Analysis of tendinous actuation in balancing the maximal fingertip force for normal and abnormal forefinger system

This work displayed the force capabilities of the musculoskeletal system of the forefinger under external loading. Different states of normal and pathological fingers are studied. We evaluated the impact of losing musculo-tendon unit strength capacities in terms of maximal output fingertip force and tendon tensions distribution. A biomechanical model for a static force analysis is developed through anatomical and kinematic studies. An optimisation approach is then used to determine tendon tension distribution when performing an isometric task. Furthermore, pathological fingers with common cases of injured flexors and extensors are analysed. The method of simulation for forefinger abnormities is described. Furthermore, the simulation results are interpreted.     

Differentiation of Fanconi anemia and aplastic anemia using mitomycin C test in Tunisia

Fanconi anemia (FA) is a recessive chromosomal instability syndrome that is clinically characterized by multiple symptoms. Chromosome breakage hypersensitivity to alkylating agents is the gold standard test for FA diagnosis. In this study, we provide a detailed laboratory protocol for accurate assessment of FA diagnosis based on mitomycin C (MMC) test. Induced chromosomal breakage study was successful in 171 out of 205 aplastic anemia (AA) patients. According to the sensitivity of MMC at 50 ng/ml, 38 patients (22.22%) were diagnosed as affected and 132 patients (77.17%) as unaffected. Somatic mosaicism was suspected in an 11-year-old patient with a FA phenotype. Twenty-six siblings of FA patients were also evaluated and five of them (19.23%) were diagnosed as FA. From this study, a standard protocol for diagnosis of FA was developed. It is routinely used as a diagnostic test of FA in Tunisia.     

Design and synthesis of antimicrobial,anticoagulant, and anticholinesterase hybrid molecules from 4-methylumbelliferone

We designed and synthesized new series of diverse triazoles, isoxazoles, isoxazolines, and aziridines linked 4-methylumbelliferone 1 using intermolecular 1,3-dipolar cycloaddition reactions. Structures of these compounds were established on the basis of ¹H NMR, ¹³C NMR, and ESI-HRMS. All prepared compounds were evaluated for their antimicrobial, anticoagulant, and anticholinesterase activities. Interestingly, among the tested molecules, some of the analogs displayed better activities than the parent 4-methylumbelliferone 1 such as 6a and 6d for their antifungal properties. Moreover, compounds 4, 5, 6, and 7 showed the importance of the added fragments to 4-methylumbelliferone 1 via the linker methylene to have good activity.     

Diversity of archaea and niche preferences among putative ammonia-oxidizing Nitrososphaeria dominating across European arable soils

Archaeal communities in arable soils are dominated by Nitrososphaeria, a class within Thaumarchaeota comprising all known ammonia-oxidizing archaea (AOA). AOA are key players in the nitrogen cycle and defining their niche specialization can help predicting effects of environmental change on these communities. However, hierarchical effects of environmental filters on AOA and the delineation of niche preferences of nitrososphaerial lineages remain poorly understood. We used phylogenetic information at fine scale and machine learning approaches to identify climatic, edaphic and geomorphological drivers of Nitrososphaeria and other archaea along a 3000 km European gradient. Only limited insights into the ecology of the low-abundant archaeal classes could be inferred, but our analyses underlined the multifactorial nature of niche differentiation within Nitrososphaeria. Mean annual temperature, C:N ratio and pH were the best predictors of their diversity, evenness and distribution. Thresholds in the predictions could be defined for C:N ratio and cation exchange capacity. Furthermore, multiple, independent and recent specializations to soil pH were detected in the Nitrososphaeria phylogeny. The coexistence of widespread ecophysiological differences between closely related soil Nitrososphaeria highlights that their ecology is best studied at fine phylogenetic scale.     

On computing the fuzzifier in downward arrow FLVQ: a data driven approach

Clustering is an important research area that has practical applications in many fields. Fuzzy clustering has shown advantages over crisp and probabilistic clustering, especially when there are significant overlaps between clusters. Most analytic fuzzy clustering approaches are derived from Bezdek's fuzzy c-means algorithm. One major factor that influences the determination of appropriate clusters in these approaches is an exponent parameter, called the fuzzifier. To our knowledge, no theoretical reason leading to an optimal setting of this parameter is available. This paper presents the development of an heuristic scheme for determining the fuzzifier. This scheme creates close interactions between the fuzzifier and the data set to be clustered. Experimental results in clustering IRIS data and in code book design required for image compression reveal a good performance of our proposal.     

Serotype Distribution,Antibiotic Resistance and Clonality of Streptococcus pneumoniae Isolated from Immunocompromised Patients in Tunisia

BackgroundPneumococcal disease, a major cause of morbidity and mortality globally, has higher incidence among young children, the elderly and the immunocompromised of all ages. In Tunisia, pneumococcal conjugate vaccines (PCVs) are not included in the national immunization program. Also, few studies have described the epidemiology of S. pneumoniae in this country and, in particular, no molecular typing studies have been performed. The aim of this study was to evaluate serotype distribution, antimicrobial resistance and clonality of Streptococcus pneumoniae isolated from neutropenic patients in Tunisia.MethodsFifty-nine S. pneumoniae were isolated from infection (n = 31) and colonization (n = 28) sites of patients (children and adults) attending the National Centre of Bone Marrow Transplantation in Tunis between 2005–2011. All isolates were characterized by serotype, antimicrobial resistance pattern and multilocus sequence typing (MLST).ResultsThe majority (66.1%) of the isolates belonged to five serotypes all included in PCVs: 6B, 9V, 14, 19F and 23F. The potential coverage of the 10-valent and 13-valent PCV was of 71.2% and 76.3% respectively. Resistance rates were very high and 69.5% of the isolates were multidrug resistant: non-susceptibility rates to penicillin, amoxicillin and cefotaxime were 66.1%, 40.7% and 27.1%, respectively; resistance rates to erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole, were 69.5%, 61.0%, 37.3%, 22.0% and 67.8%, respectively. The most frequent serotypes had STs characteristic of multidrug resistant international clones known to be highly successful and important causes of pneumococcal infection: Spain 23F-ST81, France 9V/14-ST156, Spain 6B-ST90, 19F-ST320, and Portugal 19F-ST177.ConclusionsThe majority of S. pneumoniae strains recovered from immunocompromised patients in Tunisia are representatives of multidrug resistant pandemic clones that express serotypes targeted by PCVs. To contain the burden of pneumococcal disease and improve treatment choices among Tunisian immunocompromised patients PCVs should be offered to all of them.     

BMP4 promotes formation of primitive vascular networks in human embryonic stem cell-derived embryoid bodies

The vasculature develops primarily through two processes, vasculogenesis and angiogenesis. Although much work has been published on angiogenesis, less is known of the mechanisms regulating the de novo formation of the vasculature commonly called vasculogenesis. Human embryonic stem cells (hESC) have the capability to produce all of the cells of the body and have been used as in vitro models to study the molecular signals controlling differentiation and vessel assembly. One such regulatory molecule is bone morphogenetic protein-4 (BMP4), which is required for mesoderm formation and vascular/hematopoietic specification in several species. However, hESC grown in feeder-free conditions and treated with BMP4 differentiate into a cellular phenotype highly expressing a trophoblast gene profile. Therefore, it is unclear what role, if any, BMP4 plays in regulating vascular development in hESC. Here we show in two National Institutes of Health-registered hESC lines (BG02 and WA09) cultured on a 3D substrate of Matrigel in endothelial cell growth medium-2 that the addition of BMP4 (100 ng/ml) for 3 days significantly increases the formation and outgrowth of a network of cells reminiscent of capillary-like structures formed by mature endothelial cells (P<0.05). Analysis of the expression of 45 genes by quantitative real time-polymerase chain reaction on a low-density array of the entire culture indicates a rapid and significant downregulation of pluripotent and most ectodermal markers with a general upregulation of endoderm, mesoderm, and endothelial markers. Of the genes assayed, BMPR2 and RUNX1 were differentially affected by exposure to BMP4 in both cell lines. Immunocytochemistry indicates the morphological structures formed were negative for the mature endothelial markers CD31 and CD146 as well as the neural marker SOX2, yet positive for the early vascular markers of endothelium (KDR, NESTIN) and smooth muscle cells (alpha-smooth muscle actin [alpha SMA]). Together, these data suggest BMP4 can enhance the formation and outgrowth of an immature vascular system.     

Potential role of rhizobia to enhance chickpea-growth and yield in low fertility-soils of Tunisia

Plant growth-promoting rhizobacteria are bacteria that improve plant growth and reduce plant pathogen damages. In this study, 100 nodule bacteria were isolated from chickpea, screened for their plant growth-promoting (PGP) traits and then characterised by PCR-RFLP of 16 S rDNA. Results showed that most of the slow-growing isolates fixed nitrogen but those exhibiting fast-growth did not. Fourteen isolates solubilized inorganic phosphorus, 16 strains produced siderophores, and 17 strains produced indole acetic acid. Co-culture experiments identified three strains having an inhibitory effect against Fusarium oxysporum, the primary pathogenic fungus for chickpea in Tunisia. Rhizobia with PGP traits were assigned to Mesorhizobium ciceri, Mesorhizobium mediterraneum, Sinorhizobium meliloti and Agrobacterium tumefaciens. We noted that PGP activities were differentially distributed between M. ciceri and M. mediterraneum. The region of Mateur in northern Tunisia, with clay–silty soil, was the origin of 53% of PGP isolates. Interestingly, we found that S. meliloti and A. tumefaciens strains did not behave as parasitic nodule-bacteria but as PGP rhizobacteria useful for chickpea nutrition and health. In fact, S. meliloti strains could solubilize phosphorus, produce siderophore and auxin. The A. tumefaciens strains could perform the previous PGP traits and inhibit pathogen growth also. Finally, one candidate strain of M. ciceri (LL10)—selected for its highest symbiotic nitrogen fixation and phosphorus solubilization—was used for field experiment. The LL10 inoculation increased grain yield more than three-fold. These finding showed the potential role of rhizobia to be used as biofertilizers and biopesticides, representing low-cost and environment-friendly inputs for sustainable agriculture.

     

Founder mutations in Tunisia: implications for diagnosis in North Africa and Middle East

Cystinuria (OMIM 220100) is an inborn congenital disorder characterised by a defective cystine metabolism resulting in the formation of cystine stones. Among the heterogeneous group of kidney stone diseases, cystinuria is the only disorder which is exclusively caused by gene mutations. So far, two genes responsible for cystinuria have been identified: SLC3A1 (chromosome 2p21) encodes the heavy subunit rBAT of a renal b^0,+ transporter while SLC7A9 (chromosome 19q12) encodes its interacting light subunit b^0,+AT. Mutations in SLC3A1 are generally associated with an autosomal-recessive mode of inheritance whereas SLC7A9 variants result in a broad clinical variability even within the same family. The detection rate for mutations in these genes is larger than 85%, but it is influenced by the ethnic origin of a patient and the pathophysiological significance of the mutations. In addition to isolated cystinuria, patients suffering from the hypotonia-cystinuria syndrome have been reported carrying deletions including at least the SLC3A1 and the PREPL genes in 2p21. By extensive molecular screening studies in large cohort of patients a broad spectrum of mutations could be identified, several of these variants were functionally analysed and thereby allowed insights in the pathology of the disease as well as in the renal trafficking of cystine and the dibasic amino acids. In our review we will summarize the current knowledge on the physiological and the genetic basis of cystinuria as an inborn cause of kidney stones, and the application of this knowledge in genetic testing strategies.