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Morales, J.

Publications and source records attributed to Morales, J..

At least 19 recordsLinked to original sources

Imatinib Reduces Right Ventricular Systolic Pressure Independent of Arterial or Venous Remodeling in an Inflammatory Murine Model of Pulmonary Hypertension

Pulmonary arterial hypertension is a progressive, fatal disease driven by pathologic vascular remodeling including arterial medial hypertrophy, occlusive neointimal lesion formation, and venous muscularization. Current vasodilatory therapies improve hemodynamics but do not reverse established remodeling. Imatinib mesylate, a tyrosine kinase inhibitor targeting the PDGF-PDGFR signaling axis, has been proposed as an anti-remodeling therapy for pulmonary arterial hypertension and has demonstrated hemodynamic benefit in both preclinical models and clinical trials. However, prior preclinical models lack the neointimal lesions characteristic of human disease, effects on venous remodeling have not been examined, and direct histologic assessment in human trials is precluded by the invasiveness of serial lung biopsy. Here, leveraging the house dust mite mouse model of pulmonary hypertension, which recapitulates medial thickening, neointimal lesion formation, and venous muscularization, we rigorously evaluate the anti-remodeling and hemodynamic effects of imatinib during two defined remodeling stages: neointimal lesion growth and neointimal lesion maintenance. Imatinib treatment significantly reduced right ventricular systolic pressure at both stages. Despite this hemodynamic improvement, quantitative vessel-level analysis of over 1,700 arteries and 1,200 veins revealed no significant effect of imatinib on arterial medial thickness, neointimal lesion growth, neointimal lesion maintenance, or venous muscularization across any vessel size class. These findings dissociate imatinibs hemodynamic benefit from structural vascular remodeling and suggest that imatinib functions primarily as a pulmonary vasodilator rather than an anti-remodeling agent.

physiology↗

Carotenoid-based ornaments predict survival in male but not female birds: a meta-analysis

Many vertebrates exhibit colourful ornaments generated by carotenoid pigments that presumably evolve as signals under sexual selection. To function as sexual signals, carotenoid-based coloured ornaments should accurately reveal an individuals quality, commonly defined as fitness potential, which includes the ability to survive. We performed a meta-analysis for testing the association between the expression level of carotenoid-based ornaments and longevity estimates (annual survival or lifespan) in birds, the taxon with the largest body of evidence. We detected a significant positive correlation in males but not in females. This result contrasts with recent meta-analytic work showing a positive association between carotenoid-based coloured traits and avian fecundity in both sexes. The link to survival was consistent among colourations produced by enzymatically transformed pigments (mostly red ketocarotenoids) and those based on dietary yellow carotenoids. The latter suggests that the association with survival holds across the physiological mechanisms involved in the production of these ornaments. In summary, our study reveals sex-specific selection in the evolution of carotenoid-based ornaments.

evolutionary biology↗

"Remote and partial clocks expand the circadian neuronal network, driving widespread molecular rhythmicity in Drosophila"

Circadian clocks orchestrate daily physiology and behavioral rhythms, yet the extent to which cells lacking canonical clock components exhibit robust temporal regulation remains unclear. Here we addressed this question using a two-step strategy. First, we systematically mapped core clock gene expression at single-cell resolution across the Drosophila brain and body. Second, leveraging these data and performing targeted experiments, we uncovered cells that lack most or all canonical clock components yet display strong mRNA rhythms. We found that lamina wide-field neurons show high-amplitude tim mRNA cycling even in constant darkness conditions (DD) despite minimal expression of other clock genes, suggesting a partial or noncanonical oscillator. In addition, C2 and C3 optic lobe neurons, which do not express core clock components, exhibit hundreds of circadian and daily cycling transcripts. Notably, circadian rhythms in C3 neurons coincide with oscillations of activity-regulated genes (ARGs), whereas C2 neurons cycle independently of ARGs, indicating distinct non-cell-autonomous mechanisms. These findings reveal a spectrum of circadian regulation, from autonomous to remote, input-driven rhythms and expand the circadian landscape to include strategies for generating and distributing temporal information across neuronal and non-neuronal cell types.

neuroscience↗

Modification and validation of a reference real-time RT-PCR method for the detection of a new African horse sickness virus variant

African horse sickness (AHS) is a disease affecting equids caused by the AHS virus (AHSV). The World Organization for Animal Health (WOAH) includes AHS as a notifiable disease and, upon detection within the European Union, immediate control and eradication measures are mandated. Thus, validated diagnostic methods for rapid AHSV detection are essential. The Aguero 2008 and Guthrie 2013 rRT-PCR methods have been widely validated for detection of any AHSV strain and are included as reference rRT-PCRs in the WOAH manual. However, the WOAH reference laboratory for AHS in the Republic of South Africa (RSA), reported an AHSV variant undetected by the Aguero 2008 rRT-PCR. Therefore, a set of modified primers and probe, containing degenerate positions to avoid mismatches with the sequence of the new RSA strain, was developed. The modified-Aguero method was validated by the WOAH reference laboratories in Spain and the UK employing a broad collection of AHSV strains, clinical samples as well as a synthetic RNA mimicking the target sequence of the new RSA AHSV variant (AHSV-sRNA-RSA). Comparative assessment of the modified-Aguero versus the WOAH reference rRT-PCRs, showed that the modified method exhibited a good diagnostic performance and enabled the detection of the new RSA AHSV variant nucleic acid.

microbiology↗

Higher frequency of homologous chromosome pairing in human adult aortic endothelial cells

We previously demonstrated that homologous chromosomes are spatially segregated, or antipaired, in neonatal human endothelial cells at metaphase/anaphase, which may help prevent abnormal recombination. However, it is unclear if this antipairing persists in adult endothelial cells. To test whether the antipairing, or one homolog per nuclear hemisphere motif, is conserved in adult endothelial cells, we examined human aortic endothelial cells at metaphase. Using ImmunoFISH and high-resolution confocal microscopy to visualize the chromosomes and centrosomes, we found that small homologous chromosomes 13, 15, 17, 19, 21, 22, and the sex chromosomes, XY, exhibit a loss of spatial segregation in human adult aortic endothelial cells. In addition, fewer adult endothelial cells showed segregation for the larger chromosomes 1, 4, and XX, as compared to neonatal endothelial cells. Notably, we observed a higher frequency of abnormal pairing in both small and large chromosomes in adult aortic endothelial cells as compared to neonatal umbilical vein endothelial cells. These findings suggest that mechanisms governing chromosome antipairing may decline with aortic endothelial cell age. Summary StatementA higher frequency of homologous chromosome pairing is observed in human adult aortic endothelial cells as compared to neonatal umbilical vein endothelial cells.

cell biology↗

Hormone-regulated dynamics of mRNA distribution on ribosomes in Sertoli cells

The effects of hormone stimulation on the cell translational profile remain poorly understood. Here, using polysome profiling combined to RNA sequencing, we analyzed the translational response to follicle-stimulating hormone (FSH) of primary rat Sertoli cells, that exhibit an active anabolic activity regulated by reproductive hormones in the male gonad. We first established that mRNA distribution to polysomes follows a bimodal pattern, with 15% of mRNAs enriched in polysomes and exhibiting high expression. Critically, this basal polysomal enrichment had a major impact on FSH-induced mRNA recruitment to the polysomes, since FSH stimulation promoted the release of polysome-enriched mRNAs, while mRNAs that were the least associated to polysomes were preferentially recruited to polysomes upon stimulation. The FSH signal did not alter the core biological functions of Sertoli cells, but shifted the proteins involved in these functions, suggesting a molecular rewiring of the FSH-induced gene expression. These findings underscore how ribosomal reallocation dynamically adapts the cellular translatome to microenvironmental changes, enabling cells to fine-tune protein production in response to external stimuli. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/629416v1_ufig1.gif" ALT="Figure 1000"> View larger version (19K): org.highwire.dtl.DTLVardef@27334forg.highwire.dtl.DTLVardef@199c630org.highwire.dtl.DTLVardef@a28b92org.highwire.dtl.DTLVardef@1794172_HPS_FORMAT_FIGEXP M_FIG C_FIG Bullet points* In Sertoli cells, most mRNAs distribute similarly between monosomes and polysomes, but a sub-population is specifically enriched in polysomes * Basal polysomal enrichment level has a major impact on FSH-induced mRNA recruitment or release from the polysomes * The FSH signal induced a global rewiring of the proteins involved in Sertoli cell basal activity * FSH-induced reassignment of ribosomes to specific mRNAs has to comply with a tightly maintained mRNA distribution landscape

systems biology↗

The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity

The NHGRI-EBI GWAS Catalog serves as a vital resource for the genetic research community, providing access to the most comprehensive database of human GWAS results. Currently, it contains close to 7,000 publications for more than 15,000 traits, from which more than 625,000 lead associations have been curated. Additionally, 85,000 full genome-wide summary statistics datasets - containing association data for all variants in the analysis - are available for downstream analyses such as meta-analysis, fine-mapping, Mendelian randomisation or development of polygenic risk scores. As a centralised repository for GWAS results, the GWAS Catalog sets and implements standards for data submission and harmonisation, and encourages the use of consistent descriptors for traits, samples and methodologies. We share processes and vocabulary with the PGS Catalog, improving interoperability for a growing user group. Here, we describe the latest changes in data content, improvements in our user interface, and the implementation of the GWAS-SSF standard format for summary statistics. We address the challenges of handling the rapid increase in large-scale molecular quantitative trait GWAS and the need for sensitivity in the use of population and cohort descriptors while maintaining data interoperability and reusability.

genetics↗

Dynamics of influenza transmission in vampire bats revealed by longitudinal monitoring and a large-scale anthropogenic perturbation

Interrupting pathogen transmission between species is a priority strategy to mitigate zoonotic threats. However, avoiding counterproductive interventions requires knowing animal reservoirs of infection and the dynamics of transmission within them, neither of which are easily ascertained from the cross-sectional surveys which currently dominate investigations into newly discovered viruses. We used biobanked sera and metagenomic data to reconstruct the transmission of recently discovered bat-associated influenza virus (BIV) over 12 years in three zones of Peru. Mechanistic models fit under a Bayesian framework, which enabled joint inference from serological and molecular data, showed that common vampire bats maintain BIV independently of the currently assumed fruit bat reservoir through immune waning and seasonal transmission pulses. A large-scale vampire bat cull targeting rabies incidentally halved BIV transmission, confirming vampire bats as maintenance hosts. Our results show how combining field studies, perturbation responses and multi-data type models can elucidate pathogen dynamics in nature and reveal pathogen-dependent effects of interventions.

ecology↗

Metabolic immaturity of newborns and breast milk bile acids are the central determinants of heightened neonatal vulnerability to norovirus diarrhea

