Bifurcation into functional niches in adaptation

One of the central questions in evolutionary biology concerns the dynamics of adaptation and diversification. This issue can be addressed experimentally if replicate populations adapting to identical environments Call be investigated in detail. We have studied 501 such replicas Using digital organisms adapting to at least two fundamentally different functional niches (survival strategies) present in the same environment: one in which fast replication is the way to live, and another where exploitation of the environment's complexity leads to complex organisms with longer life spans and smaller replication rates. While these two modes of survival are closely analogous to those expected to emerge in so-called r and K selection scenarios respectively, the bifurcation of evolutionary histories according to these functional niches occurs in identical environments, under identical selective pressures. We find that the branching occurs early, and leads to drastic phenotypic differences (in fitness, sequence length, and gestation time) that are permanent and irreversible. This study confirms an earlier experimental effort using microorganisms, in that diversification can be understood at least in part in terms of bifurcations on saddle points leading to peak shifts, as in the picture drawn by Sewall Wright

Challenges to generating political prioritization for adolescent sexual and reproductive health in Kenya: A qualitative study.

BackgroundDespite the high burden of adverse adolescent sexual and reproductive health (SRH) outcomes, it has remained a low political priority in Kenya. We examined factors that have shaped the lack of current political prioritization of adolescent SRH service provision.MethodsWe used the Shiffman and Smith policy framework consisting of four categories-actor power, ideas, political contexts, and issue characteristics-to analyse factors that have shaped political prioritization of adolescent SRH. We undertook semi-structured interviews with 14 members of adolescent SRH networks between February and April 2019 at the national level and conducted thematic analysis of the interviews.FindingsSeveral factors hinder the attainment of political priority for adolescent SRH in Kenya. On actor power, the adolescent SRH community was diverse and united in adoption of international norms and policies, but lacked policy entrepreneurs to provide strong leadership, and policy windows were often missed. Regarding ideas, community members lacked consensus on a cohesive public positioning of the problem. On issue characteristics, the perception of adolescents as lacking political power made politicians reluctant to act on the existing data on the severity of adolescent SRH. There was also a lack of consensus on the nature of interventions to be implemented. Pertaining to political contexts, sectoral funding by donors and government treasury brought about tension within the different government ministries resulting in siloed approaches, lack of coordination and overall inefficiency. However, the SRH community has several strengths that augur well for future political support. These include the diverse multi-sectoral background of its members, commitment to improving adolescent SRH, and the potential to link with other health priorities such as maternal health and HIV/AIDS.ConclusionIn order to increase political attention to adolescent SRH in Kenya, there is an urgent need for policy actors to: 1) create a more cohesive community of advocates across sectors, 2) develop a clearer public positioning of adolescent SRH, 3) agree on a set of precise approaches that will resonate with the political system, and 4) identify and nurture policy entrepreneurs to facilitate the coupling of adolescent SRH with potential solutions when windows of opportunity arise

Can family planning outreach bridge the urban-rural divide in Zambia?

Abstract: Background: Zambia experienced declining aggregate fertility and increasing aggregate contraceptive use from 1990 to 2000. Yet, in rural Zambia, progress in family planning has lagged far behind the advances made in Zambia's urban areas. The contraceptive prevalence rate in Lusaka and other urban areas outstripped the rate in rural Zambia by nearly 25 percentage points (41.2 percent versus 16.6 percent) in 2001. The total fertility rate varied between urban and rural areas by 2.5 children (4.3 versus 6.9 children). This paper considers the urban-rural differentials in Zambia and assesses family planning outreach as a tool to narrow this divide. Methods: This study uses the Zambia Demographic and Health Survey (DHS) data, collected between 2001 and 2002. Logistic regression techniques were employed to examine factors associated with contraceptive use. The first analysis tested modern contraceptive use versus traditional method use and no use. In addition, separate models were run for samples stratified by type of residence (rural or urban) to determine if different factors were associated with use by residence. A simulation determined the effect of all women receiving at least one household visit from a health worker if all other variables were held constant. Results: Differences in modern contraceptive use between urban and rural areas persist (OR: 1.56, 95 percent CI: 1.24–1.96) even after adjusting for a number of demographic, socioeconomic, cognitive, and attitudinal factors. Household visits by a community health worker significantly increased the likelihood of modern contraceptive use among rural women (OR: 1.83; 95 percent CI: 1.29–2.58). If all rural women received at least one outreach visit per year, the prevalence rate for modern contraceptive methods would be expected to increase for this group by 5.9 percentage points, a marked increase but less than one-quarter of the total urban-rural differential. Conclusion: Outreach in the form of health worker visits can improve access to family planning services, but it does not eliminate barriers to access or address continued high-fertility desires in Zambia. Until policymakers consider strategies that address both family planning demand creation and supply of services, progress in Zambia and the rest of sub-Saharan Africa will continue to lag behind the rest of the world

