Extent and mechanism of sealing in transected giant axons of squid and earthworms

Transected axons are often assumed to seal at their cut ends by the formation of continuous membrane barriers that allow for the restoration of function in the axonal stumps. We have used several electrophysiological measures (membrane potential, input resistance, injury current density) and several morphological measures (phase-contrast, video-enhanced differential interference contrast, light, and electron microscopies) of living and fixed material to assess the extent and mechanism of sealing within hours after transecting giant axons of squid (Loligo pealeiand Sepioteuthis lessoniana) and earthworms (Lumbricus terrestris). Our electrophysiological data suggest that the proximal and distal ends of transected squid giant axons do not completely seal within 2.5 hr in physiological saline. In contrast, the same set of measures suggest that proximal and distal ends of transected earthworm giant axons seal within 1 hr in physiological saline. Our morphological data show that the cut ends of both squid and earthworm axons constrict, but that a 20- 70-am-diameter opening always remains at the cut end that is filled with vesicles. Axonal transection induces the formation of vesicles that are observed in the axoplasm within minutes in standard salines and that rapidly migrate to the cut ends. These injury-induced vesicles are loosely packed near the cut ends of squid giant axons, which do not functionally seal within 2.5 hr of transection. In contrast, vesicles formed a tightly packed plug at the cut ends of earthworm medial giant axons, which do functionally seal within 1 hr of transection in physiological saline. Since we detect no single continuous membrane that spans the cut end, sealing does not appear to occur by the fusion of constricted axolemmal membrane or the formation of a membranous partition at the cut end. Rather, our data are consistent with the hypothesis that a tightly packed vesicular plug is responsible for sealing of earthworm giant axons.This work was supported in part by NIH Grant NS31256 and ONR Grant N00014-90-J-1137 to H.M.F., an NIAAA fellowship to T.L.K., and an ATP grant to G.D.B.Neuroscienc

Endocytotic formation of vesicles and other membranous structures induced by Ca2+ and axolemmal injury

Vesicles and/or other membranous structures that form after axolemmal damage have recently been shown to repair (seal) the axolemma of various nerve axons. To determine the origin of such membranous structures, (1) we internally dialyzed isolated intact squid giant axons (GAs) and showed that elevation of intracellular Ca21 .100 uM produced membranous structures similar to those in axons transected in Ca21-containing physiological saline; (2) we exposed GA axoplasm to Ca21- containing salines and observed that membranous structures did not form after removing the axolemma and glial sheath but did form in severed GAs after .99% of their axoplasm was removed by internal perfusion; (3) we examined transected GAs and crayfish medial giant axons (MGAs) with time-lapse confocal fluorescence microscopy and showed that many injuryinduced vesicles formed by endocytosis of the axolemma; (4) we examined the cut ends of GAs and MGAs with electron microscopy and showed that most membranous structures were single-walled at short (5–15 min) post-transection times, whereas more were double- and multi-walled and of probable glial origin after longer (30–150 min) post-transection times; and (5) we examined differential interference contrast and confocal images and showed that large and small lesions evoked similar injury responses in which barriers to dye diffusion formed amid an accumulation of vesicles and other membranous structures. These and other data suggest that Ca21 inflow at large or small axolemmal lesions induces various membranous structures (including endocytotic vesicles) of glial or axonal origin to form, accumulate, and interact with each other, preformed vesicles, and/or the axolemma to repair the axolemmal damage.This work was supported by grants from National Institutes of Health (NIH; NS31256) and the State of Texas (Advanced Technology 3658-446).Neuroscienc

Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats

Dialysis solution containing hyaluronan: Effect on peritoneal permeability and inflammation in rats.BackgroundHyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks.MethodsWistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment.ResultsAfter four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P < 0.001; 33% lower for total protein, P < 0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P < 0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 ± 6.7 vs. 22.8 ± 9.5%, P < 0.01) and lower levels of the cytokines, tumor necrosis factor-α (11.2 ± 14.7 vs. 42.3 ± 35.3 pg/mL, P < 0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 ± 86.5 vs. 402.4 ± 258.3 pg/mL, P < 0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P < 0.01) than tissue from control animals.ConclusionsThe addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis

A First Look at Spatially Resolved Balmer Decrements at 1.0<z<2.41.0<z<2.4 from JWST NIRISS Slitless Spectroscopy

