Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for rapid identification of mold and yeast cultures of Penicillium marneffei

published_or_final_versio

The highly rearranged mitochondrial genomes of the crabs Maja crispata and Maja squinado (Majidae) and gene order evolution in Brachyura

Abstract We sequenced the mitochondrial genomes of the spider crabs Maja crispata and Maja squinado (Majidae, Brachyura). Both genomes contain the whole set of 37 genes characteristic of Bilaterian genomes, encoded on both \u3b1- and \u3b2-strands. Both species exhibit the same gene order, which is unique among known animal genomes. In particular, all the genes located on the \u3b2-strand form a single block. This gene order was analysed together with the other nine gene orders known for the Brachyura. Our study confirms that the most widespread gene order (BraGO) represents the plesiomorphic condition for Brachyura and was established at the onset of this clade. All other gene orders are the result of transformational pathways originating from BraGO. The different gene orders exhibit variable levels of genes rearrangements, which involve only tRNAs or all types of genes. Local homoplastic arrangements were identified, while complete gene orders remain unique and represent signatures that can have a diagnostic value. Brachyura appear to be a hot-spot of gene order diversity within the phylum Arthropoda. Our analysis, allowed to track, for the first time, the fully evolutionary pathways producing the Brachyuran gene orders. This goal was achieved by coupling sophisticated bioinformatic tools with phylogenetic analysis

Glucose-dependent insulinotropic polypeptide receptor signalling in oligodendrocytes increases the weight loss action of GLP1R agonism

The next-generation of obesity medicines harness the activity of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors (GIPR, GLP-1R), but their mechanism of action remains to be fully elucidated. Here, we report that the GIPR is enriched in oligodendrocytes of the median eminence (ME) and GIPR signalling bidirectionally regulates oligodendrogenesis in the adult ME of diet-induced obese (DIO) mice. In mice with adult-onset deletion of the GIPR in oligodendrocytes, GIPR agonism fails to enhance the weight-loss and appetite-suppressive effects of GLP-1R agonism. Mechanistically, GIPR agonism increases the access of GLP-1R agonists to the ME and ARH, and GIPR signalling in oligodendrocytes is required for this effect. In addition, we show that vasopressin neurons of the paraventricular hypothalamus, which are necessary for the weight loss induced by GLP1R activation, are targeted by peripherally administered GLP1R agonists via their axonal compartment in the ME. This access is increased by activation of the GIPR in oligodendrocytes in obese mice. Collectively, our findings identify a novel mechanism by which incretin therapies may function to promote synergistic weight loss in the management of excess adiposity

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

Liquid-gas phase transition in nuclear multifragmentation

The equation of state of nuclear matter suggests that at suitable beam energies the disassembling hot system formed in heavy ion collisions will pass through a liquid-gas coexistence region. Searching for the signatures of the phase transition has been a very important focal point of experimental endeavours in heavy ion collisions, in the last fifteen years. Simultaneously theoretical models have been developed to provide information about the equation of state and reaction mechanisms consistent with the experimental observables. This article is a review of this endeavour.Comment: 63 pages, 27 figures, submitted to Adv. Nucl. Phys. Some typos corrected, minor text change

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Modular construction of mammalian gene circuits using TALE transcriptional repressors

An important goal of synthetic biology is the rational design and predictable implementation of synthetic gene circuits using standardized and interchangeable parts. However, engineering of complex circuits in mammalian cells is currently limited by the availability of well-characterized and orthogonal transcriptional repressors. Here, we introduce a library of 26 reversible transcription activator–like effector repressors (TALERs) that bind newly designed hybrid promoters and exert transcriptional repression through steric hindrance of key transcriptional initiation elements. We demonstrate that using the input-output transfer curves of our TALERs enables accurate prediction of the behavior of modularly assembled TALER cascade and switch circuits. We also show that TALER switches using feedback regulation exhibit improved accuracy for microRNA-based HeLa cancer cell classification versus HEK293 cells. Our TALER library is a valuable toolkit for modular engineering of synthetic circuits, enabling programmable manipulation of mammalian cells and helping elucidate design principles of coupled transcriptional and microRNA-mediated post-transcriptional regulation.National Institutes of Health (U.S.) (Grant 5R01CA155320-04)National Institutes of Health (U.S.) (Grant P50GM098792)National Institutes of Health (U.S.) (Grant 1R01CA173712-01

Outcomes, Microbiology and Antimicrobial Usage in Pressure Ulcer-Related Pelvic Osteomyelitis: Messages for Clinical Practice

Abstract. Introduction: Pressure ulcer-related pelvic osteomyelitis is a relatively under-studied entity in the field of bone infection. We sought to add to the limited evidence base for managing this challenging syndrome.Methods: Cases were identified retrospectively from a surgical database and hospital discharge codes at a U.K. tertiary centre (2009-2018). Risk factors associated with outcomes were analysed by logistic regression.Results: We identified 35 patients (mean age 57.4 years), 69% managed with a combined medical and surgical approach, with mean follow-up of 3.7 years from index admission. Treatment failure (requiring further surgery or intravenous antimicrobials) occurred in 71% and eventual ulcer healing in 36%. One-year mortality was 23%. Lack of formal care support on discharge, post-traumatic (asensate) neurological deficit and index CRP (&gt;184mg/L) were associated with treatment failure (p=0.001). Age (&gt;59.5 years), lack of attempted soft tissue coverage, haemoglobin (&lt;111g/L) and albumin (&lt;25g/L) were associated with non-healing ulcers (p=0.003). Superficial wound swabs had low sensitivity and specificity compared to deep bone microbiology. Infection (based on deep bone microbiology from 46 infection episodes) was usually polymicrobial (87%), commonly involving S. aureus, Enterococci, GNB and anaerobes. Antimicrobial duration ranged from 0-103 days (mean 54) and was not associated with subsequent treatment failure.Conclusions: Attempted soft tissue coverage after surgical debridement, ensuring appropriate support for personal care after discharge and nutritional optimisation could improve outcomes. Superficial wound swabs are uninformative and deep bone sampling should be pursued. Long antimicrobial courses do not improve outcomes. Clinicians should engage patients in anticipatory care planning.</jats:p

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO