Cultural value orientations and alcohol consumption in 74 countries: A societal-level analysis

A significant proportion of all deaths globally can be attributed to alcohol consumption. Although a range of correlates of alcohol consumption have already been identified at the individual level, less is understood about correlates at the macro level, such as cultural values. As a development in this understanding may prove useful for global health organizations aiming to tackle the problems associated with excessive drinking, our aim was to investigate the association between encultured alcohol consumption and Cultural Value Orientations. We obtained data describing average alcohol consumption and Cultural Value Orientations, for 74 countries, from an online data repository. To assess whether Cultural Value Orientations are associated with alcohol consumption we calculated partial correlations and performed a ridge regression analysis. Our analyses revealed that Cultural Value Orientations were significantly associated with alcohol consumption, even after controlling for average income and education level. A profile emerged in which values of autonomy and harmony were shown to be positively associated with alcohol consumption, and hierarchy and embeddedness negatively associated with alcohol consumption. The effect was modified by gender. Changes in cultural Harmony, Mastery, Autonomy and Egalitarianism were associated with increases in alcohol consumption in males, but not females, while changes in cultural Embeddedness and Hierarchy were associated with decreases in consumption in females, but no change in males. Finally, we demonstrate that latitude, and by extension its covariates such as climatic demands, partially accounted for the effect of harmony and affective autonomy on alcohol consumption. This research highlights that cultural values, and their interaction with gender, should be an important consideration for international public health organizations aiming to tackle the problems associated with alcohol consumption, but that future research is required to fully understand the link between cultural values and alcohol

Human skeletal muscle has large capacity to increase carnosine content in response to beta-alanine supplementation: a systematic review with Bayesian individual and aggregate data E-Max model and meta-analysis.

Beta-alanine (BA) supplementation increases muscle carnosine content (MCarn) and is ergogenic in many situations. Currently, many questions on the nature of the Mcarn response to supplementation are open, and the responses to these have considerable potential to enhance the efficacy and applications of this supplementation strategy. The objective of this study was to conduct a Bayesian analysis of available data on the Mcarn response to BA supplementation. A systematic review (with meta-analysis) of individual and published aggregate data was conducted, using a dose response (Emax) model. The protocol was designed according to PRISMA guidelines. A three-step screening strategy was undertaken in order to identify studies that measured the Mcarn response to BA supplementation. In addition, the research analysed individual data from five separate studies, conducted in the authors' laboratory. Data were extracted from all controlled and uncontrolled supplementation studies conducted on healthy humans. Meta-regression was used to consider the influence of potential moderators on the primary outcome, including dose, sex, age, baseline Mcarn and analysis method used. The Emax model indicated that human skeletal muscle has a large capacity for non-linear Mcarn accumulation and that commonly-used BA supplementation protocols may not come close to saturating muscle carnosine content. Neither baseline values nor sex appear to influence subsequent response to supplementation. Analysis of individual data indicated that Mcarn is relatively stable in the absence of intervention, and effectually all participants respond to BA supplementation (99.3% response [95%CrI: 96.2 –100])

Development of Leishmania mexicana in Lutzomyia longipalpis in the absence of sugar feeding

The leishmaniases are caused by Leishmania parasites and transmitted through the bites of phlebotomine sand flies. During parasite development inside the vector's midgut, promastigotes move towards the stomodeal valve, a mechanism that is crucial for transmission. It has been reported that the sugar meal acquired by sand flies during feeding between bloodmeals is essential for the development and migration of parasites. We demonstrated that the distribution of Leishmania mexicana parasites was affected by the sugar meals obtained by the sand flies. Promastigote migration towards the cardia region seems to be only partially based on the stimuli provided by sugar molecules. In the absence of sugars, significant amounts of parasites developed in the hindgut. In addition, sugar meals were important for the survival of sand flies, especially during blood digestion, presumably supporting their energy requirements

Magnetocaloric Ln(HCO2_2)(C2_2O4_4) frameworks: Synthesis, Structure and Magnetic Properties