We present the first results on the spatial distribution of dust attenuation at $1.0<z<2.4$ traced by the Balmer Decrement, H$\alpha$/H$\beta$, in emission-line galaxies using deep JWST NIRISS slitless spectroscopy from the CAnadian NIRISS Unbiased Cluster Survey (CANUCS). H$\alpha$ and H$\beta$ emission line maps of emission-line galaxies are extracted and stacked in bins of stellar mass for two grism redshift bins, $1.0<z_{grism}<1.7$ and $1.7<z_{grism}<2.4$. Surface brightness profiles for the Balmer Decrement are measured and radial profiles of the dust attenuation towards H$\alpha$, $A_{\mathrm{H}\alpha}$, are derived. In both redshift bins, the integrated Balmer Decrement increases with stellar mass. Lower mass ($7.6\leqslant$Log($M_{*}$/M$_{\odot}$)$<10.0$) galaxies have centrally concentrated, negative dust attenuation profiles whereas higher mass galaxies ($10.0\leqslant$Log($M_{*}$/M$_{\odot}$)$<11.1$) have flat dust attenuation profiles. The total dust obscuration is mild, with on average $0.07\pm0.07$ and $0.14\pm0.07$ mag in the low and high redshift bins respectively. We model the typical light profiles of star-forming galaxies at these redshifts and stellar masses with GALFIT and apply both uniform and radially varying dust attenuation corrections based on our integrated Balmer Decrements and radial dust attenuation profiles. If these galaxies were observed with typical JWST NIRSpec slit spectroscopy ($0.2\times0.5^{\prime\prime}$ shutters), on average, H$\alpha$ star formation rates (SFRs) measured after slit-loss corrections assuming uniform dust attenuation will overestimate the total SFR by $6\pm21 \%$ and $26\pm9 \%$ at $1.0\leqslant z < 1.7$ and $1.7\leqslant z < 2.4$ respectively.Comment: 7 pages, 5 figures, submitted to ApJ

The near-infrared imager and slitless spectrograph for the James Webb Space Telescope. II. Wide field slitless spectroscopy

We acknowledge support from the Natural Sciences and Engineering Research Council of Canada (NSERC) through a variety of its funding programs. This work is in part supported by Canadian Space Agency grant 18JWSTGTO1. C.P., S.R. and K.V. are supported by the Canadian Space Agency under a contract with NRC Herzberg Astronomy and Astrophysics. K.M. acknowledges funding by the Science and Technology Foundation of Portugal (FCT), grants No. IF/00194/2015, PTDC/FIS-AST/28731/2017, UIDB/00099/2020.We present the wide field slitless spectroscopy mode of the NIRISS instrument on the James Webb Space Telescope. This mode employs two orthogonal low-resolution (resolving power ≈150) grisms in combination with a set of six blocking filters in the wavelength range 0.8–2.3 μm to provide a spectrum of almost every source across the field-of-view. When combined with the low background, high sensitivity and high spatial resolution afforded by the telescope, this mode will enable unprecedented studies of the structure and evolution of distant galaxies. We describe the performance of the as-built hardware relevant to this mode and expected imaging and spectroscopic sensitivity. We discuss operational and calibration procedures to obtain the highest quality data. As examples of the observing mode usage, we present details of two planned Guaranteed Time Observations programs: The Canadian NIRISS Unbiased Cluster Survey and The NIRISS Survey for Young Brown Dwarfs and Rogue Planets.Publisher PDFPeer reviewe

Prevalence and Predictors of Persistence of COVID-19 Symptoms in Older Adults: A Single-Center Study

Objectives: Symptom persistence weeks after laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance is a relatively common long-term complication of Coronavirus disease 2019 (COVID-19). Little is known about this phenomenon in older adults. The present study aimed at determining the prevalence of persistent symptoms among older COVID-19 survivors and identifying symptom patterns. Design: Cross-sectional study. Setting and Participants: We analyzed data collected in people 65 years and older (n = 165) who were hospitalized for COVID-19 and then admitted to the Day Hospital Post-COVID 19 of the Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS (Rome, Italy) between April and December 2020. All patients tested negative for SARS-CoV-2 and met the World Health Organization criteria for quarantine discontinuation. Measures: Patients were offered multidisciplinary individualized assessments. The persistence of symptoms was evaluated on admission using a standardized questionnaire. Results: The mean age was 73.1 ± 6.2 years (median 72, interquartile range 27), and 63 (38.4%) were women. The average time elapsed from hospital discharge was 76.8 ± 20.3 days (range 25−109 days). On admission, 137 (83%) patients reported at least 1 persistent symptom. Of these, more than one-third reported 1 or 2 symptoms and 46.3% had 3 or more symptoms. The rate of symptom persistence was not significantly different when patients were stratified according to median age. Compared with those with no persistent symptoms, patients with symptom persistence reported a greater number of symptoms during acute COVID-19 (5.3 ± 3.0 vs 3.3 ± 2.0; P &lt; .001). The most common persistent symptoms were fatigue (53.1%), dyspnea (51.5%), joint pain (22.2%), and cough (16.7%). The likelihood of symptom persistence was higher in those who had experienced fatigue during acute COVID-19. Conclusions and Implications: Persistent symptoms are frequently experienced by older adults who have been hospitalized for COVID-19. Follow-up programs should be implemented to monitor and care for long-term COVID-19–related health issues

Multiview classification and dimensionality reduction of scalp and intracranial EEG data through tensor factorisation

Electroencephalography (EEG) signals arise as a mixture of various neural processes that occur in different spatial, frequency and temporal locations. In classification paradigms, algorithms are developed that can distinguish between these processes. In this work, we apply tensor factorisation to a set of EEG data from a group of epileptic patients and factorise the data into three modes; space, time and frequency with each mode containing a number of components or signatures. We train separate classifiers on various feature sets corresponding to complementary combinations of those modes and components and test the classification accuracy of each set. The relative influence on the classification accuracy of the respective spatial, temporal or frequency signatures can then be analysed and useful interpretations can be made. Additionaly, we show that through tensor factorisation we can perform dimensionality reduction by evaluating the classification performance with regards to the number mode components and by rejecting components with insignificant contribution to the classification accuracy

Gaussian Mixture Model of Heart Rate Variability

Heart rate variability (HRV) is an important measure of sympathetic and parasympathetic functions of the autonomic nervous system and a key indicator of cardiovascular condition. This paper proposes a novel method to investigate HRV, namely by modelling it as a linear combination of Gaussians. Results show that three Gaussians are enough to describe the stationary statistics of heart variability and to provide a straightforward interpretation of the HRV power spectrum. Comparisons have been made also with synthetic data generated from different physiologically based models showing the plausibility of the Gaussian mixture parameters

The growth of a culture of evidence-based obstetrics in South Africa: a qualitative case study

<p>Abstract</p> <p>Background</p> <p>While the past two decades have seen a shift towards evidence-based obstetrics and midwifery, the process through which a culture of evidence-based practice develops and is sustained within particular fields of clinical practice has not been well documented, particularly in LMICs (low- and middle-income countries). Forming part of a broader qualitative study of evidence-based policy making, this paper describes the development of a culture of evidence-based practice amongst maternal health policy makers and senior academic obstetricians in South Africa</p> <p>Methods</p> <p>A qualitative case-study approach was used. This included a literature review, a policy document review, a timeline of key events and the collection and analysis of 15 interviews with policy makers and academic clinicians involved in these policy processes and sampled using a purposive approach. The data was analysed thematically.</p> <p>Results</p> <p>The concept of evidence-based medicine became embedded in South African academic obstetrics at a very early stage in relation to the development of the concept internationally. The diffusion of this concept into local academic obstetrics was facilitated by contact and exchange between local academic obstetricians, opinion leaders in international research and structures promoting evidence-based practice. Furthermore the growing acceptance of the concept was stimulated locally through the use of existing professional networks and meetings to share ideas and the contribution of local researchers to building the evidence base for obstetrics both locally and internationally. As a testimony to the extent of the diffusion of evidence-based medicine, South Africa has strongly evidence-based policies for maternal health.</p> <p>Conclusion</p> <p>This case study shows that the combined efforts of local and international researchers can create a culture of evidence-based medicine within one country. It also shows that doing so required time and perseverance from international researchers combined with a readiness by local researchers to receive and actively promote the practice.</p