Retention of native-like structure in an acyclic counterpart of a β-sheet antibiotic

AbstractAn acyclic derivative of the cyclic peptide antibiotic, ramoplanin, has been prepared. In aqueous solution, two-dimensional NMR spectroscopy indicates that the acyclic form adopts a threshold population of conformers in which at least part of the β-sheet characteristic of the intact ramoplanin persists. Thus, despite losing the entropic benefit which the macrocycle must lend to β-sheet formation, the polypeptide chain of the acyclic ramoplanin appears to display an innate tendency to adopt a native-like conformation

The Functional Nasal Anatomy of the Pike, <i>Esox lucius</i> L.

Olfactory flow in fishes is a little-explored area of fundamental and applied importance. We investigated olfactory flow in the pike, Esox lucius, because it has an apparently simple and rigid nasal region. We characterised olfactory flow by dye visualisation and computational fluid dynamics, using models derived from X-ray micro-computed tomography scans of two preserved specimens. An external current induced a flow of water through the nasal chamber at physiologically relevant Reynolds numbers (200 – 300). We attribute this externally-induced flow to: the location of the incurrent nostril in a region of high static pressure; the nasal bridge deflecting external flow into the nasal chamber; an excurrent nostril normal to external flow; and viscous entrainment. A vortex in the incurrent nostril may be instrumental in viscous entrainment. Flow was dispersed over the olfactory sensory surface when it impacted on the floor of the nasal chamber. Dispersal may be assisted by: the radial array of nasal folds; a complementary interaction between a posterior nasal fold and the ventral surface of the nasal bridge; and the incurrent vortex. The boundary layer could delay considerably (up to ~ 3 s) odorant transport from the external environment to the nasal region. The drag incurred by olfactory flow was almost the same as the drag incurred by models in which the nasal region had been replaced by a smooth surface. The boundary layer does not detach from the nasal region. We conclude that the nasal bridge and the incurrent vortex are pivotal to olfaction in the pike

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Olfactory flow in the sea catfish, Ariopsis felis (L.): Origin, regulation, and resampling

The olfactory epithelium of the sea catfish, Ariopsis felis, is found on a pinnate array of lamellae (the olfactory rosette) housed within a nasal chamber. The nasal anatomy of A. felis suggests an ability to capture external water currents. We prepared models from X-ray micro-computed tomography scans of two preserved specimens of A. felis. We then used dye visualisation and computational fluid dynamics to show that an external current induced a flow of water through a) the nasal chamber and b) the sensory channels of the olfactory rosette. The factors responsible for inducing flow through the nasal chamber are common to fishes from two other orders. The dye visualisation experiments, together with observations of sea catfishes in vivo, indicate that flow through the nasal chamber is regulated by a mobile nasal flap. The position of the nasal flap - elevated (significant flow) or depressed (reduced flow) - is controlled by the sea catfish's movements. Flow in the sensory channels of the olfactory rosette can pass through either a single channel or, via multiple pathways, up to four consecutive channels. Flow through consecutive sensory channels (olfactory resampling) is more extensive at lower Reynolds numbers (200 and 300, equivalent to swimming speeds of 0.5-1.0 total lengths s-1), coinciding with the mean swimming speed of the sea catfishes observed in vivo (0.6 total lengths s-1). Olfactory resampling may also occur, via a vortex, within single sensory channels. In conclusion, olfactory flow in the sea catfish is regulated and thoroughly sampled by novel mechanisms

Data for: Olfactory Flow in the Sturgeon is Externally Driven

TIFF images from an X-ray scan of the head of a sturgeon, Huso dauricu

Hydrodynamic aspects of fish olfaction

Flow into and around the olfactory chamber of a fish determines how odorant from the fish's immediate environment is transported to the sensory surface (olfactory epithelium) lining the chamber. Diffusion times in water are long, even over comparatively short distances (millimetres). Therefore, transport from the external environment to the olfactory epithelium must be controlled by processes that rely on convection (i.e. the bulk flow of fluid). These include the beating of cilia lining the olfactory chamber and the relatively inexpensive pumping action of accessory sacs. Flow through the chamber may also be induced by an external flow. Flow over the olfactory epithelium appears to be laminar. Odorant transfer to the olfactory epithelium may be facilitated in several ways: if the olfactory organs are mounted on stalks that penetrate the boundary layer; by the steep velocity gradients generated by beating cilia; by devices that deflect flow into the olfactory chamber; by parallel arrays of olfactory lamellae; by mechanical agitation of the chamber (or olfactory stalks); and by vortices. Overall, however, our knowledge of the hydrodynamics of fish olfaction is far from complete. Several areas of future research are outlined