Analysis of Alzheimer's disease severity across brain regions by topological analysis of gene co-expression networks

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder involving variations in the transcriptome of many genes. AD does not affect all brain regions simultaneously. Identifying the differences among the affected regions may shed more light onto the disease progression. We developed a novel method involving the differential topology of gene coexpression networks to understand the association among affected regions and disease severity.</p> <p>Methods</p> <p>We analysed microarray data of four regions - entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC) and middle temporal gyrus (MTG) from AD affected and normal subjects. A coexpression network was built for each region and the topological overlap between them was examined. Genes with zero topological overlap between two region-specific networks were used to characterise the differences between the two regions.</p> <p>Results and conclusion</p> <p>Results indicate that MTG shows early AD pathology compared to the other regions. We postulate that if the MTG gets affected later in the disease, post-mortem analyses of individuals with end-stage AD will show signs of early AD in the MTG, while the EC, HIP and PCC will have severe pathology. Such knowledge is useful for data collection in clinical studies where sample selection is a limiting factor as well as highlighting the underlying biology of disease progression.</p

Hox gene function in vertebrate gut morphogenesis: the case of the caecum

The digestive tract is made of different subdivisions with various functions. During embryonic development, the developing intestine expresses combinations of Hox genes along its anterior to posterior axis, suggesting a role for these genes in this regionalization process. In particular, the transition from small to large intestine is labelled by the transcription of all Hoxd genes except Hoxd12 and Hoxd13, the latter two genes being transcribed only near the anus. Here, we describe two lines of mice that express Hoxd12 ectopically within this morphological transition. As a consequence, budding of the caecum is impeded, leading to complete agenesis in homozygous individuals. This effect is concurrent with a dramatic reduction of both Fgf10 and Pitx1 expression. Furthermore, the interactions between ;anterior' Hox genes and ectopic Hoxd12 suggest a model whereby anterior and posterior Hox products compete in controlling Fgf10 signalling, which is required for the growth of this organ in mice. These results illuminate components of the genetic cascade necessary for the emergence of this gut segment, crucial for many vertebrates

Interactions between HOXD and Gli3 genes control the limb apical ectodermal ridge via Fgf10

The development of the vertebrate limb is dependent upon two signaling centers, the apical ectodermal ridge (AER), which provides the underlying mesenchyme with essential growth factors, and the zone of polarizing activity (ZPA), the source of the Sonic hedgehog (SHH) product. Recent work involving gain and loss of function of Hox genes has emphasized their impact both on AER maintenance and Shh transcriptional activation. Here, we describe antagonistic interactions between posterior Hoxd genes and Gli3, suggesting that the latter product protects the AER from the deleterious effect of the formers, and we present evidence that Fgf10 is the mediator of HOX-dependent AER expansion. Furthermore, the striking similarity between some of the hereby observed Hox/Gli3-dependent morphogenetic defects and those displayed by fetuses with severely altered retinoic acid metabolism suggests a tight connection between these various pathways. The nature of these potential interactions is discussed in the context of proximal-distal growth and patterning

Fluorimetric approaches to the study of calcium transients in living cells

This paper is a short review of the fluorimetric methods used to measure intracellular free Ca++ concentration in living cells. The availability of fluorescent probes has greatly contributed to the understanding of the mechanisms responsible for the cellular homeostasis of this second messenger. Data can be collected from populations of cells by spectrofluorimetry or from small groups or single cells by spectromicroscopy. Finally the fluorescent images can be captured by a high sensitivity camera, digitally processed and convert in Ca++ images of the cell. The technique allows recognition of differences in [Ca++]i transients among adjacent cells in a same field or in different regions of a cell and greatly contributes to the identification of the cellular mechanisms modulating [Ca++]i

The significance of cyclic EEG changes in Creutzfeldt-Jakob disease: prognostic value of their course in 9 patients.

The diagnostic value of the EEG in Creutzfeldt-Jakob disease is based not only on the presence of a typical pattern of periodic discharges but also on the appearance of cyclic changes in the EEG. The pattern of the cyclic EEG changes was analysed in 9 patients with Creutzfeldt-Jakob disease. The changes appear when the level of wakefulness is reduced. The alternating pattern rate increases as the disease progresses and accounts for as much as 100 per cent of the tracing when the patient is in coma. During the cyclic changes the cardiorespiratory rate is always higher in phase A than in phase B. Hypertonic fits and most myoclonic jerks are present only in the A-phase, whereas partial myoclonus and fasciculations are present in both phases. The cyclic change pattern in Creutzfeldt-Jakob disease reveals a progressive. The cyclic change pattern in Creutzfeldt-Jakob disease reveals a progressive, serious involvement of the waking system

La cura della depressione fra illusioni e speranze. Esperienze e interventi in psicologia clinica

La cura della depressione fra illusioni e speranze. Esperienze e interventi in psicologia clinic

[Epilepsy in later life: seizures persisting after the age of 60].

In a group of 657 epileptic patients there were 51 presenting with fits even after having reached the age of 60. The onset of seizures dated back to the first 20 years in 15 patients between 20 and 40 years in 15 and between 40 and 60 years in 21. In 67\% of the cases it was possible to determine the cause of seizures. The aetiology was unevenly distributed within each group. In the first group (up to 20 years) the P.G.E. forms prevail. In the second (up to 40 years) post traumatic epilepsy and inflammatory processes were predominant, while in the third (up to 60 years) vascular and tumoral pathology seem to be prevalent. 43\% of the patients showed paroxysmal abnormalities in the EEG and these were still present even after to age of 60 years in more than fifty per cent. After the age of 60 we found no case of benign epilepsy amenable to complete recovery. Patients older than 60 present epilepsies of mild severity. In symptomatic epilepsies the lesional factors were not subject to evolution and the epileptogenic focuses were stable and persistent. In partial epilepsy there were more cases of complex symptomatology (86\%) than cases of elementary symptomatology (14\%) The evolution of seizures in old age is considered together with the importance of all factors influencing recurrency