Apraxia of speech and cerebellar mutism syndrome: a case study

Background Cerebellar mutism syndrome (CMS) or posterior fossa syndrome (PFS) consists of a constellation of neuropsychiatric, neuropsychological and neurogenic speech and language deficits. It is most commonly observed in children after posterior fossa tumor surgery. The most prominent feature of CMS is mutism, which generally starts after a few days after the operation, has a limited duration and is typically followed by motor speech deficits. However, the core speech disorder subserving CMS is still unclear. Case presentation This study investigates the speech and language symptoms following posterior fossa medulloblastoma surgery in a 12-year-old right-handed boy. An extensive battery of formal speech (DIAS = Diagnostic Instrument Apraxia of Speech) and language tests were administered during a follow-up of 6 weeks after surgery. Although the neurological and neuropsychological (affective, cognitive) symptoms of this patient are consistent with Schmahmann’s syndrome, the speech and language symptoms were markedly different from what is typically described in the literature. In-depth analyses of speech production revealed features consistent with a diagnosis of apraxia of speech (AoS) while ataxic dysarthria was completely absent. In addition, language assessments showed genuine aphasic deficits as reflected by distorted language production and perception, wordfinding difficulties, grammatical disturbances and verbal fluency deficits. Conclusion To the best of our knowledge this case might be the first example that clearly demonstrates that a higher level motor planning disorder (apraxia) may be the origin of disrupted speech in CMS. In addition, identification of non-motor linguistic disturbances during follow-up add to the view that the cerebellum not only plays a crucial role in the planning and execution of speech but also in linguistic processing. Whether the cerebellum has a direct or indirect role in motor speech planning needs to be further investigated

NEAT: An efficient network enrichment analysis test

Background: Network enrichment analysis is a powerful method, which allows to integrate gene enrichment analysis with the information on relationships between genes that is provided by gene networks. Existing tests for network enrichment analysis deal only with undirected networks, they can be computationally slow and are based on normality assumptions. Results: We propose NEAT, a test for network enrichment analysis. The test is based on the hypergeometric distribution, which naturally arises as the null distribution in this context. NEAT can be applied not only to undirected, but to directed and partially directed networks as well. Our simulations indicate that NEAT is considerably faster than alternative resampling-based methods, and that its capacity to detect enrichments is at least as good as the one of alternative tests. We discuss applications of NEAT to network analyses in yeast by testing for enrichment of the Environmental Stress Response target gene set with GO Slim and KEGG functional gene sets, and also by inspecting associations between functional sets themselves. Conclusions: NEAT is a flexible and efficient test for network enrichment analysis that aims to overcome some limitations of existing resampling-based tests. The method is implemented in the R package neat, which can be freely downloaded from CRAN ( https://cran.r-project.org/package=neat )

Stage-I osteochondritis dissecans versus normal variants of ossification in the knee in children

Background: Juvenile osteochondritis dissecans (OCD) has a better prognosis than the adult type. Objective : We postulated that the excellent prognosis of juvenile OCD could be explained, at least in part, by the erroneous diagnosis of some developmental variants of ossification as stage-I OCD. Materials and methods : Knee MRIs of 38 children, ages 7.5–17.7 years (mean and median age 13 years), were retrospectively reviewed to look for features that might separate normal variants of ossification from stage-I OCD. These included age, gender, site, configuration of the lesion, residual cartilaginous model and presence of edema. Results : Twenty-three patients (32 condyles) had ossification defects with intact articular cartilage suggestive of stage-I lesions. No stage-II lesions were seen in the posterior femoral condyles. Accessory ossification centers were seen in 11/16 posterior condyles and 3/16 central condyles. Spiculation of existing ossification was seen in 12/16 posterior condylar lesions and 1/16 central condyles. There was a predominance of accessory ossifications and spiculations in the patients with 10% or greater residual cartilaginous model. No edema signal greater than diaphyseal red-marrow signal was seen in the posterior condyles. Clinical follow-up ranged from 0.5 to 38 months, with clinical improvement in 22 out of 23 patients. Conclusion : Inclusion of normal variants in the stage-I OCD category might explain, in part, the marked difference in published outcome between the juvenile and adult forms of OCD. Ossification defects in the posterior femoral condyles with intact overlying articular cartilage, accessory ossification centers, spiculation, residual cartilaginous model, and lack of bone-marrow edema are features of developmental variants rather than OCD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46719/1/247_2005_Article_1507.pd

Transcriptional Responses of Arabidopsis thaliana during Wilt Disease Caused by the Soil-Borne Phytopathogenic Bacterium, Ralstonia solanacearum

Bacterial wilt is a common disease that causes severe yield and quality losses in many plants. In the present study, we used the model Ralstonia solanacearum-Arabidopsis thaliana pathosystem to study transcriptional changes associated with wilt disease development. Susceptible Col-5 plants and RRS1-R-containing resistant Nd-1 plants were root-inoculated with R. solanacearum strains harbouring or lacking the matching PopP2 avirulence gene. Gene expression was marginally affected in leaves during the early stages of infection. Major changes in transcript levels took place between 4 and 5 days after pathogen inoculation, at the onset of appearance of wilt symptoms. Up-regulated genes in diseased plants included ABA-, senescence- and basal resistance-associated genes. The influence of the plant genetic background on disease-associated gene expression is weak although some genes appeared to be specifically up-regulated in Nd-1 plants. Inactivation of some disease-associated genes led to alterations in the plant responses to a virulent strain of the pathogen. In contrast to other pathosystems, very little overlap in gene expression was detected between the early phases of the resistance response and the late stages of disease development. This observation may be explained by the fact that above-ground tissues were sampled for profiling whereas the bacteria were applied to root tissues

