Neurotransmitter profile of saccadic omnipause neurons in nucleus raphe interpositus

Saccadic omnipause neurons (OPNs) are essential for the generation of saccadic eye movements. In primates OPNs are located near the midline within the nucleus raphe interpositus (rip). In the present study we used several different neuroanatomical methods to investigate the transmitters associated with OPNs in the monkey. Immunolabeling for the calcium-binding protein parvalbumin was employed to mark OPNs in the monkey and define the homologous cell group in cat and human. The use of antibodies against GABA, glycine (GLY), glutamate (GLU), serotonin (5-HT), and tyrosine hydroxylase revealed that the somata of OPNs are GLY immunoreactive, but they are devoid of GABA and 5-HT immunostaining. In situ hybridization with the GAD67 mRNA probe confirmed the negative GABA immunostaining of OPNs. 3H-GLY was injected into a projection field of OPNs, the rostral interstitial nucleus of the medial longitudinal fascicle (riMLF)--the vertical saccadic burst neuron area. This resulted in selective retrograde labeling of the OPNs in rip, while no labeling was found in the superior colliculus, which sends an excitatory projection to the riMLF. The somata and dendrites of putative burst neurons in the riMLF were contacted by numerous GLY- immunoreactive terminals. The quantitative analysis of immunoreactive terminal-like structures contacting OPNs revealed a strong input from GLY- and GABA-positive terminals on somata and dendrites, whereas GLU- positive puncta were mainly confined to the dendrites. Very few 5-HT and catecholaminergic terminals contacted OPN somata. Our findings suggest that OPNs use GLY as a neurotransmitter, and they receive numerous contacts from GABAergic, glycinergic, and glutaminergic afferents, and significantly fewer from monoaminergic inputs.</jats:p

Effects of nebulised iloprost on pulmonary function and gas exchange in severe pulmonary hypertension

SummaryNebulised iloprost is established therapy of severe pulmonary hypertension; however, the effects on the bronchoalveolar compartment have not been investigated so far. We studied the short- and long-term effects of nebulised iloprost on pulmonary function tests and gas exchange in 63 patients with severe pulmonary hypertension (idiopathic n=17, chronic thromboembolism n=15, connective tissue disease n=12, congenital heart disease n=11, respiratory diseases n=8). Patients received iloprost in increasing dose up to 140μg iloprost/24h via an ultrasonic nebuliser.Short-term effects were assessed before and after every nebulisation: peak expiration flow decreased in mean by 1.9% (423±98 to 415±98) and percutaneous oxygen saturation increased in mean by 0.7% (90±6 to 91±5) post-nebulisation. There were no significant differences concerning underlying diagnosis or dose of nebulised iloprost. Within 3 months, 9 patients stopped treatment due to non-compliance with frequent nebulisations (n=3), or severe side effects (n=4); 2 patients with additional obstructive lung disease developed bronchoconstriction.Long-term effects were assessed by pulmonary function tests and gas exchange parameters at baseline and after 3 months treatment. There were no significant differences after 3 months therapy neither in FEV1, FVC, TLC, residual volume nor in diffusions capacity, SO2 at rest and during 6min walking test, also in respect of the underlying diseases. However, there was a significant increase in 6min walking distance (6 MWD) after 3 months (246±113 to 294±115m, P<0.05).In conclusion, treatment with nebulised iloprost leads to functional improvement in severe pulmonary hypertension without systematic adverse short- and long-term effects on pulmonary function test or gas exchange. Patients with additional obstructive lung disease might develop bronchoconstriction. Severe side effects leading to discontinuation of treatment occurred in 9% of patients

The role of SH3BP2 in the pathophysiology of cherubism

Cherubism is a rare bone dysplasia that is characterized by symmetrical bone resorption limited to the jaws. Bone lesions are filled with soft fibrous giant cell-rich tissue that can expand and cause severe facial deformity. The disorder typically begins in children at ages of 2-5 years and the bone resorption and facial swelling continues until puberty; in most cases the lesions regress spontaneously thereafter. Most patients with cherubism have germline mutations in the gene encoding SH3BP2, an adapter protein involved in adaptive and innate immune response signaling. A mouse model carrying a Pro416Arg mutation in SH3BP2 develops osteopenia and expansile lytic lesions in bone and some soft tissue organs. In this review we discuss the genetics of cherubism, the biological functions of SH3BP2 and the analysis of the mouse model. The data suggest that the underlying cause for cherubism is a systemic autoinflammatory response to physiologic challenges despite the localized appearance of bone resorption and fibrous expansion to the jaws in humans

Carcinoid tumours of the lung and the ’PEPPS’ approach: evaluation of preoperative bronchoscopic tumour debulking as preparation for subsequent parenchyma-sparing surgery

