Prior studies on emerging economies contend that increasing returns to human capital has contributed to the growth of wage inequality over the last few decades. However, this explanation fails to ...account for an important dynamic of contemporary wage inequality: the growth of top labor incomes. Research on advanced economies show the emergence of a wage premium in the financial sector increased top labor incomes, but studies have yet to investigate whether a financial wage premium is contributing to the growth of top labor incomes in emerging economies. The present study addresses this theoretical and empirical gap by conceptualizing and measuring the financial wage premium across the distributions of labor income in the most important subset of emerging economies: Brazil, Russia, India, and China (BRIC). Drawing on harmonized labor force data from the Luxembourg Income Study, we utilize unconditional quantile regression modeling and treatment effect estimation to examine the financial wage premium across the distributions of labor income in the BRIC before and after the Great Recession. Consistent with studies on advanced economies, we find a substantial wage premium among top earners in the financial sectors of the BRIC, which has grew in the post-recession period. However, we find significant variation in size and growth of the financial wage premium because of the variegated nature of financialization across the BRIC. We conclude by suggesting that subsequent studies should explore the heterogeneous effects of subordinate and state financialization on wage dynamics in emerging economies.
1. The scarcity of reliable long‐term phenological data has severely hindered the study of the responses of species to climate change. Biological collections in herbaria and museums are potential ...sources of long‐term data for such study, but their use for this purpose needs independent validation. Here we report a rigorous test of the validity of using herbarium specimens for phenological studies, by comparing relationships between climate and time of peak flowering derived from herbarium records and from direct field‐based observations, for the terrestrial orchid Ophrys sphegodes. 2. We examined herbarium specimens of O. sphegodes collected between 1848 and 1958, and recorded peak flowering time directly in one population of O. sphegodes between 1975 and 2006. The response of flowering time to variation in mean spring temperature (March-May) was virtually identical in both sets of data, even though they covered different periods of time which differ in extent of anthropogenic temperature change. In both cases flowering was advanced by c. 6 days per °C rise in average spring temperature. 3. The proportion of variation in flowering time explained by spring temperature was lower in the herbarium record than in direct field observations. It is likely that some of the additional variation was due to geographical variation in collection site, as flowering was significantly earlier at more westerly sites, which have had warmer springs, over their range of 3.44° of longitude. 4. Predictions of peak flowering time based on the herbarium data corresponded closely with observed peak flowering times in the field, indicating that flowering response to temperature had not altered between the two separate periods over which the herbarium and field data were collected. 5. Synthesis. These results provide the first direct validation of the use of herbarium collections to examine the relationships between phenology and climate when field‐based observational data are not available.
We previously reported on a randomised trial demonstrating the effectiveness and cost-effectiveness of a pharmacist-led information technology intervention (PINCER). We sought to investigate whether ...PINCER was effective in reducing hazardous prescribing when rolled out at scale in UK general practices.
We used a multiple interrupted time series design whereby successive groups of general practices received the PINCER intervention between September 2015 and April 2017. We used 11 prescribing safety indicators to identify potentially hazardous prescribing and collected data over a maximum of 16 quarterly time periods. The primary outcome was a composite of all the indicators; a composite for indicators associated with gastrointestinal (GI) bleeding was also reported, along with 11 individual indicators of hazardous prescribing. Data were analysed using logistic mixed models for the quarterly event numbers with the appropriate denominator, and calendar time included as a covariate. PINCER was implemented in 370 (94.1%) of 393 general practices covering a population of almost 3 million patients in the East Midlands region of England; data were successfully extracted from 343 (92.7%) of these practices. For the primary composite outcome, the PINCER intervention was associated with a decrease in the rate of hazardous prescribing of 16.7% (adjusted odds ratio (aOR) 0.83, 95% confidence interval (CI) 0.80 to 0.86) at 6 months and 15.3% (aOR 0.85, 95% CI 0.80 to 0.90) at 12 months postintervention. The unadjusted rate of hazardous prescribing reduced from 26.4% (22,503 patients in the numerator/853,631 patients in the denominator) to 20.1% (11,901 patients in the numerator/591,364 patients in the denominator) at 6 months and 19.1% (3,868 patients in the numerator/201,992 patients in the denominator). The greatest reduction in hazardous prescribing associated with the intervention was observed for the indicators associated with GI bleeding; for the GI composite indicator, there was a decrease of 23.9% at both 6 months (aOR 0.76, 95% CI 0.73 to 0.80) and 12 months (aOR 0.76, 95% CI 0.70 to 0.82) postintervention. The unadjusted rate of hazardous prescribing reduced from 31.4 (16,185 patients in the numerator/515,879 patients in the denominator) to 21.2% (7,607 patients in the numerator/358,349 patients in the denominator) at 6 months and 19.5% (2,369 patients in the numerator/121,534 patients in the denominator). We adjusted for calendar time and practice, but since this was an observational study, the findings may have been influenced by unknown confounding factors or behavioural changes unrelated to the PINCER intervention. Data were also not collected for all practices at 6 months and 12 months postintervention.
