Structure and dynamics of the fullerene polymer Li4 C60 studied with neutron scattering

The two-dimensional polymer structure and lattice dynamics of the superionic conductor Li4 C60 are investigated by neutron diffraction and spectroscopy. The peculiar bonding architecture of this compound is definitely confirmed through the precise localisation of the carbon atoms involved in the intermolecular bonds. The spectral features of this phase are revealed through ab-initio lattice dynamics calculations and inelastic neutron scattering experiments. The neutron observables are found to be in very good agreement with the simulations which predict a partial charge transfer from the Li atoms to the C60 cage. The absence of a well defined band associated to one category of the Li atoms in the experimental spectrum suggests that this species is not ordered even at the lowest temperatures. The calculations predict an unstable Li sublattice at a temperature of 200 K, that we relate to the large ionic diffusivity of this system. This specificity is discussed in terms of coupling between the low frequency optic modes of the Li ions to the soft structure of the polymer.Comment: 29 pages, 13 Figure

Direct current stimulation modulates the excitability of the sensory and motor fibres in the human posterior tibial nerve, with a long-lasting effect on the H-reflex

Several studies demonstrated that transcutaneous direct current stimulation (DCS) may modulate central nervous system excitability. However, much less is known about how DC affects peripheral nerve fibres. We investigated the action of DCS on motor and sensory fibres of the human posterior tibial nerve, with supplementary analysis in acute experiments on rats. In forty human subjects, electric pulses at the popliteal fossa were used to elicit either M-waves or H-reflexes in the Soleus, before (15 min), during (10 min) and after (30 min) DCS. Cathodal or anodal current (2 mA) was applied to the same nerve. Cathodal DCS significantly increased the H-reflex amplitude; the post-polarization effect lasted up to ~ 25 min after the termination of DCS. Anodal DCS instead significantly decreased the reflex amplitude for up to ~ 5 min after DCS end. DCS effects on M-wave showed the same polarity dependence but with considerably shorter after-effects, which never exceeded 5 min. DCS changed the excitability of both motor and sensory fibres. These effects and especially the long-lasting modulation of the H-reflex suggest a possible rehabilitative application of DCS that could be applied either to compensate an altered peripheral excitability or to modulate the afferent transmission to spinal and supraspinal structures. In animal experiments, DCS was applied, under anaesthesia, to either the exposed peroneus nerve or its Dorsal Root, and its effects closely resembled those found in human subjects. They validate therefore the use of the animal models for future investigations on the DCS mechanisms

Identification of suitable internal control genes for expression studies in Coffea arabica under different experimental conditions

<p>Abstract</p> <p>Background</p> <p>Quantitative data from gene expression experiments are often normalized by transcription levels of reference or housekeeping genes. An inherent assumption for their use is that the expression of these genes is highly uniform in living organisms during various phases of development, in different cell types and under diverse environmental conditions. To date, the validation of reference genes in plants has received very little attention and suitable reference genes have not been defined for a great number of crop species including <it>Coffea arabica</it>. The aim of the research reported herein was to compare the relative expression of a set of potential reference genes across different types of tissue/organ samples of coffee. We also validated the expression profiles of the selected reference genes at various stages of development and under a specific biotic stress.</p> <p>Results</p> <p>The expression levels of five frequently used housekeeping genes (reference genes), namely <it>alcohol dehydrogenase </it>(<it>adh</it>), <it>14-3-3</it>, <it>polyubiquitin </it>(<it>poly</it>), <it>β-actin </it>(<it>actin</it>) and <it>glyceraldehyde-3-phosphate dehydrogenase </it>(<it>gapdh</it>) was assessed by quantitative real-time RT-PCR over a set of five tissue/organ samples (root, stem, leaf, flower, and fruits) of <it>Coffea arabica </it>plants. In addition to these commonly used internal controls, three other genes encoding a cysteine proteinase (<it>cys</it>), a caffeine synthase (<it>ccs</it>) and the 60S ribosomal protein L7 (<it>rpl7</it>) were also tested. Their stability and suitability as reference genes were validated by geNorm, NormFinder and BestKeeper programs. The obtained results revealed significantly variable expression levels of all reference genes analyzed, with the exception of <it>gapdh</it>, which showed no significant changes in expression among the investigated experimental conditions.</p> <p>Conclusion</p> <p>Our data suggests that the expression of housekeeping genes is not completely stable in coffee. Based on our results, <it>gapdh</it>, followed by <it>14-3-3 </it>and <it>rpl7 </it>were found to be homogeneously expressed and are therefore adequate for normalization purposes, showing equivalent transcript levels in different tissue/organ samples. <it>Gapdh </it>is therefore the recommended reference gene for measuring gene expression in <it>Coffea arabica</it>. Its use will enable more accurate and reliable normalization of tissue/organ-specific gene expression studies in this important cherry crop plant.</p