Noroviruses are the leading global cause of acute gastroenteritis, responsible for 685 million annual cases. While all age groups are susceptible to noroviruses, children are vulnerable to more severe infections than adults, underscored by 200 million pediatric cases and up to 200,000 deaths in children annually. Understanding the basis for the increased vulnerability of young hosts is critical to developing effective treatments. The pathogenic outcome of any enteric virus infection is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors. A central mediator in these complex relationships are host- and microbiota-derived metabolites. Noroviruses bind a specific class of metabolites, bile acids, which are produced by the host and then modified by commensal bacterial enzymes. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Considering these opposing effects, the microbiota-regulated balance of the bile acid pool may be a key determinant of the pathogenic outcome of a norovirus infection. The bile acid pool in newborns is unique due to immaturity of host metabolic pathways and developing gut microbiota, which could underlie the vulnerability of these hosts to severe norovirus infections. Supporting this concept, we demonstrate herein that microbiota and their bile acid metabolites protect from severe norovirus diarrhea whereas host-derived bile acids promote disease. Remarkably, we also report that maternal bile acid metabolism determines neonatal susceptibility to norovirus diarrhea during breastfeeding by delivering proviral bile acids to the newborn. Finally, directed targeting of maternal and neonatal bile acid metabolism can protect the neonatal host from norovirus disease. Altogether, these data support the conclusion that metabolic immaturity in newborns and ingestion of proviral maternal metabolites in breast milk are the central determinants of heightened neonatal vulnerability to norovirus disease.

microbiology↗

The essential chaperone DNAJC17 activates HSP70 to coordinate RNA splicing and G2-M progression.

Molecular chaperones including the heat-shock protein 70-kilodalton (HSP70) family and the J-domain containing protein (JDP) co-chaperones maintain homeostatic balance in eukaryotic cells through regulation of the proteome. The expansive JDP family helps direct specific HSP70 functions, and yet loss of single JDP-encoding genes is widely tolerated by mammalian cells, suggesting a high degree of redundancy. By contrast, essential JDPs might carry out HSP70-independent functions or fill cell-context dependent, highly specialized roles within the proteostasis network. Using a genetic screen of JDPs in human cancer cell lines, we found the RNA recognition motif (RRM) containing DNAJC17 to be pan-essential and investigated the contribution of its structural domains to biochemical and cellular function. We found that the RRM exerts an auto-inhibitory effect on the ability of DNAJC17 to allosterically activate ATP hydrolysis by HSP70. The J-domain, but neither the RRM nor a distal C-terminal alpha helix are required to rescue cell viability after loss of endogenous DNAJC17. Knockdown of DNAJC17 leads to relatively few conserved changes in the abundance of individual mRNAs, but instead deranges gene expression through exon skipping, primarily of genes involved in cell cycle progression. Concordant with cell viability experiments, the C-terminal portions of DNAJC17 are dispensable for restoring splicing and G2-M progression. Overall, our findings identify essential cellular JDPs and suggest that diversification in JDP structure extends the HSP70-JDP system to control divergent processes such as RNA splicing. Future investigations into the structural basis for auto-inhibition of the DNAJC17 J-domain and the molecular regulation of splicing by these components may provide insights on how conserved biochemical mechanisms can be programmed to fill unique, non-redundant cellular roles and broaden the scope of the proteostasis network.

cell biology↗

Role of transcription and translation during the early development of the brown alga Ectocarpus

Background and aimsParthenogenesis, the embryonal development of an unfused gamete, is a widespread trait within the brown algae (Phaeophyceae). We hypothesized that the parthenogenetic development of male gametes of the model brown alga Ectocarpus species 7 would rapidly be dependent on de novo transcription and translation because of the small size of the gamete cell. MethodsWe followed the development of male Ectocarpus gametes to parthenosporophytes in the presence of either the transcription inhibitor thiolutin or the translation inhibitor emetine. Responses in morphology and growth were compared to development in inhibitor-free control conditions at three time points over 12 days. Potentially persistent inhibitor effects were then investigated by growing parthenosporophytes in an inhibitor-free post-culture for 14 days. Key resultsThiolutin did not affect gamete germination, but growth of parthenosporophytes was significantly delayed. While almost all control parthenosporophytes had grown larger than 10 cells over 12 days, thiolutin inhibited growth beyond a size of 5-10 cells. The effects of thiolutin were reversible in the post-culture. Consequences of the emetine treatment were more severe, germination was already strongly inhibited by day 5, and on average only 27.5% of emetine-treated gametes had completed the first cell division on day 12. Emetine fully inhibited development beyond the 5-cell stage during the treatment, and induced morphological abnormalities (i.e., round cell shape and abnormal cell division planes) which persisted throughout the post-culture. ConclusionsThese results imply that Ectocarpus gametes contain sufficient proteins to germinate, and that the first cell cycles of parthenogenetic gamete development presumably utilize mRNA already present in the gametes. We discuss that storing mRNA and proteins in the developing gametes before release may be an adaptive trait in Ectocarpus to ensure quick development after fertilization, or alternatively the vegetative completion of the life cycle in the absence of mates.

