British Journal of Cancer, Published online: 06 September 2019; doi:10.1038/s41416-019-0563-xIn utero exposure to breast cancer treatment: a population-based perinatal outcome study
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British Journal of Cancer, Published online: 06 September 2019; doi:10.1038/s41416-019-0559-6Intratumoural-infiltrating CD4 + and FOXP3 + T cells as strong positive predictive markers for the prognosis of resectable colorectal cancer
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RX-5902 is a first-in-class anti-cancer agent targeting phosphorylated-p68 and attenuating nuclear shuttling of β-catenin. The purpose of this study was to evaluate the efficacy of RX-5902 in preclinical models of TNBC and to explore effects on β-catenin expression. A panel of 18 TNBC cell lines were exposed to RX-5902 and changes in proliferation, apoptosis, cellular ploidy and effector protein expression were assessed. Gene expression profiling was used in sensitive and resistant cell lines with...
Thu Sep 05, 2019 17:13
Multidrug resistance and tumor migration and invasion are still the main obstacles to effective breast cancer chemotherapies. Transgelin 2 has recently been shown to induce drug resistance, tumor migration, and invasion. The aim of this study was to determine the biological functions of Transgelin 2 and the mechanism underlying how Transgelin 2 induces paclitaxel (PTX) resistance and the migration and invasion of breast cancer. We detected that the protein level of Transgelin 2 was significantly...
Thu Sep 05, 2019 17:13
Arry-520 is an advanced drug candidate from the Eg5 inhibitor class undergoing clinical evaluation in patients with relapsed or refractory multiple myeloma. Here we show by structural analysis that Arry-520 binds stoichiometrically to the motor domain of Eg5 in the conventional allosteric loop L5 pocket in a complex that suggests the same structural mechanism as other Eg5 inhibitors. We have previously shown that acquired resistance through mutations in the allosteric binding site located at loop...
Thu Sep 05, 2019 17:13
Multiple signaling pathways in the adult Drosophila enterocyte sense cellular damage or stress and signal to intestinal stem cells (ISCs) to undergo proliferation and differentiation, thereby maintaining intestinal homeostasis. Here we show that misregulation of mitochondrial pyruvate metabolism in enterocytes can stimulate ISC proliferation and differentiation. Our studies focus on the Mitochondrial Pyruvate Carrier (MPC), which is an evolutionarily-conserved protein complex that resides in the...
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Thu Sep 05, 2019 18:49
An organism Tree of Life (organism ToL) is a conceptual and metaphorical tree to capture a simplified narrative of the evolutionary course and kinship among the extant organisms of today. Such tree cannot be experimentally validated, but may be reconstructed based on characteristics associated with the organisms. Since the whole genome sequence of an organism is, at present, the most comprehensive descriptor of the organism, a genome Tol can be an empirically derivable surrogate for the organism...
Thu Sep 05, 2019 03:00
Background: Meiosis is essential for sexual reproduction, and generates genetically diverse haploid gametes from a diploid germ cell. Reduction of ploidy depends on active chromosome movements during early meiotic prophase I. Chromosome movements require telomere attachment to the nuclear envelope. This attachment is mediated by telomere adaptor proteins. Telomere adaptor proteins have to date been identified in fission yeast and mice. In the mouse, they form a complex composed of the meiotic proteins...
Thu Sep 05, 2019 03:00
We consider a homogeneous birth-death process with three different sampling schemes. First, individuals can be sampled through time and included in a reconstructed tree. Second, they can be sampled through time and only recorded as a point 'occurrence' along a timeline. Third, extant individuals are sampled and included in the reconstructed tree with a fixed probability. We further consider that sampled individuals can be removed or not from the process, upon sampling, with fixed probability. Given...
Thu Sep 05, 2019 03:00
A key question in social evolution is how worker and queen castes diverged to give rise to social insect societies. The Diapause Ground Plan hypothesis (DGPH) proposes that caste differences are driven by ancestral genetic and physiological signatures that are triggered during larval development. This has been demonstrated in Polistes wasps, but the applicability of this theory to other species remained unexplored. Primitively eusocial bumble bees are excellent models to examine the DGPH since they...
