Medical Library

Autosomal dominant sensory ataxia: a neuroaxonal dystrophy.

Autosomal dominant sensory ataxia (ADSA), a rare hereditary ataxia, is characterized by progressive dysfunction of central sensory pathways. Its pathological features have not been previously documented. We report a case of a 61-year-old man with ADSA who died of congestive heart failure. Autopsy specimens of brain, thoracolumbar spinal cord, peripheral nerve and skeletal muscle were examined. There was no abnormality on gross examination. Microscopically, there were occasional swollen axons within the cerebral cortex and deep nuclei, particularly the subthalamic nucleus, with no neuronal loss, gliosis or microglial activation. There were many axonal spheroids within the medulla, particularly in the dorsal column nuclei. Axonal spheroids were also seen in the dorsal columns and ventral horns in the thoracolumbar spinal cord, but there was no Wallerian degeneration or demyelination. Amyloid precursor protein (APP) immunostaining of some of the spheroids suggested continuing dysfunction of axoplasmic flow in some regions. There was mild inflammation of peripheral nerve roots but no spheroid, and patchy chronic inflammation of skeletal muscle. In summary, the major pathological process in ADSA is a neuroaxonal dystrophy most prominent in the dorsal columns and dorsal column nuclei, consistent with the clinical pattern of central sensory pathway degeneration.

Moeller JJ, Macaulay RJ, Valdmanis PN, Weston LE, Rouleau GA, Dupré N.

Division of Neurology, Department of Medicine, Dalhousie University, Halifax, NS, Canada.

Twenty-first century brain banking: at the crossroads.

Brain banks form an increasingly important resource for research. In view of declining autopsy rates, brain banks are also gaining importance for medical diagnostics, quality control and teaching. In the case of neurodegenerative diseases, brain banks have become drivers of discovery and are yielding invaluable taxonomic references for neuropathologists. This article provides comments on two recent landmark papers in the field (Bell JE et al. Acta Neuropathol 2008. doi:10.1007/s00401-008-0358-8; Vonsattel JP et al. Acta Neuropathol 2008. doi:10.1007/s00401-007-0311-9). Professionalisation of brain banking standards, ethical principles safeguarding the running of a brain bank and a proposed code of conduct for brain bank staff are outlined and discussed. Special emphasis is placed on the need to enable sustainability of the human brain tissue resource in the face of increased financial pressures on medical institutions and raised public expectations towards ethical human brain banking in a globalised economic environment. It is proposed that brain banks undergo rigorous international audit as a prerequisite for their registration with the relevant national neuropathological society. This promises to be an important safeguard so that proper standards can be assured when tissue is handed out to commercial companies. Honesty, accountability and complete transparency are mandatory to allow long-lasting success of the brain banking operation by guaranteeing that the best possible use is made of the tissue. Preferred access by private tissue users must be avoided and money must never be allowed to buy access to a brain bank. Since brain banks operate internationally, any mistake made may be felt around the globe and could endanger the public\’s willingness to donate brains for research. The much-needed increase in the number of control brain donations will only be achievable if broad-based support from the general public can be won and maintained.

Graeber MB.

The Athenaeum, Pall Mall, London, SW1Y 5ER, UK, manuel@graeber.net.

A local imbalance between MMP and TIMP may have an implication on the severity and course of appendicitis.

BACKGROUND: Matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) have been demonstrated to be involved in inflammatory conditions in the intestine. The purpose of this study was to investigate whether the alterations of the MMP/TIMP balance might reflect the course of the inflammatory process in acute appendicitis and if the expression and localisation of MMPs and TIMP is variable in the various clinical manifestations of appendicitis. MATERIALS AND METHODS: The study comprises 40 patients (26 men and 14 women) having emergency appendectomy and a control group constituting of 10 patients (5 men and 5 women) having a hemicolectomy for other reasons. MMP and TIMP expressions were assessed and compared in tissue specimens from phlegmonous (n = 15), gangrenous (n = 7), perforated appendicitis (n = 11) and controls with noninflamed appendices (n = 10) by means of enzyme-linked immunosorbent assay technique. Localisation of the enzymes was performed by immunohistochemistry. RESULTS: MMP-1 was significantly higher in gangrenous and perforated appendicitis compared with phlegmonous appendicitis and controls (p < 0.05) while MMP-2 was significantly lower in gangrenous appendicitis compared with phlegmonous appendicitis and controls. MMP-2 was also lower in perforated appendicitis when compared with controls (p < 0.01). Elevated expression of MMP-9 was demonstrated in all groups of appendicitis compared with the controls (p < 0.001). CONCLUSIONS: MMP-9 is the most abundantly expressed MMP of those investigated in inflamed appendix. We postulate that a local imbalance between MMP-9 and TIMP-1 may trigger a perforation. These results suggest that MMPs might be useful as biomarkers of appendices prone to perforation.

Solberg A, Holmdahl L, Falk P, Palmgren I, Ivarsson ML.

