Unravelling the mysterious roles of melanocortin-3 receptors in metabolic homeostasis and obesity using mouse genetics.

The central nervous melanocortin system maintains body mass and adiposity within a 'healthy' range by regulating satiety and metabolic homeostasis. Neural melanocortin-4 receptors (MC4R) modulate satiety signals and regulate autonomic outputs governing glucose and lipid metabolism in the periphery. The functions of melanocortin-3 receptors (MC3R) have been less well defined. We have observed that food anticipatory activity (FAA) is attenuated in Mc3r-/- mice housed in light:dark or constant dark conditions. Mc3r-/- mice subjected to the restricted feeding protocol that was used to induce FAA also developed insulin resistance, dyslipidaemia, impaired glucose tolerance and evidence of a cellular stress response in the liver. MC3Rs may thus function as modulators of oscillator systems that govern circadian rhythms, integrating signals from nutrient sensors to facilitate synchronizing peak foraging behaviour and metabolic efficiency with nutrient availability. To dissect the functions of MC3Rs expressed in hypothalamic and extra-hypothalamic structures, we inserted a 'lox-stop-lox' (TB) sequence into the Mc3r gene. Mc3r (TB/TB) mice recapitulate the phenotype reported for Mc3r-/- mice: increased adiposity, accelerated diet-induced obesity and attenuated FAA. The ventromedial hypothalamus exhibits high levels of Mc3r expression; however, restoring the expression of the LoxTB Mc3r allele in this nucleus did not restore FAA. However, a surprising outcome came from studies using Nestin-Cre to restore the expression of the LoxTB Mc3r allele in the nervous system. These data suggest that 'non-neural' MC3Rs have a role in the defence of body weight. Future studies examining the homeostatic functions of MC3Rs should therefore consider actions outside the central nervous system.

Control of carbon nanotube handedness using a supramolecular chiral surface.

Sorting diameter and handedness of carbon nanotubes still appears as an important challenge in nanotechnology. In this context, supramolecular structures formed by self-assembled chiral molecules deposited on well-defined metal surfaces can be used to discriminate the two isomers of carbon nanotubes. Calculations are carried out to determine the adsorption energy of nanotube enantiomers on alaninate coated Cu(110) surface. The results show a significant discrimination of the L and R handed isomers by such a surface and an additional selectivity in terms of small and large tube diameters.

Chiral interaction in double-wall carbon nanotubes: simple rules deduced from a large sampling of tubes.

We study a large sampling of chiral double-wall carbon nanotubes to propose simple formula describing the dependence of the interwall energy, the chiral discrimination energy, and the radial breathing mode frequencies as a function of the main characteristics of the tubes, i.e., their radius, length and chiral angle. It is shown that tube pairs with the same handedness are more stable than enantiomeric pairs, and this discrimination, though small, mainly occurs in the first step of the growth of an inner tube inside an outer one. Chiral splittings of the breathing mode frequencies for the two DWCNT diastereoisomers (n(i),m(i))@(n(o),m(o)) and (m(i),n(i))@(n(o),m(o)) can reach a few wave numbers.

Enantioselectivity of amino acids using chiral sensors based on nanotubes.

The selective detection of amino acid enantiomers can be achieved by considering chiral nanotubes used in a resonator configuration. We show that this enantioselectivity is appreciably increased when a peptide molecule is inserted in the tube. The chiral polarization of the nanotube at the linear and nonlinear levels due to the inserted polar peptide is very sensitive to the adsorption of left- or right-handed alanine molecules. This leads to a difference in the resonance frequency of the sensor which can increase to 12 MHz when the nanotube is not chiral (instead of 0 for the bare tube) and can reach 38 MHz for a chiral tube (instead of 14 MHz for the bare tube). The influence of the various parameters which are responsible for such a differential frequency shift, i.e., the tube hyperpolarizability, the polar electric properties of the peptide, and the screening effect due to the tube on the peptide-alanine interactions, is discussed and some general rules are given regarding the optimization of the enantioselectivity of these sensors.

