Contemporary gene flow between wild An. gambiae s.s. and An. arabiensis

Background In areas where the morphologically indistinguishable malaria mosquitoes Anopheles gambiae Giles and An. arabiensis Patton are sympatric, hybrids are detected occasionally via species-diagnostic molecular assays. An. gambiae and An. arabiensis exhibit both pre- and post-reproductive mating barriers, with swarms largely species-specific and male F1 (first-generation) hybrids sterile. Consequently advanced-stage hybrids (back-crosses to parental species), which would represent a route for potentially-adaptive introgression, are expected to be very rare in natural populations. Yet the use of one or two physically linked single-locus diagnostic assays renders them indistinguishable from F1 hybrids and levels of interspecific gene flow are unknown. Methods We used data from over 350 polymorphic autosomal SNPs to investigate post F1 gene flow via patterns of genomic admixture between An. gambiae and An. arabiensis from eastern Uganda. Simulations were used to investigate the statistical power to detect hybrids with different levels of crossing and to identify the hybrid category significantly admixed genotypes could represent. Results A range of admixture proportions were detected for 11 field-collected hybrids identified via single-locus species-diagnostic PCRs. Comparison of admixture data with simulations indicated that at least seven of these hybrids were advanced generation crosses, with backcrosses to each species identified. In addition, of 36 individuals typing as An. gambiae or An. arabiensis that exhibited outlying admixture proportions, ten were identified as significantly mixed backcrosses, and at least four of these were second or third generation crosses. Conclusions Our results show that hybrids detected using standard diagnostics will often be hybrid generations beyond F1, and that in our study area around 5% (95% confidence intervals 3%-9%) of apparently ‘pure’ species samples may also be backcrosses. This is likely an underestimate because of rapidly-declining detection power beyond the first two backcross generations. Post-F1 gene flow occurs at a far from inconsequential rate between An. gambiae and An. arabiensis, and, especially for traits under strong selection, could readily lead to adaptive introgression of genetic variants relevant for vector control

Hydrodeoxygenation of isocyanates : snapshots of a magnesium-mediated C=O bond cleavage

Organic isocyanates are readily converted to methyl amine products through their hydroboration with HBpin in the presence of a β-diketiminato magnesium catalyst. Although borylated amide and N-,O-bis(boryl)hemiaminal species have been identified as intermediates during the reductive catalysis, the overall reduction and C–O activation is metal-mediated and proposed to occur through the further intermediacy of well-defined magnesium formamidato, formamidatoborate and magnesium boryloxide derivatives. Examples of all these species have been identified and fully characterised through stoichiometric reactivity studies and the stability of the borate species leads us to suggest that, under catalytic conditions, the onward progress of the deoxygenation reaction is crucially dependent on the further activation provided by the Lewis acidic HBpin substrate. These deductions have been explored and ratified through a DFT study

Limited genomic divergence between intraspecific forms of Culex pipiens under different ecological pressures

Abstract Background: Divergent selection can be a major driver of ecological speciation. In insects of medical importance, understanding the speciation process is both of academic interest and public health importance. In the West Nile virus vector Culex pipiens, intraspecific pipiens and molestus forms vary in ecological and physiological traits. Populations of each form appear to share recent common ancestry but patterns of genetic differentiation across the genome remain unknown. Here, we undertook an AFLP genome scan on samples collected from both sympatric and allopatric populations from Europe and the USA to quantify the extent of genomic differentiation between the two forms. Results: The forms were clearly differentiated but each exhibited major population sub-structuring between continents. Divergence between pipiens and molestus forms from USA was higher than in both inter- and intra-continental comparisons with European samples. The proportion of outlier loci between pipiens and molestus (≈3 %) was low but consistent in both continents, and similar to those observed between sibling species of other mosquito species which exhibit contemporary gene flow. Only two of the outlier loci were shared between inter-form comparisons made within Europe and USA. Conclusion: This study supports the molestus and pipiens status as distinct evolutionary entities with low genomic divergence. The low number of shared divergent loci between continents suggests a relatively limited number of genomic regions determining key typological traits likely to be driving incipient speciation and/or adaptation of molestus to anthropogenic habitats

Magnesium-catalysed nitrile hydroboration

A β-diketiminato n-butylmagnesium complex is presented as a selective precatalyst for the reductive hydroboration of organic nitriles with pinacolborane (HBpin). Stoichiometric reactivity studies indicate that catalytic turnover ensues through the generation of magnesium aldimido, aldimidoborate and borylamido intermediates, which are formed in a sequence of intramolecular nitrile insertion and inter- and intramolecular B–H metathesis events. Kinetic studies highlight variations in mechanism for the catalytic dihydroboration of alkyl nitriles, aryl nitriles bearing electron withdrawing (Ar(EWG)CN) and aryl nitriles bearing electron donating (Ar(EDG)CN) substitution patterns. Kinetic isotope effects (KIEs) for catalysis performed with DBpin indicate that B–H bond breaking and C–H bond forming reactions are involved in the rate determining processes during the dihydroboration of alkyl nitriles and Ar(EDG)CN substrates, which display divergent first and second order rate dependences on [HBpin] respectively. In contrast, the hydroboration of Ar(EWG)CN substrates provides no KIE and HBpin is not implicated in the rate determining process during catalysis. Irrespective of these differences, a common mechanism is proposed in which the rate determining steps are deduced to vary through the establishment of several pre-equilibria, the relative positions of which are determined by the respective stabilities of the dimeric and monomeric magnesium aldimide and magnesium aldimidoborate intermediates as a result of adjustments to the basicity of the nitrile substrate. More generally, these observations indicate that homogeneous processes performed under heavier alkaline earth catalysis are likely to demonstrate previously unappreciated mechanistic diversity

Getting into hot water:sick guppies frequent warmer thermal conditions

Ectotherms depend on the environmental temperature for thermoregulation and exploit thermal regimes that optimise physiological functioning. They may also frequent warmer conditions to up-regulate their immune response against parasite infection and/or impede parasite development. This adaptive response, known as ‘behavioural fever’, has been documented in various taxa including insects, reptiles and fish, but only in response to endoparasite infections. Here, a choice chamber experiment was used to investigate the thermal preferences of a tropical freshwater fish, the Trinidadian guppy (Poecilia reticulata), when infected with a common helminth ectoparasite Gyrodactylus turnbulli, in female-only and mixed-sex shoals. The temperature tolerance of G. turnbulli was also investigated by monitoring parasite population trajectories on guppies maintained at a continuous 18, 24 or 32 °C. Regardless of shoal composition, infected fish frequented the 32 °C choice chamber more often than when uninfected, significantly increasing their mean temperature preference. Parasites maintained continuously at 32 °C decreased to extinction within 3 days, whereas mean parasite abundance increased on hosts incubated at 18 and 24 °C. We show for the first time that gyrodactylid-infected fish have a preference for warmer waters and speculate that sick fish exploit the upper thermal tolerances of their parasites to self medicate

Candidate-gene based GWAS identifies reproducible DNA markers for metabolic pyrethroid resistance from standing genetic variation in East African Anopheles gambiae.

Metabolic resistance to pyrethroid insecticides is widespread in Anopheles mosquitoes and is a major threat to malaria control. DNA markers would aid predictive monitoring of resistance, but few mutations have been discovered outside of insecticide-targeted genes. Isofemale family pools from a wild Ugandan Anopheles gambiae population, from an area where operational pyrethroid failure is suspected, were genotyped using a candidate-gene enriched SNP array. Resistance-associated SNPs were detected in three genes from detoxification superfamilies, in addition to the insecticide target site (the Voltage Gated Sodium Channel gene, Vgsc). The putative associations were confirmed for two of the marker SNPs, in the P450 Cyp4j5 and the esterase Coeae1d by reproducible association with pyrethroid resistance in multiple field collections from Uganda and Kenya, and together with the Vgsc-1014S (kdr) mutation these SNPs explained around 20% of variation in resistance. Moreover, the >20 Mb 2La inversion also showed evidence of association with resistance as did environmental humidity. Sequencing of Cyp4j5 and Coeae1d detected no resistance-linked loss of diversity, suggesting selection from standing variation. Our study provides novel, regionally-validated DNA assays for resistance to the most important insecticide class, and establishes both 2La karyotype variation and humidity as common factors impacting the resistance phenotype

