Ion channels and pain in Fabry disease

Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A (α-Gal A) activity which results in progressive accumulation of globotriaosylceramide (Gb3) and related metabolites. One prominent feature of Fabry disease is neuropathic pain. Accumulation of Gb3 has been documented in dorsal root ganglia (DRG) as well as other neurons, and has lately been associated with the mechanism of pain though the pathophysiology is still unclear. Small fiber (SF) neuropathy in FD differs from other entities in several aspects related to the perception of pain, alteration of fibers as well as drug therapies used in the practice with patients, with therapies far from satisfying. In order to develop better treatments, more information on the underlying mechanisms of pain is needed. Research in neuropathy has gained momentum from the development of preclinical models where different aspects of pain can be modelled and further analyzed. This review aims at describing the different in vitro and FD animal models that have been used so far, as well as some of the insights gained from their use. We focus especially in recent findings associated with ion channel alterations -that apart from the vascular alterations-, could provide targets for improved therapies in pain.Fil: Weissmann, Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Albanese, Adriana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Contreras, Natalia Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Gobetto, María Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Salinas Castellanos, Libia Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Gender and youth responsiveness considerations for targeting, testing and scaling suitable CSA practices and technologies: Learnings from the Climate-Smart Villages

This working paper summarizes the findings of a portfolio review conducted to explore the gender and youth responsiveness of climate-smart agriculture technologies tested across climate-smart villages. The innovative and integrative aspect of the Climate-Smart Village (CSV) approach can provide useful insights into how to decrease the gender gap in the context of climate change. The diverse settings of CSVs (across East and West Africa, South and Southeast Asia and Latin America) and long program timeline, present a unique opportunity to gather learnings for the broader agriculture research for development community and practitioners. Toward these points, this paper aims to assess how gender and youth responsiveness was integrated into the process of identifying, testing, promoting, and scaling suitable CSA practices and technologies in the context of the implementation of the CSV approach. The review found that collective action and local partner engagement has proved to be very successful in the CSVs in regards to gender outcomes. To improve the gender and youth responsiveness of CSVs, it is essential taking those considerations into account from the very beginning of the project design, as well as having a GSI expert involved

Lessons Learned on Participatory Action Research to Adoption of Climate Smart Agricultural Options with an Emphasis on Gender and Social Inclusion

Participatory action research (PAR) has been around for years, and can add significant value to agriculture research for development projects. The use of PAR in climate-smart villages (CSVs) is no different. This review aimed to assess the impact that PAR approaches had on the adoption of CSA practices and technologies, with an emphasis on gender and social inclusion. Through a portfolio review, interviews with regional CSV teams, and surveys sent to local partners, this report demonstrates the benefit of PAR use in the implementation of the CSV approach. Specifically, the working paper discusses how the use of PAR methods can facilitate social learning, increase adoption rates and improve access to climate information services (CIS) to inform better decision-making. It can also foster conversations around gender roles and dynamics, improve women and youth’s participation in CSA activities, and contribute to scaling. Additionally, PAR can provide communities with a sense of ownership over projects, which can make interventions more sustainable even after the project cycle has ended

CCAFS Outcome Synthesis Report: Outcomes Achieved Within the Context of Climate-Smart Village Approach

This working paper aims to assess outcome cases related to the AR4D Climate-Smart Village (CSV) approach. It presents results from a review of annual outcome case studies reported under the CCAFS program between 2012-2020. This review focused on outcomes directly related to the implementation of the CSV approach as well as those that took place within the context of CSV work or were informed by evidence generated in the CSV specifically aimed to address the following key questions: 1. What types of outcomes based on CSV related work were achieved? What changed in the next user? 2. How were these outcomes achieved? What was crucial to the change in next users? What key partners were involved

Hacia una visión compartida sobre la seguridad climática en Guatemala

Este infore explora las interconexiones entre el cambio climático, la seguridad humana y los conflictos en Guatemala basándose en el Taller sobre Seguridad Climática celebrado en Ciudad de Guatemala los días 21 y 22 de febrero de 2023. Las implicaciones del cambio climático para la seguridad, comúnmente conocidas como el nexo clima-seguridad, han sido ampliamente discutidas tanto en círculos políticos como académicos. La seguridad climática se refiere las amenazas y riesgos de seguridad a estados, sociedades e individuos causados directa o indirectamente por los efectos del cambio climático. Los riesgos de seguridad en este documento son entendidos de una manera amplia enfocándose no solo en los riesgos de seguridad nacional vistos desde el punto de vista de los estados sino, principalmente, en los riesgos de seguridad humana enfocados en los retos para la supervivencia y los medios de vida de la población que incluye la seguridad económica, alimentaria, sanitaria, medioambiental, personal, comunitaria y política (UNTFHS, 2016)

Multiplicity dependence of light (anti-)nuclei production in p–Pb collisions at sNN=5.02 TeV

The measurement of the deuteron and anti-deuteron production in the rapidity range −1 < y < 0 as a function of transverse momentum and event multiplicity in p–Pb collisions at √sNN = 5.02 TeV is presented. (Anti-)deuterons are identified via their specific energy loss dE/dx and via their time-of- flight. Their production in p–Pb collisions is compared to pp and Pb–Pb collisions and is discussed within the context of thermal and coalescence models. The ratio of integrated yields of deuterons to protons (d/p) shows a significant increase as a function of the charged-particle multiplicity of the event starting from values similar to those observed in pp collisions at low multiplicities and approaching those observed in Pb–Pb collisions at high multiplicities. The mean transverse particle momenta are extracted from the deuteron spectra and the values are similar to those obtained for p and particles. Thus, deuteron spectra do not follow mass ordering. This behaviour is in contrast to the trend observed for non-composite particles in p–Pb collisions. In addition, the production of the rare 3He and 3He nuclei has been studied. The spectrum corresponding to all non-single diffractive p-Pb collisions is obtained in the rapidity window −1 < y < 0 and the pT-integrated yield dN/dy is extracted. It is found that the yields of protons, deuterons, and 3He, normalised by the spin degeneracy factor, follow an exponential decrease with mass number