Chiral response of single walled carbon nanotube based sensors to adsorption of amino acids: a theoretical model.

Calculations of the interaction energy and dielectric responses of chiral single walled carbon nanotubes to the presence of amino acid enantiomers are carried out. A theoretical study is developed to show that the frequency shifts of selected nanotubes conveniently tailored to the size of the probed molecules and used in a resonator configuration can selectively detect different species of amino acids and the left- and right-handed enantiomers of these species. Criteria for an optimization of the adsorption energy and frequency response on the size and chiral angle of the nanotubes are given. It is found that a very small set of carbon tubes obeys these conditions.

Long nanotube dielectric properties used as sensors of large molecules: a semicontinuum approach.

A semicontinuum approach on the basis of an effective polarizability tensor per length and radius units is used to describe the dielectric response of a long single wall nanotube to the adsorption of an extended molecule. Changes in the permittivity ratio of the nanotube+molecule over the nanotube alone, which are directly connected to frequency shifts of the nanotube in a resonator configuration due to the presence of the molecule, provide a test of sensitivity of the system. The behavior of this ratio is analyzed for linear and circular geometries of the molecule, as a function of the tube characteristics (length and radius) and of the molecular size and polarizability distribution. Extension to three dimensional systems with a large set of polarizable centers is discussed in terms of self-polarization of the centers and morphology of the surface of the sensed system.

Role of water molecules in the KcsA protein channel by molecular dynamics calculations.

Molecular dynamics simulations supported by electrostatic calculations have been conducted on the KcsA channel to determine the role of water molecules in the pore. Starting from the X-ray structure of the KcsA channel in its closed state at 2.0 angstroms resolution, the opening of the pore towards a conformation built on the basis of EPR results is studied. We show that water molecules act as a structural element for the K+ ions inside the filter and the hydrophobic cavity of the channel. In the filter, water tends to enhance the depth of the wells occupied by the K+ ions, while in the cavity there is a strong correlation between the water molecules and the cavity ion. As a consequence, the protein remains very stable in the presence of three K+ ions in the selectivity filter and one in the cavity. The analysis of the dynamics of water molecules in the cavity reveals preferred orientations of the dipoles along the pore axis, and a correlated behavior between this dipole orientation and the displacement of the K+ ion during the gating process.

Influence of molecular adsorption on the dielectric properties of a single wall nanotube: a model sensor.

Recent measurements of the resonance frequency of a copper disk covered with carbon nanotube bundles have shown characteristic resonance shifts during exposure with various gas molecules. The shifts were interpreted as the change of the dielectric permittivity of the system forming the sensor due to the electric properties of the adsorbed molecules. Starting from a simplified sensor model formed by one single wall nanotube, we develop a self-consistent approach to describe the variation of the linear dielectric susceptibility of the tube at the atomic scale when molecules are adsorbed at its external surface. The sensitivity of this model sensor is tested as a function of the apolar or polar nature of the admolecules, their adsorption geometry, their concentration, and the characteristics of the tube (length, diameter,...). The comparison with data on dielectric constant changes vs adsorption, coming from measurements of the resonance frequency shifts, displays striking agreement for most of the molecular species considered.

Diagnosis of a gastric mucosa-associated lymphoid tissue lymphoma by endoscopic ultrasonography-guided biopsies in a patient with a parotid gland localization.

