Targeting senescence to prevent diabetic kidney disease: Exploring molecular mechanisms and potential therapeutic targets for disease management.

Background/aims: As a microvascular complication, diabetic kidney disease is the leading cause of chronic kidney disease and end-stage renal disease worldwide. While the underlying pathophysiology driving transition of diabetic kidney disease to renal failure is yet to be fully understood, recent studies suggest that cellular senescence is central in disease development and progression. Consequently, understanding the molecular mechanisms which initiate and drive senescence in response to the diabetic milieu is crucial in developing targeted therapies that halt progression of renal disease.

Tonabersat suppresses priming/activation of the NOD-like receptor protein-3 (NLRP3) inflammasome and decreases renal tubular epithelial-to-macrophage crosstalk in a model of diabetic kidney disease.

Background: Accompanied by activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, aberrant connexin 43 (Cx43) hemichannel-mediated ATP release is situated upstream of inflammasome assembly and inflammation and contributes to multiple secondary complications of diabetes and associated cardiometabolic comorbidities. Evidence suggests there may be a link between Cx43 hemichannel activity and inflammation in the diabetic kidney. The consequences of blocking tubular Cx43 hemichannel-mediated ATP release in priming/activation of the NLRP3 inflammasome in a model of diabetic kidney disease (DKD) was investigated.

Reliability of Markerless Motion Capture Systems for Assessing Movement Screenings.

Background: Movement screenings are commonly used to detect unfavorable movement patterns. Markerless motion capture systems have been developed to track 3-dimensional motion.

Purpose: To determine the reliability of movement screenings assessed using a markerless motion capture system when comparing the results of multiple systems and multiple collection periods.

ψ(2S) Suppression in Pb-Pb Collisions at the LHC.

The production of the ψ(2S) charmonium state was measured with ALICE in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV, in the dimuon decay channel. A significant signal was observed for the first time at LHC energies down to zero transverse momentum, at forward rapidity (2.

CDKN2A-p16 Deletion and Activated KRAS Drive Barrett's-Like Gland Hyperplasia-Metaplasia and Synergize in the Development of Dysplasia Precancer Lesions.

Background & Aims: Barrett's esophagus is the precursor of esophageal dysplasia and esophageal adenocarcinoma. CDKN2A-p16 deletions were reported in 34%-74% of patients with Barrett's esophagus who progressed to dysplasia and esophageal adenocarcinoma, suggesting that p16 loss may drive neoplastic progression. KRAS activation frequently occurs in esophageal adenocarcinoma and precancer lesions.

Connexin-43 hemichannels orchestrate NOD-like receptor protein-3 (NLRP3) inflammasome activation and sterile inflammation in tubular injury.

Background: Without a viable cure, chronic kidney disease is a global health concern. Inflammatory damage in and around the renal tubules dictates disease severity and is contributed to by multiple cell types. Activated in response to danger associated molecular patterns (DAMPs) including ATP, the NOD-like receptor protein-3 (NLRP3) inflammasome is integral to this inflammation.

Measurement of the Lifetime and Λ Separation Energy of _{Λ}^{3}H.

The most precise measurements to date of the _{Λ}^{3}H lifetime τ and Λ separation energy B_{Λ} are obtained using the data sample of Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV collected by ALICE at the LHC. The _{Λ}^{3}H is reconstructed via its charged two-body mesonic decay channel (_{Λ}^{3}H→^{3}He+π^{-} and the charge-conjugate process).

Enhanced Deuteron Coalescence Probability in Jets.

The transverse-momentum (p_{T}) spectra and coalescence parameters B_{2} of (anti)deuterons are measured in p-p collisions at sqrt[s]=13  TeV for the first time in and out of jets. In this measurement, the direction of the leading particle with the highest p_{T} in the event (p_{T}^{lead}>5  GeV/c) is used as an approximation for the jet axis. The event is consequently divided into three azimuthal regions, and the jet signal is obtained as the difference between the toward region, that contains jet fragmentation products in addition to the underlying event (UE), and the transverse region, which is dominated by the UE.

Measurement of the J/ψ Polarization with Respect to the Event Plane in Pb-Pb Collisions at the LHC.

We study the polarization of inclusive J/ψ produced in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV at the LHC in the dimuon channel, via the measurement of the angular distribution of its decay products. We perform the study in the rapidity region 2.

Blocking connexin 43 hemichannel-mediated ATP release reduces communication within and between tubular epithelial cells and medullary fibroblasts in a model of diabetic nephropathy.

Introduction: Fibrosis of renal tubules is the final common pathway in diabetic nephropathy and develops in the face of tubular injury and fibroblast activation. Aberrant connexin 43 (Cx43) hemichannel activity has been linked to this damage under euglycaemic conditions, however, its role in glycaemic injury is unknown. This study investigated the effect of a Cx43 blocker (Tonabersat) on hemichannel activity and cell-cell interactions within and between tubular epithelial cells and fibroblasts in an in vitro model of diabetic nephropathy.

