Diversity of coryneforms found in infections following prosthetic joint insertion and open fractures

Summary: In a 5-year period, 73 coryneform isolates from prosthetic joint and open fracture infections in 60 patients treated in a hospital specialized in orthopedic surgery were speciated. The most frequent species wereCorynebacterium amycolatum, Corynebacterium striatum, Corynebacterium diphtheriae biotypemitis, andCorynebacterium jeikeium. At least 14 isolates were deemed clinically significant as sole agents of infectio

The ribosome stabilizes partially folded intermediates of a nascent multi-domain protein

Co-translational folding is crucial to ensure the production of biologically active proteins. The ribosome can alter the folding pathways of nascent polypeptide chains, yet a structural understanding remains largely inaccessible experimentally. We have developed site-specific labelling of nascent chains to detect and measure, using 19F nuclear magnetic resonance (NMR) spectroscopy, multiple states accessed by an immunoglobulin-like domain within a tandem repeat protein during biosynthesis. By examining ribosomes arrested at different stages during translation of this common structural motif, we observe highly broadened NMR resonances attributable to two previously unidentified intermediates, which are stably populated across a wide folding transition. Using molecular dynamics simulations and corroborated by cryo-electron microscopy, we obtain models of these partially folded states, enabling experimental verification of a ribosome-binding site that contributes to their high stabilities. We thus demonstrate a mechanism by which the ribosome could thermodynamically regulate folding and other co-translational processes

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Mass transfer in the lower crust: Evidence for incipient melt assisted flow along grain boundaries in the deep arc granulites of Fiordland, New Zealand

Knowledge of mass transfer is critical in improving our understanding of crustal evolution, however mass transfer mechanisms are debated, especially in arc environments. The Pembroke Granulite is a gabbroic gneiss, passively exhumed from depths of >45 km from the arc root of Fiordland, New Zealand. Here, enstatite and diopside grains are replaced by coronas of pargasite and quartz, which may be asymmetric, recording hydration of the gabbroic gneiss. The coronas contain microstructures indicative of the former presence of melt, supported by pseudosection modeling consistent with the reaction having occurred near the solidus of the rock (630–710°C, 8.8–12.4 kbar). Homogeneous mineral chemistry in reaction products indicates an open system, despite limited metasomatism at the hand sample scale. We propose the partial replacement microstructures are a result of a reaction involving an externally derived hydrous, silicate melt and the relatively anhydrous, high-grade assemblage. Trace element mapping reveals a correlation between reaction microstructure development and bands of high-Sr plagioclase, recording pathways of the reactant melt along grain boundaries. Replacement microstructures record pathways of diffuse porous melt flow at a kilometer scale within the lower crust, which was assisted by small proportions of incipient melt providing a permeable network. This work recognizes melt flux through the lower crust in the absence of significant metasomatism, which may be more common than is currently recognized. As similar microstructures are found elsewhere within the exposed Fiordland lower crustal arc rocks, mass transfer of melt by diffuse porous flow may have fluxed an area >10,000 km2

Swiss students and young physicians want a flexible goal-oriented GP training curriculum.

A growing shortage of general practitioners (GPs), in Switzerland and around the world, has forced countries to find new ways to attract young physicians to the specialty. In 2017, Switzerland began to fund hundreds of new study places for medical students. This wave of young physicians will soon finish University and be ready for postgraduate training. We hypothesized that an attractive postgraduate training program would encourage interested young physicians to pursue a GP career. This is a cross-sectional survey of young physicians from the Swiss Young General Practitioners Association (JHaS), members of Cursus Romand de médecine de famille (CRMF), and all current medical students (5 <sup>th</sup> or 6 <sup>th</sup> years) (n = 554) in Switzerland, excluding students indicating definitely not to become GPs. We asked all if they were likely to become a GP (Likert: 1-10), and then asked them to score general features of a GP training curriculum, and likely effects of the curriculum on their career choice (Likert scale). They then rated our model curriculum (GO-GP) for attractiveness and effect (Likert Scales, open questions). Most participants thought they would become GPs (Likert: 8 of 10). Over 90% identified the same features as an important part of a curriculum ("yes" or "likely yes"): Our respondents thought the GO-GP curriculum was attractive (7.3 of 10). It was most attractive to those highly motivated to become GPs. After reviewing the curriculum, most respondents (58%) felt GO-GP would make them more likely to become a GP. Almost 80% of respondents thought an attractive postgraduate training program like GO-GP could motivate more young physicians to become GPs. Overall, medical students and young physicians found similar features attractive in the general and GO-GP curriculum, regardless of region or gender, and thought an attractive curriculum would attract more young doctors to the GP specialty. Key points An attractive postgraduate training program in general practice can attract more young physicians to become GPs. In this study cross-sectional survey including medical students (n = 242) and young physicians (n = 312) we presented general features for a curriculum and a model curriculum for general practice training, for evaluation of attractiveness to our study population. General practice training curriculum provides flexibility in choice of rotations, access to short rotations in a wide variety of medical specialties, training in specialty practices as well, mentoring and career guidance by GPs and guidance in choosing courses/certificate programs necessary for general practice. These findings help building attractive postgraduate training programs in general practice and fight GP shortage

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

N-3 polyunsaturated fatty acid and neuroinflammation in aging and Alzheimer's disease

The innate immune system of the brain is mainly composed of microglial cells, which play a key role in the maintenance of synapses and the protection of neurons against noxious agents or lesions owing to their phagocytic activity. In the healthy brain, microglia are highly motile and strongly interact with neurons either by physical contact, induction of oxidative stress or through specific mediators, such as chemokines and cytokines. In response to inflammatory insult however, microglial cells get activated and produce inflammatory cytokines. The action of cytokines on specific receptors expressed in the brain triggers the development of sickness behavior and altered cognitive and emotional processes. The effects are acute and reversible as normal behavior is restored once the synthesis of inflammatory brain cytokines returns to baseline after a few hours. However, in pathological situations, these cytokines may reach toxic levels and have irreversible consequences such as neuronal death, as observed in neurodegenerative disorders such as Alzheimer’s disease. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients and fundamental components of neuronal and glial cell membranes. They accumulate in the brain during the perinatal period in a dietary supply-dependent fashion. Their brain levels may diminish with age, but can be increased by diets enriched in n-3 PUFAs. Changes in the immune profile have been associated with n-3 PUFAs intake in humans and animal models. Therefore, the increasing exposure of the population to diets low in n-3 PUFAs could contribute to the deleterious effects of the chronic activation of microglia in the brain