Stimulation of the brain serotonin receptor 7 rescues mitochondrial dysfunction in female mice from two models of Rett syndrome

Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2) cause more than 95% of classic cases, and currently there is no cure for this devastating disorder. Recently we have demonstrated that neurobehavioral and brain molecular alterations can be rescued in a RTT mouse model, by pharmacological stimulation of the brain serotonin receptor 7 (5-HT7R). This member of the serotonin receptor family, crucially involved in the regulation of brain structural plasticity and cognitive processes, can be stimulated by systemic repeated treatment with LP-211, a brain-penetrant selective agonist. The present study extends previous findings by demonstrating that LP-211 treatment (0.25 mg/kg, once per day for 7 days) rescues mitochondrial respiratory chain impairment, oxidative phosphorylation deficiency and the reduced energy status in the brain of heterozygous female mice from two highly validated mouse models of RTT (MeCP2-308 and MeCP2-Bird mice). Moreover, LP-211 treatment completely restored the radical species overproduction by brain mitochondria in the MeCP2-308 model and partially recovered the oxidative imbalance in the more severely affected MeCP2-Bird model. These results provide the first evidence that RTT brain mitochondrial dysfunction can be rescued targeting the brain 5-HT7R and add compelling preclinical evidence of the potential therapeutic value of LP-211 as a pharmacological approach for this devastating neurodevelopmental disorder

PRELIMINARY STUDIES ON BIOPRECIPITATION PROCESSES MEDIATED BY SULFATE REDUCING BACTERIA (SRB) AND METAL IMMOBILIZATION IN MINE IMPACTED ENVIRONMENTS.

Mining activity often leaves a critical legacy represented by huge volumes of mine wastes and residues, usually made up of highly reactive materials, which lead to the mobilization and dispersion of harmful elements in soils and waters. Although these extreme environments are adverse to the development of living organisms, it has been observed that some microorganisms are able to adapt, playing a role in metal mobility, and becoming part of the resilience of the system itself. The Iglesiente and Arburese (SW Sardinia, Italy) mine districts, now abandoned, have been exploited for centuries by mining activities aimed at Pb-Zn extraction from sulfides and non-sulfides (calamine) deposits. Here, biogeochemical barriers naturally occur as an adaptation of the ecosystem to environmental stresses. Studies, from macroscale to microscale, showed that sulfate-reducing bacteria (SRB) may influence metal mobility by mediating the precipitation of secondary authigenic metal sulfides under reducing conditions. Specifically, framboids of Zn sulfides and Fe sulfides have been observed in the sections of stream sediments core characterized by the presence of abundant organic matter, especially residues of vegetal tissues (e.g. roots and stems of Juncus acutus and Phragmites australis). Laboratory-scale experiments were performed to better understand the bioprecipitation processes. For this purpose, anaerobic batch tests were carried out using high polluted mining waters (Zn and sulfate concentrations up to 102 and 103 mg/l, respectively) inoculated with native selected sulfate-reducing bacteria from stream sediments collected in the investigated areas. Dramatic decrease (up to 100%) in Zn and sulfate was observed in solutions. Moreover, scanning electron microscopy - energy dispersive spectroscopy (SEM-EDS) analysis, performed on solids recovered at the end of the experiments, showed the presence of precipitates characterized by a tubular morphology and made up by S and Zn. SRB inocula were studied by next-generation sequencing (NGS) approach, with the aim to compare the microbial diversity of the different SRB communities and to search for indigenous novel metal-tolerant sulfidogenic microorganisms. These findings represent a valuable step forward to plan effective bioremediation strategies for reducing metal mobility and dispersion. Also, bioprecipitation mediated by SRB can have great potentialities for metal recovery and our results can help to develop biomining techniques. The authors acknowledge CESA (E58C16000080003) from RAS and RAS/FBS (F72F16003080002) grants, and the CeSAR (Centro Servizi d'Ateneo per la Ricerca) of the University of Cagliari, Italy, for SEM analysis

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Measurement of the J/ψ pair production cross-section in pp collisions at s=13 \sqrt{s}=13 TeV

The production cross-section of J/ψ pairs is measured using a data sample of pp collisions collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=13$ TeV, corresponding to an integrated luminosity of 279 ±11 pb$^{−1}$. The measurement is performed for J/ψ mesons with a transverse momentum of less than 10 GeV/c in the rapidity range 2.0 < y < 4.5. The production cross-section is measured to be 15.2 ± 1.0 ± 0.9 nb. The first uncertainty is statistical, and the second is systematic. The differential cross-sections as functions of several kinematic variables of the J/ψ pair are measured and compared to theoretical predictions.The production cross-section of $J/\psi$ pairs is measured using a data sample of $pp$ collisions collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s} = 13 \,{\mathrm{TeV}}$, corresponding to an integrated luminosity of $279 \pm 11 \,{\mathrm{pb^{-1}}}$. The measurement is performed for $J/\psi$ mesons with a transverse momentum of less than $10 \,{\mathrm{GeV}}/c$ in the rapidity range $2.0<y<4.5$. The production cross-section is measured to be $15.2 \pm 1.0 \pm 0.9 \,{\mathrm{nb}}$. The first uncertainty is statistical, and the second is systematic. The differential cross-sections as functions of several kinematic variables of the $J/\psi$ pair are measured and compared to theoretical predictions

