Suivi technique, analytique et microbiologique de la « bili bili »,bière traditionnelle tchadienne

Technical, analytical and microbiological follow-up of the "bili bili", Chadian traditional beerTo improve our knowledge of the artisanal process of manufacture of the "bili bili", carried out some measurements (operation time, temperature, pH, concentrations and we mass of dry matter, total carbohydrates, fermentable carbohydrates, lactic acid, ethanol,number of total bacteria, lactic bacteria and yeast) at different stages. The influence of operating conditions on the artisanal process of malting, mixing, acidification and fermentation were analyzed. The results obtained made it possible to identify and characterize the main physico-chemical and biological changes during the production of this beer. Moreover, as the European beers the "bili bili" results the same  technological process but showed a double lactic fermentation. These results also made it possible to suggest improvements of the production procedure that could economize the energy significantly

Number of active transcription factor binding sites is essential for the Hes7 oscillator

BACKGROUND: It is commonly accepted that embryonic segmentation of vertebrates is regulated by a segmentation clock, which is induced by the cycling genes Hes1 and Hes7. Their products form dimers that bind to the regulatory regions and thereby repress the transcription of their own encoding genes. An increase of the half-life of Hes7 protein causes irregular somite formation. This was shown in recent experiments by Hirata et al. In the same work, numerical simulations from a delay differential equations model, originally invented by Lewis, gave additional support. For a longer half-life of the Hes7 protein, these simulations exhibited strongly damped oscillations with, after few periods, severely attenuated the amplitudes. In these simulations, the Hill coefficient, a crucial model parameter, was set to 2 indicating that Hes7 has only one binding site in its promoter. On the other hand, Bessho et al. established three regulatory elements in the promoter region. RESULTS: We show that – with the same half life – the delay system is highly sensitive to changes in the Hill coefficient. A small increase changes the qualitative behaviour of the solutions drastically. There is sustained oscillation and hence the model can no longer explain the disruption of the segmentation clock. On the other hand, the Hill coefficient is correlated with the number of active binding sites, and with the way in which dimers bind to them. In this paper, we adopt response functions in order to estimate Hill coefficients for a variable number of active binding sites. It turns out that three active transcription factor binding sites increase the Hill coefficient by at least 20% as compared to one single active site. CONCLUSION: Our findings lead to the following crucial dichotomy: either Hirata's model is correct for the Hes7 oscillator, in which case at most two binding sites are active in its promoter region; or at least three binding sites are active, in which case Hirata's delay system does not explain the experimental results. Recent experiments by Chen et al. seem to support the former hypothesis, but the discussion is still open

Integrative data mining highlights candidate genes for monogenic myopathies

Inherited myopathies are a heterogeneous group of disabling disorders with still barely understood pathological mechanisms. Around 40% of afflicted patients remain without a molecular diagnosis after exclusion of known genes. The advent of high-throughput sequencing has opened avenues to the discovery of new implicated genes, but a working list of prioritized candidate genes is necessary to deal with the complexity of analyzing large-scale sequencing data. Here we used an integrative data mining strategy to analyze the genetic network linked to myopathies, derive specific signatures for inherited myopathy and related disorders, and identify and rank candidate genes for these groups. Training sets of genes were selected after literature review and used in Manteia, a public web-based data mining system, to extract disease group signatures in the form of enriched descriptor terms, which include functional annotation, human and mouse phenotypes, as well as biological pathways and protein interactions. These specific signatures were then used as an input to mine and rank candidate genes, followed by filtration against skeletal muscle expression and association with known diseases. Signatures and identified candidate genes highlight both potential common pathological mechanisms and allelic disease groups. Recent discoveries of gene associations to diseases, like B3GALNT2, GMPPB and B3GNT1 to congenital muscular dystrophies, were prioritized in the ranked lists, suggesting a posteriori validation of our approach and predictions. We show an example of how the ranked lists can be used to help analyze high-throughput sequencing data to identify candidate genes, and highlight the best candidate genes matching genomic regions linked to myopathies without known causative genes. This strategy can be automatized to generate fresh candidate gene lists, which help cope with database annotation updates as new knowledge is incorporated

Activated leukocyte cell adhesion molecule in breast cancer: prognostic indicator

