Imaging of melanoma: usefulness of ultrasonography before and after contrast injection for diagnosis and early evaluation of treatment

High-frequency ultrasound (8–14 MHz) is routinely used to display cutaneous melanomas. Maximum thickness measurement (Breslow index) has been shown to be well correlated to histologic findings for lesions of more than 0.75 mm. Some morphological criteria (strong delineation, hypoechoic texture, homogeneity) have been reported to help differentiate between malignant and benign pigmented blue lesions, but remain insufficient. Vascular ultrasound analysis using Doppler mode provides additional information and showed good specificity for malignancy (90%–100%), but variable sensitivity (34%–100%). Recent advances in ultrasound imaging allow functional evaluation. Likewise, dynamic contrast-enhanced ultrasound using contrast medium injection and specific perfusion and quantification software showed promising results in clinical and preclinical trials for early prediction of tumor response to target treatments

Label-free, optical sensing of the supramolecular assembly into fibrils of a ditryptophan-DNA hybrid

The grafting of a short nucleic acid strand to ditryptophan dipeptide (WW) results in a peptide-DNA hybrid, which assembles into fibrils under controlled aggregation conditions as evidenced by label free optical sensing owing to the intrinsic fluorescence of the dipeptide

Rate baladeuse associée à une anomalie de Neuhauser: à propos d’un cas

La rate baladeuse est une entité anatomique rare pouvant être d’origine congénitale ou acquise. Son diagnostic se fait souvent suite à une torsion de son pédicule ou fortuitement lors d’un examen d’imagerie. L’association à une autre anomalie congénitale est exceptionnelle et n’a pas été décrite dans la littérature. Nous rapportant le cas d’une association d’une rate pelvienne à une anomalie de Neuhauser longtemps asymptomatiques et de découverte fortuite lors d’une TDM thoraco-abdomino-pelvienne faite dans le cadre d’un bilan d’extension d’un adénocarcinome chez un homme de 86 ans.Pan African Medical Journal 2016; 2

DNA-Mediated Self-Organization of Polymeric Nanocompartments Leads to Interconnected Artificial Organelles

Self-organization of nanocomponents was mainly focused on solid nanoparticles, quantum dots, or liposomes to generate complex architectures with specific properties, but intrinsically limited or not developed enough, to mimic sophisticated structures with biological functions in cells. Here, we present a biomimetic strategy to self-organize synthetic nanocompartments (polymersomes) into clusters with controlled properties and topology by exploiting DNA hybridization to interconnect polymersomes. Molecular and external factors affecting the self-organization served to design clusters mimicking the connection of natural organelles: fine-tune of the distance between tethered polymersomes, different topologies, no fusion of clustered polymersomes, and no aggregation. Unexpected, extended DNA bridges that result from migration of the DNA strands inside the thick polymer membrane (about 12 nm) represent a key stability and control factor, not yet exploited for other synthetic nano-object networks. The replacement of the empty polymersomes with artificial organelles, already reported for single polymersome architecture, will provide an excellent platform for the development of artificial systems mimicking natural organelles or cells and represents a fundamental step in the engineering of molecular factories

Assessing the conformational changes of pb5, the receptor-binding protein of phage T5, upon binding to its Escherichia coli receptor FhuA

Within tailed bacteriophages, interaction of the receptor-binding protein (RBP) with the target cell triggers viral DNA ejection into the host cytoplasm. In the case of phage T5, the RBP pb5 and the receptor FhuA, an outer membrane protein of Escherichia coli, have been identified. Here, we use small angle neutron scattering and electron microscopy to investigate the FhuA-pb5 complex. Specific deuteration of one of the partners allows the complete masking in small angle neutron scattering of the surfactant and unlabeled proteins when the complex is solubilized in the fluorinated surfactant F6-DigluM. Thus, individual structures within a membrane protein complex can be described. The solution structure of FhuA agrees with its crystal structure; that of pb5 shows an elongated shape. Neither displays significant conformational changes upon interaction. The mechanism of signal transduction within phage T5 thus appears different from that of phages binding cell wall saccharides, for which structural information is available

Phage T5 straight tail fiber is a multifunctional protein acting as a tape measure and carrying fusogenic and muralytic activities

We report a bioinformatic and functional characterization of Pb2, a 121-kDa multimeric protein that forms phage T5 straight fiber and is implicated in DNA transfer into the host. Pb2 was predicted to consist of three domains. Region I (residues 1-1030) was mainly organized in coiled coil and shared features of tape measure proteins. Region II (residues 1030-1076) contained two alpha-helical transmembrane segments. Region III (residues 1135-1148) included a metallopeptidase motif. A truncated version of Pb2 (Pb2-Cterm, residues 964-1148) was expressed and purified. Pb2-Cterm shared common features with fusogenic membrane polypeptides. It formed oligomeric structures and inserted into liposomes triggering their fusion. Pb2-Cterm caused beta-galactosidase release from Escherichia coli cells and in vitro peptidoglycan hydrolysis. Based on these multifunctional properties, we propose that binding of phage T5 to its receptor triggers large conformational changes in Pb2. The coiled coil region would serve as a sensor for triggering the opening of the head-tail connector. The C-terminal region would gain access to the host envelope, permitting the local degradation of the peptidoglycan and the formation of the DNA pore by fusion of the two membranes

Mild Cognitive Impairment among Type II Diabetes Mellitus Patients Attending University Teaching Hospital

BACKGROUND: Type II diabetes mellitus (TIIDM) has been associated with structural and functional changes in the brain. TIIDM is commonly associated with obesity, insulin resistance, hypertension, and dyslipidemia, all of which can have negative impact on brain. AIM: The aim of the study was to study the risk of mild cognitive impairment (MCI) among both diabetics and non-diabetics and to identify risk factors to MCI among both groups. METHODS: Two comparative cross-sectional studies were carried out enrolling 100 diabetics and 100 age, sex, and education matching non-diabetics. Cognitive function was assessed using Montreal Cognitive Assessment (MoCA) test and risk factors for MCI were assessed. RESULTS: The subjective complaint of memory impairment among diabetics was significantly higher (34%) compared to non-diabetics (13.0%), p < 0.05. The mean of objective MoCA score was significantly lower among diabetics (25.9 ± 2.5) compared to non-diabetics (27.4 ± 2.4), p < 0.001. The rate of MCI was significantly higher among TIIDM patients (22%) compared to non-diabetics (9%), p < 0.01 and odds ratio (OR) 2.8 (95% confidence interval 1.2–6.5). Among the two studied groups, the rate of MCI was significantly higher among those aged over 50 years compared to younger age as well as among hypertensive compared to non-hypertensive persons, (p < 0.05). Among diabetics, the MCI was significantly higher among those with secondary education, having heart diseases, longer duration of DM, or repeated hypoglycemia attack, p < 0.05. A healthy diet, brain training, and social activities were found to be significantly associated with normal cognition. Logistic analysis revealed that diabetics aged above 50 was the only significant predicting factor for MCI with an OR 2.9 (95% CI: 3.8–123.3), p < 0.001. CONCLUSION: TIIDM is significantly associated with 3-times increasing risk of having MCI compared to non-diabetics. The age, hypertension, cardiovascular diseases, duration of diabetes, and frequency of hypoglycemic episodes are risk factors for cognitive impairment. A healthy diet, brain training, and social activities were associated with better cognitive function

How Do the Properties of Amphiphilic Polymer Membranes Influence the Functional Insertion of Peptide Pores?

