Explore, edit and leverage genomic annotations using Python GTF toolkit.

MOTIVATION: While Python has become very popular in bioinformatics, a limited number of libraries exist for fast manipulation of gene coordinates in Ensembl GTF format. RESULTS: We have developed the GTF toolkit Python package (pygtftk), which aims at providing easy and powerful manipulation of gene coordinates in GTF format. For optimal performances, the core engine of pygtftk is a C dynamic library (libgtftk) while the Python API provides usability and readability for developing scripts. Based on this Python package, we have developed the gtftk command line interface that contains 57 sub-commands (v0.9.10) to ease handling of GTF files. These commands may be used to (i) perform basic tasks (e.g. selections, insertions, updates or deletions of features/keys), (ii) select genes/transcripts based on various criteria (e.g. size, exon number, transcription start site location, intron length, GO terms) or (iii) carry out more advanced operations such as coverage analyses of genomic features using bigWig files to create faceted read-coverage diagrams. In conclusion, the pygtftk package greatly simplifies the annotation of GTF files with external information while providing advance tools to perform gene analyses. AVAILABILITY AND IMPLEMENTATION: pygtftk and gtftk have been tested on Linux and MacOSX and are available from https://github.com/dputhier/pygtftk under the MIT license. The libgtftk dynamic library written in C is available from https://github.com/dputhier/libgtftk.

TCRα rearrangements identify a subgroup of NKL-deregulated adult T-ALLs associated with favorable outcome.

T-cell acute lymphoblastic leukemia (T-ALL) results from leukemic transformation of T-cell precursors arrested at specific differentiation stages, including an 'early-cortical' thymic maturation arrest characterized by expression of cytoplasmic TCRß but no surface T-cell receptor (TCR) and frequent ectopic expression of the TLX1/3 NK-like homeotic proteins (NKL). We designed a TCRα VJC PCR to identify clonal TCRα rearrangements in 32% of 127 T-ALLs, including 0/52 immature/TCRγδ lineage cases and 41/75 (55%) TCRαß lineage cases. Amongst the latter, TCRα rearrangements were not identified in 30/54 (56%) of IMß/pre-αß early-cortical T-ALLs, of which the majority (21/30) expressed TLX1/3. We reasoned that the remaining T-ALLs might express other NKL proteins, so compared transcript levels of 46 NKL in T-ALL and normal thymic subpopulations. Ectopic overexpression of 10 NKL genes, of which six are unreported in T-ALL (NKX2-3, BARHL1, BARX2, EMX2, LBX2 and MSX2), was detectable in 17/104 (16%) T-ALLs. Virtually all NKL overexpressing T-ALLs were TCRα unrearranged and ectopic NKL transcript expression strongly repressed Eα activity, suggesting that ectopic NKL expression is the major determinant in early-cortical thymic T-ALL maturation arrest. This immunogenetic T-ALL subtype, defined by TCRß VDJ but no TCRα VJ rearrangement, is associated with a favorable outcome in GRAALL-treated adult T-ALLs.

Immunoexpression of gelatinase (MMP-2 and MMP-9) in the seminal vesicles and ventral prostate of Libyan jird (Meriones libycus) during the seasonal cycle of reproduction.

An immunohistochemical study of matrix metalloproteinases (MMP-2 and MMP-9) or gelatinase (gelatinase A and gelatinase B) was performed on the seminal vesicles and ventral prostate of the Libyan jird (Meriones libycus) collected in the Beni-Abbes area during breeding period (spring and early summer), during resting phase (late summer, autumn, winter) and from castrated animals in the spring. The work was done using the indirect immunohistochemistry protocol by amplification with streptavidin-biotin-peroxidase and AEC as chromogen. In the seminal vesicles, during the breeding period, an important immunohistochemical signal of MMP-2 and MMP-9 was observed in epithelial cells and smooth muscle cells (SMC) without any immunoexpression in the extracellular matrix (ECM) and secretion. During resting phase and in thirty days castrated Meriones libycus, the MMP-2 and MMP-9 immunoexpression was weak in the epithelial cells and persisted with the same intensity in the SMC. The ECM, with no immunostaining in active season, showed a pronounced immunoresponse of both the two gelatinase. Three days after castration, the MMP-9 immunohistochemical reaction in epithelial cells and SMC was as intense as during active season. A prolonged castration of 50 and 90 days resulted in the maintenance of the MMP-9 immunostaining in epithelial cells and SMC and its disappearance from the ECM, suggesting a slow process of regression. During the breeding period, in the ventral prostate, MMP-2 immunostaining was more important in the SMC than in epithelial cells. The MMP-9 immunoexpression pattern was the opposite, the epithelial cells showed a higher immunoreaction than SMC. ECM and secretion lacked MMP-2 and MMP-9 immunostaining. The ventral prostate lumen contained a granular secretion without any gelatinase immunolabelling and was hollowed by empty circular forms reflecting the disappearance of the product in these areas. Part of the secretion showed a positive MMP-2 and MMP-9 immunoreaction. The latter was subsequently filled and seemed involved in the progression of the secretion in the tubules, preventing their filling. In resting phase and in animals castrated since thirty days, the immunoreactivity of both the two gelatinases was maintained in the epithelial cells and in the SMC, and was absent in the ECM. The gelatinases are involved in the seasonal reproductive cycle of Meriones libycus.

Ecophysiological responses of the seminal vesicle of Libyan jird (Meriones libycus) to the Saharan conditions: histological, morphometric and immunohistochemical analysis.

The Libyan jird (Meriones libycus) is a nocturnal Saharan Rodent submitted to a seasonal cycle of reproduction characterized by a short active period during spring and beginning of summer, and a long phase of sexual quiescence from the end of summer until the end of winter. During this cycle, the male reproductive organs, and more particularly seminal vesicles, experience some important weight and histological variations. During the breeding period, the wall of each seminal vesicle describes several folds radiating inside a broad lumen filled with a very abundant secretion. The wall is limited with high columnar epithelial cells surrounded with extracellular matrix restricted to some connnective fibres located in the narrow axis of the folds and in the chorion. The fibro-muscular wall is narrow. During sexual quiescence, the seminal vesicles regress. No secretion has been observed inside the lumen. The wall of lumen is now surrounded with a single cubic epithelium. The persistent epithelial folds possess a wide axis. The hypertrophied extracellular matrix is constituted with a very tight and abundant connective tissue. The fibro-muscular wall is thick. A quantitative morphometric study was performed with automatic image analysis that allowed to quantify the seasonal variations of the histological components. The numerical values obtained agree with the histological images observed, the epithelial surface area (microm2) is high in spring and significantly weak during sexual quiescence. The stroma and the fibro-muscular wall occupy an important surface area on sections during the resting period compared with the value collected during the active phase. The study of the apoptosis by TUNEL method revealed the presence of a considerable number of apoptotic nuclei in the epithelial fraction during the resting phase. The indirect immunohistochemical method allowed us to visualize the presence of types I and III collagen in the extracellular matrix, weak during the period of breeding, intense and diffuse during the resting season like in castrated Meriones libycus.

[Risks of pulmonary vein isolation by radiofrequency for the treatment of paroxysmal atrial fibrillation: a single centre experience of the first 200 patients]. / Risques liés a l'isolement par radiofréquence des veines pulmonaires pour le traitement de la fibrillation auriculaire paroxystique: expérience monocentrique des 200 premiers patients.

The authors report the initial experience of an electrophysiological laboratory starting ablation for atrial fibrillation, a promising technique which is not yet widely practiced because of the risks related to the procedure. The incidence of severe complications (tamponade, pulmonary vein stenosis, ischaemic events) did not appear to be different in the first 100 procedures compared with the next 100 procedures: 3% in the two groups. The selection of patients, strict perioperative management and the initial support by confirmed operators seem to be the factors which minimise the complications rate of the procedure.

[Brugada syndrome and supraventricular arrhythmias]. / Syndrome de Brugada et arythmies supraventriculaires. A propos d'une observation clinique.

The author reports the case of a 46-year old patient diagnosed with idiopathic ventricular fibrillation (Brugada syndrome) further to induction of class Ic antiarrhythmic therapy for the management of paroxystic ventricular fibrillation. It would appear that this diagnosis is increasingly frequent in young patients with Brugada syndrome shown to be minimal or intermittent on electrocardiograms. Atrial arrhythmia was the only rhythmic pathology objectively evidenced in this patient and the author was consequently led to reconsider its prevalence in patients presenting this syndrome both in the literature and according to his personal experience.

Can we improve the management of chronic obstructive respiratory disease? The example of asthma in adults.

SETTING: Zeralda health district, Algeria. OBJECTIVE: To analyse the impact of asthma refresher courses on the knowledge, attitudes and practice of general practitioners (GPs) working in primary health centres (PHC); to improve the system of referral between the PHCs and the district reference centre; and to measure the impact of the intervention on the management of asthma patients. METHODS: Before and after study: situation analysis with an epidemiological survey in the general population and a study of the demand for care in three PHCs and an emergency department, three refresher training workshops for voluntary GPs and adoption of new consensual methods of collaboration. RESULTS: Despite a district asthma prevalence of 1.6%, patients were usually seen in emergency situations and sent to the district reference centre for follow-up. The refresher courses were attended by 56 GPs. Apart from improvements in knowledge, their practices and prescribing habits changed, with more beta-agonists (68.5% after vs. 12% before) and inhaled anti-inflammatories (52% vs. 0%), and less theophylline (2% vs. 55%), antibiotics (13% vs. 59%) and mucolytics (9% vs. 73.5%). The referral system was improved as follows: 69 health personnel were trained by GPs, recording and reporting forms designed during the workshops were implemented, essential emergency drugs were identified and collaboration between GPs and specialists at the reference centre was enhanced.

Prevalence of asthma in a region of Algeria.

In 1984-85 an epidemiological survey on asthma was carried out on a representative population sample in the "Daira de Chéraga" region in Algeria. It had two objectives: to estimate the prevalence of asthma and to describe its epidemiological pattern. The study was divided into two parts: the first was a household survey based on a questionnaire and the second, another interview at hospital, with clinical examination and pulmonary function tests with pharmacodynamic tests. The cumulative prevalence of respiratory symptoms was 2.38%. The cumulative prevalence of asthma was 1.34% and the annual prevalence 1.21%. Asthma was more prevalent in boys than girls aged under 20 years (sex ratio = 2.66) with an equal proportion after age 20 years. Asthma most often occurred in childhood in males and at an adult age in females. In 40% of cases there were family antecedents of asthma. It is impossible to extrapolate these results to the entire country and the existence of regional disparities pleads in favour of further research in this field.