INTRODUCTION: Activated leukocyte cell adhesion molecule (ALCAM) (CD166) is an immunoglobulin molecule that has been implicated in cell migration. The present study examined the expression of ALCAM in human breast cancer and assessed its prognostic value. METHODS: The immunohistochemical distribution and location of ALCAM was assessed in normal breast tissue and carcinoma. The levels of ALCAM transcripts in frozen tissue (normal breast, n = 32; breast cancer, n = 120) were determined using real-time quantitative PCR. The results were then analyzed in relation to clinical data including the tumor type, the grade, the nodal involvement, distant metastases, the tumor, node, metastasis (TNM) stage, the Nottingham Prognostic Index (NPI), and survival over a 6-year follow-up period. RESULTS: Immunohistochemical staining on tissue sections in ducts/acini in normal breast and in breast carcinoma was ALCAM-positive. Differences in the number of ALCAM transcripts were found in different types of breast cancer. The level of ALCAM transcripts was lower (P = 0.05) in tumors from patients who had metastases to regional lymph nodes compared with those patients without, in higher grade tumors compared with Grade 1 tumors (P < 0.01), and in TNM Stage 3 tumors compared with TNM Stage 1 tumors (P < 0.01). Tumors from patients with poor prognosis (with NPI > 5.4) had significantly lower levels (P = 0.014) of ALCAM transcripts compared with patients with good prognosis (with NPI < 3.4), and tumors from patients with local recurrence had significantly lower levels than those patients without local recurrence or metastases (P = 0.04). Notably, tumors from patients who died of breast cancer had significantly lower levels of ALCAM transcripts (P = 0.0041) than those with primary tumors but no metastatic disease or local recurrence. Patients with low levels of ALCAM transcripts had significantly (P = 0.009) more incidents (metastasis, recurrence, death) compared with patients with primary breast tumors with high levels of ALCAM transcripts. CONCLUSIONS: In the present panel of breast cancer specimens, decreased levels of ALCAM correlated with the nodal involvement, the grade, the TNM stage, the NPI, and the clinical outcome (local recurrence and death). The data suggest that decreased ALCAM expression is of clinical significance in breast cancer, and that reduced expression indicates a more aggressive phenotype and poor prognosis

Cross-linguistic adaptations of The Comprehensive Aphasia Test: Challenges and solutions

Comparative research on aphasia and aphasia rehabilitation is challenged by the lack of comparable assessment tools across different languages. In English, a large array of tools is available, while in most other languages, the selection is more limited. Importantly, assessment tools are often simple translations and do not take into consideration specific linguistic and psycholinguistic parameters of the target languages. As a first step in meeting the needs for comparable assessment tools, the Comprehensive Aphasia Test is currently being adapted into a number of languages spoken in Europe. In this article, some key challenges encountered in the adaptation process and the solutions to ensure that the resulting assessment tools are linguistically and culturally equivalent, are proposed. Specifically, we focus on challenges and solutions related to the use of imageability, frequency, word length, spelling-to-sound regularity and sentence length and complexity as underlying properties in the selection of the testing material

Computational Models of the Notch Network Elucidate Mechanisms of Context-dependent Signaling

The Notch signaling pathway controls numerous cell fate decisions during development and adulthood through diverse mechanisms. Thus, whereas it functions as an oscillator during somitogenesis, it can mediate an all-or-none cell fate switch to influence pattern formation in various tissues during development. Furthermore, while in some contexts continuous Notch signaling is required, in others a transient Notch signal is sufficient to influence cell fate decisions. However, the signaling mechanisms that underlie these diverse behaviors in different cellular contexts have not been understood. Notch1 along with two downstream transcription factors hes1 and RBP-Jk forms an intricate network of positive and negative feedback loops, and we have implemented a systems biology approach to computationally study this gene regulation network. Our results indicate that the system exhibits bistability and is capable of switching states at a critical level of Notch signaling initiated by its ligand Delta in a particular range of parameter values. In this mode, transient activation of Delta is also capable of inducing prolonged high expression of Hes1, mimicking the “ON” state depending on the intensity and duration of the signal. Furthermore, this system is highly sensitive to certain model parameters and can transition from functioning as a bistable switch to an oscillator by tuning a single parameter value. This parameter, the transcriptional repression constant of hes1, can thus qualitatively govern the behavior of the signaling network. In addition, we find that the system is able to dampen and reduce the effects of biological noise that arise from stochastic effects in gene expression for systems that respond quickly to Notch signaling

α5β1 Integrin-Mediated Adhesion to Fibronectin Is Required for Axis Elongation and Somitogenesis in Mice

The arginine-glycine-aspartate (RGD) motif in fibronectin (FN) represents the major binding site for α5β1 and αvβ3 integrins. Mice lacking a functional RGD motif in FN (FNRGE/RGE) or α5 integrin develop identical phenotypes characterized by embryonic lethality and a severely shortened posterior trunk with kinked neural tubes. Here we show that the FNRGE/RGE embryos arrest both segmentation and axis elongation. The arrest is evident at about E9.0, corresponding to a stage when gastrulation ceases and the tail bud-derived presomitic mesoderm (PSM) induces α5 integrin expression and assumes axis elongation. At this stage cells of the posterior part of the PSM in wild type embryos are tightly coordinated, express somitic oscillator and cyclic genes required for segmentation, and form a tapered tail bud that extends caudally. In contrast, the posterior PSM cells in FNRGE/RGE embryos lost their tight associations, formed a blunt tail bud unable to extend the body axis, failed to induce the synchronised expression of Notch1 and cyclic genes and cease the formation of new somites. Mechanistically, the interaction of PSM cells with the RGD motif of FN is required for dynamic formation of lamellipodia allowing motility and cell-cell contact formation, as these processes fail when wild type PSM cells are seeded into a FN matrix derived from FNRGE/RGE fibroblasts. Thus, α5β1-mediated adhesion to FN in the PSM regulates the dynamics of membrane protrusions and cell-to-cell communication essential for elongation and segmentation of the body axis