Pore-forming peptides are of high biological relevance particularly as cytotoxic agents, but their properties are also applicable for the permeabilization of lipid membranes for biotechnological applications, which can then be translated to the more stable and versatile polymeric membranes. However, their interactions with synthetic membranes leading to pore formation are still poorly understood, hampering the development of peptide-based nanotechnological applications, such as biosensors or catalytic compartments. To elucidate these interactions, we chose the model peptide melittin, the main component of bee venom. Here, we present our systematic investigation on how melittin interacts with and inserts into synthetic membranes, based on amphiphilic block copolymers, to induce pore formation in three different setups (planar membranes and micrometric and nanometric vesicles). By varying selected molecular properties of block copolymers and resulting membranes (e.g., hydrophilic to hydrophobic block ratio, membrane thickness, surface roughness, and membrane curvature) and the stage of melittin addition to the synthetic membranes, we gained a deeper understanding of melittin insertion requirements. In the case of solid-supported planar membranes, melittin interaction was favored by membrane roughness and thickness, but its insertion and pore formation were hindered when the membrane was excessively thick. The additional property provided by micrometric vesicles, curvature, increased the functional insertion of melittin, which was evidenced by the even more curved nanometric vesicles. Using nanometric vesicles allowed us to estimate the pore size and density, and by changing the stage of melittin addition, we overcame the limitations of peptideâEuro"polymer membrane interaction. Mirroring the functionality assay of planar membranes, we produced glucose-sensing vesicles. The design of synthetic membranes permeabilized with melittin opens a new path toward the development of biosensors and catalytic compartments based on pore-forming peptides functionally inserted in synthetic planar or three-dimensional membranes

DNA-directed arrangement of soft synthetic compartments and their behavior in vitro and in vivo

DNA has been widely used as a key tether to promote self-organization of super-assemblies with emergent properties. However, control of this process is still challenging for compartment assemblies and to date the resulting assemblies have unstable membranes precluding in vitro and in vivo testing. Here we present our approach to overcome these limitations, by manipulating molecular factors such as compartment membrane composition and DNA surface density, thereby controlling the size and stability of the resulting DNA-linked compartment clusters. The soft, flexible character of the polymer membrane and low number of ssDNA remaining exposed after cluster formation determine the interaction of these clusters with the cell surface. These clusters exhibit in vivo stability and lack of toxicity in a zebrafish model. To display the breadth of therapeutic applications attainable with our system, we encapsulated the medically established enzyme laccase within the inner compartment and demonstrated its activity within the clustered compartments. Most importantly, these clusters can interact selectively with different cell lines, opening a new strategy to modify and expand cellular functions by attaching such pre-organized soft DNA-mediated compartment clusters on cell surfaces for cell engineering or therapeutic applications

Functional Reconstitution into Liposomes of Purified Human RhCG Ammonia Channel

BACKGROUND: Rh glycoproteins (RhAG, RhBG, RhCG) are members of the Amt/Mep/Rh family which facilitate movement of ammonium across plasma membranes. Changes in ammonium transport activity following expression of Rh glycoproteins have been described in different heterologous systems such as yeasts, oocytes and eukaryotic cell lines. However, in these complex systems, a potential contribution of endogenous proteins to this function cannot be excluded. To demonstrate that Rh glycoproteins by themselves transport NH(3), human RhCG was purified to homogeneity and reconstituted into liposomes, giving new insights into its channel functional properties. METHODOLOGY/PRINCIPAL FINDINGS: An HA-tag introduced in the second extracellular loop of RhCG was used to purify to homogeneity the HA-tagged RhCG glycoprotein from detergent-solubilized recombinant HEK293E cells. Electron microscopy analysis of negatively stained purified RhCG-HA revealed, after image processing, homogeneous particles of 9 nm diameter with a trimeric protein structure. Reconstitution was performed with sphingomyelin, phosphatidylcholine and phosphatidic acid lipids in the presence of the C(12)E(8) detergent which was subsequently removed by Biobeads. Control of protein incorporation was carried out by freeze-fracture electron microscopy. Particle density in liposomes was a function of the Lipid/Protein ratio. When compared to empty liposomes, ammonium permeability was increased two and three fold in RhCG-proteoliposomes, depending on the Lipid/Protein ratio (1/300 and 1/150, respectively). This strong NH(3) transport was reversibly inhibited by mercuric and copper salts and exhibited a low Arrhenius activation energy. CONCLUSIONS/SIGNIFICANCE: This study allowed the determination of ammonia permeability per RhCG monomer, showing that the apparent Punit(NH3) (around 1x10(-3) microm(3)xs(-1)) is close to the permeability measured in HEK293E cells expressing a recombinant human RhCG (1.60x10(-3) microm(3)xs(-1)), and in human red blood cells endogenously expressing RhAG (2.18x10(-3) microm(3)xs(-1)). The major finding of this study is that RhCG protein is active as an NH(3) channel and that this function does not require any protein partner