5,414 research outputs found
Complete mitochondrial DNA sequence of the tropical hornet Vespa affinis (Insecta, Hymenoptera)
We analyzed the complete mitochondrial genome of the Asian tropical hornet Vespa affinis from Ishigaki Island, Japan. It consisted of a circular molecule with 19,109 bp, which is larger to other hornet species e.g. V. velutina. We predicted the genome contained 13 protein-coding, 22 tRNA, and two rRNA genes, along with one A+T-rich control region. The repetitive sequences were confirmed at multiple positions in the non-coding genes. The initiation codons ATA was found in one, ATG in seven, ATT in five genes, while the termination codons TAA and TAG were observed 11 and two genes, respectively. The average AT content of the genome was 78.4%
Challenges and solutions for the analysis of<i>in situ</i>,<i>in crystallo</i>micro-spectrophotometric data
Combining macromolecular crystallography within crystallomicro-spectrophotometry yields valuable complementary information on the sample, including the redox states of metal cofactors, the identification of bound ligands and the onset and strength of undesired photochemistry, also known as radiation damage. However, the analysis and processing of the resulting data differs significantly from the approaches used for solution spectrophotometric data. The varying size and shape of the sample, together with the suboptimal sample environment, the lack of proper reference signals and the general influence of the X-ray beam on the sample have to be considered and carefully corrected for. In the present article, how to characterize and treat these sample-dependent artefacts in a reproducible manner is discussed and theSLS-APEin situ,in crystallooptical spectroscopy data-analysis toolbox is demonstrated.</jats:p
Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer
Background
Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility.
Methods
A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies.
Results
Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001.
Conclusions
Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER
A Statistical Method for Reassociating Human Tali and Calcanei from a Commingled Context.
In a commingled context, assessing that a talus and a calcaneus correspond to the same individual could become a primary step for accurately sorting human remains. For this purpose, the lengths and widths of the trochlea, posterior calcaneal articular surface, and posterior talar articular surface were measured in 197 individuals (105 males, 92 females) from the Athens Collection. A total of 12 highly accurate equations for reassociating tali and calcanei were developed, using simple and multiple linear regression analysis and they were found to be suitable for sorting commingled human remains. Bilateral asymmetry and sex did not have an effect on the accuracy of the method
Spontaneous and deliberate future thinking: A dual process account
© 2019 Springer Nature.This is the final published version of an article published in Psychological Research, licensed under a Creative Commons Attri-bution 4.0 International License. Available online at: https://doi.org/10.1007/s00426-019-01262-7.In this article, we address an apparent paradox in the literature on mental time travel and mind-wandering: How is it possible that future thinking is both constructive, yet often experienced as occurring spontaneously? We identify and describe two ‘routes’ whereby episodic future thoughts are brought to consciousness, with each of the ‘routes’ being associated with separable cognitive processes and functions. Voluntary future thinking relies on controlled, deliberate and slow cognitive processing. The other, termed involuntary or spontaneous future thinking, relies on automatic processes that allows ‘fully-fledged’ episodic future thoughts to freely come to mind, often triggered by internal or external cues. To unravel the paradox, we propose that the majority of spontaneous future thoughts are ‘pre-made’ (i.e., each spontaneous future thought is a re-iteration of a previously constructed future event), and therefore based on simple, well-understood, memory processes. We also propose that the pre-made hypothesis explains why spontaneous future thoughts occur rapidly, are similar to involuntary memories, and predominantly about upcoming tasks and goals. We also raise the possibility that spontaneous future thinking is the default mode of imagining the future. This dual process approach complements and extends standard theoretical approaches that emphasise constructive simulation, and outlines novel opportunities for researchers examining voluntary and spontaneous forms of future thinking.Peer reviewe
Two Simple W' Models for the Early LHC
W' gauge bosons are good candidates for early LHC discovery. We define two
reference models, one containing a W'_R and one containing a W'_L, which may
serve as ``simplified models'' for presenting experimental results of W'
searches at the LHC. We present the Tevatron bounds on each model and compute
the constraints from precision electroweak observables. We find that indirect
low-energy constraints on the W'_L are quite strong. However, for a W'_R
coupling to right-handed fermions there exists a sizeable region in parameter
space beyond the bounds from the Tevatron and low-energy precision measurements
where even 50 inverse picobarns of integrated LHC luminosity are sufficient to
discover the W'_R. The most promising final states are two leptons and two
jets, or one lepton recoiling against a ``neutrino jet''. A neutrino jet is a
collimated object consisting of a hard lepton and two jets arising from the
decay of a highly boosted massive neutrino.Comment: 20 pages, 8 figures. v2: references adde
Release of Lungworm Larvae from Snails in the Environment: Potential for Alternative Transmission Pathways
Background: Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis). In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host.
Methodology/Principal Findings: Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior) and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior). Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior.
Conclusions: Results of this study indicate that A. abstrusus and T. brevior infective L3 are shed in the mucus of H. aspersa or in water where infected gastropods had died submerged. Both elimination pathways may represent alternative route(s) of environmental contamination and source of the infection for these nematodes under field conditions and may significantly affect the epidemiology of feline lungworms. Considering that snails may act as intermediate hosts for other metastrongyloid species, the environmental contamination by mucus-released larvae is discussed in a broader context
Imbibition in Disordered Media
The physics of liquids in porous media gives rise to many interesting
phenomena, including imbibition where a viscous fluid displaces a less viscous
one. Here we discuss the theoretical and experimental progress made in recent
years in this field. The emphasis is on an interfacial description, akin to the
focus of a statistical physics approach. Coarse-grained equations of motion
have been recently presented in the literature. These contain terms that take
into account the pertinent features of imbibition: non-locality and the
quenched noise that arises from the random environment, fluctuations of the
fluid flow and capillary forces. The theoretical progress has highlighted the
presence of intrinsic length-scales that invalidate scale invariance often
assumed to be present in kinetic roughening processes such as that of a
two-phase boundary in liquid penetration. Another important fact is that the
macroscopic fluid flow, the kinetic roughening properties, and the effective
noise in the problem are all coupled. Many possible deviations from simple
scaling behaviour exist, and we outline the experimental evidence. Finally,
prospects for further work, both theoretical and experimental, are discussed.Comment: Review article, to appear in Advances in Physics, 53 pages LaTe
Quantum Gravity in Everyday Life: General Relativity as an Effective Field Theory
This article is meant as a summary and introduction to the ideas of effective
field theory as applied to gravitational systems.
Contents:
1. Introduction
2. Effective Field Theories
3. Low-Energy Quantum Gravity
4. Explicit Quantum Calculations
5. ConclusionsComment: 56 pages, 2 figures, JHEP style, Invited review to appear in Living
Reviews of Relativit
Fitness Ranking of Individual Mutants Drives Patterns of Epistatic Interactions in HIV-1
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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