Extending the reservoir of bla IMP-5: the emerging pathogen Acinetobacter bereziniae

Acinetobacter bereziniae clinical relevance is starting to be recognized; however, very few descriptions of its carbapenem resistance currently exist. Here we characterize two carbapenem-resistant A. bereziniae isolates. Materials & methods: Isolates were obtained from environmental and clinical samples. Carbapenemases were searched by phenotypic, biochemical and PCR assays. Clonality was studied by ApaI-PFGE and genetic location for carbapenemase genes were assessed by I-CeuI and S1 hybridizations. Results: Isolates were not clonally related but both produced the exclusively Portuguese IMP-5, with the clinical isolate also producing an OXA-58. The carbapenemase genes were plasmid located. Conclusion: Our results emphasize the role of non-baumannii Acinetobacter species as important reservoirs of clinically relevant resistance genes that could also contribute to their emergence as nosocomial pathogensThis work was funded by FEDER funds through the Operational Programme for Competitiveness Factors – COMPETE and by National Funds through FCT – Foundation for Science and Technology under the project Pest-C/EQB/LA0006/2013. L Silva and F Grosso were supported by grants from FCT (SFRH/BD/88028/2012 and SFRH/BPD/95556/2013, respectively). C Sousa was funded by an FCT contract CIENCIA2008. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript

Nuclear and magnetic structures of the frustrated quantum antiferromagnet barlowite, Cu-4(OH)(6)FBr

Barlowite, Cu$_{4}$(OH)$_{6}$FBr, has attracted much attention as the parent compound of a new series of quantum spin liquid candidates, Zn$_{x}$Cu$_{4-x}$(OH)$_{6}$FBr. While it is known to undergo a magnetic phase transition to a long-range ordered state at $T_{N} = 15$ K, there is still no consensus over either its nuclear or magnetic structures. Here, we use comprehensive powder neutron diffraction studies on deuterated samples of barlowite to demonstrate that the only space group consistent with the observed nuclear and magnetic diffraction at low-temperatures is the orthorhombic $Pnma$ space group. We furthermore conclude that the magnetic intensity at $T < T_{N}$ is correctly described by the $Pn^\prime m^\prime a$ magnetic space group, which crucially allows the ferromagnetic component observed in previous single-crystal and powder magnetisation measurements. As such, the magnetic structure of barlowite resembles that of the related material clinoatacamite, Cu$_{4}$(OH)$_{6}$Cl$_{2}$, the parent compound of the well-known quantum spin liquid candidate hebertsmithite, ZnCu$_{3}$(OH)$_{6}$Cl$_{2}$.Comment: 11 pages, 4 figures, supplemental materia

Exploration of the Eucalyptus globulus gene pool

The first Europeans to discover Eucalyptus globulus were French explorers in 1792. Its seed was rapidly spread throughout the world in the 19th century and this was the species by which much of the world first knew the genus. However, it was in the industrial forests of the 20th century that this species, once considered the ‘Prince of Eucalypts’, achieved greatest prominence due to its fast growth and superior pulp qualities. Formal breeding first commenced in 1966 in Portugal and in the late 1980’s large base population trials from open-pollinated seed collections from native stands were established in many countries. These trials have provided unprecedented insights into the quantitative genetic control of numerous traits of economic and ecological importance and how this variation is spatially distributed in the native range of the species. However with large, fully pedigreed breeding populations becoming available for quantitative analysis and the rapidly expanding knowledge of DNA sequence variation, we are now at the threshold of a new understanding of this important eucalypt gene pool. Indications of the significance of non-additive genetic effects are becoming available. The E. globulus chloroplast genome has now been sequenced and several genome maps have been published. Studies of the variation in nuclear microsatellites and the lignin biosynthesis gene CCR confirm the complex, spatially structured nature of the native gene pool. Strong spatial structuring of the chloroplast genome has provided a tool for tracking seed migration and the geographic origin of exotic landraces. Highly divergent lineages of chloroplast DNA have been discovered and studies of the hypervariable JLA+ region argue that some components of the E. globulus gene pool have been assimilated from other species following hybridisation

Time-to-birth prediction models and the influence of expert opinions

Preterm birth is the leading cause of death among children under five years old. The pathophysiology and etiology of preterm labor are not yet fully understood. This causes a large number of unnecessary hospitalizations due to high--sensitivity clinical policies, which has a significant psychological and economic impact. In this study, we present a predictive model, based on a new dataset containing information of 1,243 admissions, that predicts whether a patient will give birth within a given time after admission. Such a model could provide support in the clinical decision-making process. Predictions for birth within 48 h or 7 days after admission yield an Area Under the Curve of the Receiver Operating Characteristic (AUC) of 0.72 for both tasks. Furthermore, we show that by incorporating predictions made by experts at admission, which introduces a potential bias, the prediction effectiveness increases to an AUC score of 0.83 and 0.81 for these respective tasks

Exercise training reveals inflexibility of the diaphragm in an animal model of patients with obesity-driven heart failure with a preserved ejection fraction

Background: Respiratory muscle weakness contributes to exercise intolerance in patients with heart failure with a preserved ejection fraction (HFpEF)—a condition characterized by multiple comorbidities with few proven treatments. We aimed, therefore, to provide novel insight into the underlying diaphragmatic alterations that occur in HFpEF by using an obese cardiometabolic rat model and further assessed whether exercise training performed only after the development of overt HFpEF could reverse impairments. Methods and Results: Obese ZSF1 rats (n=12) were compared with their lean controls (n=8) at 20 weeks, with 3 additional groups of obese ZSF1 rats compared at 28 weeks following 8 weeks of either sedentary behavior (n=13), high‐intensity interval training (n=11), or moderate‐continuous training (n=11). Obese rats developed an obvious HFpEF phenotype at 20 and 28 weeks. In the diaphragm at 20 weeks, HFpEF induced a shift towards an oxidative phenotype and a fiber hypertrophy paralleled by a lower protein expression in MuRF1 and MuRF2, yet mitochondrial and contractile functional impairments were observed. At 28 weeks, neither the exercise training regimen of high‐intensity interval training or moderate‐continuous training reversed any of the diaphragm alterations induced by HFpEF. Conclusions: This study, using a well‐characterized rat model of HFpEF underpinned by multiple comorbidities and exercise intolerance (ie, one that closely resembles the patient phenotype), provides evidence that diaphragm alterations and dysfunction induced in overt HFpEF are not reversed following 8 weeks of aerobic exercise training. As such, whether alternative therapeutic interventions are required to treat respiratory muscle weakness in HFpEF warrants further investigation

Genome-wide interaction and pathway-based identification of key regulators in multiple myeloma.

Inherited genetic susceptibility to multiple myeloma has been investigated in a number of studies. Although 23 individual risk loci have been identified, much of the genetic heritability remains unknown. Here we carried out genome-wide interaction analyses on two European cohorts accounting for 3,999 cases and 7,266 controls and characterized genetic susceptibility to multiple myeloma with subsequent meta-analysis that discovered 16 unique interacting loci. These risk loci along with previously known variants explain 17% of the heritability in liability scale. The genes associated with the interacting loci were found to be enriched in transforming growth factor beta signaling and circadian rhythm regulation pathways suggesting immunoglobulin trait modulation, TH17 cell differentiation and bone morphogenesis as mechanistic links between the predisposition markers and intrinsic multiple myeloma biology. Further tissue/cell-type enrichment analysis associated the discovered genes with hemic-immune system tissue types and immune-related cell types indicating overall involvement in immune response

Effect of Dietary Components on Larval Life History Characteristics in the Medfly (Ceratitis capitata: Diptera, Tephritidae)

Background: The ability to respond to heterogenous nutritional resources is an important factor in the adaptive radiation of insects such as the highly polyphagous Medfly. Here we examined the breadth of the Medfly’s capacity to respond to different developmental conditions, by experimentally altering diet components as a proxy for host quality and novelty. Methodology/Principal Findings: We tested responses of larval life history to diets containing protein and carbohydrate components found in and outside the natural host range of this species. A 40% reduction in the quantity of protein caused a significant increase in egg to adult mortality by 26.5%±6% in comparison to the standard baseline diet. Proteins and carbohydrates had differential effects on larval versus pupal development and survival. Addition of a novel protein source, casein (i.e. milk protein), to the diet increased larval mortality by 19.4%±3% and also lengthened the duration of larval development by 1.93±0.5 days in comparison to the standard diet. Alteration of dietary carbohydrate, by replacing the baseline starch with simple sugars, increased mortality specifically within the pupal stage (by 28.2%±8% and 26.2%±9% for glucose and maltose diets, respectively). Development in the presence of the novel carbohydrate lactose (milk sugar) was successful, though on this diet there was a decrease of 29.8±1.6 µg in mean pupal weight in comparison to pupae reared on the baseline diet. Conclusions: The results confirm that laboratory reared Medfly retain the ability to survive development through a wide range of fluctuations in the nutritional environment. We highlight new facets of the responses of different stages of holometabolous life histories to key dietary components. The results are relevant to colonisation scenarios and key to the biology of this highly invasive species

Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics.

Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives

Effects of endurance training on detrimental structural, cellular, and functional alterations in skeletal muscles of heart failure with preserved ejection fraction

Background: HFpEF is underpinned by detrimental skeletal muscle alterations that contribute to disease severity, yet underlying mechanisms and therapeutic treatments remain poorly established. This study used an animal model of HFpEF to better understand whether skeletal muscle abnormalities were: 1) fiber-type specific; and 2) reversible by various exercise training regimes. Methods and Results: Lean controls were compared to obese ZSF1 rats at 20 weeks, and 8 weeks later following sedentary, high-intensity interval training, or moderate-continuous treadmill exercise. Oxidative-soleus and glycolytic-extensor digitorum longus (EDL) muscles were assessed for fiber size, capillarity, glycolytic metabolism, autophagy, and contractile function. HFpEF reduced fiber size and capillarity by 20-50% (P<0.05) in both soleus and EDL, but these effects were not reversed by endurance training. In contrast, both endurance training regimes in HFpEF attenuated the elevated lactate dehydrogenase activity observed in the soleus. Autophagy was downregulated in EDL and upregulated in soleus (P<0.05), with no influence following endurance training. HFpEF impaired contractile forces of both muscles by ∼20 % (P<0.05) and these were not reversed by training. Conclusion: Obesity-related HFpEF was associated with detrimental structural, cellular, and functional alterations to both slow-oxidative and fast-glycolytic skeletal muscles that could not be reversed by endurance training