685 research outputs found

    Spermiogenesis in three species of cicadas (Hemiptera: Cicadidae)

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    Spermiogenesis in three species of cicadas representing one cicadettine (Monomatapa matoposa Boulard) and two cicadines (Diceroprocta biconica [Walker] and Kongota punctigera [Walker]) was investigated by light and electron microscopy. Although spermiogenesis was occurring in the testis of adult males of all species, earlier spermiogenic stages were observed in D. biconica only. While spermiogenesis was similar to that described for other insects, some differences were noted. For example granular material did not assemble around the centriole to form a centriolar adjunct but did accumulate in the cytoplasm of early spermatids adjacent to a region of the nuclear membrane where nuclear pores were aggregated. In late spermatids this material accumulated anterior to the mitochondrial derivatives in a developing postero-lateral nuclear groove. While this material has been named the ‘centriolar adjunct’ by previous authors, its formation away from the centriole raises questions about its true identity. Second, during acrosome maturation an ante-acrosomal region of cytoplasm develops. Although present in later spermatids, this region is lost in spermatozoa. Interspecific variations in chromatin condensation patterns and the number of microtubule layers encircling the spermatid nucleus during spermiogenesis were noted

    Reply to Rouder (2014) : good frequentist properties raise confidence

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    Established psychological results have been called into question by demonstrations that statistical significance is easy to achieve, even in the absence of an effect. One often-warned-against practice, choosing when to stop the experiment on the basis of the results, is guaranteed to produce significant results. In response to these demonstrations, Bayes factors have been proposed as an antidote to this practice, because they are invariant with respect to how an experiment was stopped. Should researchers only care about the resulting Bayes factor, without concern for how it was produced? Yu, Sprenger, Thomas, and Dougherty (2014) and Sanborn and Hills (2014) demonstrated that Bayes factors are sometimes strongly influenced by the stopping rules used. However, Rouder (2014) has provided a compelling demonstration that despite this influence, the evidence supplied by Bayes factors remains correct. Here we address why the ability to influence Bayes factors should still matter to researchers, despite the correctness of the evidence. We argue that good frequentist properties mean that results will more often agree with researchers’ statistical intuitions, and good frequentist properties control the number of studies that will later be refuted. Both help raise confidence in psychological results

    Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture

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    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging.National Human Genome Research Institute (U.S.) (Grant HG003067

    The Minimum-Uncertainty Squeezed States for for Atoms and Photons in a Cavity

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    We describe a six-parameter family of the minimum-uncertainty squeezed states for the harmonic oscillator in nonrelativistic quantum mechanics. They are derived by the action of corresponding maximal kinematical invariance group on the standard ground state solution. We show that the product of the variances attains the required minimum value 1/4 only at the instances that one variance is a minimum and the other is a maximum, when the squeezing of one of the variances occurs. The generalized coherent states are explicitly constructed and their Wigner function is studied. The overlap coefficients between the squeezed, or generalized harmonic, and the Fock states are explicitly evaluated in terms of hypergeometric functions. The corresponding photons statistics are discussed and some applications to quantum optics, cavity quantum electrodynamics, and superfocusing in channeling scattering are mentioned. Explicit solutions of the Heisenberg equations for radiation field operators with squeezing are found.Comment: 27 pages, no figures, 174 references J. Phys. B: At. Mol. Opt. Phys., Special Issue celebrating the 20th anniversary of quantum state engineering (R. Blatt, A. Lvovsky, and G. Milburn, Guest Editors), May 201

    Principles of meiotic chromosome assembly revealed in S. cerevisiae

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    During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

    Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome

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    Background: Glioblastoma (GBM) is the most common malignant brain cancer occurring in adults, and is associated with dismal outcome and few therapeutic options. GBM has been shown to predominantly disrupt three core pathways through somatic aberrations, rendering it ideal for precision medicine approaches. Methods: We describe a 35-year-old female patient with recurrent GBM following surgical removal of the primary tumour, adjuvant treatment with temozolomide and a 3-year disease-free period. Rapid whole-genome sequencing (WGS) of three separate tumour regions at recurrence was carried out and interpreted relative to WGS of two regions of the primary tumour. Results: We found extensive mutational and copy-number heterogeneity within the primary tumour. We identified a TP53 mutation and two focal amplifications involving PDGFRA, KIT and CDK4, on chromosomes 4 and 12. A clonal IDH1 R132H mutation in the primary, a known GBM driver event, was detectable at only very low frequency in the recurrent tumour. After sub-clonal diversification, evidence was found for a whole-genome doubling event and a translocation between the amplified regions of PDGFRA, KIT and CDK4, encoded within a double-minute chromosome also incorporating miR26a-2. The WGS analysis uncovered progressive evolution of the double-minute chromosome converging on the KIT/PDGFRA/PI3K/mTOR axis, superseding the IDH1 mutation in dominance in a mutually exclusive manner at recurrence, consequently the patient was treated with imatinib. Despite rapid sequencing and cancer genome-guided therapy against amplified oncogenes, the disease progressed, and the patient died shortly after. Conclusion: This case sheds light on the dynamic evolution of a GBM tumour, defining the origins of the lethal sub-clone, the macro-evolutionary genomic events dominating the disease at recurrence and the loss of a clonal driver. Even in the era of rapid WGS analysis, cases such as this illustrate the significant hurdles for precision medicine success

    Pesticide-related illness reported to and diagnosed in Primary Care: implications for surveillance of environmental causes of ill-health

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    BACKGROUND: In Great Britain (GB), data collected on pesticide associated illness focuses on acute episodes such as poisonings caused by misuse or abuse. This study aimed to investigate the extent and nature of pesticide-related illness presented and diagnosed in Primary Care and the feasibility of establishing a routine monitoring system. METHODS: A checklist, completed by General Practitioners (GP) for all patients aged 18+ who attended surgery sessions, identified patients to be interviewed in detail on exposures and events that occurred in the week before their symptoms appeared. RESULTS: The study covered 59320 patients in 43 practices across GB and 1335 detailed interviews. The annual incidence of illness reported to GPs because of concern about pesticide exposure was estimated to be 0.04%, potentially 88400 consultations annually, approximately 1700 per week. The annual incidence of consultations where symptoms were diagnosed by GPs as likely to be related to pesticide exposure was 0.003%, an annual estimate of 6630 consultations i.e. about 128 per week. 41% of interviewees reported using at least one pesticide at home in the week before symptoms occurred. The risk of having symptoms possibly related to pesticide exposure compared to unlikely was associated with home use of pesticides after adjusting for age, gender and occupational pesticide exposure (OR = 1.88, 95% CI 1.51 - 2.35). CONCLUSION: GP practices were diverse and well distributed throughout GB with similar symptom consulting patterns as in the Primary Care within the UK. Methods used in this study would not be feasible for a routine surveillance system for pesticide related illness. Incorporation of environmental health into Primary Care education and practice is needed

    Integrating transposable elements in the 3D genome

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    Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

    Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome

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    In a glioblastoma tumour with multi-region sequencing before and after recurrence, we find an IDH1 mutation that is clonal in the primary but lost at recurrence. We also describe the evolution of a double-minute chromosome encoding regulators of the PI3K signalling axis that dominates at recurrence, emphasizing the challenges of an evolving and dynamic oncogenic landscape for precision medicin
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