Preliminary effects of pagoclone, a partial GABAA agonist, on neuropsychological performance

Pagoclone is a novel cyclopyrrolone that acts as a partial GABAA receptor agonist. Preclinical studies suggest that pagoclone may have clinical utility as an anxiolytic agent, as well as a reduced incidence of side-effects. The present study was conducted to determine whether pagoclone would affect healthy individuals’ performances on neuropsychological measures as a function of dose within the projected therapeutic range. Twelve healthy adult subjects were randomly assigned to dosage groups in a 3-way crossover study. Participants were administered neuropsychological measures six hours following dosing on Day 1 and Day 6 of administration of the drug. Dose effects were noted on measures of alertness, learning, and memory and movement time. Significant effects were also noted on measures of alertness, learning and memory, information processing and psychomotor speed. Overall, the results of this small, preliminary study do not support a finding of behavioral toxicity for these doses of pagoclone. Rather, a pattern was found of transient and mild negative effects on learning and memory scores at the highest dose administered, though these changes were small and no longer evident by the sixth day of use

Do longer sequences improve the accuracy of identification of forensically important Calliphoridae species?

Species identification is a crucial step in forensic entomology. In several cases the calculation of the larval age allows the estimation of the minimum Post-Mortem Interval (mPMI). A correct identification of the species is the first step for a correct mPMI estimation. To overcome the difficulties due to the morphological identification especially of the immature stages, a molecular approach can be applied. However, difficulties in separation of closely related species are still an unsolved problem. Sequences of 4 different genes (COI, ND5, EF-1\u3b1, PER) of 13 different fly species collected during forensic experiments (Calliphora vicina, Calliphora vomitoria, Lucilia sericata, Lucilia illustris, Lucilia caesar, Chrysomya albiceps, Phormia regina, Cynomya mortuorum, Sarcophaga sp., Hydrotaea sp., Fannia scalaris, Piophila sp., Megaselia scalaris) were evaluated for their capability to identify correctly the species. Three concatenated sequences were obtained combining the four genes in order to verify if longer sequences increase the probability of a correct identification. The obtained results showed that this rule does not work for the species L. caesar and L. illustris. Future works on other DNA regions are suggested to solve this taxonomic issue

Specific LTR-Retrotransposons Show Copy Number Variations between Wild and Cultivated Sunflowers

The relationship between variation of the repetitive component of the genome and domestication in plant species is not fully understood. In previous work, variations in the abundance and proximity to genes of long terminal repeats (LTR)-retrotransposons of sunflower (Helianthus annuus L.) were investigated by Illumina DNA sequencingtocompare cultivars and wild accessions. In this study, we annotated and characterized 22 specific retrotransposon families whose abundance varies between domesticated and wild genotypes. These families mostly belonged to the Chromovirus lineage of the Gypsy superfamily and were distributed overall chromosomes. They were also analyzed in respect to their proximity to genes. Genes close to retrotransposon were classified according to biochemical pathways, and differences between domesticated and wild genotypes are shown. These data suggest that structural variations related to retrotransposons might have occurred to produce phenotypic variation between wild and domesticated genotypes, possibly by affecting the expression of genes that lie close to inserted or deleted retrotransposons and belong to specific biochemical pathways as those involved in plant stress responses

Genome-wide analysis of LTR retrotransposon diversity and its impact on the evolution of the genus Helianthus (L.)

Background: Genome divergence by mobile elements activity and recombination is a continuous process that plays a key role in the evolution of species. Nevertheless, knowledge on retrotransposon-related variability among species belonging to the same genus is still limited. Considering the importance of the genus Helianthus, a model system for studying the ecological genetics of speciation and adaptation, we performed a comparative analysis of the repetitive genome fraction across ten species and one subspecies of sunflower, focusing on long terminal repeat retrotransposons at superfamily, lineage and sublineage levels. Results: After determining the relative genome size of each species, genomic DNA was isolated and subjected to Illumina sequencing. Then, different assembling and clustering approaches allowed exploring the repetitive component of all genomes. On average, repetitive DNA in Helianthus species represented more than 75% of the genome, being composed mostly by long terminal repeat retrotransposons. Also, the prevalence of Gypsy over Copia superfamily was observed and, among lineages, Chromovirus was by far the most represented. Although nearly all the same sublineages are present in all species, we found considerable variability in the abundance of diverse retrotransposon lineages and sublineages, especially between annual and perennial species. Conclusions: This large variability should indicate that different events of amplification or loss related to these elements occurred following species separation and should have been involved in species differentiation. Our data allowed us inferring on the extent of interspecific repetitive DNA variation related to LTR-RE abundance, investigating the relationship between changes of LTR-RE abundance and the evolution of the genus, and determining the degree of coevolution of different LTR-RE lineages or sublineages between and within species. Moreover, the data suggested that LTR-RE abundance in a species was affected by the annual or perennial habit of that species

Comparative genome-wide analysis of repetitive DNA in the genus Populus L.

