Genomic and Physiological Traits of the Marine Bacterium Alcaligenes aquatilis QD168 Isolated From Quintero Bay, Central Chile, Reveal a Robust Adaptive Response to Environmental Stressors

Alcaligenes aquatilis QD168 is a marine, aromatic hydrocarbon-degrading bacterium, isolated from an oil-polluted sediment of Quintero Bay, an industrial-coastal zone that has been chronically impacted by diverse pollutants. The aims of this study were to characterize the phylogenomic positions of Alcaligenes spp. and to characterize the genetic determinants and the physiological response of A. aquatilis QD168 to model environmental stressors (benzene, oxidizing agents, and salt). Phylogenomic analyses, using 35 housekeeping genes, clustered A. aquatilis QD168 with four other strains of Alcaligenes spp. (A. aquatilis BU33N, A. faecalis JQ135, A. faecalis UBA3227, and A. faecalis UBA7629). Genomic sequence analyses of A. aquatilis QD168 with 25 Alcaligenes spp., using ANIb, indicated that A. aquatilis BU33N is the closest related strain, with 96.8% ANIb similarity. Strain QD168 harbors 95 genes encoding proteins of seven central catabolic pathways, as well as sixteen peripheral catabolic pathways/reactions for aromatic compounds. A. aquatilis QD168 was able to grow on 3-hydroxybenzoate, 4-hydroxybenzoate, benzoate, benzene, 3-hydroxycinnamate, cinnamate, anthranilate, benzamide, 4-aminobenzoate, nicotinate, toluene, biphenyl and tryptophan, as sole carbon or nitrogen source. Benzene degradation was further analyzed by growth, metabolite identification and gene expression analyses. Benzene strongly induced the expression of the genes encoding phenol hydroxylase (dmpP) and catechol 1,2-dioxygenase (catA). Additionally, 30 genes encoding transcriptional regulators, scavenging enzymes, oxidative damage repair systems and isozymes involved in oxidative stress response were identified. Oxidative stress response of strain QD168 to hydrogen peroxide and paraquat was characterized, demonstrating that A. aquatilis QD168 is notably more resistant to paraquat than to H2O2. Genetic determinants (47 genes) for osmoprotective responses were identified, correlating with observed high halotolerance by strain QD168. The physiological adaptation of A. aquatilis QD168 to environmental stressors such as pollutants, oxidative stress and salinity may be exploited for bioremediation of oil-polluted saline sites

Orobanche olbiensis (Coss.) Nyman, taxon minusvalorado del Mediterráneo occidental

Se indica, por primera vez para la flora ibérica, la presencia de Orobanche olbiensis, a partir de poblaciones localizadas en ecosistemas dunares costeros de la provincia de Alicante. Se trata de un taxon que ha pasado desapercibido casi desde su descripción, probablemente por su afinidad con O. mutelii, planta con la que ha sido confundida. Se aporta una descripción e iconografía detalladas del material alicantino, así como datos sobre su ecología. fitosociología y distribución. Se destacan las diferencias más significativas con O. mutelii en una clave de identificación.Orobanche olbiensis is reported for the first time in the Iberian flora, growing on coastal sand-dune ecosystems of Alicante province (southeastern Spain). This taxon was neglected by most of European authors. probably due to its affinity to O. mutelii, with which it has been usually misidentified. A detailed description and drawing of the Alicantine plants are presented, and data on their ecology, phytosociology and distribution are also reported. Main differences with O. mutelii are pointed out in an identification key

Acinetobacter portensis sp. nov. and Acinetobacter guerrae sp. nov., isolated from raw meat

The taxonomic status of six strains of Acinetobacter obtained from meat samples, collected from supermarkets in Porto, Portugal, was investigated using polyphasic analysis. Partial rpoB sequence similarities lower than 95 % to other Acinetobacter species with validly published names led to the hypothesis that these strains represented novel species. This was confirmed based on comparative multilocus sequence analysis, which included the gyrB, recA and 16S rRNA genes, revealing that these strains represented two coherent lineages that were distinct from each other and from all known species. The names Acinetobacter portensis sp. nov. (comprising four strains) and Acinetobacter guerrae sp. nov. (comprising two strains) are proposed for these novel species. The species status of these two groups was confirmed by low (below 95 %) whole-genome sequence average nucleotide identity values and low (below 70 %) digital DNA–DNA hybridization similarities between the whole-genome sequences of the proposed type strains of each novel species and the representatives of the known Acinetobacter species. Phylogenomic treeing from core genome analysis supported these results. The coherence of each new species lineage was supported by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry differentiation of the species at the protein level, by cellular fatty acid profiles, and by unique and differential combinations of metabolic and physiological properties shared by each novel species. The type strain of A. portensis sp. nov. is AC 877T (=CCUG 68672T=CCM 8789T) and the type strain of A. guerrae sp. nov. is AC 1271T (=CCUG 68674T=CCM 8791T).info:eu-repo/publishedVersio

