126 research outputs found
Dysregulation of Ribosome Biogenesis and Translational Capacity Is Associated with Tumor Progression of Human Breast Cancer Cells
Protein synthesis is a fundamental cell process and ribosomes - particularly through the ribosomal RNA that display ribozyme activity - are the main effectors of this process. Ribosome biogenesis is a very complex process involving transcriptional a
Nucleolin Inhibits G4 Oligonucleotide Unwinding by Werner Helicase
The Werner protein (WRNp), a member of the RecQ helicase family, is strongly associated with the nucleolus, as is nucleolin (NCL), an important nucleolar constituent protein. Both WRNp and NCL respond to the effects of DNA damaging agents. Therefore, we have investigated if these nuclear proteins interact and if this interaction has a possible functional significance in DNA damage repair.Here we report that WRNp interacts with the RNA-binding protein, NCL, based on immunoprecipitation, immunofluorescent co-localization in live and fixed cells, and direct binding of purified WRNp to nucleolin. We also map the binding region to the C-terminal domains of both proteins. Furthermore, treatment of U2OS cells with 15 ”M of the Topoisomerase I inhibitor, camptothecin, causes the dissociation of the nucleolin-Werner complex in the nucleolus, followed by partial re-association in the nucleoplasm. Other DNA damaging agents, such as hydroxyurea, Mitomycin C, and aphidicolin do not have these effects. Nucleolin or its C-terminal fragment affected the helicase, but not the exonuclease activity of WRNp, by inhibiting WRN unwinding of G4 tetraplex DNA structures, as seen in activity assays and electrophoretic mobility shift assays (EMSA).These data suggest that nucleolin may regulate G4 DNA unwinding by WRNp, possibly in response to certain DNA damaging agents. We postulate that the NCL-WRNp complex may contain an inactive form of WRNp, which is released from the nucleolus upon DNA damage. Then, when required, WRNp is released from inhibition and can participate in the DNA repair processes
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36â39) and median bodyweight at presentation was 2·8 kg (2·3â3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; pâ€0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88â4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59â2·79], p<0·0001), sepsis at presentation (1·20 [1·04â1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4â5 vs ASA 1â2, 1·82 [1·40â2·35], p<0·0001; ASA 3 vs ASA 1â2, 1·58, [1·30â1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02â1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41â2·71], p=0·0001; parenteral nutrition 1·35, [1·05â1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47â0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50â0·86], p=0·0024) or percutaneous central line (0·69 [0·48â1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030
Test of lepton universality in decays
The first simultaneous test of muon-electron universality using
and decays is performed, in two ranges of the dilepton
invariant-mass squared, . The analysis uses beauty mesons produced in
proton-proton collisions collected with the LHCb detector between 2011 and
2018, corresponding to an integrated luminosity of 9 . Each
of the four lepton universality measurements reported is either the first in
the given interval or supersedes previous LHCb measurements. The
results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-046.html (LHCb
public pages
Observation of Two New Excited Îb0 States Decaying to Îb0 K-Ï+
Two narrow resonant states are observed in the Îb0K-Ï+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Îb0K-Ï+ system indicates that these are excited Îb0 baryons. The masses of the Îb(6327)0 and Îb(6333)0 states are m[Îb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Îb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Îm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Îb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Î[Îb(6327)0]<2.20(2.56) and Î[Îb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Îb0 resonances
Precision measurement of violation in the penguin-mediated decay
A flavor-tagged time-dependent angular analysis of the decay
is performed using collision data collected
by the LHCb experiment at % at TeV, the center-of-mass energy of
13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The
-violating phase and direct -violation parameter are measured
to be rad and
, respectively, assuming the same values
for all polarization states of the system. In these results, the
first uncertainties are statistical and the second systematic. These parameters
are also determined separately for each polarization state, showing no evidence
for polarization dependence. The results are combined with previous LHCb
measurements using collisions at center-of-mass energies of 7 and 8 TeV,
yielding rad and . This is the most precise study of time-dependent violation
in a penguin-dominated meson decay. The results are consistent with
symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb
public pages
Observation of a resonant structure near the threshold in the decay
An amplitude analysis of the decay is carried out to
study for the first time its intermediate resonant contributions, using
proton-proton collision data collected with the LHCb detector at centre-of-mass
energies of 7, 8 and 13 TeV. A near-threshold peaking structure, referred to as
, is observed in the invariant-mass spectrum with
significance greater than 12 standard deviations. The mass, width and the
quantum numbers of the structure are measured to be MeV,
MeV and , respectively, where the first
uncertainties are statistical and the second systematic. The properties of the
new structure are consistent with recent theoretical predictions for a state
composed of quarks. Evidence for an additional structure is
found around 4140 MeV in the invariant mass, which might be
caused either by a new resonance with the assignment or by a coupled-channel effect.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-018.html (LHCb
public pages
Measurement of the differential branching fraction
The branching fraction of the rare decay is measured for the first time, in the squared dimuon mass
intervals, , excluding the and regions. The data
sample analyzed was collected by the LHCb experiment at center-of-mass energies
of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\
\mathrm{fb}^{-1}q^{2}q^{2} >15.0\
\mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model
dependence, agrees with the predictions.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-050.html (LHCb
public pages
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