Tree-unitarity bounds for THDM Higgs masses revisited

We have reconsidered theoretical upper bounds on the scalar boson masses within the two-Higgs-doublet model (THDM), employing the well-known technical condition of tree-level unitarity. Our treatment provides a modest extension and generalization of some previous results of other authors. We present a rather detailed discussion of the solution of the relevant inequalities and offer some new analytic formulae as well as numerical values for the Higgs mass bounds in question. A comparison is made with the earlier results on the subject that can be found in the literature.Comment: 20 pages, 6 figures; correction to typos; will appear in Eur. Phys. J.

Triple gauge vertices at one-loop level in THDM

Renormalized triple gauge vertices (TGV) are examined within the two-Higgs-doublet model of electroweak interactions. Deviations of the TGV from their standard-model values are calculated at the one-loop level, in the on-shell renormalization scheme. As a consistency check, UV divergence cancellations anticipated on symmetry grounds are verified explicitly. Dependence of the TGV finite parts on the masses of possible heavy Higgs scalars is discussed briefly.Comment: 10pages, 13figure

Possible non-decoupling effects of heavy Higgs bosons in e+ e- -> W+ W- within THDM

We discuss the origin of the nondecoupling effects of the heavy Higgs bosons within the two Higgs doublet extension (THDM) of the Standard Model (SM) and illustrate it by means of the one-loop calculation of the differential cross-sections of the process e+ e- -> W+ W- in both the decoupling and the non-decoupling regimes. We argue that there are many regions in the THDM parametric space in which the THDM and SM predictions differ by several percents and such effects could, at least in principle, be testable at the future experimental facilities.Comment: 8 pages, 2 figures; to appear soon in EPJC. v2 - several minor corrections (typos), references adde

Human RIF1 and protein phosphatase 1 stimulate DNA replication origin licensing but suppress origin activation

We thank David Stead at the Aberdeen Proteomics Service for help in mass spectrometry interpretation, and Raif Yücel and his team at the University of Aberdeen Iain Fraser Cytometry Centre for assistance with flow cytometry. We thank Robert Alver and Julian Blow at University of Dundee for advice on the use of tautomycetin. Peter Cherepanov of the Francis Crick Institute gifted XL413. Daniel Durocher of Lunenfeld-Tanenbaum Research Institute gifted DNA constructs. Work by ADD and SH was supported by Cancer Research UK Grant A13356, Cancer Research UK Programme Award A19059, and BBSRC grant (BB/K006304/1). AIL was supported by Wellcome Trust Awards (108058/Z/15/Z & 105024/Z/14/Z). This work was also supported by JSPS KAKENHI Grant # 16H04739, 25116004 to CO and 16J04327 to YO.Peer reviewedPublisher PD

γ-Tubulin 2 Nucleates Microtubules and Is Downregulated in Mouse Early Embryogenesis

γ-Tubulin is the key protein for microtubule nucleation. Duplication of the γ-tubulin gene occurred several times during evolution, and in mammals γ-tubulin genes encode proteins which share ∼97% sequence identity. Previous analysis of Tubg1 and Tubg2 knock-out mice has suggested that γ-tubulins are not functionally equivalent. Tubg1 knock-out mice died at the blastocyst stage, whereas Tubg2 knock-out mice developed normally and were fertile. It was proposed that γ-tubulin 1 represents ubiquitous γ-tubulin, while γ-tubulin 2 may have some specific functions and cannot substitute for γ-tubulin 1 deficiency in blastocysts. The molecular basis of the suggested functional difference between γ-tubulins remains unknown. Here we show that exogenous γ-tubulin 2 is targeted to centrosomes and interacts with γ-tubulin complex proteins 2 and 4. Depletion of γ-tubulin 1 by RNAi in U2OS cells causes impaired microtubule nucleation and metaphase arrest. Wild-type phenotype in γ-tubulin 1-depleted cells is restored by expression of exogenous mouse or human γ-tubulin 2. Further, we show at both mRNA and protein levels using RT-qPCR and 2D-PAGE, respectively, that in contrast to Tubg1, the Tubg2 expression is dramatically reduced in mouse blastocysts. This indicates that γ-tubulin 2 cannot rescue γ-tubulin 1 deficiency in knock-out blastocysts, owing to its very low amount. The combined data suggest that γ-tubulin 2 is able to nucleate microtubules and substitute for γ-tubulin 1. We propose that mammalian γ-tubulins are functionally redundant with respect to the nucleation activity

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments