Assessing Early Access to Care and Child Survival during a Health System Strengthening Intervention in Mali: A Repeated Cross Sectional Survey

Background

In 2012, 6.6 million children under age five died worldwide, most from diseases with known means of prevention and treatment. A delivery gap persists between well-validated methods for child survival and equitable, timely access to those methods. We measured early child health care access, morbidity, and mortality over the course of a health system strengthening model intervention in Yirimadjo, Mali. The intervention included Community Health Worker active case finding, user fee removal, infrastructure development, community mobilization, and prevention programming.

Methods and Findings

We conducted four household surveys using a cluster-based, population-weighted sampling methodology at baseline and at 12, 24, and 36 months. We defined our outcomes as the percentage of children initiating an effective antimalarial within 24 hours of symptom onset, the percentage of children reported to be febrile within the previous two weeks, and the under-five child mortality rate. We compared prevalence of febrile illness and treatment using chi-square statistics, and estimated and compared under-five mortality rates using Cox proportional hazard regression. There was a statistically significant difference in under-five mortality between the 2008 and 2011 surveys; in 2011, the hazard of under-five mortality in the intervention area was one tenth that of baseline (HR 0.10, p<0.0001). After three years of the intervention, the prevalence of febrile illness among children under five was significantly lower, from 38.2% at baseline to 23.3% in 2011 (PR = 0.61, p = 0.0009). The percentage of children starting an effective antimalarial within 24 hours of symptom onset was nearly twice that reported at baseline (PR = 1.89, p = 0.0195).

Conclusions

Community-based health systems strengthening may facilitate early access to prevention and care and may provide a means for improving child survival.     

Structure analysis of FAAP24 reveals single-stranded DNA-binding activity and domain functions in DNA damage response

The FANCM/FAAP24 heterodimer has distinct functions in protecting cells from complex DNA lesions such as interstrand crosslinks. These functions rely on the biochemical activity of FANCM/FAAP24 to recognize and bind to damaged DNA or stalled replication forks. However, the DNA-binding activity of this complex was not clearly defined. We investigated how FAAP24 contributes to the DNA-interacting functions of the FANCM/FAAP24 complex by acquiring the N-terminal and C-terminal solution structures of human FAAP24. Modeling of the FAAP24 structure indicates that FAAP24 may possess a high affinity toward single-stranded DNA (ssDNA). Testing of various FAAP24 mutations in vitro and in vivo validated this prediction derived from structural analyses. We found that the DNA-binding and FANCM-interacting functions of FAAP24, although both require the C-terminal (HhH)₂ domain, can be distinguished by segregation-of-function mutations. These results demonstrate dual roles of FAAP24 in DNA damage response against crosslinking lesions, one through the formation of FANCM/FAAP24 heterodimer and the other via its ssDNA-binding activity required in optimized checkpoint activation.     

Herbivore-induced volatile emissions are altered by soil legacy effects in cereal cropping systems

Plant and Soil - Demonstrating the potential of MRI as a 3D, non-invasive and continuous measurement technique to map Na+ concentration distributions in soil and around roots. Dissolved NaCl in...     

Why preen others? Predictors of allopreening in parrots and corvids and comparisons to grooming in great apes