Venom gland transcriptomes of two elapid snakes (Bungarus multicinctus and Naja atra) and evolution of toxin genes

<p>Abstract</p> <p>Background</p> <p>Kraits (genus <it>Bungarus</it>) and cobras (genus <it>Naja</it>) are two representative toxic genera of elapids in the old world. Although they are closely related genera and both of their venoms are very toxic, the compositions of their venoms are very different. To unveil their detailed venoms and their evolutionary patterns, we constructed venom gland cDNA libraries and genomic bacterial artificial chromosome (BAC) libraries for <it>Bungarus multicinctus </it>and <it>Naja atra</it>, respectively. We sequenced about 1500 cDNA clones for each of the venom cDNA libraries and screened BAC libraries of the two snakes by blot analysis using four kinds of toxin probes; <it>i.e</it>., three-finger toxin (3FTx), phospholipase A2 (PLA2), kunitz-type protease inhibitor (Kunitz), and natriuretic peptide (NP).</p> <p>Results</p> <p>In total, 1092 valid expressed sequences tags (ESTs) for <it>B. multicinctus </it>and 1166 ESTs for <it>N. atra </it>were generated. About 70% of these ESTs can be annotated as snake toxin transcripts. 3FTx (64.5%) and <it>β </it>bungarotoxin (25.1%) comprise the main toxin classes in <it>B. multicinctus</it>, while 3FTx (95.8%) is the dominant toxin in <it>N. atra</it>. We also observed several less abundant venom families in <it>B. multicinctus </it>and <it>N. atra</it>, such as PLA2, C-type lectins, and Kunitz. Peculiarly a cluster of NP precursors with tandem NPs was detected in <it>B. multicinctus</it>. A total of 71 positive toxin BAC clones in <it>B. multicinctus </it>and <it>N. atra </it>were identified using four kinds of toxin probes (3FTx, PLA2, Kunitz, and NP), among which 39 3FTx-postive BACs were sequenced to reveal gene structures of 3FTx toxin genes.</p> <p>Conclusions</p> <p>Based on the toxin ESTs and 3FTx gene sequences, the major components of <it>B. multicinctus </it>venom transcriptome are neurotoxins, including long chain alpha neurotoxins (<it>α</it>-ntx) and the recently originated <it>β </it>bungarotoxin, whereas the <it>N. atra </it>venom transcriptome mainly contains 3FTxs with cytotoxicity and neurotoxicity (short chain <it>α</it>-ntx). The data also revealed that tandem duplications contributed the most to the expansion of toxin multigene families. Analysis of nonsynonymous to synonymous nucleotide substitution rate ratios (<it>dN</it>/<it>dS</it>) indicates that not only multigene toxin families but also other less abundant toxins might have been under rapid diversifying evolution.</p

Trehalose-6-phosphate-mediated toxicity determines essentiality of OtsB2 in Mycobacterium tuberculosis in vitro and in mice

Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA and T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose and glucose-6-phosphate. In order to assess the drug target potential of T6P phosphatase, we generated a conditional mutant of M. tuberculosis allowing the regulated gene silencing of the T6P phosphatase gene otsB2. We found that otsB2 is essential for growth of M. tuberculosis in vitro as well as for the acute infection phase in mice following aerosol infection. By contrast, otsB2 is not essential for the chronic infection phase in mice, highlighting the substantial remodelling of trehalose metabolism during infection by M. tuberculosis. Blocking OtsB2 resulted in the accumulation of its substrate T6P, which appears to be toxic, leading to the self-poisoning of cells. Accordingly, blocking T6P production in a ΔotsA mutant abrogated otsB2 essentiality. T6P accumulation elicited a global upregulation of more than 800 genes, which might result from an increase in RNA stability implied by the enhanced neutralization of toxins exhibiting ribonuclease activity. Surprisingly, overlap with the stress response caused by the accumulation of another toxic sugar phosphate molecule, maltose-1-phosphate, was minimal. A genome-wide screen for synthetic lethal interactions with otsA identified numerous genes, revealing additional potential drug targets synergistic with OtsB2 suitable for combination therapies that would minimize the emergence of resistance to OtsB2 inhibitors

Diagnostic techniques for inflammatory eye disease: past, present and future: a review

Investigations used to aid diagnosis and prognosticate outcomes in ocular inflammatory disorders are based on techniques that have evolved over the last two centuries have dramatically evolved with the advances in molecular biological and imaging technology. Our improved understanding of basic biological processes of infective drives of innate immunity bridging the engagement of adaptive immunity have formed techniques to tailor and develop assays, and deliver targeted treatment options. Diagnostic techniques are paramount to distinguish infective from non-infective intraocular inflammatory disease, particularly in atypical cases. The advances have enabled our ability to multiplex assay small amount of specimen quantities of intraocular samples including aqueous, vitreous or small tissue samples. Nevertheless to achieve diagnosis, techniques often require a range of assays from traditional hypersensitivity reactions and microbe specific immunoglobulin analysis to modern molecular techniques and cytokine analysis. Such approaches capitalise on the advantages of each technique, thereby improving the sensitivity and specificity of diagnoses. This review article highlights the development of laboratory diagnostic techniques for intraocular inflammatory disorders now readily available to assist in accurate identification of infective agents and appropriation of appropriate therapies as well as formulating patient stratification alongside clinical diagnoses into disease groups for clinical trials