A resonant sextuplet of sub-Neptunes transiting the bright star HD 110067.

Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars1,2. However, their composition, formation and evolution remain poorly understood3. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment. Those in resonance (with their orbital periods related by a ratio of small integers) are particularly valuable because they imply a system architecture practically unchanged since its birth. Here we present the observations of six transiting planets around the bright nearby star HD 110067. We find that the planets follow a chain of resonant orbits. A dynamical study of the innermost planet triplet allowed the prediction and later confirmation of the orbits of the rest of the planets in the system. The six planets are found to be sub-Neptunes with radii ranging from 1.94R⊕ to 2.85R⊕. Three of the planets have measured masses, yielding low bulk densities that suggest the presence of large hydrogen-dominated atmospheres.

A candidate super-Earth planet orbiting near the snow line of Barnard's star.

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

Amino acid profiles of young adults differ by sex, body mass index and insulin resistance.

BACKGROUND AND AIMS: An increase in plasma branched-chain amino acids is associated with a higher risk of developing type 2 diabetes and cardiovascular diseases. However, little is known about the basal plasma amino acid concentrations in young adults. Our aim was to determine the plasma amino acid profiles of young adults and to evaluate how these profiles were modified by sex, body mass index (BMI) and insulin resistance (IR). METHODS AND RESULTS: We performed a transversal study with 608 Mexican young adults aged 19.9 ± 2.4 years who were applicants to the Universidad Autónoma de San Luis Potosí. The subjects underwent a physical examination and provided a clinical history and a blood sample for biochemical, hormonal and amino acid analyses. The women had higher levels of arginine, aspartate and serine and lower levels of α-aminoadipic acid, cysteine, isoleucine, leucine, methionine, proline, tryptophan, tyrosine, urea and valine than the men. The obese subjects had higher levels of alanine, aspartate, cysteine, ornithine, phenylalanine, proline and tyrosine and lower levels of glycine, ornithine and serine than the normal weight subjects. Subjects with IR (defined as HOMA > 2.5) had higher levels of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine than the subjects without IR. Furthermore, we identified two main groups in the subjects with obesity and/or IR; one group was composed of amino acids that positively correlated with the clinical, biochemical and hormonal parameters, whereas the second group exhibited negative correlations. CONCLUSION: This study demonstrates that young adults with obesity or IR have altered amino acid profiles characterized by an increase in alanine, aspartate, proline and tyrosine and a decrease in glycine.

Methylmercury decreases cellular excitability by a direct blockade of sodium and calcium channels in bovine chromaffin cells: an integrative study.

Methylmercury, a potent environmental pollutant responsible for fatal food poisoning, blocked calcium channels of bovine chromaffin cells in a time- and concentration-dependent manner with an IC50 of 0.93 µM. This blockade was not reversed upon wash-out and was greater at more depolarising holding potentials (i.e. 21 % at -110 mV and 60 % at -50 mV, after 3 min perfusion with methylmercury). In ω-toxins-sensitive calcium channels, methylmercury caused a higher blockade of I Ba than in ω-toxins-resistant ones, in which a lower blockade was detected. The sodium current was also blocked by acute application of methylmercury in a time- and concentration-dependent manner with an IC50 of 1.05 µM. The blockade was not reversed upon wash-out of the drug. The drug inhibited sodium current at all test potentials and shows a shift of the I-V curve to the left of about 10 mV. Intracellular dialysis with methylmercury caused no blockade of calcium or sodium channels. Voltage-dependent potassium current was not affected by methylmercury. Calcium- and voltage-dependent potassium current was also drastically depressed. This blockade was related to the prevention of Ca(2+) influx through voltage-dependent calcium channels coupled to BK channels. Under current-clamp conditions, the blockade of ionic current present during the generation and termination of action potentials led to a drastic alteration of cellular excitability. The application of methylmercury greatly reduced the shape and the number of electrically evoked action potentials. Taken together, these results point out that the neurotoxic action evoked by methylmercury may be associated to alteration of cellular excitability by blocking ionic currents responsible for the generation and termination of action potentials.

Histopathologic, immunohistochemical and ultrastructural features of a granular cell tumour in an Australian parakeet (Melopsittacus undulatus).

