Variation in Basal Body Localisation and Targeting of Trypanosome RP2 and FOR20 Proteins

TOF-LisH-PLL motifs defines FOP family proteins; some members are involved in flagellum assembly. The critical role of FOP family protein FOR20 is poorly understood. Here, we report relative localisations of the four FOP family proteins in parasitic Trypanosoma brucei: TbRP2, TbOFD1 and TbFOP/FOP1-like are mature basal body proteins whereas TbFOR20 is present on pro- and mature basal bodies – on the latter it localises distal to TbRP2. We discuss how the data, together with published work for another protist Giardia intestinalis, informs on likely FOR20 function. Moreover, our localisation study provides convincing evidence that the antigen recognised by monoclonal antibody YL1/2 at trypanosome mature basal bodies is FOP family protein TbRP2, not tyrosinated α-tubulin as widely stated in the literature. Curiously, FOR20 proteins from T. brucei and closely related African trypanosomes possess short, negatively-charged N-terminal extensions absent from FOR20 in other trypanosomatids and other eukaryotes. The extension is necessary for protein targeting, but insufficient to re-direct TbRP2 to probasal bodies. Yet, FOR20 from the American trypanosome T. cruzi, which lacks any extension, localises to pro- and mature basal bodies when expressed in T. brucei. This identifies unexpected variation in FOR20 architecture that is presently unique to one clade of trypanosomatids

The debris disk around gamma Doradus resolved with Herschel

We present observations of the debris disk around gamma Doradus, an F1V star, from the Herschel Key Programme DEBRIS (Disc Emission via Bias-free Reconnaissance in the Infrared/Submillimetre). The disk is well-resolved at 70, 100 and 160 micron, resolved along its major axis at 250 micron, detected but not resolved at 350 micron, and confused with a background source at 500 micron. It is one of our best resolved targets and we find it to have a radially broad dust distribution. The modelling of the resolved images cannot distinguish between two configurations: an arrangement of a warm inner ring at several AU (best-fit 4 AU) and a cool outer belt extending from ~55 to 400 AU or an arrangement of two cool, narrow rings at ~70 AU and ~190 AU. This suggests that any configuration between these two is also possible. Both models have a total fractional luminosity of ~10^{-5} and are consistent with the disk being aligned with the stellar equator. The inner edge of either possible configuration suggests that the most likely region to find planets in this system would be within ~55 AU of the star. A transient event is not needed to explain the warm dust's fractional luminosity.Comment: 12 pages, 6 figures, accepted for publication in Ap

Computerised speechreading training for deaf children: A randomised controlled trial

Purpose: We developed and evaluated in a randomised controlled triala computerised speechreading training programme to determine a) whether it is possible to train speechreading in deaf children and b) whether speechreading training results in improvements in phonological and reading skills.Previous studies indicate a relationship between speechreading and reading skill and further suggest this relationshipmay be mediated by improved phonological representations. This is important since many deaf children find learning to read to be very challenging. Method: Sixty-six deaf 5-7 year olds were randomised into speechreading and maths training arms. Each training programme was comprised of10 minutesessionsa day, 4 days a week for 12 weeks. Children were assessed on a battery of language and literacy measures before training, immediately after training, 3 months and 10 months after training. Results: We found no significant benefits for participants who completed the speechreading training, compared to those who completed the maths training, on the speechreading primary outcome measure. However, significantly greater gains were observed in the speechreading training group on one of the secondary measures of speechreading. There was also some evidence of beneficial effects of the speechreading training on phonological representations, however these effects were weaker. No benefits were seen toword reading. Conclusions: Speechreading skill is trainable in deaf children. However, to support early reading, training may need to be longer or embedded in a broader literacy programme. Nevertheless, a training tool that can improve speechreading is likely to be of great interest to professionals working with deaf children

A Comparison of Flexed Vs. Relaxed Skinfold Methodology in College Aged Males and Females

Skinfold caliper measurements are routinely utilized in assessing individual’s body composition and subcutaneous fat thicknesses. The precise separation of subcutaneous fat from muscle is critical to obtaining accurate measurements of body composition. The current investigation examined the accuracy of a flexed skinfold method (FSM) compared to the traditional relaxed skinfold method (RSF) and DEXA in 20 males (mean age = 20.8 + 2.5 yrs) and 20 females (mean age = 20.8 + 1.6 yrs). Body composition was assessed by FSM and RSF in a counterbalanced design within gender for RSF and FSM, using Lange skinfold calipers with the Jackson-Pollock 3-site method and the Siri’s percent body fat equation. Each site (chest, umbilical, and thigh for males; triceps, super iliac, and thigh for females) was measured three times and the average was utilized to calculate body density and percent body fat. The same researcher performed all skinfold measurements and DEXA scan on a single occasion. A 2 X 3 ANOVA was used to determine the effect of gender (females and males) and different body composition methods (FSM, RSM, and DEXA) along with Bland-Altman plots. No statistical differences were observed between FSM and RSM in body fat percentage (FSM: 15.7 + 7.5% vs. RSM: 16.0 + 7.5%; p = 0.74), chest (FSM: 4.3 + 1.2mm vs. RSM: 4.6 + 1.6mm; p = 0.83), triceps (FSM: 18.7 + 6.1mm vs. RSM: 18.6 + 5.4mm; p = 0.52), super iliac (FSM: 15.2 + 4.3mm vs. RSM: 15.1 + 4.8mm; p = 0.62), or umbilical measurement (FSM: 17.1 + 6.3mm vs. RSM: 17.3 + 6.2mm; p = 0.62). However, there was a significant difference in thigh skinfold location, indicating that subcutaneous fat measured by FSM was lower than one measured by RSM (FL: 17.5 + 7.2mm, RL: 18.5 + 7.4mm; p = 0.003). Additionally, both FSM and RSM underestimated body fat percentage as compared to DEXA (FSM: 15.7 + 7.5%, RSM: 16.0 + 7.5%, vs. DEXA: 18.9 + 7.5%; p \u3c 0.01). It appears that assessing overall body composition using a flexed skinfold method does not necessarily improve the overall accuracy of skinfold body composition measurement when compared against a relaxed method

