Measurement of prehension force during microsurgical gesture: a pilot study

During the last decades and still nowadays the practical teaching of surgical residents was only evaluated, guided and taught through the expertise of a senior surgeon, which is highly subjective and unequal between experts (Ramachandran, 2013). This training based on the Halstedian model depended on the opportunities and relationship the residents build with their mentor and could lead to an unfair and heterogeneous training. Consequently, only little objectives elements is known about what makes a surgical gesture optimal. Indeed, the resident performs and modifies his/her gesture as taught by his mentor. No objective technique, data or knowledge underlie his/her new learning to ensure him/her that the applied gesture is the best. Another issue brought by the Halstedian model is that a lot of what improves a surgeon’s gesture (e.g the pressure applied on the clamps, muscle activity, etc) cannot be assessed by direct observation. However, these last few years, more objective types of assessments have been studied to fill the lack of objective and updated training. Most of the recent studies focus on a few data, such as width of movement and time, but none have been interested by other data such as cerebral activity or muscular activity. Nevertheless, no study has yet compared measurements to find out which parameter is the most discriminative, nor the most efficient to use in pedagogical tools. The aim of this pilot project has been to create a microsurgery-connected clamp enabling to measure the prehension force during a microsurgical gesture and to compare it according to the subject experience (expert, intermediate, novice)

The Melanin Pigmentary Disorder in a Family with Hermansky-Pudlak Syndrome

The albinotic skin and hair of 2 patients with Hermansky-Pudlak syndrome were investigated by light and electron microscopy. Incubation of hairbulbs and epidermis in l-dopa revealed a weak tyrosinase activity. The epidermal melanocyte population was of normal density. The most striking feature was the presence of numerous giant melanosomes resembling those mainly reported in various hyperpigmented skin lesions. The association of this melanosomal disorder with the platelet dysfunction and ceroid storage typical of the autosomal recessive Hermansky-Pudlak syndrome might provide new insights into the mechanism leading to formation of giant melanosomes

Differences in the signaling pathways of α1A- and α1B-adrenoceptors are related to different endosomal targeting

Aims: To compare the constitutive and agonist-dependent endosomal trafficking of α1A- and α1B-adrenoceptors (ARs) and to establish if the internalization pattern determines the signaling pathways of each subtype. Methods: Using CypHer5 technology and VSV-G epitope tagged α1A- and α1B-ARs stably and transiently expressed in HEK 293 cells, we analyzed by confocal microscopy the constitutive and agonist-induced internalization of each subtype, and the temporal relationship between agonist induced internalization and the increase in intracellular calcium (determined by FLUO-3 flouorescence), or the phosphorylation of ERK1/2 and p38 MAP kinases (determined by Western blot). Results and Conclusions: Constitutive as well as agonist-induced trafficking of α1A and α1B ARs maintain two different endosomal pools of receptors: one located close to the plasma membrane and the other deeper into the cytosol. Each subtype exhibited specific characteristics of internalization and distribution between these pools that determines their signaling pathways: α1A-ARs, when located in the plasma membrane, signal through calcium and ERK1/2 pathways but, when translocated to deeper endosomes, through a mechanism sensitive to β-arrestin and concanavalin A, continue signaling through ERK1/2 and also activate the p38 pathway. α1B-ARs signal through calcium and ERK1/2 only when located in the membrane and the signals disappear after endocytosis and by disruption of the membrane lipid rafts by methyl-β-cyclodextrin

Members of the nuclear factor κB family transactivate the murine c-myb gene

Expression of the c-myb proto-oncogene is primarily detected in normal tissue and tumor cell lines of immature hematopoietic origin, and the down- regulation of c-myb expression is associated with hematopoietic maturation. Cell lines that represent mature, differentiated hematopoietic cell types contain 10-100-fold less c-myb mRNA than immature hematopoietic cell types. Differences in steady-state c-myb mRNA levels appear to be primarily maintained by a conditional block to transcription elongation that occurs in the first intron of the gene. The block to transcription elongation has been mapped, using nuclear run-on analysis, to a region of DNA sequence that is highly conserved between mouse and man. Two sets of DNA-protein interactions, flanking the site of the block to transcription elongation, were detected that exhibited DNA-binding activities that strongly correlated with low steady-state c-myb mRNA levels. Several criteria demonstrated that members of the nuclear factor κB (NF-κB) family of transcription factors were involved in the DNA-protein interactions identified in these two sets. Surprisingly, cotransfection experiments demonstrated that coexpression of members of the NF-κB family, specifically p50 with p65 and p65 with c-Rel, transactivated a c-myb/chloramphenicol acetyltransferase reporter construct that contained 5'flanking sequences, exon I, intron I, and exon II of the c-myb gene. Transactivation by these heterodimer combinations was dependent on regions of the c-myb first intron containing the NF-κB-binding sites. These findings suggest that NF-κB family members may be involved in either modifying the efficiency of transcription attenuation or acting as an enhancer-like activity to increase transcription initiation. Thus, the regulation of c-myb transcription may be quite complex, and members of the NF-κB family likely play an important role in this regulation