We report the case of a 32-year-old man with a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland associated with Sjögren syndrome. He underwent an upper endoscopy as part of the screening of a gastric localization which showed a diffuse non-specific gastritis. However, endoscopic ultrasonography (EUS) evidenced a focal wall thickening of the vertical portion of the smaller curvature. EUS-guided biopsies of this area disclosed a MALT lymphoma, whereas biopsies under endoscopy concluded to mild chronic gastritis. The search for Helicobacter pylori infection remained negative. Four months after treatment with anti-CD20 antibodies, EUS showed a diminution of the abnormal thickening of the second layer. Regression was confirmed histologically on new EUS-guided biopsies. MALT lymphoma is usually considered a localized disease; however, dissemination is probably more frequent than initially believed. Our case reflects the importance of a systematic screening for a gastric localization in patients with MALT lymphoma of the salivary glands. In this situation, association to autoimmune disease such as Sjögren syndrome is more likely to explain the gastric location than infection with H. pylori. Endoscopic ultrasonography has a major impact for the staging of gastric MALT lymphoma, but may also help diagnose focal infiltration by the disease.

Marfan's syndrome and multiple extracranial aneurysms.

Dissecting aneurysms of the extracranial cervical arteries in Marfan's syndrome are most frequently caused by the extension of aortic dissection. Spontaneous and isolated aneurysms limited to the major extracranial cervical arteries have also been reported in Marfan's syndrome, although very rarely. In these cases, the aneurysms are usually asymptomatic or may present as a pulsatile mass. Transient ischemic attacks (TIAs) or strokes, associated with isolated extracranial aneurysms, have not been mentioned in Marfan's syndrome. We report a patient with Marfan's syndrome presenting with TIAs in whom we detected a saccular aneurysm of the vertebral artery as well as bilateral fusiform aneurysms of the internal carotid arteries.

Cardiac sarcoma originating from the tricuspid valve.

Primary cardiac sarcomas are uncommon. We report an unusual presentation of a cardiac sarcoma that originated from the posterior leaflet of the tricuspid valve. This tumor, which provided a working diagnosis of tricuspid valve myxoma before and during surgery, should be considered in the differential diagnosis of right atrial and ventricular masses.

Diffuse calcinosis cutis in a patient with congenital leukemia and leukemia cutis.

We report an unusual case of congenital leukemia with leukemia cutis (LC) and diffuse calcinosis cutis. A newborn girl presented with widespread dusky red and yellowish cutaneous nodules and papules. Bone marrow morphology was consistent with the diagnosis of acute monocytic leukemia of the FAB M5 type. Skin biopsy specimens confirmed the presence of a leukemic infiltrate and revealed calcium salt deposition in the papillary and reticular dermis. Calcinosis was diffuse in the whole skin but spared other organs. Vascular calcification was not present. Serum calcium levels oscillated between 2.5 and 2.86 mmol/l, and phosphorus, parathyroid hormone and 25-hydroxyvitamin D(3) levels were normal. There were diffuse osteoporosis and spontaneous fractures of small tubular bones. The patient responded to chemotherapy but, following consolidation treatment, developed sepsis and died at 120 days of age. Congenital leukemia is rare and LC is uncommon. Hypercalcemia may be a complication of leukemia, which leads to multiorgan metastatic calcification. Despite the absence of frank hypercalcemia, the presence of bone lesions suggests that the patient's calcinosis cutis was of the metastatic type. However, the cutaneous leukemic infiltrate may also represent a triggering factor for calcium deposition in the skin.

Hypocomplementemic panniculitis with paraprotein.

Two episodes of severe panniculitis accompanied by fever and an acute phase response were the main clinical features in a patient who had an unusual IgG kappa paraprotein. Both episodes responded promptly to steroids. Complement proteins of the early classical pathway were depleted in the patient's serum, and in vitro experiments indicated that the IgG kappa paraprotein activated complement directly. The association of recurrent panniculitis and paraproteinemia-hypocomplementemia has been described in 2 other patients. It should be recognized since its response to steroids is immediate.

Spontaneous hemorrhage of thymus and thymoma in adults.

Spontaneous hemorrhage from the thymus is extremely rare. In adults, it may occur in patients without underlying coagulopathy and mimic aortic dissection. To the best of our knowledge, only three previous adult cases have been reported in the English literature. This report presents two additional adult patients who were admitted in our institution with different clinical presentations of spontaneous thymic hemorrhage.