The emerging structure of the Extended Evolutionary Synthesis: where does Evo-Devo fit in?

The Extended Evolutionary Synthesis (EES) debate is gaining ground in contemporary evolutionary biology. In parallel, a number of philosophical standpoints have emerged in an attempt to clarify what exactly is represented by the EES. For Massimo Pigliucci, we are in the wake of the newest instantiation of a persisting Kuhnian paradigm; in contrast, Telmo Pievani has contended that the transition to an EES could be best represented as a progressive reformation of a prior Lakatosian scientific research program, with the extension of its Neo-Darwinian core and the addition of a brand-new protective belt of assumptions and auxiliary hypotheses. Here, we argue that those philosophical vantage points are not the only ways to interpret what current proposals to ‘extend’ the Modern Synthesis-derived ‘standard evolutionary theory’ (SET) entail in terms of theoretical change in evolutionary biology. We specifically propose the image of the emergent EES as a vast network of models and interweaved representations that, instantiated in diverse practices, are connected and related in multiple ways. Under that assumption, the EES could be articulated around a paraconsistent network of evolutionary theories (including some elements of the SET), as well as models, practices and representation systems of contemporary evolutionary biology, with edges and nodes that change their position and centrality as a consequence of the co-construction and stabilization of facts and historical discussions revolving around the epistemic goals of this area of the life sciences. We then critically examine the purported structure of the EES—published by Laland and collaborators in 2015—in light of our own network-based proposal. Finally, we consider which epistemic units of Evo-Devo are present or still missing from the EES, in preparation for further analyses of the topic of explanatory integration in this conceptual framework

An evaluation of the integration of non-traditional learning tools into a community based breast and cervical cancer education program: The witness project of Buffalo

BACKGROUND: Breast and cervical cancer continue to represent major health challenges for African American women. among Caucasian women. The underlying reasons for this disparity are multifactorial and include lack of education and awareness of screening and early detection. Traditional educational methods have enjoyed varied success in the African American community and spawned development of novel educational approaches. Community based education programs employing a variety of educational models have been introduced. Successful programs must train and provide lay community members with the tools necessary to deliver strong educational programs. METHODS: The Witness Project is a theory-based, breast and cervical cancer educational program, delivered by African American women, that stresses the importance of early detection and screening to improve survival and teaches women how to perform breast self examination. Implementing this program in the Buffalo Witness Project of Buffalo required several modifications in the curriculum, integration of non-traditional learning tools and focused training in clinical study participation. The educational approaches utilized included repetition, modeling, building comprehension, reinforcement, hands on learning, a social story on breast health for African American women, and role play conversations about breast and cervical health and support. RESULTS: Incorporating non-traditional educational approaches into the Witness Project training resulted in a 79% improvement in the number of women who mastered the didactic information. A seventy-two percent study participation rate was achieved by educating the community organizations that hosted Witness Project programs about the informed consent process and study participation. CONCLUSION: Incorporating non-traditional educational approaches into community outreach programs increases training success as well as community participation

Systematic Single-Cell Analysis of Pichia pastoris Reveals Secretory Capacity Limits Productivity

Biopharmaceuticals represent the fastest growing sector of the global pharmaceutical industry. Cost-efficient production of these biologic drugs requires a robust host organism for generating high titers of protein during fermentation. Understanding key cellular processes that limit protein production and secretion is, therefore, essential for rational strain engineering. Here, with single-cell resolution, we systematically analysed the productivity of a series of Pichia pastoris strains that produce different proteins both constitutively and inducibly. We characterized each strain by qPCR, RT-qPCR, microengraving, and imaging cytometry. We then developed a simple mathematical model describing the flux of folded protein through the ER. This combination of single-cell measurements and computational modelling shows that protein trafficking through the secretory machinery is often the rate-limiting step in single-cell production, and strategies to enhance the overall capacity of protein secretion within hosts for the production of heterologous proteins may improve productivity

Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration.

Understanding the molecular mechanisms that promote successful tissue regeneration is critical for continued advancements in regenerative medicine. Vertebrate amphibian tadpoles of the species Xenopus laevis and Xenopus tropicalis have remarkable abilities to regenerate their tails following amputation, through the coordinated activity of numerous growth factor signalling pathways, including the Wnt, Fgf, Bmp, Notch and TGF-β pathways. Little is known, however, about the events that act upstream of these signalling pathways following injury. Here, we show that Xenopus tadpole tail amputation induces a sustained production of reactive oxygen species (ROS) during tail regeneration. Lowering ROS levels, using pharmacological or genetic approaches, reduces the level of cell proliferation and impairs tail regeneration. Genetic rescue experiments restored both ROS production and the initiation of the regenerative response. Sustained increased ROS levels are required for Wnt/β-catenin signalling and the activation of one of its main downstream targets, fgf20 (ref. 7), which, in turn, is essential for proper tail regeneration. These findings demonstrate that injury-induced ROS production is an important regulator of tissue regeneration