Allogrooming in primates serves not only a hygienic function, but also plays a crucial role in maintaining strong affiliative bonds between group members, which in turn, underpin the emergence of cooperative behavior. In contrast, although allopreening occurs in many avian species, we know little about its social functions. Our study addresses this issue by investigating allopreening in a broad comparative data set including six corvid and nine parrot species. We assessed whether rates of allopreening initiations, proportion of time spent allopreening, and the number of grooming partners in captive group-housed birds were comparable to patterns observed in captive chimpanzees and bonobos. While parrots and corvids were found to have similar rates of social grooming to bonobos and chimpanzees, Pan species dedicated significantly more time to social grooming. Animals in larger groups had more grooming partners, but when controlling for the number of potential partners, birds tended to have fewer grooming interaction partners than Pan species. We then investigated whether allopreening in parrots and corvids was predicted by behavioral markers of affiliative social bonds (close physical proximity, active feeding, and low levels of agonistic behavior). Results revealed that providing allopreening to a partner was significantly predicted by often being in close proximity, but not engagement in active feeding or agonistic behavior. We examined the region allopreened in a subset of species and found that preening a partner's head was predicted by both close physical proximity and active feeding, while body allopreening was only predicted by close physical proximity. Head preening may confer more hygienic benefits to recipients, and thus, may be more selectively provided to valued partners. Results support the hypothesis that allopreening in corvids and parrots helps maintain social bonds with an individual's most important social partners, showing some similarities to allogrooming in primates.     

Essential krill species habitat resolved by seasonal upwelling and ocean circulation models within the large marine ecosystem of the California Current System

Due to their global distribution, high biomass and energy content, euphausiids (krill) are important prey for many mid and upper trophic level marine organisms. Understanding drivers of krill habitat is essential for forecasting range shifts, and to better understand the response of krill predators to climate change. We hypothesized that the distribution and abundance of krill species derived from ecosystem surveys in spring/summer relates to geomorphic features, coastal upwelling during the preceding winter, and spring mesoscale oceanographic conditions. To test this hypothesis, we used boosted regression trees with environmental data and ocean model output to quantify the habitat associations of two primary krill species (Euphausia pacifica and Thysanoessa spinifera) in the central California Current Ecosystem from 2002 to 2018. Models confirmed the neritic distribution of T. spinifera and pelagic, outer slope association of E. pacifica (deviance explained ~35%). Distribution of these species were influenced by depth and bottom rugosity; chlorophyll-a concentrations and increased winter upwelling conditions; and spring surface currents and wind stress. Thysanoessa spinifera and E. pacifica abundance responded negatively (positively) to warm (cold) climate events, confirming known relationships. As an independent evaluation of krill models, observations of krill predator (seabirds, marine mammals) distribution indicated they were present within habitats of predicted high krill species abundance. Our framework indicates species-specific habitat relationships for these foundational forage species and their negative response to large-scale climate variations, such as El Niño and marine heatwave conditions. The approach can be easily transferred to other ecosystems or krill species that respond to similar ocean and climate forcing.     

Evidence for genetic structuring and limited dispersal ability in the Great Barrier Reef sponge Carteriospongia foliascens

Coral Reefs - Understanding connectivity patterns for coral reef organisms is important for their effective management. Despite sponges being an important component of the benthic fauna on the...     

Independent translation of ORFs in dicistronic operons,synthetic building blocks for polycistronic chloroplast gene expression

We designed a dicistronic plastid marker system that relies on the plastid's ability to translate polycistronic mRNAs. The identification of transplastomic clones is based on selection for antibiotic resistance encoded in the first open reading frame (ORF) and accumulation of the reporter gene product in tobacco chloroplasts encoded in the second ORF. The antibiotic resistance gene may encode spectinomycin or kanamycin resistance based on the expression of aadA or neo genes, respectively. The reporter gene used in the study is the green fluorescent protein (GFP). The mRNA level depends on the 5′‐untranslated region of the first ORF. The protein output depends on the strengths of the ribosome binding, and is proportional with the level of translatable mRNA. Because the dicistronic mRNA is not processed, we could show that protein output from the second ORF is independent from the first ORF. High‐level GFP accumulation from the second ORF facilitates identification of transplastomic events under ultraviolet light. Expression of multiple proteins from an unprocessed mRNA is an experimental design that enables predictable protein output from polycistronic mRNAs, expanding the toolkit of plant synthetic biology.     

