Development and validation of a simple and economical spectrofluorimetric method for estimation of quinine in pharmaceutical dosage forms

A new simple, sensitive, precise, economic and “green” spectrofluorimetric method for the determination of quinine both as a bulk drug and in tablet formulations was developed and validated using water as solvent. At a predetermined excitation wavelength (330 nm) and emission wavelength (380 nm), it was proved linear in the concentration range of 50-500 ng/mL, exhibited good correlation coefficient (R2= 0.999) and excellent mean recovery (97.5-103%). The results of the recovery studies showed that the method was not affected by the presence of common excipients. The method was applied for the analysis of the drug in the pure, tablet and injectable forms. The method was validated for precision, accuracy and recovery studies. Limit of Detection and Limit of Quantification for quinine were found to be 16.6 ng/mL and 19.8 ng/mL respectively. The method has been successfully applied for the analysis of marketed formulations available in Senegal. © 2013 International Formulae Group. All rights reserved.Keywords: Spectrofluorometric analysis, validation, quinine, green method

The intensification of thermal extremes in west Africa

International audienceThis study aims in filling the gap in understanding the relationship between trend and extreme in diurnal and nocturnal temperatures (Tx and Tn) over the Gulf of Guinea area and the Sahel. Time-evolution and trend of Tx and Tn anomalies, extreme temperatures and heat waves are examined using regional and station-based indices over the 1900–2012 and 1950–2012 periods respectively. In investigating extreme temperature anomalies and heat waves, a percentile method is used. At the regional and local scales, rising trends in Tx and Tn anomalies, which appear more pronounced over the past 60 years, are identified over the two regions. The trends are characterized by an intensification of: i) nocturnal/Tn warming over the second half of the 20th century; and ii) diurnal/Tx warming over the post-1980s. This is the same scheme with extreme warm days and warm nights. Finally annual number of diurnal and nocturnal heat waves has increase over the Gulf of Guinea coastal regions over the second half of the 20th century, and even more substantially over the post-1980s period. Although this trend in extreme warm days and nights is always overestimated in the simulations, from the Coupled Model Intercomparison Project Phase 5 (CMIP5), those models display rising trends whatever the scenario, which are likely to be more and more pronounced over the two regions in the next 50 years

Physiological and genetic control of transpiration efficiency in African rice, Oryza glaberrima Steud

Improving crop water use efficiency, the amount of carbon assimilated as biomass per unit of water used by a plant, is of major importance as water for agriculture becomes scarcer. In rice, the genetic bases of transpiration efficiency, the derivation of water use efficiency at the whole-plant scale, and its putative component trait transpiration restriction under high evaporative demand remain unknown. These traits were measured in 2019 in a panel of 147 African rice (Oryza glaberrima) genotypes known to be potential sources of tolerance genes to biotic and abiotic stresses. Our results reveal that higher transpiration efficiency is associated with transpiration restriction in African rice. Detailed measurements in a subset of highly contrasted genotypes in terms of biomass accumulation and transpiration confirmed these associations and suggested that root to shoot ratio played an important role in transpiration restriction. Genome wide association studies identified marker-trait associations for transpiration response to evaporative demand, transpiration efficiency, and its residuals, with links to genes involved in water transport and cell wall patterning. Our data suggest that root-shoot partitioning is an important component of transpiration restriction that has a positive effect on transpiration efficiency in African rice. Both traits are heritable and define targets for breeding rice with improved water use strategies.This work was supported by the Institut de Recherche pour le Développement, the CGIAR Research Program (CRP) on rice-agrifood systems (RICE, 2017-2022) and the Agence Nationale de la Recherche (grant ANR-17-MPGA-0011 to VV). Financial support by the Access to Research Infrastructures activity in the Horizon 2020 Programme of the EU (EPPN2020 Grant Agreement 731013) is gratefully acknowledged. PA was supported by a doctoral fellowship from the French Ministry of Higher Education. BEE was supported by the Centre National de la Recherche Scientifique et Technologique of Gabon. The authors acknowledge the IRD iTrop HPC (South Green Platform) at IRD Montpellier for providing HPC resources (https://bioinfo.ird.fr, http://www.southgreen.fr)

Natural history, phenotypic spectrum, and discriminative features of multisystemic RFC1 disease