Examining the Effects of Formal Education Level on the Montreal Cognitive Assessment

Background: Brief, global assessments such as the Montreal Cognitive Assessment (MoCA) are widely used in primary care for assessing cognition in older adults. Like other neuropsychological instruments, lower formal education can influence MoCA interpretation. Methods: Data from 2 large studies of cognitive aging were used—Alzheimer’s Disease Neuroimaging Initiative (ADNI) and National Alzheimer’s Coordinating Center (NACC). Both use comprehensive examinations to determine cognitive status and have brain amyloid status for many participants. Mixed models were used to account for random variation due to data source. Results: Cognitively intact participants with lower education (≤12 years) were more likely than those with higher education (\u3e12 years) to be classified as potentially impaired using the MoCA cutoff of \u3c26 (P \u3c .01). Backwards selection revealed 4 MoCA items significantly associated with education (cube copy, serial subtraction, phonemic fluency, abstraction). Subtracting these items scores yielded an alternative MoCA score with a maximum of 24 and a cutoff of ≤19 for classifying participants with mild cognitive impairment. Using the alternative MoCA score and cutoff, among cognitively intact participants, both education groups were similarly likely to be classified as potentially impaired (P \u3e .67). Conclusions: The alternative MoCA score neutralized the effects of formal education. Although further research is needed, this alternative score offers a simple procedure for interpreting MoCAs administered to older adults with ≤12 years education. These educational effects also highlight that the MoCA is part of the assessment process—not a singular diagnostic test—and a comprehensive workup is necessary to accurately diagnose cognitive impairments

Probing Spectral Line Gradients Beyond One Effective Radius in NGC 3610

The outer region (0.75--1.25 r_e in the B-band) of the merger-remnant elliptical NGC 3610 is studied using extremely high signal to noise Keck spectra, with a supplementary spectrum of the galaxy center. Stellar population parameters -- age, [Z/H], [$\alpha$/Fe] -- are measured in several apertures along the slit. Using the multi-index simultaneous fitting method of Proctor et al. (2004), no significant stellar population gradients are detected in the outer parts of the galaxy. The overall gradients relative to the galaxy center are consistent with those found in many other early-type galaxies, though the metallicity gradient is much steeper than would be expected if NGC 3610 formed in a major merger event. Standard analysis methods using the H$\beta$ index are found to produce spurious radially variable gradients.Comment: 15 pages, 9 figures, accepted by A

Metallophosphite-Catalyzed Asymmetric Acylation of α,β-Unsaturated Amides

The l-menthone-derived TADDOL phosphite 6b catalyzes highly enantioselective conjugate additions of acyl silanes to α,β-unsaturated amides. p-Methoxybenzoyl cyclohexyldimethylsilane adds to a variety of N,N-dimethyl acrylamide derivatives in the presence of the lithium salt of 6b. In many instances the α-silyl-γ-ketoamide product undergoes facile enantioenrichment (to 97–99% ee) upon recrystallization. Desilylation with HF·pyr affords the formal Stetter addition products. Baeyer–Villiger oxidation of the desilylated γ-ketoamides affords useful ester products. An X-ray diffraction study of 6b reveals that the isopropyl group of the menthone ketal influences the position of the syn-pseudoaxial phenyl group in the TADDOL structure. Through a crossover experiment, the silicon migration step in the reaction mechanism is shown to be strictly intramolecular

Microvascular Endothelial Dysfunction in Sedentary, Obese Humans Is Mediated by NADPH Oxidase Influence of Exercise Training