Measurement of forward W→eνW\to e\nu production in pppp collisions at s=8 \sqrt{s}=8\,TeV

A measurement of the cross-section for $W \to e\nu$ production in $pp$ collisions is presented using data corresponding to an integrated luminosity of $2\,$fb$^{-1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8\,$TeV. The electrons are required to have more than $20\,$GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive $W$ production cross-sections, where the $W$ decays to $e\nu$, are measured to be \begin{align*} \begin{split} \sigma_{W^{+} \to e^{+}\nu_{e}}&=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\,\mathrm{pb},\\ \sigma_{W^{-} \to e^{-}\bar{\nu}_{e}}&=\,\,\,809.0\pm 1.9\pm 18.1\pm\,\,\,7.0\pm \phantom{0}9.4\,\mathrm{pb}, \end{split} \end{align*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. Differential cross-sections as a function of the electron pseudorapidity are measured. The $W^{+}/W^{-}$ cross-section ratio and production charge asymmetry are also reported. Results are compared with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics. Finally, in a precise test of lepton universality, the ratio of $W$ boson branching fractions is determined to be \begin{align*} \begin{split} \mathcal{B}(W \to e\nu)/\mathcal{B}(W \to \mu\nu)=1.020\pm 0.002\pm 0.019, \end{split} \end{align*} where the first uncertainty is statistical and the second is systematic.A measurement of the cross-section for $W \to e\nu$ production in $pp$ collisions is presented using data corresponding to an integrated luminosity of $2\,$fb$^{-1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8\,$TeV. The electrons are required to have more than $20\,$GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive $W$ production cross-sections, where the $W$ decays to $e\nu$, are measured to be \begin{equation*} \sigma_{W^{+} \to e^{+}\nu_{e}}=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\,\mathrm{pb}, \end{equation*} \begin{equation*} \sigma_{W^{-} \to e^{-}\bar{\nu}_{e}}=\,\,\,809.0\pm 1.9\pm 18.1\pm\,\,\,7.0\pm \phantom{0}9.4\,\mathrm{pb}, \end{equation*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. Differential cross-sections as a function of the electron pseudorapidity are measured. The $W^{+}/W^{-}$ cross-section ratio and production charge asymmetry are also reported. Results are compared with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics. Finally, in a precise test of lepton universality, the ratio of $W$ boson branching fractions is determined to be \begin{equation*} \mathcal{B}(W \to e\nu)/\mathcal{B}(W \to \mu\nu)=1.020\pm 0.002\pm 0.019, \end{equation*} where the first uncertainty is statistical and the second is systematic.A measurement of the cross-section for W → eν production in pp collisions is presented using data corresponding to an integrated luminosity of 2 fb$^{−1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8$ TeV. The electrons are required to have more than 20 GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive W production cross-sections, where the W decays to eν, are measured to be ${\sigma}_{W^{+}\to {e}^{+}{\nu}_e}=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\kern0.5em \mathrm{p}\mathrm{b},$ ${\sigma}_{W^{-}\to {e}^{-}{\overline{\nu}}_e}=809.0\pm 1.9\pm 18.1\pm \kern0.5em 7.0\pm \kern0.5em 9.4\,\mathrm{p}\mathrm{b},$ where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination

Measurement of the B0s→μ+μ− Branching Fraction and Effective Lifetime and Search for B0→μ+μ− Decays

A search for the rare decays Bs0→μ+μ- and B0→μ+μ- is performed at the LHCb experiment using data collected in pp collisions corresponding to a total integrated luminosity of 4.4  fb-1. An excess of Bs0→μ+μ- decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be B(Bs0→μ+μ-)=(3.0±0.6-0.2+0.3)×10-9, where the first uncertainty is statistical and the second systematic. The first measurement of the Bs0→μ+μ- effective lifetime, τ(Bs0→μ+μ-)=2.04±0.44±0.05  ps, is reported. No significant excess of B0→μ+μ- decays is found, and a 95% confidence level upper limit, B(B0→μ+μ-)<3.4×10-10, is determined. All results are in agreement with the standard model expectations.A search for the rare decays $B^0_s\to\mu^+\mu^-$ and $B^0\to\mu^+\mu^-$ is performed at the LHCb experiment using data collected in $pp$ collisions corresponding to a total integrated luminosity of 4.4 fb$^{-1}$. An excess of $B^0_s\to\mu^+\mu^-$ decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be ${\cal B}(B^0_s\to\mu^+\mu^-)=\left(3.0\pm 0.6^{+0.3}_{-0.2}\right)\times 10^{-9}$, where the first uncertainty is statistical and the second systematic. The first measurement of the $B^0_s\to\mu^+\mu^-$ effective lifetime, $\tau(B^0_s\to\mu^+\mu^-)=2.04\pm 0.44\pm 0.05$ ps, is reported. No significant excess of $B^0\to\mu^+\mu^-$ decays is found and a 95 % confidence level upper limit, ${\cal B}(B^0\to\mu^+\mu^-)<3.4\times 10^{-10}$, is determined. All results are in agreement with the Standard Model expectations

