Gray matter imaging in multiple sclerosis: what have we learned?

At the early onset of the 20^th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis (MS). However, as white matter pathology long received predominant attention in this disease, and histological staining techniques for detecting myelin in the gray matter were suboptimal, it was not until the beginning of the 21^st century that the true extent and importance of gray matter pathology in MS was finally recognized. Gray matter damage was shown to be frequent and extensive, and more pronounced in the progressive disease phases. Several studies subsequently demonstrated that the histopathology of gray matter lesions differs from that of white matter lesions. Unfortunately, imaging of pathology in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques. However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage in MS has considerably improved. This has important consequences for studying the clinical correlates of gray matter damage. In this review, we provide an overview of what has been learned about imaging of gray matter damage in MS, and offer a brief perspective with regards to future developments in this field.     

Proteome analysis of the plant pathogen Xylella fastidiosa reveals major cellular and extracellular proteins and a peculiar codon bias distribution

The bacteria Xylella fastidiosa is the causative agent of a number of economically important crop diseases, including citrus variegated chlorosis. Although its complete genome is already sequenced, X. fastidiosa is very poorly characterized by biochemical approaches at the protein level. In an initial effort to characterize protein expression in X. fastidiosa we used one- and two-dimensional gel electrophoresis and mass spectrometry to identify the products of 142 genes present in a whole cell extract and in an extracellular fraction of the citrus isolated strain 9a5c. Of particular interest for the study of pathogenesis are adhesion and secreted proteins. Homologs to proteins from three different adhesion systems (type IV fimbriae, mrk pili and hsf surface fibrils) were found to be coexpressed, the last two being detected only as multimeric complexes in the high molecular weight region of one-dimensional electrophoresis gels. Using a procedure to extract secreted proteins as well as proteins weakly attached to the cell surface we identified 30 different proteins including toxins, adhesion related proteins, antioxidant enzymes, different types of proteases and 16 hypothetical proteins. These data suggest that the intercellular space of X. fastidiosa colonies is a multifunctional microenvironment containing proteins related to in vivo bacterial survival and pathogenesis. A codon usage analysis of the most expressed proteins from the whole cell extract revealed a low biased distribution, which we propose is related to the slow growing nature of X. fastidiosa. A database of the X. fastidiosa proteome was developed and can be accessed via the internet (URL: www.proteome.ibi.unicamp.br).     

Reproductive cycle,sexual maturity and longevity of Odontophrynus americanus (Anura: Odontophrynidae) in South Brazil

Studies on the reproductive biology and age of amphibians provide primary information about the life history and population demographic parameters of species. Here, we describe the reproductive cycle, size–fecundity relationships, reproductive effort, sexual dimorphism and sexual maturity of Odontophrynus americanus, the flood frog, from South Brazil. A total of 96 individuals were analysed. The reproductive cycles of males and females were described through morphoanatomical analysis of testis and ovary. Age at onset of sexual maturity and estimated longevity were determined by skeletochronology. Individuals of O. americanus presented a potentially continuous reproductive cycle with a peak of reproductive activity in the warmer months. Females presented a higher reproductive investment than males. Sexual maturity was reached at around one year of age for both sexes while longevity differed between the sexes, with females living up to six years and males up to ten years. No evidence of sexual size dimorphism was found. This study is among the few that have assessed age at sexual maturity and longevity in a Neotropical anuran. Basic aspects of life history are of paramount importance because they allow comparisons and test of hypotheses to be made, which can help to build generalizations about the evolutionary meaning of ecological strategies.     

Hypoxia-Inducible Factor-1α (HIF-1α) Inhibition Impairs Retinoic Acid-Induced Differentiation in SH-SY5Y Neuroblastoma Cells,Leading to Reduced Neurite Length and Diminished Gene Expression Related to Cell Differentiation

Neuroblastoma is the most common extracranial solid tumour in childhood, originated from cells of the neural crest during the development of the Sympathetic Nervous System. Retinoids are vitamin-A derived differentiating agents utilised to avoid disease resurgence in high-risk neuroblastoma treatment. Several studies indicate that hypoxia—a common feature of the tumoural environment—is a key player in cell differentiation and proliferation. Hypoxia leads to the accumulation of the hypoxia-inducible factor-1α (HIF-1α). This work aims to investigate the effects of the selective inhibition of HIF-1α on the differentiation induced by retinoic acid in human neuroblastoma cells from the SH-SY5Y lineage to clarify its role in cell differentiation. Our results indicate that HIF-1α inhibition impairs RA-induced differentiation by reducing neuron-like phenotype and diminished immunolabeling and expression of differentiation markers.

Graphic Abstract

HIF1A is involved in Retinoic Acid (RA) induced differentiation in SH-SY5Y neuroblastoma cells. siRNA HIF1A gene silencing leads to a weaker response to RA, demonstrated by changes in the neuro-like phenotype and diminished expression of differentiation markers.

     

Relationship between blood or milk polymorphisms and size measures of Holstein heifers1

Polymorphisms of Holstein heifers from ten state-owned dairy herds were compared with their birth weights and four measures of body size taken at 3, 6, and 12 months of age, and three months after first calving. The eleven polymorphic systems included the A, B, FV, J, L, S and Z blood group systems, the serum transferrins, and the β-lactoglobulin, αs₁-casein, and β-casein milk protein systems. Possible effects of polymorphisms on body measurements were investigated by analysis of variance. The numbers of animals included in the analyses ranged from 2600 in one analysis to about 100 heifers with precalving measurements and identified polymorphism types for the systems studied. Most of the analysis involved over 1000 animals. No meaningful evidence of relationship between polymorphism type and single measurement, type of measurement or measurements taken at the same age was observed. Enumeration of the probabilities that the F values could have resulted from chance alone indicated that, as a whole and generally for various groupings, fewer F values associated with low probabilities were observed than expected.     

Anticonvulsant properties of linalool in glutamate-related seizure models.

In order to investigate the pharmacodynamic basis of the previously-established anticonvulsant properties of linalool, we examined the effects of this compound on behavioral and neurochemical aspects of glutamate expression in experimental seizure models. Specifically, linalool effects were investigated to determine its inhibition of (i) L-[3H]glutamate binding at CNS (central nervous system membranes), (ii) N-methyl-D-aspartate (NMDA)-induced convulsions, (iii) quinolinic acid (QUIN)-induced convulsions, and the behavioral and neurochemical correlates of PTZ-kindling. The data indicate that linalool modulates glutamate activation expression in vitro (competitive antagonism of L-[3H]glutamate binding) and in vivo (delayed NMDA convulsions and blockage of QUIN convulsions). Linalool partially inhibited and significantly delayed the behavioral expression of PTZ-kindling, but did not modify the PTZ-kindling-induced increase in L-[3H]glutamate binding.