A child without kneecaps

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Effects of onabotulintoxinA on habituation of laser evoked responses in chronic migraine

Onabotulintoxin A (BontA) is an efficacious preventive treatment for chronic migraine, though the specific mechanism of action is still under discussion. The study aims: (1) To evaluate pain processing modifications in chronic migraine patients (CM) under single BontA administration in pericranial muscles, by means of CO2 Laser Evoked Potentials (LEPs) obtained by the stimulation of the skin over the right frontal and trapezius injection sites and hand dorsum, in a double blind placebo controlled crossover design. (2) To correlate main LEPs findings with clinical outcome after one year of BontA treatment. Twenty refractory CM patients were included in the analysis. The LEPs were recorded in basal conditions and seven days after BontA (PREEMPT protocol) and saline solution injection. The N1, N2 and P2 amplitude and latencies and N2P2 habituation index were evaluated and correlated with the percent change of headache frequency after one year of toxin treatment. After seven days of BontA treatment, a normalization of the trigeminal habituation index was observed, which was correlated with the clinical outcome after one year of BontA therapy. Patients displaying trigeminal LEPs facilitation at T0 time showed a more efficient therapeutic outcome. Neurotoxin may exert a modulating effect on trigeminal nociception, normalizing central neurotransmission

Interference of the Developing and Toxin Production of Clostridium botulinum by Lactobacillus paracasei subspecies paracasei

Infant botulism is an intestinal toxic-infection affecting infants younger than one year of age, and currently in some country is the most important form of human botulism by its frequency of occurrence. It is a rare neuroparalytic disease, but potentially fatal, especially if it is not early diagnosed and properly treated. It is caused by botulinum neurotoxins produced by species of Clostridium, principally C. botulinum. C. botulinum spores are widely distributed in nature, and its most common habitat and natural reservoir is the soil, the main source of contamination for the different forms of botulism. C. botulinum spores have been identified in some foods, such as honey, corn syrup, infant formula and in some medicinal plants. Considering the difficulty to prevent the swallowing of spores, is particularly relevant have adequate arrangements to interfere with colonization and/or toxin formation of C. botulinum in the intestine. Different probiotics have been demonstrated utility against several intestinal pathogens. So, we studied and demonstrated the interference of Lactobacillus paracasei subsp. paracasei on the growth and toxin formation of one strain of C. botulinum type A. Therefore, administering probiotics to infants, perhaps from birth, would be effective in preventing or treating the disease.Fil: Fernandez, Rafael Alfredo. Universidad Nacional de Cuyo; Argentina;Fil: Carbone, María Laura.Fil: Sánchez, María Laura. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución. Laboratorio de Limnología; Argentina;Fil: Pareja, Virtudes.Fil: de Jong, Laura Irene Teresita.Fil: Bianco, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología

Population structure and diversity of an invasive pine needle pathogen reflects anthropogenic activity

Dothistroma septosporum is a haploid fungal pathogen that causes a serious needle blight disease of pines, particularly as an invasive alien species on Pinus radiata in the Southern Hemisphere. During the course of the last two decades, the pathogen has also incited unexpected epidemics on native and non-native pine hosts in the Northern Hemisphere. Although the biology and ecology of the pathogen has been well documented, there is a distinct lack of knowledge regarding its movement or genetic diversity in many of the countries where it is found. In this study we determined the global population diversity and structure of 458 isolates of D. septosporum from 14 countries on six continents using microsatellite markers. Populations of the pathogen in the Northern Hemisphere, where pines are native, displayed high genetic diversities and included both mating types. Most of the populations from Europe showed evidence for random mating, little population differentiation and gene flow between countries. Populations in North America (USA) and Asia (Bhutan) were genetically distinct but migration between these continents and Europe was evident. In the Southern Hemisphere, the population structure and diversity of D. septosporum reflected the anthropogenic history of the introduction and establishment of plantation forestry, particularly with Pinus radiata. Three introductory lineages in the Southern Hemisphere were observed. Countries in Africa, that have had the longest history of pine introductions, displayed the greatest diversity in the pathogen population, indicating multiple introductions. More recent introductions have occurred separately in South America and Australasia where the pathogen population is currently reproducing clonally due to the presence of only one mating type.The Department of Science and Technology (DST)/National Research Foundation (NRF), the Tree Protection Co-operative Programme (TPCP), the Claude Leon Foundation and the THRIP initiative of the Department of Trade and Industry, South Africa.http://onlinelibrary.wiley.comjournal/10.1002/(ISSN)2045-7758am201