Exploring 4D Quantum Hall Physics with a 2D Topological Charge Pump

The discovery of topological states of matter has profoundly augmented our understanding of phase transitions in physical systems. Instead of local order parameters, topological phases are described by global topological invariants and are therefore robust against perturbations. A prominent example thereof is the two-dimensional integer quantum Hall effect. It is characterized by the first Chern number which manifests in the quantized Hall response induced by an external electric field. Generalizing the quantum Hall effect to four-dimensional systems leads to the appearance of a novel non-linear Hall response that is quantized as well, but described by a 4D topological invariant - the second Chern number. Here, we report on the first observation of a bulk response with intrinsic 4D topology and the measurement of the associated second Chern number. By implementing a 2D topological charge pump with ultracold bosonic atoms in an angled optical superlattice, we realize a dynamical version of the 4D integer quantum Hall effect. Using a small atom cloud as a local probe, we fully characterize the non-linear response of the system by in-situ imaging and site-resolved band mapping. Our findings pave the way to experimentally probe higher-dimensional quantum Hall systems, where new topological phases with exotic excitations are predicted

Role of Acid Sphingomyelinase in Shifting the Balance Between Proinflammatory and Reparative Bone Marrow Cells in Diabetic Retinopathy

The metabolic insults associated with diabetes lead to low-grade chronic inflammation, retinal endothelial cell damage, and inadequate vascular repair. This is partly due to the increased activation of bone marrow (BM)-derived proinflammatory monocytes infiltrating the retina, and the compromised function of BM-derived reparative circulating angiogenic cells (CACs), which home to sites of endothelial injury and foster vascular repair. We now propose that a metabolic link leading to activated monocytes and dysfunctional CACs in diabetes involves upregulation of a central enzyme of sphingolipid signaling, acid sphingomyelinase (ASM). Selective inhibition of ASM in the BM prevented diabetes-induced activation of BM-derived microglia-like cells and normalized proinflammatory cytokine levels in the retina. ASM upregulation in diabetic CACs caused accumulation of ceramide on their cell membrane, thereby reducing membrane fluidity and impairing CAC migration. Replacing sphingomyelin with ceramide in synthetic membrane vesicles caused a similar decrease in membrane fluidity. Inhibition of ASM in diabetic CACs improved membrane fluidity and homing of these cells to damaged retinal vessels. Collectively, these findings indicate that selective modulation of sphingolipid metabolism in BM-derived cell populations in diabetes normalizes the reparative/proinflammatory cell balance and can be explored as a novel therapeutic strategy for treating diabetic retinopathy

Long-term survival and center volume for functionally single-ventricle congenital heart disease in England and Wales

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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

Experimental Measurement of the Berry Curvature from Anomalous Transport

Geometrical properties of energy bands underlie fascinating phenomena in a wide-range of systems, including solid-state materials, ultracold gases and photonics. Most famously, local geometrical characteristics like the Berry curvature can be related to global topological invariants such as those classifying quantum Hall states or topological insulators. Regardless of the band topology, however, any non-zero Berry curvature can have important consequences, such as in the semi-classical evolution of a wave packet. Here, we experimentally demonstrate for the first time that wave packet dynamics can be used to directly map out the Berry curvature. To this end, we use optical pulses in two coupled fibre loops to study the discrete time-evolution of a wave packet in a 1D geometrical "charge" pump, where the Berry curvature leads to an anomalous displacement of the wave packet under pumping. This is both the first direct observation of Berry curvature effects in an optical system, and, more generally, the proof-of-principle demonstration that semi-classical dynamics can serve as a high-resolution tool for mapping out geometrical properties

Quantifying Additional Procedures in Functionally Single-Ventricle Disease: A National Cohort Study

Background: Given their importance as a metric for health care evaluation, this study’s aim was to evaluate the rates of surgical and catheter reinterventions for children with functionally single-ventricle (f-SV) congenital heart disease (CHD) undergoing staged palliation. // Methods: We undertook a retrospective cohort study of children born with f-SV CHD between 2000 and 2018 in England and Wales, using the national registry, with survival ascertained in 2020. Competing risk analysis was used to describe the incidence of additional procedures that occurred first, during follow-up, accounting for competing events of death or transplantation. // Results: Of 56,039 patients who received an intervention for CHD, 3307 (5.9%) had f-SV. The largest diagnostic subcategories were hypoplastic left heart syndrome (1266 [38.3%]), tricuspid atresia (448 [13.5%]), and double-inlet left ventricle (328 [9.9%]). During a median follow-up of 5.4 (interquartile range, 0.8-10.8) years, 921 (27.9%) patients had at least 1 additional interstage surgery and 1293 (39.1%) had at least 1 additional interstage catheter intervention. The cumulative incidence of additional surgery at 6 months after stage 1 was 17.6% (95% CI, 16.2%-19.0%); at 2 years after stage 2, 8.3% (7.2%-9.5%); and at 5 years after stage 3, 8.4% (7.0%-9.9%). The cumulative incidence of additional catheter at 6 months after stage 1 was 18.0% (16.6%-19.4%); at 2 years after stage 2, 14.7% (13.3%-16.2%); and at 5 years after stage 3, 23.7% (21.5%-26.0%). // Conclusions: It is important to quantify additional procedures for children with f-SV disease to inform parents and health professionals, potentially facilitating the development of interventions that aim to reduce these important adverse outcomes