developmental biology↗

Microfabrication-based engineering of biomimetic dentin-like constructs to simulate dental aging

1.Human dentin is a highly organized dental tissue displaying a complex microarchitecture consisting of micrometer-sized tubules encased in a mineralized type-I collagen matrix. As such, it serves as an important substrate for the adhesion of microbial colonizers and oral biofilm formation in the context of dental caries disease, including root caries in the elderly. Despite this issue, there remains a current lack of effective biomimetic in-vitro dentin models that facilitate the study of oral microbial adhesion by considering the surface architecture at the micro- and nanoscales. Therefore, the aim of this study was to develop a novel in-vitro microfabricated biomimetic dentin surface that simulates the complex surface microarchitecture of exposed dentin. For this, a combination of soft lithography microfabrication and biomaterial science approaches were employed to construct a micropitted PDMS substrate functionalized with mineralized type-I collagen. These dentin analogues were subsequently glycated with methylglyoxal (MGO) to simulate dentin matrix aging in-vitro and analyzed utilizing an interdisciplinary array of techniques including atomic force microscopy (AFM), elemental analysis, and electron microscopy. AFM force-mapping demonstrated that the nanomechanical properties of the biomimetic constructs were within the expected biological parameters, and that mineralization was mostly predominated by hydroxyapatite deposition. Finally, dual-species biofilms of Streptococcus mutans and Candida albicans were grown and characterized on the biofunctionalized PDMS microchips, demonstrating biofilm specific morphologic characteristics and confirming the suitability of this model for the study of early biofilm formation under controlled conditions. Overall, we expect that this novel biomimetic dentin model could serve as an in-vitro platform to study oral biofilm formation or dentin-biomaterial bonding in the laboratory without the need for animal or human tooth samples in the future.

bioengineering↗

Evolution of a putative, host-derived endosymbiont division ring and symbiosis-induced proteome rearrangements in the trypanosomatid Angomonas deanei

The transformation of endosymbiotic bacteria into genetically integrated organelles was central to eukaryote evolution. During organellogenesis, control over endosymbiont division, proteome composition, and physiology largely shifted from the endosymbiont to the host cell nucleus. However, to understand the order and timing of events underpinning organellogenesis novel model systems are required. The trypanosomatid Angomonas deanei contains a {beta}-proteobacterial endosymbiont that divides synchronously with the host1, contributes essential metabolites to host cell metabolism2-5, and transferred one bacterial gene [encoding an ornithine cyclodeaminase (OCD)] to the nucleus2. However, the molecular mechanisms mediating the intricate host/symbiont interactions are largely unexplored. Here we identified seven nucleus-encoded proteins by protein mass spectrometry that are targeted to the endosymbiont. Expression of fluorescent fusion proteins revealed recruitment of these proteins to specific sites within the endosymbiont including its cytoplasm and a ring-shaped structure surrounding its division site. This structure remarkably resembles in shape and predicted functions mitochondrial and plastid division machineries. The endosymbiotic gene transfer-derived OCD localizes to glycosomes instead of being retargeted to the endosymbiont. Hence, scrutiny of protein re-localization patterns that are induced by endosymbiosis, yielded profound insights into how an endosymbiotic relationship can stabilize and deepen over time far beyond the level of metabolite exchange.

microbiology↗

Amyloid aggregation of Streptococcus mutans Cnm influences its collagen-binding activity

The glycosylated collagen- and laminin-binding surface adhesin Cnm is present in approximately 20% of S. mutans clinical isolates and is associated with systemic infections and increased caries risk. Other surface-associated collagen-binding proteins of S. mutans such as P1 and WapA have been demonstrated to form an amyloid quaternary structure with functional implications within biofilms. In silico analysis predicted that the {beta}-sheet rich N-terminal collagen-binding domain (CBD) of Cnm has propensity for amyloid aggregation, whereas the threonine-rich C-terminal domain was predicted to be disorganized. In this study, thioflavin-T fluorescence and electron microscopy were used to show that Cnm forms amyloids either in its native glycosylated or recombinant non-glycosylated forms and that the CBD of Cnm is the main amyloidogenic unit of Cnm. We then performed a series of in vitro, ex vivo and in vivo assays to characterize the amylogenic properties of Cnm. In addition, Congo red birefringence indicated that Cnm is a major amyloidogenic protein of S. mutans biofilms. Competitive binding assays using collagen-coated microtiter plates and dental roots, a substrate rich in collagen, revealed that Cnm monomers inhibit S. mutans binding to collagenous substrates whereas Cnm amyloid aggregates lose this property. Thus, while Cnm contributes to recognition and initial binding of S. mutans to collagen-rich surfaces, Cnm amyloid aggregation appears to represent a mechanism to modulate this activity in mature biofilms. IMPORTANCEStreptococcus mutans is a keystone pathogen that promotes caries by acidifying the dental biofilm milieu. The collagen- and laminin-binding glycoprotein Cnm is a virulence factor found in about 20% of the clinical isolates of S. mutans. Expression of Cnm by S. mutans is associated with niche expansion, allowing colonization of multiple sites in the body including collagen-rich surfaces such as dentin and heart valves. Here, we demonstrate for the first time that Cnm function appears to be modulated by its aggregation status. As a monomer, its primary function is to promote attachment to collagenous substrates via its collagen binding domain (CBD). However, in later stages of biofilm maturation, the same CBD of Cnm self-assembles into amyloid fibrils, losing the ability to bind to collagen and likely becoming a component of the biofilm matrix. Our findings shed light into the role of functional amyloids in S. mutans pathobiology and ecology.

microbiology↗

Experimental evidence that UV/yellow colouration functions as a signal of parental quality in the blue tit

In bi-parental species, reproduction is not only a crucial life-history stage where individuals must take fitness-relevant decisions, but these decisions also need to be adjusted to the behavioural strategies of a partner. Hence, communication is required, which could be facilitated by condition-dependent signals of parental quality. Yet, these traits have (co-)evolved in multiple contexts within the family, as during reproduction different family members may coincide and interact at the site of breeding. In this study we explore whether a condition-dependent trait acts a quality signal and regulates intra-family interactions in a bird species, the blue tit (Cyanistes caeruleus). As a family is a complex network where signals could be perceived by multiple receivers, we expected that experimentally blocking the reflectance of an adults UV/yellow colouration of breast feathers may affect the behavioural strategies of all family members. We found an increase of parental investment in nests with an UV-blocked adult, as the partner compensated for the perceived lower rearing capacity. As the UV-blocked adult did not change its provisioning behaviour, as was to be expected, their partner must have responded to the (manipulated) signal but not to a behavioural change. However, offspring did not co-adjust their begging intensity to a signal of parental quality. Opposite to adults, we propose that offspring respond to the behaviour but not to the parental signal. Overall, our results show experimentally at the first time that UV/yellow colouration of blue tits acts as a quality signal revealing the rearing capacity to mates.