Reduced lysosomal acid lipase activity in blood and platelets is associated with nonalcoholic fatty liver disease

OBJECTIVES: To investigate whether blood total lysosomal acid lipase activity (BT-LAL) levels are uniquely associated with the noncirrhotic and cirrhotic stages of nonalcoholic fatty liver disease (NAFLD) and with protection from NAFLD in metabolically/genetically predisposed subjects and a normal liver. To clarify which enzyme-carrying circulating cells are involved in reduced BT-LAL of NAFLD.METHODS: In a cross-sectional study, BT-LAL was measured by a fluorigenic method in patients with NAFLD (n = 118), alcoholic (n = 116), and hepatitis C virus-related disease (n = 49), in 103 controls with normal liver and in 58 liver transplant recipients. Intracellular platelet and leukocyte LAL was measured in 14 controls and 28 patients with NAFLD.RESULTS: Compared with controls, (i) BT-LAL and LAL in platelets, but not in leukocytes, were progressively reduced in noncirrhotic NAFLD and in nonalcoholic steatohepatitis-related cirrhosis; (ii) platelet and leukocyte counts did not differ in patients with noncirrhotic NAFLD; and (iii) BT-LAL did not differ in alcoholic and hepatitis C virus noncirrhotic patients. BT-LAL progressively increased in controls with metabolic syndrome features according to their PNPLA3 rs738409 steatosis-associated variant status (II vs IM vs MM), and their BT-LAL was higher than that of noncirrhotic NAFLD, only when carriers of the PNPLA3 unfavorable alleles were considered. Liver transplant recipients with de novo NAFLD compared with those without de novo NAFLD had lower BT-LAL.DISCUSSION: LAL in blood and platelets is progressively and uniquely reduced in NAFLD according to disease severity. High BT-LAL is associated with protection from NAFLD occurrence in subjects with metabolic and genetic predisposition. Low LAL in platelets and blood could play a pathogenetic role in NAFLD

p140Cap Regulates GABAergic Synaptogenesis and Development of Hippocampal Inhibitory Circuits

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CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin

Limited therapeutic options are available for advanced colorectal cancer (CRC). Herein, we report that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads to an initial reduction of proliferative and clonogenic potential of CRC sphere cells (CR-CSphCs), followed by an adaptive response selecting the CR-CSphC-resistant compartment. Cells spared by the treatment with NORA234 express high levels of CD44v6, associated with a constitutive activation of Wnt pathway. In CR-CSphC-based organoids, NORA234 causes a genotoxic stress paralleled by G2-M cell cycle arrest and activation of CHK1, driving the DNA damage repair of CR-CSphCs, regardless of the mutational background, microsatellite stability, and consensus molecular subtype. Synergistic combination of NORA234 and CHK1 (rabusertib) targeting is synthetic lethal inducing death of both CD44v6-negative and CD44v6-positive CRC stem cell fractions, aside from Wnt pathway activity. These data could provide a rational basis to develop an effective strategy for the treatment of patients with CRC

Measurements of projectile fragments from 70 Zn (15 MeV/nucleon) + 64 Ni collisions with the MAGNEX spectrometer at INFN-LNS

The present work is focused on our efforts to produce and identify neutron-richrare isotopes from peripheral reactions below the Fermi energy. High-quality experimental data were obtained from a recent experiment with the MAGNEX spectrometer at INFN-LNS in Catania, Italy. The main goal of this effort is to describe the adopted identification techniques used to analyze the data from the reaction 70 Zn (15 MeV/nucleon) + 64 Ni. The particle identification procedure is based on a novel approach that involves the reconstruction of both the atomic number Z and the ionic charge q of the ions, followed by the identification of themass. Our method was successfully applied to identify neutron-rich ejectiles from multinucleon transfer in the above reaction 70 Zn + 64 Ni at 15 MeV/nucleon. The analysis of the data is ongoing. We expect to obtain the angular and momentum distributions of the fragments, along with their production cross sections. These data, along with comparisons with theoretical models are expected to contribute to a better understanding of the complex reaction mechanisms of multinucleon transfer that dominate this energy regime