Thu Sep 05, 2019 03:00
The ribosome is an essential cellular machine performing protein biosynthesis. Its structure and composition are highly conserved in all species. However, some bacteria have been reported to have an incomplete set of ribosomal proteins. We have analyzed ribosomal protein composition in 214 small bacterial genomes (< 1 Mb) and found that although the ribosome composition is fairly stable, some ribosomal proteins may be absent, especially in bacteria with dramatically reduced genomes. The protein...
Thu Sep 05, 2019 03:00
The determination of the last common ancestor (LCA) of a group of species plays a vital role in evolutionary theory. Traditionally, an LCA is inferred by the rooting of a fully resolved species tree. From a theoretical perspective, however, inference of the LCA amounts to the reconstruction of just one branch - the root branch - of the true unrooted species tree, and should therefore be a much easier task than the full resolution of the species tree. Discarding the reliance on a hypothesised species...
Thu Sep 05, 2019 03:00
We evaluated the effects of variation in the number and distribution of gaps (i.e., no base; coded as IUPAC "." or "-") treated as missing data (i.e., any base, coded as "?" or IUPAC "N") in standard maximum likelihood (ML) analysis. We obtained alignments with variable numbers and arrangements of gaps by aligning seven diverse empirical datasets under different gap opening costs using MAFFT. We selected the optimal substitution model for each alignment using the corrected Akaike Information Criterion...
Thu Sep 05, 2019 03:00
Acanthamoeba castellanii species complex (genotype T4) comprises of more than ten species with unclear synonymy, as molecular phylogeny has several conflicts with published morphological data. In this paper, we analyze quantitative traits and temperature preferences in six new strains belonging to A. castellanii complex isolated from Arctic permafrost in the framework of molecular phylogeny. This integrative approach allows us to cross-link genotypic and phenotypic variability and identify species-level...
Thu Sep 05, 2019 03:00
While mutualisms are widespread and essential in ecosystem functioning, the emergence of uncooperative cheaters threatens their stability, unless there are functional or evolutionary mechanisms limiting cheaters interactions. Here, we evaluated the constraints upon mycoheterotrophic (MH) cheating plants in the mutualistic interaction network of autotrophic (AT) plants and arbuscular mycorrhizal fungi. For this purpose, we assembled a world-scale network of >25,000 interactions in order to investigate...
Thu Sep 05, 2019 03:00
Hybridization is a natural process at species range boundaries, but increasing numbers of species are hybridizing due to direct or indirect human activities. In such cases of anthropogenic hybridization, subsequent introgression can threaten the survival of native species. To date many such systems have been studied with too few genetic markers to assess the level of threat resulting from advanced backcrossing. Here we use 44,999 single nucleotide polymorphisms and the ADMIXTURE program to study...
Thu Sep 05, 2019 03:00
This paper aims to understand the dynamics of cultural accumulation when cultural knowledge is costly to produce and costly to learn. We first show that the cost of social learning prevents any significant cultural accumulation, as individuals rapidly reach a maximum amount of knowledge that they can barely learn over the course of their lives, without being able to go any further. However, we then show that cultural knowledge can accumulate durably and even experience phases of acceleration if it...
Thu Sep 05, 2019 03:00
In eukaryotes, the three-dimensional (3D) conformation of the genome is far from random, and this nonrandom chromatin organization is strongly correlated with gene expression and protein function, which are two critical determinants of the selective constraints and evolutionary rates of genes. However, whether genes and other elements that are located close to each other in the 3D genome evolve in a coordinated way has not been investigated in any organism. To address this question, we constructed...
Thu Sep 05, 2019 03:00
Cardio-metabolic disease is a leading cause of death worldwide, with extremely high prevalence in western, industrialized societies relative to developing nations and subsistence-level populations. The high prevalence in western societies has been attributed to dietary and lifestyle changes associated with industrialization, but current work has relied on health comparisons between separate, genetically distinct populations to draw these conclusions. To more robustly determine how lifestyle affects...