An adult male Australian parakeet (Melopsittacus undulatus) presented a firm nodular lesion in the lateral metacarpal region of the right wing. Microscopically, there were neoplastic cells, round and polyhedral in shape, with abundant, slightly eosinophilic granular cytoplasm; they were strongly periodic-acid Schiff-positive and resistant to diastase digestion. Some groups of neoplastic cells were immunopositive for smooth muscle actin and desmin. There was no immunopositivity for S-100 protein, CD68 and cytokeratin. Ultrastructurally, the neoplastic cells were round and polygonal in shape, and they were characterized by abundant cytoplasm with numerous homogeneous osmophilic bodies covered by an electron-dense membrane (lysosomes). The histopathologic, immunohistochemical and ultrastructural features of the neoplastic tissue are consistent with a granular cell tumour, which has been described in different animal species and anatomic locations; however, this seems to be an infrequent neoplasm in Australian parakeets. The immunopositivity of the neoplastic cells for smooth muscle actin and desmin, as well as slight positivity for muscle with Masson's trichrome, suggest that this is a tumour of myogenic origin.

[Our experience in the diagnosis and treatment of cerebral pseudoaneurysms]. / Nuestra experiencia en el diagnóstico y tratamiento de los seudoaneurismas cerebrales.

OBJECTIVE: To present our experience in the diagnosis and intravascular treatment of cerebral pseudoaneurysms. MATERIAL AND METHODS: We present 11 pseudoaneurysms (2 traumatic, 2 mycotic, 3 iatrogenic, and 4 with other causes). We analyze the methods and diagnostic criteria, radiological and clinical outcome, the criteria used in making decisions about treatment, the method of treatment, and the complications. RESULTS: Digital subtraction angiography is the gold standard for the diagnosis of cerebral pseudoaneurysms; the diagnostic criteria in the literature include: aneurysms with early morphological changes and distal aneurysms or proximal aneurysms associated with another distal one, in the context of the right symptoms and signs. In the nine patients treated with endovascular techniques, the treatment objective was achieved and rebleeding did not occur. CONCLUSIONS: In cases with clinical suspicion of a pseudoaneurysm, the patient should undergo angiography. This is especially important in patients with inexplicable cerebral hemorrhage and in those with septicemia. CT angiography and MR angiography have good diagnostic accuracy and can replace conventional angiography. However, the treatment of choice is endovascular and treatment should not be delayed unless access to the pseudoaneurysm is impeded, usually due to severe cerebral vasospasm.

A nearby transiting rocky exoplanet that is suitable for atmospheric investigation.

Spectroscopy of transiting exoplanets can be used to investigate their atmospheric properties and habitability. Combining radial velocity (RV) and transit data provides additional information on exoplanet physical properties. We detect a transiting rocky planet with an orbital period of 1.467 days around the nearby red dwarf star Gliese 486. The planet Gliese 486 b is 2.81 Earth masses and 1.31 Earth radii, with uncertainties of 5%, as determined from RV data and photometric light curves. The host star is at a distance of ~8.1 parsecs, has a J-band magnitude of ~7.2, and is observable from both hemispheres of Earth. On the basis of these properties and the planet's short orbital period and high equilibrium temperature, we show that this terrestrial planet is suitable for emission and transit spectroscopy.

[The role of the hospital pharmacist in the prevention, treatment and management of the side effects associated with antiretroviral treatment]. / Papel del farmacéutico de hospital en la prevención, identificación y manejo de los efectos adversos asociados al tratamiento antirretroviral.

At present, the side effects associated with antiretroviral treatment are the main reasons for discontinuation of this kind of therapy, both in clinical trials and in regular clinical practise. On the other hand, due to the change of direction that our profession has suffered in recent years, we face the need to establish a different relationship with the patient, achieving direct and effective Pharmaceutical Care within a framework of shared responsibility for therapeutic results. Pharmacist interventions should be aimed at improving the quality of life of patients, which can only be achieved with a multidisciplinary approach and individualised and adjusted to new patterns of toxicity of the drugs currently used. The pharmacist who does this work must know how to interpret these side effects, giving accurate information to the patient about both pharmacological and non-pharmacological treatment and correct pharmaceutical follow-up which clearly sets forth the criteria for referral to medical appointments. The aim of this paper is to establish baselines so that the hospital pharmacist can perform clearly and uniformly in the prevention, identification and management of major side effects: gastrointestinal, cardiovascular, dermatological, at the central nervous system and kidney level, associated with antiretroviral therapy.

Carbohydrate-naphthalene diimide conjugates as potential antiparasitic drugs: Synthesis, evaluation and structure-activity studies.

The neglected tropical diseases Human African Trypanosomiasis and leishmaniasis are caused by infection with trypanosomatid parasites Trypanosoma brucei and Leishmania spp, respectively. The genomes of these organisms contain multiple putative G-quadruplex (G4) forming sequences which have recently been proposed to mediate processes relevant for parasite survival. Therefore, G4 could be considered as potential targets for a novel approach towards the development of antiparasitic drugs. Recently, we have demonstrated that G4 ligands such as carbohydrate naphthalene diimide conjugates (carb-NDIs) possess notable antiparasitic activity. Herein, we have synthesized a new family of carb-NDIs, characterized by significant structural variability, and evaluated their anti-parasitic activity, with special focus on T. brucei. The interaction with relevant G4 sequences was evaluated in vitro through independent biophysical methods (FRET melting assays under competing conditions with double stranded DNA, circular dichroism and fluorescence titrations). Finally, flow cytometry and confocal microscopy experiments demonstrated that the conjugates exhibit excellent uptake into T. brucei parasites, localizing in the nuclei and kinetoplasts. Promising antiparasitic activity and selectivity against control mammalian cells, together with their peculiar mechanism of action, render the carb-NDI conjugates as suitable candidates for the development of an innovative treatment of trypanosomiasis.

Combined surgery and embolization to treat ruptured cerebral aneurysms with cerebral hematoma and intracranial hypertension: a retrospective analysis and review of the literature. / Tratamiento combinado, mediante embolización y cirugía, de los aneurismas cerebrales rotos con hematoma cerebral e hipertensión intracraneal: Análisis retrospectivo y revisión de la bibliografía.

OBJECTIVE: To determine whether the urgent embolization of a cerebral aneurysms and posterior surgery on cerebral hematomas is safe and efficacious in patients with hematomas and signs of intracranial hypertension due to the rupture of cerebral aneurysms. METHODS: We included 23 consecutive patients in poor clinical condition due to an intracranial hematoma caused by a ruptured cerebral aneurysm who were treated with both embolization and surgery within 4hours of the onset of symptoms. All patients had clinical signs of intracranial hypertension and / or altered levels of consciousness, including coma due to rostrocaudal deterioration. We evaluated the efficacy of the combined technique by determining the degree of closure of the aneurysms and the patients' prognosis one month after the procedures; we evaluated safety by analyzing the complications of the treatments. RESULTS: All but two of the patients (21/23; 91.3%) had an aneurysm of the middle cerebral artery. All patients scored 4 on the Fisher scale and were classified as Hunt and Hess IV or V. The mean time from the identification of the aneurysm on computed tomography to embolization was 115minutes. A balloon remodeling technique was used in 18 (78%) patients; embolization achieved adequate closure in 19 (82.6%) patients. During surgery, a ventricular drain was placed in 9 (39.1%) patients. One month after treatment, 13 (56.5%) patients were functionally independent and 3 (13%) had died. No episodes of rebleeding were observed. CONCLUSION: In our experience, combined treatment including embolization of the aneurysm and surgical decompression with evacuation of the hematoma is a safe and effective alternative to surgical treatment alone.

A giant exoplanet orbiting a very-low-mass star challenges planet formation models.

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.

"A bridge over troubled gaps": up-conversion driven photocatalysis for hydrogen generation and pollutant degradation by near-infrared excitation.

Spectral up-conversion (UC) has been attracting growing interest for the effective harvesting of the near-infrared (NIR) part of sunlight for photocatalytic hydrogen production and environmental purification. We present evidence of NIR-to-UV-VIS photon conversion for degradation of organic dyes and hydrogen and oxygen evolution via water-splitting by TiO2 and Rh-Cr oxide-loaded SrTiO3:Al photocatalysts, respectively.

The effect of diabetes and centrally administered insulin on anterior hypothalamic estrogen receptor alpha immunoreactivity.

Diabetic rats have characteristic reproductive deficits. Peripheral and central (intra-cerebro-ventricular [ICV]) insulin restores the reproductive phenotype to control levels. In this experiment, we evaluated a possible defect in steroid feedback by evaluating hypothalamic estrogen receptor (ER) alpha availability using ERalpha immunocytochemistry. Animals were ovariectomised and given estradiol and progesterone. Diabetic and control animals were given ICV insulin or saline. Nuclear and/or cytoplasmic ERalpha immunoreactivity was evaluated in the paraventricular nucleus (PVN) and the organum vasculosum laminae terminalis (OVLT). In the PVN, nuclear immunoreactivity was increased among diabetic, ICV insulin-treated animals. Diabetic saline-treated and nondiabetic animals had similar ERalpha immunoreactivity. The OVLT had lower numbers of immunoreactive neurons compared to the PVN; no differences among the treatment groups were found in the OVLT. Central insulin treatment increased the number of PVN nuclear ERalpha immunoreactive neurons among diabetic animals. However, there was no reduction in ERalpha when comparing saline-treated diabetic animals to non-diabetic rats, suggesting that decreases in hypothalamic ERalpha in the regions studied do not account for diabetes-induced reproductive deficits.

Improved sample treatment for the determination of fructooligosaccharides in milk related products by liquid chromatography with electrochemical and refractive index detection.