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Precision Measurement of the Mass of the h_c(1P1) State of Charmonium

A precision measurement of the mass of the h_c(1P1) state of charmonium has been made using a sample of 24.5 million psi(2S) events produced in e+e- annihilation at CESR. The reaction used was psi(2S) -> pi0 h_c, pi0 -> gamma gamma, h_c -> gamma eta_c, and the reaction products were detected in the CLEO-c detector. Data have been analyzed both for the inclusive reaction and for the exclusive reactions in which eta_c decays are reconstructed in fifteen hadronic decay channels. Consistent results are obtained in the two analyses. The averaged results of the present measurements are M(h_c)=3525.28+-0.19 (stat)+-0.12(syst) MeV, and B(psi(2S) -> pi0 h_c)xB(h_c -> gamma eta_c)= (4.19+-0.32+-0.45)x10^-4. Using the 3PJ centroid mass, Delta M_hf(1P)= - M(h_c) = +0.02+-0.19+-0.13 MeV.Comment: 9 pages, available through http://www.lns.cornell.edu/public/CLNS/, submitted to PR

Precision Measurement of B(D+ -> mu+ nu) and the Pseudoscalar Decay Constant fD+

We measure the branching ratio of the purely leptonic decay of the D+ meson with unprecedented precision as B(D+ -> mu+ nu) = (3.82 +/- 0.32 +/- 0.09)x10^(-4), using 818/pb of data taken on the psi(3770) resonance with the CLEO-c detector at the CESR collider. We use this determination to derive a value for the pseudoscalar decay constant fD+, combining with measurements of the D+ lifetime and assuming |Vcd| = |Vus|. We find fD+ = (205.8 +/- 8.5 +/- 2.5) MeV. The decay rate asymmetry [B(D+ -> mu+ nu)-B(D- -> mu- nu)]/[B(D+ -> mu+ nu)+B(D- -> mu- nu)] = 0.08 +/- 0.08, consistent with no CP violation. We also set 90% confidence level upper limits on B(D+ -> tau+ nu) < 1.2x10^(-3) and B(D+ -> e+ nu) < 8.8x10^(-6).Comment: 24 pages, 11 figures and 6 tables, v2 replaced some figure vertical axis scales, v3 corrections from PRD revie

Ancient micrometeorites suggestive of an oxygen-rich Archaean upper atmosphere

It is widely accepted that Earth’s early atmosphere contained less than 0.001 per cent of the present-day atmospheric oxygen (O2) level, until the Great Oxidation Event resulted in a major rise in O2 concentration about 2.4 billion years ago1. There are multiple lines of evidence for low O2 concentrations on early Earth, but all previous observations relate to the composition of the lower atmosphere2 in the Archaean era; to date no method has been developed to sample the Archaean upper atmosphere. We have extracted fossil micrometeorites from limestone sedimentary rock that had accumulated slowly 2.7 billion years ago before being preserved in Australia’s Pilbara region. We propose that these micrometeorites formed when sand-sized particles entered Earth’s atmosphere and melted at altitudes of about 75 to 90 kilometres (given an atmospheric density similar to that of today3). Here we show that the FeNi metal in the resulting cosmic spherules was oxidized while molten, and quench-crystallized to form spheres of interlocking dendritic crystals primarily of magnetite (Fe3O4), with wüstite (FeO)+metal preserved in a few particles. Our model of atmospheric micrometeorite oxidation suggests that Archaean upper-atmosphere oxygen concentrations may have been close to those of the present-day Earth, and that the ratio of oxygen to carbon monoxide was sufficiently high to prevent noticeable inhibition of oxidation by carbon monoxide. The anomalous sulfur isotope (Δ33S) signature of pyrite (FeS2) in seafloor sediments from this period, which requires an anoxic surface environment4, implies that there may have been minimal mixing between the upper and lower atmosphere during the Archaean

J/psi and psi(2S) Radiative Transitions to eta_c

Using 24.5 million psi(2S) decays collected with the CLEO-c detector at CESR we present the most precise measurements of magnetic dipole transitions in the charmonium system. We measure B(psi(2S)->gamma eta_c) = (4.32+/-0.16+/-0.60)x10^-3, B(J/psi->gamma eta_c)/B(psi(2S)->gamma eta_c) = 4.59+/-0.23+/-0.64, and B(J/psi->gamma eta_c) = (1.98+/-0.09+/-0.30)%. We observe a distortion in the eta_c line shape due to the photon-energy dependence of the magnetic dipole transition rate. We find that measurements of the eta_c mass are sensitive to the line shape, suggesting an explanation for the discrepancy between measurements of the eta_c mass in radiative transitions and other production mechanisms.Comment: 11 pages, 3 figure