Objective—The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. Approach and Results—Young, sedentary men and women were divided into lean (body mass index 18–25; n=14), intermediate (body mass index 28–32.5; n=13), and obese (body mass index 33–40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2 O2 ) and superoxide levels in the vastus lateralis of obese compared with both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase inhibitor, lowered (normalized) H2 O2 and superoxide levels, and reversed microvascular endothelial dysfunction in obese subjects. After 8 weeks of exercise, H2 O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the NADPH oxidase subunits p22phox, p47phox, and p67phox was increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. Conclusions—This study implicates NADPH oxidase as a source of excessive ROS production in skeletal muscle of obese individuals and links excessive NADPH oxidase–derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these malad

KRAS mutation and Consensus Molecular Subtypes 2 and 3 are independently associated with reduced immune infiltration and reactivity in colorectal cancer

Abstract Purpose: KRAS mutation is a common canonical mutation in colorectal cancer, found at differing frequencies in all consensus molecular subtypes (CMS). The independent immunobiological impacts of RAS mutation and CMS are unknown. Thus, we explored the immunobiological effects of KRAS mutation across the CMS spectrum. Experimental Design: Expression analysis of immune genes/signatures was performed using The Cancer Genome Atlas (TCGA) RNA-seq and the KFSYSCC microarray datasets. Multivariate analysis included KRAS status, CMS, tumor location, MSI status, and neoantigen load. Protein expression of STAT1, HLA-class II, and CXCL10 was analyzed by digital IHC. Results: The Th1-centric co-ordinate immune response cluster (CIRC) was significantly, albeit modestly, reduced in KRAS-mutant colorectal cancer in both datasets. Cytotoxic T cells, neutrophils, and the IFNγ pathway were suppressed in KRAS-mutant samples. The expressions of STAT1 and CXCL10 were reduced at the mRNA and protein levels. In multivariate analysis, KRAS mutation, CMS2, and CMS3 were independently predictive of reduced CIRC expression. Immune response was heterogeneous across KRAS-mutant colorectal cancer: KRAS-mutant CMS2 samples have the lowest CIRC expression, reduced expression of the IFNγ pathway, STAT1 and CXCL10, and reduced infiltration of cytotoxic cells and neutrophils relative to CMS1 and CMS4 and to KRAS wild-type CMS2 samples in the TCGA. These trends held in the KFSYSCC dataset. Conclusions: KRAS mutation is associated with suppressed Th1/cytotoxic immunity in colorectal cancer, the extent of the effect being modulated by CMS subtype. These results add a novel immunobiological dimension to the biological heterogeneity of colorectal cancer. Clin Cancer Res; 24(1); 224–33. ©2017 AACR.</jats:p

Constraining the Evolution of Dark Energy with a Combination of Galaxy Cluster Observables

We show that the abundance and redshift distribution ($dN/dz$) of galaxy clusters in future high--yield cluster surveys, combined with the spatial power spectrum ($P_c(k)$) of the same clusters, can place significant constraints on the evolution of the dark energy equation of state, $w=w(a)$. We evaluate the expected errors on $w_a=-dw/da$ and other cosmological parameters using a Fisher matrix approach, and simultaneously including cluster structure evolution parameters in our analysis. We study three different types of forthcoming surveys that will identify clusters based on their X-ray emission (such as DUO, the Dark Universe Observatory), their Sunyaev--Zel'dovich (SZ) decrement (such as SPT, the South Pole Telescope), or their weak lensing (WL) shear (such as LSST, the Large Synoptic Survey Telescope). We find that combining the cluster abundance and power spectrum significantly enhances constraints from either method alone. We show that the weak-lensing survey can deliver a constraint as tight as $\Delta w_a \sim 0.1$ on the evolution of the dark energy equation of state, and that the X-ray and SZ surveys each yield $\Delta w_a \sim 0.4$ separately, or $\Delta w_a \sim 0.2$ when these two surveys are combined. For the X-ray and SZ surveys, constraints on dark energy parameters are improved by a factor of two by combining the cluster data with cosmic microwave background (CMB) anisotropy measurements by Planck, but degrade by a factor of two if the survey is required to solve simultaneously for cosmological and cluster structure evolution parameters. The constraint on $w_a$ from the weak lensing survey is improved by $\sim 25$% with the addition of Planck data.Comment: 13 pages. v2: Expanded discussion of weak lensing survey (LSST), improved CMB analysis, references added, final version published in PR