Biliary cystic disease and neoplasia: surgical management

Background Congenital cystic dilatation of the extra- and intrahepatic bile ducts is a rare condition with several potential complications, especially a high risk of malignant degeneration, which may develop from an anomalous arrangement of the pancreatico-biliary ductal junction. Patients Twenty-two patients with cystic dilatation of the biliary tree, subdivided according to the Todani classification, were observed and treated during a 17-year period. The intrahepatic ducts were involved in 15 patients. Results Surgical treatment involved either total excision of extrahepatic cysts, hepatic resection in cases of segmental intrahepatic disease or, in the presence of diffuse intrahepatic disease, a wide biliary-digestive anastomosis performed onto the biliary confluence, with the intent of reducing the risk of neoplastic degeneration. One patient with extensive and symptomatic liver involvement complicated by biliary cirrhosis has already undergone liver transplantation, and another two patients who are currently asymptomatic may require this procedure in future. Neoplastic degeneration was found in three patients (one each of Todani type I, type IVa and type V), or 14% of the series. The postoperative course was complicated by cholangitis in only two patients, who were treated successfully with antibiotics. Except for one patient with a type I cyst complicated by carcinoma, who died 14 months post-operatively, all patients are alive and well at a mean follow-up of eight years (range 8 months to 17 years). Discussion The ideal surgical procedures to cure the disease and prevent malignant degeneration are: (a) complete excision of the extrahepatic biliary cysts; (b) hepatic resection in cases of segmental intrahepatic involvement; (c) wide bilio-digestive anastomosis in cases of multiple intrahepatic involvement, or liver transplantation when this is complicated by secondary biliary cirrhosis

An exon-specific U1 small nuclear RNA (snRNA) strategy to correct splicing defects

A significant proportion of disease-causing mutations affect precursor-mRNA splicing, inducing skipping of the exon from the mature transcript. Using F9 exon 5, CFTR exon 12 and SMN2 exon 7 models, we characterized natural mutations associated to exon skipping in Haemophilia B, cystic fibrosis and spinal muscular atrophy (SMA), respectively, and the therapeutic splicing rescue by using U1 small nuclear RNA (snRNA). In minigene expression systems, loading of U1 snRNA by complementarity to the normal or mutated donor splice sites (5′ss) corrected the exon skipping caused by mutations at the polypyrimidine tract of the acceptor splice site, at the consensus 5′ss or at exonic regulatory elements. To improve specificity and reduce potential off-target effects, we developed U1 snRNA variants targeting non-conserved intronic sequences downstream of the 5′ss. For each gene system, we identified an exon-specific U1 snRNA (ExSpeU1) able to rescue splicing impaired by the different types of mutations. Through splicing-competent cDNA constructs, we demonstrated that the ExSpeU1-mediated splicing correction of several F9 mutations results in complete restoration of secreted functional factor IX levels. Furthermore, two ExSpeU1s for SMA improved SMN exon 7 splicing in the chromosomal context of normal cells. We propose ExSpeU1s as a novel therapeutic strategy to correct, in several human disorders, different types of splicing mutations associated with defective exon definition

Increasing the bandwidth of resonant gravitational antennas: The case of Explorer

Resonant gravitational wave detectors with an observation bandwidth of tens of hertz are a reality: the antenna Explorer, operated at CERN by the ROG collaboration, has been upgraded with a new read-out. In this new configuration, it exhibits an unprecedented useful bandwidth: in over 55 Hz about its frequency of operation of 919 Hz the spectral sensitivity is better than 10^{-20} /sqrt(Hz) . We describe the detector and its sensitivity and discuss the foreseable upgrades to even larger bandwidths.Comment: 4 pages- 4 figures Acceted for publication on Physical Review Letter