The use of PBPK/PD to establish clinically relevant dissolution specifications for zolpidem immediate release tablets

Background: Zolpidem is a non-benzodiazepine hypnotic agent which has been shown to be effective in inducing and maintaining sleep in adults and is one of the most frequently prescribed hypnotics in the world. For drugs that are used to treat sleeping disorders, the time to reach the maximum concentration (Tmax) of the drug in plasma is important to achieving a fast onset of action and this must be maintained when switching from one product to another. Objectives: The main objective of the present work was to create a PBPK/PD model for zolpidem and establish a clinically relevant “safe space” for dissolution of zolpidem from the commercial immediate release (IR) formulation. A second objective was to analyze literature pharmacokinetic data to verify the negative food effect ascribed to zolpidem and consider its ramifications in terms of the “safe space” for dissolution. Methods: Using dissolution, pharmacokinetic and pharmacodynamic data, an integrated PBPK/PD model for immediate release zolpidem tablets was constructed in Simcyp®. This model was used to identify the clinically relevant dissolution specifications necessary to ensure efficacy. Results: According to the simulations, as long as 85% of the drug is released in 45 minutes or less, the impact on the PK and PD profiles of zolpidem would be minimal. According to the FDA, the drug has to dissolve from the test and reference products at a similar rate and to an extent of 85% in not more than 30 minutes to pass bioequivalence via the BCS-biowaiver test. Thus, the BCS-biowaiver specifications are somewhat more stringent than the “safe space” based on the PBPK/PD model. Published data from fasted and fed state pharmacokinetic studies suggest but do not prove a negative food effect of zolpidem. Conclusions: A PBPK/PD model indicates that current BCS biowaiver criteria are more restrictive for immediate release zolpidem tablets than they need to be. In view of the close relationship between PK and PD, it remains advisable to avoid taking zolpidem tablets with or immediately after a meal, as indicated by the Stilnox® labeling

The SITLESS project: Exercise referral schemes enhanced by self-management strategies to battle sedentary behaviour in older adults: Study protocol for a randomised controlled trial

Abstract Background Older adults are the fastest growing segment of the world‘s population. Recent evidence indicates that excessive sitting time is harmful to health, independent of meeting the recommended moderate to vigorous physical activity (PA) guidelines. The SITLESS project aims to determine whether exercise referral schemes (ERS) can be enhanced by self-management strategies (SMSs) to reduce sedentary behaviour (SB), increase PA and improve health, quality of life and function in the long term, as well as psychosocial outcomes in community-dwelling older European citizens from four countries, within a three-armed pragmatic randomised controlled trial, compared with ERS alone and also with general recommendations about PA. Methods A total of 1338 older adults will be included in this study, recruited from four European countries through different existing primary prevention pathways. Participants will be randomly allocated into an ERS of 16 weeks (32 sessions, 45–60 min per session), ERS enhanced by seven sessions of SMSs and four telephone prompts, or a control group. Outcomes will be assessed at baseline, month 4 (end of ERS intervention), month 16 (12 months post intervention) and month 22 (18 months post intervention). Primary outcomes will include measures of SB (time spent sedentary) and PA (counts per minute). Secondary outcomes will include muscle and physical function, health economics’ related outcomes, anthropometry, quality of life, social networks, anxiety and depressive symptoms, disability, fear of falling, executive function and fatigue. A process evaluation will be conducted throughout the trial. The full analysis set will follow an intention-to-treat principle and will include all randomised participants for whom a baseline assessment is conducted. The study hypothesis will be tested with mixed linear models with repeated measures, to assess changes in the main outcomes (SB and PA) over time (baseline to month 22) and between study arms. Discussion The findings of this study may help inform the design and implementation of more effective interventions to reduce SB and increase PA levels, and hence improve long-term health outcomes in the older adult population. SITLESS aims to support policy-makers in deciding how or whether ERS should be further implemented or restructured in order to increase its adherence, impact and cost-effectiveness. Trial registration ClinicalTrials.gov, NCT02629666 . Registered 19 November 2015

