Bardet-Biedl syndrome proteins control cilia length through regulation of actin polymerisation.

Primary cilia are cellular appendages important for signal transduction and sensing the environment. Bardet-Biedl syndrome proteins form a complex that is important for several cytoskeleton-related processes such as ciliogenesis, cell migration and division. However, the mechanisms by which BBS proteins may regulate the cytoskeleton remain unclear. We discovered that Bbs4 and Bbs6 deficient renal medullary cells display a characteristic behaviour comprising poor migration, adhesion and division with an inability to form lamellipodial and filopodial extensions. Moreover, fewer mutant cells were ciliated (48% ± 6 for wild-type cells vs 23% ± 7 for Bbs4 null cells; P-value < 0.0001) and their cilia were shorter (2.55&emsp14;μm ± 0.41 for wild-type cells vs 2.16&emsp14;μm ± 0.23 for Bbs4 null cells; P-value < 0.0001). Whilst the microtubular cytoskeleton and cortical actin were intact, actin stress fibre formation was severely disrupted, forming abnormal apical stress fibre aggregates. Furthermore, we observed over-abundant focal adhesions in Bbs4, Bbs6 and Bbs8-deficient cells. In view of these findings and the role of RhoA in regulation of actin filament polymerisation, we showed that RhoA-GTP levels were highly upregulated in the absence of Bbs proteins. Upon treatment of Bbs4-deficient cells with chemical inhibitors of RhoA, we were able to restore cilia length and number as well as the integrity of the actin cytoskeleton. Together these findings indicate that Bbs proteins play a central role in the regulation of the actin cytoskeleton and control cilia length through alteration of RhoA levels

Sorption direct air capture with CO2 utilization

Direct air capture (DAC) is gathering momentum since it has vast potential and high flexibility to collect CO2 from discrete sources as “synthetic tree” when compared with current CO2 capture technologies, e.g., amine based post-combustion capture. It is considered as one of the emerging carbon capture technologies in recent decades and remains in a prototype investigation stage with many technical challenges to be overcome. The objective of this paper is to comprehensively discuss the state-of-the-art of DAC and CO2 utilization, note unresolved technology bottlenecks, and give investigation perspectives for commercial large-scale applications. Firstly, characteristics of physical and chemical sorbents are evaluated. Then, the representative capture processes, e.g., pressure swing adsorption, temperature swing adsorption and other ongoing absorption chemical loops, are described and compared. Methods of CO2 conversion including synthesis of fuels and chemicals as well as biological utilization are reviewed. Finally, techno-economic analysis and life cycle assessment for DAC application are summarized. Based on research achievements, future challenges of DAC and CO2 conversion are presented, which include providing synthesis guidelines for obtaining sorbents with the desired characteristics, uncovering the mechanisms for different working processes and establishing evaluation criteria in terms of technical and economic aspects

Clinical debriefing during the COVID-19 pandemic: hurdles and opportunities for healthcare teams

The COVID-19 pandemic and the subsequent pressures on healthcare staff and resources have exacerbated the need for clinical teams to reflect and learn from workplace experiences. Surges in critically ill patients, the impact of the disease on the workforce and long term adjustments in work and life have upturned our normality. Whilst this situation has generated a new 'connectedness' within healthcare workers, it also continues to test our resilience. An international multi-professional collaboration has guided the identification of ongoing difficulties to effective communication and debriefing, as well as emerging opportunities to promote a culture of dialogue. This article outlines pandemic related barriers and new possibilities categorising them according to task management, teamwork, situational awareness and decision making. It describes their direct and indirect impact on clinical debriefing and signposts towards solutions to overcome challenges and, building on new bridges, advance team conversations that allow us to learn, improve and support each other. This pandemic has brought clinical professionals together; nevertheless, it is essential to invest in further developing and supporting cohesive teams. Debriefing enables healthcare teams and educators to mitigate stress, build resilience and promote a culture of continuous learning and patient care improvement

Short-term regulation of peptide YY secretion by a mixed meal or peritoneal glucose-based dialysate in patients with chronic renal failure

This is a pre-copyedited, author-produced version of an article accepted for publication in "Nephrology Dialysis Trasnplantation" following peer review. The version of the record is avaliable online at Oxford Academic website.Instituto de Salud Carlos III, PI051024Instituto de Salud Carlos III, PI070413Xunta de Galicia, PS07/12Xunta de Galicia, 2006/2

R-parity violation in SU(5)

We show that judiciously chosen R-parity violating terms in the minimal renormalizable supersymmetric SU(5) are able to correct all the phenomenologically wrong mass relations between down quarks and charged leptons. The model can accommodate neutrino masses as well. One of the most striking consequences is a large mixing between the electron and the Higgsino. We show that this can still be in accord with data in some regions of the parameter space and possibly falsified in future experiments.Comment: 30 pages, 1 figure. Revised version. To appear in JHE

Realistic Standard Model Fermion Mass Relations in Generalized Minimal Supergravity (GmSUGRA)

Grand Unified Theories (GUTs) usually predict wrong Standard Model (SM) fermion mass relation m_e/m_{\mu} = m_d/m_s toward low energies. To solve this problem, we consider the Generalized Minimal Supergravity (GmSUGRA) models, which are GUTs with gravity mediated supersymmetry breaking and higher dimensional operators. Introducing non-renormalizable terms in the super- and K\"ahler potentials, we can obtain the correct SM fermion mass relations in the SU(5) model with GUT Higgs fields in the {\bf 24} and {\bf 75} representations, and in the SO(10) model. In the latter case the gauge symmetry is broken down to SU(3)_C X SU(2)_L X SU(2)_R X U(1)_{B-L}, to flipped SU(5)X U(1)_X, or to SU(3)_C X SU(2)_L X U(1)_1 X U(1)_2. Especially, for the first time we generate the realistic SM fermion mass relation in GUTs by considering the high-dimensional operators in the K\"ahler potential.Comment: JHEP style, 29 pages, no figure,references adde

Experimental aspects of SU(5)xU(1) supergravity

We study various aspects of $SU(5)\times U(1)$ supergravity as they relate to the experimental verification or falsification of this model. We consider two string-inspired, universal, one-parameter, no-scale soft-supersymmetry-breaking scenarios, driven by the $F$-terms of the moduli and dilaton fields. The model is described in terms of the supersymmetry mass scale (\ie, the chargino mass $m_{\chi^\pm_1}$), $\tan\beta$, and the top-quark mass. We first determine the combined effect on the parameter space of all presently available direct and indirect experimental constraints, including the LEP lower bounds on sparticle and Higgs-boson masses, the $b\to s\gamma$ rate, the anomalous magnetic moment of the muon, the high-precision electroweak parameters $\epsilon_1,\epsilon_b$ (which imply m_t\lsim180\GeV), and the muon fluxes in underground detectors (neutrino telescopes). For the still-allowed points in $(m_{\chi^\pm_1},\tan\beta)$ parameter space, we re-evaluate the experimental situation at the Tevatron, LEPII, and HERA. In the 1994 run, the Tevatron could probe chargino masses as high as 100 GeV. At LEPII the parameter space could be explored with probes of different resolutions: Higgs boson searches, selectron searches, and chargino searches. Moreover, for m_t\lsim150\GeV, these Higgs-boson searches could explore all of the allowed parameter space with \sqrt{s}\lsim210\GeV.Comment: latex, 36 pages, 25 figures (not included). Figures are available via anonymous ftp from hplaa02.cern.ch (/pub/lopez) as either 33 ps files (Easpects*.ps, 8.1MB) or one uuencoded file (AllFigures.uu, 3.7MB

A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies

Despite rapid advances in the identification of genes involved in disease, the predictive power of the genotype remains limited, in part owing to poorly understood effects of second-site modifiers. Here we demonstrate that a polymorphic coding variant of RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein-1 like), a ciliary gene mutated in Meckel-Gruber (MKS) and Joubert (JBTS) syndromes, is associated with the development of retinal degeneration in individuals with ciliopathies caused by mutations in other genes. As part of our resequencing efforts of the ciliary proteome, we identified several putative loss-of-function RPGRIP1L mutations, including one common variant, A229T. Multiple genetic lines of evidence showed this allele to be associated with photoreceptor loss in ciliopathies. Moreover, we show that RPGRIP1L interacts biochemically with RPGR, loss of which causes retinal degeneration, and that the Thr229-encoded protein significantly compromises this interaction. Our data represent an example of modification of a discrete phenotype of syndromic disease and highlight the importance of a multifaceted approach for the discovery of modifier alleles of intermediate frequency and effect.This work was supported by grants R01EY007961 from the National Eye Institute (H.K. and A.S.), R01HD04260 from the National Institute of Child Health and Development (N.K.), R01DK072301, R01DK075972 (N.K.), R01DK068306, R01DK064614, R01DK069274 (F.H.), NRSA fellowship F32 DK079541 (E.E.D.) from the National Institute of Diabetes, Digestive and Kidney disorders, Intramural program of NEI (A.S.), the Macular Vision Research Foundation (N.K.), the Foundation for Fighting Blindness (H.K., S.S.B., A.S. and N.K.), the Foundation for Fighting Blindness Canada (R.K.K.), Le Fonds de la recherche en sante du Québec (FRSQ) (R.K.K.), Research to Prevent Blindness (A.S.), Harold Falls Collegiate Professorship (A.S.), the Midwest Eye Banks and Transplantation Center (H.K.), the Searle Scholars Program (M.A.B.), the Deutsche Forschungsgemeinschaft (DFG grant BE 3910/4-1; C.B.) the UK Medical Research Council (grant number G0700073; C.A.J.), NIHR Biomedical Research Centre for Ophthalmology (S.S.B.) and EU-GENORET Grant LSHG-CT-2005-512036 (S.S.B.). F.H. is an investigator of the Howard Hughes Medical Institute (HHMI) and a Doris Duke Distinguished Clinical Scientist (DDCF)

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia

Introduction: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. Patients and methods: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. Results: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94–1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97–1.22). Discussion and conclusion: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself