Evolution of the complementary sex-determination gene of honey bees: Balancing selection and trans-species polymorphisms

The mechanism of sex determination varies substantively among evolutionary lineages. One important mode of genetic sex determination is haplodiploidy, which is used by ∼20% of all animal species, including >200,000 species of the entire insect order Hymenoptera. In the honey bee Apis mellifera, a hymenopteran model organism, females are heterozygous at the csd (complementary sex determination) locus, whereas males are hemizygous (from unfertilized eggs). Fertilized homozygotes develop into sterile males that are eaten before maturity. Because homozygotes have zero fitness and because common alleles are more likely than rare ones to form homozygotes, csd should be subject to strong overdominant selection and negative frequency-dependent selection. Under these selective forces, together known as balancing selection, csd is expected to exhibit a high degree of intraspecific polymorphism, with long-lived alleles that may be even older than the species. Here we sequence the csd genes as well as randomly selected neutral genomic regions from individuals of three closely related species, A. mellifera, Apis cerana, and Apis dorsata. The polymorphic level is approximately seven times higher in csd than in the neutral regions. Gene genealogies reveal trans-species polymorphisms at csd but not at any neutral regions. Consistent with the prediction of rare-allele advantage, nonsynonymous mutations are found to be positively selected in csd only in early stages after their appearances. Surprisingly, three different hypervariable repetitive regions in csd are present in the three species, suggesting variable mechanisms underlying allelic specificities. Our results provide a definitive demonstration of balancing selection acting at the honey bee csd gene, offer insights into the molecular determinants of csd allelic specificities, and help avoid homozygosity in bee breeding

Reflective Perspectives of Host and Guest Participants of an International Professional Development Experience

Global competence is a skill set that has become a necessity in every discipline in the agricultural sciences. With an increasingly diverse student population in our school systems coupled with an increasingly complex global agrisystem, now more than ever we need globally competent educators and learners to develop a globally competent workforce and society. A common intervention in cultivating global competency is the study abroad immersive experience for the traveling participants, but little is known about the global competency gains in hosting individuals. The immersive study abroad experience provided the opportunity for school-based agricultural educators (both candidates and practicing educators) to engage in a four-week experience with their Malaysian counterparts exploring the interconnected nature of culture, agriculture, and education. Throughout the experience the participants engaged in daily structured reflection sessions using the TIPS method. Journal entries were coded and analyzed for both Malaysia and United States participants. Participants from both countries respectively became more globally competent educators and learners

Spin chirality on a two-dimensional frustrated lattice

The collective behavior of interacting magnetic moments can be strongly influenced by the topology of the underlying lattice. In geometrically frustrated spin systems, interesting chiral correlations may develop that are related to the spin arrangement on triangular plaquettes. We report a study of the spin chirality on a two-dimensional geometrically frustrated lattice. Our new chemical synthesis methods allow us to produce large single crystal samples of KFe3(OH)6(SO4)2, an ideal Kagome lattice antiferromagnet. Combined thermodynamic and neutron scattering measurements reveal that the phase transition to the ordered ground-state is unusual. At low temperatures, application of a magnetic field induces a transition between states with different non-trivial spin-textures.Comment: 7 pages, 4 figure

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. METHODS: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ(2) tests or Fisher exact tests for categorical variables. RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date

Brokered Graph State Quantum Computing

We describe a procedure for graph state quantum computing that is tailored to fully exploit the physics of optically active multi-level systems. Leveraging ideas from the literature on distributed computation together with the recent work on probabilistic cluster state synthesis, our model assigns to each physical system two logical qubits: the broker and the client. Groups of brokers negotiate new graph state fragments via a probabilistic optical protocol. Completed fragments are mapped from broker to clients via a simple state transition and measurement. The clients, whose role is to store the nascent graph state long term, remain entirely insulated from failures during the brokerage. We describe an implementation in terms of NV-centres in diamond, where brokers and clients are very naturally embodied as electron and nuclear spins.Comment: 5 pages, 3 figure

The Ship of Theseus Puzzle

Does the Ship of Theseus present a genuine puzzle about persistence due to conflicting intuitions based on “continuity of form” and “continuity of matter” pulling in opposite directions? Philosophers are divided. Some claim that it presents a genuine puzzle but disagree over whether there is a solution. Others claim that there is no puzzle at all since the case has an obvious solution. To assess these proposals, we conducted a cross-cultural study involving nearly 3,000 people across twenty-two countries, speaking eighteen different languages. Our results speak against the proposal that there is no puzzle at all and against the proposal that there is a puzzle but one that has no solution. Our results suggest that there are two criteria—“continuity of form” and “continuity of matter”— that constitute our concept of persistence and these two criteria receive different weightings in settling matters concerning persistence

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

Toward reconstructing the evolution of advanced moths and butterflies (Lepidoptera: Ditrysia): an initial molecular study

<p>Abstract</p> <p>Background</p> <p>In the mega-diverse insect order Lepidoptera (butterflies and moths; 165,000 described species), deeper relationships are little understood within the clade Ditrysia, to which 98% of the species belong. To begin addressing this problem, we tested the ability of five protein-coding nuclear genes (6.7 kb total), and character subsets therein, to resolve relationships among 123 species representing 27 (of 33) superfamilies and 55 (of 100) families of Ditrysia under maximum likelihood analysis.</p> <p>Results</p> <p>Our trees show broad concordance with previous morphological hypotheses of ditrysian phylogeny, although most relationships among superfamilies are weakly supported. There are also notable surprises, such as a consistently closer relationship of Pyraloidea than of butterflies to most Macrolepidoptera. Monophyly is significantly rejected by one or more character sets for the putative clades Macrolepidoptera as currently defined (<it>P </it>< 0.05) and Macrolepidoptera excluding Noctuoidea and Bombycoidea sensu lato (<it>P </it>≤ 0.005), and nearly so for the superfamily Drepanoidea as currently defined (<it>P </it>< 0.08). Superfamilies are typically recovered or nearly so, but usually without strong support. Relationships within superfamilies and families, however, are often robustly resolved. We provide some of the first strong molecular evidence on deeper splits within Pyraloidea, Tortricoidea, Geometroidea, Noctuoidea and others.</p> <p>Separate analyses of mostly synonymous versus non-synonymous character sets revealed notable differences (though not strong conflict), including a marked influence of compositional heterogeneity on apparent signal in the third codon position (nt3). As available model partitioning methods cannot correct for this variation, we assessed overall phylogeny resolution through separate examination of trees from each character set. Exploration of "tree space" with GARLI, using grid computing, showed that hundreds of searches are typically needed to find the best-feasible phylogeny estimate for these data.</p> <p>Conclusion</p> <p>Our results (a) corroborate the broad outlines of the current working phylogenetic hypothesis for Ditrysia, (b) demonstrate that some prominent features of that hypothesis, including the position of the butterflies, need revision, and (c) resolve the majority of family and subfamily relationships within superfamilies as thus far sampled. Much further gene and taxon sampling will be needed, however, to strongly resolve individual deeper nodes.</p

Supporting the Changing Research Practices of Asian Studies Scholars

Ithaka S+R’s Research Support Services Program investigates how the research support needs of scholars vary by discipline and includes reports on history, chemistry, art history, religious studies, agriculture, and public health. In 2017-2018, Ithaka S+R examined the changing research methods and practices of Asian studies scholars conducting research through U.S. institutions. This project was undertaken collaboratively with research teams at 11 academic libraries with the goal of identifying services to better support Asian studies scholars. This report aims to provide actionable findings for the organizations, institutions, and professionals who support the research process of Asian studies scholars. One hundred and sixty-nine scholars were interviewed during the project, and Ithaka S+R sampled 50 of the resulting transcripts for the analysis presented in this report. These transcripts yielded findings in several thematic areas in which Asian studies would benefit from new or improved services, including its position within the academy, discovering and accessing information, managing research workflows, and producing outputs that reach target audiences and have the desired impact

Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells

© 2014 The Authors. Approximately half of poor prognosis neuroblastomas (NBs) are characterized by pathognomonic MYCN gene amplification and MYCN over-expression. Here we present data showing that short-interfering RNA mediated depletion of the protein arginine methyltransferase 5 (PRMT5) in cell-lines representative of NBs with MYCN gene amplification leads to greatly impaired growth and apoptosis. Growth suppression is not apparent in the MYCN-negative SH-SY5Y NB cell-line, or in two immortalized human fibroblast cell-lines. Immunoblotting of NB cell-lines shows that high PRMT5 expression is strongly associated with MYCN-amplification (P < 0.004, Mann-Whitney U-test) and immunohistochemical analysis of primary NBs reveals that whilst PRMT5 protein is ubiquitously expressed in the cytoplasm of most cells, MYCN-amplified tumours exhibit pronounced nuclear PRMT5 staining. PRMT5 knockdown in MYCN-overexpressing cells, including the SHEP-21N cell-line with inducible MYCN expression leads to a dramatic decrease in MYCN protein and MYCN-associated cell-death in SHEP-21N cells. Quantitative gene expression analysis and cycloheximide chase experiments suggest that PRMT5 regulates MYCN at a post-transcriptional level. Reciprocal co-immunoprecipitation experiments demonstrated that endogenous PRMT5 and MYCN interact in both SK-N-BE(2)C and NGP cell lines. By using liquid chromatography - tandem mass spectrometry (LC-MS/MS) analysis of immunoprecipitated MYCN protein, we identified several potential sites of arginine dimethylation on the MYCN protein. Together our studies implicate PRMT5 in a novel mode of MYCN post-translational regulation and suggest PRMT5 plays a major role in NB tumorigenesis. Small-molecule inhibitors of PRMT5 may therefore represent a novel therapeutic strategy for neuroblastoma and other cancers driven by the MYCN oncogene