Board of Directors' characteristics and environmental SDGs adoption: an international study

Drivers of environmentally conscious firm behaviour have gained increasing attention over past decades. The Board of Directors holds a central role in corporate decision-making, and previous empirical evidence suggests that its characteristics could influence corporate environmental performance. This paper contributes to the literature with the first evidence of the influence certain board characteristics have on whether a firm ulti-mately supports one or more environmental SDGs. Our focus is on board size, gender diversity, board independence and CEO duality. Logistic and fractional regressions on 4417 globally listed firms highlight that board size, the share of female directors, and the share of independent directors are significant drivers of support for environmental SDGs. The results and insights revealed in this study should be helpful to policymakers, investors and corporations in evaluating the effectiveness of corporate governance characteristics and fostering corporate contributions to the 2030 Agenda

Triterpenoids from vitellaria paradoxa stem barks reduce nitrite levels in lps-stimulated macrophages

open7siVitellaria paradoxa C. F. Gaertn is widely used in African traditional medicine as an anti-inflammatory remedy to treat rheumatism, gastric problems, diarrhea, and dysentery. The phyto-chemical investigation of the ethyl acetate extract of V. paradoxa stem bark collected in Burkina Faso led to the isolation of eight known and two triterpenes undescribed to date (7 and 10), in the free alcohol form or as acetyl and cinnamyl ester derivatives. The stereostructures of the new compounds were elucidated using HR-ESIMS and 1D and 2D NMR data. The isolated compounds were evaluated in vitro for their inhibitory effect on nitrite levels on murine macrophages J774 stimulated with the lipopolysaccharide (LPS). Among all the compounds tested, lupeol cinnamate (3) and betulinic acid (5) showed a beneficial effect in reducing nitrite levels produced after LPS stimulation.openSirignano C.; Nadembega P.; Poli F.; Romano B.; Lucariello G.; Rigano D.; Taglialatela-Scafati O.Sirignano C.; Nadembega P.; Poli F.; Romano B.; Lucariello G.; Rigano D.; Taglialatela-Scafati O

A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability

Mutations in the KCNQ2 gene encoding for voltage-gated potassium channel subunits have been found in patients affected with early-onset epilepsies with wide phenotypic expression, ranging from Benign Familial Neonatal Seizures (BFNS) to epileptic encephalopathy with cognitive impairment, drug resistance, and characteristic EEG and neuroradiological features. By contrast, only few KCNQ3 mutations have been rarely described, mostly in patients with typical BFNS. We report clinical, genetic, and functional data from a family in which early-onset epilepsy and neurocognitive deficits segregated with a novel mutations in KCNQ3 (c.989G>T; p.R330L). Electrophysiological studies in mammalian cells revealed that incorporation of KCNQ3 R330L mutant subunits impaired channel function, suggesting a pathogenetic role for such mutation. The degree of functional impairment of channels incorporating KCNQ3 R330L subunits was larger than that of channels carrying another KCNQ3 mutation affecting the same codon but leading to a different amino acid substitution (p.R330C), previously identified in two families with typical BFNS. These data suggest that mutations in KCNQ3, similarly to KCNQ2, can be found in patients with more severe phenotypes including intellectual disability, and that the degree of the functional impairment caused by mutations at position 330 in KCNQ3 may contribute to clinical disease severity

Activation of Kv7 potassium channels inhibits intracellular Ca2+ increases triggered by TRPV1-mediated pain-inducing stimuli in F11 immortalized sensory neurons

Kv7.2-Kv7.5 channels mediate the M-current (IKM), a K+-selective current regulating neuronal excitability and representing an attractive target for pharmacological therapy against hyperexcitability diseases such as pain. Kv7 channels interact functionally with transient receptor potential vanilloid 1 (TRPV1) channels activated by endogenous and/or exogenous pain-inducing substances, such as bradykinin (BK) or capsaicin (CAP), respectively; however, whether Kv7 channels of specific molecular composition provide a dominant contribution in BK- or CAP-evoked responses is yet unknown. To this aim, Kv7 transcripts expression and function were assessed in F11 immortalized sensorial neurons, a cellular model widely used to assess nociceptive molecular mechanisms. In these cells, the effects of the pan-Kv7 activator retigabine were investigated, as well as the effects of ICA-27243 and (S)-1, two Kv7 activators acting preferentially on Kv7.2/Kv7.3 and Kv7.4/Kv7.5 channels, respectively, on BK- and CAP-induced changes in intracellular Ca2+ concentrations ([Ca2+]i). The results obtained revealed the expression of transcripts of all Kv7 genes, leading to an IKM-like current. Moreover, all tested Kv7 openers inhibited BK- and CAP-induced responses by a similar extent (~60%); at least for BK-induced Ca2+ responses, the potency of retigabine (IC50~1 µM) was higher than that of ICA-27243 (IC50~5 µM) and (S)-1 (IC50~7 µM). Altogether, these results suggest that IKM activation effectively counteracts the cellular processes triggered by TRPV1-mediated pain-inducing stimuli, and highlight a possible critical contribution of Kv7.4 subunits

Effects of Azadirachta indica seed kernel extracts on early erythrocytic schizogony of Plasmodium berghei and pro-inflammatory response in inbred mice

Background: Medicinal plant research may contribute to develop new pharmacological control tools for vector borne diseases, such as malaria. Methods: The effects of methanol extracts (ME) obtained from seed kernel of ripe and unripe Azadirachta indica fruits were studied on erythrocytic proliferation of the rodent malaria parasite Plasmodium berghei strain ANKA and on mice pro-inflammatory response, as evaluated by measuring the matrix-metalloproteinase-9 (MMP-9) and tumour necrosis factor (TNF) plasma levels, in two mouse strains (C57BL/6 and BALB/c) which are considered as prototypical of Th1 and Th2 immune response, respectively. Results: ME obtained from seed kernel of unripe Azadirachta indica fruits decreased by about 30% the proportion of erythrocytes infected with the malaria parasite in C57BL/6 mice in the 4 days suppressive test. In this treatment group, MMP-9 and TNF levels were notably higher than those measured in the same mouse strain treated with the anti-malarial drug artesunate, Azadirachta indica kernel extracts from ripe fruits or solvent. In BALB/c mice, treatment with kernel extracts did not influence parasitaemia. MMP-9 and TNF levels measured in this mouse strain were notably lower than those recorded in C57BL/6 mice and did not vary among treatment groups. Conclusions: The effects of the ME on the parasite-host interactions appeared to be mouse strain-dependent, but also related to the ripening stage of the neem fruits, as only the unripe fruit seed kernel extracts displayed appreciable bioactivity

A novel hyperekplexia-causing mutation in the pre-transmembrane segment 1 of the human glycine receptor alpha1 subunit reduces membrane expression and impairs gating by agonists

In this study, we have compared the functional consequences of three mutations (R218Q, V260M, and Q266H) in the 1 subunit of the glycine receptor (GlyRA1) causing hyperekplexia, an inherited neurological channelopathy. In HEK-293 cells, the agonist EC50s for glycine- activated Cl currents were increased from 26 M in wtGlyRA1, to 5747, 135, and 129 M in R218Q, V260M, and Q266H GlyRA1 channels, respectively. Cl currents elicited by -alanine and taurine, which behave as agonists at wtGlyRA1, were decreased in V260M and Q266H mutant receptors and virtually abolished in GlyRA1 R218Q receptors. Gly-gated Cl currents were similarly antagonized by low concentrations of strychnine in both wild-type (wt) and R218Q GlyRA1 channels, suggesting that the Arg-218 residue plays a crucial role in GlyRA1 channel gating, with only minor effects on the agonist/ antagonist binding site, a hypothesis supported by our molecular model of the GlyRA1 subunit. The R218Q mutation, but not the V260M or the Q266H mutation, caused a marked decrease of receptor subunit expression both in total cell lysates and in isolated plasma membrane proteins. This decreased expression does not seem to explain the reduced agonist sensitivity of GlyRA1 R218Q channels since no difference in the apparent sensitivity to glycine or taurine was observed when wtGlyRA1 receptors were expressed at levels comparable with those of R218Q mutant receptors. In conclusion, multiple mechanisms may explain the dramatic decrease in GlyR function caused by the R218Q mutation, possibly providing the molecular basis for its association with a more severe clinical phenotype