Objective To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Methods Multimodal RFC1 repeat screening (PCR, Southern blot, whole-exome/genome sequencing?based approaches) combined with cross-sectional and longitudinal deep phenotyping in (1) cross-European cohort A (70 families) with ?2 features of CANVAS or ataxia with chronic cough (ACC) and (2) Turkish cohort B (105 families) with unselected late-onset ataxia. Results Prevalence of RFC1 disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1 disease was also identified in Western and Eastern Asian individuals and even by whole-exome sequencing. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea or dystonia (11%). Ataxia progression was ?1.3 Scale for the Assessment and Rating of Ataxia points per year (32 cross-sectional, 17 longitudinal assessments, follow-up ?9 years [mean 3.1 years]) but also included early falls, variable nonlinear phases of MSA-C?like progression (SARA points 2.5?5.5 per year), and premature death. Treatment trials require 330 (1-year trial) and 132 (2-year trial) patients in total to detect 50% reduced progression. Conclusions RFC1 disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1 treatment trials. Classification of Evidence This study provides Class II evidence that RFC1 repeat expansions are associated with CANVAS and ACC.FUNDING: Study Funding This work was supported via the European Union’s Horizon 2020 research and innovation program by the BMBF under the frame of the E-Rare-3 network PREPARE (01GM1607; to M. Synofzik,M.A., H.P., B.P.v.d.W.), by the DFG under the frame of EJP-RD network PROSPAX (No. 441409627; M. Synofzik, B.P.v.d.W., A.N.B.), and grant 779257 “Solve-RD” (toM. Synofzik, B.P.v.d.W.). B.P.v.d.W. receives additional research support from ZonMW, Hersenstichting, Gossweiler Foundation, uniQure, and Radboud University Medical Centre. T.B.H. was supported by the DFG (No 418081722). A.T. receives funding from the University of T¨ubingen, medical faculty, for the Clinician Scientist Program grant 439-0-0. A.C. thanks Medical Research Council, MR/T001712/1) and Fondazione CARIPLO (2019-1836) for grant support. L.S., T.K., B.P.v.d.W., and M. Synofzik are members of the European Reference Network for Rare Neurological Diseases, project 739510. A.N.B. is supported by the Suna and Inan Kirac Foundation and Koç University School of Medicine

Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1-disease

OBJECTIVE: To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of RFC1-repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). METHODS: Multimodal RFC1 repeat screening (PCR, southern blot, whole-exome/genome (WES/WGS)-based approaches) combined with cross-sectional and longitudinal deep-phenotyping in (i) cross-European cohort A (70 families) with ≥2 features of CANVAS and/or ataxia-with-chronic-cough (ACC); and (ii) Turkish cohort B (105 families) with unselected late-onset ataxia. RESULTS: Prevalence of RFC1-disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1-disease was also identified in Western and Eastern Asians, and even by WES. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (=overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea and/or dystonia (11%). Ataxia progression was ∼1.3 SARA points/year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1]), but also included early falls, variable non-linear phases of MSA-C-like progression (SARA 2.5-5.5/year), and premature death. Treatment trials require 330 (1-year-trial) and 132 (2-year-trial) patients in total to detect 50% reduced progression. CONCLUSIONS: RFC1-disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes, yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1-treatment trials. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that RFC1-repeat expansions are associated with CANVAS and ACC

Overexpression of a Common Wheat Gene TaSnRK2.8 Enhances Tolerance to Drought, Salt and Low Temperature in Arabidopsis

Drought, salinity and low temperatures are major factors limiting crop productivity and quality. Sucrose non-fermenting1-related protein kinase 2 (SnRK2) plays a key role in abiotic stress signaling in plants. In this study, TaSnRK2.8, a SnRK2 member in wheat, was cloned and its functions under multi-stress conditions were characterized. Subcellular localization showed the presence of TaSnRK2.8 in the cell membrane, cytoplasm and nucleus. Expression pattern analyses in wheat revealed that TaSnRK2.8 was involved in response to PEG, NaCl and cold stresses, and possibly participates in ABA-dependent signal transduction pathways. To investigate its role under various environmental stresses, TaSnRK2.8 was transferred to Arabidopsis under control of the CaMV-35S promoter. Overexpression of TaSnRK2.8 resulted in enhanced tolerance to drought, salt and cold stresses, further confirmed by longer primary roots and various physiological characteristics, including higher relative water content, strengthened cell membrane stability, significantly lower osmotic potential, more chlorophyll content, and enhanced PSII activity. Meanwhile, TaSnRK2.8 plants had significantly lower total soluble sugar levels under normal growing conditions, suggesting that TaSnRK2.8 might be involved in carbohydrate metabolism. Moreover, the transcript levels of ABA biosynthesis (ABA1, ABA2), ABA signaling (ABI3, ABI4, ABI5), stress-responsive genes, including two ABA-dependent genes (RD20A, RD29B) and three ABA-independent genes (CBF1, CBF2, CBF3), were generally higher in TaSnRK2.8 plants than in WT/GFP controls under normal/stress conditions. Our results suggest that TaSnRK2.8 may act as a regulatory factor involved in a multiple stress response pathways

The human imperative of stabilizing global climate change at 1.5°C

Global mean surface temperature is now 1.0°C higher than the pre-industrial period due to increasing atmospheric greenhouse gases. Significant changes to natural and human (managed) systems have already occurred emphasizing serious near-term risks. Here, we expand on the recent IPCC Special Report on global warming of 1.5°C as well as additional risks associated with dangerous and irreversible states at higher levels of warming, each having major implications for multiple geographies, climates and ecosystems. Limiting warming to 1.5°C rather than 2.0°C is very beneficial, maintaining significant proportions of systems such as Arctic summer sea ice, forests and coral reefs as well as having clear benefits for human health and economies. These conclusions are relevant for people everywhere, particularly in low- and middle-income countries, where climate related risks to livelihoods, health, food, water, and economic growth are escalating with major implications for the achievement of the United Nations Sustainable Development Goals