Biochemical Characterization of APPL Endosomes: The Role of Annexin A2 in APPL Membrane Recruitment

APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. They exhibit only limited colocalization with EEA1, another Rab5 effector and a marker of the canonical early endosomes. Although APPL endosomes appear to play important roles in cargo trafficking and signal transduction, their protein composition and biochemical properties remain largely unknown. Here we employed membrane fractionation methods to characterize APPL endosomes biochemically. We demonstrate that they represent heterogeneous membrane structures which can be discriminated from the canonical EEA1-positive early endosomes by their partly different physical properties and a distinct migration pattern in the continuous density gradients. In search for other potential markers of APPL endosomes we identified Annexin A2 as an interacting partner of both APPL1 and APPL2. Annexin A2 is a Ca2+ and phosphatidylinositol 4,5-bisphosphate binding protein, previously implicated in several endocytic steps. We show that Annexin A2 co-fractionates and colocalizes with APPL endosomes. Moreover, silencing of its expression causes solubilization of APPL2 from endosomes. Although Annexin A2 is not an exclusive marker of APPL endosomes, our data suggest that it has an important function in membrane recruitment of APPL proteins, acting in parallel to Rab5

Revealing important nocturnal and day-to-day variations in fire smoke emissions through a multiplatform inversion

We couple airborne, ground-based, and satellite observations; conduct regional simulations; and develop and apply an inversion technique to constrain hourly smoke emissions from the Rim Fire, the third largest observed in California, USA. Emissions constrainedwithmultiplatform data show notable nocturnal enhancements (sometimes over a factor of 20), correlate better with daily burned area data, and are a factor of 2–4 higher than a priori estimates, highlighting the need for improved characterization of diurnal profiles and day-to-day variability when modeling extreme fires. Constraining only with satellite data results in smaller enhancements mainly due to missing retrievals near the emissions source, suggesting that top-down emission estimates for these events could be underestimated and a multi-platform approach is required to resolve them. Predictions driven by emissions constrained with multi-platform data present significant variations in downwind air quality and in aerosol feedback on meteorology, emphasizing the need for improved emissions estimates during exceptional events

Landscape homogenization due to agricultural intensification disrupts the relationship between reproductive success and main prey abundance in an avian predator

Selecting high-quality habitat and the optimal time to reproduce can increase individual fitness and is a strong evolutionary factor shaping animal populations. However, few studies have investigated the interplay between land cover heterogeneity, limitation in food resources, individual quality and spatial variation in fitness parameters. Here, we explore how individuals of different quality respond to possible mismatches between a cue for prey availability (land cover heterogeneity) and the actual fluctuating prey abundance.Peer reviewe

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn(2+) atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes

Updated measurements of exclusive J/ψ and ψ(2S) production cross-sections in pp collisions at √s = 7 TeV

The differential cross-section as a function of rapidity has been measured for the exclusive production of J/ψ and ψ(2S) mesons in proton–proton collisions at √s = 7 TeV, using data collected by the LHCb experiment, corresponding to an integrated luminosity of 930 pb−1. The cross-sections times branching fractions to two muons having pseudorapidities between 2.0 and 4.5 are measured to be where the first uncertainty is statistical and the second is systematic. The measurements agree with next-to-leading order QCD predictions as well as with models that include saturation effects

Measurement of the Λb0, Ξb-, and Ωb- Baryon Masses

Bottom baryons decaying to a J/ψ meson and a hyperon are reconstructed using 1.0  fb-1 of data collected in 2011 with the LHCb detector. Significant Λb0→J/ψΛ, Ξb-→J/ψΞ- and Ωb-→J/ψΩ- signals are observed and the corresponding masses are measured to be M(Λb0)=5619.53±0.13(stat.)±0.45(syst.)  MeV/c2, M(Ξb-)=5795.8±0.9(stat.)±0.4(syst.)  MeV/c2, M(Ωb-)=6046.0±2.2(stat.)±0.5(syst.)  MeV/c2, while the differences with respect to the Λb0 mass are M(Ξb-)-M(Λb0)=176.2±0.9(stat.)±0.1(syst.)  MeV/c2, M(Ωb-)-M(Λb0)=426.4±2.2(stat.)±0.4(syst.)  MeV/c2. These are the most precise mass measurements of the Λb0, Ξb- and Ωb- baryons to date. Averaging the above Λb0 mass measurement with that published by LHCb using 35  pb-1 of data collected in 2010 yields M(Λb0)=5619.44±0.13(stat.)±0.38(syst.)  MeV/c2

Global injury morbidity and mortality from 1990 to 2017 : results from the Global Burden of Disease Study 2017

Correction:Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.Peer reviewe

Measurement of ZZ boson production cross-section in pppp collisions at s=5.02\sqrt{s} = 5.02 TeV

The first measurement of the $Z$ boson production cross-section at centre-of-mass energy $\sqrt{s} = 5.02\,$TeV in the forward region is reported, using $pp$ collision data collected by the LHCb experiment in year 2017, corresponding to an integrated luminosity of $100 \pm 2\,\rm{pb^{-1}}$. The production cross-section is measured for final-state muons in the pseudorapidity range $2.0 20\,\rm{GeV/}\it{c}$. The integrated cross-section is determined to be $$\sigma_{Z \rightarrow \mu^{+}\mu^{-}} = 39.6 \pm 0.7\,(\rm{stat}) \pm 0.6\,(\rm{syst}) \pm 0.8\,(\rm{lumi}) \ \rm{pb}$$ for the di-muon invariant mass in the range $60<M_{\mu\mu}<120\,\rm{GeV/}\it{c^{2}}$. This result and the differential cross-section results are in good agreement with theoretical predictions at next-to-next-to-leading order in the strong coupling. Based on a previous LHCb measurement of the $Z$ boson production cross-section in $p$Pb collisions at $\sqrt{s_{NN}}=5.02$ TeV, the nuclear modification factor $R_{p\rm{Pb}}$ is measured for the first time at this energy. The measured values are $1.2^{+0.5}_{-0.3}\,(\rm{stat}) \pm 0.1\,(\rm{syst})$ in the forward region ($1.53<y^*_{\mu}<4.03$) and $3.6^{+1.6}_{-0.9}\,(\rm{stat}) \pm 0.2\,(\rm{syst})$ in the backward region ($-4.97<y^*_{\mu}<-2.47$), where $y^*_{\mu}$ represents the muon rapidity in the centre-of-mass frame.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-010.html (LHCb public pages