The PINCER intervention, when rolled out at scale in routine clinical practice, was associated with a reduction in hazardous prescribing by 17% and 15% at 6 and 12 months postintervention. The greatest reductions in hazardous prescribing were for indicators associated with risk of GI bleeding. These findings support the wider national rollout of PINCER in England.
Coupling between ATPase and track binding sites is essential for molecular motors to move along cytoskeletal tracks. In dynein, these sites are separated by a long coiled coil stalk that must mediate ...communication between them, but the underlying mechanism remains unclear. Here we show that changes in registration between the two helices of the coiled coil can perform this function. We locked the coiled coil at three specific registrations using oxidation to disulfides of paired cysteine residues introduced into the two helices. These trapped ATPase activity either in a microtubule-independent high or low state, and microtubule binding activity either in an ATP-insensitive strong or weak state, depending on the registry of the coiled coil. Our results provide direct evidence that dynein uses sliding between the two helices of the stalk to couple ATPase and microtubule binding activities during its mechanochemical cycle.
Infectious diseases caused by apicomplexan parasites remain a global public health threat. The presence of multiple ligand‐binding sites in tubulin makes this protein an attractive target for ...anti‐parasite drug discovery. However, despite remarkable successes as anti‐cancer agents, the rational development of protozoan parasite‐specific tubulin drugs has been hindered by a lack of structural and biochemical information on protozoan tubulins. Here, we present atomic structures for a protozoan tubulin and microtubule and delineate the architectures of apicomplexan tubulin drug‐binding sites. Based on this information, we rationally designed the parasite‐specific tubulin inhibitor parabulin and show that it inhibits growth of parasites while displaying no effects on human cells. Our work presents for the first time the rational design of a species‐specific tubulin drug providing a framework to exploit structural differences between human and protozoa tubulin variants enabling the development of much‐needed, novel parasite inhibitors.
Synopsis
In an effort to discover novel drug‐scaffolds targeting unique parasite proteins and pathways, specific inhibition of parasite tubulin was achieved using structure‐guided rational drug design.
The atomic architecture of apicomplexan tubulin‐drug binding sites was resolved.
Species‐specific tubulin binding drugs were studied.
A parasite tubulin inhibitor dubbed parabulin was designed.
In an effort to discover novel drug‐scaffolds targeting unique parasite proteins and pathways, specific inhibition of parasite tubulin was achieved using structure‐guided rational drug design.
Dynein ATPases are the largest known cytoskeletal motors and perform critical functions in cells: carrying cargo along microtubules in the cytoplasm and powering flagellar beating. Dyneins are ...members of the AAA+ superfamily of ring-shaped enzymes, but how they harness this architecture to produce movement is poorly understood. Here, we have used cryo-EM to determine 3D maps of native flagellar dynein-c and a cytoplasmic dynein motor domain in different nucleotide states. The structures show key sites of conformational change within the AAA+ ring and a large rearrangement of the “linker” domain, involving a hinge near its middle. Analysis of a mutant in which the linker “undocks” from the ring indicates that linker remodeling requires energy that is supplied by interactions with the AAA+ modules. Fitting the dynein-c structures into flagellar tomograms suggests how this mechanism could drive sliding between microtubules, and also has implications for cytoplasmic cargo transport.
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► Structural changes in axonemal and cytoplasmic dynein motors seen by cryo-EM ► Movement is amplified by a hinge action within dynein's linker domain ► The linker is a stable structure that is actively remodeled by dynein's AAA+ modules ► Dynein's neck subdomain interacts with AAA4 and is an intrinsic site of flexibility
Dyneins are AAA+ motor proteins that power both microtubule-based transport and flagellar motility. Now, Roberts et al. present cryo-EM structures of both classes of dynein, revealing nucleotide-induced bending and indicating that dynein generates movement by using the AAA+ ring to actively remodel its own linker.
Objectives
To evaluate how an intervention, which combined hand washing promotion aimed at 5‐year‐olds with provision of free soap, affected illnesses among the children and their families and ...children's school absenteeism.
Methods
We monitored illnesses, including diarrhoea and acute respiratory infections (ARIs), school absences and soap consumption for 41 weeks in 70 low‐income communities in Mumbai, India (35 communities per arm).
Results
Outcomes from 847 intervention households (containing 847 5‐year‐olds and 4863 subjects in total) and 833 control households (containing 833 5‐year‐olds and 4812 subjects) were modelled using negative binomial regression. Intervention group 5‐year‐olds had fewer episodes of diarrhoea (−25%, 95% confidence intervals CI = −37%, −2%), ARIs (−15%, 95% CI = −30%, −8%), school absences due to illnesses (−27%, 95% CI = −41%, −18%) and eye infections (−46%, 95% CI = −58%, −31%). Further, there were fewer episodes of diarrhoea and ARIs in the intervention group for ‘whole families’ (−31%, 95% CI = −37%, −5%; and −14%, 95% CI = −23%, −6%, respectively), 6‐ to 15‐year‐olds (−30%, 95% CI = −39%, −7%; and −15%, 95% CI = −24%, −6%) and under 5 s (−32%, 95% CI = −41%, −4%; and −20%, 95% CI = −29%, −8%).
Conclusions
Direct‐contact hand washing interventions aimed at younger school‐aged children can affect the health of the whole family. These may be scalable through public–private partnerships and classroom‐based campaigns. Further work is required to understand the conditions under which health benefits are transferred and the mechanisms for transference.
Objectifs
Evaluer comment une intervention, qui combine la promotion du lavage des mains visant les enfants de 5 ans, avec la provision de savon gratuit, affecte les maladies chez les enfants et leurs familles et l'absentéisme scolaire des enfants.
Méthodes
Nous avons surveillé les maladies diarrhéiques et les infections respiratoires aiguës (IRA), l'absentéisme scolaire et l'utilisation de savon pendant 41 semaines dans 70 communautés à faibles revenus à Mumbai, en Inde (35 communautés par bras d’étude).
Résultats
Les résultats de 847 ménages d'intervention (comprenant 847 sujets de 5 ans et 4863 sujets au total) et 833 ménages témoins (comprenant 833 sujets de 5 ans et 4812 sujets au total) ont été modélisés en utilisant une régression binomiale négative. Les sujets de 5 ans dans le groupe d'intervention avaient moins d’épisodes de diarrhée (−25%, intervalles de confiance IC 95%: −37%, −2%); IRA (−15%; IC95%: −30%, −8%); absences à l’école en raison de maladies (−27%, IC95%: −41%, −18%) et des infections oculaires (−46%; IC95%: −58%, −31%). En outre, il y avait moins d’épisodes de diarrhée et d’IRA dans le groupe d'intervention pour les ‘familles entières’ (−31%; IC95%: −37%, −5% et −14%; IC95%: −23%, − 6%, respectivement); chez les 6 à 15 ans (−30%, IC95%: −39%, −7% et −15%; IC95%: 24%, −6%) et chez les moins de 5 ans (−32%; IC95%: −41%, −4% et −20%; IC95%: −29%, −8%).
Conclusions
Les interventions de lavage des mains et de contact direct destinées à de plus jeunes enfants d’âge scolaire peuvent affecter la santé de toute la famille. Celles‐ci peuvent être évolutives grâce à des partenariats public‐privé et des campagnes basées sur la classe d’école. Des travaux supplémentaires sont nécessaires pour comprendre les conditions dans lesquelles les bénéfices de santé sont transférés et les mécanismes de ce transfert.
Objetivos
Evaluar como una intervención en la que se combina la promoción del lavado de manos entre niños de 5 años con el suministro gratuito de jabón, tiene efecto sobre la incidencia de enfermedades entre los niños y sus familias y el ausentismo escolar de los niños.
Métodos
Hemos monitorizado la diarrea y las infecciones respiratorias agudas (IRAs), las ausencias escolares y el consumo de jabón durante 41 semanas en 70 comunidades con ingresos bajos en Mumbai, India (35 comunidades por brazo).
Resultados
Los resultados de 847 hogares intervenidos (que contenían 847 niños con 5 años y 4863 sujetos en total) y 833 hogares control (que contenían 833 niños de 5 años de edad y 4812 sujetos en total) se modelaron mediante una regresión binomial negativa. El grupo de intervención de niños de 5 años tenía menos episodios de diarrea (−25%, IC 95% = −37%, −2%); IRAs (−15%, IC 95% = −30%, −8%); ausencias escolares debido a enfermedad (−27%, IC 95% = −41%, −18%) e infecciones oculares (−46%, IC 95% = −58%, −31%). Más aún, dentro del grupo de intervención, habían menos episodios de diarrea e IRAs en “las familias enteras” (−31%, IC 95% = −37%, −5%; y −14%, IC 95% = −23%, −6%, respectivamente); entre los niños con edades entre los 6–15 años (−30%, IC 95% = −39%, −7%; y −15%, IC 95% = −24%, −6%); y entre los menores de 5 años (−32%, IC 95% = −41%, −4%; y 20%, IC 95% = −29%, −8%).