The perseverance of Pacioli's goods inventory accounting system

This paper details sources of the 'undoubtedly strange' (Yamey, 1994a, p.119) system of goods inventory records described in Pacioli’s 1494 bookkeeping treatise and traces the longevity and widespread use of this early perpetual inventory recording (EPIR) system in English language texts. By doing so and contrasting this system with the bookkeeping treatment of modern texts, it is shown that the EPIR system persisted as the dominant form of goods inventory accounting for between 400 and 500 years and that the reasons for its demise are worthy of further consideration and research

Effect of a care transition intervention by pharmacists: an RCT

Abstract Background Pharmacists may improve medication-related outcomes during transitions of care. The aim of the Iowa Continuity of Care Study was to determine if a pharmacist case manager (PCM) providing a faxed discharge medication care plan from a tertiary care institution to primary care could improve medication appropriateness and reduce adverse events, rehospitalization and emergency department visits. Methods Design. Randomized, controlled trial of 945 participants assigned to enhanced, minimal and usual care groups conducted 2007 to 2012. Subjects. Participants with cardiovascular-related conditions and/or asthma or chronic obstructive pulmonary disease were recruited from the University of Iowa Hospital and Clinics following admission to general medicine, family medicine, cardiology or orthopedics. Intervention. The minimal group received admission history, medication reconciliation, patient education, discharge medication list and medication recommendations to inpatient team. The enhanced group also received a faxed medication care plan to their community physician and pharmacy and telephone call 3–5 days post-discharge. Participants were followed for 90 days post-discharge. Main Outcomes and Measures. Medication appropriateness index (MAI), adverse events, adverse drug events and post-discharge healthcare utilization were compared by study group using linear and logistic regression, as models accommodating random effects due to pharmacists indicated little clustering. Results Study groups were similar at baseline and the intervention fidelity was high. There were no statistically significant differences by study group in medication appropriateness, adverse events or adverse drug events at discharge, 30-day and 90-day post-discharge. The average MAI per medication as 0.53 at discharge and increased to 0.75 at 90 days, and this was true across all study groups. Post-discharge, about 16% of all participants experienced an adverse event, and this did not differ by study group (p > 0.05). Almost one-third of all participants had any type of healthcare utilization within 30 days post-discharge, where 15% of all participants had a 30-day readmission. Healthcare utilization post-discharge was not statistically significant different at 30 or 90 days by study group. Conclusion The pharmacist case manager did not affect medication use outcomes post-discharge perhaps because quality of care measures were high in all study groups. Trial registration Clinicaltrials.gov registration: NCT00513903 , August 7, 2007.http://deepblue.lib.umich.edu/bitstream/2027.42/109686/1/12913_2014_Article_3640.pd

Synthesis, characterisation, and catalytic application of a soluble molecular carrier of sodium hydride activated by a substituted 4-(dimethylamino)pyridine

Recently main group compounds have stepped into the territory of precious transition metal compounds with respect to utility in the homogeneous catalysis of fundamentally important organic transformations. Inspired by the need to promote more sustainability in chemistry because of their greater abundance in nature, this change of direction is surprising since main group metals generally do not possess the same breadth of reactivity as precious transition metals. Here, we introduce the dihydropyridylsodium compound, Na-1,2-tBu-DH(DMAP), and its monomeric variant [Na-1,2-tBu-DH(DMAP)]·Me6TREN, and demonstrate their effectiveness in transfer hydrogenation catalysis of the representative alkene 1,1-diphenylethylene to the alkane 1,1-diphenylethane using 1,4-cyclohexadiene as hydrogen source [DMAP = 4-dimethylaminopyridine; Me6TREN = tris(N,N-dimethyl-2-aminoethyl)amine]. Sodium is appealing because of its high abundance in the earth's crust and oceans, but organosodium compounds have been rarely used in homogeneous catalysis. The success of the dihydropyridylsodium compounds can be attributed to their high solubility and reactivity in organic solvents