Genome skimming was performed, using Illumina sequence reads, in order to obtain a detailed comparative picture of the repetitive component of the genome of Populus species. Read sets of seven Populus and two Salix species (as outgroups) were subjected to clustering using RepeatExplorer (Novák et al. BMC Bioinformatics 11:378 2010). The repetitive portion of the genome ranged from 33.8 in Populus nigra to 46.5% in Populus tremuloides. The large majority of repetitive sequences were long terminal repeat-retrotransposons. Gypsy elements were over-represented compared to Copia ones, with a mean ratio Gypsy to Copia of 6.7:1. Satellite DNAs showed a mean genome proportion of 2.2%. DNA transposons and ribosomal DNA showed genome proportions of 1.8 and 1.9%, respectively. The other repeat types accounted for less of 1% each. Long terminal repeat-retrotransposons were further characterized, identifying the lineage to which they belong and studying the proliferation times of each lineage in the different species. The most abundant lineage was Athila, which showed large differences among species. Concerning Copia lineages, similar transpositional profiles were observed among all the analysed species; by contrast, differences in transpositional peaks of Gypsy lineages were found. The genome proportions of repeats were compared in the seven species, and a phylogenetic tree was built, showing species separation according to the botanical section to which the species belongs, although significant differences could be found within sections, possibly related to the different geographical origin of the species. Overall, the data indicate that the repetitive component of the genome in the poplar genus is still rapidly evolving

Variations of neck structures after supracricoid partial laryngectomy: a multislice computed tomography evaluation

Background: Surgery of laryngeal cancer used to profoundly alter the anatomy of the cervical region. Accurate anatomo-embryologic studies and repeated surgical trials allowed recognition of the cricoarytenoid complex as the smallest anatomofunctional unit able to maintain all the laryngeal functions. Objectives: The aim of this study was to determine whether significant variations of neck anatomical parameters exist after partial laryngectomy, and to analyze whether some of these parameters are associated with a positive functional outcome. Methods: Out of 48 patients treated with a surgical technique according to Mayer-Piquet (cricohyoidoepiglottopexy, CHEP) over a 6-year period, 18 patients were enrolled in the study. Patients were all males with a mean age of 60 years. Cervical structures and their relationships were measured by computed tomography, and the measurements before and after surgery were compared. Results: Our data showed that hyoid bone is modified, both in morphology and position during CHEP. More specifically the relation of the hyoid bone to other neck structures ( identified by the alpha-angle) is modified. The neolarynx and trachea undergo a caudocranial shift. All diameters of the cricoid cartilage remain unchanged after surgery. The position of the epiglottis after CHEP, in particular its relation with the arytenoid cartilage, is closely related to swallowing function outcome and recovery time. Conclusions: Our study showed that these structures, and more specifically the relations among them, undergo significant variations after CHEP. Our results identify some parameters, i.e. the alpha-angle, width of the hyoid bone and position of the epiglottis, that may predispose to a positive functional outcome after surgery

Recent advances in smart biotechnology: Hydrogels and nanocarriers for tailored bioactive molecules depot

Over the past ten years, the global biopharmaceutical market has remarkably grown, with ten over the top twenty worldwide high performance medical treatment sales being biologics. Thus, biotech R&D (research and development) sector is becoming a key leading branch, with expanding revenues. Biotechnology offers considerable advantages compared to traditional therapeutic approaches, such as reducing side effects, specific treatments, higher patient compliance and therefore more effective treatments leading to lower healthcare costs. Within this sector, smart nanotechnology and colloidal self-assembling systems represent pivotal tools able to modulate the delivery of therapeutics. A comprehensive understanding of the processes involved in the self assembly of the colloidal structures discussed therein is essential for the development of relevant biomedical applications. In this review we report the most promising and best performing platforms for specific classes of bioactive molecules and related target, spanning from siRNAs, gene/plasmids, proteins/growth factors, small synthetic therapeutics and bioimaging probes.Istituto Italiano di Tecnologia (IIT)COST Action [CA 15107]People Program (Marie Curie Actions) of the European Union's Seventh Framework Program under REA [606713 BIBAFOODS]Portuguese Foundation for Science and Technology (FCT) [PTDC/AGR-TEC/4814/2014, IF/01005/2014]Fundacao para a Ciencia e Tecnologia [SFRH/BPD/99982/2014]Danish National Research Foundation [DNRF 122]Villum Foundation [9301]Italian Ministry of Instruction, University and Research (MIUR), PRIN [20109PLMH2]"Fondazione Beneficentia Stiftung" VaduzFondo di Ateneo FRAFRAinfo:eu-repo/semantics/publishedVersio

The Sensitivity and Psychometric Properties of a Brief Computer-Based Cognitive Screening Battery in a Depression Clinic

At present, there is poor accuracy in assessing cognitive and vegetative symptoms in depression using clinician or self-rated measures, suggesting the need for development of standardized tasks to assess these functions. The current study assessed the psychometric properties and diagnostic specificity of a brief neuropsychological screening battery designed to assess core signs of depression; psychomotor retardation, attention and executive functioning difficulties, and impaired emotion perception within an outpatient psychiatry setting. Three hundred eighty-four patients with mood disorders and 77 healthy volunteers participated. A large percentage of patients met diagnostic criteria for Major Depressive Disorder alone (49%) or with another comorbid psychiatric disorder (24%). A brief, 25-min battery of computer-based tests was administered to control participants and patients measuring the constructs of inhibitory control, attention, visual perception, and both executive and visual processing speed. The patient groups performed significantly worse than the control group regardless of diagnosis on visual perception and attention accuracy and processing speed factors. Surprisingly, the anxiety disorder group performed better than several other psychiatric disorder groups in inhibitory control accuracy. Developing valid and reliable measures of cognitive signs in mood disorders creates excellent opportunities for tracking cognitive status prior to initiation of treatment, and allows for reliable retest following treatment