chemokines, chemokine receptors, B- and T-cell genes), endothelial and angiogenic activation, tissue destruction and remodelling [MMP-3, BMP-4, TIMPs]. Interestingly, a large set of genes was down-regulated in RA (TGF-β superfamily, apoptosis-related genes, transcription factors). Osteopontin-like genes (n=46) — up-regulated in RA — and glutathione peroxidase-3-like genes (n=85) — down-regulated in RA — yielded the highest correlation coefficients (>0.94). Megakaryocyte stimulating factor (MSF), down-regulated in a subset of RA, may hold the key to subclassification: a loss-of-function mutation in the MSF-encoding gene leads to synovial hyperplasia in camptodactyly–arthropathy–coxa vara–pericarditis syndrome, and, as in RA, also to pericardial involvement. A further candidate, vitamin-D3-up-regulated protein-1 (VDUP-1), is regulated like MSF and predisposes to premature coronary artery disease when mutated, again a feature of a subset of RA. Conclusion: RA specific gene profiles were identified and are useful to improve diagnostics of the disease. Novel gene candidates not yet in the focus of RA pathogenesis have been identified that are likely to further the understanding of RA

Monoallelic maternal expression of STAT5A affects embryonic survival in cattle

<p>Abstract</p> <p>Background</p> <p>Reproductive disorders and infertility are surprisingly common in the human population as well as in other species. The decrease in fertility is a major cause of cow culling and economic loss in the dairy herd. The conception rate has been declining for the past 30–50 years. Conception rate is the product of fertilization and embryonic survival rates. In a previous study, we have identified associations of several single nucleotide polymorphisms (SNPs) in the signal transducer and activator 5A (<it>STAT5A</it>) with fertilization and survival rates in an <it>in </it>vitro experimental system. The objectives of this study are to fine map the <it>STAT5A </it>region in a search for causative mutations and to investigate the parent of origin expression of this gene.</p> <p>Results</p> <p>We have performed a total of 5,222 fertilizations and produced a total of 3,696 in vitro fertilized embryos using gametes from 440 cows and eight bulls. A total of 37 SNPs were developed in a 63.4-kb region of genomic sequence that includes <it>STAT5A</it>, <it>STAT3</it>, and upstream and downstream sequences of these genes. SNP153137 (G/C) in exon 8 of <it>STAT5A </it>was associated with a significant variability in embryonic survival and fertilization rate compared to all other examined SNPs. Expression analysis revealed that <it>STAT5A </it>is primarily monoallelically expressed in early embryonic stages but biallelically expressed in later fetal stages. Furthermore, the occurrence of monoallelic maternal expression of <it>STAT5A </it>was significantly higher in blastocysts, while paternal expression was more frequent in degenerative embryos.</p> <p>Conclusion</p> <p>Our results imply that <it>STAT5A </it>affects embryonic survival in a manner influenced by developmental stage and allele parent of origin.</p

On the origin of the O and B-type stars with high velocities II Runaway stars and pulsars ejected from the nearby young stellar groups

We use milli-arcsecond accuracy astrometry (proper motions and parallaxes) from Hipparcos and from radio observations to retrace the orbits of 56 runaway stars and nine compact objects with distances less than 700 pc, to identify the parent stellar group. It is possible to deduce the specific formation scenario with near certainty for two cases. (i) We find that the runaway star zeta Ophiuchi and the pulsar PSR J1932+1059 originated about 1 Myr ago in a supernova explosion in a binary in the Upper Scorpius subgroup of the Sco OB2 association. The pulsar received a kick velocity of about 350 km/s in this event, which dissociated the binary, and gave zeta Oph its large space velocity. (ii) Blaauw & Morgan and Gies & Bolton already postulated a common origin for the runaway-pair AE Aur and mu Col, possibly involving the massive highly-eccentric binary iota Ori, based on their equal and opposite velocities. We demonstrate that these three objects indeed occupied a very small volume \sim 2.5Myr ago, and show that they were ejected from the nascent Trapezium cluster. We identify the parent group for two more pulsars: both likely originate in the 50 Myr old association Per OB3, which contains the open cluster alpha Persei. At least 21 of the 56 runaway stars in our sample can be linked to the nearby associations and young open clusters. These include the classical runaways 53 Arietis (Ori OB1), xi Persei (Per OB2), and lambda Cephei (Cep OB3), and fifteen new identifications, amongst which a pair of stars running away in opposite directions from the region containing the lambda Ori cluster. Other currently nearby runaways and pulsars originated beyond 700 pc, where our knowledge of the parent groups is very incomplete.Comment: Accepted for publication in the A&A. 29 pages, 19 figure

Desafio anatômico: uma metodologia capaz de auxiliar no aprendizado de anatomia humana

In 2007 the city of Cajazeiras-PB received the implantation of the School of Medicine from Federal University of Campina Grande. In this process professors were faced with several difficulties. To propose improvements and even supplementation in Anatomy concepts, they created a didactic activity called “Anatomical Challenge” in which the students were instructed to fabricate didactical anatomical models to be used in classrooms, helping the content of the discipline. After work, the students were satisfied with the results, especially from the point of view of knowledge transmission and absorption of content. Thus, this experience was positive and unique to the process of teaching and learning of anatomy in medical school, because it stimulated creativity in many ways, memory and group working by the participants.Em 2007 a cidade de Cajazeiras-PB recebeu a implantação do curso de Medicina pela Universidade Federal de Campina Grande. Neste processo, os docentes se depararam com várias dificuldades. Para propor melhoras e até, suplementação da carga de conceitos em Anatomia Humana, foi criada uma atividade didática chamada “Desafio Anatômico”, no qual os discentes eram instruídos a confeccionar modelos anatômicos que fossem didáticos a ponto de serem usados nas aulas, auxiliando o conteúdoda disciplina. Após a apresentação dos trabalhos, os discentes mostraram-se satisfeitos com os resultados, sobretudo sob o ponto de vista de transmissão de conhecimento e absorção de conteúdo. Desta maneira, esta experiência mostrou-se positiva e singular para o processo de ensino-aprendizagem da anatomia no curso médico, pois a mesma estimulou de diversas formas a criatividade, memória e trabalho em grupo dos participantes

Simple sequence repeat variation in the Daphnia pulex genome

Background: Simple sequence repeats (SSRs) are highly variable features of all genomes. Their rapid evolution makes them useful for tracing the evolutionary history of populations and investigating patterns of selection and mutation across gnomes. The recently sequenced Daphnia pulex genome provides us with a valuable data set to study the mode and tempo of SSR evolution, without the inherent biases that accompany marker selection. Results: Here we catalogue SSR loci in the Daphnia pulex genome with repeated motif sizes of 1-100 nucleotides with a minimum of 3 perfect repeats. We then used whole genome shotgun reads to determine the average heterozygosity of each SSR type and the relationship that it has to repeat number, motif size, motif sequence, and distribution of SSR loci. We find that SSR heterozygosity is motif specific, and positively correlated with repeat number as well as motif size. For non-repeat unit polymorphisms, we identify a motif-dependent end-nucleotide polymorphism bias that may contribute to the patterns of abundance for specific homopolymers, dimers, and trimers. Our observations confirm the high frequency of multiple unit variation (multistep) at large microsatellite loci, and further show that the occurrence of multiple unit variation is dependent on both repeat number and motif size. Using the Daphnia pulex genetic map, we show a positive correlation between dimer and trimer frequency and recombination. Conclusions: This genome-wide analysis of SSR variation in Daphnia pulex indicates that several aspects of SSR variation are motif dependent and suggests that a combination of unit length variation and end repeat biased base substitution contribute to the unique spectrum of SSR repeat loci

Delimitation of Funga as a valid term for the diversity of fungal communities: the Fauna, Flora & Funga proposal (FF&F)

As public policies and conservation requirements for biodiversity evolve there is a need for a term for the kingdom Fungi equivalent to Fauna and Flora. Thisneed is considered to be urgent in order to simplify projects oriented toward implemention of educational and conservation goals. In an informal meeting held duringthe IX Congreso Latinoamericano de Micología by the authors, the idea of clarifying this matter initiated an extensive search of pertinent terminologies. As a result ofthese discussions and reviews, we propose that the word Funga be employed as an accurate and encompassing term for these purposes. This supports the proposal of thethree Fs, Fauna, Flora and Funga, to highlight parallel terminology referring to treatments of these macrorganism of particular geographical areas. Alternative terms andproposals are acknowledged and discussedFil: Kuhar, José Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Furci, Giuliana. Fundación Fungi; ChileFil: Drechsler-Santos, Elisandro Ricardo. Universidade Federal de Santa Catarina; BrasilFil: Pfister, Donald H.. Harvard University; Estados Unido

Observational Evidence for Massive Black Holes in the Centers of Active Galaxies

Naturally occurring water vapor maser emission at 1.35 cm wavelength provides an accurate probe for the study of accretion disks around highly compact objects, thought to be black holes, in the centers of active galaxies. Because of the exceptionally fine angular resolution, 200 microarcseconds, obtainable with very long baseline interferometry, accompanied by high spectral resolution, < 0.1 km/s, the dynamics and structures of these disks can be probed with exceptional clarity. The data on the galaxy NGC4258 are discussed here in detail. The mass of the black hole binding the accretion disk is 3.9 times 10^7 solar masses. Although the accretion disk has a rotational period of about 800 years, the physical motions of the masers have been directly measured with VLBI over a period of a few years. These measurements also allow the distance from the earth to the black hole to be estimated to an accuracy of 4 percent. The status of the search for other maser/black hole candidates is also discussed.Comment: 24 pages, 11 figures, latex, uses aaspp4 style file. To be published in the Journal of Astronomy and Astrophysics (India), proceedings of the Discussion Meeting on the Physics of Black Holes, Bangalore, India: December 199