Orobanche olbiensis (Coss.) Nyman, taxon minusvalorado del Mediterráneo

Orobanche olbiensis is reported for the first time in the Iberian flora. growing on coastal sand-dune ecosystems of Alicante province (southeastern Spain). This taxon was neglected by most of European authors. probably due to its affinity to O.mutelii, with which it has been usually misidentified. A detailed description and drawing of the Alicantine plants are presented, and data on their ecology, phytosociology and distribution are also reported. Main differencess with O. mutelii are pointed out in an identification key.Se indica, por primera vez para la flora ibérica. la presencia de Orobanche olbiensis, a partir de poblaciones localizadas en ecosistemas dunares costeros de la provincia de Alicante. Se trata de un taxon que ha pasado desapercibido casi desde su descripción, probablemente por su afinidad con O. mutelii, planta con la que ha sido confundida. Se aporta una descripción e iconografía detalladas del material alicantino, así como datos sobre su ecología. fitosociología y distribución. Se destacan las diferencias más significativas con O.mutelii en una clave de identificación

Comparative genomics of Stutzerimonas balearica (Pseudomonas balearica): diversity, habitats, and biodegradation of aromatic compounds

Stutzerimonas balearica (Pseudomonas balearica) has been found principally in oil-polluted environments. The capability of S. balearica to thrive from the degradation of pollutant compounds makes it a species of interest for potential bioremediation applications. However, little has been reported about the diversity of S. balearica. In this study, genome sequences of S. balearica strains from different origins were analyzed, revealing that it is a diverse species with an open pan-genome that will continue revealing new genes and functionalities as the genomes of more strains are sequenced. The nucleotide signatures and intra- and inter-species variation of the 16S rRNA genes of S. balearica were reevaluated. A strategy of screening 16S rRNA gene sequences in public databases enabled the detection of 158 additional strains, of which only 23% were described as S. balearica. The species was detected from a wide range of environments, although mostly from aquatic and polluted environments, predominantly related to petroleum oil. Genomic and phenotypic analyses confirmed that S. balearica possesses varied inherent capabilities for aromatic compounds degradation. This study increases the knowledge of the biology and diversity of S. balearica and will serve as a basis for future work with the species

Expression of Aurora kinases in adrenocortical tumors

Background: Both secreting and non-secreting adrenocortical tumors (ACT) are frequently found and are mostly benign, but among them, adrenocortical carcinomas (ACC), although rare, show poor prognosis and metastatic potential. Aurora kinase (AK) family members are serine/threonine kinase involved in the regulation of mitosis. Aim: To investigate the expression of Aurora kinase A, B, C (AKA, AKB, AKC) in adrenocortical tumors and to evaluate the pan-Aurora kinase inhibitor, MK-0457, in adrenocortical cell lines. Materials and methods: 12 ACT were analyzed: 4 ACC, 3 aldosterone producing adenoma (APA), 3 cortisol producing adenomas (CPA) and 2 non-secreting adenomas (NSA). Also 3 normal adrenal tissues and SW13 and H295R cells were studied. All the samples were evaluated by quantitative RT-PCR for AURKA, AURKB, AURKC. MTT test and 3H thymidine assay were performed in SW13 and H295R cells after treatment with MK-0457. Results: All tissues and cell lines expressed AKA, AKB and AKC. ACC samples overexpressed AKA and AKB, while among ACT only CPA showed increased AKA. MK-0457 inhibited SW13 cell viability at 72h with IC50 of 85nM. Furthermore we observed a significant time-dependent reduction in cell proliferation for SW13 cells at 24 and 72h. No appreciable change was perceived in H295R cells. Conclusions: our preliminary results demonstrated AKA, AKB and AKC expression in ACT. AKA overexpression in ACC may suggest the potential anti-mitotic effect of AK inhibitor in adrenocortical cells. Nevertheless MK-0457 seems to act only in SW13 cells. Further analysis are needed to substantiate these data