The Golgi is the cellular hub for complex glycosylation, controlling accurate processing of complex proteoglycans, receptors, ligands and glycolipids. Its structure and organisation are dependent on ...golgins, which tether cisternal membranes and incoming transport vesicles. Here, we show that knockout of the largest golgin, giantin, leads to substantial changes in gene expression but only limited effects on Golgi structure. Notably, 22 Golgi-resident glycosyltransferases, but not glycan-processing enzymes or the ER glycosylation machinery, are differentially expressed following giantin ablation. This includes near-complete loss of function of GALNT3 in both mammalian cell and zebrafish models. Giantin-knockout zebrafish exhibit hyperostosis and ectopic calcium deposits, recapitulating phenotypes of hyperphosphatemic familial tumoral calcinosis, a disease caused by mutations in GALNT3. These data reveal a new feature of Golgi homeostasis: the ability to regulate glycosyltransferase expression to generate a functional proteoglycome.
To ensure genomic medicine is delivered safely and effectively, it is crucial that healthcare professionals are able to understand and communicate genomic results. This Education Innovation describes ...a nationally agreed, cross‐professional competency framework outlining the knowledge, skills and behaviors required to communicate genomic results. Using principles of the nominal group technique, consensus meetings with clinical, scientific and educational experts identified six stages in the return of results process, drafted and iterated competencies. Competencies were then mapped across three levels to acknowledge different degrees of experiences and scopes of practice. The framework was open for consultation with healthcare professionals and patient communities before being published. The finalized framework includes six core competency statements required to communicate genomic results. This framework is designed to be a guide for best practice and a developmental tool to support individuals and organizations. It can be used by healthcare professionals, such as genetic counselors, to identify individual learning needs or to structure the development of training for other healthcare professionals who are increasingly involved in requesting and returning results for genomic tests.
Abstract
Despite considerable advances in knowledge of the anatomy, ecology and evolution of early mammals, far less is known about their physiology. Evidence is contradictory concerning the timing ...and fossil groups in which mammalian endothermy arose. To determine the state of metabolic evolution in two of the earliest stem-mammals, the Early Jurassic
Morganucodon
and
Kuehneotherium
, we use separate proxies for basal and maximum metabolic rate. Here we report, using synchrotron X-ray tomographic imaging of incremental tooth cementum, that they had maximum lifespans considerably longer than comparably sized living mammals, but similar to those of reptiles, and so they likely had reptilian-level basal metabolic rates. Measurements of femoral nutrient foramina show
Morganucodon
had blood flow rates intermediate between living mammals and reptiles, suggesting maximum metabolic rates increased evolutionarily before basal metabolic rates. Stem mammals lacked the elevated endothermic metabolism of living mammals, highlighting the mosaic nature of mammalian physiological evolution.
This study assessed the transfer of patients from paediatric cardiac to adult congenital heart disease (ACHD) services in England and the factors impacting on this process.
This retrospective cohort ...study used a population-based linked data set (LAUNCHES QI data set: 'Linking Audit and National datasets in Congenital Heart Services for Quality Improvement') including all patients born between 1987 and 2000, recorded as having a congenital heart disease (CHD) procedure in childhood. Hospital Episode Statistics data identified transfer from paediatric to ACHD services between the ages of 16 and 22 years.
Overall, 63.8% of a cohort of 10 298 patients transferred by their 22nd birthday. The estimated probability of transfer by age 22 was 96.5% (95% CI 95.3 to 97.7), 86.7% (95% CI 85.6 to 87.9) and 41.0% (95% CI 39.4 to 42.6) for severe, moderate and mild CHD, respectively. 166 patients (1.6%) died between 16 and 22 years; 42 of these (0.4%) died after age 16 but prior to transfer. Multivariable ORs in the moderate and severe CHD groups up to age 20 showed significantly lower likelihood of transfer among female patients (0.87, 95% CI 0.78 to 0.97), those with missing ethnicity data (0.31, 95% CI 0.18 to 0.52), those from deprived areas (0.84, 95% CI 0.72 to 0.98) and those with moderate (compared with severe) CHD (0.30, 95% CI 0.26 to 0.35). The odds of transfer were lower for the horizontal compared with the vertical care model (0.44, 95% CI 0.27 to 0.72). Patients who did not transfer had a lower probability of a further National Congenital Heart Disease Audit procedure between ages 20 and 30 compared with those who did transfer: 12.3% (95% CI 5.1 to 19.6) vs 32.5% (95% CI 28.7 to 36.3).
Majority of patients with moderate or severe CHD in England transfer to adult services. Patients who do not transfer undergo fewer elective CHD procedures over the following decade.
Cementum, the tissue attaching mammal tooth roots to the periodontal ligament, grows appositionally throughout life, displaying a series of circum-annual incremental features. These have been studied ...for decades as a direct record of chronological lifespan. The majority of previous studies on cementum have used traditional thin-section histological methods to image and analyse increments. However, several caveats have been raised in terms of studying cementum increments in thin-sections. Firstly, the limited number of thin-sections and the two-dimensional perspective they impart provide an incomplete interpretation of cementum structure, and studies often struggle or fail to overcome complications in increment patterns that complicate or inhibit increment counting. Increments have been repeatedly shown to both split and coalesce, creating accessory increments that can bias increment counts. Secondly, identification and counting of cementum increments using human vision is subjective, and it has led to inaccurate readings in several experiments studying individuals of known age. Here, we have attempted to optimise a recently introduced imaging modality for cementum imaging; X-ray propagation-based phase-contrast imaging (PPCI). X-ray PPCI was performed for a sample of rhesus macaque (Macaca mulatta) lower first molars (n = 10) from a laboratory population of known age. PPCI allowed the qualitative identification of primary/annual versus intermittent secondary increments formed by splitting/coalescence. A new method for semi-automatic increment counting was then integrated into a purpose-built software package for studying cementum increments, to count increments in regions with minimal complications. Qualitative comparison with data from conventional cementochronology, based on histological examination of tissue thin-sections, confirmed that X-ray PPCI reliably and non-destructively records cementum increments (given the appropriate preparation of specimens prior to X-ray imaging). Validation of the increment counting algorithm suggests that it is robust and provides accurate estimates of increment counts. In summary, we show that our new increment counting method has the potential to overcome caveats of conventional cementochronology approaches, when used to analyse three-dimensional images provided by X-ray PPCI.
Infection is a common complication in open fractures that compromises the healing of bone and can result in loss of limb or life. Currently, the clinical standard of care for treating contaminated ...open fractures comprises a staged approach, wherein the wound is first treated with non-biodegradable antibiotic-laden poly(methyl methacrylate) (PMMA) beads to control the infection followed by bone grafting. Considering that tissue regeneration is associated with new blood vessel formation, which takes up to 6
weeks in segmental defects, a biodegradable bone graft with sustained release of an antibiotic is desired to prevent the implant from becoming infected, thus allowing the processes of both vascularization and new bone formation to occur unimpeded. In the present study, we utilized biodegradable porous polyurethane (PUR) scaffolds as the delivery vehicle for vancomycin. Hydrophobic vancomycin free base (V-FB) was obtained by precipitating the hydrophilic vancomycin hydrochloride (V-HCl) at pH 8. The decreased solubility of V-FB resulted in an extended vancomycin release profile
in vitro, as evidenced by the fact that active vancomycin was released for up to 8
weeks at concentrations well above both the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Using PUR prepared from lysine triisocyanate (LTI) (PUR(LTI)), the extended
in vitro release profile observed for V-FB translated to improved infection control
in vivo compared to V-HCl in a contaminated critical-sized fat femoral segmental defect. The performance of PUR(LTI)/V-FB was comparable to PMMA/V-HCl beads
in vivo. However, compared with PMMA, PUR is a biodegradable system which does not require the extra surgical removal step in clinical use. These results suggest that PUR scaffolds incorporating V-FB could be a potential clinical therapy for treatment of infected bone defects.
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Understanding people’s willingness to participate in projects and programmes of payments for ecosystem services (PES) has not been a key analytical concern of the scholarly literature around this new ...field of environmental policy and practice. This paper analyses participation in four communities benefiting from payments for biodiversity and carbon fixation in Mexico, and contrasts the results for each case with neighbouring communities that do not receive payments. We take a holistic approach that accounts for procedural rules, actors’ interactions, institutions and values, and individuals’ characteristics. We show that the nature of PES rules and the effectiveness of communication with government officers and NGOs influence resource managers’ ability and willingness to participate. We highlight community size, resource managers’ ability to diversify livelihood activities and local perspectives on the conservation of common forests, particularly sacred values and intergenerational concerns on forest conservation, as critical participation drivers. This analysis provides insights on why and how these new institutions may be attractive for some resource managers and permits to draw some recommendations for the future design of PES projects and programmes.
Bubble nucleation in a cold spin 1 gas Billam, Thomas P; Brown, Kate; Moss, Ian G
New journal of physics,
04/2023, Letnik:
25, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract
Cold atomic gases offer the prospect of simulating the physics of the very early Universe in the laboratory. In the condensate phase, the gas is described by a field theory with key features ...of high energy particle theory. This paper describes a three level system which undergoes a first order phase transition through the nucleation of bubbles. The theoretical investigation shows bubbles nucleating in two dimensions at non-zero temperature. There is good agreement between the bubble nucleation rates calculated from a stochastic projected Gross–Pitaevskii equation and from a non-perturbative instanton method. When an optical box trap is included in the simulations, the bubbles nucleate preferentially near the walls of the trap.
Long-term survival is an important metric for health care evaluation, especially in functionally single-ventricle (f-SV) congenital heart disease (CHD). This study's aim was to evaluate the ...relationship between center volume and long-term survival in f-SV CHD within the centralized health care service of England and Wales.
This was a retrospective cohort study of children born with f-SV CHD between 2000 and 2018, using the national CHD procedure registry, with survival ascertained in 2020.
Of 56,039 patients, 3293 (5.9%) had f-SV CHD. Median age at first intervention was 7 days (interquartile range IQR, 4, 27), and median follow-up time was 7.6 years (IQR, 1.0, 13.3). The largest diagnostic subcategories were hypoplastic left heart syndrome, 1276 (38.8%); tricuspid atresia, 440 (13.4%); and double-inlet left ventricle, 322 (9.8%). The survival rate at 1 year and 5 years was 76.8% (95% confidence interval CI, 75.3%-78.2%) and 72.1% (95% CI, 70.6%-73.7%), respectively. The unadjusted hazard ratio for each 5 additional patients with f-SV starting treatment per center per year was 1.04 (95% CI, 1.02-1.06), P < .001. However, after adjustment for significant risk factors (diagnostic subcategory; antenatal diagnosis; younger age, low weight, acquired comorbidity, increased severity of illness at first procedure), the hazard ratio for f-SV center volume was 1.01 (95% CI, 0.99-1.04) P = .28. There was strong evidence that patients with more complex f-SV (hypoplastic left heart syndrome, Norwood pathway) were treated at centers with greater f-SV case volume (P < .001).
After adjustment for case mix, there was no evidence that f-SV center volume was linked to longer-term survival in the centralized health service provided by the 10 children's cardiac centers in England and Wales.
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