Conclusiones
Las intervenciones de lavado de manos cuyo grupo objetivo es el de escolares jóvenes, puede afectar la salud de toda la familia. Estas intervenciones podrían realizarse a mayor escala mediante alianzas público‐privadas y a través de las aulas. Se necesitan más estudios para entender las condiciones bajo las cuales se transfieren los beneficios sanitarios y los mecanismos de transferencia.
Populations of greater sage-grouse (Centrocercus urophasianus; sage-grouse) have been in a decline since the nineteenth century. We used our research, unpublished reports, and scientific literature ...to identify which predators kill sage-grouse and to assess whether lethal control of these predators benefited the species. We also asked state wildlife biologists and scientists whether they had ever witnessed a predator kill sage-grouse. We identified 266 instances where the predator responsible for depredating nests or killing juvenile or adult sage-grouse could be ascertained. Most adult sage-grouse were killed by eagles (Accipitridae), owls (Strigiformes), coyotes (Canis latrans), or red foxes (Vuples vulpes). Based on nest cameras, most depredated eggs are taken by common ravens (Corvus corax), badgers (Taxidae taxus), or coyotes. There are too few studies to conclude that predator removal increases survival rates of juvenile or adult sage-grouse. No study has been conducted to determine whether badger removal increases nest success of sage-grouse, and the only study on coyote removal produced ambiguous results. Several studies reported that more sage-grouse nests are successful (i.e., >1 eggs hatched) in areas where common ravens were removed or in areas where raven densities were lower than in other areas. The data we reviewed did not indicate predators played a role in the decline during the past century, but increasing numbers of ravens since the 1970s may have contributed to the declining sage-grouse populations in recent decades. We conclude that removing common ravens can increase nest success, although not necessarily sage-grouse abundance. Without a better understanding of sage-grouse and their predators, wildlife biologists will be handicapped in their efforts to prevent sage-grouse populations from continuing to decline.
Protein phosphorylation plays a role in many important cellular functions such as cellular plasticity, gene expression, and intracellular trafficking. All of these are dysregulated in Huntington’s ...disease (HD), a devastating neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the
huntingtin
gene. However, no studies have yet found protein phosphorylation differences in preclinical HD mouse models. Our current study investigated changes occurring in the cortical phosphoproteome of 8-week-old (prior to motor deficits) and 20-week-old (fully symptomatic) R6/1 transgenic HD mice. When comparing 8-week-old HD mice with their wild-type (WT) littermates, we found 660 peptides differentially phosphorylated, which were mapped to 227 phosphoproteins. These proteins were mainly involved in synaptogenesis, cytoskeleton organization, axon development, and nervous system development. Tau protein, found hyperphosphorylated at multiple sites in early symptomatic HD mice, also appeared as a main upstream regulator for the changes observed. Surprisingly, we found fewer changes in the phosphorylation profile of HD mice at the fully symptomatic stage, with 29 peptides differentially phosphorylated compared to WT mice, mapped to 25 phosphoproteins. These proteins were involved in cAMP signaling, dendrite development, and microtubule binding. Furthermore, huntingtin protein appeared as an upstream regulator for the changes observed at the fully symptomatic stage, suggesting impacts on kinases and phosphatases that extend beyond the mutated polyglutamine tract. In summary, our findings show that the most extensive changes in the phosphorylation machinery appear at an early presymptomatic stage in HD pathogenesis and might constitute a new target for the development of treatments.
CAMSAP and Patronin family members regulate microtubule minus-end stability and localization and thus organize noncentrosomal microtubule networks, which are essential for cell division, polarization ...and differentiation. Here, we found that the CAMSAP C-terminal CKK domain is widely present among eukaryotes and autonomously recognizes microtubule minus ends. Through a combination of structural approaches, we uncovered how mammalian CKK binds between two tubulin dimers at the interprotofilament interface on the outer microtubule surface. In vitro reconstitution assays combined with high-resolution fluorescence microscopy and cryo-electron tomography suggested that CKK preferentially associates with the transition zone between curved protofilaments and the regular microtubule lattice. We propose that minus-end-specific features of the interprotofilament interface at this site serve as the basis for CKK's minus-end preference. The steric clash between microtubule-bound CKK and kinesin motors explains how CKK protects microtubule minus ends against kinesin-13-induced depolymerization and thus controls the stability of free microtubule minus ends.
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