Department of Surgery, Colorectal unit, Sahlgrenska University Hospital/Östra, Gothenburg University, 416 85, Gothenburg, Sweden, anna.solberg@surgery.gu.se.

Inducible expression of Pisum sativum xyloglucan fucosyltransferase in the pea root cap meristem, and effects of antisense mRNA expression on root cap cell wall structural integrity.

Mitosis and cell wall synthesis in the legume root cap meristem can be induced and synchronized by the nondestructive removal of border cells from the cap periphery. Newly synthesized cells can be examined microscopically as they differentiate progressively during cap development, and ultimately detach as a new population of border cells. This system was used to demonstrate that Pisum sativum L. fucosyl transferase (PsFut1) mRNA expression is strongly expressed in root meristematic tissues, and is induced >2-fold during a 5-h period when mitosis in the root cap meristem is increased. Expression of PsFut1 antisense mRNA in pea hairy roots under the control of the CaMV35S promoter, which exhibits meristem localized expression in pea root caps, resulted in a 50-60% reduction in meristem localized endogenous PsFut1 mRNA expression measured using whole mount in situ hybridization. Changes in gross levels of cell wall fucosylated xyloglucan were not detected, but altered surface localization patterns were detected using whole mount immunolocalization with CCRC-M1, an antibody that recognizes fucosylated xyloglucan. Emerging hairy roots expressing antisense PsFut1 mRNA appeared normal macroscopically but scanning electron microscopy of tissues with altered CCRC-M1 localization patterns revealed wrinkled, collapsed cell surfaces. As individual border cells separated from the cap periphery, cell death occurred in correlation with extrusion of cellular contents through breaks in the wall.

Wen F, Celoy RM, Nguyen T, Zeng W, Keegstra K, Immerzeel P, Pauly M, Hawes MC.

Division of Plant Pathology and Microbiology, Department of Plant Sciences, Forbes Hall, University of Arizona, Tucson, AZ, 85721, USA.

Hypocotyl-based Agrobacterium-mediated transformation of soybean (Glycine max) and application for RNA interference.

An efficient system of gene transformation is necessary for soybean [Glycine max (L.) Merrill] functional genomics and gene modification by using RNA interference (RNAi) technology. To establish such system, we improved the conditions of tissue culture and transformation for increasing the frequency of adventitious shoots and decreasing the browning and necrosis of hypocotyls. Adding N(6)-benzylaminopurine (BAP) and silver nitrate in culture medium enhanced the shoot formation on hypocotyls. BAP increased the frequency of the hypocotyls containing adventitious shoots, while silver nitrate increased the number of shoots on the hypocotyls. As a result, the number of adventitious shoots on hypocotyls cultured in medium containing both BAP and silver nitrate was 5-fold higher than the controls. Adding antioxidants in co-cultivation medium resulted in a significant decrease in occurrence of browning and necrosis of hypocotyls and increase in levels of beta-Glucuronidase (GUS) gene expression. Histochemical assays showed that the apical meristem of hypocotyls was the \”target tissue\” for Agrobacterium tumefaciens transformation of soybean. Gene silencing of functional gene by using RNAi technology was carried out under above conditions. A silencing construct containing an inverted-repeat fragment of the GmFAD2 gene was introduced into soybean by using the A. tumefaciens-mediated transformation. Several lines with high oleic acid were obtained, in which mean oleic acid content ranged from 71.5 to 81.9%. Our study demonstrates that this transgenic approach could be efficiently used to improve soybean quality and productivity through functional genomics.

Wang G, Xu Y.

Key Laboratory of Photosynthesis and Environmental Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, 100093, Beijing, China.

Chromosomal DNA content of sweet pepper determined by association of cytogenetic and cytometric tools.

The nuclear DNA content of sweet pepper (Capsicum annuum L. var. annuum, 2n = 24) has been measured by flow and image cytometries but the DNA content of each chromosome of this species has not yet been regarded. DNA content of individual chromosomes has been quantified by the flow karyotyping technique, which requires a great quantity of intact metaphasic chromosomes and methods that allow the characterization of individual chromosomes; however, the obtainment of adequate number of metaphases can be difficult in some species like C. annuum. In order to estimate the DNA content of each C. annuum var. annuum cv. \”New Mexican\” chromosome, flow and image cytometries were associated with the cytogenetic methodology. First, the DNA amount (2C = 6.90 pg) was established by flow cytometry. Integrated optical density (IOD) values were calculated by image cytometry for each Feulgen stained metaphasic chromosome. Then, by distributing the correspondent metaphasic value (4C = 13.80 pg) proportionally to average IOD values, the following chromosomal DNA contents were obtained in pg: 0.74 (chromosome 1), 0.67 (2), 0.61 (3, 4), 0.60 (5), 0.59 (6, 7), 0.58 (8), 0.57 (9), 0.56 (10) and 0.39 (11, 12). This study reports an alternative and reproducible technique that makes quantifying the chromosomal DNA content possible.

de Abreu IS, Carvalho CR, Clarindo WR.