BACKGROUND: Preoperative bronchoscopic tumour ablation has been suggested as a beneficial treatment for bronchopulmonary carcinoid tumours, although data regarding its effects and long-term outcome are lacking. METHODS: In our case-matched cohort study with 208 patients with bronchopulmonary carcinoid tumours we investigated the role of preoperative bronchoscopic interventions before subsequent surgery and analysed the safety of this Procedure of Endobronchial Preparation for Parenchyma-sparing Surgery (PEPPS) based on metastasis and recurrence rates as well as survival data from 1991 to 2010. The subsequent surgery was classified into parenchyma-sparing procedures and classical lobectomies, bilobectomies and pneumonectomies. Data were obtained from the tumour registry and medical reports. Outcomes were the frequency of parenchyma-sparing surgery after bronchoscopic treatment as well as rates of metastasis, recurrence and survival. RESULTS: 132 of 208 carcinoids were located centrally. Among them, 77 patients could be recanalised preoperatively. After bronchoscopic preparation, the rate of subsequent parenchyma-sparing surgery methods was higher (p=0.021). The effect was measured by the number of segments removed. The 10-year survival rate was 89% (typical carcinoids) and 68% (atypical carcinoids), respectively. After applying PEPPS, long-term survival was slightly higher (p=0.23). Metastasis and recurrence rates showed no relevant differences between the bronchoscopically treated or non-treated groups, or between the two types of surgery classes or between the PEPPS and non-PEPPS groups. CONCLUSIONS: After preoperative bronchoscopic treatment, parenchyma-sparing surgery techniques can be applied more frequently. Furthermore, we detected no negative effects after PEPPS based on metastasis, recurrence and survival rates

Cherubism: best clinical practice

Cherubism is a skeletal dysplasia characterized by bilateral and symmetric fibro-osseous lesions limited to the mandible and maxilla. In most patients, cherubism is due to dominant mutations in the SH3BP2 gene on chromosome 4p16.3. Affected children appear normal at birth. Swelling of the jaws usually appears between 2 and 7 years of age, after which, lesions proliferate and increase in size until puberty. The lesions subsequently begin to regress, fill with bone and remodel until age 30, when they are frequently not detectable

NBC: the Naïve Bayes Classification tool webserver for taxonomic classification of metagenomic reads

Motivation: Datasets from high-throughput sequencing technologies have yielded a vast amount of data about organisms in environmental samples. Yet, it is still a challenge to assess the exact organism content in these samples because the task of taxonomic classification is too computationally complex to annotate all reads in a dataset. An easy-to-use webserver is needed to process these reads. While many methods exist, only a few are publicly available on webservers, and out of those, most do not annotate all reads

A c.1244G>A (p.Arg415Gln) mutation in SH3BP2 gene causes cherubism in a Turkish family: report of a family with review of the literature

Objectives: The present study was aimed at advancing the understanding of the pathogenesis of cherubism by presenting a case study based on history, physical examination, typical radiological features, molecular and histo - pathological laboratory tests and a review of the literature. Study Design: This study began with a 7-year-old boy who was referred due to mandibular overgrowth. A pan - oramic radiograph revealed multilocular radiolucent lesions of the upper/lower jaws suggestive of cherubism. Overall, a total of four family members were tested for SH3BP2 mutations, namely two siblings and their parents. Both siblings had been clinically diagnosed with cherubism; however, the parents were clinically normal. Periph - eral blood was collected from all participants and genomic DNA sequencing was carried out. Results: A missense mutation was found in the two affected siblings and their asymptomatic mother. The mu - tation was a 1244 G>A transversion which resulted in an amino acid substitution from arginine to glutamine (p.Arg415Gln) in exon 9. Conclusions: The present study emphasized the importance of further clinical and molecular investigation even when only a single case of cherubism is identified within a family. Genotype-phenotype association studies in individuals with cherubism are necessary to provide important insights into the molecular mechanisms associated with this disease

Genomic and proteomic biases inform metabolic engineering strategies for anaerobic fungi.

Anaerobic fungi (Neocallimastigomycota) are emerging non-model hosts for biotechnology due to their wealth of biomass-degrading enzymes, yet tools to engineer these fungi have not yet been established. Here, we show that the anaerobic gut fungi have the most GC depleted genomes among 443 sequenced organisms in the fungal kingdom, which has ramifications for heterologous expression of genes as well as for emerging CRISPR-based genome engineering approaches. Comparative genomic analyses suggest that anaerobic fungi may contain cellular machinery to aid in sexual reproduction, yet a complete mating pathway was not identified. Predicted proteomes of the anaerobic fungi also contain an unusually large fraction of proteins with homopolymeric amino acid runs consisting of five or more identical consecutive amino acids. In particular, threonine runs are especially enriched in anaerobic fungal carbohydrate active enzymes (CAZymes) and this, together with a high abundance of predicted N-glycosylation motifs, suggests that gut fungal CAZymes are heavily glycosylated, which may impact heterologous production of these biotechnologically useful enzymes. Finally, we present a codon optimization strategy to aid in the development of genetic engineering tools tailored to these early-branching anaerobic fungi