A simple and reliable method for the determination of the fructooligosaccharides (FOS) kestose (GF2), nystose (GF3), fructofuranosylnystose (GF4), in the presence of fructose, glucose and lactose in dairy products is proposed. The most relevant advantages of the proposed method are the simultaneous determination of the most common FOS in enriched products and a reduction of the time required for sample treatment since the method consists merely in addition of a precipitation solution for the removal of lipids and proteins. Furthermore, the method saves a substantial amount of reagents compared with other methods and sample manipulation is reduced. Two chromatographic separations are proposed. The first one is carried out on an amino phase column for liquid chromatography with refractive index detection (HPLC-RI) (concentration of analytes higher than 0.1 mg mL(-1)) and the second one on an anion-exchange Carbopac PA-1 column for high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) (concentration of FOS lower than 0.1 mg mL(-1)). The method was validated by recovery assays with spiked samples using matrix-matched calibration. The limits of quantification of the method ranged from 1.2 to 2.0 µg mL(-1) for HPAEC-PAD and from 140 to 200 µg mL(-1) for HPLC-RI, while inter- and intra-day variability was under 3.5% in all cases. The proposed method was applied to the determination of compounds in supplemented milk, infant formulas and milk related juices with good recoveries in all cases.

Somatosensory stimuli evoke norepinephrine release in the anterior ventromedial hypothalamus of sexually receptive female rats.

We used in vivo brain microdialysis to determine the role of specific copulatory stimuli in mating-induced release of norepinephrine in the lateral ventromedial hypothalamus (VMH) of hormone-treated, sexually receptive female rats. Ovariectomized rats implanted with a unilateral guide cannula aimed at the ventrolateral VMH received systemic injections of estradiol benzoate daily for 2 days before and progesterone 4 h before the initiation of a 1-h behavioural test. Dialysis probes were lowered immediately after progesterone administration, and 20-min dialysis samples were collected until 1 h after the termination of behavioural testing. Norepinephrine content of dialysates was quantified by high performance liquid chromatography with electrochemical detection. During mating tests with male rats, dialysate levels of norepinephrine increased significantly over baseline in sexually receptive females with probe placements in the anterior but not posterior VMH. Norepinephrine levels were unchanged if rats were nonreceptive, even if males mounted vigorously and probes were located in the anterior VMH. Hormone-treated females that were placed on male-soiled bedding for 1 h showed no changes in dialysate levels of norepinephrine. Similarly, females in which vaginocervical stimulation was prevented by a vaginal mask failed to show increased levels of norepinephrine in dialysates collected from the anterior VMH, even if they displayed high levels of lordosis behaviour. Thus, the release of norepinephrine is not a result of executing the lordosis posture. The findings suggest that mating-induced increases in norepinephrine release in hormone-treated, sexually receptive rats are confined to the anterior VMH and that somatosensory rather than chemosensory stimuli evoke norepinephrine release. Moreover, experiments with vaginal masks indicate that vaginocervical stimulation is necessary for mating-evoked norepinephrine release in the anterior VMH.

Cyclic GMP may potentiate lordosis behaviour by progesterone receptor activation.

The purpose of this study was to test the hypothesis that cGMP acts as a progesterone substitute to facilitate lordosis in oestrogen-primed rats. Female Sprague-Dawley rats underwent stereotaxic surgery to place a 26-gauge guide cannula into the third ventricle. Bilateral ovariectomy was done at the same time as stereotaxic surgery. Five days later ovariectomized rats were primed with 2 microg estradiol benzoate 24 and 48 h prior to behaviour testing. Some animals were further injected with 200 microg progesterone 4 h before behaviour testing. A nitric oxide synthase inhibitor infused into the third ventricle before progesterone administration significantly reduced lordosis performance. 8-Bromo-cGMP, a cell permeable cGMP analogue, or saline vehicle was infused into the third ventricle of hormone-primed animals approximately 4 h prior to the first of 3-h behaviour tests. This cGMP analogue facilitated lordosis behaviour. We next used KT5823, a highly specific inhibitor of protein kinase G (PKG), to test the hypothesis that cGMP action is mediated by this kinase. In this experiment, KT5823 was infused 15 min before progesterone. KT5823 significantly decreased lordosis behaviour. RU486, a progesterone receptor antagonist, was used to assess whether the stimulatory effects of cGMP are mediated through the progesterone receptor. Oestrogen-primed animals were injected with 5 mg of RU486 or vehicle 60 min before infusion with 8-bromo-cGMP. RU486 significantly attenuated cGMP-facilitated lordosis behaviour. These data show that cGMP facilitates lordosis through activation of PKG and the progesterone receptor.