Laboratório de Citogenética e Citometria, Departamento de Biologia Geral, Universidade Federal de Viçosa, Av. PH Rolfs, s/n, Viçosa, Minas Gerais, CEP 36570-000, Brazil.

Complex regional pain syndrome (CPRS type I) after a burn injury of the hand.

Complex regional pain syndrome (CRPS) type I is a clinical condition characterized by persistent pain in one part or the entire extremity after a minor trauma, fracture, or after an operation which does not involve nerve damage and/or sympathetic hyperactivity. Despite large-scale studies on the complications that arise after burns, literature reveals few reports on neurological problems and CRPS developing after burns. It is a rare complication of a burn injury to an extremity. Its early signs and symptoms are similar to those of burn wound itself. This study describes an unusual cause of complex regional pain syndrome in burn patients. The report highlights physical examination findings, the new diagnostic criteria of complex regional pain syndrome, and difficulties in diagnosis.

Ordu Gokkaya NK, Karakus D, Oktay F, Ucan H.

Ankara Physical Medicine and Rehabilitation Education and Research Hospital, Ankara, Turkey, kutayordu@yahoo.com.

Repeat induced point mutation in two asexual fungi, Aspergillus niger and Penicillium chrysogenum.

Repeat induced point mutation (RIP) is a gene silencing mechanism present in fungal genomes. During RIP, duplicated sequences are efficiently and irreversibly mutated by transitions from C:G to T:A. For the first time, we have identified traces of RIP in transposable elements of Aspergillus niger and Penicillium chrysogenum, two biotechnologically relevant fungi. We found that RIP in P. chrysogenum has affected a large set of sequences, which also contain other mutations. On the other hand, RIP in A. niger is limited to only few sequences, but literally all mutations are RIP-like. Surprisingly, RIP occurred only in transposon sequences that have disrupted open reading frames in A. niger, a phenomenon not yet reported for other fungi. In both fungal species, we identified two sequences with strong sequence similarity to Neurospora crassa RID. RID is a putative DNA methyltransferase and the only known enzyme involved in the RIP process. Our findings suggest that both A. niger and P. chrysogenum either had a sexual past or have a sexual potential. These findings have important implications for future strain development of these fungi.

Braumann I, van den Berg M, Kempken F.

Abteilung Botanik mit Schwerpunkt Genetik und Molekularbiologie, Botanisches Institut und Botanischer Garten, Christian-Albrechts-Universität zu Kiel, Olshausenstraße 40, 24098, Kiel, Germany.

Continuous versus pulse harvesting for population models in constant and variable environment.

We consider both autonomous and nonautonomous population models subject to either impulsive or continuous harvesting. It is demonstrated in the paper that the impulsive strategy can be as good as the continuous one, but cannot outperform it. We introduce a model, where certain harm to the population is incorporated in each harvesting event, and study it for the logistic and the Gompertz laws of growth. In this case, impulsive harvesting is not only the optimal strategy but is the only possible one.

Braverman E, Mamdani R.

Department of Mathematics and Statistics, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada, maelena@math.ucalgary.ca.

Computing likelihoods for coalescents with multiple collisions in the infinitely many sites model.

One of the central problems in mathematical genetics is the inference of evolutionary parameters of a population (such as the mutation rate) based on the observed genetic types in a finite DNA sample. If the population model under consideration is in the domain of attraction of the classical Fleming-Viot process, such as the Wright-Fisher- or the Moran model, then the standard means to describe its genealogy is Kingman\’s coalescent. For this coalescent process, powerful inference methods are well-established. An important feature of the above class of models is, roughly speaking, that the number of offspring of each individual is small when compared to the total population size, and hence all ancestral collisions are binary only. Recently, more general population models have been studied, in particular in the domain of attraction of so-called generalised Lambda-Fleming-Viot processes, as well as their (dual) genealogies, given by the so-called Lambda-coalescents, which allow multiple collisions. Moreover, Eldon and Wakeley (Genetics 172:2621-2633, 2006) provide evidence that such more general coalescents might actually be more adequate to describe real populations with extreme reproductive behaviour, in particular many marine species. In this paper, we extend methods of Ethier and Griffiths (Ann Probab 15(2):515-545, 1987) and Griffiths and Tavaré (Theor Pop Biol 46:131-159, 1994a, Stat Sci 9:307-319, 1994b, Philos Trans Roy Soc Lond Ser B 344:403-410, 1994c, Math Biosci 12:77-98, 1995) to obtain a likelihood based inference method for general Lambda-coalescents. In particular, we obtain a method to compute (approximate) likelihood surfaces for the observed type probabilities of a given sample. We argue that within the (vast) family of Lambda-coalescents, the parametrisable sub-family of Beta(2 - alpha, alpha)-coalescents, where alpha in (1, 2], are of particular relevance. We illustrate our method using simulated datasets, thus obtaining maximum-likelihood estimators of mutation and demographic parameters.

Birkner M, Blath J.

Weierstraß-Institut für Angewandte Analysis und Stochastik, Mohrenstraße 39, 10117, Berlin, Germany, birkner@wias-berlin.de.