Thu Sep 05, 2019 03:00
Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information by sharing relevant background and reasoning with the reader (regular type). The authors’ commentary follows. Stage. A 54-year-old man…
Thu Sep 05, 2019 03:00
Abstract Clinical diagnosis of voice pathologies is performed by analyzing audio, color, shape, and vibration patterns of the laryngeal recordings which are taken with medical imaging devices such as video-laryngostroboscope, direct laryngoscopy, and high-speed videoendoscopes. This paper examines state-of-the-art methods and reveals open issues and problems of computing solutions for analysis and identification of laryngeal disorders. We propose a categorical representation of...
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Antidepressants that primarily enhance monoaminergic neurotransmission involving serotonin or norepinephrine are used in the treatment of major depressive disorder, and their clinical effects are generally evident in 4 to 8 weeks. One hypothesis for the mechanism of depression implicates deficits…
Thu Sep 05, 2019 03:00
Major depressive disorder is a serious mental health condition that affects up to 16% of people in the United States during their lifetimes and about 7% of the U.S. population in a given year. In addition, patients with major depressive disorder have an outsized risk of suicidal behavior.…
Thu Sep 05, 2019 03:00
The advent of BRAF and MEK inhibitors changed the landscape of the management of BRAF mutated melanoma patients. In this article, we report the case of a 51-year-old man with BRAF mutated locally advanced cutaneous melanoma of the head who demonstrated a limited response to initial anti-BRAF monotherapy followed by extensive surgery. Anti-PD1 therapy failed to reverse the disease progression. However, subsequent double inhibition of the BRAF and MEK pathways induced a fast and remarkable tumour response. ...
Tue Sep 03, 2019 03:00
Triple-negative breast cancer subtype is the most aggressive type of breast cancer due to the lack of specific therapeutic targets, having limited treatment options, low survival prognosis and high recurrence rates. In this work, we describe the effects of a semisynthetic derivative of [6]-gingerol (6G) called SSi6, produced by the addition of a 2,4-dinitrophenylhydrazine reagent on several aspects of triple-negative breast cancer biology. Human breast cancer cell lines MDA-MB-231 and MCF-10A were...
Tue Sep 03, 2019 03:00
Ferroptosis is a newly discovered type of cell death decided by iron-dependent lipid peroxidation, but its role in glioblastoma cell death remains unclear. Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), has been associated with antitumorigenic effects in many cancers. In this study, we first found that ibuprofen inhibited the viabilities of glioblastoma cells in vitro and in vivo, accompanied by abnormal increase in intracellular lipid peroxidation. Further study showed that the cell growth...
Tue Sep 03, 2019 03:00
Sirtuin-1 (Sirt-1), an NAD-dependent deacetylase, promotes tumorigenesis in glioma; however, whether the Sirt-1 specific inhibitor, EX527 exerts antitumor effects and the underlying mechanism in glioma requires further investigation. In the present study, the proliferative and colony formation abilities of two glioma cell lines (U87MG and LN-299) were inhibited by EX527. Treatment with EX527 increased the number of apoptotic cells (Annexin V-fluorescein isothiocyanate+/propidium iodide+/−); pretreatment...
Tue Sep 03, 2019 03:00
Abstract Background The swim start requires an explosive muscular response of the lower body musculature to effectively initiate movement off the starting blocks. There are currently key gaps in the literature evaluating the relationship between dry-land resistance training and swim start performance and the effects of this training on swim start performance, as assessed by the time to 5, 10 or 15 m. ...
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Abstract Change of direction (COD) manoeuvres are associated with anterior cruciate ligament (ACL) injury risk due to the propensity to generate large multiplanar knee joint loads. Given the short- and long-term consequences of ACL injury, practitioners are interested in methods that reduce knee joint loads and subsequent ACL loading. An effective strategy to reduce ACL loading is modifying an athlete’s movement mechanics to reduce knee joint loading. The purpose of this scoping...
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