Molecular and metabolic mechanisms underlying diabetic neuropathy

Diabetes is a metabolic disease with increasing incidence worldwide and with important economic effects. The disease is characterized by hyperglycaemia, which may be caused by an alteration of insulin production secondary to degeneration of pancreatic beta cells (type-1 diabetes), or by an insulin resistance and insufficient secretion from the pancreas (type-2 diabetes). Diabetic neuropathy is the most frequent complication of diabetes mellitus and is characterised by demyelination of neurons accompanied by sensory loss. In addition, hyperglycaemia and local hypoxia can cause glucose oxidation, formation and accumulation of glycation end-products, which lead to oxidative stress. In this work, we investigated the sequence of event occurring in alteration of metabolic pathways in relation to nerve damage and sensory loss in C57BL6/j mice in the model of type 1 diabetes. We employed a mass spectrometry-based screen to study alterations in levels of metabolites in peripheral sciatic nerve and amino acids in serum over several months. Our results indicated that the impaired metabolites in peripheral nerve are the primary cause of shunting metabolic substrate to compensatory pathways, which leads to sensory nerve fibre loss in skin and contribute to onset and progression of peripheral neuropathy. Furthermore, hyperglycaemia-induced mitochondrial dysfunction and the generation of reactive oxygen species (ROS) have gained attention as possible mechanisms of organ damage in diabetes. We analysed the regulation of transcription factor HIF1α in response to prolonged hyperglycaemia in mutant mice, lacking HIF1α in peripheral sensory neurons. Our results indicated that HIF1α is an upstream modulator of ROS in peripheral sensory neurons and possess a protective function in suppressing hyperglycaemia-induced nerved damage by limiting ROS levels, therefore, HIF1α stabilization may be thus a new strategy target for limiting sensory loss, a debilitating late complication of diabetes. In peripheral nervous system, Schwann cells wrap and myelinate spirally around axons, which is indispensable for the efficient propagation of nerve impulses along axons by saltatory conduction. Periaxin protein is expressed in the membrane of myelinating Schwann cells and it is a scaffold protein for coupling peripheral proteins to elements of the Schwann cell cytoskeleton. Post-translational modification via sumoylation has emerged as a central regulatory mechanism of protein function in health and disease. We studied the role of sumoylation on Periaxin by generating conditional PLP-CreERT2+/+Ubc9fl/fl mice lacking sumo conjugating enzyme (Ubc9), which is expected to delete sumoylation in Schwann cells and oligodendrocytes. The conditional deletion of Ubc9 in Schwann cells considerably reduced the walking and running behaviour of PLP-CreERT2+/+Ubc9fl/fl mice, which can be considered as early symptoms of onset of peripheral neuropathy. Although our results cannot be generalised to other mouse genotypes, our conditional Ubc9-knock-out mice may be useful for assessing the cell-specific role of sumoylation in myelination and peripheral neuropathies

¿Está el juez de conocimiento contaminado antes del juicio oral? La imparcialidad, la concentración, la inmediación y la prevalencia puestas en peligro

El proceso penal colombiano bajo la ley 906 de 2004, estableció al juez de conocimiento la competencia para conocer del escrito de acusación, la audiencia oral de formulación de acusación, la audiencia preparatoria y el juicio oral. En este sentido, este trabajo busca resaltar las falencias de dicha normatividad, al identificar los momentos anteriores al juicio oral, como son la formulación de acusación o la audiencia preparatoria, en las cuales preside el juez de conocimiento como una clara contaminación de su criterio respecto al proceso judicial en el cual debe actuar con completa neutralidad e imparcialidad, sin todas aquellas ideas preconcebidas surgidas de los debates anteriores al juicio; un ejemplo son los criterios de inocencia o culpabilidad que pueden surgir de pruebas que fueron denegadas por estar legalmente prohibidas o por tener algún otro tipo de causal de rechazo.The Colombian criminal proceedings under Law 906 of 2004 established the trial judge’s jurisdiction to hear the indictment, the oral hearing formulation indictment, the preliminary hearing and the trial, in this sense this paper seeks to highlight the shortcomings of that regulation, to identify previous performances at trial in which the judge presides knowledge as a clear contamination of judgment with all those preconceived ideas arising from previous discussions the trial

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb public pages

Fraction of χc\chi_c decays in prompt J/ψJ/\psi production measured in pPb collisions at sNN=8.16\sqrt{s_{NN}}=8.16 TeV

The fraction of $\chi_{c1}$ and $\chi_{c2}$ decays in the prompt $J/\psi$ yield, $F_{\chi c}=\sigma_{\chi_c \to J/\psi}/\sigma_{J/\psi}$, is measured by the LHCb detector in pPb collisions at $\sqrt{s_{NN}}=8.16$ TeV. The study covers the forward ($1.5<y^*<4.0$) and backward ($-5.0<y^*<-2.5$) rapidity regions, where $y^*$ is the $J/\psi$ rapidity in the nucleon-nucleon center-of-mass system. Forward and backward rapidity samples correspond to integrated luminosities of 13.6 $\pm$ 0.3 nb$^{-1}$ and 20.8 $\pm$ 0.5 nb$^{-1}$, respectively. The result is presented as a function of the $J/\psi$ transverse momentum $p_{T,J/\psi}$ in the range 1$<p_{T, J/\psi}<20$ GeV/$c$. The $F_{\chi c}$ fraction at forward rapidity is compatible with the LHCb measurement performed in $pp$ collisions at $\sqrt{s}=7$ TeV, whereas the result at backward rapidity is 2.4 $\sigma$ larger than in the forward region for $1<p_{T, J/\psi}<3$ GeV/$c$. The increase of $F_{\chi c}$ at low $p_{T, J/\psi}$ at backward rapidity is compatible with the suppression of the $\psi$(2S) contribution to the prompt $J/\psi$ yield. The lack of in-medium dissociation of $\chi_c$ states observed in this study sets an upper limit of 180 MeV on the free energy available in these pPb collisions to dissociate or inhibit charmonium state formation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-028.html (LHCb public pages

A measurement of ΔΓs\Delta \Gamma_{s}

Using a dataset corresponding to $9~\mathrm{fb}^{-1}$ of integrated luminosity collected with the LHCb detector between 2011 and 2018 in proton-proton collisions, the decay-time distributions of the decay modes $B_s^0 \rightarrow J/\psi \eta'$ and $B_s^0 \rightarrow J/\psi \pi^{+} \pi^{-}$ are studied. The decay-width difference between the light and heavy mass eigenstates of the $B_s^0$ meson is measured to be $\Delta \Gamma_s = 0.087 \pm 0.012 \pm 0.009 \, \mathrm{ps}^{-1}$, where the first uncertainty is statistical and the second systematic.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-025.htm