Measurements of prompt charm production cross-sections in pp collisions at s=5 \sqrt{s}=5 TeV

Production cross-sections of prompt charm mesons are measured using data from $pp$ collisions at the LHC at a centre-of-mass energy of $5\,$TeV. The data sample corresponds to an integrated luminosity of $8.60\pm0.33\,$pb$^{-1}$ collected by the LHCb experiment. The production cross-sections of $D^0$, $D^+$, $D_s^+$, and $D^{*+}$ mesons are measured in bins of charm meson transverse momentum, $p_{\text{T}}$, and rapidity, $y$. They cover the rapidity range $2.0 < y < 4.5$ and transverse momentum ranges $0 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D^0$ and $D^+$ and $1 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D_s^+$ and $D^{*+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of $1 < p_{\text{T}} < 8\, \text{GeV}/c$ are determined to be \begin{equation*} \sigma(pp\rightarrow D^0 X) = 1190 \pm 3 \pm 64\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D^+ X) = 456 \pm 3 \pm 34\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D_s^+ X) = 195 \pm 4 \pm 19\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D^{*+} X)= 467 \pm 6 \pm 40\,\mu\text{b} \end{equation*} where the uncertainties are statistical and systematic, respectively.Production cross-sections of prompt charm mesons are measured using data from pp collisions at the LHC at a centre-of-mass energy of 5 TeV. The data sample corresponds to an integrated luminosity of 8.60 ± 0.33 pb$^{−1}$ collected by the LHCb experiment. The production cross-sections of D$^{0}$, D$^{+}$, D$_{s}^{+}$ , and D$^{∗+}$ mesons are measured in bins of charm meson transverse momentum, p$_{T}$, and rapidity, y. They cover the rapidity range 2.0 < y < 4.5 and transverse momentum ranges 0 < p$_{T}$ < 10 GeV/c for D$^{0}$ and D$^{+}$ and 1 < p$_{T}$ < 10 GeV/c for D$_{s}^{+}$ and D$^{∗+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of 1 < p$_{T}$ < 8 GeV/c are determined to be $\begin{array}{l}\sigma \left( pp\to {D}^0X\right)=1004\pm 3\pm 54\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}^{+}X\right)=402\pm 2\pm 30\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}_s^{+}X\right)=170\pm 4\pm 16\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}^{\ast +}X\right)=421\pm 5\pm 36\mu \mathrm{b},\end{array}$ where the uncertainties are statistical and systematic, respectively.Production cross-sections of prompt charm mesons are measured using data from $pp$ collisions at the LHC at a centre-of-mass energy of $5\,$TeV. The data sample corresponds to an integrated luminosity of $8.60\pm0.33\,$pb$^{-1}$ collected by the LHCb experiment. The production cross-sections of $D^0$, $D^+$, $D_s^+$, and $D^{*+}$ mesons are measured in bins of charm meson transverse momentum, $p_{\text{T}}$, and rapidity, $y$. They cover the rapidity range $2.0<y<4.5$ and transverse momentum ranges $0 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D^0$ and $D^+$ and $1 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D_s^+$ and $D^{*+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of $1 < p_{\text{T}} < 8\, \text{GeV}/c$ are determined to be \sigma(pp\rightarrow D^0 X) = 1004 \pm 3 \pm 54\,\mu\text{b} \sigma(pp\rightarrow D^+ X) = 402 \pm 2 \pm 30\,\mu\text{b} \sigma(pp\rightarrow D_s^+ X) = 170 \pm 4 \pm 16\,\mu\text{b} \sigma(pp\rightarrow D^{*+} X)= 421 \pm 5 \pm 36\,\mu\text{b} where the uncertainties are statistical and systematic, respectively

Primary and Secondary Mitochondrial Diseases: Etiologies and Therapeutic Strategies

Mitochondria are complex and multifaceted organelles that constitute a dynamic network of signaling platforms playing a pivotal role in cellular energy-generating processes [...