Population genetic structure and demographic history of the lone star tick,Amblyomma americanum (Ixodida: Ixodidae): New evidence supporting old records

Range expansions are a potential outcome of changes in habitat suitability, which commonly result as a consequence of climate change. Hypotheses on such changes in the geographic distribution of a certain species can be evaluated using population genetic structure and demography. In this study we explore the population genetic structure, genetic variability, demographic history of, and habitat suitability for Amblyomma americanum, a North American tick species that is a known vector of several pathogenic microorganisms. We used a double digestion restriction site‐associated DNA sequencing technique (dd‐RAD seq) and discovered 8,181 independent single nucleotide polymorphisms (SNPs) in 189 ticks from across the geographic range of the species. Genetic diversity was low, particularly when considering the broad geographic range of this species. The edge populations were less diverse than populations belonging to the historic range, possibly indicative of a range expansion, but this hypothesis was not statistically supported by a test based on genetic data. Nonetheless, moderate levels of population structure and substructure were detected between geographic regions. For New England, demographic and species distribution models support a scenario where A. americanum was present in more northern locations in the past, underwent a bottleneck, and subsequently recovered. These results are consistent with a hypothesis that this species is re‐establishing in this area, rather than one focused on range expansion from the south. This hypothesis is consistent with old records describing the presence of A. americanum in the northeastern US in the early colonial period.     

Breeding season length predicts duet coordination and consistency in Neotropical wrens (Troglodytidae)

Many animals produce coordinated signals, but few are more striking than the elaborate male–female vocal duets produced by some tropical songbirds. Yet, little is known about the factors driving the extreme levels of vocal coordination between mated pairs in these taxa. We examined evolutionary patterns of duet coordination and their potential evolutionary drivers in Neotropical wrens (Troglodytidae), a songbird family well known for highly coordinated duets. Across 23 wren species, we show that the degree of coordination and precision with which pairs combine their songs into duets varies by species. This includes some species that alternate their song phrases with exceptional coordination to produce rapidly alternating duets that are highly consistent across renditions. These highly coordinated, consistent duets evolved independently in multiple wren species. Duet coordination and consistency are greatest in species with especially long breeding seasons, but neither duet coordination nor consistency are correlated with clutch size, conspecific abundance or vegetation density. These results suggest that tightly coordinated duets play an important role in mediating breeding behaviour, possibly by signalling commitment or coalition of the pair to mates and other conspecifics.     

PKB signaling and atrogene expression in skeletal muscle of aged mice

The purpose of this study was to determine if PKB signaling is decreased and contractile protein degradation is increased in extensor digitorum longus (EDL) and soleus (SOL) muscles from middle-aged (MA) and aged (AG) mice. We also examined the effect of age on atrogene expression in quadriceps muscle. PKB activity, as assessed by Thr(308) and Ser(473) phosphorylation, was significantly higher in EDL and SOL muscles from AG than MA mice. The age-related increase in PKB activity appears to be due to an increase in expression of the kinase, as PKB-α and PKB-β levels were significantly higher in EDL and SOL muscles from AG than MA mice. The phosphorylation of forkhead box 3a (FOXO3a) on Thr(32), a PKB target, was significantly higher in EDL muscles from AG than MA mice. The rate of contractile protein degradation was similar in EDL and SOL muscles from AG and MA mice. Atrogin-1 and muscle-specific RING finger protein 1 (MuRF-1) mRNA levels did not change in muscles from AG compared with MA mice, indicating that ubiquitin-proteasome proteolysis does not contribute to sarcopenia. A significant decrease in Bcl-2 and 19-kDa interacting protein 3 (Bnip3) and GABA receptor-associated protein 1 (Gabarap1) mRNA was observed in muscles from AG compared with MA mice, which may contribute to age-related contractile dysfunction. In conclusion, the mechanisms responsible for sarcopenia are distinct from experimental models of atrophy and do not involve atrogin-1 and MuRF-1 or enhanced proteolysis. Finally, a decline in autophagy-related gene expression may provide a novel mechanism for impaired contractile function and muscle metabolism with advancing age.