This study probes the structure and the magnetic properties of members of the Ln(HCO$_2$)(C$_2$O$_4$) (Ln = Sm$^{3+}$–Er$^{3+}$) family of coordination frameworks. These frameworks adopt Pnma orthorhombic symmetry with one-dimensional chains arranged on a distorted triangular lattice. The magnetic properties of the Gd–Ho members of this series indicate they remain paramagnetic down to 2 K, with Dy(HCO$_2$)(C$_2$O$_4$) magnetically ordering at 0.6 K. The magnetocaloric effect of Gd(HCO$_2$)(C$_2$O$_4$) is amongst the highest found in frameworks with a peak entropy change of 55.97 J kg$^{-1}$ K$^{-1}$ (218.42 mJ cm$^{-3}$ K$^{-1}$) for a 5–0 T field change at T$_{max}$ = 2 K, making this material a very good candidate for ultra-low temperature magnetic cooling. In contrast with related magnetocaloric materials lanthanides with high magnetocrystalline anisotropy do not generally improve the magnetocaloric performance of this family at higher temperatures and lower fields. Neutron diffraction experiments suggest that Tb(HCO$_2$)(C$_2$O$_4$) and Ho(HCO$_2$)(C$_2$O$_4$) lack significant local magnetic correlations, highlighting the key role these play in optimising the magnetocaloric performance in low fields in related phases; this emphasises the importance of designing materials with specific magnetic interactions to optimise magnetocaloric performance

Drug discovery for male subfertility using high-throughput screening:a new approach to an unsolved problem

STUDY QUESTIONCan pharma drug discovery approaches be utilized to transform investigation into novel therapeutics for male infertility?SUMMARY ANSWERHigh-throughput screening (HTS) is a viable approach to much-needed drug discovery for male factor infertility.WHAT IS KNOWN ALREADYThere is both huge demand and a genuine clinical need for new treatment options for infertile men. However, the time, effort and resources required for drug discovery are currently exorbitant, due to the unique challenges of the cellular, physical and functional properties of human spermatozoa and a lack of appropriate assay platform.STUDY DESIGN, SIZE, DURATIONSpermatozoa were obtained from healthy volunteer research donors and subfertile patients undergoing IVF/ICSI at a hospital-assisted reproductive techniques clinic between January 2012 and November 2016.PARTICIPANTS/MATERIALS, SETTING, METHODSA HTS assay was developed and validated using intracellular calcium ([Ca2+]i) as a surrogate for motility in human spermatozoa. Calcium fluorescence was detected using a Flexstation microplate reader (384-well platform) and compared with responses evoked by progesterone, a compound known to modify a number of biologically relevant behaviours in human spermatozoa. Hit compounds identified following single point drug screen (10 μM) of an ion channel-focussed library assembled by the University of Dundee Drug Discovery Unit were rescreened to ensure potency using standard 10 point half-logarithm concentration curves, and tested for purity and integrity using liquid chromatography and mass spectrometry. Hit compounds were grouped by structure activity relationships and five representative compounds then further investigated for direct effects on spermatozoa, using computer-assisted sperm assessment, sperm penetration assay and whole-cell patch clamping.MAIN RESULTS AND THE ROLE OF CHANCEOf the 3242 ion channel library ligands screened, 384 compounds (11.8%) elicited a statistically significant increase in calcium fluorescence, with greater than 3× median absolute deviation above the baseline. Seventy-four compounds eliciting ≥50% increase in fluorescence in the primary screen were rescreened and evaluated further, resulting in 48 hit compounds that produced a concentration-dependent increase in [Ca2+]i. Sperm penetration studies confirmed in vitro exposure to two hit compounds (A and B) resulted in significant improvement in functional motility in spermatozoa from healthy volunteer donors (A: 1 cm penetration index 2.54, 2 cm penetration index 2.49; P &lt; 0.005 and B: 1 cm penetration index 2.1, 2 cm penetration index 2.6; P &lt; 0.005), but crucially, also in patient samples from those undergoing fertility treatment (A: 1 cm penetration index 2.4; P = 0.009, 2 cm penetration index 3.6; P = 0.02 and B: 1 cm penetration index 2.2; P = 0.0004, 2 cm penetration index 3.6; P = 0.002). This was primarily as a result of direct or indirect CatSper channel action, supported by evidence from electrophysiology studies of individual sperm.LIMITATIONS, REASONS FOR CAUTIONIncrease and fluxes in [Ca2+]i are fundamental to the regulation of sperm motility and function, including acrosome reaction. The use of calcium signalling as a surrogate for sperm motility is acknowledged as a potential limitation in this study.WIDER IMPLICATIONS OF THE FINDINGSWe conclude that HTS can robustly, efficiently, identify novel compounds that increase [Ca2+]i in human spermatozoa and functionally modify motility, and propose its use as a cornerstone to build and transform much-needed drug discovery for male infertility.</p

