Melanism in Peromyscus Is Caused by Independent Mutations in Agouti

Identifying the molecular basis of phenotypes that have evolved independently can provide insight into the ways genetic and developmental constraints influence the maintenance of phenotypic diversity. Melanic (darkly pigmented) phenotypes in mammals provide a potent system in which to study the genetic basis of naturally occurring mutant phenotypes because melanism occurs in many mammals, and the mammalian pigmentation pathway is well understood. Spontaneous alleles of a few key pigmentation loci are known to cause melanism in domestic or laboratory populations of mammals, but in natural populations, mutations at one gene, the melanocortin-1 receptor (Mc1r), have been implicated in the vast majority of cases, possibly due to its minimal pleiotropic effects. To investigate whether mutations in this or other genes cause melanism in the wild, we investigated the genetic basis of melanism in the rodent genus Peromyscus, in which melanic mice have been reported in several populations. We focused on two genes known to cause melanism in other taxa, Mc1r and its antagonist, the agouti signaling protein (Agouti). While variation in the Mc1r coding region does not correlate with melanism in any population, in a New Hampshire population, we find that a 125-kb deletion, which includes the upstream regulatory region and exons 1 and 2 of Agouti, results in a loss of Agouti expression and is perfectly associated with melanic color. In a second population from Alaska, we find that a premature stop codon in exon 3 of Agouti is associated with a similar melanic phenotype. These results show that melanism has evolved independently in these populations through mutations in the same gene, and suggest that melanism produced by mutations in genes other than Mc1r may be more common than previously thought

Skipping of Exons by Premature Termination of Transcription and Alternative Splicing within Intron-5 of the Sheep SCF Gene: A Novel Splice Variant

Stem cell factor (SCF) is a growth factor, essential for haemopoiesis, mast cell development and melanogenesis. In the hematopoietic microenvironment (HM), SCF is produced either as a membrane-bound (−) or soluble (+) forms. Skin expression of SCF stimulates melanocyte migration, proliferation, differentiation, and survival. We report for the first time, a novel mRNA splice variant of SCF from the skin of white merino sheep via cloning and sequencing. Reverse transcriptase (RT)-PCR and molecular prediction revealed two different cDNA products of SCF. Full-length cDNA libraries were enriched by the method of rapid amplification of cDNA ends (RACE-PCR). Nucleotide sequencing and molecular prediction revealed that the primary 1519 base pair (bp) cDNA encodes a precursor protein of 274 amino acids (aa), commonly known as ‘soluble’ isoform. In contrast, the shorter (835 and/or 725 bp) cDNA was found to be a ‘novel’ mRNA splice variant. It contains an open reading frame (ORF) corresponding to a truncated protein of 181 aa (vs 245 aa) with an unique C-terminus lacking the primary proteolytic segment (28 aa) right after the D175G site which is necessary to produce ‘soluble’ form of SCF. This alternative splice (AS) variant was explained by the complete nucleotide sequencing of splice junction covering exon 5-intron (5)-exon 6 (948 bp) with a premature termination codon (PTC) whereby exons 6 to 9/10 are skipped (Cassette Exon, CE 6–9/10). We also demonstrated that the Northern blot analysis at transcript level is mediated via an intron-5 splicing event. Our data refine the structure of SCF gene; clarify the presence (+) and/or absence (−) of primary proteolytic-cleavage site specific SCF splice variants. This work provides a basis for understanding the functional role and regulation of SCF in hair follicle melanogenesis in sheep beyond what was known in mice, humans and other mammals

Search for a vector-like quark T′ → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for the electroweak production of a vector-like quark T′, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first T′ search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet T′ states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a T′ quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength κT = 0.25 and a relative decay width Γ/MT′ < 5%

Search for new physics in multijet events with at least one photon and large missing transverse momentum in proton-proton collisions at 13 TeV

A search for new physics in final states consisting of at least one photon, multiple jets, and large missing transverse momentum is presented, using proton-proton collision events at a center-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 137 fb−1, recorded by the CMS experiment at the CERN LHC from 2016 to 2018. The events are divided into mutually exclusive bins characterized by the missing transverse momentum, the number of jets, the number of b-tagged jets, and jets consistent with the presence of hadronically decaying W, Z, or Higgs bosons. The observed data are found to be consistent with the prediction from standard model processes. The results are interpreted in the context of simplified models of pair production of supersymmetric particles via strong and electroweak interactions. Depending on the details of the signal models, gluinos and squarks of masses up to 2.35 and 1.43 TeV, respectively, and electroweakinos of masses up to 1.23 TeV are excluded at 95% confidence level

Search for Scalar Leptoquarks Produced via τ-Lepton-Quark Scattering in pppp Collisions at s=13TeV\sqrt{s}=13 TeV

The first search for scalar leptoquarks produced in τ-lepton–quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138  fb$^{−1}$. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength

Observation of the Rare Decay of the η Meson to Four Muons

A search for the rare η→μ+μ−μ+μ− double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101  fb−1. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ+μ− decay as normalization, the branching fraction B(η→μ+μ−μ+μ−)=[5.0±0.8(stat)±0.7(syst)±0.7(B2μ)]×10−9 is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions

A search for new physics in central exclusive production using the missing mass technique with the CMS detector and the CMS-TOTEM precision proton spectrometer

A generic search is presented for the associated production of a Z boson or a photon with an additional unspecified massive particle X, pp → pp + Z/γ + X, in proton-tagged events from proton–proton collisions at √s = 13 TeV, recorded in 2017 with the CMS detector and the CMS-TOTEM precision proton spectrometer. The missing mass spectrum is analysed in the 600–1600 GeV range and a fit is performed to search for possible deviations from the background expectation. No significant excess in data with respect to the background predictions has been observed. odelindependent upper limits on the visible production cross section of pp → pp + Z/γ + X are set

Measurement of the cross section of top quark-antiquark pair production in association with a W boson in proton-proton collisions at s \sqrt{s} = 13 TeV

The production of a top quark-antiquark pair in association with a W boson $(t\bar{t}W)$ is measured in proton-proton collisions at a center-of-mass energy of 13 TeV. The analyzed data was recorded by the CMS experiment at the CERN LHC and corresponds to an integrated luminosity of 138 fb$^{−1}$. Events with two or three leptons (electrons and muons) and additional jets are selected. In events with two leptons, a multiclass neural network is used to distinguish between the signal and background processes. Events with three leptons are categorized based on the number of jets and of jets originating from b quark hadronization, and the lepton charges. The inclusive $(t\bar{t}W)$ production cross section in the full phase space is measured to be 868 ± 40(stat) ± 51(syst) fb. The $(t\bar{t}W)+$ and $(t\bar{t}W)−$ cross sections are also measured as 553 ± 30(stat) ± 30(syst) and 343 ± 26(stat) ± 25(syst) fb, respectively, and the corresponding ratio of the two cross sections is found to be 1.61±0.15(stat)$^{+0.07}_{−0.05}$(syst). The measured cross sections are larger than but consistent with the standard model predictions within two standard deviations, and represent the most precise measurement of these cross sections to date