Energy dependence of coherent photonuclear production of J/ψ mesons in ultra-peripheral Pb-Pb collisions at sNN \sqrt{{\textrm{s}}_{\textrm{NN}}} = 5.02 TeV

International audienceThe cross section for coherent photonuclear production of J/ψ is presented as a function of the electromagnetic dissociation (EMD) of Pb. The measurement is performed with the ALICE detector in ultra-peripheral Pb-Pb collisions at a centre-of-mass energy per nucleon pair of $\sqrt{{\textrm{s}}_{\textrm{NN}}}$ = 5.02 TeV. Cross sections are presented in five different J/ψ rapidity ranges within |y| < 4, with the J/ψ reconstructed via its dilepton decay channels. In some events the J/ψ is not accompanied by EMD, while other events do produce neutrons from EMD at beam rapidities either in one or the other beam direction, or in both. The cross sections in a given rapidity range and for different configurations of neutrons from EMD allow for the extraction of the energy dependence of this process in the range 17 < W$_{γ Pb,n}$ < 920 GeV, where W$_{γ Pb,n}$ is the centre-of-mass energy per nucleon of the γPb system. This range corresponds to a Bjorken-x interval spanning about three orders of magnitude: 1.1 × 10$^{−5}$ < x < 3.3 × 10$^{−2}$. In addition to the ultra-peripheral and photonuclear cross sections, the nuclear suppression factor is obtained. These measurements point to a strong depletion of the gluon distribution in Pb nuclei over a broad, previously unexplored, energy range. These results, together with previous ALICE measurements, provide unprecedented information to probe quantum chromodynamics at high energies.[graphic not available: see fulltext

Measurement of inclusive charged-particle jet production in pp and p-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}}=5.02 TeV

International audienceMeasurements of inclusive charged-particle jet production in pp and p-Pb collisions at center-of-mass energy per nucleon-nucleon collision $\sqrt{s_{\rm NN}} = 5.02$ TeV and the corresponding nuclear modification factor $R_{\rm pPb}^{\rm ch\,jet}$ are presented, using data collected with the ALICE detector at the LHC. Jets are reconstructed in the central rapidity region $|\eta_{\rm jet}| < 0.5$ from charged particles using the anti-$k_{\rm T}$ algorithm with resolution parameters $R = 0.2$, 0.3, and 0.4. The $p_{\rm T}$-differential inclusive production cross section of charged-particle jets, as well as the corresponding cross-section ratios, are reported for pp and p-Pb collisions in the transverse momentum range $10 < p^{\rm ch}_{\rm T,jet} < 140$ GeV/$c$ and $10 < p^{\rm ch}_{\rm T,jet} < 160$ GeV/$c$, respectively, together with the nuclear modification factor $R_{\rm pPb}^{\rm ch\,jet}$ in the range $10 < p^{\rm ch}_{\rm T,jet} < 140$ GeV/$c$. The analysis extends the $p_{\rm T}$ range of the previously-reported charged-particle jet measurements by the ALICE Collaboration. The nuclear modification factor is found to be consistent with one and independent of the jet resolution parameter with the improved precision of this study, indicating that the possible influence of cold nuclear matter effects on the production cross section of charged-particle jets in p-Pb collisions at $\sqrt{s_{\rm NN}} = 5.02$ TeV is smaller than the current precision. The obtained results are in agreement with other minimum bias jet measurements available for RHIC and LHC energies, and are well reproduced by the NLO perturbative QCD POWHEG calculations with parton shower provided by PYTHIA8 as well as by JETSCAPE simulations

Pseudorapidity dependence of anisotropic flow and its decorrelations using long-range multiparticle correlations in Pb-Pb and Xe-Xe collisions

International audienceThe pseudorapidity dependence of elliptic ($v_2$), triangular ($v_3$), and quadrangular ($v_4$) flow coefficients of charged particles measured in Pb-Pb collisions at a centre-of-mass energy per nucleon pair of $\sqrt{s_{\rm NN}}=5.02$ TeV and in Xe-Xe collisions at $\sqrt{s_{\rm NN}}=5.44$ TeV with ALICE at the LHC are presented. The measurements are performed in the pseudorapidity range $-3.5 < \eta < 5$ for various centrality intervals using two- and multi-particle cumulants with the subevent method. The flow probability density function (p.d.f.) is studied with the ratio of flow coefficient $v_2$ calculated with four- and two-particle cumulant, and suggests that the variance of flow p.d.f. is independent of pseudorapidity. The decorrelation of the flow vector in the longitudinal direction is probed using two-particle correlations. The results measured with respect to different reference regions in pseudorapidity exhibit differences, argued to be a result of saturating decorrelation effect above a certain pseudorapidity separation, in contrast to previous publications which assign this observation to non-flow effects. The results are compared to $3+1$ dimensional hydrodynamic and the AMPT transport model calculations. Neither of the models is able to simultaneously describe the pseudorapidity dependence of measurements of anisotropic flow and its fluctuations. The results presented in this work highlight shortcomings in our current understanding of initial conditions and subsequent system expansion in the longitudinal direction. Therefore, they provide input for its improvement