evolutionary biology↗

Dietary carotenoid supplementation facilitates egg laying in a wild passerine

During egg laying, female birds face a trade-off between self-maintenance and investment into current reproduction. Providing eggs with resources is energetically demanding, since in most species females lay one egg per day. However, the costs of egg laying not only relate to energetic requirements, but also depend on the availability of specific resources that are vital for egg production and embryonic development. One of these compounds are carotenoids, pigments with antioxidant properties and immuno-stimulatory functions, which are crucial during embryonic development. In this study, we explore how carotenoid availability alleviates this trade-off and facilitates egg laying in the blue tit. Blue tit females lay one egg per day and have the largest clutch size of all European passerines. We performed a lutein supplementation experiment, and measured potential consequences for egg laying capacity and egg quality. We found that lutein-supplemented females had less laying interruptions and thus completed their clutch faster than control females. No effects of treatment were found on the onset of egg laying or clutch size. Experimentally enhanced carotenoid availability did not elevate yolk carotenoid levels or egg mass, but negatively affected eggshell thickness. Our results provide hence evidence on the limiting role of carotenoids during egg laying, However, the benefits of laying faster following lutein supplementation were counterbalanced by a lower accumulation of calcium in the eggshell. Thus, even though single components may constrain egg laying, it is the combined availability of a range of different resources which ultimately determines egg quality and thus embryonic development.

animal behavior and cognition↗

Defining variation in pre-human ecosystems can guide conservation: An example from a Caribbean coral reef

There is a consensus that Caribbean coral reefs are a pale shadow of what they once were, yet a reef’s pre-human state is typically assumed or estimated using space-for-time substitution approaches. These approaches may fail to account for past variation before human impact which could mislead conservation priorities and actions. In this study we use a suite of fossilised mid-Holocene (7.2-5.6 ka) fringing reefs in Caribbean Panama to define the Historical Range of Variation (HRV) in coral community structure before human-impact to provide context for the states of modern reefs in the same area. Using the abundances of coral taxa to quantify communities, we found that most of the modern coral communities exist in novel ecosystem states with no fossil precedence. We do however identify one modern reef that is indistinguishable in coral community structure from the mid-Holocene reefs. Reef-matrix cores show that the community on this reef has remained in a stable state for over 760 years, suggesting long-term resistance to the region-wide shift to novel states. Without historical context this robust and stable reef would be overlooked since it does not fulfil expectations of what a “pristine” coral reef should look like. This example illustrates how defining past variation using the fossil record can place modern degradation in historical context and improve conservation recommendations.View Full Text

paleontology↗

Evaluation of the Accelerate Pheno(TM)system to identify bacteria and determine antimicrobial susceptibility in positive blood cultures

IntroductionNew platforms have recently been developed to reduce response time of identification and antimicrobial susceptibility of bacterial isolates in positive blood cultures from patients with bloodstream infections. The Accelerate Pheno system (Accelerate Diagnostics, Inc.) provides information on pathogen identification and antibiotic susceptibility in approximately 1.5 and 7 hours, respectively.\n\nMethodsIn this study we compared the Accelerate Pheno system with the standard procedure used in our laboratory. A total of 41 blood cultures were prospectively analysed with the Accelerate Pheno system and our standard methods, which include identification by MALDI-TOF mass spectrometry and antibiotic susceptibility testing (AST) by BD Phoenix system and E-test.\n\nResultsThe correlation between the two methods using Cohens kappa coefficient was 0.82; mean (sd) time of identification for MALDI-TOF MS was 0.7 (0.22) hours and 1.43 (0.14) hours for the Accelerate Pheno system. The mean (sd) time of AST with the BD Phoenix system was 15.85 (2.57) hours and with the Accelerate Pheno system 6.7 (0.12) hours. AST results showed an overall essential agreement of 92% for the minimal inhibitory concentrations (MIC) and an overall category agreement of 96%. Among Gram positive isolates, essential and category agreements of 100% were observed. In Gram negative isolates 10 discrepancies were detected, which were classified as 7 major and 3 minor errors. Discrepancies in the Accelerate Pheno system were observed particularly for P. aeruginosa.\n\nConclusionThe Accelerate Pheno system can improve turn-around time in the management of patients with bloodstream infections.

microbiology↗