Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus

Elucidating the genetic basis of metabolic resistance to insecticides in malaria vectors is crucial to prolonging the effectiveness of insecticide-based control tools including long lasting insecticidal nets (LLINs). Here, we show that cis-regulatory variants of the cytochrome P450 gene, CYP6P9b, are associated with pyrethroid resistance in the African malaria vector Anopheles funestus. A DNA-based assay is designed to track this resistance that occurs near fixation in southern Africa but not in West/Central Africa. Applying this assay we demonstrate, using semi-field experimental huts, that CYP6P9b-mediated resistance associates with reduced effectiveness of LLINs. Furthermore, we establish that CYP6P9b combines with another P450, CYP6P9a, to additively exacerbate the reduced efficacy of insecticide-treated nets. Double homozygote resistant mosquitoes (RR/RR) significantly survive exposure to insecticide-treated nets and successfully blood feed more than other genotypes. This study provides tools to track and assess the impact of multi-gene driven metabolic resistance to pyrethroids, helping improve resistance management

Changes and drivers of freshwater mussel diversity and distribution in northern Borneo

Human activities are threatening Borneo's unique biodiversity, but little is known on the status of freshwater invertebrates. We assessed changes in diversity and distribution of freshwater mussels (Bivalvia: Unionida) in northern Borneo, and identified drivers of present distribution and threats. Past distribution data were collected from literature and museum resources. Present distribution data were collected from 21 river basins, and 47 water quality, climatic, landscape and human variables explored as potential predictors of species presence/absence. Species delimitations were identified by morphology and COI barcoding, and haplotype networks generated. Our data indicate that over the past 50 years, four of originally five native species have become very rare or possibly locally extirpated. Since these four species are endemic to Borneo, other Bornean river basins should urgently be surveyed to identify any remaining populations. In the same time span, the non-native Sinanodonta woodiana has become the most widespread freshwater mussel in northern Borneo. The fifth native species was identified as Rectidens sumatrensis and found in four Sarawakian river basins, thus contradicting previous assumptions of an endemic Bornean Rectidens species. Although a number of stable R. sumatrensis populations are retained across Sarawak, the species' strong spatial contraction in mainland Sundaland and apparent low tolerance to eutrophication suggest that it is vulnerable to further habitat alteration. Our results indicate that Borneo's (endemic) freshwater invertebrate biodiversity is declining rapidly. Comprehensive surveys targeting an array of invertebrate and vertebrate taxa are needed to identify Borneo's freshwater biodiversity hotspots, where conservation efforts should be concentrated

The Biochemical and Cellular Basis for Nutraceutical Strategies to Attenuate Neurodegeneration in Parkinson’s Disease

Future therapeutic intervention that could effectively decelerate the rate of degeneration within the substantia nigra pars compacta (SNc) could add years of mobility and reduce morbidity associated with Parkinson’s disease (PD). Neurodegenerative decline associated with PD is distinguished by extensive damage to SNc dopaminergic (DAergic) neurons and decay of the striatal tract. While genetic mutations or environmental toxins can precipitate pathology, progressive degenerative succession involves a gradual decline in DA neurotransmission/synaptic uptake, impaired oxidative glucose consumption, a rise in striatal lactate and chronic inflammation. Nutraceuticals play a fundamental role in energy metabolism and signaling transduction pathways that control neurotransmission and inflammation. However, the use of nutritional supplements to slow the progression of PD has met with considerable challenge and has thus far proven unsuccessful. This review re-examines precipitating factors and insults involved in PD and how nutraceuticals can affect each of these biological targets. Discussed are disease dynamics (Sections 1 and 2) and natural substances, vitamins and minerals that could impact disease processes (Section 3). Topics include nutritional influences on α-synuclein aggregation, ubiquitin proteasome function, mTOR signaling/lysosomal-autophagy, energy failure, faulty catecholamine trafficking, DA oxidation, synthesis of toxic DA-quinones, o-semiquinones, benzothiazolines, hyperhomocyseinemia, methylation, inflammation and irreversible oxidation of neuromelanin. In summary, it is clear that future research will be required to consider the multi-faceted nature of this disease and re-examine how and why the use of nutritional multi-vitamin-mineral and plant-based combinations could be used to slow the progression of PD, if possible

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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