cyclohexane oxidation in homogeneous and carbon-supported catalysis

The authors are grateful for the Financial support from Fundação para a Ciência e a Tecnologia (FCT), Portugal, through project UIDB/00100/2020 of Centro de Quίmica Estrutural. The work was also funded by national funds through FCT, under the Scientific Employment Stimulus-Institutional Call (CEEC-INST/00102/2018). We also acknowledge the Associate Laboratory for Green Chemistry – LAQV financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/5006/2020) and Base-UIDB/50020/ 2020 and Programmatic-UIDP/50020/2020 funding of the Associate Laboratory LSRE-LCM. I. L. L. acknowledges the CATSUS Ph.D. Program from FCT for her grant PD/BD/135555/2018. A. P. is grateful to FCT and Instituto Superior Técnico (IST), Portugal through DL/57/2017 (Contract no. IST-ID/197/2019). AGM is grateful to Associação do Instituto Superior Técnico para Investigação e Desenvolvimento for his post-doctoral fellowship through grant no. BL133/2021-IST-ID. This publication is also supported by the RUDN University Strategic Academic Leadership Program (recipient AJLP, preparation). A. V. G. thanks FCT, Instituto Superior Técnico (DL 57/2016, L 57/2017 and CEEC Institutional 2018 Programs, Contract no: IST-ID/110/2018) and Baku State University for financial support. The authors also acknowledge the Portuguese NMR Network (IST-UL Centre) for access to the NMR facility. CFGCG thanks the FCT for funding the Coimbra Chemistry Centre through the programmes UIDB/00313/2020 and UIDP/00313/2020, also co-founded by FEDER/ COMPETE 2020-EU. The authors are also thankful to Benjoe Rey B. Visayas (University of Massachusetts Dartmouth) for the help with the graphics.In accordance with UN's Sustainable Development Goal (UN's SDG) 12 which encompasses the sustainable use of chemical products and a sound circular economy, this work is focused on the synthesis of Co(II), Ni(II) and Mn(II) complexes bearing combined 1,3,5-triaza-7-phosphaadamantane and benzyl terpyridine core moieties (PTA–Bztpy) as ligand, followed by their evaluation as catalysts for the microwave-assisted cyclohexane oxidation using tert-butyl hydroperoxide (TBHP) as oxidant. The most active catalyst, with a manganese metal center, was heterogenized on six different carbon materials. The results disclosed the influence of several reaction parameters, such as catalyst loading, temperature, reaction time and solvent, on the catalytic activity and selectivity of the homogeneous and carbon-supported catalysts. Recyclability of the carbon-supported catalyst allowed facile separations, recovery and reuse for five consecutive cycles.publishersversionpublishe

Clinically relevant enhancement of human sperm motility using compounds with reported phosphodiesterase inhibitor activity

STUDY QUESTION: Can we identify compound(s) with reported phosphodiesterase inhibitor (PDEI) activity that could be added to human spermatozoa in vitro to enhance their motility without compromising other sperm functions? SUMMARY ANSWER: We have identified several compounds that produce robust and effective stimulation of sperm motility and, importantly, have a positive response on patient samples. WHAT IS KNOWN ALREADY: For &gt;20 years, the use of non-selective PDEIs, such as pentoxifylline, has been known to influence the motility of human spermatozoa; however, conflicting results have been obtained. It is now clear that human sperm express several different phosphodiesterases and these are compartmentalized at different regions of the cells. By using type-specific PDEIs, differential modulation of sperm motility may be achieved without adversely affecting other functions such as the acrosome reaction (AR). STUDY DESIGN, SIZE, DURATION: This was a basic medical research study examining sperm samples from normozoospermic donors and subfertile patients attending the Assisted Conception Unit (ACU), Ninewells Hospital Dundee for diagnostic semen analysis, IVF and ICSI. Phase 1 screened 43 commercially available compounds with reported PDEI activity to identify lead compounds that stimulate sperm motility. Samples were exposed (20 min) to three concentrations (1, 10 and 100 µM) of compound, and selected candidates (n = 6) progressed to Phase 2, which provided a more comprehensive assessment using a battery of in vitro sperm function tests.  PARTICIPANTS/MATERIALS, SETTING, METHODS: All healthy donors and subfertile patients were recruited at the Medical Research Institute, University of Dundee and ACU, Ninewells Hospital Dundee (ethical approval 08/S1402/6). In Phase 1, poor motility cells recovered from the 40% interface of the discontinuous density gradient were used as surrogates for patient samples. Pooled samples from three to four different donors were utilized in order to reduce variability and increase the number of cells available for simultaneous examination of multiple compounds. During Phase 2 testing, semen samples from 23 patients attending for either routine diagnostic andrology assessment or IVF/ICSI were prepared and exposed to selected compounds. Additionally, 48 aliquots of prepared samples, surplus to clinical use, were examined from IVF (n = 32) and ICSI (n = 16) patients to further determine the effects of selected compounds under clinical conditions of treatment. Effects of compounds on sperm motility were assessed by computer-assisted sperm analysis. A modified Kremer test using methyl cellulose was used to assess sperm functional ability to penetrate into viscous media. Sperm acrosome integrity and induction of apoptosis were assessed using the acrosomal content marker PSA-FITC and annexin V kit, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In Phase 1, six compounds were found to have a strong effect on poor motility samples with a magnitude of response of ≥60% increase in percentage total motility. Under capacitating and non-capacitating conditions, these compounds significantly (P ≤ 0.05) increased the percentage of total and progressive motility. Furthermore, these compounds enhanced penetration into a cervical mucus substitute (P ≤ 0.05). Finally, the AR was not significantly induced and these compounds did not significantly increase the externalization of phosphatidylserine (P = 0.6, respectively). In general, the six compounds maintained the stimulation of motility over long periods of time (180 min) and their effects were still observed after their removal. In examinations of clinical samples, there was a general observation of a more significant stimulation of sperm motility in samples with lower baseline motility. In ICSI samples, compounds #26, #37 and #38 were the most effective at significantly increasing total motility (88, 81 and 79% of samples, respectively) and progressive motility (94, 93 and 81% of samples, respectively). In conclusion, using a two-phased drug discovery screening approach including the examination of clinical samples, 3/43 compounds were identified as promising candidates for further study. LIMITATIONS, REASONS FOR CAUTION: This is an in vitro study and caution must be taken when extrapolating the results. Data for patients were from one assessment and thus the robustness of responses needs to be established. The n values for ICSI samples were relatively small. WIDER IMPLICATIONS OF THE FINDINGS: We have systematically screened and identified several compounds that have robust and effective stimulation (i.e. functional significance with longevity and no toxicity) of total and progressive motility under clinical conditions of treatment. These compounds could be clinical candidates with possibilities in terms of assisted reproductive technology options for current or future patients affected by asthenozoospermia or oligoasthenozoospermia