Quantification of bush-cricket acoustic trachea mechanics using Atomic Force Microscopy nanoindentation.

Derived from the respiratory tracheae, bush-crickets' acoustic tracheae (or ear canals) are hollow tubes evolved to transmit sounds from the external environment to the interior ear. Due to the location of the ears in the forelegs, the acoustic trachea serves as a structural element that can withstand large stresses during locomotion. In this study, we report a new Atomic Force Microscopy Force Spectroscopy (AFM-FS) approach to quantify the mechanics of taenidia in the bush-cricket Mecopoda elongata.

Hypertriton Production in p-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The study of nuclei and antinuclei production has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. The first measurement of the production of _{Λ}^{3}H in p-Pb collisions at sqrt[s_{NN}]=5.02  TeV is presented in this Letter.

The Role of the NLRP3 Inflammasome in Mediating Glomerular and Tubular Injury in Diabetic Nephropathy.

The NOD-like receptor protein 3 (NLRP3) inflammasome is a multi-protein signalling complex integral to the chronic inflammatory response, activated in response to sterile and non-sterile cellular damage. The assembly and activation of the NLRP3 inflammasome comprise a two-step process involving nuclear factor kappa B (NFkB)-mediated priming, followed by canonical, non-canonical or alternative signalling pathways. These result in the maturation and release of inflammatory cytokines interleukin 1 beta (IL1ß) and interleukin-18 (IL18), which are associated with chronic inflammatory conditions including diabetic kidney disease.

Polarization of Λ and Λ[over ¯] Hyperons along the Beam Direction in Pb-Pb Collisions at sqrt[s]_{NN}=5.02 TeV.

The polarization of the Λ and Λ[over ¯] hyperons along the beam (z) direction, P_{z}, has been measured in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV recorded with ALICE at the Large Hadron Collider (LHC). The main contribution to P_{z} comes from elliptic flow-induced vorticity and can be characterized by the second Fourier sine coefficient P_{z,s2}=⟨P_{z}sin(2φ-2Ψ_{2})⟩, where φ is the hyperon azimuthal emission angle and Ψ_{2} is the elliptic flow plane angle.

Measurement of Prompt D^{0}, Λ_{c}^{+}, and Σ_{c}^{0,++}(2455) Production in Proton-Proton Collisions at sqrt[s]=13 TeV.

The p_{T}-differential production cross sections of prompt D^{0}, Λ_{c}^{+}, and Σ_{c}^{0,++}(2455) charmed hadrons are measured at midrapidity (|y|<0.5) in pp collisions at sqrt[s]=13  TeV. This is the first measurement of Σ_{c}^{0,++} production in hadronic collisions.

Measurement of the Cross Sections of Ξ_{c}^{0} and Ξ_{c}^{+} Baryons and of the Branching-Fraction Ratio BR(Ξ_{c}^{0}→Ξ^{-}e^{+}ν_{e})/BR(Ξ_{c}^{0}→Ξ^{-}π^{+}) in pp Collisions at sqrt[s]=13 TeV.

The p_{T}-differential cross sections of prompt charm-strange baryons Ξ_{c}^{0} and Ξ_{c}^{+} were measured at midrapidity (|y|<0.5) in proton-proton (pp) collisions at a center-of-mass energy sqrt[s]=13  TeV with the ALICE detector at the LHC. The Ξ_{c}^{0} baryon was reconstructed via both the semileptonic decay (Ξ^{-}e^{+}ν_{e}) and the hadronic decay (Ξ^{-}π^{+}) channels.

Connexin 43: A Target for the Treatment of Inflammation in Secondary Complications of the Kidney and Eye in Diabetes.

Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working population, more than ever is there a demand to develop clinical interventions which can both delay and prevent disease progression. Connexins are membrane bound proteins that can form pores (hemichannels) in the cell membrane.

Λ_{c}^{+} Production and Baryon-to-Meson Ratios in pp and p-Pb Collisions at sqrt[s_{NN}]=5.02 TeV at the LHC.

The prompt production of the charm baryon Λ_{c}^{+} and the Λ_{c}^{+}/D^{0} production ratios were measured at midrapidity with the ALICE detector in pp and p-Pb collisions at sqrt[s_{NN}]=5.02  TeV. These new measurements show a clear decrease of the Λ_{c}^{+}/D^{0} ratio with increasing transverse momentum (p_{T}) in both collision systems in the range 2 View Article and Find Full Text PDF

Experimental Evidence for an Attractive p-ϕ Interaction.

This Letter presents the first experimental evidence of the attractive strong interaction between a proton and a ϕ meson. The result is obtained from two-particle correlations of combined p-ϕ⊕ p[over ¯]-ϕ pairs measured in high-multiplicity pp collisions at sqrt[s]=13  TeV by the ALICE Collaboration. The spin-averaged scattering length and effective range of the p-ϕ interaction are extracted from the fully corrected correlation function employing the Lednický-Lyuboshits approach.