Towards Structure-Property-Function Relationships for Eumelanin

We discuss recent progress towards the establishment of important structure-property-function relationships in eumelanins - key functional bio-macromolecular systems responsible for photo-protection and immune response in humans, and implicated in the development of melanoma skin cancer. We focus on the link between eumelanin's secondary structure and optical properties such as broad band UV-visible absorption and strong non-radiative relaxation; both key features of the photo-protective function. We emphasise the insights gained through a holistic approach combining optical spectroscopy with first principles quantum chemical calculations, and advance the hypothesis that the robust functionality characteristic of eumelanin is related to extreme chemical and structural disorder at the secondary level. This inherent disorder is a low cost natural resource, and it is interesting to speculate as to whether it may play a role in other functional bio-macromolecular systems.Comment: 19 pages, 8 figures, Invited highlight article for Soft Matte

Novel organotin-PTA complexes supported on mesoporous carbon materials as recyclable catalysts for solvent-free cyanosilylation of aldehydes

The work was also funded by national funds through FCT, under the Scientific Employment Stimulus-Institutional Call (CEEC-INST/00102/2018). AGM is grateful to Associação do Instituto Superior Técnico para a Investigação e Desenvolvimento ( IST-ID ) for his post-doctoral fellowship through grant no. BL133/2021-IST-ID . AP and AMF are grateful to FCT and Instituto Superior Técnico (IST), Portugal through DL/57/2017 (Contract no. IST-ID/197/2019 and IST-ID/131/2018). This publication is also supported by the RUDN University Strategic Academic Leadership Program (recipient AJLP, preparation). The authors also acknowledge the Portuguese NMR Network (IST-UL Centre) for access to the NMR facility. Publisher Copyright: © 2023 Elsevier B.V.New organotin compounds with general formula [(PTA-CH2-C6H4-p-COO)SnR3]Br (where R is Me for 3 and Ph for 4; PTA = 1,3,5-triaza-7-phosphaadamantane), bearing the methylene benzoate PTA derivative, were synthesized through a mild two-step process. The compounds were characterized by Fourier transform infrared spectroscopy, electrospray ionization mass spectrometry, elemental analysis and nuclear magnetic resonance spectroscopy (NMR). They were heterogenized on commercially available activated carbon (AC) and multi-walled carbon nanotubes (CNT), as well as on their chemically modified analogues. The obtained materials were characterized by scanning electron microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy. Complex 3 supported on activated carbon (3-AC) was found to be an active and recyclable catalyst for the cyanosilylation of several aromatic and aliphatic aldehydes. Using 3-AC with a low loading of 0.1 mol% several substrates were quantitatively converted, within just 5 min at 50 °C and under microwave irradiation in solvent-free conditions. Multinuclear NMR analysis suggested a mechanism that potentially involves a double activation process, where the nucleophilic phosphorus at the PTA derivative acts as a Lewis base and the Sn(IV) metal centre as a Lewis acid.publishersversionpublishe

Genome analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared t